The evidence grading system for clinical practice recommendations (A through C, E) is defined at the end of the "Major Recommendations" field.
Cardiovascular Disease (CVD)
Hypertension (HTN)/Blood Pressure Control
Screening and Diagnosis
- Blood pressure should be measured at every routine diabetes visit. Patients found to have systolic blood pressure >130 mmHg or diastolic blood pressure >80 mmHg should have blood pressure confirmed on a separate day. Repeat systolic blood pressure >130 mmHg or diastolic blood pressure >80 mmHg confirms a diagnosis of hypertension. (C)
Goals
- Patients with diabetes should be treated to a systolic blood pressure <130 mmHg. (C)
- Patients with diabetes should be treated to a diastolic blood pressure <80 mmHg. (B)
Treatment
- Patients with a systolic blood pressure of 130 to 139 mmHg or a diastolic blood pressure of 80 to 89 mmHg may be given lifestyle therapy alone for a maximum of 3 months and then, if targets are not achieved, be treated with addition of pharmacological agents. (E)
- Patients with more severe hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg) at diagnosis or follow-up should receive pharmacologic therapy in addition to lifestyle therapy. (A)
- Pharmacologic therapy for patients with diabetes and hypertension should be with a regimen that includes either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB). If one class is not tolerated, the other should be substituted. If needed to achieve blood pressure targets, a thiazide diuretic should be added to those with an estimated glomerular filtration rate (GFR) >50 ml/min per 1.73 m2 and a loop diuretic for those with an estimated GFR <50 ml/min per 1.73 m2. (E)
- Multiple drug therapy (two or more agents at maximal doses) is generally required to achieve blood pressure targets. (B)
- If ACE inhibitors, ARBs, or diuretics are used, kidney function and serum potassium levels should be closely monitored. (E)
- In pregnant patients with diabetes and chronic hypertension, blood pressure target goals of 110 to 129/65 to 79 mmHg are suggested in the interest of long-term maternal health and minimizing impaired fetal growth. ACE inhibitors and ARBs are contraindicated during pregnancy. (E)
Dyslipidemia/Lipid Management
Screening
- In most adult patients, measure fasting lipid profile at least annually. In adults with low-risk lipid values (low-density lipoprotein [LDL] cholesterol <100 mg/dL, high-density lipoprotein [HDL] cholesterol >50 mg/dL, and triglycerides <150 mg/dL), lipid assessments may be repeated every 2 years. (E)
Treatment Recommendations and Goals
- Lifestyle modification focusing on the reduction of saturated fat, trans fat, and cholesterol intake; weight loss (if indicated); and increased physical activity has been shown to improve the lipid profile in patients with diabetes. (A)
- Statin therapy should be added to lifestyle therapy, regardless of baseline lipid levels, for diabetic patients:
- With overt cardiovascular disease (CVD) (A)
- Without CVD who are over the age of 40 and have one or more other CVD risk factors. (A)
- For lower-risk patients than those specified above (e.g., without overt CVD and under the age of 40), statin therapy should be considered in addition to lifestyle therapy if LDL cholesterol remains >100 mg/dL or in those with multiple CVD risk factors. (E)
- In individuals without overt CVD, the primary goal is an LDL cholesterol <100 mg/dL (2.6 mmol/l). (A)
- In individuals with overt CVD, a lower LDL cholesterol goal of <70 mg/dl (1.8 mmol/l), using a high dose of a statin, is an option. (E)
- If drug-treated patients do not reach the above targets on maximal tolerated statin therapy, a reduction in LDL cholesterol of ~40% from baseline is an alternative therapeutic goal. (A)
- Triglycerides levels <150 mg/dL (1.7 mmol/l) and HDL cholesterol >40 mg/dL (1.0 mmol/l) in men and >50 mg/dL (1.3 mmol/l) in women are desirable. However, LDL cholesterol-targeted statin therapy remains the preferred strategy. (C)
- Combination therapy using statins and other lipid-lowering agents may be considered to achieve lipid targets but has not been evaluated in outcomes studies for either CVD outcomes or safety. (E)
- Statin therapy is contraindicated in pregnancy. (E)
Anti-platelet Agents
- Use aspirin therapy (75 to 162 mg/day) as a secondary prevention strategy in those with diabetes with a history of CVD. (A)
- Use aspirin therapy (75 to 162 mg/day) as a primary prevention strategy in those with type 1 and 2 diabetes at increased cardiovascular risk, including those who are >40 years of age or who have additional risk factors (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria) (A)
- Aspirin therapy is not recommended in people under 30 years of age, due to lack of evidence of benefit, and is contraindicated in patients under the age of 21 years because of the associated risk of Reye's syndrome. (E)
