The levels of evidence (1 to 4) and the recommendation grades (A to D) are defined at the end of the "Major Recommendations" field.
Executive Summary of Recommendations
The following recommendations (labeled "R") are evidence based (Grades A, B, and C) or are based on expert opinion because of a lack of conclusive clinical evidence (Grade D). The best evidence level (BEL), which corresponds to the best conclusive evidence found, accompanies the recommendation grade in this Executive Summary.
How is Diabetes Mellitus (DM) Diagnosed and Classified?
Diagnosis of DM
R1. The following criteria may be used to diagnose DM (see Table below) (Grade A; BEL 1):
- Fasting plasma glucose (FPG) concentration (after 8 or more hours of no caloric intake) of 126 mg/dL or greater, or
- Plasma glucose concentration of 200 mg/dL or greater 2 hours after ingesting 75-g oral glucose load in the morning after an overnight fast of at least 8 hours, or
- Symptoms of uncontrolled hyperglycemia (e.g., polyuria, polydipsia, polyphagia) and a random (casual, nonfasting) plasma glucose concentration of 200 mg/dL or greater, or
- Hemoglobin A1C (A1C) level of 6.5% or higher.
In the absence of unequivocal hyperglycemia or severe metabolic stress, the same test (glucose or A1C measurement) should be repeated on a different day to confirm the diagnosis of DM (Grade D; BEL 4). Screening should be considered in the presence of risk factors for DM (see Table below) (Grade D; BEL 4).
R2. There is a continuum of risk for poor patient outcomes in the progression from normal glucose tolerance to overt type 2 DM (T2DM) (Grade D; BEL 4). Prediabetes can be identified by the presence of impaired glucose tolerance, which is an oral glucose tolerance test glucose value of 140 to 199 mg/dL, 2 hours after ingesting 75 g of glucose, and/or impaired fasting glucose, which is a fasting glucose value of 100 to 125 mg/dL (see Table below) (Grade D; BEL 4). A1C values between 5.5% and 6.4% should be a signal to do more specific glucose testing (Grade D; BEL 4). A1C testing should be used as a screening tool only; FPG measurement or an oral glucose tolerance test should be used for definitive diagnosis (Grade D; BEL 4). Metabolic syndrome based on National Cholesterol Education Program IV Adult Treatment Panel III criteria is a prediabetes equivalent (Grade C; BEL 3).
R3. In pregnancy, elevated plasma glucose levels (FPG concentration >92 mg/dL; 1-hour postchallenge glucose value ≥180 mg/dL; or 2-hour value ≥153 mg/dL) satisfy the criteria for a diagnosis of gestational DM (GDM) (Grade C; BEL 3). All pregnant women should be screened for GDM at 24 to 28 weeks' gestation, using a 75-g (glucose), 2-hour oral glucose tolerance test.
Table. Glucose Testing and Interpretation
| Test |
Result |
Diagnosis |
| Fasting plasma glucose, mg/dL |
≤99 |
Normal |
| 100-125 |
Impaired fasting glucose |
| ≥126 |
Diabetes, confirmed by repeating the test on a different day |
| Glucose, mg/dL (oral glucose tolerance test, 2 hours after ingestion of 75-g glucose load) |
≤139 |
Normal |
| 140-199 |
Impaired glucose tolerance |
| ≥200 |
Diabetes, confirmed by repeating the test on a different day |
| Hemoglobin A1C, % (as a screening test) |
≤5.4 |
Normal |
| 5.5-6.4 |
High risk/prediabetes; requires screening by glucose criteria |
| ≥6.5 |
Diabetes, confirmed by repeating the test on a different day |
Classification of DM
DM represents a group of heterogeneous metabolic disorders that develop when insulin secretion is insufficient to maintain normal plasma glucose levels.
R4. T2DM is the most common form of DM, accounting for more than 90% of cases. It is typically identified in patients older than 30 years who are overweight or obese and/or have a positive family history, but do not have autoantibodies characteristic of type 1 DM (T1DM). Most persons with T2DM have evidence of insulin resistance (such as high triglycerides or low high-density lipoprotein cholesterol [HDL-C]) (Grade A; BEL 1).
