CVD is the major cause of morbidity and mortality for individuals with diabetes, and the largest contributor to the direct and indirect costs of diabetes. The common conditions coexisting with type 2 diabetes (e.g., hypertension and dyslipidemia) are clear risk factors for CVD, and diabetes itself confers independent risk. Numerous studies have shown the efficacy of controlling individual cardiovascular risk factors in preventing or slowing CVD in people with diabetes. Large benefits are seen when multiple risk factors are addressed globally (188
). Risk for coronary heart disease (CHD) and for CVD in general can be estimated using multivariable risk factor approaches, and such a strategy may be desirable to undertake in adult patients prior to instituting preventive therapy.
1. Hypertension/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)
- A goal systolic blood pressure <130 mmHg is appropriate for most patients with diabetes. (C)
- Based on patient characteristics and response to therapy, higher or lower systolic blood pressure targets may be appropriate. (B)
- Patients with diabetes should be treated to a diastolic blood pressure <80 mmHg. (B)
- Patients with a systolic blood pressure of 130–139 mmHg or a diastolic blood pressure of 80–89 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 or diastolic blood pressure ≥90 mmHg) at diagnosis or follow-up should receive pharmacologic therapy in addition to lifestyle therapy. (A)
- Lifestyle therapy for hypertension consists of: weight loss, if overweight; Dietary Approaches to Stop Hypertension (DASH)-style dietary pattern including reducing sodium and increasing potassium intake; moderation of alcohol intake; and increased physical activity. (B)
- Pharmacologic therapy for patients with diabetes and hypertension should be with a regimen that includes either an ACE inhibitor or an 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 GFR (eGFR) (see below) ≥30 ml/min/1.73 m2 and a loop diuretic for those with an eGFR <30 ml/min/1.73 m2. (C)
- 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 monitored. (E)
- In pregnant patients with diabetes and chronic hypertension, blood pressure target goals of 110–129/65–79 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)
Hypertension is a common comorbidity of diabetes, affecting the majority of patients, with prevalence depending on type of diabetes, age, obesity, and ethnicity. Hypertension is a major risk factor for both CVD and microvascular complications. In type 1 diabetes, hypertension is often the result of underlying nephropathy, while in type 2 diabetes it usually coexists with other cardiometabolic risk factors.
Screening and diagnosis
Measurement of blood pressure in the office should be done by a trained individual and should follow the guidelines established for nondiabetic individuals: measurement in the seated position, with feet on the floor and arm supported at heart level, after 5 min of rest. Cuff size should be appropriate for the upper arm circumference. Elevated values should be confirmed on a separate day. Because of the clear synergistic risks of hypertension and diabetes, the diagnostic cut-off for a diagnosis of hypertension is lower in people with diabetes (blood pressure ≥130/80) than those without diabetes (blood pressure 140/90 mmHg) (190
Home blood pressure self-monitoring and 24-h ambulatory blood pressure monitoring may provide additional evidence of “white coat” and masked hypertension and other discrepancies between office and “true” blood pressure, and in studies in nondiabetic populations, home measurements may better correlate with CVD risk than office measurements (191
). However, the preponderance of the clear evidence of benefits of treatment of hypertension in people with diabetes is based on office measurements.
Epidemiologic analyses show that blood pressure values >115/75 mmHg are associated with increased cardiovascular event rates and mortality in individuals with diabetes (190
). Randomized clinical trials have demonstrated the benefit (reduction in CHD events, stroke, and nephropathy) of lowering blood pressure to <140 mmHg systolic and <80 mmHg diastolic in individuals with diabetes (190
). The ACCORD trial examined whether lowering blood pressure to a systolic <120 mmHg provides greater cardiovascular protection than a systolic blood pressure level of 130–140 mmHg in patients with type 2 diabetes at high risk for CVD (198
). The blood pressure achieved was 119/64 mmHg in the intensive group and 133/70 mmHg in the standard group; the difference achieved was attained with an average of 3.4 medications per participant in the intensive group and 2.1 in the standard therapy group. The primary outcome was a composite of nonfatal MI, nonfatal stroke, and CVD death; the hazard ratio for the primary end point in the intensive group was 0.88 (95% CI 0.73–1.06; P
= 0.20). Of the prespecified secondary end points, only stroke and nonfatal stroke were statistically significantly reduced by intensive blood pressure treatment, with a hazard ratio of 0.59 (95% CI 0.39–0.89, P
= 0.01) and 0.63 (95% CI 0.41–0.96, P
= 0.03), respectively. If this finding is real, the number needed to treat to prevent one stroke over the course of 5 years with intensive blood pressure management is 89.
In predefined subgroup analyses, there was a suggestion of heterogeneity (P = 0.08) based on whether participants were randomized to standard or intensive glycemia intervention. In those randomized to standard glycemic control, the event rate for the primary end point was 1.89 per year in the intensive blood pressure arm and 2.47 in the standard blood pressure arm, while the respective rates in the intensive glycemia arm were 1.85 and 1.73. If this observation is true, it suggests that intensive management to a systolic blood pressure target of <120 mmHg may be of benefit in those who are not targeting an A1C of <6% and/or that the benefit of intensive blood pressure management is diminished by more intensive glycemia management targeting an A1C of <6%.
Other recent randomized trial data include those from ADVANCE, in which treatment with an angiotensin-converting enzyme inhibitor and a thiazide-type diuretic reduced the rate of death but not the composite macrovascular outcome. However, the ADVANCE trial had no specified targets for the randomized comparison, and the mean systolic blood pressure in the intensive group (135 mmHg) was not as low as the mean systolic blood pressure in the ACCORD standard therapy group (199
). A post hoc analysis of blood pressure control in 6,400 patients with diabetes and CAD enrolled in the International Verapamil-Trandolapril (INVEST) trial demonstrated that “tight control” (<130 mmHg) was not associated with improved CV outcomes compared with “usual care” (130–140 mmHg) (200
Only the ACCORD blood pressure trial formally has examined treatment targets <130 mmHg in diabetes. It is possible that lowering systolic blood pressure from the low-130s to less than 120 mmHg does not further reduce coronary events or death, and that most of the benefit from lowering blood pressure is achieved by targeting a goal of <140 mmHg. However, this has not been formally assessed.
