diff --git a/data/ChronicHypertension_inline_GATE.xml b/data/ChronicHypertension_inline_GATE.xml
new file mode 100644
index 0000000..c42b10d
--- /dev/null
+++ b/data/ChronicHypertension_inline_GATE.xml
@@ -0,0 +1,85 @@
+
+Chronic hypertension in pregnancy
+
+
Chronic hypertension in pregnancy
+
Mild chronic hypertension ( systolic blood pressure of 140-159 mm Hg or diastolic blood pressure of 90-109 mm Hg )
+
Severe chronic hypertension ( systolic blood pressure of 160 mm Hg or greater or diastolic blood pressure of 110 mm Hg or greater )
+
+
Clinical Specialty
Cardiology
+
Internal Medicine
+
Obstetrics and Gynecology
+
+
Guideline Objective(s)
To review the effects of chronic hypertension on pregnancy
+
To clarify the terminology and criteria used to define and diagnose chronic hypertension during pregnancy
+
To review the available evidence for management options for chronic hypertension during pregnancy
+
+
Interventions and Practices Considered
+
+
Diagnosis/Evaluation
Initial evaluation before pregnancy or early in pregnancy with specific testing that may include electrocardiography, echocardiography, ophthalmologic examination, and assessment of renal function.
Counseling regarding effective contraception for women taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers
+
+
Major Outcomes Considered
Rate of small-for-gestational-age (SGA) infant, prematurity, perinatal mortality, neonatal morbidity, and placental abruption in pregnant women with chronic hypertension
+
Maternal mortality and morbidity
+
The benefits and potential adverse fetal effects of treatment of mild chronic hypertension during pregnancy
+
+
Recommendations
+
+
Major Recommendations
+
+
The grades of evidence (I-III) and levels of recommendations (A-C) are defined at the end of the "Major Recommendations" field.
+
+
The following recommendation is based on good and consistent scientific evidence (Level A):
Angiotensin-converting enzyme inhibitors (ACE) and angiotensin receptor blockers (ARB) are contraindicated in all trimesters of pregnancy.
+
+
The following recommendations and conclusions are based on limited or inconsistent scientific evidence (Level B):
Women with severe hypertensionrequire antihypertensive medications for acute elevation of blood pressure.
+
Based on the overall low rate of adverse effects and good efficacy, labetalol is a good option for first-line treatment of chronic hypertension in pregnancy .
+
Atenolol, a pure beta antagonist, was shown to be associated with growth restriction in infants and is not currently recommended for the treatment of chronic hypertension in pregnancy.
+
Thiazide diuretic therapy used in women before pregnancy does not need to be discontinued during pregnancy.
+
+
The following recommendations are based primarily on consensus and expert opinion (Level C):
Ideally, a woman with chronic hypertensionshould be evaluated before conception to ascertain possible end-organ involvement. Specific testing before pregnancy or early in pregnancy might include assessment of renal function , electrocardiography , echocardiography , and ophthalmologic evaluation . The choice of appropriate tests is dependent on the severity of the chronic hypertension.
+
Women taking ACE inhibitors or ARBsshould receive counseling about the importance of effective contraception , emphasizing that long-acting reversible contraception is most efficacious.
+
Evaluation of fetal growth by ultrasonography in women with chronic hypertension is warranted . If growth restriction is suspected , the fetal status should be monitored .
+
+
Definitions:
+
+
Grades of Evidence
+
+
I Evidence obtained from at least one properly designed randomized controlled trial
+
+
II-1 Evidence obtained from well-designed controlled trials without randomization
+
+
II-2 Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group
+
+
II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this type of evidence.
+
+
III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees
+
+
Levels of Recommendation
+
+
Level A ??? Recommendations are based on good and consistent scientific evidence.
+
+
Level B ??? Recommendations are based on limited or inconsistent scientific evidence.
+
+
Level C ??? Recommendations are based primarily on consensus and expert opinion.
+
Benefits/Harms of Implementing the Guideline Recommendations
+
+
Potential Benefits
+
Improved understanding of the effects of chronic hypertension on pregnancy and the terminology and criteria used to define and diagnose chronic hypertension during pregnancy
+
Appropriate management of chronic hypertension during pregnancy
+
Potential Harms
+
Oral Antihypertensives Used Commonly in Pregnancy
+
Labetalol: Headache
+
Nifedipine: Headache
+
Methyldopa: Maternal sedation, elevated liver function tests (LFTs), depression
+
Hydralazine: Use with methyldopa or labetalol to prevent reflex tachycardia; risk of neonatal thrombocytopenia
+
Hydrochlorothiazide: Can cause volume depletion and electrolyte disorders
+
Drugs for Urgent Control of Severe Acute Hypertension in Pregnancy
+
Hydralazine: Risk of delayed maternal hypotension, fetal bradycardia
+
Labetalol: Probably less risk of tachycardia and arrhythmia than with other vasodilators; increasingly preferred as first-line agent
+
Nifedipine: Possible interference with labor
+
Contraindications
+
+
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are contraindicated during all trimesters of pregnancy.
+
\ No newline at end of file
diff --git a/data/Diabetes_inline_LASSIE.xml b/data/Diabetes_inline_LASSIE.xml
new file mode 100644
index 0000000..8bc79ac
--- /dev/null
+++ b/data/Diabetes_inline_LASSIE.xml
@@ -0,0 +1,872 @@
+
+Diagnosis and management of type 2 diabetes mellitus in adults.
+
+
Diagnosis and management of type 2 diabetes mellitus in adults.
+
Prediabetes
+
Type 2 diabetes mellitus
+
Recommendations
+
+
Major Recommendations
+
+
Note from the National Guideline Clearinghouse (NGC) and the Institute for Clinical Systems Improvement (ICSI): For a description of what has changed since the previous version of this guidance, refer to Summary of Changes Report - April 2012 . In addition, ICSI has made a decision to transition to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This document is in transition to the GRADE methodology. Transition steps incorporating GRADE methodology for this document include the following:
+
Priority placed upon available systematic reviews in literature searches.
+
All existing Class A (randomized controlled trials [RCTs]) studies have been considered as high quality evidence unless specified differently by a work group member.
+
All existing Class B, C and D studies have been considered as low quality evidence unless specified differently by a work group member.
+
All existing Class M and R studies are identified by study design versus assigning a quality of evidence. (Refer to Crosswalk between ICSI Evidence Grading System and GRADE below in the "Definitions" section).
+
All new literature considered by the work group for this revision has been assessed using GRADE methodology.
+
+
The recommendations for the management of type 2 diabetes mellitus are presented in the form of 2 algorithms with a total of 24 components, accompanied by detailed annotations. Algorithms are provided in the original guideline document for: Diagnosis and Management of Type 2 Diabetes Mellitus (main algorithm) and Glycemic Control; clinical highlights and selected annotations (numbered to correspond with the algorithm) follow.
+
+
Class of evidence (Low Quality, Moderate Quality, High Quality, Meta-analysis, Systematic Review, Decision Analysis, Cost-Effectiveness Analysis, Guideline, and Reference) and conclusion grade (I-III, Not Assignable) definitions are repeated at the end of the "Major Recommendations" field.
+
Clinical Highlights
+
Education and self-management support is necessary for people with prediabetes and diabetes to manage their disease. (Annotation #10)
+
Focus on cardiovascular risk reduction (blood pressure control, low-density lipoprotein cholesterol control and statin use, aspirin use and tobacco cessation). (Annotations #11, 13, 14)
+
Glycosylated hemoglobin (A1c) levels should be individualized to the patient. (Annotation #11)
+
Aggressive blood pressure control is just as important as glycemic control. Systolic blood pressure level should be the major factor for detection, evaluation, and treatment of hypertension. The use of two or more blood pressure lowering agents is often required to meet blood pressure goal. (Annotations #13, 14 )
+
Prevent microvascular complications through annual or biannual eye exams, foot risk assessments and foot care counseling, and annual screening for proteinuria. (Annotation # 18)
+
Initial therapy with lifestyle treatment and metformin is advised unless contraindicated. (Annotations #3, 10)
+
Diagnosis and Management of Type 2 Diabetes Mellitus Algorithm Annotations
+
Diagnostic Testing for Diabetes
+
Recommendation:
+
Type 2 diabetes is frequently not diagnosed until complications appear, and approximately one-third of all people with diabetes may be undiagnosed [Guideline]. Possible tests to assess for diabetes include a fasting plasma glucose , an oral glucose tolerance test or an A1c measurement .
+
+
The decision about which test to use is at the discretion of the health care professional and may be influenced by health care coverage [Guideline].
+
+
Patients presenting with symptoms of diabetesshould be tested .
+
+
Risk factors for diabetes include:
+
Risk factors for atherosclerosis : smoking, hypertension, dyslipidemia
+
Age, race/ethnicity, family history of diabetes, prior history of diabetes, physical inactivity, cardiovascular disease, cerebral vascular disease, hyperlipidemia, overweight/obese (as defined by body mass index), low high-density lipoprotein, high triglycerides, polycystic ovarian syndrome
+
Gestation history of an infant weighing more than nine pounds, toxemia, stillbirth or previous diagnosis of gestational diabetes.
+
+
Testing patients with hypertension, dyslipidemia or heart disease is also recommended .
+
+
See the NGC summaries of the ICSI guidelines Hypertension Diagnosis and Treatment, Lipid Management in Adults, Preventive Services for Adults, Prevention and Management of Obesity (Mature Adolescents and Adults) and Stable Coronary Artery Disease for more information.
+
Diagnosis of Prediabetes
+
+
Prediabetes: Prediabetes is defined as hyperglycemia not sufficient to meet the diagnostic criteria for diabetes, but that which is associated with an increased risk of progression to type 2 diabetes mellitus. Diagnosis of prediabetes is made when an individual meets one or more of the following criteria:
+
A1c 5.7% to 6.4% (as measured according to laboratory specifications in Annotation #4)
+
Fasting plasma glucose of 100 mg/dL to 125 mg/dL
+
Oral glucose tolerance test two-hour plasma glucose: 140 mg/dL to 199 mg/dL
+
+
[Guideline]
+
Treatment to Prevent or Delay the Progression to Diabetes
+
Recommendation:
+
Patients who are identified with prediabetesshould be referred for education and lifestyle interventions .
+
+
Health care clinicians should follow up with patients diagnosed with prediabetes on an annual basis to monitor their progress and review treatment goals [Guideline].
+
+
Intensive lifestyle change programs have been proven effective in delaying or preventing the onset of diabetes by about 50%. Effective lifestyle changes include setting achievable goals, obtaining weight loss when needed (ideally at least 5% total body weight), and increasing physical activity [High Quality Evidence].
+
Lifestyle modifications, such as nutrition, exercise and even modest weight loss, are recommended for prevention or delayed progression of patients with prediabetes.
+
Pharmacotherapy, such as metformin, is effectivein some patients with prediabetes .
+
+
[Conclusion Grade II: See Conclusion Grading Worksheet A - Annotation #3 (Prediabetes) in the original guideline document]
+
+
The following initial approaches are recommended for people with prediabetes :
+
Intensive lifestyle behavioral change including a nutrition and activity plan by a registered dietitian, health educator or other qualified health professional . Ongoing support of behavioral change is necessary.
+
Cardiovascular risk reduction appropriate to the needs of the individual .
+
+
Patients who respond to lifestyle interventions :
+
Annual follow-up and reassessment of risks for developing diabetes [Guideline, Moderate Quality Evidence, High Quality Evidence, Low Quality Evidence]
+
+
Patients who are high risk and not responding to lifestyle interventions :
+
Intensify education and counseling on lifestyle interventions .
+
There is some evidence of prevention of diabetes through pharmacotherapy with biguanides and alpha glycosidase inhibitors [High Quality Evidence]. Lifestyle change remains the preferred method to prevent diabetes [High Quality Evidence].
+
Diagnosis of Type 2 Diabetes
+
+
Type 2 Diabetes Mellitus : Type 2 diabetes is defined as diabetes that results from a progressive insulin secretory defect on the background of insulin resistance. The diagnosis of diabetes is made when an individual meets one or more of the following criteria:
+
A1c ?6.5% on two occasions
The A1c test should be performed in a laboratory using a method that is National Glycohemoglobin Standardization Program certified and standardized to the Diabetes Control and Complications Trial assay.
+
+
Fasting plasma glucose of greater than or equal to 126 mg/dL (7.0 mmol/L)
Fasting is defined as no caloric intake for at least eight hours.
+
+
Oral glucose tolerance test - two-hour plasma glucose of 200 mg/dL (11.1 mmol/L) on two occasions
The oral glucose tolerance test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water.
+
+
Symptoms of diabetes and a casual plasma glucose of greater than or equal to 200 mg/dL (11.1 mmol/L)
Casual is defined as any time of day without regard to time since last meal.
+
The classic symptoms of diabetes include polyuria, polydipsia and unexplained weight loss, excessive hunger, fatigue or wounds that are slow to heal or frequent skin infections .
+
+
Notes:
+
In the absence of unequivocal hyperglycemia , an abnormal A1c, fasting glucose or oral glucose tolerance test result that meets criteria for diabetes should be confirmed by repeat testing before assigning a diagnosis of type 2 diabetes.
+
It is preferable that the same test be repeated for confirmation of diabetes. There may be cases in which two different tests are available (e.g., A1c and fasting glucose). If both tests meet diagnostic criteria for diabetes, then diagnosis of diabetes can be made.
+
If two different tests are available and are discordant (e.g., A1c ?6.5%, fasting glucose <126 mg/dL), then the test whose result is above the diagnostic threshold should be repeated . If it is again above the diagnostic threshold on repeat testing, then a diagnosis of diabetes can be assigned.
+
+
[Guideline, Reference]
+
Evaluation of Patients Who Meet Criteria for Type 2 Diabetes
+
+
Evaluation may be completed in one or more visits over a reasonably short period of time. Clinical judgment is needed to determine the urgency of completing the evaluation.