R5. T1DM is usually characterized by absolute insulin deficiency and may be confirmed by the presence of autoantibodies to glutamic acid decarboxylase, pancreatic islet b cells (tyrosine phosphatase IA-2), and/or insulin (Grade A; BEL 1). Some forms of T1DM have no evidence of autoimmunity and have been termed idiopathic. T1DM or monogenic DM can also occur in obese children and adolescents. Therefore, documenting the levels of insulin and C-peptide and the presence or absence of immune markers and obtaining a careful family history in addition to the clinical presentation may be useful in establishing the correct diagnosis, determining treatment, and helping to distinguish between T1DM and T2DM in children (Grade A; BEL 1).
R6. GDM is a condition in which women without previously diagnosed DM exhibit elevated plasma glucose levels (see R3 above) (Grade C; BEL 3).
R7. Evaluation for monogenic DM (formerly maturity-onset diabetes of the young) is recommended for any child with an atypical presentation, course, or response to therapy. Diagnostic likelihood is strengthened by a family history over 3 generations suggesting autosomal dominant inheritance. This type of DM can occur in the child before appearing in the parent or other relatives (Grade A; BEL 1).
How Can DM Be Prevented?
R8. T2DM can be prevented or at least delayed by intervening in persons who have prediabetes (see Table below for prediabetes risk factors suggesting a need for screening). Monitoring of patients with prediabetes to assess their glycemic status should include at least annual measurement of FPG and/or an oral glucose tolerance test (see Table above) (Grade D; BEL 4). A1C should be for screening use only (Grade D; BEL 4). Cardiovascular disease (CVD) risk factors (especially elevated blood pressure and/or dyslipidemia) and excessive weight should be addressed and monitored at regular intervals (Grade D; BEL 4).
R9. Persons with prediabetes should modify their lifestyle, including initial attempts to lose 5% to 10% of body weight if overweight or obese and participation in moderate physical activity (e.g., walking) at least 150 minutes per week (Grade D; BEL 4). Organized programs with follow-up appear to benefit these efforts (Grade A; BEL 1).
R10. In addition to lifestyle measures, metformin or perhaps thiazolidinediones (TZDs) should be considered for younger patients who are at moderate to high risk for developing DM; for patients with additional CVD risk factors including hypertension, dyslipidemia, or polycystic ovarian syndrome; for patients with a family history of DM in a first-degree relative; and/or for patients who are obese (Grade A; BEL 1).
R11. Obesity is a major risk factor for T2DM and for CVD. Lifestyle modification (primarily calorie reduction and appropriately prescribed physical activity) is the cornerstone in the control of obesity in T2DM (Grade A; BEL 1). Pharmacotherapy for weight loss may be considered when lifestyle modification fails to achieve the targeted goal in patients with T2DM and a body mass index greater than 27 kg/m2 (Grade D; BEL 4). Consideration may be given to laparoscopic-assisted gastric banding in patients with T2DM who have a body mass index greater than 30 kg/m2 or Roux-en-Y gastric bypass for patients with a body mass index greater than 35 kg/m2 to achieve at least short-term weight reduction (Grade A; BEL 1). Patients with T2DM who undergo Roux-en-Y gastric bypass must have meticulous metabolic postoperative follow-up because of a risk of vitamin and mineral deficiencies and hypoglycemia (Grade D; BEL 4).
Table. Prediabetes Risk Factors Suggesting a Need for Screening (2 [EL 4; consensus no evidence (NE)])
|
Family history of diabetes mellitus
Cardiovascular disease
Being overweight or obese
Sedentary lifestyle
Nonwhite ancestry
Previously identified impaired glucose tolerance, impaired fasting glucose, and/or metabolic syndrome
Hypertension
Increased levels of triglycerides, low concentrations of high-density lipoprotein cholesterol, or both
History of gestational diabetes mellitus
Delivery of a baby weighing more than 4 kg (9 lb)
Polycystic ovary syndrome
Antipsychotic therapy for schizophrenia and/or severe bipolar disease
|
What Is the Role of a DM Comprehensive Care Plan?