The absence of significant harm, the trends toward benefit in stroke, and the potential heterogeneity with respect to intensive glycemia management suggests that previously recommended targets are reasonable pending further analyses and results. Systolic blood pressure targets more or less stringent than <130 mmHg may be appropriate for individual patients, based on response to therapy, medication tolerance, and individual characteristics, keeping in mind that most analyses have suggested that outcomes are worse if the systolic blood pressure is >140 mmHg.
Although there are no well-controlled studies of diet and exercise in the treatment of hypertension in individuals with diabetes, the Dietary Approaches to Stop Hypertension (DASH) study in nondiabetic individuals has shown anti-hypertensive effects similar to pharmacologic monotherapy. Lifestyle therapy consists of reducing sodium intake (to <1,500 mg/day) and excess body weight; increasing consumption of fruits, vegetables (8–10 servings/day), and low-fat dairy products (2–3 servings/day); avoiding excessive alcohol consumption (no more than 2 servings/day in men and no more than 1 serving/day in women) (201
); and increasing activity levels (190
). These nonpharmacological strategies may also positively affect glycemia and lipid control. Their effects on cardiovascular events have not been established. An initial trial of nonpharmacologic therapy may be reasonable in diabetic individuals with mild hypertension (systolic blood pressure 130–139 mmHg or diastolic blood pressure 80–89 mmHg). If systolic blood pressure is ≥140 mmHg and/or diastolic is ≥90 mmHg at the time of diagnosis, pharmacologic therapy should be initiated along with nonpharmacologic therapy (190
Lowering of blood pressure with regimens based on a variety of antihypertensive drugs, including ACE inhibitors, ARBs, β-blockers, diuretics, and calcium channel blockers, has been shown to be effective in reducing cardiovascular events. Several studies suggested that ACE inhibitors may be superior to dihydropyridine calcium channel blockers in reducing cardiovascular events (202
). However, a variety of other studies have shown no specific advantage to ACE inhibitors as initial treatment of hypertension in the general hypertensive population, but rather an advantage on cardiovascular outcomes of initial therapy with low-dose thiazide diuretics (190
In people with diabetes, inhibitors of the renin-angiotensin system (RAS) may have unique advantages for initial or early therapy of hypertension. In a nonhypertension trial of high-risk individuals, including a large subset with diabetes, an ACE inhibitor reduced CVD outcomes (207
). In patients with congestive heart failure (CHF), including diabetic subgroups, ARBs have been shown to reduce major CVD outcomes (208
), and in type 2 patients with significant nephropathy, ARBs were superior to calcium channel blockers for reducing heart failure (212
). Though evidence for distinct advantages of RAS inhibitors on CVD outcomes in diabetes remains conflicting (195
), the high CVD risks associated with diabetes, and the high prevalence of undiagnosed CVD, may still favor recommendations for their use as first-line hypertension therapy in people with diabetes (190
). Recently, the blood pressure arm of the ADVANCE trial demonstrated that routine administration of a fixed combination of the ACE inhibitor perindopril and the diuretic indapamide significantly reduced combined microvascular and macrovascular outcomes, as well as CVD and total mortality. The improved outcomes could also have been due to lower achieved blood pressure in the perindopril-indapamide arm (199
). In addition, the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed a decrease in morbidity and mortality in those receiving benazapril and amlodipine versus benazapril and hydrochlorothiazide. The compelling benefits of RAS inhibitors in diabetic patients with albuminuria or renal insufficiency provide additional rationale for use of these agents (see VI.B. Nephropathy screening and treatment).
An important caveat is that most patients with hypertension require multi-drug therapy to reach treatment goals, especially diabetic patients whose targets are lower. Many patients will require three or more drugs to reach target goals (190
). If blood pressure is refractory to optimal doses of at least three antihypertensive agents of different classifications, one of which should be a diuretic, clinicians should consider an evaluation for secondary forms of hypertension.
During pregnancy in diabetic women with chronic hypertension, target blood pressure goals of systolic blood pressure 110–129 mmHg and diastolic blood pressure 65–79 mmHg are reasonable, as they contribute to long-term maternal health. Lower blood pressure levels may be associated with impaired fetal growth. During pregnancy, treatment with ACE inhibitors and ARBs is contraindicated, since they can cause fetal damage. Antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, labetalol, diltiazem, clonidine, and prazosin. Chronic diuretic use during pregnancy has been associated with restricted maternal plasma volume, which might reduce uteroplacental perfusion (213
2. Dyslipidemia/lipid management
- In most adult patients, measure fasting lipid profile at least annually. In adults with low-risk lipid values (LDL cholesterol <100 mg/dl, 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; increase of omega-3 fatty acids, viscous fiber, and plant stanols/sterols; weight loss (if indicated); and increased physical activity should be recommended 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 CVD. (A)
- without CVD who are over age 40 years and have one or more other CVD risk factors. (A)
- For patients at lower risk than above (e.g., without overt CVD and under age 40 years), statin therapy should be considered in addition to lifestyle therapy if LDL cholesterol remains above 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. (B)
- If drug-treated patients do not reach the above targets on maximal tolerated statin therapy, a reduction in LDL cholesterol of ~30–40% from baseline is an alternative therapeutic goal. (A)
- Triglyceride 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)
- If targets are not reached on maximally tolerated doses of statins, combination therapy using statins and other lipid-lowering agents may be considered to achieve lipid targets but has not been evaluated in outcome studies for either CVD outcomes or safety. (E)
- Statin therapy is contraindicated in pregnancy. (E)
Evidence for benefits of lipid-lowering therapy
Patients with type 2 diabetes have an increased prevalence of lipid abnormalities, contributing to their high risk of CVD. For the past decade or more, multiple clinical trials demonstrated significant effects of pharmacologic (primarily statin) therapy on CVD outcomes in subjects with CHD and for primary CVD prevention (214
). Sub-analyses of diabetic subgroups of larger trials (215
) and trials specifically in subjects with diabetes (220
) showed significant primary and secondary prevention of CVD events ± CHD deaths in diabetic populations. As shown in , and similar to findings in nondiabetic subjects, reduction in “hard” CVD outcomes (CHD death and nonfatal MI) can be more clearly seen in diabetic subjects with high baseline CVD risk (known CVD and/or very high LDL cholesterol levels), but overall the benefits of statin therapy in people with diabetes at moderate or high risk for CVD are convincing.