+
+
History [Guideline]
+
Symptoms
+
Eating habits, weight history
+
Physical activity
+
Prior or current infections, particularly skin, foot, dental, and genitourinary Symptoms and treatment of chronic complications associated with diabetes: eye, heart, kidney, nerve, genitourinary (including sexual function), peripheral vascular, and cerebrovascular (these may be present at diagnosis)
+
Current medications including over-the-counter medications, dietary supplements and alternative therapies with a focus on medications known to induce diabetes-type states (e.g., steroids, atypical antipsychotics)
+
Psychosocial, cultural, and economic factors that might influence the management of diabetes
+
Alcohol/drug use
+
+
Physical Examination [Guideline]
+
Weight, height, body mass index (BMI), blood pressure
+
Cardiovascular system: heart, blood pressure, peripheral vascular including pulses and bruits (abdominal, carotid, femoral)
+
Feet: nails, web spaces, ulcers, pulses, calluses, structural deformities, protective sensation and shoes
+
Other examinations as guided by the patient's symptoms and/or concerns:
Skin: infections or diseases such as acanthosis nigricans, xanthoma
+
Neurological symptoms: sensory state of hands and feet, muscle wasting, deep tendon reflexes
+
Mental health: screen for depression and/or anxiety
+
Referral to an eye specialist to assess optic health
+
Referral to a dentist to assess oral health
+
+
Laboratory Evaluation
+
Fasting plasma glucose or random plasma glucose
+
A1c
+
Lipid profile: total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides
+
Serum creatinine and liver function test (alanine aminotransferase [ALT] and aspartate aminotransferase [AST])
+
Urine: ketones, glucose, protein, microalbuminuria, culture if microscopic is abnormal or symptoms of infection present
+
Urine microalbumin tests can identify patients with early diabetic nephropathy when intervention may be most effective in delaying or preventing end stage renal disease. Single tests for urinary microalbumin and urinary creatinine can accurately detect urinary microalbumin excretion. Increased urinary microalbumin is a predictor of increased cardiovascular mortality [Guideline].
+
Should Patient Be Hospitalized?
+
+
Inpatient care may be appropriate in the following situations [Guideline]:
+
Elderly patients with infection or illness, weight loss, dehydration, polyuria or polydipsia
+
Life-threatening acute metabolic complications of diabetes :
Hyperglycemic hyperosmolar state with impaired mental status, elevated plasma osmolality that includes plasma glucose greater than 600 mg/dL
+
Diabetic ketoacidosis with a plasma glucose greater than 250 mg/dL, arterial pH less than 7.30 and serum bicarbonate level less than 15 mEq/L and the presence of moderate ketonuria and/or ketonemia
+
Hypoglycemia with neuroglycopenia that includes blood glucose less than 50 mg/dL and treatment has not resulted in prompt recovery, coma, seizures or altered behavior
+
+
Uncontrolled insulin-requiring diabetes during pregnancy
+
Surgery, infection, steroids - if these conditions cause significant hyperglycemia and rapid initiation of rigorous insulin is needed
+
Inpatient Diabetes Management
+
+
The following are recommended in the inpatient setting [Guideline, Low Quality Evidence]:
+
Insulin therapy with intravenous insulin in critically ill patients [Moderate Quality Evidence]
+
Oral glycemic agents may need to be held or the dose adjusted if the patient is hospitalized. Insulin therapy is recommended for many patients during hospitalization.
+
Use of scheduled insulin, with basal coverage (improves glucose control compared to sliding scale coverage alone)
+
For insulin-deficient patients, despite reductions or the absence of caloric intake , basal insulin must be provided to prevent diabetic ketoacidosis.
+
Target preprandial plasma glucose levels are 90 to 140 mg/dL [Guideline, High Quality Evidence, Low Quality Evidence]
+
The random target plasma glucose is less than 180 mg/dL [Guideline, High Quality Evidence, Low Quality Evidence]
+
Hypoglycemia is <70 mg/dL and should be treated with a protocol [Guideline, Low Quality Evidence] Establishing a multidisciplinary team that sets and implements institutional guidelines, protocols, and standardized order sets for the hospital results in reduced hypoglycemic and hyperglycemic events.
+
+
Other considerations include [Low Quality Evidence]:
+
For patients who are alert and demonstrate accurate insulin self-administration and glucose monitoring, insulin self-management should be allowed as an adjunct to standard nurse-delivered diabetes management.
+
Patients with no prior history of diabetes who are found to have hyperglycemia (random fasting blood glucose greater than 125 mg/dL or random glucose of 200 mg/dL or more) during hospitalizationshould have follow-up testing for diabetes within 1 month of hospital discharge [Low Quality Evidence].
+
+
See Appendix A, "Order Set: Subcutaneous Insulin Management," in the original guideline document for more information.
+
Does Patient Need Outpatient Stabilization?
+
+
Indications for immediate insulin treatmentin type 2 diabetes mellitus [High Quality Evidence], [Reference]:
+
Severe symptoms, marked weight loss, polyuria, polydipsia
Fasting plasma glucose greater than 300 mg/dL fasting, or
+
Random glucose over 350 mg/dL, or
+
A1c over 10%, or
+
Presence of ketonuria
+
+
Insulin therapy may not be permanent once patient is stabilized.
See Annotation #21, "Prescribe Insulin Therapy," for prescribing information.
+
+
At presentation, all patients should be instructed on glucose monitoring, hypoglycemia recognition and treatment, and how/when to contact health care support . Patients should check glucose frequently when insulin is initiated . Patients should receive daily phone or visit contact for at least 3 days and have 24-hour emergency phone support if needed .
+
+
Patients should be seen timely for nutrition and diabetes education (e.g., within 1 to 7 days).
+
+
Insulin therapy may not be permanent, particularly if oral agents are added or if, at presentation, the patient is in metabolic stress such as infections, acute metabolic complications, recent surgery [Low Quality Evidence]. As the metabolic stress resolves, the insulin dose requirements may rapidly fall.
+
+
For the occasional unstable patient with type 2 diabetes, maximal doses of oral hypoglycemic agents may afford an approach to the patient who is psychologically resistant to or refuses insulin initiation.
+
Recommend Education and Self-Management
+
Recommendations:
+
Nutrition
+
Patients with prediabetes or diabetesshould receive individualized medical nutrition therapy (MNT) , preferably provided by a registered dietitian knowledgeable in the components of diabetes MNT, as needed, to achieve treatment goals.
+
Weight loss is recommendedfor all overweight or obese patients who have or are at risk for diabetes . For weight loss, calorie-restricted diets - either low-carbohydrate, low-fat or Mediterranean - can be effective for up to two years.
+
Utilize meal plans that incorporate a mix of carbohydrate, protein and fat, and are adjusted to meet metabolic goals, individual preferences and recommended daily allowances/recommended daily intakes (RDAs/DRIs) .
+
Monitor carbohydrate by carbohydrate counting, choices or experience-based estimation to achieve glycemic control.
+
Reduction of saturated fat, trans fats and cholesterol intake, an increase in omega-3 fatty acids, soluble fiber, plant sterols/stanols is recommended to improve lipid profiles.
+
Include Dietary Approaches to Stop Hypertension (DASH)-style dietary pattern in lifestyle therapy for hypertension along with weight loss (if overweight) and increased physical activity.
+
Physical Activity
+
Perform at least 150 minutes/week of moderate-intensity aerobic physical activity (50%-70% of maximum heart rate) spread over at least three days per week with no more than two consecutive days without exercise .
+
In the absence of contraindications , encourage performance of resistance training at least three times per week .
+
Weight Management
+
Lifestyle change should be the primary approach to weight loss.
+
Weight loss programs should include physical activity and behavior modification.
+
Bariatric surgery may be considered for adults with BMI >35 if diabetes or comorbidities are difficult to control with lifestyle and pharmacologic therapy.
+
Diabetes Self-Management Education (DSME)
+
+
People with diabetesshould receive DSME according to national standards and diabetes self-management supportwhen their diabetes is first diagnosed and as needed thereafter .
+
+
DSME should address psychosocial issues, since emotional well-being is associated with positive diabetes outcomes.
+
Nutrition Therapy
+
+
Medical nutrition therapy for diabetes emphasizes improving metabolic outcomes by modifying nutrient intake and lifestyle. Major goals are to attain and maintain in the normal or as close to normal range as is safely possible glucose, blood pressure, and lipid/lipoprotein levels. These prevent or slow the development of chronic complications of diabetes [Guideline].
+
+
The priority for nutrition therapy for type 2 diabetes is to implement lifestyle strategies that will reduce hyperglycemia and hypertension and improve dyslipidemias [Guideline]. Because many individuals are insulin resistant and overweight or obese, nutrition therapy often begins with strategies that reduce energy intake and increase energy expenditure through physical activity. Many individuals may have already tried unsuccessfully to lose weight and it is important to note that lifestyle strategies, independent of weight loss, can improve glucose control and risk factors for cardiovascular disease.
+
+
Moderate weight loss (5% of body weight) is associated with decreased insulin resistance, improved measures of glycemia and lipidemia, and reduced blood pressure. The optimal macronutrient distribution of weight loss diets has not been established.
+
+
Restricting total carbohydrate to less than 130 g/day is not recommended in the management of diabetes [Guideline].
+
+
Appropriate nutrition therapy will be developed collaboratively with the person who has diabetes . Instruction may require a clinician with expertise in medical nutrition therapy, and instruction may be obtained through individual or group consultation [Low Quality Evidence]. It is important that clinicians understand the general principles of medical nutrition therapy and support them for patients with diabetes. In most people, nutrition recommendations are similar to those of the general population.
+
Evaluate the patient's current eating habits and modify as needed . Recommend:
Working together toward gradual, realistic and culturally appropriate lifestyle change goals
+
Maintaining the pleasure of eating by limiting only food choices indicated by scientific evidence
+
Healthful food choices: foods containing carbohydrates from whole grains, fruits, vegetables, legumes, and low fat milk should be included in a healthy eating plan.
+
Reducing total caloric intake by moderating food/beverage and limiting total fat intake
+
Distributing carbohydrates evenly throughout the day to smaller meals and snacks
+
Monitoring carbohydrates remains a key strategy in achieving glycemic control, whether by carbohydrate counting, exchanges, or experience-based estimation [Guideline]
+
If one chooses to drink alcohol, and has not been cautioned against it, limit intake to one drink per day for women and two drinks per day for men, according to U.S. Department of Agriculture (USDA) guidelines. A drink is defined as 12 oz. of regular beer, 5 oz. of wine, or 1.5 oz. of 80-proof distilled spirits. To reduce the risk of hypoglycemia, alcohol should be consumed with food.
+
+
Individualize the nutrition prescription based on the nutrition assessment and treatment goals of each patient . For example, if the patient has been eating 45% of calories from fat, lowering fat to even 40% can be helpful.
+
+
Carbohydrate [Guideline]
+
+
Both the quantity and the type or source of carbohydrate in food influences post-prandial glucose levels.
+
+
For individuals with diabetes, the use of glycemic index and glycemic load may provide a modest additional benefit for glycemic control over that observed when total carbohydrate is considered alone.
+
+
Sucrose (e.g., table sugar) and sucrose-containing foods do not need to be restricted. However, they should be substituted for other carbohydrate sources, or if added, covered with insulin or other glucose-lowering medication. They should be eaten within the context of a healthy diet and avoid excess energy intake.
+
+
Added fructose as a sweetening agent is not recommended as it may adversely affect plasma lipids. Naturally occurring fructose in fruits, vegetables and other foods does not need to be avoided.
+
+
The use of sugar alcohols, such as sorbitol or mannitol in small amounts, appears to be safe; however, they may cause gastrointestinal side effects [Guideline]. Sugar alcohols and non-nutritive sweeteners are safe when consumed within the acceptable daily intake levels established by the Food and Drug Administration.
+
+
Encourage consuming a wide variety of fiber-containing foods such as legumes, fiber-rich cereals, fruits, vegetables and whole grain products to achieve fiber intake goals of 14 g/1,000 calories.
+
+
Protein [Guideline]
+
+
15%-20% of the total calories. Avoid protein intakes of greater than 20% of total daily energy . The long-term effects of consuming more than 20% of energy as protein on the development of nephropathy have not been determined. High-protein diets are not recommended as a method of weight loss at this time.
+
+
Reduction of protein intake to 0.8-1 g/kg in individuals with diabetes in the earlier stages of chronic kidney disease and to 0.8 g/kg in the later stages of chronic kidney disease is recommended and may improve measures of renal function (urine albumin excretion rate, glomerular filtration rate).
+
+
Protein does not increase plasma glucose concentrations but does increase serum insulin responses, and thus protein should not be used to treat acute or prevent nighttime hypoglycemia.
+
+
Fat [Guideline]
+
+
Patients with normal weight and lipids : continue maintaining healthy weight and lipids that include less than or equal to 30% calories from fat, less than 7% saturated fats, limit of trans fats, and less than 200 mg cholesterol [Consensus Statement]
+
+
Patients with elevated cholesterol and low-density lipoprotein cholesterol : implement National Cholesterol Education Program-Therapeutic Lifestyle recommendations . Program-Therapeutic Lifestyle diet: reduce saturated fat to less than 7% calories and cholesterol to less than 200 mg, consider increased soluble fiber intake (10-25 g/day) and plant stanols/sterols (2 g/day), and minimize trans fat intake .
+
+
Two or more servings of fish per week (with the exception of commercially fried fish fillets) provide omega-3 fatty acids and are recommended .
+
+
Patients with elevated triglycerides : improve glucose control , encourage weight loss , increase physical activity , moderate carbohydrate intake and limit dietary saturated fat and trans fat . Increase consumption of omega-3 fatty acids from fish or supplements , which has been shown to reduce adverse cardiovascular outcomes [Systematic Review].
+
+
Sodium [Guideline]
+
+
Medical nutrition therapy for hypertension focuses on the use of the DASH diet including reducing sodium intake (to <1,500 mg/day) and excess body weight, increasing consumption of fruits and vegetables (8-10 servings per day) and low-fat dairy products (2-3 servings/day), and avoiding excess alcohol consumption.
+
+
Supplements [Guideline]
+
+
Routine supplementation with antioxidants, such as vitamins E and C and carotene, is not advised because of lack of evidence of efficacy and concern related to long-term safety.
+
+
Benefit from chromium supplementation in people with diabetes or obesity has not been conclusively demonstrated and, therefore, cannot be recommended.
+
+
Patients should be provided with ongoing nutrition self-management and care support [Guideline].
+
Physical Activity
+
+
People with diabetesshould perform at least 150 minutes a week of moderate intensity activity (50%-70% maximum heart rate) , and resistance training three times a weekunless contraindicated .
+
+
The positive benefits of physical activity include improved blood pressure values, improved lipid profile, improved cardiac status, increased insulin sensitivity, more effective weight management, and improved glycemic control, and it helps in the management of depressive symptoms. Because the positive effects of increased physical activity diminish within days of the cessation of exercise, regular activity is recommended [Low Quality Evidence].
+
+
Reinforce the ongoing need and benefits of physical activity at each visit, offering support and advice on ways to incorporate 30 minutes of physical activity into most days of the week [Consensus Statement].
+
+
Results of self-monitoring glucose can be useful in preventing hypoglycemia and adjusting medications, medical nutrition therapy and physical activity.
+
+
Hypoglycemia is a risk in individuals who participate in physical activity and are taking insulin, sulfonylureas and/or meglitinides. Depending on the level of physical activity, the medication dosage or the amount of carbohydrate ingested, hypoglycemia can occur. For patients on these drug classes and pre-exercise glucose monitor results less than 100 mg/dL, additional carbohydrate should be ingested for prevention of hypoglycemia [Guideline].
+Strategies for Initiation of Increased Physical Activity
Start by incorporating 10 minutes of increased activity into each day.
Use stairs instead of elevator.