R12. Every patient with documented DM requires a comprehensive treatment program, which takes into account the patient's unique medical history, behaviors and risk factors, ethnocultural background, and environment (Grade A; BEL 4; upgraded by unanimous consensus as prime importance in this CPG).
Multidisciplinary Team Approach
R13. An organized multidisciplinary team may best deliver care for patients with DM. Members of such a team can include a primary care physician, endocrinologist, physician assistant, nurse practitioner, registered nurse, certified diabetes educator (CDE), dietitian, exercise specialist, and mental health care professional. The educational, social, and logistical elements of therapy and the variation in successful care delivery associated with age and maturation present additional complexity when caring for children with DM (Grade D; BEL 4).
DM Self-Management Education
R14. Persons with DM should receive comprehensive DM self-management education at the time of DM diagnosis and subsequently as appropriate. Therapeutic lifestyle management must be discussed with all patients with DM and prediabetes at the time of diagnosis and throughout their lifetime. This includes medical nutrition therapy (with reduction and modification of caloric and fat intake to achieve weight loss in those who are overweight or obese), appropriately prescribed physical activity, avoidance of tobacco products, and adequate quantity and quality of sleep (Grade D; BEL 4).
See Appendix in the original guideline document for Q4: What is the Imperative for Education and Team Approach in DM Management?
What Are the Comprehensive Treatment Goals for Persons With DM?
Glycemic and A1C Goals
Outpatient Glucose Targets for Nonpregnant Adults
R15. Glucose targets should be individualized and take into account residual life expectancy, duration of disease, presence or absence of microvascular and macrovascular complications, CVD risk factors, comorbid conditions and risk for severe hypoglycemia. Glucose targets should also be formulated in the context of the patient's psychological, social, and economic status (Grade A; BEL 1). In general, therapy should target a A1C level of 6.5% or less for most nonpregnant adults, if it can be achieved safely (Grade D; BEL 4) (see Table 7 in the original guideline document). To achieve this target A1C level, FPG should usually be less than 110 mg/dL and the 2-hour postprandial glucose concentration should be less than 140 mg/dL (Grade B; BEL 2) (see Table 7 in the original guideline document).
In adults with recent onset of T2DM and no clinically significant CVD, glycemic control aimed at normal (or near-normal) glycemia may be considered, with the aim of preventing the development of microvascular (Grade A; BEL 1) and macrovascular complications over a lifetime, if it can be achieved without substantial hypoglycemia or other unacceptable adverse consequences. Although it is uncertain that the clinical course of established CVD is improved by strict glycemic control, the progression of microvascular complications clearly is benefitted (Grade A; BEL 1). In certain patients, a less stringent goal may be considered (A1C 7%-8%) (Grade A; BEL 1). Such individuals those with history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions, or long-standing DM in which the general goal has been difficult to attain despite intensive efforts (Grade A; BEL 1).
Inpatient Glucose Targets for Nonpregnant Adults
R16. For most hospitalized persons with hyperglycemia, a glucose range of 140 to 180 mg/dL is recommended, provided these targets can be safely achieved (see Table 7 in the original guideline document) (Grade D; BEL 4).
Outpatient Glucose Targets for Pregnant Women
R17. For women with GDM, treatment goals are a preprandial glucose concentration of 95 mg/dL or lower and either a 1-hour postmeal glucose value of 140 mg/dL or less or a 2-hour postmeal glucose value of 120 mg/dL or less (Grade D; BEL 4). For women with preexisting T1DM or T2DM who become pregnant, glycemic goals are a premeal, bedtime, and overnight glucose values of 60 to 99 mg/dL; a peak postprandial glucose value of 100 to 129 mg/dL; and a A1C value of 6.0% or less—only if they can be achieved safely (Grade D; BEL 4).
CVD Risk Reduction Targets
R18. CVD is the primary cause of death for most persons with DM; therefore a DM comprehensive care plan should include modification of CVD risk factors (Grade A; BEL 1). Cardiovascular risk reduction targets are summarized in Table 7 in the original guideline document.