Reduction in 10-year risk of major CVD endpoints (CHD death/non-fatal MI) in major statin trials, or substudies of major trials, in diabetic subjects (n = 16,032)
Low levels of HDL cholesterol, often associated with elevated triglyceride levels, are the most prevalent pattern of dyslipidemia in persons with type 2 diabetes. However, the evidence base for drugs that target these lipid fractions is significantly less robust than that for statin therapy (222
). Nicotinic acid has been shown to reduce CVD outcomes (223
), although the study was done in a nondiabetic cohort. Gemfibrozil has been shown to decrease rates of CVD events in subjects without diabetes (224
) and in the diabetic subgroup in one of the larger trials (224
). However, in a large trial specific to diabetic patients, fenofibrate failed to reduce overall cardiovascular outcomes (226
Dyslipidemia treatment and target lipid levels
For most patients with diabetes, the first priority of dyslipidemia therapy (unless severe hypertriglyceridemia is the immediate issue) is to lower LDL cholesterol to a target goal of <100 mg/dl (2.60 mmol/l) (227
). Lifestyle intervention, including MNT, increased physical activity, weight loss, and smoking cessation, may allow some patients to reach lipid goals. Nutrition intervention should be tailored according to each patient's age, type of diabetes, pharmacological treatment, lipid levels, and other medical conditions and should focus on the reduction of saturated fat, cholesterol, and trans
unsaturated fat intake and increases in omega-3 fatty acids, viscous fiber (such as in oats, legumes, citrus), and plant stanols/sterols. Glycemic control can also beneficially modify plasma lipid levels, particularly in patients with very high triglycerides and poor glycemic control.
In those with clinical CVD or over age 40 years with other CVD risk factors, pharmacological treatment should be added to lifestyle therapy regardless of baseline lipid levels. Statins are the drugs of choice for LDL cholesterol lowering.
In patients other than those described above, statin treatment should be considered if there is an inadequate LDL cholesterol response to lifestyle modifications and improved glucose control, or if the patient has increased cardiovascular risk (e.g., multiple cardiovascular risk factors or long duration of diabetes). Very little clinical trial evidence exists for type 2 diabetic patients under age 40 years or for type 1 patients of any age. In the Heart Protection Study (lower age limit 40 years), the subgroup of 600 patients with type 1 diabetes had a proportionately similar reduction in risk as patients with type 2 diabetes, although not statistically significant (216
). Although the data are not definitive, consideration should be given to similar lipid-lowering goals in type 1 diabetic patients as in type 2 diabetic patients, particularly if they have other cardiovascular risk factors.
Alternative LDL cholesterol goals
Virtually all trials of statins and CVD outcomes tested specific doses of statins against placebo, other doses of statin, or other statins, rather than aiming for specific LDL cholesterol goals (228
). As can be seen in , placebo-controlled trials generally achieved LDL cholesterol reductions of 30–40% from baseline. Hence, LDL cholesterol lowering of this magnitude is an acceptable outcome for patients who cannot reach LDL cholesterol goals due to severe baseline elevations in LDL cholesterol and/or intolerance of maximal, or any, statin doses. Additionally for those with baseline LDL cholesterol minimally above 100 mg/dl, prescribing statin therapy to lower LDL cholesterol about 30–40% from baseline is probably more effective than prescribing just enough to get LDL cholesterol slightly below 100 mg/dl.
Recent clinical trials in high-risk patients, such as those with acute coronary syndromes or previous cardiovascular events (229
), have demonstrated that more aggressive therapy with high doses of statins to achieve an LDL cholesterol of <70 mg/dl led to a significant reduction in further events. Therefore, a reduction in LDL cholesterol to a goal of <70 mg/dl is an option in very-high-risk diabetic patients with overt CVD (232
In individual patients, LDL cholesterol lowering with statins is highly variable, and this variable response is poorly understood (233
). Reduction of CVD events with statins correlates very closely with LDL cholesterol lowering (214
). When maximally tolerated doses of statins fail to significantly lower LDL cholesterol (<30% reduction from patients baseline), the primary aim of combination therapy should be to achieve additional LDL cholesterol lowering. Niacin, fenofibrate, ezetimibe, and bile acid sequestrants all offer additional LDL cholesterol lowering. The evidence that combination therapy provides a significant increment in CVD risk reduction over statin therapy alone is still elusive.
In 2008, a consensus panel convened by the American Diabetes Association and the American College of Cardiology recommended a greater focus on non-HDL cholesterol and apo lipoprotein B (apo B) in patients who are likely to have small LDL particles, such as people with diabetes (234
). The consensus panel suggested that for statin-treated patients in whom the LDL cholesterol goal would be <70 mg/dl (non-HDL cholesterol <100 mg/dl), apo B should be measured and treated to <80 mg/dl. For patients on statins with an LDL cholesterol goal of <100 mg/dl (non-HDL cholesterol <130 mg/dl), apo B should be measured and treated to <90 mg/dl.
Treatment of other lipoprotein fractions or targets
Severe hypertriglyceridemia may warrant immediate therapy of this abnormality with lifestyle and usually pharmacologic therapy (fibric acid derivative, niacin, or fish oil) to reduce the risk of acute pancreatitis. In the absence of severe hypertriglyceridemia, therapy targeting HDL cholesterol or triglycerides has intuitive appeal but lacks the evidence base of statin therapy. If the HDL cholesterol is <40 mg/dl and the LDL cholesterol between 100 and 129 mg/dl, gemfibrozil or niacin might be used, especially if a patient is intolerant to statins. Niacin is the most effective drug for raising HDL cholesterol. It can significantly increase blood glucose at high doses, but recent studies demonstrate that at modest doses (750–2,000 mg/day), significant improvements in LDL cholesterol, HDL cholesterol, and triglyceride levels are accompanied by only modest changes in glucose that are generally amenable to adjustment of diabetes therapy (235
Combination therapy, with a statin and a fibrate or statin and niacin, may be efficacious for treatment for all three lipid fractions, but this combination is associated with an increased risk for abnormal transaminase levels, myositis, or rhabdomyolysis. The risk of rhabdomyolysis is higher with higher doses of statins and with renal insufficiency and seems to be lower when statins are combined with fenofibrate than gemfibrozil (237
). In the recent ACCORD study, the combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone, in patients with type 2 diabetes who were at high risk for CVD. However, prespecified subgroup analyses suggested heterogeneity in treatment effects according to sex, with a benefit for men and possible harm for women, and a possible benefit of combination therapy for patients with both triglyceride level ≥204 mg/dl and HDL cholesterol level ≤34 mg/dl (238
). Other ongoing trials may provide much-needed evidence for the effects of combination therapy on cardiovascular outcomes.
summarizes common treatment goals for A1C, blood pressure, and HDL cholesterol.