- Combination therapy using other antiplatelet agents such as clopidogrel in addition to aspirin should be used in patients with severe and progressive CVD. (C)
- Other antiplatelet agents may be a reasonable alternative for high-risk patients with aspirin allergy, with bleeding tendency, who are receiving anticoagulant therapy, with recent gastrointestinal bleeding, and with clinically active hepatic disease who are not candidates for aspirin therapy. (E)
Smoking Cessation
- Advise all patients not to smoke. (A)
- Include smoking cessation counseling and other forms of treatment as a routine component of diabetes care. (B)
Coronary Heart Disease (CHD) Screening and Treatment
Screening
- In asymptomatic patients, evaluate risk factors to stratify patients by 10-year risk, and treat risk factors accordingly. (B)
Treatment
- In patients with known CVD, ACE inhibitor, aspirin, and statin therapy (if not contraindicated) should be used to reduce the risk of cardiovascular events. (A)
- In patients with a prior myocardial infarction, add beta-blockers (if not contraindicated) to reduce mortality. (A)
- In patients >40 years of age with another cardiovascular risk factor (hypertension, family history, dyslipidemia, microalbuminuria, cardiac autonomic neuropathy, or smoking), ACE inhibitor, aspirin, and statin therapy (if not contraindicated) should be used to reduce the risk of cardiovascular events. (B)
- In patients with treated congestive heart failure (CHF), metformin and thiazolidinedione (TZD) use are contraindicated. (C)
Nephropathy Screening and Treatment
General Recommendations
- To reduce the risk or slow the progression of nephropathy, optimize glucose control. (A)
- To reduce the risk or slow the progression of nephropathy, optimize blood pressure control. (A)
Screening
- Perform an annual test to assess urine albumin excretion in type 1 diabetic patients with diabetes duration of >5 years and in all type 2 diabetic patients, starting at diagnosis. (E)
- Measure serum creatinine at least annually in all adults with diabetes regardless of the degree of urine albumin excretion. The serum creatinine should be used to estimate glomerular filtration rate (GFR) and stage the level of chronic kidney disease (CKD), if present. (E)
Treatment
- In the treatment of the nonpregnant patient with micro- and macroalbuminuria, either ACE inhibitors or ARBs should be used. (A)
- While there are no adequate head-to-head comparisons of ACE inhibitors and ARBs, there is clinical trial support for each of the following statements:
- In patients with type 1 diabetes, with hypertension and any degree of albuminuria, ACE inhibitors have been shown to delay the progression of nephropathy. (A)
- In patients with type 2 diabetes, hypertension, and microalbuminuria, both ACE inhibitors and ARBs have been shown to delay the progression to macroalbuminuria. (A)
- In patients with type 2 diabetes, hypertension, macroalbuminuria, and renal insufficiency (serum creatinine >1.5 mg/dL), ARBs have been shown to delay the progression of nephropathy. (A)
- If one class is not tolerated, the other should be substituted. (E)
- Reduction of protein intake to 0.8 to 1.0 g/kg body wt/day in individuals with diabetes and the earlier stages of CKD and to 0.8 g/kg body wt/day in the later stages of CKD may improve measures of renal function (e.g., urine albumin excretion rate and GFR) and is recommended. (B)
- When ACE inhibitors, ARBs, or diuretics are used, monitor serum creatinine and potassium levels for the development of acute kidney disease and hyperkalemia.(E)
- Continued monitoring of urine albumin excretion to assess both response to therapy and progression of disease is recommended. (E)
- Consider referral to a physician experienced in the care of kidney disease when there is uncertainty about the etiology of kidney disease (active urine sediment, absence of retinopathy, rapid decline in GFR), difficult management issues, or advanced kidney disease. (B)
Retinopathy Screening and Treatment
General Recommendations
- To reduce the risk or slow the progression of retinopathy, optimize glycemic control. (A)
- To reduce the risk or slow the progression of retinopathy, optimize blood pressure control. (A)
Screening
- Adults and adolescents with type 1 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist or optometrist within 5 years after the onset of diabetes. (B)
- Patients with type 2 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist or optometrist shortly after the diagnosis of diabetes. (B)
- Subsequent examinations for type 1 and type 2 diabetic patients should be repeated annually by an ophthalmologist or optometrist. Less frequent exams (every 2 to 3 years) may be considered following one or more normal eye exams. Examinations will be required more frequently if retinopathy is progressing. (B)