Blood Pressure
R19. The blood pressure goal for persons with DM or prediabetes is less than 130/80 mm Hg (see Table 7 in the original guideline document) (Grade D; BEL 4).
Lipids
R20. Treatment targets for dyslipidemia are based on established CVD risk reduction recommendations. In persons with DM or prediabetes and no CVD or minimal CV risk, the low-density lipoprotein cholesterol (LDL-C) goal of less than 100 mg/dL is the primary target for therapy. The goal for non–HDL-C is less than 130 mg/dL. The highest-risk patients are those with established CVD or more than 2 major CVD risk factors. For these patients, LDL-C remains the primary target for therapy with a goal of less than 70 mg/dL. The non–HDL-C treatment goal is less than 100 mg/dL (see Table 7 in the original guideline document) (Grade A; BEL 1). HDL-C values greater than 40 mg/dL in men and greater than 50 mg/dL in women are desirable. If the triglyceride concentration is 200 mg/dL or greater, non–HDL-C becomes a secondary target (Grade C; BEL 3).
How Can DM Comprehensive Care Plan Guideline Targets Be Achieved?
Therapeutic Lifestyle Changes
R21. Medical nutritional therapy must be individualized, and this generally means evaluation and teaching by a trained nutritionist/registered dietitian or knowledgeable physician (Grade D; BEL 4). Insulin dosage adjustments to match carbohydrate intake (e.g., use of carbohydrate counting), sucrose-containing or high glycemic index food limitations, adequate protein intake, "heart healthy" diet use, weight management, and sufficient physical activity are recommended.
R22. Regular physical activity, both aerobic and strength training, are important to improve a variety of CVD risk factors, decrease risk of falls and fractures, improve functional capacity and sense of well-being, and improve glucose control in persons with T2DM. Increased physical activity is also a major component in weight loss and weight maintenance programs. The current recommendations of at least 150 minutes per week of moderate-intensity exercise, such as brisk walking or its equivalent, are now well accepted and part of the nationally recommended guidelines. For persons with T2DM, it is also recommended to incorporate flexibility and strength training exercises. Patients must be evaluated initially for contraindications and/or limitations to physical activity, and then an exercise prescription should be developed for each patient according to both their goals and exercise limitations. Physical activity programs should begin slowly and build up gradually (Grade D; BEL 4).
Antihyperglycemic Pharmacotherapy
The choice of therapeutic agents should be based on their differing metabolic actions and adverse effect profiles as described in the 2009 American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) Diabetes Algorithm for Glycemic Control (Grade D; BEL 4).
R23. Insulin is required in all patients with T1DM, and it should be considered for patients with T2DM when noninsulin antihyperglycemic therapy fails to achieve target glycemic control or when a patient, whether drug naïve or not, has symptomatic hyperglycemia (Grade A; BEL 1).
R24. Antihyperglycemic agents may be broadly categorized by whether they predominantly target FPG or PPG levels. These effects are not exclusive; drugs acting on FPG passively reduce PPG, and drugs acting on PPG passively reduce FPG, but these broad categories can aid in therapeutic decision-making. TZDs and sulfonylureas are examples of oral agents primarily affecting FPG. Metformin and incretin enhancers (dipeptidyl-peptidase 4 inhibitors [DPP-4 inhibitors]) also favorably affect FPG. When insulin therapy is indicated in patients with T2DM to target FPG, therapy with long-acting basal insulin should be the initial choice in most cases; insulin analogues glargine and detemir are preferred over intermediate-acting neutral protamine Hagedorn (NPH) because they are associated with less hypoglycemia (Grade A; BEL 1). The initial choice of an agent targeting FPG or PPG involves comprehensive patient assessment with emphasis given to the glycemic profile obtained by self-monitoring of blood glucose (SMBG).