Summary of recommendations for glycemic blood pressure and lipid control for most adults with diabetes
- Consider aspirin therapy (75–162 mg/day) as a primary prevention strategy in those with type 1 or type 2 diabetes at increased cardiovascular risk (10-year risk >10%). This includes most men >50 years of age or women >60 years of age who have at least one additional major risk factor (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria). (C)
- Aspirin should not be recommended for CVD prevention for adults with diabetes at low CVD risk (10-year CVD risk <5%, such as in men <50 and women <60 years of age with no major additional CVD risk factors), since the potential adverse effects from bleeding likely offset the potential benefits. (C)
- In patients in these age-groups with multiple other risk factors (e.g., 10-year risk 5–10%), clinical judgment is required. (E)
- Use aspirin therapy (75–162 mg/day) as a secondary prevention strategy in those with diabetes with a history of CVD. (A)
- For patients with CVD and documented aspirin allergy, clopidogrel (75 mg/day) should be used. (B)
- Combination therapy with ASA (75–162 mg/day) and clopidogrel (75 mg/day) is reasonable for up to a year after an acute coronary syndrome. (B)
ADA and the American Heart Association (AHA) have, in the past, jointly recommended that low-dose aspirin therapy be used as a primary prevention strategy in those with diabetes at increased cardiovascular risk, including those who are over 40 years of age or those with additional risk factors (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria) (188
). These recommendations were derived from several older trials that included small numbers of patients with diabetes.
Aspirin has been shown to be effective in reducing cardiovascular morbidity and mortality in high-risk patients with previous myocardial infarction or stroke (secondary prevention). Its net benefit in primary prevention among patients with no previous cardiovascular events is more controversial, both for patients with and without a history of diabetes (239
). Two recent randomized controlled trials of aspirin specifically in patients with diabetes failed to show a significant reduction in CVD end points, raising further questions about the efficacy of aspirin for primary prevention in people with diabetes (240
The Anti-thrombotic Trialists' (ATT) collaborators recently published an individual patient-level meta-analysis of the six large trials of aspirin for primary prevention in the general population. These trials collectively enrolled over 95,000 participants, including almost 4,000 with diabetes. Overall, they found that aspirin reduced the risk of vascular events by 12% (RR 0.88 [95% CI 0.82– 0.94]). The largest reduction was for nonfatal myocardial infarction with little effect on CHD death (RR 0.95 [95% CI 0.78–1.15]) or total stroke. There was some evidence of a difference in aspirin effect by sex. Aspirin significantly reduced CHD events in men but not in women. Conversely, aspirin had no effect on stroke in men but significantly reduced stroke in women. Notably, sex differences in aspirin's effects have not been observed in studies of secondary prevention (239
). In the six trials examined by the ATT collaborators, the effects of aspirin on major vascular events were similar for patients with or without diabetes: RR 0.88 (95% CI 0.67–1.15) and 0.87 (0.79–0.96), respectively. The CI was wider for those with diabetes because of their smaller number.
Based on the currently available evidence, aspirin appears to have a modest effect on ischemic vascular events with the absolute decrease in events depending on the underlying CVD risk. The main adverse effects appear to be an increased risk of gastrointestinal bleeding. The excess risk may be as high as 1–5 per 1,000 per year in real-world settings. In adults with CVD risk greater than 1% per year, the number of CVD events prevented will be similar to or greater than the number of episodes of bleeding induced, although these complications do not have equal effects on long-term health (242
In 2010, a position statement of the ADA, AHA, and American College of Cardiology Foundation (ACCF) updated prior joint recommendations for primary prevention (243
). Low dose (75–162 mg/day) aspirin use for primary prevention is reasonable for adults with diabetes and no previous history of vascular disease who are at increased CVD risk (10-year risk of CVD events over 10%) and who are not at increased risk for bleeding. This generally includes most men over age 50 years and women over age 60 years who also have one or more of the following major risk factors: smoking, hypertension, dyslipidemia, family history of premature CVD, and albuminuria.
However, aspirin is no longer recommended for those at low CVD risk (women under age 60 years and men under age 50 years with no major CVD risk factors; 10-year CVD risk under 5%) as the low benefit is likely to be outweighed by the risks of significant bleeding. Clinical judgment should be used for those at intermediate risk (younger patients with one or more risk factors, or older patients with no risk factors; those with 10-year CVD risk of 5–10%) until further research is available. Use of aspirin in patients under the age of 21 years is contraindicated due to the associated risk of Reye's syndrome.
Average daily dosages used in most clinical trials involving patients with diabetes ranged from 50 to 650 mg but were mostly in the range of 100 to 325 mg/day. There is little evidence to support any specific dose, but using the lowest possible dosage may help reduce side effects (244
). Although platelets from patients with diabetes have altered function, it is unclear what, if any, impact that finding has on the required dose of aspirin for cardioprotective effects in the patient with diabetes. Many alternate pathways for platelet activation exist that are independent of thromboxane A2
and thus not sensitive to the effects of aspirin (245
). Therefore, while “aspirin resistance” appears higher in the diabetic patients when measured by a variety of ex vivo and in vitro methods (platelet aggrenometry, measurement of thromboxane B2
), these observations alone are insufficient to empirically recommend higher doses of aspirin be used in the diabetic patient at this time.
Clopidogrel has been demonstrated to reduce CVD events in diabetic individuals (246
). It is recommended as adjunctive therapy in the first year after an acute coronary syndrome or as alternative therapy in aspirin-intolerant patients.