- Women with pre-existing diabetes who are planning pregnancy or who have become pregnant should have a comprehensive eye examination and be counseled on the risk of development and/or progression of diabetic retinopathy. Eye examinations should occur in the first trimester with close follow-up throughout pregnancy and for 1 year postpartum. (B)
Treatment
- Promptly refer patients with any level of macular edema, severe nonproliferative diabetic retinopathy (NPDR), or any proliferative diabetic retinopathy (PDR) to an ophthalmologist who is knowledgeable and experienced in the management and treatment of diabetic retinopathy. (A)
- Laser photocoagulation therapy is indicated to reduce the risk of vision loss in patients with high-risk PDR, clinically significant macular edema, and in some cases of severe NPDR. (A)
- The presence of retinopathy is not a contraindication to aspirin therapy for cardioprotection, as this therapy does not increase the risk of retinal hemorrhage. (A)
Neuropathy Screening and Treatment
- All patients should be screened for distal symmetric polyneuropathy (DPN) at diagnosis and at least annually thereafter, using simple clinical tests. (B)
- Electrophysiological testing is rarely needed, except in situations where the clinical features are atypical. (E)
- Educate all patients about self-care of the feet. For those with DPN, facilitate enhanced foot care education and refer for special footwear. (B)
- Screening for signs and symptoms of autonomic neuropathy should be instituted at diagnosis of type 2 diabetes and 5 years after the diagnosis of type 1 diabetes. Special testing is rarely needed and may not affect management or outcomes. (E)
- Medications for the relief of specific symptoms related to DPN and autonomic neuropathy are recommended, as they improve the quality of life of the patient. (E)
Foot Care
- For all patients with diabetes, perform an annual comprehensive foot examination to identify risk factors predictive of ulcers and amputations. The foot examination can be accomplished in a primary care setting and should include the use of a monofilament, tuning fork, palpation, and a visual examination. (B)
- Provide general foot self-care education to all patients with diabetes (B)
- A multidisciplinary approach is recommended for individuals with foot ulcers and high-risk feet, especially those with a history of prior ulcer or amputation. (B)
- Refer patients who smoke, have loss of protective sensation and structural abnormalities, or have history of prior lower-extremity complications to foot care specialists for ongoing preventive care and life-long surveillance. (C)
- Initial screening for peripheral arterial disease (PAD) should include a history for claudication and an assessment of the pedal pulses. Consider obtaining an ankle-brachial index (ABI), as many patients with peripheral arterial disease are asymptomatic. (C)
- Refer patients with significant claudication or a positive ABI for further vascular assessment and consider exercise, medications, and surgical options. (C)
Definitions:
American Diabetes Association's Evidence Grading System for Clinical Practice Recommendations
A
Clear evidence from well-conducted, generalizable, randomized controlled trials that are adequately powered, including:
- Evidence from a well-conducted multicenter trial
- Evidence from a meta-analysis that incorporated quality ratings in the analysis
- Compelling non-experimental evidence (i.e., "all or none" rule developed by the Center for Evidence Based Medicine at Oxford*)
Supportive evidence from well-conducted randomized, controlled trials that are adequately powered, including:
- Evidence from a well-conducted trial at one or more institutions
- Evidence from a meta-analysis that incorporated quality ratings in the analysis
*
Either all patients died before therapy and at least some survived with therapy, or some patients died without therapy and none died with therapy. Example: use of insulin in the treatment of diabetic ketoacidosis.
B
Supportive evidence from well-conducted cohort studies, including:
- Evidence from a well-conducted prospective cohort study or registry
- Evidence from a well-conducted meta-analysis of cohort studies
Supportive evidence from a well-conducted case-control study
C
Supportive evidence from poorly controlled or uncontrolled studies, including:
- Evidence from randomized clinical trials with one or more major or three or more minor methodological flaws that could invalidate the results
- Evidence from observational studies with high potential for bias (such as case series with comparison with historical controls)
- Evidence from case series or case reports
Conflicting evidence with the weight of evidence supporting the recommendation
E
Expert consensus or clinical experience