R25. When postprandial hyperglycemia is present, glinides and/or a-glucosidase inhibitors, short- or rapid-acting insulin, and metformin should be considered (Grade A; BEL 1). Incretin-based therapy (DPP-4 inhibitors and glucagon-like peptide 1 [GLP-1] receptor agonists, especially short-acting GLP-1 agonists) also target postprandial hyperglycemia in a glucose-dependent fashion, which reduces the risks of hypoglycemia. When control of postprandial hyperglycemia is needed and insulin is indicated, rapid-acting insulin analogues are preferred over regular human insulin because they have a more rapid onset and offset of action and are associated with less hypoglycemia (Grade A; BEL 1). Pramlintide can be used as an adjunct to prandial insulin therapy to reduce postprandial hyperglycemia, A1C, and weight (Grade A; BEL 1).
R26. Premixed insulin (fixed combination of shorter- and longer-acting components) analogue therapy may be considered for patients in whom adherence to a drug regimen is an issue; however, these preparations lack component dosage flexibility and may increase the risk for hypoglycemia compared with basal insulin or basal-bolus insulin (Grade D; BEL 4). Basal-bolus insulin therapy is flexible and is recommended for intensive insulin therapy (Grade B; BEL 3).
R27. Intensification of pharmacotherapy requires glucose monitoring and medication adjustment at appropriate intervals when treatment goals are not achieved or maintained (Grade D; BEL 4). Most patients with an initial A1C level greater than 7.5% will require combination therapy using agents with complementary mechanisms of action (Grade D; BEL 4). The AACE algorithm outlines treatment choices on the basis of the current A1C level (Grade D; BEL 4).
What Are Some Special Considerations for Treatment of Hyperglycemia?
Treatment of Hyperglycemia in T1DM
R28. Physiologic insulin regimens, which provide both basal and prandial insulin, are recommended for most patients with T1DM (Grade A; BEL 1). These regimens include (a) use of multiple daily injections (MDI), which usually provide 1 or 2 injections daily of basal insulin to control glycemia between meals and overnight and injections of prandial insulin before each meal to control meal-related glycemia; (b) the use of continuous subcutaneous insulin infusion (CSII) to provide a more physiologic way to deliver insulin, which may improve glucose control while reducing risks of hypoglycemia; and (c) for other patients (especially if hypoglycemia is a problem), the use of insulin analogues (Grade A; BEL 1).
CSII (Insulin Pump Therapy)
R29. CSII is useful in motivated and DM-educated patients with T1DM and in certain insulinopenic patients with T2DM who are unable to achieve optimal glycemic control with MDI. Thorough education and periodic reevaluation of CSII users, as well as CSII expertise of the prescribing physician, is necessary to ensure patient safety (Grade D; BEL 4). Sensor-augmented CSII should be considered in patients in whom it is deemed appropriate (Grade B; BEL 2).
Treatment of Hyperglycemia in Children and Adolescents
R30. The pharmacologic treatment of any form of DM in children does not, at this stage of our knowledge, differ in substance from treatment in adults (Grade D; BEL 4). In children or adolescents with T1DM, insulin regimens should be MDI or CSII (Grade D; BEL 4), but injection frequencies may become problematic in some school settings. Higher insulin to carbohydrate ratios may be needed during puberty (Grade D; BEL 4). In children or adolescents with T2DM, diet and lifestyle modification are implemented first; addition of metformin and/or insulin should be considered when glycemic targets are not achievable with lifestyle measures alone (Grade C; BEL 3). An extensive review of guidelines for the care of children with DM from the International Society of Pediatric and Adolescent Diabetes was published in 2009 and is available on their Web site (http://www.ispad.org 
).
Treatment of Hyperglycemia in Pregnancy
R31. All women with preexisting DM (T1DM, T2DM, or previous GDM) should have access to preconception care to ensure adequate nutrition and glucose control before conception, during pregnancy, and in the postpartum period (Grade B; BEL 2). Regular or rapid-acting insulin analogues are the preferred treatment for postprandial hyperglycemia in pregnant women. Basal insulin needs can be provided by using rapid-acting insulin via CSII or by using long-acting insulin (e.g., NPH; US Food and Drug Administration [FDA] pregnancy category B) (Grade B; BEL 2). Although insulin is the preferred treatment approach, metformin and glyburide have been shown to be effective alternatives and without adverse effects in some women.