+
Park car away from building entrance and walk.
+
Walk to do errands.
+
+
Overcome barriers
Self-monitor activity performed using pedometer, time record, and/or journal.
+
Be consistent.
+
Have alternative activities for inclement weather.
+
Find enjoyable activities.
+
Be active at the time of day that is best for the individual.
+
Doing a physical activity with a partner and/or being accountable to someone regarding your progress greatly improves the ability to be successful [Guideline].
+
+
Medical Evaluation to Assess Safety of Exercise Program
+
Assess physical condition and limitations of the patient .
+
+
Assess for cardiovascular disease . Atypical symptoms and painless ischemia are more common in patients with diabetes [Low Quality Evidence].
+
+
Cardiac stress testing: there is no evidence that stress testing is routinely necessary in asymptomatic people before beginning a moderate-intensity exercise program such as walking.
+
+
Cardiac stress testing should be consideredfor the previously sedentary individual at moderate to high-risk for cardiovascular disease or other patients who are clinically indicated who want to undertake vigorous aerobic exercise that exceeds the demands of everyday living [Guideline].
+
+
Assess blood glucose control .
+
+
Assess knowledge of physical activity in relation to blood glucose control .
+
+
When making a referral , make other health care clinicians aware of limitations for exercise .
+
+
Physical activity can be intermittent or cumulative [Narrative Review], [Consensus Statement], [Low Quality Evidence].
+
Weight Management
+
+
Weight loss is also an important goal because it improves insulin resistance, glycemic control, blood pressure and lipid profiles. Moderate weight loss (5% of body weight) can improve fasting blood glucose in many overweight or obese persons [Narrative Review].
+
+
Physical activity and behavior modification are important components of weight loss programs and are most helpful in maintenance of weight loss.
+
+
Structured programs that emphasize lifestyle changes including education, reduced energy and fat intake (approximately 30% of total energy), regular physical activity and frequent participant contact are necessary to produce long-term weight loss of 5% to 7% of starting weight. Lifestyle change should be the primary approach to weight loss [Guideline].
+
+
Identification of the optimal mix of macronutrients for diabetes meal plans is unlikely. The best mix of carbohydrate, protein and fat appears to vary depending on individual circumstances but must be appropriate for individual metabolic status, total calories for weight management goal and/or food preferences. A variety of meal patterns is likely effective, including Mediterranean-style, plant-based (vegan or vegetarian), low-fat and lower-carbohydrate eating patterns [Guideline].
+
+
Long-term metabolic effects of very-low-carbohydrate diets are unclear, and such diets eliminate important sources of energy, fiber, vitamins and minerals [Guideline]. For patients on low-carbohydrate diets, monitor lipid profiles, renal function and protein intake (in those with nephropathy), and adjust hypoglycemic therapy as needed [Guideline].
+
+
When usual measures to promote weight loss are unsuccessful in severely obese individuals with comorbidities, there may be a role for adjunctive pharmacotherapy or surgical procedures.
+
+
There is some evidence that pharmacotherapy for weight loss may offer short-term benefit for a subset of patients with type 2 diabetes [High Quality Evidence]. The studies, however, were of relatively weak design, and pharmacotherapy for weight loss cannot be recommended for most patients with type 2 diabetes.
+
+
Bariatric surgery has recently been discussed as an option for some individuals with type 2 diabetes who have a body mass index of 35 kg/m2 or more. Bariatric surgery can result in marked improvements in glycemia; however, the long-term benefits and risks need to be studied further [Guideline].
+
+
Please see the NGC summary of the ICSI guideline Prevention and Management of Obesity (Mature Adolescents and Adults) for more information.
+
Education for Self-Management
+
+
Adequate self-management support for patients requires integration of available self-management education and support resources into routine care. Usually appropriate education may require the expertise of the diabetes educator. This instruction can be obtained through individual or group consultation [Low Quality Evidence]. Medicare reimbursement for diabetes self-management training requires this service be provided by an education program that has achieved recognition by the American Diabetes Association or American Association of Diabetes Educators; the staff in such a program are multidisciplinary and include at least a registered dietitian and a registered nurse with experiential preparation in education and diabetes management [Low Quality Evidence]. A number of studies involving a clinical pharmacist in program with cardiac risk factors in select patients with diabetes have proven to be effective [Low Quality Evidence]. Clinicians should be aware of culturally appropriate educational and community resources to support persons with diabetes and their families.
+
+
An education plan should be identified based on the needs of the individual and referral made to either an internal or external education resource. Periodic reassessment of educational goals is recommended [Low Quality Evidence].
+
+
See the Implementation Tools and Resources Table in the original guideline document for a list of American Diabetes Association-recognized education programs available.
+
Components of self-management include:
+
Description of the diabetes disease process and treatment options
+
Goal setting to promote health, and problem solving for daily living
+
Preventing, detecting, and treating acute complications
+
Preventing (through risk reduction behavior), detecting, and adhering to treatments for chronic complications
+
Self-monitoring blood glucose, ketones (when appropriate), and using results to improve control
+
Incorporation of appropriate nutrition management [Low Quality Evidence]
+
Incorporation of physical activity into lifestyle [Low Quality Evidence]
+
Utilizing medications (if applicable) for therapeutic effectiveness
+
Awareness of culturally appropriate community resources/support for persons with diabetes mellitus and their families, and ability to access community resources
+
Psychosocial adjustment to daily life
+
Promotion of preconception care, counseling, and management during pregnancy, if applicable
+
Foot Care Education
+
+
Education should be tailored to patient's current knowledge, individual needs, and risk factors. Patients should be aware of their risk factors and appropriate measures to avoid complications [Guideline, Low Quality Evidence]. (See Annotation #18, "Maintain Treatment Goals and Address Complications, the "Comprehensive Foot Exam with Risk Assessment" section below.)
+
+
Education should cover:
+
Self-inspect feet daily for cuts, bruises, bleeding, redness, and nail problems .
+
Wash feet daily and dry thoroughly including between the toes .
+
Do not soak feet unless specified by a health care clinician.
+
Be careful of hot water.
+
Use of lotions, creams or moisturizer is acceptable, but do not use between the toes.
+
Do not walk barefoot.
+
Check shoes each day for objects that may have fallen inside, excessive wear, or areas that may cause irritation .
+
Avoid injuries from cutting toenails; avoid self-cutting calluses or corns.
+
+
When to seek care
+
+
+
Community Resources
+
+
There is some evidence for the effectiveness of community-based diabetes self-management education and support. These programs may complement the care and education that are routinely part of standard medical practice, and may enhance a patient's ability to self-manage diabetes. The Task Force on Community Preventive Services, supported by the Centers for Disease Control and Prevention, recommends diabetes self-management education in community gathering places.
+
Set Personalized A1c Goal: A1c Less Than 7% or Individualized to a Goal Less Than 8% Based on Factors in 11a
+
(see the algorithm box 11a in the original guideline document)
+
Recommendations:
+
Set personalized A1c goal to less than 7% or less than 8% based on the risks and benefits for each patient.
+ This recommendation places high value on trying to optimize the balance of risks versus benefits of more intensive glycemic control for each individual. Potential risks of <7% may include higher mortality rates, hypoglycemia, and weight gain. Potential benefits may include lower risk of diabetes complications such as retinopathy, nephropathy and heart disease. Individual patient factors that may increase risks include known cardiovascular disease, history of severe hypoglycemia, polypharmacy-related challenges, limited life expectancy, cognitive impairment and extensive comorbid conditions.
+
Blood glucose goals should be individualized according to the patient's A1c goals and treatment plan.
+ This recommendation places a high value on using self-monitored blood glucose (SMBG) values to guide treatment decisions, but this benefit may not be equal for patients and is probably more helpful in patients having trouble reaching or sustaining A1c goals and in those treated with insulin. This recommendation places a relatively low value on the burden and cost of SMBG testing.
+
+
A1c target in type 2 diabetes is aimed at reducing microvascular complications while not increasing risk of morbidity or mortality. All patients with type 2 diabetes should aim to achieve an A1c less than 8%. This will reduce microvascular disease and not increase risk substantially. Many patients with type 2 diabetes may derive additional benefit in reduction of microvascular disease by reaching a target A1c less than 7% and not increase risks as long as the target is not A1c less than 6%. For patients with type 2 diabetes and the following factors, an A1c goal of less than 8% may be more appropriate than an A1c goal of less than 7% [High Quality Evidence], [Moderate Quality Evidence]. [Conclusion Grade II: See Conclusion Grading Worksheet B - Annotation #11 (A1c) in the original guideline document].
+
+
Known cardiovascular disease or high risk cardiovascular risk. Cardiovascular risk can be determined by the Framingham or the United Kingdom Prospective Diabetes Study (UKPDS) risk equations, or alternatively as having two or more cardiovascular risks (BMI >30, hypertension, dyslipidemia, smoking and microalbuminuria).
+
Inability to recognize and treat hypoglycemia, history of severe hypoglycemia requiring assistance
+
Inability to comply with standard goals, such a polypharmacy issues
+
Limited life expectancy or estimated survival of less than 10 years
+
Cognitive impairment
+
Extensive comorbid conditions such as renal failure, liver failure, and end-stage disease complications
+
+
The clinician and patient should discuss and document specific treatment goals and develop a plan to achieve all desired goals. A multifactorial approach to diabetes care that includes emphasis on blood pressure, lipids, glucose, aspirin use, and non-use of tobacco will maximize health outcomes far more than a strategy that is limited to just one or two of these clinical domains [Guideline], [Moderate Quality Evidence], [High Quality Evidence].
+
Glycosylated Hemoglobin Assays
+
+
Glycosylated hemoglobin assays provide an accurate indication of long-term glycemic control. A1c is formed by the continuous non-enzymatic glycosylation of hemoglobin throughout the lifespan of an erythrocyte. This assay yields an accurate measure of time-averaged blood glucose during the previous six to eight weeks. Clinically it can assist in determining duration and severity of hyperglycemia and can help guide treatment.
+
+
Eating, physical activity or acute metabolic stress do not influence the A1c test. The test can be done at any time of day and does not require fasting.
+
+
Glucose should also be used to assess level of glycemic control, in addition to A1c. It is appropriate to determine need for medication changes based on blood glucose whenever this information is available.
+
Self-Monitoring Blood Glucose (SMBG)
+
+
Major clinical trials assessing the impact of glycemic control on diabetes complications have included SMBG as part of multifactorial interventions, suggesting that self-monitoring blood glucose is a component of effective therapy [Guideline]. Several diabetes management strategies reliant on SMBG testing have demonstrated improved glucose control in patients [High Quality Evidence], [Moderate Quality Evidence]. Refer to Table 1 in the original guideline document for information on ranges of self-monitored glucose readings that would be expected as goals for patients with the corresponding A1c levels. More than half of the plasma blood glucose readings should fall in the desired goal range. Bedtime glucose goals vary dependent on the patient's treatment program, risks for hypoglycemia and time after last meal.
+
+
Self-monitoring blood glucose allows patients to evaluate their individual response to therapy and assess whether glucose targets are being achieved. Results of SMBG can be useful in preventing hypoglycemia and adjusting medications, medical nutrition therapy and physical activity [Low Quality Evidence].
+
+
The frequency and timing of SMBG should be dictated by the particular needs and goals of the individual patient. Patients with type 2 diabetes on insulin typically need to perform SMBG more frequently than those not using insulin, particularly if using glucose readings to guide mealtime insulin dosing. It is recommended that patients using multiple insulin injections perform SMBG three or more times daily [Guideline]. The optimal frequency and timing of SMBG for patients with type 2 diabetes on oral agent therapy are not known but should be sufficient to facilitate reaching glucose goals. SMBG should be performed more frequently when adding or modifying therapy; two-hour postprandial glucose testing is useful in some patients. The role of SMBG in stable diet-treated patients with type 2 diabetes is not known.
+
+
Because the accuracy of SMBG is instrumental and user dependent, it is important for health care clinicians to evaluate each patient's monitoring technique and accuracy of equipment. In addition, optimal use of SMBG requires proper interpretation of the data. Patients should be taught how to use the data to adjust food intake, exercise or pharmacological therapy to achieve specific glycemic goals.
+
+
See the original guideline document for information on ranges of self-monitored blood glucose values for various A1c goals.
+
Cardiovascular Risk Factor Treatment Goals for Patients without Cardiovascular Disease
+
Recommendations:
+
+
The following treatment goals should be achieved:
+
Use of statins in all adult type 2 diabetes patients if tolerated; statins should be titrated to achieve low-density lipoprotein cholesterol of less than 100 mg/dL without coronary artery disease.
+
Blood pressure less than 140/90 mm Hg.
+
Smoking cessation if indicated.
+
Daily aspirin use is optional for primary prevention of cardiovascular events.
+
+
This recommendation places a high value on a multifactorial approach to lowering the cardiovascular risk of patients with diabetes. The recommendation does not place value on prioritizing these treatment interventions, and some may be more important than others for different individuals. For the lipid and blood pressure recommendations, there is low value placed on the burden of these treatment approaches, the age of the patient (the evidence is less established in patients under age 40 and over 75), and whether patients can tolerate the treatments needed to obtain the recommended goals without side effects. The aspirin recommendation places high value on assessing an individual's age and risk of bleeding related to aspirin use prior to recommending it for primary prevention.
+
+
The clinician and patient should discuss and document specific treatment goals and develop a plan to achieve all desired goals. A multifactorial approach to diabetes care that includes emphasis on blood pressure, lipids, glucose, aspirin use and non-use of tobacco will maximize health outcomes far more than a strategy that is limited to just one or two of these clinical domains [Guideline], [Moderate Quality Evidence], [High Quality Evidence].
+
Consider Statin , Unless Contraindicated
+
+
Seventy to seventy-five percent of adult patients with diabetes die of macrovascular disease, specifically coronary, carotid and/or peripheral vascular disease. Diabetes is considered a coronary artery disease equivalent. Dyslipidemia is a known risk factor for macrovascular disease. Patients with diabetes develop more atherosclerosis than patients without diabetes with the same quantitative lipoprotein profiles. In most patients with diabetes, use of a statin can reduce major vascular events in patients with diabetes substantially [High Quality Evidence]. Beneficial effects of statins on cardiovascular risk reduction may go beyond their effects on lipid levels.
+
+
For patients with type 2 diabetes mellitus , consider the use of a statin . Randomized controlled trials, including a number of large trials, and observational data consistently show a benefit of statin therapy for patients with type 2 diabetes. Some studies also report that statin therapy was well tolerated in these patients. None of these studies was able to assess long-term effects of statin treatment/use. [Conclusion Grade I: See Conclusion Grading Worksheet C - Annotations #13, 14 (Statin Use) in the original guideline document]. However, doses of simvastatin greater than 40 mg may potentially increase risk of myopathy [High Quality Evidence]. Evidence [High Quality Evidence] and Adult Treatment Panel III consensus guidelines [Low Quality Evidence] suggest that statins are beneficial for high-risk patients ages 40 to 80 years with a 10-year risk of cardiovascular event of more than 20% based on Framingham or UKPDS risk calculators, even with baseline untreated low-density lipoprotein of less than 100 mg/dL [Low Quality Evidence].