- Advise all patients not to smoke. (A)
- Include smoking cessation counseling and other forms of treatment as a routine component of diabetes care. (B)
A large body of evidence from epidemiological, case-control, and cohort studies provides convincing documentation of the causal link between cigarette smoking and health risks. Much of the work documenting the impact of smoking on health did not separately discuss results on subsets of individuals with diabetes, but suggests that the identified risks are at least equivalent to those found in the general population. Other studies of individuals with diabetes consistently demonstrate that smokers have a heightened risk of CVD, premature death, and increased rate of microvascular complications of diabetes. Smoking may have a role in the development of type 2 diabetes.
The routine and thorough assessment of tobacco use is important as a means of preventing smoking or encouraging cessation. A number of large randomized clinical trials have demonstrated the efficacy and cost-effectiveness of brief counseling in smoking cessation, including the use of quit lines, in the reduction of tobacco use. For the patient motivated to quit, the addition of pharmacological therapy to counseling is more effective than either treatment alone. Special considerations should include assessment of level of nicotine dependence, which is associated with difficulty in quitting and relapse (247
5. CHD screening and treatment
- In asymptomatic patients, routine screening for CAD is not recommended, as it does not improve outcomes as long as CVD risk factors are treated. (A)
- In patients with known CVD, ACE inhibitor (C) and aspirin and statin therapy (A) (if not contraindicated) should be used to reduce the risk of cardiovascular events.
- In patients with a prior myocardial infarction, β-blockers should be continued for at least 2 years after the event (B).
- Longer term use of β-blockers in the absence of hypertension is reasonable if well tolerated, but data are lacking. (E)
- Avoid TZD treatment in patients with symptomatic heart failure. (C)
- Metformin may be used in patients with stable CHF if renal function is normal. It should be avoided in unstable or hospitalized patients with CHF. (C)
Screening for CAD is reviewed in a recently updated consensus statement (154
). To identify the presence of CAD in diabetic patients without clear or suggestive symptoms, a risk factor–based approach to the initial diagnostic evaluation and subsequent follow-up has intuitive appeal. However, recent studies concluded that using this approach fails to identify which patients with type 2 diabetes will have silent ischemia on screening tests (159
Candidates for cardiac testing include those with 1
) typical or atypical cardiac symptoms and 2
) an abnormal resting ECG. The screening of asymptomatic patients remains controversial, especially as intensive medical therapy, indicated in diabetic patients at high risk for CVD, has an increasing evidence base for providing equal outcomes to invasive revascularization, including in diabetic patients (249
). There is also some evidence that silent myocardial ischemia may reverse over time, adding to the controversy concerning aggressive screening strategies (251
). Finally, a recent randomized observational trial demonstrated no clinical benefit to routine screening of asymptomatic patients with type 2 diabetes and normal ECGs (252
). Despite abnormal myocardial perfusion imaging in more than one in five patients, cardiac outcomes were essentially equal (and very low) in screened versus unscreened patients. Accordingly, the overall effectiveness, especially the cost-effectiveness, of such an indiscriminate screening strategy is now questioned.
Newer noninvasive CAD screening methods, such as computed tomography (CT) and CT angiography have gained in popularity. These tests infer the presence of coronary atherosclerosis by measuring the amount of calcium in coronary arteries and, in some circumstances, by direct visualization of luminal stenoses. Although asymptomatic diabetic patients found to have a higher coronary disease burden have more future cardiac events (253
), the role of these tests beyond risk stratification is not clear. Their routine use leads to radiation exposure and may result in unnecessary invasive testing such as coronary angiography and revascularization procedures. The ultimate balance of benefit, cost, and risks of such an approach in asymptomatic patients remains controversial, particularly in the modern setting of aggressive CVD risk factor control.
In all patients with diabetes, cardiovascular risk factors should be assessed at least annually. These risk factors include dyslipidemia, hypertension, smoking, a positive family history of premature coronary disease, and the presence of micro- or macroalbuminuria. Abnormal risk factors should be treated as described elsewhere in these guidelines. Patients at increased CHD risk should receive aspirin and a statin and ACE inhibitor or ARB therapy if hypertensive, unless there are contraindications to a particular drug class. While clear benefit exists for ACE inhibitor and ARB therapy in patients with nephropathy or hypertension, the benefits in patients with CVD in the absence of these conditions is less clear, especially when LDL cholesterol is concomitantly controlled (256
B. Nephropathy screening and treatment
- 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)
- 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 GFR and stage the level of chronic kidney disease (CKD), if present. (E)
- In the treatment of the nonpregnant patient with micro- or 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 0.8–1.0 g · kg body wt−1 · day−1 in individuals with diabetes and the earlier stages of CKD and to 0.8 g · kg body wt−1 · day−1 in the later stages of CKD may improve measures of renal function (urine albumin excretion rate, 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)
- When eGFR <60 ml/min/1.73 m2, evaluate and manage potential complications of CKD. (E)
- Consider referral to a physician experienced in the care of kidney disease when there is uncertainty about the etiology of kidney disease (heavy proteinuria, active urine sediment, absence of retinopathy, rapid decline in GFR), difficult management issues, or advanced kidney disease. (B)
Diabetic nephropathy occurs in 20–40% of patients with diabetes and is the single leading cause of end-stage renal disease (ESRD). Persistent albuminuria in the range of 30–299 mg/24 h (microalbuminuria) has been shown to be the earliest stage of diabetic nephropathy in type 1 diabetes and a marker for development of nephropathy in type 2 diabetes. Microalbuminuria is also a well-established marker of increased CVD risk (258
). Patients with microalbuminuria who progress to macroalbuminuria (300 mg/24 h) are likely to progress to ESRD (260
). However, a number of interventions have been demonstrated to reduce the risk and slow the progression of renal disease.