Treatment of Hyperglycemia in Hospitalized Patients
R32. Insulin can rapidly control hyperglycemia and, therefore, is the drug of choice for hospitalized patients with hyperglycemia (Grade D; BEL 4). Subcutaneous insulin orders should be specified as "basal," "prandial," or "correction" (Grade D; BEL 4). Insulin dosing should be synchronized with provision of enteral or parenteral nutrition (Grade D; BEL 4). Exclusive use of "sliding scale insulin" should be discouraged (Grade D; BEL 4). Oral antihyperglycemic agents have a limited role in acute care settings, and practitioners should consider discontinuing them in favor of insulin during acute illness that might reasonably be expected to affect glucose levels and/or increase the risk for medication-related adverse events (Grade D; BEL 4). Regular insulin is acceptable for intravenous administration, but insulin analogues are preferred for subcutaneous administration. Intravenous insulin is preferred for critically ill patients.
When and How Should Glucose Monitoring Be Used?
R33. A1C should be measured at least twice yearly in all patients with DM and at least 4 times yearly in patients not at target (Grade D; BEL 4).
R34. SMBG should be performed by all patients using insulin (minimum of twice daily and ideally at least before any injection of insulin) (Grade D; BEL 4). More frequent SMBG after meals or in the middle of the night may be required for insulin-taking patients with frequent hypoglycemia, patients not at A1C targets, or those with symptoms (Grade D; BEL 4). Patients not requiring insulin therapy may benefit from SMBG, especially to provide feedback about the effects of their lifestyle and pharmacologic therapy; testing frequency must be personalized (Grade D; BEL 4). Although still early in its development, continuous glucose monitoring (CGM) can be useful for many patients to improve A1C levels and reduce hypoglycemia (Grade D; BEL 4).
How Should Hypoglycemia Be Prevented, Identified, and Managed in Patients With DM?
R35. Hypoglycemia treatment requires oral administration of rapidly absorbed glucose (Grade D; BEL 4). If the patient is unable to swallow, parenteral glucagon may be given by a trained family member or by medical personnel (Grade D; BEL 4). In unresponsive patients, intravenous glucose should be given (Grade D; BEL 4). Patients may need to be hospitalized for observation if a sulfonylurea or a very large dose of insulin is the cause of the hypoglycemia because prolonged hypoglycemia can occur (Grade D; BEL 4). If the patient has hypoglycemic unawareness and hypoglycemia-associated autonomic failure, several weeks of hypoglycemia avoidance may reduce the risk or prevent the recurrence of severe hypoglycemia (Grade A; BEL 1). In patients with T2DM who become hypoglycemic and have been treated with an alpha-glucosidase inhibitor in addition to insulin or an insulin secretagogue, oral glucose must be given because alpha-glucosidase inhibitors inhibit the breakdown and absorption of complex carbohydrates and disaccharides (Grade D; BEL 4).
How Should Microvascular and Neuropathic Disease Be Prevented, Diagnosed, and Treated in Patients With DM?
Microvascular and neuropathic complications are most closely associated with glycemic status; the risk for and progression of these complications are reduced by improving glycemic control.
Diabetic Nephropathy
R36. Beginning 5 years after diagnosis in patients with T1DM and at diagnosis in patients with T2DM, an annual assessment of serum creatinine to estimate the glomerular filtration rate (GFR) and urine albumin excretion should be performed to identify, stage, and monitor progression of diabetic nephropathy (Grade D; BEL 4). Patients with diabetic nephropathy should be counseled regarding the increased need for optimal glycemic control, blood pressure control, dyslipidemia control, and smoking cessation (Grade A; BEL 1). When therapy with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers is initiated, renal function and serum potassium levels must be closely monitored (Grade A; BEL 1).