For additional information on statin therapy, refer to the NGC summary of the ICSI guideline Lipid Management in Adults.
+
LDL Less Than 100 mg/dL or on a Statin
+
+
The LDL cholesterol goal for people with diabetes mellitus without coronary artery disease is less than 100 mg/dL .
+
+
Three pathways to improve lipids are:
+
Medical nutrition therapy
+
Increased physical exercise
+
Pharmacotherapy
+
+
Intensify statin to meet LDL cholesterol goals [High Quality Evidence]. If the LDL goal cannot be met with high-dose statin therapy, there is not current evidence to prove that adding LDL-lowering drug classes will improve outcomes for people with diabetes. A combination of statin and ezetimibe versus statin monotherapy has not been proven advantageous.
+
+
High triglycerides and low high-density lipoprotein cholesterol levels are independent risk factors for cardiovascular disease in the patient with diabetes [Guideline]. Individuals with elevated triglycerides have significant cardiovascular risk reduction with the use of fibrates [High Quality Evidence] or statins [High Quality Evidence].
+
+
The current evidence does not support the use of combination therapy with statins and other lipid drugs for most patients with type 2 diabetes. The combination of statin plus ezetimibe versus statin monotherapy has not been proven advantageous [High Quality Evidence]. The National Institutes of Health-sponsored ACCORD lipid study showed no significant reduction in myocardial infarct, stroke or cardiovascular death with a fibrate-statin combination compared to statin monotherapy. However, a subgroup analysis of the primary outcome suggested that there was a gender effect with a possible benefit for men and possible harm for women, as well as a possible benefit for men and women with both low HDL (<34 mg/dL) and elevated triglycerides (>204 mg/dL). AIM-HIGH was a study designed to evaluate the cardiovascular outcomes with niacin and statin combination therapy compared to statin monotherapy in patients with coronary heart disease, including a subgroup with diabetes. The study was stopped early in 2011 because of lack of benefit compared to statin therapy alone, including the diabetes subgroup [Moderate Quality Evidence].
+
Goals for Blood Pressure Control: Blood Pressure Less Than 140/90 mm Hg
+
+
Uncontrolled hypertension is a major cardiovascular risk factor that also accelerates the progression of diabetic nephropathy [Low Quality Evidence]. When hypertension is identified, it should be aggressively treated to achieve a target blood pressure of less than 140/90 mm Hg. In many patients with diabetes , two or three or more antihypertensive agents may be needed to achieve this goal. The use of generic combination tablets (such as angiotensin-converting enzyme [ACE] inhibitor plus calcium-channel blocker, or beta-blocker plus diuretic) can reduce the complexity of the regimen and out-of-pocket costs.
+
+
Several studies support a systolic blood pressure goal <140 mm Hg for people with type 2 diabetes. The work group would estimate that targeting a systolic blood pressure <140 mm Hg would result in an achieved blood pressure around 135 mm Hg for most people.
+
+
The work group acknowledges that the evidence is not definitive for any particular general blood pressure goal for patients with diabetes. The work group feels that a blood pressure goal of <140/90 mm Hg is reasonable and defensible based on the evidence previously presented. This goal is also consistent with the current blood pressure measure for people with diabetes specified by the Physician Quality Reporting System. See https://www.cms.gov/PQRS for more information. The work group will continue to review the blood pressure goal to consider any new evidence and the recommendations of other national practice guidelines (e.g., American Diabetes Association [ADA] and the Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [JNC8]) that are expected to announce revisions. The general recommendation of blood pressure <140/90 mm Hg does not preclude setting individual patient goals lower than that based on patient characteristics, comorbidities, risks or the preference of an informed patient.
+
+
Refer to Table 2 in the original guideline document for comparison of goal versus mean achieved blood pressure levels in randomized trials of blood pressure control in people with type 2 diabetes.
+
+
While ACE inhibitors and angiotensin receptor blockers (ARBs) are preferred first-line therapy, two or more agents (to include thiazide diuretics) may be required. For patients with type 2 diabetes mellitus, thiazide diuretics in the treatment of hypertension can reduce cardiovascular events, particularly heart failure. [Conclusion Grade I: See Conclusion Grading Worksheet F - Annotations #13, 18 (Thiazide Diuretics) in the original guideline document] [Low Quality Evidence], [Moderate Quality Evidence], [High Quality Evidence]
Patients with type 2 diabetes are at a significantly increased risk for development of heart disease [Guideline]. There is insufficient evidence to recommend for or against aspirin use in the primary prevention of cardiovascular events in patients with type 2 diabetes, although there is no evidence of significant harm. [Conclusion Grade I: See Conclusion Grading Worksheet D - Annotations #13, 14 (Aspirin Use) in the original guideline document]. Recent trials of aspirin use in diabetes have shown less benefit than older trials (perhaps due to better background A1c, blood pressure, and low-density lipoprotein control and lower smoking rates in recent trials) [High Quality Evidence]. Results of an aspirin meta-analysis in 2012 shows no significant benefits of aspirin for primary prevention. There are significant limitations identified in these studies, and more definitive studies would be helpful. [Meta-analysis]. Therefore, based on current evidence, low-dose aspirin is considered optional for primary prevention.
+
+
Regular use of ibuprofen may undermine aspirin's anti-platelet effects; patients taking both medications regularly should take immediate release aspirin at least 30 minutes prior to taking ibuprofen or wait at least eight hours after ingestion of ibuprofen .
+
Goals for Tobacco Use - Smoking Cessation , if Indicated
+
+
Tobacco smoking increases risk of macrovascular complications about 4% to 400% in adults with type 2 diabetes and also increases risk of macrovascular complications. Tobacco cessation is very likely to be the single most beneficial intervention that is available, and should be emphasized by providers as described below.
+
Identify and document tobacco use status .
+
Treat every tobacco user. If the patient is unwilling , the clinician should implement motivational treatments .
+
Individual, group and telephone counseling are effective, and their effectiveness increases with treatment intensity.
+
Practical counseling (problem-solving/skills training and social support delivered as part of the treatment) is an especially effective counseling strategy and should be implemented by clinicians .
+
Numerous effective medications are available.
+
The combination of counseling and medication is more effective than either alone. Therefore, clinicians should encourage all individuals making a quit attempt to use both .
+
Telephone quit line counseling is effective. Therefore, clinicians and health care delivery systems should ensure patient access to quit lines and promote their use .
+
Tobacco dependence treatments are both clinically effective and cost effective. Effective interventions require coordinated interventions. Just as the clinician must intervene with the patient, so must the health care administrator, insurer and purchaser foster and support tobacco intervention as an integral element of health care delivery.
+
+
Numerous effective pharmacotherapies for smoking cessation now exist. Except in the presence of contraindications , these may be used with all patients attempting to quit smoking . Please see the NGC summary of the ICSI guideline Preventive Services for Adults for additional information.
+
+
Tobacco telephone quit lines: HHS National Quit line (1-800-QUITNOW) connects you to counseling and information about quitting smoking in your state.
+
Cardiovascular Risk Factor Treatment Goalsfor Patients with Cardiovascular Disease
+
Recommendation:
+
+
The following treatment goals should be achieved:
+
Use of statinsif tolerated ; to achieve LDL cholesterol of less than 70 mg/dL;
+
Blood pressure less than 140/90 mm Hg;
+
Tobacco cessationif indicated ; and
+
Daily aspirin use is recommendedin patients with cardiovascular disease .
+
+
This recommendation places a very high value on a multifactorial approach to lowering the cardiovascular risk of patients with diabetes. The recommendation does not place value on prioritizing these treatment interventions, and some may be more important than others for different individuals. For the lipid and blood pressure recommendations, there is low value placed on the burden of these treatment approaches, the age of the patient (the evidence is less established in patients under age 40 and over 75), and whether patients can tolerate the treatments needed to obtain the recommended goals without side effects. The aspirin recommendation places high value on the benefits of aspirin for secondary prevention of cardiovascular events compared to the risks of bleeding.
+
On a statin with LDL less than 70 mg/dL
+
+
The low-density lipoprotein cholesterol goal for people with diabetes mellitus with coronary artery disease is less than 70 mg/dL.
+
+
Refer to Annotation #13, "Cardiovascular Risk Factor Treatment Goals for Patients without Cardiovascular Disease" above. For further information, refer to the NGC summaries of the ICSI guidelines Lipid Management in Adults and Stable Coronary Artery Disease.
+
Goals for blood pressure control: blood pressure less than 140/90 mm Hg
+
+
The goals and treatment of blood pressure are similar for patients with and without coronary artery disease. For further information, please see Annotation #13, "Cardiovascular Risk Factor Treatment Goals for Patients without Cardiovascular Disease."
+
Aspirin/antiplatelet medication use unless contraindicated [Moderate Quality Evidence]
+
+
There is sufficient evidence to support the use of aspirin for secondary prevention of cardiovascular events in patients with type 2 diabetes. [Conclusion Grade I: See Conclusion Grading Worksheet D - Annotations #13, 14 (Aspirin Use) in the original guideline document.]
+
+
If aspirin is contraindicated, consider use of clopidogrel or ticlopidine. For more information, please refer to the NGC summaries of the ICSI guidelines Stable Coronary Artery Disease and the Antithrombotic Therapy Supplement.
+
+
Regular use of ibuprofen may undermine aspirin's antiplatelet effects; patients taking both medications regularly should take immediate-release aspirin at least 30 minutes prior to taking ibuprofen or wait at least 8 hours after ingestion of ibuprofen.
+
Tobacco cessation, if indicated
+
+
Please see Annotation #13, "Cardiovascular Risk Factor Treatment Goals for Patients without Cardiovascular Disease," for more information on tobacco cessation.
+
Are Treatment Goals Met?
+
+
Major long-term goals of care in type 2 diabetes are cardiovascular disease prevention and achieving optimal glycemic control (see the related Glycemic Control algorithm annotations).
+
+
Setting initial goals that are achievable, however modest they may be, may encourage patients to take further steps along the way to the more ambitious long-term goals.
+
+
Goals and progress towards agreed-upon goals should be briefly reviewed at each office visit for diabetes. Adjustment of goals will likely be required over time, and patient involvement in this process can increase levels of patient involvement in care, give patients a greater sense of control of their diabetes, and allow flexibility in management of diabetes during periods of high stress or major life transitions.
+
Treatment Goals Not Met
+
Recommendations:
+
+
If patients are having difficulty achieving treatment goals , consider a modification of treatment goals . In addition, evaluate for potential contributing issues such as adherence, depression, and obstructive sleep apnea .
+
+
A referral to an extended care team clinician can be helpful ; this could be as an endocrinologist or other specialist, diabetes educator, dietitian or pharmacist.
+
Modify Treatment Based on Appropriate Related Guidelines
+
+
See the NGC summaries of the ICSI guidelines:
+
Prevention and Management of Obesity (Mature Adolescents and Adults)
+
Hypertension Diagnosis and Treatment
+
Lipid Management in Adults
+
Major Depression In Adults in Primary Care
+
+
See the Glycemic Control Algorithm in the original guideline document.
+
Consider Referral to Diabetes Care Team or Specialists
+Assess Patient Adherence
+
Non-adherence with medications can limit the success of therapy and help to explain why a patient is not achieving treatment goals. To screen for non-adherence, clinicians can ask patients open-ended, non-threatening questions at each office visit. The assessment should include probes for factors that can contribute to non-adherence (fear of adverse reactions, misunderstanding of chronic disease treatment, depression, cognitive impairment, complex dosing regimens, or financial constraints).
+
Assess the patient's knowledge of his/her condition and his/her expectations for treatment .
+
Assess the patient's medication administration process .
+
Assess the patient's barriers to adherence .
+
+
Interventions to enhance medication adherence should be directed at risk factors or causes of non-adherence. Interventions may include simplifying the medication regimen, using reminder systems, involving family or caregivers in care, involving multiple disciplines in team care, providing written and verbal medication instructions, setting collaborative goals with patients, and providing education about medications (including potential adverse effects) and about diabetes in general [Low Quality Evidence].
+Evaluate for Depression
+
There is a substantial increase in the prevalence of depression among people with diabetes as compared to the general adult population [Meta-analysis]. Depression impacts the ability of a person with diabetes to achieve blood glucose control, which in turn impacts the rate of development of diabetes complications [Meta-analysis], [Reference].
+
+
Identification and management of depression is an important aspect of diabetes care. Self-administered or professionally administered instruments (such as the Patient Health Questionnaire [PHQ]-9) are useful adjuncts to the clinical interview in the identification of depression. The NGC summary of the ICSI guideline Major Depression in Adults in Primary Care provides more suggestions for the management of depression. Intervention studies have demonstrated that when depression is treated, both quality of life and glycemic control improve. Counseling may be effective, especially among those who are having difficulty adjusting to the diagnosis of diabetes or are having difficulty living with diabetes. Pharmacotherapy for depression is also effective.
+Evaluate for Obstructive Sleep Apnea (OSA)
+
Sleep apnea is a prevalent condition in obese patients with type 2 diabetes and is associated with significant comorbidities including hypertension, cardiovascular disease, and insulin resistance. Consider referral of symptomatic patients for sleep evaluation .
+
+
Physicians should be cognizant of potential obstructive sleep apnea, especially among obese patients [High Quality Evidence], [Reference].
+Diabetes Care Team
+
Assure the patient has an adequate care team .
+Diabetes Educator
+
Consultation with a diabetes educator is suggestedif the patient is having difficulty adhering to a nutrition, exercise and medication regimen and the patient is having difficulty adhering to, or accurately completing, blood glucose monitoring or may need answers to his/her questions .
+
+
Every primary care clinician must develop a relationship with a diabetes education program to provide other options for management. The American Diabetes Association publishes a list of recognized educational programs in each state. These programs may be staffed with endocrinologists or primary care clinicians plus diabetes educators including dietitians, nurses and other health care clinicians who are Certified Diabetes Educators or have didactic and experiential expertise in diabetes care and education.
+Endocrinologist/Nephrologist
+
Most type 2 diabetes management can be managed by a primary care clinician with periodic consultation as needed by an endocrinologist.
+
+
Consultation with a specialist is suggestedif persistent proteinuria, worsening microalbuminuria and elevation in serum creatinine or blood urea nitrogen, or hypertension unresponsive to treatment is seen . For additional discussion, see Annotation #18, "Maintain Treatment Goals and Address Complications," the "Nephropathy" section.
+Endocrinologist/Neurologist
+
Consultation with a specialist is suggestedif neuropathy progresses and becomes disabling .
Consultation with a specialist is suggestedif blood pressure is refractory to treatment, or the patient has marked associated postural hypotension, or symptoms of coronary artery disease .
