1、84 ENDOCRINE PRACTICE Vol 22 No. 1 January 2016 AACE/ACE Consensus StatementCONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM 2016 EXECUTIVE SUMMARYAlan J. Garber, MD, PhD, FACE
2、1; Martin J. Abrahamson, MD2; Joshua I. Barzilay, MD, FACE3; Lawrence Blonde, MD, FACP, FACE4; Zachary T. Bloomgarden, MD, MACE5; Michael A. Bush, MD6; Samuel Dagogo-Jack, MD, DM, FRCP, FACE7; Ralph A. DeFronzo, MD, BMS, MS, BS8; Daniel Einhorn, MD, FACP, FACE9; Vivian A. Fonseca, MD, FACE10; Jeffre
3、y R. Garber, MD, FACP, FACE11; W. Timothy Garvey, MD, FACE12; George Grunberger, MD, FACP, FACE13; Yehuda Handelsman, MD, FACP, FNLA, FACE14; Robert R. Henry, MD, FACE15; Irl B. Hirsch, MD16; Paul S. Jellinger, MD, MACE17; Janet B. McGill, MD, FACE18; Jeffrey I. Mechanick, MD, FACN, FACP, FACE, ECNU
4、19; Paul D. Rosenblit, MD, PhD, FNLA, FACE20; Guillermo E. Umpierrez, MD, FACP, FACE21From the 1Chair, Professor, Departments of Medicine, Biochemistry and Molecular Biology, and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, 2Beth Israel Deaconess Medical Center, Depart
5、ment of Medicine and Harvard Medical School, Boston, Massachusetts, 3Division of Endocrinology, Kaiser Permanente of Georgia and the Division of Endocrinology, Emory University School of Medicine, Atlanta, Georgia, 4Director, Ochsner Diabetes Clinical Research Unit, Department of Endocrinology, Diab
6、etes and Metabolism, Ochsner Medical Center, New Orleans, Louisiana, 5Clinical Professor, Mount Sinai School of Medicine, Editor, Journal of Diabetes, New York, New York, 6Clinical Chief, Division of Endocrinology, Cedars-Sinai Medical Center, Associate Clinical Professor of Medicine, Geffen School
7、of Medicine, UCLA, Los Angeles, California, 7A.C. Mullins Professor AACE = American Association of Clinical Endocrinologists; ACCORD = Action to Control Cardiovascular Risk in Diabetes; ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure; ACEI = angiotensin-converting enzyme
8、 inhibitor; AGI = alpha-glucosidase inhibitor; apo B = apolipoprotein B; ARB = angiotensin II receptor blocker; ASCVD = atherosclerotic cardio-vascular disease; BAS = bile acid sequestrant; BMI = body mass index; BP = blood pressure; CHD = coro-nary heart disease; CKD = chronic kidney disease; CVD =
9、 cardiovascular disease; DKA = diabetic ketoac-idosis; DPP-4 = dipeptidyl peptidase 4; EPA = eicosa-pentaenoic acid; FDA = Food and Drug Administration; GLP-1 = glucagon-like peptide 1; HDL-C = high-density-lipoprotein cholesterol; LDL-C = low-density-lipoprotein cholesterol; LDL-P = low-density-lip
10、opro-tein particle; Look AHEAD = Look Action for Health in Diabetes; NPH = neutral protamine Hagedorn; OSA = obstructive sleep apnea; SFU = sulfonylurea; SGLT-2 = sodium glucose cotransporter-2; SMBG = self-moni-toring of blood glucose; T2D = type 2 diabetes; TZD = thiazolidinedioneEXECUTIVE SUMMARY
11、This algorithm for the comprehensive management of persons with type 2 diabetes (T2D) was developed to provide clinicians with a practical guide that considers the whole patient, their spectrum of risks and complica-tions, and evidence-based approaches to treatment. It is now clear that the progress
12、ive pancreatic beta-cell defect that drives the deterioration of metabolic control over time begins early and may be present before the diagnosis of diabetes (1). In addition to advocating glycemic control to reduce microvascular complications, this document high-lights obesity and prediabetes as un
13、derlying risk factors for the development of T2D and associated macrovascular complications. In addition, the algorithm provides recom-mendations for blood pressure (BP) and lipid control, the two most important risk factors for cardiovascular disease (CVD).Since originally drafted in 2013, the algo
14、rithm has been updated as new therapies, management approach-es, and important clinical data have emerged. The 2016 edition includes a new section on lifestyle therapy as well as discussion of all classes of obesity, antihyperglycemic, lipid-lowering, and antihypertensive medications approved by the
15、 U.S. Food and Drug Administration (FDA) through December 2015.This algorithm supplements the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) 2015 Clinical Practice Guidelines for Developing a Diabetes Mellitus Comprehensive Care Plan (2) and is o
16、rganized into discrete sections that address the following topics: the founding principles of the algo-rithm, lifestyle therapy, obesity, prediabetes, glucose control with noninsulin antihyperglycemic agents and insulin, management of hypertension, and management of dyslipidemia. In the accompanying
17、 algorithm, a chart summarizing the attributes of each antihyperglycemic class and the principles of the algorithm appear at the end. (Endocr Pract. 2016;22:84-113)PrinciplesThe founding principles of the Comprehensive Type 2 Diabetes Management Algorithm are as follows (see Comprehensive Type 2 Dia