Diabetic Retinopathy
R37. At the time of diagnosis, patients with T2DM should be referred to an experienced ophthalmologist or optometrist for annual dilated eye examination (Grade D; BEL 4). In patients with T1DM, a referral should be made within 5 years of diagnosis (Grade B; BEL 2). Women who are pregnant and have DM should be referred for frequent/repeated eye examinations during pregnancy and 1 year postpartum (Grade C; BEL 3). Patients with active retinopathy should have examinations more frequently than once a year, as should patients receiving vascular endothelial growth factor therapy (Grade D; BEL 4). Optimal glucose, blood pressure, and lipid control should be implemented to slow the progression of retinopathy (Grade D; BEL 4).
Diabetic Neuropathy
R38. Diabetic painful neuropathy is diagnosed clinically and must be differentiated from other painful conditions (Grade D; BEL 4). Interventions that reduce oxidative stress, improve glycemic control, and/or improve dyslipidemia and hypertension might have a beneficial effect on diabetic neuropathy (Grade A; BEL 1). Exercise and balance training may also be beneficial (Grade C; BEL 3). Tricyclic antidepressants, anticonvulsants, and serotonin and norepinephrine reuptake inhibitors are useful treatments (Grade A; BEL 1). Large-fiber neuropathies are managed with strength, gait, and balance training; pain management; orthotics to treat and prevent foot deformities; tendon lengthening for pes equinus from Achilles tendon shortening; and/or surgical reconstruction and full contact casting as needed (Grade A; BEL 1). Small-fiber neuropathies are managed with foot protection (e.g., padded socks), supportive shoes with orthotics if necessary, regular foot and shoe inspection, prevention of heat injury, and use of emollient creams; however, for pain management, the medications mentioned above must be used (Grade A; BEL 1).
How Should Macrovascular Disease Be Prevented, Diagnosed, and Treated in Patients With Prediabetes or DM?
Antiplatelet Therapy
R39. The use of low-dosage aspirin (75-162 mg daily) is recommended for secondary prevention of CVD (Grade A; BEL 1). For primary prevention of CVD, its use may be considered for those at high risk (10-year risk >10%) (Grade D; BEL 4).
Hypertension
R40. Therapeutic recommendations for hypertension should include lifestyle modification to include DASH diet (Dietary Approaches to Stop Hypertension), in particular reduced salt intake, physical activity, and, as needed, consultation with a registered dietician and/or CDE (Grade A; BEL 1). Pharmacologic therapy is used to achieve targets unresponsive to therapeutic lifestyle changes alone. Initially, antihypertensive agents are selected on the basis of their ability to reduce blood pressure and to prevent or slow the progression of nephropathy and retinopathy; angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are considered the preferred choice in patients with DM (Grade D; BEL 4). The use of combination therapy is likely required to achieve blood pressure targets, including calcium channel antagonists, diuretics, combined a/b-adrenergic blockers, and newer-generation beta-adrenergic blockers in addition to agents that block the renin-angiotensin system (Grade A; BEL 1).
Dyslipidemia
R41. All patients with DM should be screened for dyslipidemia (Grade A; BEL 1). Therapeutic recommendations should include therapeutic lifestyle changes and, as needed, consultation with a registered dietitian and/or CDE (Grade A; BEL 1). Pharmacologic therapy is used to achieve targets unresponsive to therapeutic lifestyle changes alone. LDL-C is the primary target for therapy. Statins are the treatment of choice in the absence of contraindications. Combinations of statins (Grade A; BEL 1) with bile acid sequestrants, niacin, and/or cholesterol absorption inhibitors should be considered in situations of inadequate goal attainment. These agents may be used instead of statins in cases of statin-related adverse events or intolerance (Grade A; BEL 2). In patients with LDL-C at goal, but with triglyceride concentrations of 200 mg/dL or higher or low HDL-C (<35 mg/dL), treatment protocols including the use of fibrates or niacin are used to achieve non–HDL-C goal (<100 mg/dL when at highest risk; <130 mg/dL when at high risk) (Grade A; BEL 1). Apolipoprotein B targets are less than 80 mg/dL in patients with CVD and less than 90 mg/dL in patients without CVD.