+Foot Care Specialist
+
A consultation with a specialist is suggestedif the patient is unable to care properly for his/her own feet, needs prescriptive footwear and/or more serious problems such as foot deformities (e.g., Charcot deformity), infected lesions, and ulcers, deformed nails or thick calluses are present .
+Ophthalmology/Optometry
+
Retinopathy is estimated to take at least five years to develop after the onset of hyperglycemia begins. Patients with type 2 diabetes, who generally have had years of undiagnosed diabetes and who have a significant risk of prevalent diabetic retinopathy at time of diabetes diagnosis , should have an initial dilated and comprehensive eye examination soon after diagnosis . Examinations should be performed by an ophthalmologist or optometrist who is knowledgeable and experienced in diagnosing the presence of diabetic retinopathy and is aware of its management. Subsequent examinations are generally repeated annually. Less frequent exams (every two to three years) may be cost effective after one or more normal eye exams, while examinations will be required more frequently if retinopathy is progressing [Guideline].
+Vascular Specialist/Surgeon
+
Consider referralif patient has symptoms of peripheral vascular disease such as loss of pulses and/or claudication .
+
Ongoing Management and Follow-Up of People with Diabetes
+
Recommendations:
+
+
Regular follow-up with the health care team (via office visit, e-visit, telephone, labs, etc.) should be scheduled yearly . More frequent visits may be necessaryif treatment goals are not achieved .
+
+
Perform a targeted history and physical yearly on all patients, with particular attention to the feet, cardiovascular system and blood pressure .
+
Targeted Annual History and Targeted Physical Exam
+
The targeted annual history should assess [Guideline]:
Results of self-monitoring blood glucose - validate results at least once a year (e.g., check patient's glucose meter against an office random capillary glucose)
+
Adjustments by the patient of the therapeutic regimen
+
Frequency, causes and severity of both hyperglycemia and hypoglycemia
+
Problems with adherence to therapeutic regimen
+
Symptoms suggesting development or progression of the complications of diabetes
+
Current prescribed medications, over-the-counter medications, dietary supplements and alternative therapies
+
Documentation of eye care specialist exam results
+
Alcohol/drug use patterns
+
+
Assessment for symptoms of depression
+
The targeted physical exam should assess:
Weight, body mass index
+
Blood pressure - all patients with diabetic nephropathy should be on either an ACE inhibitor or ARB
+
Cardiovascular - evaluation of preexisting problems
+
Feet (nails, web spaces, calluses, ulcers, structural deformities, protective sensation and shoes)
+
+
In studies of general population groups, coronary artery disease deaths have been substantially reduced by the treatment of hypertension, dyslipidemia, and smoking. Lipid treatment has also been shown to be of benefit in diabetes. Therefore, risk factor reduction is prudent for patients with diabetes [Guideline], [Moderate Quality Evidence].
+
Frequency of visits depends on blood glucose control, changes in the treatment regimen, and presence of complications of diabetes or other medical conditions.
+
Patients starting or having a major change in their treatment program (such as initiating insulin therapy) may need to be in contact with their care clinician as often as daily until glucose control is achieved, the risk of hypoglycemia is low, and the patient is competent to conduct the treatment program.
+
Contact with the patient after a major modification of the treatment plan (such as introducing a new medication) should ideally not be delayed greater than one week.
+
Regular follow-up (e.g., office visits, e-visit, lab work, phone consult) should be scheduled yearly. More frequent follow-up may be necessary if treatment goals are not achieved.
+
Cardiovascular disease is the primary cause of morbidity and mortality in people with type 2 diabetes. The risk of coronary artery disease is approximately doubled in men and quadrupled in women with diabetes.
+
At each encounter, ask if the patient has experienced symptoms of hypoglycemia or low blood glucose, review and educate the patient on appropriate recognition, prevention, and management.
+
If the patient has a history of severe hypoglycemia (assistance of another person was needed to treat a low glucose) or has developed hypoglycemia unawareness, evaluate the treatment goals for appropriate safety.
+
Maintain Treatment Goals and Address Complications
+
Recommendations:
+
+
Annually screen for microalbuminuria .
+
+
All patients with diabetic nephropathyshould be on either an ACE inhibitor or ARBunless contraindicated .
+
+
Consider early nephrology consultationfor patients with macroalbuminuria and/or creatinine (Cr) above 1.5 mg/dL .
+
+
Aggressive control of hypertension, dyslipidemia, obesity and protein restriction is recommendedin all patients with nephropathy .
+
Specialist Dilated Eye Exam
+
+
A dilated eye examination for diabetic eye disease performed by an ophthalmologist or optometrist is recommended annuallyfor patients with type 2 diabetes mellitus [Guideline]. Less frequent exams (every two to three years) may be consideredin the setting of a normal eye exam . The role of fundus photography is still being considered but doesn't replace a comprehensive exam.
+
Retinopathy
+
+
Prevalence of retinopathy is related to the duration of diabetes mellitus. After 20 years of type 2 diabetes mellitus, more than 60% of patients have some degree of retinopathy [Guideline]. Diabetic retinopathy is estimated to be the most frequent cause of new cases of blindness among adults ages 20 to 74 years.
+
+
Up to 21% of patients with type 2 diabetes mellitus are found to have retinopathy at the time of diagnosis of diabetes mellitus [Guideline]. Generally retinopathy progresses from mild background abnormalities to preproliferative retinopathy to proliferative retinopathy.
+
+
Poor glucose control is associated with progression of retinopathy. High blood pressure is a risk factor for the development of macular edema and is associated with the development of proliferative retinopathy [Guideline].
+
+
Screening for diabetic retinopathy saves vision at a relatively low cost. In fact, screening costs may be less than the costs of disability payments for those who become blind. Laser photocoagulation surgery is effective in preventing visual loss in diabetic retinopathy.
+
+
Studies have shown that retinal examinations by clinicians who are not eye care specialists are not reliable in detecting retinopathy [Guideline, High Quality Evidence, Consensus Statement, Low Quality Evidence, Narrative Review].
+
+
Treatment includes glycemic and blood pressure control. Periodic screening and dilated eye exams by an eye specialist and early treatment of diabetic retinopathy can prevent visual loss [Guideline].
+
Renal Assessment and Nephrology
+
+
Urinary albumin excretion should be tested annually by a microalbuminuria method . There is racial/ethnic variability with regard to the prevalence of end-stage renal disease with Native Americans, Latinos (especially Mexican Americans), and African Americans having higher rates than non-Hispanic whites with type 2 diabetes [Guideline]. If albuminuria is above normal , serum creatinine should be measured [Reference], [Low Quality Evidence].
+
+
The recommended screening method to detect microalbuminuria is:
+
Measurement of the albumin-to-creatinine ratio in a random, spot collection. Consider early nephrology consultationfor patients with macroalbuminuria and/or Cr >1.5 mg/dL. Aggressive control of hypertension, dyslipidemia, obesity and protein restriction is recommendedin all patients with nephropathy .
+
+
Several factors can artificially increase the levels of albumin in the urine and should be avoided at the time of the urine collection. These include blood in the urine, prolonged heavy exercise, fever, congestive heart failure, uncontrolled diabetes, severe hypertension, urinary tract infection, and vaginal fluid contamination of specimen.
+
+
If two out of three screening microalbuminuria tests are positive, the individual has microalbuminuria and interventions should be considered . A negative findingshould be followed annually ; a positive findingshould be followed periodically, for example annually , to see if the interventions are effective in diminishing the albuminuria [Low Quality Evidence].
+Nephropathy
+
In type 2 diabetes, albuminuria may be present at the time of diagnosis in about 10% of patients, and another 10% later develop it. Progression to renal failure is less certain in type 2 patients than in type 1 patients, and appears to be modulated by genetic and other factors.
+
+
Patients with clinical nephropathy almost always have retinopathy and coronary artery disease.
+
+
Numerous interventions are appropriate at different stages of renal function in order to prevent or slow the progression of renal disease and associated cardiovascular disease and include [Guideline]:
+
Glucose Control - Improved glucose control at any stage of renal function reduces renal disease progression. See the Glycemic Control algorithm in the original guideline document.
+
ACE inhibitor or ARB should be usedin all nonpregnant patients with micro or macroalbuminuria . For patients with type 2 diabetes mellitus, ACE inhibitors or ARBs can reduce progression of macrovascular complications. [Conclusion Grade I: See Conclusion Grading Worksheet E - Annotations #18 (Treatment with ACE Inhibitors or ARBs) in the original guideline document] [High Quality Evidence]. Within one week of initiation, check for elevations in potassium and creatinine levels.
+
Measure serum creatinine at least annually and more often based on stage of chronic kidney disease (CKD) .
+
Hypertension Control - An ACE inhibitor or ARB should be the initial agent of choice. Current JNC 7 and National Kidney Foundation Disease Outcomes Quality Initiative (NKF DOQI) recommendations call for treatment of blood pressure to <130/80 in patients with CKD. However, no single, adequately powered intent-to-treat randomized control trial has shown a benefit of this blood pressure goal in CKD [High Quality Evidence], [Meta-analysis], [Systematic Review]. Hence, the recommendation for lower blood pressure goals in all patients with CKD is based on expert opinion and not fully supported by available prospective clinical trials. Determining whether therapy should specifically be titrated to goals lower than 140/90 mm Hg for specific subgroups of CKD patients (e.g., those with moderate proteinuria) should be considered on an individual patient basis, based on clinical judgment and patient preference.
+
Cardiovascular Risk Factor Intervention - Dyslipidemia is often present with microalbuminuria and should be treated aggressively . Dyslipidemia may be an independent risk factor for progression of renal disease. Smoking is associated with the onset and progression of microalbuminuria.
+
Restriction of dietary protein has been shown to slow progression of overt nephropathy (macroalbuminuria), and there may be some benefit in dietary protein reduction in microalbuminuric patients. In these circumstances, protein intake should be reduced to the adult recommended daily allowance of 0.8 to 1 g/kg body weight per day with microalbuminuria present, and 0.8 g/kg body weight per day with macroalbuminuria present [Guideline].
+ Treatment for microalbuminuria includes aggressive blood pressure control with ACE or ARB use as first-line therapy, glycemic control, and aggressive cardiovascular risk factor screening and management .
+ Strongly consider referral to nephrologyany patients with a creatinine greater than 1.5 mg or nephrotic range proteinuria (greater than 3 g/24 hr) .
+ Patients with a creatinine clearance of less than 30 mL/minshould be referred to nephrology for discussions of future options and to enhance the ability to receive a future transplant. These patients also have significant enough renal impairment that they also benefit from more intensive nutritional interventions and proper management of anemia and bone disease [Guideline], [Low Quality Evidence], [High Quality Evidence], [Moderate Quality Evidence].
+
+
See Appendix B, "Treatment of Diabetic Nephropathy," in the original guideline document.
+
Neuropathy
+
+
Peripheral neuropathy is difficult to prevent and treat. Most patients with type 2 diabetes and peripheral neuropathy have few symptoms. All patients found to have neuropathyshould see a foot care specialist for preventive measures aimed at reducing the incidence of diabetic foot complications. Good glycemic control should be the first control to symptomatic neuropathy.
+
+
For those patients with painful neuropathy treatment choices include:
+
Antidepressants such as the tricyclics (amitriptyline, nortriptyline or desipramine), duloxetine or venlafaxine
+
Anticonvulsants (gabapentin, pregabalin)
+
Topical treatment with capsaicin
+
+
[Low Quality Evidence]
+Comprehensive Foot Exam with Risk Assessment
+
Patients with one or more risk factors for foot complicationsshould be educated about their risk factors and appropriate measures taken to avoid complications . Measures may include self-management education, more intensive follow-up, and/or referral to appropriate specialist [Guideline], [Low Quality Evidence].
+
+
A foot exam should include assessment for the following risk factor for complications:
+
Loss of protective sensation. Protective sensation can be assessed using either a 5.07 Semmes-Weinstein monofilament for light touch or by testing vibration using a 128-Hz tuning fork at the dorsum of the interphalangeal joint of the great toe, or both. Patients with reduced or absent sensation with either of these tests should be educated about their risk and the need for proper foot care to prevent foot complications (see Appendix C, "Using a Semmes-Weinstein Monofilament to Screen the Diabetic Foot for Peripheral Sensory Neuropathy" and Appendix D, "Using a Tuning Fork to Screen the Diabetic Foot for Peripheral Neuropathy" in the original guideline document).
+
Peripheral vascular disease (absent pedal pulse, history of claudication, or ischemic skin changes)
Skin disorders (nail deformity, callus, fissure, tinea, or ulceration)
+
Footwear (excessively worn, ill fitting, or inappropriate shoes)
+
Medications can improve quality of life in patients with painful neuropathy
+
Peripheral Vascular Disease
+
+
Peripheral arterial disease is commonly associated with diabetes [Guideline]. As many as 36% of patients with diabetes have lower-extremity peripheral arterial disease based on lower-extremity blood pressure readings. However, a typical history of intermittent claudication or an absent peripheral pulse is less commonly noted.
+
+
Initial screening for peripheral arterial disease should include asking about claudication and assessment of pedal pulses. Consider obtaining ankle-brachial indexif clinically indicated .
+
+
Peripheral vascular disease in combination with peripheral neuropathy places patients with diabetes at increased risk for non-traumatic amputations of the lower extremity. Peripheral vascular disease may be slowed by smoking cessation and treatment of hypertension and dyslipidemia. See Annotation #14, "Cardiovascular Risk Factor Treatment Goals for Patients with Cardiovascular Disease."
+
+
Aggressive daily foot care, inspection of the feet at every office visit for diabetes mellitus, early treatment of foot infections, treatment of callus, use of moisturizing lotion and proper footwear may forestall problems, including amputation. Vascular surgery may also prevent amputation in some patients with established severe peripheral vascular disease [Guideline].
+
+
Proper high-risk foot management is necessary to prevent ulceration and amputation. Consider referral of patients with claudication and/or absent pedal pulses to vascular surgery .
+
Cardiovascular and Cerebrovascular Complication Assessment
+
History of cardiovascular symptoms such as chest pain, vascular claudication, transient ischemic attack (TIA)
+
Cardiac and carotid exams
+
Screening for coronary heart disease
Screening is no longer recommended with cardiac stress testing
+
+
Evaluate cardiovascular status before advising increased intensity of exercise [Guideline], [Low Quality Evidence].
+
Cardiovascular and Cerebrovascular Disease
+
+
Treatment includes control of cardiovascular risk factors (hypertension, dyslipidemia, and smoking cessation) and aspirin use. Consider referring patients with known coronary artery disease to cardiology and patients with known carotid disease to a specialist .
+
+
Heart failure is also common in patients with diabetes. Metformin may be usedin stable congestive heart failure if renal function is normal .
+
+
Close monitoring of potassium and renal function is necessary especially if patients have concomitant chronic kidney disease as the common use of diuretics, ACE/ARBs and aldosterone antagonists in these patients may cause hyperkalemia and worsening renal function. Thiazolidinediones should be avoided in patients with congestive heart failure.