18、betes Management AlgorithmPrinciples):1. Lifestyle optimization is essential for all patients with diabetes. Lifestyle optimization is multifac-eted, ongoing, and should engage the entire diabe-tes team. However, such efforts should not delay needed pharmacotherapy, which can be initiated simultaneo
19、usly and adjusted based on patient response to lifestyle efforts. The need for medical therapy should not be interpreted as a failure of lifestyle management, but as an adjunct to it.2. The hemoglobin A1C (A1C) target should be individualized based on numerous factors, such as age, life expectancy,
20、comorbid conditions, dura-tion of diabetes, risk of hypoglycemia or adverse consequences from hypoglycemia, patient moti-vation, and adherence. An A1C level of 6.5% is considered optimal if it can be achieved in a safe and affordable manner, but higher targets may be appropriate for certain individu
21、als and may change for a given individual over time.3. Glycemic control targets include fasting and post-prandial glucose as determined by self-monitor-ing of blood glucose (SMBG).4. The choice of diabetes therapies must be individu-alized based on attributes specific to both patients and the medica
22、tions themselves. Medication attri-butes that affect this choice include antihyper-glycemic efficacy, mechanism of action, risk of inducing hypoglycemia, risk of weight gain, other adverse effects, tolerability, ease of use, likely adherence, cost, and safety in heart, kidney, or liver disease.5. Mi
23、nimizing risk of both severe and nonsevere hypoglycemia is a priority. It is a matter of safety, adherence, and cost.6. Minimizing risk of weight gain is also a priority. It too is a matter of safety, adherence, and cost.7. The initial acquisition cost of medications is only a part of the total cost
24、 of care, which includes monitoring requirements and risks of hypoglyce-86 mia and weight gain. Safety and efficacy should be given higher priority than medication cost.8. This algorithm stratifies choice of therapies based on initial A1C level. It provides guidance as to what therapies to initiate
25、and add but respects individual circumstances that could lead to differ-ent choices.9. Combination therapy is usually required and should involve agents with complementary mech-anisms of action.10. Comprehensive management includes lipid and BP therapies and treatment of related comorbidi-ties.11. T
26、herapy must be evaluated frequently (e.g., every 3 months) until stable using multiple criteria, including A1C, SMBG records (fasting and post-prandial), documented and suspected hypoglyce-mia events, lipid and BP values, adverse events (weight gain, fluid retention, hepatic or renal impairment, or
27、CVD), comorbidities, other rele-vant laboratory data, concomitant drug adminis-tration, diabetic complications, and psychosocial factors affecting patient care. Less frequent moni-toring is acceptable once targets are achieved.12. The therapeutic regimen should be as simple as possible to optimize a
28、dherence.13. This algorithm includes every FDA-approved class of medications for T2D (as of December 2015).Lifestyle TherapyThe key components of lifestyle therapy include medical nutrition therapy, regular physical activity, suffi-cient amounts of sleep, behavioral support, and smok-ing cessation a
29、nd avoidance of all tobacco products (see Comprehensive Type 2 Diabetes Management AlgorithmLifestyle Therapy). In the algorithm, recommendations appearing on the left apply to all patients. Patients with increasing burden of obesity or related comorbidities may also require the additional intervent
30、ions listed in the middle and right side of the figure.Lifestyle therapy begins with nutrition counseling and education. All patients should strive to attain and maintain an optimal weight through a primarily plant-based diet high in polyunsaturated and monounsaturated fatty acids, with limited inta
31、ke of saturated fatty acids and avoidance of trans fats. Patients who are overweight (body mass index BMI of 25 to 29.9 kg/m2) or obese (BMI 30 kg/m2) should also restrict their caloric intake with the goal of reducing body weight by at least 5 to 10%. As shown in the Look AHEAD (Action for Health i
32、n Diabetes) and Diabetes Prevention Program studies, lowering caloric intake is the main driver for weight loss (3-6). The clini-cian or a registered dietitian (or nutritionist) should discuss recommendations in plain language at the initial visit and periodically during follow-up office visits. Dis
33、cussion should focus on foods that promote health versus those that promote metabolic disease or complications and should include information on specific foods, meal plan-ning, grocery shopping, and dining-out strategies. In addi-tion, education on medical nutrition therapy for patients with diabete
34、s should also address the need for consisten-cy in day-to-day carbohydrate intake, limiting sucrose-containing or high-glycemic-index foods, and adjusting insulin doses to match carbohydrate intake (e.g., use of carbohydrate counting with glucose monitoring) (2,7). Structured counseling (e.g., weekl