Asymptomatic Coronary Artery Disease
R42. Measurement of coronary artery calcification or coronary imaging may be used to assess whether a patient is a reasonable candidate for intensification of glycemic, lipid, and/or blood pressure control (Grade C; BEL 3). Screening for asymptomatic coronary artery disease with various stress tests in patients with T2DM has not been clearly demonstrated to improve cardiac outcomes and is therefore not recommended (Grade D; BEL 4).
How Should Other Common Comorbidities of DM Be Addressed?
Sleep-Related Problems
R43. Obstructive sleep apnea is common and should be screened for in adults with T2DM, especially in men older than 50 years (Grade D; BEL 4). Continuous positive airway pressure should be considered for treating patients with obstructive sleep apnea (Grade A; BEL 1). This condition can be diagnosed by history or by home monitoring, but referral to a sleep specialist should be considered in patients suspected of having obstructive sleep apnea or restless leg syndrome (Grade D; BEL 4).
Depression
R44. Routine depression screening is recommended for adults with DM. Untreated comorbid depression can have serious clinical implications for patients with DM (Grade A; BEL 1).
Definitions:
2010 American Association of Clinical Endocrinologists Protocol for Production of Clinical Practice Guidelines—Step I: Evidence Ratinga
Numerical Descriptor
(evidence level)b |
Semantic Descriptor (reference methodology) |
| 1 |
Meta-analysis of randomized controlled trials (MRCT) |
| 1 |
Randomized controlled trials (RCT) |
| 2 |
Meta-analysis of nonrandomized prospective or case-controlled trials (MNRCT) |
| 2 |
Nonrandomized controlled trial (NRCT) |
| 2 |
Prospective cohort study (PCS) |
| 2 |
Retrospective case-control study (RCCS) |
| 3 |
Cross-sectional study (CSS) |
| 3 |
Surveillance study (registries, surveys, epidemiologic study, retrospective chart review, mathematical modeling of database) (SS) |
| 3 |
Consecutive case series (CCS) |
| 3 |
Single case reports (SCR) |
| 4 |
No evidence (theory, opinion, consensus, review, or preclinical study) (NE) |
a Adapted from: American Association of Clinical Endocrinologists Protocol for Standardized Production of Clinical Practice Guidelines--2010 update. Endocr Pract. 2010;16:270-283.
b 1 = strong evidence; 2 = intermediate evidence; 3 = weak evidence; and 4 = no evidence.
2010 American Association of Clinical Endocrinologists Protocol for Production of Clinical Practice Guidelines—Step III: Grading of Recommendations; How Different Evidence Levels Can Be Mapped to the Same Recommendation Gradea,b
| Best Evidence Level |
Subjective Factor Impact |
Two-thirds Consensus |
Mapping |
Recommendation Grade |
| 1 |
None |
Yes |
Direct |
A |
| 2 |
Positive |
Yes |
Adjust up |
A |
| 2 |
None |
Yes |
Direct |
B |
| 1 |
Negative |
Yes |
Adjust down |
B |
| 3 |
Positive |
Yes |
Adjust up |
B |
| 3 |
None |
Yes |
Direct |
C |
| 2 |
Negative |
Yes |
Adjust down |
C |
| 4 |
Positive |
Yes |
Adjust up |
C |
| 4 |
None |
Yes |
Direct |
D |
| 3 |
Negative |
Yes |
Adjust down |
D |
| 1, 2, 3, 4 |
NA |
No |
Adjust down |
D |
a Starting with the left column, best evidence levels (BELs), subjective factors, and consensus map to recommendation grades in the right column. When subjective factors have little or no impact ("none"), then the BEL is directly mapped to recommendation grades. When subjective factors have a strong impact, then recommendation grades may be adjusted up ("positive" impact) or down ("negative" impact). If a two-thirds consensus cannot be reached, then the recommendation grade is D. NA, not applicable (regardless of the presence or absence of strong subjective factors, the absence of a two-thirds consensus mandates a recommendation grade D).
b Adapted from: American Association of Clinical Endocrinologists Protocol for Standardized Production of Clinical Practice Guidelines--2010 update. Endocr Pract. 2010;16:270-283.