Intensive diabetes management with the goal of achieving near-normoglycemia has been shown in large prospective randomized studies to delay the onset of microalbuminuria and the progression of micro- to macroalbuminuria in patients with type 1 (262
) and type 2 (55
) diabetes. The UKPDS provided strong evidence that control of blood pressure can reduce the development of nephropathy (195
). In addition, large prospective randomized studies in patients with type 1 diabetes have demonstrated that achievement of lower levels of systolic blood pressure (<140 mmHg) resulting from treatment using ACE inhibitors provides a selective benefit over other antihypertensive drug classes in delaying the progression from micro- to macroalbuminuria and can slow the decline in GFR in patients with macroalbuminuria (264
). In type 2 diabetes with hypertension and normoalbuminuria, RAS inhibition has been demonstrated to delay onset of microalbuminuria (267
In addition, ACE inhibitors have been shown to reduce major CVD outcomes (i.e., myocardial infarction, stroke, death) in patients with diabetes (207
), thus further supporting the use of these agents in patients with microalbuminuria, a CVD risk factor. ARBs do not prevent microalbuminuria in normotensive patients with type 1 or type 2 diabetes (268
); however, ARBs have been shown to reduce the rate of progression from micro- to macroalbuminuria as well as ESRD in patients with type 2 diabetes (270
). Some evidence suggests that ARBs have a smaller magnitude of rise in potassium compared with ACE inhibitors in people with nephropathy (273
). Combinations of drugs that block the renin-angiotensin-aldosterone system (e.g., an ACE inhibitor plus an ARB, a mineralocorticoid antagonist, or a direct renin inhibitor) have been shown to provide additional lowering of albuminuria (275
). However, the long-term effects of such combinations on renal or cardiovascular outcomes have not yet been evaluated in clinical trials, and they are associated with increased risk for hyperkalemia.
Other drugs, such as diuretics, calcium channel blockers, and β-blockers should be used as additional therapy to further lower blood pressure in patients already treated with ACE inhibitors or ARBs (212
), or as alternate therapy in the rare individual unable to tolerate ACE inhibitors or ARBs.
Studies in patients with varying stages of nephropathy have shown that protein restriction of dietary protein helps slow the progression of albuminuria, GFR decline, and occurrence of ESRD (279
). Dietary protein restriction should be considered particularly in patients whose nephropathy seems to be progressing despite optimal glucose and blood pressure control and use of ACE inhibitor and/or ARBs (282
Assessment of albuminuria status and renal function
Screening for microalbuminuria can be performed by measurement of the albumin-to-creatinine ratio in a random spot collection; 24-h or timed collections are more burdensome and add little to prediction or accuracy (283
). Measurement of a spot urine for albumin only, whether by immunoassay or by using a dipstick test specific for microalbumin, without simultaneously measuring urine creatinine, is somewhat less expensive but susceptible to false-negative and -positive determinations as a result of variation in urine concentration due to hydration and other factors.
Abnormalities of albumin excretion are defined in . Because of variability in urinary albumin excretion, two of three specimens collected within a 3- to 6-month period should be abnormal before considering a patient to have crossed one of these diagnostic thresholds. Exercise within 24 h, infection, fever, CHF, marked hyperglycemia, and marked hypertension may elevate urinary albumin excretion over baseline values.
Definitions of abnormalities in albumin excretion
Information on presence of abnormal urine albumin excretion in addition to level of GFR may be used to stage CKD. The National Kidney Foundation classification () is primarily based on GFR levels and therefore differs from other systems, in which staging is based primarily on urinary albumin excretion (285
). Studies have found decreased GFR in the absence of increased urine albumin excretion in a substantial percentage of adults with diabetes (286
). Serum creatinine should therefore be measured at least annually in all adults with diabetes, regardless of the degree of urine albumin excretion.
Serum creatinine should be used to estimate GFR and to stage the level of CKD, if present. eGFR is commonly co-reported by laboratories or can be estimated using formulae such as the Modification of Diet in Renal Disease (MDRD) study equation (287
). Recent reports have indicated that the MDRD is more accurate for the diagnosis and stratification of CKD in patients with diabetes than the Cockcroft-Gault formula (288
). GFR calculators are available at http://www.nkdep.nih.gov
The role of continued annual quantitative assessment of albumin excretion after diagnosis of microalbuminuria and institution of ACE inhibitor or ARB therapy and blood pressure control is unclear. Continued surveillance can assess both response to therapy and progression of disease. Some suggest that reducing abnormal albuminuria (>30 mg/g) to the normal or near-normal range may improve renal and cardiovascular prognosis, but this approach has not been formally evaluated in prospective trials.
Complications of kidney disease correlate with level of kidney function. When the eGFR is less than 60 ml/min/1.73 m2, screening for complications of CKD is indicated (). Early vaccination against hepatitis B is indicated in patients likely to progress to end-stage kidney disease.
Consider referral to a physician experienced in the care of kidney disease when there is uncertainty about the etiology of kidney disease (heavy proteinuria, active urine sediment, absence of retinopathy, rapid decline in GFR, resistant hypertension), difficult management issues, or advanced kidney disease. The threshold for referral may vary depending on the frequency with which a provider encounters diabetic patients with significant kidney disease. Consultation with a nephrologist when stage 4 CKD develops has been found to reduce cost, improve quality of care, and keep people off dialysis longer (289
). However, nonrenal specialists should not delay educating their patients about the progressive nature of diabetic kidney disease; the renal preservation benefits of aggressive treatment of blood pressure, blood glucose, and hyperlipidemia; and the potential need for renal replacement therapy.
C. Retinopathy screening and treatment
- 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)
- Adults and children aged 10 years or older 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 2–3 years) may be considered following one or more normal eye exams. Examinations will be required more frequently if retinopathy is progressing. (B)
- High-quality fundus photographs can detect most clinically significant diabetic retinopathy. Interpretation of the images should be performed by a trained eye care provider. While retinal photography may serve as a screening tool for retinopathy, it is not a substitute for a comprehensive eye exam, which should be performed at least initially and at intervals thereafter as recommended by an eye care professional. (E)
- Women with preexisting diabetes who are planning a pregnancy or who have become pregnant should have a comprehensive eye examination and should be counseled on the risk of development and/or progression of diabetic retinopathy. Eye examination should occur in the first trimester with close follow-up throughout pregnancy and for 1 year postpartum. (B)
- Promptly refer patients with any level of macular edema, severe NPDR, or any 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)
Diabetic retinopathy is a highly specific vascular complication of both type 1 and type 2 diabetes, with prevalence strongly related to the duration of diabetes. Diabetic retinopathy is the most frequent cause of new cases of blindness among adults aged 20–74 years. Glaucoma, cataracts, and other disorders of the eye occur earlier and more frequently in people with diabetes.