+
+
For patients with type 2 diabetes mellitus, thiazide diuretics in the treatment of hypertension can reduce cardiovascular events, particularly heart failure [Conclusion Grade I: See Conclusion Grading Worksheet F -- Annotations #13, 18 (Thiazide Diuretics) in the original guideline document] [Moderate Quality Evidence, High Quality Evidence].
+
+
Patients with type 2 diabetes have twice the average risk of suffering a stroke [Low Quality Evidence]. It is unclear whether optimal glycemic control reduces this risk. However, treatment of hypertension, smoking, and dyslipidemia reduces the risk of stroke in most persons. See Annotation #14, "Cardiovascular Risk Factor Treatment Goals for Patients with Cardiovascular Disease".
+
Special Considerations
+
Hepatitis B vaccine should be administered to unvaccinated adults with diabetes who are <60 years of age. It may be administered to unvaccinated adults with diabetes who are ?60 years of age [Guideline].
+
Influenza vaccine every year
+
Pneumococcal vaccine - repeat the vaccinationonce after age 65 if the initial vaccination was given prior to 65 . Consider repeating the immunization for those at risk of losing immunity after five years including:
Nephrotic syndrome
+
Chronic renal disease
+
Other immunocompromised states
+
+
Glycemic Control Algorithm Annotations
+
Glycemic Control
+
+
Medical nutrition therapy should be initiated and maintained throughout the course of the disease, even as pharmacologic agents are used .
+
+
The goal of glycemic control is to both prevent acute, symptomatic hyperglycemia and prevent the development of long-term microvascular and macrovascular complications related to chronic hyperglycemia.
+
+
Medical nutrition therapy is an essential component of glycemic control for all people with type 2 diabetes. In addition, pharmacologic therapy is appropriate and necessary for most people with type 2 diabetes in order to attain appropriate glycemic control. There are a number of pharmacologic agents and strategies for glycemic control in people with type 2 diabetes. These are discussed in Annotation #20, "Pharmacologic Agent(s) - Which is Best?"
+
Pharmacologic Agent(s) - Which Is Best?
+
Recommendations:
+
Concurrent initiation of metformin with medical nutrition therapy is recommendedfor most patients at diagnosis .
+
At the time of diagnosis, if patients have severe symptomatic disease , insulin should be initiated .
+
Metformin and alpha glucosidase inhibitors should not be used with renal dysfunction.
+
Metformin should be used with caution for patients with conditions that predispose them to risk of hypoxia.
+
Metformin and thiazolidinediones should not be usedif alanine aminotransferase (ALT) is 2.5-3 times normal upper limits .
+
+
A recent consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes recommended concurrent initiation of metformin with medical nutrition therapy for most patients at diagnosis. Arguments for this approach include the infrequent success of medical nutrition therapy alone, and the absence of weight gain and hypoglycemia, general tolerability and relatively low cost of metformin [Reference]. Metformin, sulfonylurea medications and insulin were recommended in this consensus statement as well-validated core therapies based on their extended history of use, demonstrated effectiveness and generally favorable cost. More recent therapies such as thiazolidinediones and glucagon-like peptide 1 agonists were viewed as less-well-validated therapies. The authors of the consensus statement note that there are few well-controlled clinical trials directly comparing different diabetes treatment regimens and that their recommendations are in part based on clinical experience [Guideline]. Clinician judgment and factors such as patient comorbidities, patient desires and cost considerations should always guide design of a glycemic control regimen at the individual patient level.
+
+
At the time of diagnosis, if patients have severe symptomatic disease , insulin should be initiated . With appropriate educational support and care, the risks of insulin may not differ from many oral agents. In some circumstances when glucose intolerance is significant and the patient is unwilling to consider insulin or it is not felt to be appropriate , the initiation of combinations of oral agents can be appropriate . Insulin is indicated when there is a failure to achieve treatment goals with oral agents.
+
+
It is important to remember that patients can move both ways on the Glycemic Control algorithm (e.g., they can move off of specific pharmacologic therapies as lifestyle changes are made that improve glycemic control). Diabetes is a progressive disease, however, and the use of pharmacologic agents will likely become necessary in the majority of patients, even if they are able to follow through with nutrition and physical activity recommendations [High Quality Evidence].
+
+
Only general guidelines can be given when deciding about which pharmacologic agent will be best for a specific patient. While each patient presents with unique circumstances, the work group offers the following clinical circumstances to consider.
+
Age of Patient
+
+
It is important to recognize that risks of medications are often increased with advancing age, but this does not justify the withholding of medications that may reduce the symptoms of polyuria, and nocturia.
+
+
With age, decline in renal function is often not reflected in a measurable change in serum creatinine because of an accompanying decline in muscle mass. Because of this, metformin should be used with caution in elderly patients (over age 80).
+
+
Decline in ventricular function and risks for volume overload can be occult in the elderly and may become clinically apparent with the use of thiazolidinediones.
+
+
In select circumstances, because of the risks of hypoglycemia, variable diet habits and renal clearance and function , it may be safer to consider initial low dose short-acting sulfonylurea (e.g., glipizide or repaglinide/nateglinide when a meal is eaten) .
+
Weight of the Patient
+
+
Type 2 diabetes is often associated with insulin resistance and weight gain. Metformin, acarbose, exenatide, sitagliptin, and human amylin are more often associated with weight loss or weight maintenance. Due to its weight benefits as well as general tolerability, lower cost and proven benefits in UK Prospective Diabetes Study Group, metformin is recommended for most diabetes patients with type 2 diabetes unless contraindicated. Insulin and thiazolidinediones may be associated with weight gain [High Quality Evidence].
+
Renal Dysfunction
+
+
Renal dysfunction increases the risk for hypoglycemia, in particular with the use of oral hypoglycemic agents.
+
+
Metformin and alpha glucosidase inhibitors should not be used.
+
+
Thiazolidinediones may be considered, but the potential risks of fluid retention and increased risk of cardiac events need to be considered.
+
+
Short-acting oral agents glipizide, glimepiride (in which serum levels have been noted to decrease in mild renal failure), repaglinide, or nateglinide may be preferred if an oral agent is felt to be necessary in the face of renal dysfunction.
+
+
Insulin may be the safest when serum creatinine is greater than 1.8 mg or creatinine clearance is less than 60 mL/min.
+
Cardiopulmonary Comorbidities
+
+
Metformin should be used with caution in patients with conditions that predispose them to risk of hypoxia such as congestive heart failure, chronic obstructive pulmonary disease or obstructive sleep apnea. Metformin should be promptly discontinuedin situations of cardiovascular collapse from acute congestive heart failure, acute myocardial infarction, or any other cause .
+
+
Patients started on thiazolidinediones should be instructed to report signs of lower extremity swelling, rapid weight gain, and shortness of breath. Risk of thiazolidinediones needs to be discussed and documented before using in patients with cardiovascular risks. Please see the thiazolidinediones warning for more information.
+
+
Short-acting sulfonylurea (e.g., glipizide), repaglinide/nateglinide, and the cautious use of long-acting sulfonylurea oral agents, or insulin may be safest.
+
Hepatic Disease
+
+
Hepatic disease or insufficiency increases the risks of lactic acidosis and hypoglycemia and influences the metabolism of many oral medications.
+
+
Metformin and thiazolidinediones should not be usedif alanine aminotransferase (ALT) is 2.5 to 3 times normal upper limits .
+
+
First generation sulfonylureas, glipizide, and glyburide have some component of hepatic metabolism and should be used with caution because of the risks of hypoglycemia. Insulin would be considered safest.
+
Prescribe Insulin Therapy
+
+
If the patient presents and is considered stable enough for outpatient care but meets indications noted in Annotation #8, "Does Patient Need Outpatient Stabilization?" for starting insulin, the work group offers several acceptable ways of initiating insulin.
+
One example is to calculate the total daily dose of insulin at 0.3 units/kg and start bedtime glargine at 50% of the total dose, splitting the remaining 50% with short acting insulin before meals .
+
Another example is to start an oral agent(s) while simultaneously initiating long-acting insulin (glargine or detemir) at a dose of approximately 0.1 units/kg .
+
A third example is to calculate the total daily dose of insulin at 0.3 units/kg and use pre-mixed insulin with two-thirds of the dose in the morning and one-third of the dose in the evening .
+
Insulin programs should be individualized based on the patient's lifestyle, treatment goals, and self-monitoring blood glucose. Many patients can be taught to interpret self-monitoring blood glucose results and adjust insulin doses [Guideline]. (See table showing the time course of action of insulin preparations in the original guideline document.)
+
Total dose ranges from 5 units/day to several hundred units/day.
+
Average insulin doses are 0.6 to 0.8 units/kg of body weight per day.
+
Obese patients often require doses equal to or exceeding 1.2 units/kg.
+
Meal times and snacks must be consistent. Synchronize insulin with food intake patterns.
+ A recent three-year randomized, multicenter, open label trial that studied the efficacy of three different insulin regimens in over 700 patients with type 2 diabetes who had A1c values >7% on maximum doses of metformin and a sulfonylurea, suggests the following:
Various insulin regimens can be effective in treating type 2 diabetes.
+
An insulin regimen based initially on one or two injections a day of a longer-acting insulin may be associated with less hypoglycemia and/or less weight gain compared to regimens initiated with fixed-ratio or rapid-acting insulin [High Quality Evidence].
+
+
Rapid-acting insulin should not be taken more than 15 minutes before meals in contrast to regular insulin, which should ideally be taken at least 30 minutes before a meal to better match the insulin peak action with post-meal hyperglycemia.
+
Patients who are testing their glucose before meals and adjusting insulin doses to match meals may find rapid-acting insulin to be more effective although generally studies have not shown an improvement in A1c when compared to regular insulin taken according to package insert (30 to 45 minutes preprandial).
+
Effective use of rapid-acting insulin usually requires the addition of basal intermediate or long-acting insulin .
+
There are several devices available on the market for the administration of insulin (e.g., insulin pump, insulin pen).
+
Insulin pump therapy may be helpfulfor patients who are interested in more intensified management of blood glucose and want more flexibility, or if pregnancy is desired . Candidates for pump therapy should be evaluated by an endocrinologist or diabetes specialist to assess patient understanding, self-care knowledge including medical nutrition therapy, responsibility, and commitment. Insulin pump therapy is more commonly used in type 1 patients, but is also being used by some type 2 patients.
+
Please note the work group left the brand names for Humalog(r) and Novolog(r) in the table (see the original guideline document). The generic mix is as follows:
Every facility needs to evaluate insulin safety per its specific situation.
+
The utilization of regular insulin U-500 may be helpful for patients with extreme insulin resistance requiring more than 200 units of exogenous insulin per day as a total daily dose. If U-500 is to be utilized for patients, it is strongly recommended that an endocrinologist and a diabetes educator be involved in the care of the patient. Caution must be exercised with dosing calculations, patient education, and instructions to pharmacy [Low Quality Evidence].
+
Prescribe Non-Insulin Agents
+
Recommendation:
+
+
Metformin is the preferred initial oral agentfor type 2 diabetes .
+
+
Please consult the manufacturer's product labeling insert for full prescribing information.
+
+
If not contraindicated, metformin is the preferred initial oral agent for type 2 diabetes due the benefits of low cost, low risk of hypoglycemia and side effects, and lack of associated weight gain. If metformin is contraindicated , sulfonylureas are acceptable secondary choices for oral agents . Sulfonylureas have the advantage of being relatively inexpensive [Reference].
+
Class
Compound
Clinical Advantages
Clinical Disadvantages
Safety/Monitoring Considerations
+
Biguanides
Metformin
No weight gain
+
No hypoglycemia
+
Reduced cardiovascular events and mortality
+
Generally well tolerated
+
Gastrointestinal side effects: diarrhea, nausea, abdominal cramping
+
Rare occurrence of lactic acidosis
+
Vitamin B12 deficiency
+
Monitor serum creatinine at least annually . Contraindicated with renal dysfunction (sCr ?1.5 mg/dl in men or ?1.4 mg/dl in women)
+
Hold at least 48 hours after IV iodinated contrast media
+
Use cautiously with liver dysfunction, CHF, ETOH abuse, severe pulmonary disease; age >80 years
+
Check B12 and folate levelsif anemia present
+
+
Sulfonylureas (2nd generation)
Glyburide
+ Glipizide
+ Glimepiride
Reduced cardiovascular events and mortality
+
Generally well tolerated
+
Hypoglycemia, particularly with deficient caloric intake
+
Weight gain
+
May blunt myocardial ischemic preconditioning
+
Loss of efficacy with prolonged use
+
Use cautiously with renal or hepatic impairment
+
Use cautiously with known hypersensitivity or severe adverse reaction to other sulfonamides
+
Glyburide is not recommended for use in the elderly
+
Glipizide/glimepiride may be safer than glyburide for patients with renal impairment and is associated with lower risks of hypoglycemia
+
+
Synthetic Analog of Human Amylin
Pramlintide acetate injection
Satiety leading to decreased caloric intake and potential weight loss
Nausea, vomiting and anorexia
Pramlintide is used with insulin and has been associated with an increased risk of insulin-induced severe hypoglycemia. When severe hypoglycemia associated with pramlintide use occurs, it is seen within three hours following a pramlintide injection. If severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities, serious injuries may occur. Appropriate patient selection, careful patient instruction, and insulin dose adjustments are critical elements for reducing this risk.
+
Meglitinides
Repaglinide
+ Nateglinide
Accentuated effects around meal ingestion
Hypoglycemia (less than sulfonylureas)
+
Weight gain
+
May blunt myocardial ischemic preconditioning
+
Dosing frequency
+
Use cautiously with renal or hepatic impairment
+
Gemfibrozil use is contraindicated with repaglinide
+
+
Thiazolidinediones (TZDs, glitazones)
Pioglitazone
No hypoglycemia
+
HDL cholesterol increased
+
Triglycerides decreased
+
Once daily dosing
+
Weight gain
+
Edema
+
Bone fractures
+
Anemia
+
Diabetic macular edema
+
Contraindicated in patients NYHA Class III/IV heart failure . Monitor for signs/symptoms of fluid retention and heart failure .
+
Periodic ALT and ophthalmic exam
+
May increase risk of bladder cancer with prolonged use or at high dose. Avoid use with concurrent or history of bladder cancer .
+
Thiazolidinediones have been associated with increased risk of hospitalization for heart failure [Systematic Review] .
+
Health care clinicians and patients must be enrolled in the Avandia-Rosiglitazone Medicines Access Program in order to prescribe and receive rosiglitazone medicines. After November 18, 2011, rosiglitazone medicines will no longer be available through retail pharmacies. Patients who are enrolled in the Avandia-Rosiglitazone Medicines Access Program will receive their medicine by mail order through specially certified pharmacies participating in the program. See the FDA Web site .