35、y or monthly sessions with a specific weight-loss curriculum) and meal replace-ment programs have been shown to be more effective than standard in-office counseling (3,6,8-15). Additional nutri-tion recommendations can be found in the 2013 Clinical Practice Guidelines for Healthy Eating for the Prev
36、ention and Treatment of Metabolic and Endocrine Diseases in Adults from AACE/ACE and The Obesity Society (16).After nutrition, physical activity is the main compo-nent in weight loss and maintenance programs. Regular physical exerciseboth aerobic exercise and strength trainingimproves glucose contro
37、l, lipid levels, and BP; decreases the risk of falls and fractures; and improves functional capacity and sense of well-being (17-24). In Look AHEAD, which had a weekly goal of 175 minutes per week of moderately intense activity, minutes of physi-cal activity were significantly associated with weight
38、 loss, suggesting that those who were more active lost more weight (3). The physical activity regimen should involve at least 150 minutes per week of moderate-intensity exer-cise such as brisk walking (e.g., 15- to 20-minute mile) and strength training; patients should start any new activity slowly
39、and increase intensity and duration gradually as they become accustomed to the exercise. Structured programs can help patients learn proper technique, establish goals, and stay motivated. Patients with diabetes and/or severe obesity or complications should be evaluated for contrain-dications and/or
40、limitations to increased physical activity, and an exercise prescription should be developed for each patient according to both goals and limitations. More detail on the benefits and risks of physical activity and the practi-cal aspects of implementing a training program in people with T2D can be fo
41、und in a joint position statement from the American College of Sports Medicine and American Diabetes Association (25).Adequate rest is important for maintaining energy levels and well-being, and all patients should be advised to sleep approximately 7 hours per night. Evidence supports an association
42、 of 6 to 9 hours of sleep per night with a reduction in cardiometabolic risk factors, whereas sleep deprivation aggravates insulin resistance, hypertension, hyperglycemia, and dyslipidemia and increases inflamma-tory cytokines (26-31). Daytime drowsinessa frequent symptom of sleep disorders such as
43、sleep apneais asso-ciated with increased risk of accidents, errors in judgment, 87 and diminished performance (32). The most common type of sleep apnea, obstructive sleep apnea (OSA), is caused by physical obstruction of the airway during sleep. The resulting lack of oxygen causes the patient to awa
44、ken and snore, snort, and grunt throughout the night. The awaken-ings may happen hundreds of times per night, often with-out the patients awareness. OSA is more common in men, the elderly, and persons with obesity (33,34). Individuals with suspected OSA should be referred to a sleep specialist for e
45、valuation and treatment (2).Behavioral support for lifestyle therapy includes the structured weight loss and physical activity programs mentioned above as well as support from family and friends. Patients should be encouraged to join commu-nity groups dedicated to a healthy lifestyle for emotional s
46、upport and motivation. In addition, obesity and diabetes are associated with high rates of anxiety and depression, which can adversely affect outcomes (35,36). Healthcare professionals should assess patients mood and psycho-logical well-being and refer patients with mood disorders to mental healthca
47、re professionals. Cognitive behavior-al therapy may be beneficial. A recent meta-analysis of psychosocial interventions provides insight into successful approaches (37).Smoking cessation is the final component of lifestyle therapy and involves avoidance of all tobacco products. Structured programs s
48、hould be recommended for patients unable to stop smoking on their own (2).ObesityObesity is a disease with genetic, environmental, and behavioral determinants that confers increased morbidity and mortality (38,39). An evidence-based approach to the treatment of obesity incorporates lifestyle, medica
49、l, and surgical options, balances risks and benefits, and empha-sizes medical outcomes that address the complications of obesity rather than cosmetic goals. Weight loss should be considered in all overweight and obese patients with prediabetes or T2D, given the known therapeutic effects of weight loss to lower glycemia, improve the lipid profile, reduce BP, and decrease mechanical strain on the lower extremities (hips and knees) (2,38).The AACE Obesity Treatment Algorithm emphasizes a complications-centric model as opposed to a BMI-centric approach for the treatment of patients