In addition to duration of diabetes, other factors that increase the risk of, or are associated with, retinopathy include chronic hyperglycemia (290
), the presence of nephropathy (291
), and hypertension (292
). Intensive diabetes management with the goal of achieving near normoglycemia has been shown in large prospective randomized studies to prevent and/or delay the onset and progression of diabetic retinopathy (47
). Lowering blood pressure has been shown to decrease the progression of retinopathy (195
). Several case series and a controlled prospective study suggest that pregnancy in type 1 diabetic patients may aggravate retinopathy (293
); laser photocoagulation surgery can minimize this risk (294
One of the main motivations for screening for diabetic retinopathy is the established efficacy of laser photocoagulation surgery in preventing vision loss. Two large trials, the Diabetic Retinopathy Study (DRS) and the Early Treatment Diabetic Retinopathy Study (ETDRS), provide the strongest support for the therapeutic benefits of photocoagulation surgery.
The DRS (295
) showed that panretinal photocoagulation surgery reduced the risk of severe vision loss from PDR from 15.9% in untreated eyes to 6.4% in treated eyes, with greatest risk-to-benefit ratio in those with baseline disease (disc neovascularization or vitreous hemorrhage).
The ETDRS (296
) established the benefit of focal laser photocoagulation surgery in eyes with macular edema, particularly those with clinically significant macular edema, with reduction of doubling of the visual angle (e.g., 20/50 to 20/100) from 20% in untreated eyes to 8% in treated eyes. The ETDRS also verified the benefits of panretinal photocoagulation for high-risk PDR and in older-onset patients with severe NPDR or less-than-high-risk PDR.
Laser photocoagulation surgery in both trials was beneficial in reducing the risk of further vision loss, but generally not beneficial in reversing already diminished acuity. This preventive effect and the fact that patients with PDR or macular edema may be asymptomatic provide strong support for a screening program to detect diabetic retinopathy.
As retinopathy is estimated to take at least 5 years to develop after the onset of hyperglycemia, patients with type 1 diabetes should have an initial dilated and comprehensive eye examination within 5 years after the onset of diabetes. Patients with type 2 diabetes, who generally have had years of undiagnosed diabetes and who have a significant risk of prevalent DR 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 for type 1 and type 2 diabetic patients are generally repeated annually. Less-frequent exams (every 2–3 years) may be cost effective after one or more normal eye exams, while examinations will be required more frequently if retinopathy is progressing (297
The use of retinal photography with remote reading by experts has great potential in areas where qualified eye care professionals are not available, and may also enhance efficiency and reduce costs when the expertise of ophthalmologists can be utilized for more complex examinations and for therapy (298
). In-person exams are still necessary when the photos are unacceptable and for follow-up of abnormalities detected. Photos are not a substitute for a comprehensive eye exam, which should be performed at least initially and at intervals thereafter as recommended by an eye care professional.
Results of eye examinations should be documented and transmitted to the referring health care professional. For a detailed review of the evidence and further discussion of diabetic retinopathy, see the ADA's technical review and position statement on this subject (297
D. Neuropathy screening and treatment (301
- 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)
- 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)
The diabetic neuropathies are heterogeneous with diverse clinical manifestations. They may be focal or diffuse. Most common among the neuropathies are chronic sensorimotor DPN and autonomic neuropathy. Although DPN is a diagnosis of exclusion, complex investigations to exclude other conditions are rarely needed.
The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons: 1
) nondiabetic neuropathies may be present in patients with diabetes and may be treatable, 2
) a number of treatment options exist for symptomatic diabetic neuropathy, 3
) up to 50% of DPN may be asymptomatic and patients are at risk of insensate injury to their feet, and 4
) autonomic neuropathy and particularly cardiovascular autonomic neuropathy is associated with substantial morbidity and even mortality. Specific treatment for the underlying nerve damage is currently not available, other than improved glycemic control, which may modestly slow progression (63
) but not reverse neuronal loss. Effective symptomatic treatments are available for some manifestations of DPN and autonomic neuropathy.
Diagnosis of neuropathy
Distal symmetric polyneuropathy.
Patients with diabetes should be screened annually for DPN using tests such as pinprick sensation, vibration perception (using a 128-Hz tuning fork), 10-g monofilament pressure sensation at the distal plantar aspect of both great toes and metatarsal joints, and assessment of ankle reflexes. Combinations of more than one test have >87% sensitivity in detecting DPN. Loss of 10-g monofilament perception and reduced vibration perception predict foot ulcers (301
). Importantly, in patients with neuropathy, particularly when severe, causes other than diabetes should always be considered, such as neurotoxic mediations, heavy metal poisoning, alcohol abuse, vitamin B12 deficiency (especially in those taking metformin for prolonged periods (302
), renal disease, chronic inflammatory demyelinating neuropathy, inherited neuropathies, and vasculitis (303
Diabetic autonomic neuropathy (304).
The symptoms and signs of autonomic dysfunction should be elicited carefully during the history and physical examination. Major clinical manifestations of diabetic autonomic neuropathy include resting tachycardia, exercise intolerance, orthostatic hypotension, constipation, gastroparesis, erectile dysfunction, sudomotor dysfunction, impaired neurovascular function, and, potentially, autonomic failure in response to hypoglycemia.
Cardiovascular autonomic neuropathy, a CVD risk factor (93
), is the most studied and clinically important form of diabetic autonomic neuropathy. Cardiovascular autonomic neuropathy may be indicated by resting tachycardia (>100 bpm) or orthostasis (a fall in systolic blood pressure >20 mmHg upon standing without an appropriate heart rate response); it is also associated with increased cardiac event rates.
Gastrointestinal neuropathies (e.g., esophageal enteropathy, gastroparesis, constipation, diarrhea, fecal incontinence) are common, and any section of the gastrointestinal tract may be affected. Gastroparesis should be suspected in individuals with erratic glucose control or with upper gastrointestinal symptoms without other identified cause. Evaluation of solid-phase gastric emptying using double-isotope scintigraphy may be done if symptoms are suggestive, but test results often correlate poorly with symptoms. Constipation is the most common lower-gastrointestinal symptom but can alternate with episodes of diarrhea.