+
+
Alpha Glucosidase Inhibitors
AcarboseMiglitol
Non-systemic medication
+
Postprandial glucose decreased
+
Gastrointestinal side effects: flatulence, abdominal pain and diarrhea
+
Dosing frequency
+
Contraindicated with serum creatinine >2.0 mg/dl, cirrhosis, colon ulcerations, inflammatory bowel disease, conditions associated with reduced absorption/digestion, partial bowel obstruction, predisposition to bowel obstruction
+
Monitor liver enzymes .
+
Treat hypoglycemia with oral glucose, no sucrose.
+
+
Glucagon-like Peptide 1 (GLP-1) Agonists
Exenatide Liraglutide
Weight loss
+
Potential for improved beta cell mass/function
+
Gastrointestinal side effects: nausea, vomiting, diarrhea
+
Pancreatitis
+
Injectable
+
Use is not recommended in patients with gastroparesis or severe gastrointestinal disease.
+
Cases of acute pancreatitis reported.
+
Liraglutide ??? thyroid C-cell tumors have developed in animal studies; relevance in humans unknown.
+
Liraglutide is contraindicated with personal or family history of medullary thyroid carcinoma (MTC), or multiple endocrine neoplasia syndrome type 2 (MEN 2).
+
Use caution with moderate to severe renal impairment. Exenatide should not be used with GFR <30.
+
Long-term safety is unknown.
+
+
Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
Sitagliptin Saxagliptin Linagliptin
No hypoglycemia
+
No weight gain
+
Once daily dosing
+
Rare pancreatitis
+
Rare urticaria, angioedema
+
Adjustments are needed for renal dysfunction (sitagliptin and saxagliptin). Monitor serum creatinine before initiation and periodically thereafter.
+
Saxagliptin dose adjustment required with use of strong CYP450 3A4/5 inhibitors
+
Long-term safety is unknown.
+
+
Bile Acid Sequestrants
Colesevelam
No hypoglycemia
+
LDL cholesterol decreased
+
Gastrointestinal side effects: constipation, dyspepsia
+
Triglycerides increased
+
Contraindicated with severe GI motility disorders, history of major GI tract surgery, history of bowel obstruction, serum triglyceride concentration >500 mg/dL, or history of hypertriglyceridemia-induced pancreatitis
+
May reduce absorption of certain medications (fat-soluble vitamins, glyburide, warfarin, levothyroxine, phenytoin, oral contraceptives)
+
+
Dopamine-2 Receptor Agonists
Bromocriptine
No hypoglycemia
Limited clinical experience
+
Dizziness/syncope
+
Nausea, vomiting
+
Headache
+
Fatigue, weakness
+
Contraindicated with past hypersensitivity to ergot-related medications, breastfeeding, history of syncopal migraine
+
Should not be used in patient with psychotic disorders, or if taking dopamine agonist/antagonist medications
+
Use cautiously with history of peptic ulcer disease or uncontrolled hypertension
+
Monitor BP, orthostatic symptoms, liver function
+
Long-term safety unknown
+
+
Intensify Therapy
+
Recommendation:
+
+
If treatment goals are not met on oral agents, or if oral agents are contraindicated, then it is necessary to begin insulin either alone or as an adjunct to oral therapy.
+
+
There are many regimens that have been studied and are efficacious [Low Quality Evidence]. The following commonly used regimens are discussed in the original guideline document: insulin as an adjunct to oral therapy, insulin alone, and oral agents as an adjunct to insulin therapy.
+
\ No newline at end of file
diff --git a/data/GDM_inline_GATE_final.xml b/data/GDM_inline_GATE_final.xml
index 902aea0..61c096d 100644
--- a/data/GDM_inline_GATE_final.xml
+++ b/data/GDM_inline_GATE_final.xml
@@ -1,4 +1,4 @@
-Gestational Diabetes Guideline (CSPT)
+Gestational Diabetes Guideline (CSPT)
Introduction
@@ -38,15 +38,17 @@
The National Institute of Health is planning a Consensus Development Conference to determine the optimal approach to screening and diagnosis in the United States.
Thus, in this guideline we are going to maintain the recommendations for diagnosis made by the Spanish Group for the study of Diabetes and Pregnancy which agree with the recommendations from the ACOG:
-
All pregnant womenshould be screened for GDM using the O'Sullivan test, that consist on a 50-g, 1-hour loading test .
First trimester (high risk for GDM)
Age ≥ 35
-
Body Mass Index (BMI)= mass (Kg)/ (Height (m))^2 ≥ 30 kg/m2
-
Previous GDM confirmed or suspected on the light of the perinatal outcomes, i.e. macrosomia .
-
Familiar history of diabetes in first degree relatives .
+
All pregnant womenshould be screened for GDM using the O'Sullivan test, that consist on a 50-g, 1-hour loading test .
First trimester (high risk for GDM)
Age ≥ 35
+
Body Mass Index (BMI)= mass (Kg)/ (Height (m))^2 ≥ 30 kg/m2
+
Previous GDM confirmed or suspected on the light of the perinatal outcomes, i.e. macrosomia .
+
Familiar history of diabetes in first degree relatives .
-
Second trimester (24-28 weeks)
All the pregnant women non previously diagnosed of GDM
+
Second trimester (24-28 weeks)
All the pregnant women non previously diagnosed of GDM
-
Third trimester
All the pregnant women non previously screened
-
Women with normal O'Sullivan test but who develop complications suggesting GDM (macrosomia, polihydramnios) . In those cases it would be performed directly a 100 gr OGTT test
+
Third trimester
All the pregnant women non previously screened
+
Women with normal O'Sullivan test but who develop complications suggesting GDM (macrosomia, polihydramnios) . In those cases it would be performed directly a 100 gr OGTT test
The diagnosis of GDM can be made based on the result of the 100-g, 3-hour oral glucose tolerance test, for which there is evidence that treatment improves outcome. The plasma levels designated by the National Diabetes Data Group are appropriate to use (see table).
Status
Plasma level
@@ -56,11 +58,11 @@
2 hour
165
9.2
3 hour
145
8.0
-
A positive diagnosis requires that two or more thresholds be met or exceeded . If only one point is exceeded , then fasting and 1h postprandial glucose control are adviced . In case of normality of all the glucose results during at least the first week of follow-up, random and sporadic tests would be enough to guarantee an appropriate carbohydrate tolerance. The patient receives nutritional recommendations and exercise recommendations . Note: These patients will be enrolled in MobiGuide.
+
A positive diagnosis requires that two or more thresholds be met or exceeded . If only one point is exceeded , then fasting and 1h postprandial glucose control are adviced . In case of normality of all the glucose results during at least the first week of follow-up, random and sporadic tests would be enough to guarantee an appropriate carbohydrate tolerance. The patient receives nutritional recommendations and exercise recommendations . Note: These patients will be enrolled in MobiGuide.
The highly concentrated hyperosmolar glucose solution can cause gastric irritation, delayed emptying, and gastrointestinal osmotic imbalance, leading to nausea and vomiting. In case of patients unable to tolerate oral hyperosmolar glucose, the recommended option is:
-
Serial glucose monitoring -- Periodic random fasting and one-hour postprandial blood glucose testing -- is a monitoring option for women at high risk for gestational diabetes who are unable to take an oral glucose load . HbA1c ≤ 6% could help to guarantee that this option is a reasonable way to start with. The patient receives nutritional recommendations and exercise recommendations . Note: These patients will be enrolled in MobiGuide.
+
Serial glucose monitoring -- Periodic random fasting and one-hour postprandial blood glucose testing -- is a monitoring option for women at high risk for gestational diabetes who are unable to take an oral glucose load . HbA1c ≤ 6% could help to guarantee that this option is a reasonable way to start with. The patient receives nutritional recommendations and exercise recommendations . Note: These patients will be enrolled in MobiGuide.
Rationale for treatment
@@ -70,18 +72,18 @@
Monitoring
Glucose monitoring
-
Women with GDMshould measure their blood glucose concentration at least four times daily (fasting and one hour after the first bite of each meal) to determine whether hyperglycemia severe enough to increase fetal risk is occurring. Results should be recorded in a glucose log, along with dietary information. This facilitates recognition of glycemic patterns and helps immeasurably in interpreting results stored in the memory of modern meters. Multiple daily measurements allow recognition of women who should begin insulin therapy and appear to decrease the risk of macrosomia. The decision to start insulin therapy (or not to start it) is taken by the endocrinologist. Note: in some not very frequent cases, the insulin therapy is not started after considering the specific patient personal context (e.g. gestational age = 39 week and fetus percentile < 60, low family support, analphabetism and post-prandial BG < 160 mg/dl and fasting BG < 120 mg/dl).
+
Women with GDMshould measure their blood glucose concentration at least four times daily (fasting and one hour after the first bite of each meal) to determine whether hyperglycemia severe enough to increase fetal risk is occurring. Results should be recorded in a glucose log, along with dietary information. This facilitates recognition of glycemic patterns and helps immeasurably in interpreting results stored in the memory of modern meters. Multiple daily measurements allow recognition of women who should begin insulin therapy and appear to decrease the risk of macrosomia. The decision to start insulin therapy (or not to start it) is taken by the endocrinologist. Note: in some not very frequent cases, the insulin therapy is not started after considering the specific patient personal context (e.g. gestational age = 39 week and fetus percentile < 60, low family support, analphabetism and post-prandial BG < 160 mg/dl and fasting BG < 120 mg/dl).
-
Although there are no data on the duration of good control sufficient to reduce the frequency of self-monitoring or the appropriate frequency of testing in GDM that is well controlled (see section 5.1.1 Glucose target) with nutritional therapy, we recommend decreasing the frequency of glucose monitoringwhen good glycemic control is accomplished with medical nutritional therapy for more than 1 month . Decrease the frequency of glucose monitoring means to measure blood glucose (fasting and 3 postprandial measurements) twice a week instead of every day.
+
Although there are no data on the duration of good control sufficient to reduce the frequency of self-monitoring or the appropriate frequency of testing in GDM that is well controlled (see section 5.1.1 Glucose target) with nutritional therapy, we recommend decreasing the frequency of glucose monitoringwhen good glycemic control is accomplished with medical nutritional therapy for more than 1 month . Decrease the frequency of glucose monitoring means to measure blood glucose (fasting and 3 postprandial measurements) twice a week instead of every day.
The advent of continuous glucose monitoring has the potential to allow determination of peak postprandial glucose levels; future research should determine whether using CGM in management of GDM will improve outcomes.
Glucose target
-
The ACOG recommends the following targets, with insulin therapy initiatedif they are exceeded .
One hour-postprandial glucose < 130 to 140 mg/dL (7.2 to 7.8 mmol/L) or
Two hour-postprandial blood concentration ≤ 120 mg/dL (6.7 mmol/L)
-
+
In 'Hospital de Sabadell', we recommend the patients to measure postprandial blood glucose one hour after the first bite of each meal. For one-hour postprandial glucose, 140 mg/dL is considered the bound to detect anomalous glycemic control.
Little guidance is available as to what proportion of measurements exceeding these thresholds should trigger intervention. Insulin should be considered if elevated blood glucose is observed (see 5.3.1 Insulin).
Glycated hemoglobin (A1C) may be a helpful test in assessing glycemic control during pregnancy, particullarly when overt diabetes is suspected . It should be noted that A1C values tend to be lower in pregnant compared to nonpregnant women because the average blood glucose concentration is about 20 percent lower in pregnant women and, in the first half of pregnancy, there is a rise in red cell mass and a slight decrease in red blood cell life span.
+
Glycated hemoglobin (A1C) may be a helpful test in assessing glycemic control during pregnancy, particullarly when overt diabetes is suspected . It should be noted that A1C values tend to be lower in pregnant compared to nonpregnant women because the average blood glucose concentration is about 20 percent lower in pregnant women and, in the first half of pregnancy, there is a rise in red cell mass and a slight decrease in red blood cell life span.
Ketonuria
-
Although there is conflicting evidence as to whether ketonuria is associated with an adverse effect on cognitive development of the fetus, we routinely monitor fasting urinary ketonesin women with GDM . The patient measures ketonuria using urine strips. Monitor ketonuria routinely means to measure ketones in the urine every day at fasting conditions. If ketonuria is suspected by the patient along the day, she could decide to additionally measure ketonuria before lunch or dinner. The results of ketonuria could be: a) positive (++); b) positive (+); c) negative (+/-); d) negative (-); e) negative (--).
+
Although there is conflicting evidence as to whether ketonuria is associated with an adverse effect on cognitive development of the fetus, we routinely monitor fasting urinary ketonesin women with GDM . The patient measures ketonuria using urine strips. Monitor ketonuria routinely means to measure ketones in the urine every day at fasting conditions. If ketonuria is suspected by the patient along the day, she could decide to additionally measure ketonuria before lunch or dinner. The results of ketonuria could be: a) positive (++); b) positive (+); c) negative (+/-); d) negative (-); e) negative (--).
Ketonuria indicates that the person is in a catabolic state and is breaking down fat, and can occur in anyone who has a negative caloric balance. Pregnant women develop elevated β-hydroxybutyrate levels more rapidly than nonpregnant individuals during a 12- to 18-hour fast, and it is not known whether such elevated levels have an adverse impact on fetal development. Several studies have suggested that early maternal malnutrition can affect neurobehavioral development in children of women with diabetes. In one such study, plasma beta-hydroxybutyrate levels independent of glucose levels had an adverse association with cognitive development in pregnancies in women with prepregnancy diabetes, GDM, and in normal pregnancies.
-
If ketonuria is negative for two weeks , the patient is recommended to measure ketonuria 2 or 3 times a week . In case of ketonuria detection (the number of ketonuria measurements with result "positive" is equal or higher than 3 in a period of time of one week) :
-
If the patient was compliant with the prescribed diet , the nurse decides to increase the carbohydrates intake either at dinner or at bedtime: the amount of carbohydrates at dinner or at bedtime is increased by 1 unit (10 grams) . If post-dinner or fasting glucose values achieve the threshold for insulin treatment as a consequence of increasing the amount of carbohydrates , starting insulin would be the best option .
-
If the patient was not compliant with the prescribed diet , the nurse insists the patient on the importance of eating enough carbohydrates . If the situation is kept for more than 1 additional week , insulin therapy should be started .
+
If ketonuria is negative for two weeks , the patient is recommended to measure ketonuria 2 or 3 times a week . In case of ketonuria detection (the number of ketonuria measurements with result "positive" is equal or higher than 3 in a period of time of one week) :
+
If the patient was compliant with the prescribed diet , the nurse decides to increase the carbohydrates intake either at dinner or at bedtime: the amount of carbohydrates at dinner or at bedtime is increased by 1 unit (10 grams) . If post-dinner or fasting glucose values achieve the threshold for insulin treatment as a consequence of increasing the amount of carbohydrates , starting insulin would be the best option .