Diabetic autonomic neuropathy is also associated with genitourinary tract disturbances. In men, diabetic autonomic neuropathy may cause erectile dysfunction and/or retrograde ejaculation. Evaluation of bladder dysfunction should be performed for individuals with diabetes who have recurrent urinary tract infections, pyelonephritis, incontinence, or a palpable bladder.
The first step in management of patients with DPN should be to aim for stable and optimal glycemic control. Although controlled trial evidence is lacking, several observational studies suggest that neuropathic symptoms improve not only with optimization of control, but also with the avoidance of extreme blood glucose fluctuations. Patients with painful DPN may benefit from pharmacological treatment of their symptoms: many agents have efficacy confirmed in published randomized controlled trials, several of which are Food and Drug Administration (FDA)-approved for the management of painful DPN.
Treatment of autonomic neuropathy
Gastroparesis symptoms may improve with dietary changes and prokinetic agents such as metoclopramide or erythromycin. Treatments for erectile dysfunction may include phosphodiesterase type 5 inhibitors, intracorporeal or intraurethral prostaglandins, vacuum devices, or penile prostheses. Interventions for other manifestations of autonomic neuropathy are described in the ADA statement on neuropathy (301
). As with DPN treatments, these interventions do not change the underlying pathology and natural history of the disease process, but may have a positive impact on the quality of life of the patient.
- For all patients with diabetes, perform an annual comprehensive foot examination to identify risk factors predictive of ulcers and amputations. The foot examination should include inspection, assessment of foot pulses, and testing for loss of protective sensation (10-g monofilament plus testing any one of: vibration using 128-Hz tuning fork, pinprick sensation, ankle reflexes, or vibration perception threshold). (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 PAD are asymptomatic. (C)
- Refer patients with significant claudication or a positive ABI for further vascular assessment and consider exercise, medications, and surgical options. (C)
Amputation and foot ulceration, consequences of diabetic neuropathy and/or PAD, are common and major causes of morbidity and disability in people with diabetes. Early recognition and management of risk factors can prevent or delay adverse outcomes.
The risk of ulcers or amputations is increased in people who have the following risk factors:
- Previous amputation
- Past foot ulcer history
- Peripheral neuropathy
- Foot deformity
- Peripheral vascular disease
- Visual impairment
- Diabetic nephropathy (especially patients on dialysis)
- Poor glycemic control
- Cigarette smoking
Many studies have been published proposing a range of tests that might usefully identify patients at risk of foot ulceration, creating confusion among practitioners as to which screening tests should be adopted in clinical practice. An ADA task force was therefore assembled in 2008 to concisely summarize recent literature in this area and then recommend what should be included in the comprehensive foot exam for adult patients with diabetes. Their recommendations are summarized below, but clinicians should refer to the task force report (305
) for further details and practical descriptions of how to perform components of the comprehensive foot examination.
At least annually, all adults with diabetes should undergo a comprehensive foot examination to identify high risk conditions. Clinicians should ask about history of previous foot ulceration or amputation, neuropathic or peripheral vascular symptoms, impaired vision, tobacco use, and foot care practices. A general inspection of skin integrity and musculoskeletal deformities should be done in a well lit room. Vascular assessment would include inspection and assessment of pedal pulses.
The neurologic exam recommended is designed to identify loss of protective sensation (LOPS) rather than early neuropathy. The clinical examination to identify LOPS is simple and requires no expensive equipment. Five simple clinical tests (use of a 10-g monofilament, vibration testing using a 128-Hz tuning fork, tests of pinprick sensation, ankle reflex assessment, and testing vibration perception threshold with a biothesiometer), each with evidence from well-conducted prospective clinical cohort studies, are considered useful in the diagnosis of LOPS in the diabetic foot. The task force agrees that any of the five tests listed could be used by clinicians to identify LOPS, although ideally two of these should be regularly performed during the screening exam—normally the 10-g monofilament and one other test. One or more abnormal tests would suggest LOPS, while at least two normal tests (and no abnormal test) would rule out LOPS. The last test listed, vibration assessment using a biothesiometer or similar instrument, is widely used in the U.S.; however, identification of the patient with LOPS can easily be carried out without this or other expensive equipment.
Initial screening for PAD should include a history for claudication and an assessment of the pedal pulses. A diagnostic ABI should be performed in any patient with symptoms of PAD. Due to the high estimated prevalence of PAD in patients with diabetes and the fact that many patients with PAD are asymptomatic, an ADA consensus statement on PAD (306
) suggested that a screening ABI be performed in patients over 50 years of age and be considered in patients under 50 years of age who have other PAD risk factors (e.g., smoking, hypertension, hyperlipidemia, or duration of diabetes >10 years). Refer patients with significant symptoms or a positive ABI for further vascular assessment and consider exercise, medications, and surgical options (306
Patients with diabetes and high-risk foot conditions should be educated regarding their risk factors and appropriate management. Patients at risk should understand the implications of the LOPS, the importance of foot monitoring on a daily basis, the proper care of the foot, including nail and skin care, and the selection of appropriate footwear. Patients with LOPS should be educated on ways to substitute other sensory modalities (hand palpation, visual inspection) for surveillance of early foot problems. Patients' understanding of these issues and their physical ability to conduct proper foot surveillance and care should be assessed. Patients with visual difficulties, physical constraints preventing movement, or cognitive problems that impair their ability to assess the condition of the foot and to institute appropriate responses will need other people, such as family members, to assist in their care.
People with neuropathy or evidence of increased plantar pressure (e.g., erythema, warmth, callus, or measured pressure) may be adequately managed with well-fitted walking shoes or athletic shoes that cushion the feet and redistribute pressure. Callus can be debrided with a scalpel by a foot care specialist or other health professional with experience and training in foot care. People with bony deformities (e.g., hammertoes, prominent metatarsal heads, bunions) may need extra-wide or -depth shoes. People with extreme bony deformities (e.g., Charcot foot) who cannot be accommodated with commercial therapeutic footwear may need custom-molded shoes.
Foot ulcers and wound care may require care by a podiatrist, orthopedic or vascular surgeon, or rehabilitation specialist experienced in the management of individuals with diabetes.