+
If the patient was not compliant with the prescribed diet , the nurse insists the patient on the importance of eating enough carbohydrates . If the situation is kept for more than 1 additional week , insulin therapy should be started .
Therapy
Nutrition
-
Patients with GDMshould receive nutritional counseling upon diagnosis and be placed on an appropriate diet . The goals of medical nutritional therapy are to:
+
Patients with GDMshould receive nutritional counseling upon diagnosis and be placed on an appropriate diet . The goals of medical nutritional therapy are to:
Achieve normoglycemia (see ACOG recommendation in 4.1.1 Glucose target)
Prevent ketosis
Provide adequate weight gain
@@ -121,30 +123,30 @@
Once the caloric needs are calculated, carbohydrate intake needs to be distributed across meals and snacks to blunt postprandial hyperglycemia. Carbohydrate intake is limited to less than 55 percent of total calories and should be distributed in 3 main meals and 2-3 snacks. In order to avoid fasting ketonuria and facilitate post-dinner glucose control, a bed-time snack may be needed. As a general recommendation, the patients are informed that complex carbohydrates, such as those in starches and vegetables, are more nutrient dense and raise postprandial blood glucose concentrations less than simple sugars, which should be avoided .
-
Close follow-up is important to ensure nutritional adequacy. Individual assessment and self blood glucose monitoring are used to determine and modify specific nutrition/food recommendations. If the patient acknowledges that she is not following nutritional prescription more than once , she receives specific recommendations about the importance of following nutritional prescription .
+
Close follow-up is important to ensure nutritional adequacy. Individual assessment and self blood glucose monitoring are used to determine and modify specific nutrition/food recommendations. If the patient acknowledges that she is not following nutritional prescription more than once , she receives specific recommendations about the importance of following nutritional prescription .
If insulin therapy is added to nutrition therapy, a primary goal is to maintain carbohydrate consistency at meals and snacks to facilitate insulin adjustments. This decision is taken by nurse + physician.
Exercise
-
The value of exercise in women with GDM requires further exploration to determine the potential range of benefits. Nevertheless, based on the data available in pregnant and in nonpregnant individuals, we recommend the regular practice (≥ 4days/week) of light or moderate exercise (16 - 28 METs hours per week) as part of the treatment planfor women with GDM and no medical or obstetrical contraindications to this level of physical activity .
+
The value of exercise in women with GDM requires further exploration to determine the potential range of benefits. Nevertheless, based on the data available in pregnant and in nonpregnant individuals, we recommend the regular practice (≥ 4days/week) of light or moderate exercise (16 - 28 METs hours per week) as part of the treatment planfor women with GDM and no medical or obstetrical contraindications to this level of physical activity .
-
If the patient does not follow recommendations related to physical activity , she is insisted by the nurse on the importance of following the recommended practice of physical activity .
+
If the patient does not follow recommendations related to physical activity , she is insisted by the nurse on the importance of following the recommended practice of physical activity .
This section of the general guideline will be further developed in more detail.
Pharmacologic therapy
-
If normoglycemia cannot be maintained by medical nutritional therapy , then anti-hyperglycemic agents should be initiated . There is only one option in pregnant patients who require medical therapy aimed at controlling blood glucose: insulin (and some insulin analogs), which is the only recommended approach in Spain.
+
If normoglycemia cannot be maintained by medical nutritional therapy , then anti-hyperglycemic agents should be initiated . There is only one option in pregnant patients who require medical therapy aimed at controlling blood glucose: insulin (and some insulin analogs), which is the only recommended approach in Spain.
Insulin
-
Women with GDMare placed on insulin therapywhen target glucose levels are exceeded despite dietary therapy .
+
Women with GDMare placed on insulin therapywhen target glucose levels are exceeded despite dietary therapy .
In the two randomized trials in which diagnosis and treatment of mild GDM improved outcomes, only 20 and 8 percent of women, respectively, required insulin, while 80 and 92 percent of women, respectively, were treated satisfactorily with diet.
-
Insulin therapy is startedif two or more elevated values are observed in a week period in the same interval (fasting, postprandial breakfast, postprandial lunch, postprandial dinner) . The endocrinologist is the person who takes the decision to start insulin therapy.
+
Insulin therapy is startedif two or more elevated values are observed in a week period in the same interval (fasting, postprandial breakfast, postprandial lunch, postprandial dinner) . The endocrinologist is the person who takes the decision to start insulin therapy.
-
If only two blood glucose targets are exceeded in one specific measurement point (fasting, 1-hour postprandial breakfast, 1-hour postprandial lunch, 1-hour postprandial dinner) and the threshold is exceeded by less than 15 mg/dL , then two situations are considered (only for the first time these situations are detected):
-
If the patient was not compliant with the prescribed diet (diet intake higher than the recommended amount of carbohydrates or eating not recommended food (such as ice cream, buns, cakes, packaged juice, plain sugar, or chocolate) or eating snacks not included in the prescribed diet)then the nurse or the doctor motivate the patient to be compliant with the diet . If the patient was not compliant for three or more different meals in a period of one week, and blood glucose is elevated as a result of non- compliance to nutritional prescription , insulin therapy should be started .
-
If the patient was compliant with the prescribed dietthen the nurse or the doctor can postpone starting insulin therapy by changing the nutritional prescription at lunch or dinner . E.g. two 1h post-dinner values of 142; 145 in a women eating more than or equal to 50 carbohydrate grams for dinner, with persistant negative fasting ketonuria. In this example the reduction at dinner of 10 grams of carbohydrates could be enough for glucose normality restoration. See table for other situations:
+
If only two blood glucose targets are exceeded in one specific measurement point (fasting, 1-hour postprandial breakfast, 1-hour postprandial lunch, 1-hour postprandial dinner) and the threshold is exceeded by less than 15 mg/dL , then two situations are considered (only for the first time these situations are detected):
+
If the patient was not compliant with the prescribed diet (diet intake higher than the recommended amount of carbohydrates or eating not recommended food (such as ice cream, buns, cakes, packaged juice, plain sugar, or chocolate) or eating snacks not included in the prescribed diet)then the nurse or the doctor motivate the patient to be compliant with the diet . If the patient was not compliant for three or more different meals in a period of one week, and blood glucose is elevated as a result of non- compliance to nutritional prescription , insulin therapy should be started .
+
If the patient was compliant with the prescribed dietthen the nurse or the doctor can postpone starting insulin therapy by changing the nutritional prescription at lunch or dinner . E.g. two 1h post-dinner values of 142; 145 in a women eating more than or equal to 50 carbohydrate grams for dinner, with persistant negative fasting ketonuria. In this example the reduction at dinner of 10 grams of carbohydrates could be enough for glucose normality restoration. See table for other situations:
Breakfast?
Lunch
Dinner
Diet 1600 kcal
60 g CARBS --≥ 50 g CARBS
50 g CARBS --≥ 40 g CARBS
Diet 1800 kcal
85 g CARBS --≥ 75 g CARBS
55 g CARBS --≥ 45 g CARBS
@@ -152,16 +154,16 @@
Furthermore, the newborn weight prognosis based on ultrasoud measurements may be taken into account in the decision of starting insulin therapy; For fetus considered large for gestational age, one hour-postprandial glucose values above 120 mg/dL are enough for starting insulin. On the contrary, when the fetus is considered small for gestational age, 140 mg/dl should be the threshold value for considering insulin treatment. Definition of Small Gestational Age (percentile ≤ 10) and Large Gestational Age (percentile > 90).
-
The dose and type of insulin used is calculated based upon the specific abnormality of blood glucose noted during monitoring. One principle we have found useful is to start with the simplest regimen and increase the complexity as needed to address the particular situation. If the post-dinner glucose level is elevated , then an injection of rapid acting insulin is given just prior to dinner . Additional doses of rapid acting insulin can be necessary to maintain euglycemia after breakfast or lunch. If fasting glucose is elevated , intermediate acting insulin can be given at bedtime , then a total of four injections per day are needed.
+
The dose and type of insulin used is calculated based upon the specific abnormality of blood glucose noted during monitoring. One principle we have found useful is to start with the simplest regimen and increase the complexity as needed to address the particular situation. If the post-dinner glucose level is elevated , then an injection of rapid acting insulin is given just prior to dinner . Additional doses of rapid acting insulin can be necessary to maintain euglycemia after breakfast or lunch. If fasting glucose is elevated , intermediate acting insulin can be given at bedtime , then a total of four injections per day are needed.
In summary:
-
If insulin is required because the fasting blood glucose concentration is high , an intermediate-acting insulin (NPH insulin), is given before bedtime; an initial dose of 0.1-0.15 unit/kg body weight is utilized .
-
If postprandial blood glucose concentrations are high , insulin aspart or insulin lispro is given before meals at an initial dose of 4-6 units .
-
In a severely obese woman , the initial doses of insulin may need to be increased to overcome the combined insulin resistance of pregnancy and obesity . This should be personalized by the endocrinologist according to each patient’s characteristics.
+
If insulin is required because the fasting blood glucose concentration is high , an intermediate-acting insulin (NPH insulin), is given before bedtime; an initial dose of 0.1-0.15 unit/kg body weight is utilized .
+
If postprandial blood glucose concentrations are high , insulin aspart or insulin lispro is given before meals at an initial dose of 4-6 units .
+
In a severely obese woman , the initial doses of insulin may need to be increased to overcome the combined insulin resistance of pregnancy and obesity . This should be personalized by the endocrinologist according to each patient’s characteristics.
Subsequent (weekly) adjustments in the various components of the insulin regimen are made based upon the corresponding glucose levels. Because any insulin regimen requires serial readjustment of dosage in response to specific fasting or postprandial glucose levels, the starting dose should be considered just that, a starting point. Adjustments in insulin dosage may be done to achieve the above mentioned objectives.
-
Hypoglycemia remote from meal or snack time is rare in women with GDM , and is treated by administering 10 to 20 g of a simple sugar like orange juice or non-fat milk . The patient is instructed to take this decision after getting a measure of blood glucose. If low glucose values are encountered more than once at the same time of day , insulin doses are adjusted downward accordingly .
+
Hypoglycemia remote from meal or snack time is rare in women with GDM , and is treated by administering 10 to 20 g of a simple sugar like orange juice or non-fat milk . The patient is instructed to take this decision after getting a measure of blood glucose. If low glucose values are encountered more than once at the same time of day , insulin doses are adjusted downward accordingly .
Long-acting insulin analogs (insulin glargine, insulin detemir) have not been studied extensively in pregnancy. However, insulin detemir has been recently approved by the EMEA for the treatment of women with diabetes and pregnancy. In vitro perfusion studies have demonstrated that insulin glargine does not cross the placenta, however, concern about transplacental transfer of glargine in vivo remains. Based on available data, we prefer use of human NPH insulin as part of a multiple injection regimen in pregnant women with GDM.
Oral anti-hyperglycemic agents
@@ -195,12 +197,12 @@
ACOG, the ADA and the Fifth International Workshop Conference on Gestational Diabetes recommend long-term follow-up of women with GDM:
-
All women with previous GDMshould undergo an oral glucose tolerance test 6 to 12 weeks after delivery, using a two-hour 75 gram oral glucose tolerance test . An abnormal fasting blood glucose level is diagnostic (diabetes if ≥ 126 mg/dL, impaired fasting glucose (IFG) if 100 to 125 mg/dL); however, sensitivity for diagnosis of diabetes is low. Impaired glucose tolerance (IGT) is diagnosed if the two-hour value is 140 to 199 mg/dL . Collectively, IFG and IGT are known as "prediabetes."
+
All women with previous GDMshould undergo an oral glucose tolerance test 6 to 12 weeks after delivery, using a two-hour 75 gram oral glucose tolerance test . An abnormal fasting blood glucose level is diagnostic (diabetes if ≥ 126 mg/dL, impaired fasting glucose (IFG) if 100 to 125 mg/dL); however, sensitivity for diagnosis of diabetes is low. Impaired glucose tolerance (IGT) is diagnosed if the two-hour value is 140 to 199 mg/dL . Collectively, IFG and IGT are known as "prediabetes."
Women with an abnormal oral glucose tolerance test are then classified as having prediabetes or overt diabetes mellitus
-
Those with prediabetesshould be counseled about their subsequent risk for developing overt diabetes and referred for discussion of management options (eg, lifetime modification such as medical nutritional therapy, indications for metformin) . They should try to achieve their ideal body weight through diet and exercise and, if possible, they should avoid drugs that may adversely affect glucose tolerance (eg, glucocorticoids). They should have yearly assessment of glycemic status.
-
A woman who has overt diabetes mellitusshould receive appropriate education and treatment. She should also be given advice regarding contraception and the planning of future pregnancies.
-
Women with prediabetes or overt diabetesshould be counseled regarding the importance of good metabolic control prior to any future pregnancies .
-
Women with normal glucose toleranceshould be counseled regarding their risk of developing GDM in subsequent pregnancies and type 2 diabetes in the future . Lifestyle interventions (weight loss, exercise) are clearly beneficial for reducing the incidence of these disorders. Drug therapy (eg, metformin) also may have a role in preventing future type 2 diabetes.
+
Those with prediabetesshould be counseled about their subsequent risk for developing overt diabetes and referred for discussion of management options (eg, lifetime modification such as medical nutritional therapy, indications for metformin) . They should try to achieve their ideal body weight through diet and exercise and, if possible, they should avoid drugs that may adversely affect glucose tolerance (eg, glucocorticoids). They should have yearly assessment of glycemic status.
+
A woman who has overt diabetes mellitusshould receive appropriate education and treatment. She should also be given advice regarding contraception and the planning of future pregnancies.
+
Women with prediabetes or overt diabetesshould be counseled regarding the importance of good metabolic control prior to any future pregnancies .
+
Women with normal glucose toleranceshould be counseled regarding their risk of developing GDM in subsequent pregnancies and type 2 diabetes in the future . Lifestyle interventions (weight loss, exercise) are clearly beneficial for reducing the incidence of these disorders. Drug therapy (eg, metformin) also may have a role in preventing future type 2 diabetes.
Visualizing Declarative Knowledge Bases of Clinical Practice Guideline Models
+
+ Declarative knowledge is factual knowledge that someone knows. It is also contained in the condition expressions to control activities, but also as definitions elsewhere in the text.
+ Hereby, we have a set of knowledge bases from different clinical guidelines modeled in the "Temporal Abstraction Knowledge" format [1]. The guidelines are from different clinical specialties. The "Gold Standard" model of gestational diabetes management (GDM) was modelled manually by a knowledge engineer. All other models have been generated automatically using the LASSIE methodology.
+
+
+
KBTA model:
+
+
-
+
Concept ID:
@@ -36,11 +48,13 @@
KBTA model:
Derived from:
Used by:
+
See also the Concept Viewer for concepts of a particular condition.
+
+
+ [1] Y. Shahar. A Framework for Knowledge-based Temporal Abstraction in Clinical Domains. Artificial Intelligence 90(1):79-133, 1997.
.
+