Vipul Lakhani, MD Oregon Medical Group Endocrinology

Vipul Lakhani, MD Oregon Medical Group Endocrinology

Disclosures None

Objectives Be able to diagnose diabetes and assess control Be able to identify appropriate classes of medications for diabetes treatment Begin to manage diabetes and comorbidities

Epidemiology of Diabetes Diabetes affects 29.1 million people of all ages 9.3% of the U.S. population Diagnosed: 21 million Undiagnosed: 8.1 million Leading cause of kidney failure, nontraumatic lower-limb amputation, new cases of blindness among adults Major cause of heart disease and stroke Seventh leading cause of death National Diabetes Statistics Report, 2014. Available at: http://www.diabetes.org/diabetesbasics/statistics/?loc=db-slabnav/

County-Level Estimates of Diagnosed Diabetes (%), Adults 20 years, 2008 Percent 0-6.5 6.5 6.6-8.0 8.0 8.1-9.4 9.4 9.5-11.1 11.1 > 11.2 www.cdc.gov

Number of Americans with Diagnosed Diabetes, 1980-2009 www.cdc.gov

STANDARDS OF MEDICAL CARE IN DIABETES 2015

ADA Evidence Grading System for Clinical Practice Recommendations Level of Evidence A B C E Description Clear or supportive evidence from adequately powered well-conducted, generalizable, randomized controlled trials Compelling nonexperimental evidence Supportive evidence from well-conducted cohort studies or case-control study Supportive evidence from poorly controlled or uncontrolled studies Conflicting evidence with the weight of evidence supporting the recommendation Expert consensus or clinical experience ADA. Diabetes Care 2015;38(suppl 1):S2; Table 1

Recommendations: Strategies for Improving Diabetes Care Care should be aligned with components of the Chronic Care Model to ensure productive interactions between a prepared proactive practice team and an informed activated patient A When feasible, care systems should support teambased care, community involvement, patient registries, and embedded decision support tools to meet patient needs B Physicians, nurse practitioners, physician s assistants, nurses, dietitians, pharmacists, mental health professionals, CDE In this collaborative and integrated team approach, essential that individuals with diabetes assume an active role in their care ADA. 1. Strategies for Improving Diabetes Care. Diabetes Care 2015;38(suppl 1):S5

CLASSIFICATION AND DIAGNOSIS OF DIABETES

Type 1 diabetes β-cell destruction Type 2 diabetes Classification of Diabetes Progressive insulin secretory defect Other specific types of diabetes Genetic defects in β-cell function, insulin action (MODY) Diseases of the exocrine pancreas (CFRD) Drug- or chemical-induced Gestational diabetes mellitus (GDM) ADA. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S8

Criteria for the Diagnosis of Diabetes A1C 6.5% OR Fasting plasma glucose (FPG) 126 mg/dl (7.0 mmol/l) OR 2-h plasma glucose 200 mg/dl (11.1 mmol/l) during an OGTT OR A random plasma glucose 200 mg/dl (11.1 mmol/l) ADA. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S9; Table 2.1

Categories of Increased Risk for Diabetes (Prediabetes)* FPG 100 125 mg/dl (5.6 6.9 mmol/l): IFG OR 2-h plasma glucose in the 75-g OGTT 140 199 mg/dl (7.8 11.0 mmol/l): IGT OR A1C 5.7 6.4% *For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately greater at higher ends of the range. ADA. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S10; Table 2.3

Recommendations: Testing for Diabetes in Asymptomatic Patients Consider testing overweight/obese adults (BMI 25 kg/m 2 or 23 kg/m 2 in Asian Americans) with one or more additional risk factors for type 2 diabetes; for all patients, particularly those who are overweight, testing should begin at age 45 years B If tests are normal, repeat testing at least at 3-year intervals is reasonable C To test for diabetes/prediabetes, the A1C, FPG, or 2-h 75-g OGTT are appropriate B In those with prediabetes, monitor for development of diabetes annually E ADA. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S11

PREVENTION/DELAY OF TYPE 2 DIABETES

Recommendations: Prevention/Delay of Type 2 Diabetes Diabetes Prevention Program Targeting weight loss of 7% of body weight Increasing physical activity to at least 150 min/week of moderate activity (eg, walking) Follow-up counseling appears to be important for success Based on cost-effectiveness of diabetes prevention, such programs should be covered by third-party payers ADA. 5. Prevention/Delay of Type 2 Diabetes. Diabetes Care 2015;38(suppl 1):S31

GLYCEMIC TARGETS

Diabetes Care: Glycemic Control Two primary techniques available for health providers and patients to assess effectiveness of management plan on glycemic control Patient self-monitoring of blood glucose (SMBG), or interstitial glucose A1C Perform the A1C test at least two times a year in patients meeting treatment goals (and have stable glycemic control) Perform the A1C test quarterly in patients whose therapy has changed or who are not meeting glycemic goals ADA. 6. Glycemic Targets. Diabetes Care 2015;38(suppl 1):S33

Approach to the Management of Hyperglycemia ADA. 6. Glycemic Targets. Diabetes Care 2015;38(suppl 1):S37. Figure 6.1; adapted with permission from Inzucchi SE, et al. Diabetes Care, 2015;38:140-149

Recommendations: Glycemic Goals in Adults (1) Lowering A1C to below or around 7% has been shown to reduce microvascular complications and, if implemented soon after the diagnosis of diabetes, is associated with long-term reduction in macrovascular disease. Therefore, a reasonable A1C goal for many nonpregnant adults is <7% Providers might reasonably suggest more stringent A1C goals (such as <6.5%) for selected individual patients, if this can be achieved without significant hypoglycemia ADA. 6. Glycemic Targets. Diabetes Care 2015;38(suppl 1):S35

Recommendations: Glycemic Goals in Adults (2) Less stringent A1C goals (such as <8%) may be appropriate for patients with History of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions Those with longstanding diabetes in whom the general goal is difficult to attain despite DSME, appropriate glucose monitoring, and effective doses of multiple glucose lowering agents including insulin ADA. 6. Glycemic Targets. Diabetes Care 2015;38(suppl 1):S35

APPROACHES TO GLYCEMIC TREATMENT

Recommendations: Pharmacological Therapy For Type 1 Diabetes Most people with type 1 diabetes should: Be treated with MDI injections (3 4 injections per day of basal and prandial insulin) or continuous subcutaneous insulin infusion (CSII) A Be educated in how to match prandial insulin dose to carbohydrate intake, premeal blood glucose, and anticipated activity E Use insulin analogs to reduce hypoglycemia risk A ADA. 7. Approaches to Glycemic Treatment. Diabetes Care 2015;38(suppl 1):S41

Recommendations: Pharmacological Therapy For Type 2 Diabetes (1) Metformin, if not contraindicated and if tolerated, is the preferred initial pharmacological agent for type 2 diabetes A ADA. 7. Approaches to Glycemic Treatment. Diabetes Care 2015;38(suppl 1):S42

Recommendations: Therapy for Type 2 Diabetes (2) A patient-centered approach should be used to guide choice of pharmacological agents Considerations include efficacy, cost, potential side effects, effects on weight, comorbidities, hypoglycemia risk, and patient preferences E Due to the progressive nature of type 2 diabetes, insulin therapy is eventually indicated for many patients with type 2 diabetes B Overall each class of noninsulin agent decreases A1c by 0.9-1.1% ADA. 7. Approaches to Glycemic Treatment. Diabetes Care 2015;38(suppl 1):S41

Antihyperglycemic Therapy in Type 2 Diabetes ADA. 7. Approaches to Glycemic Treatment. Diabetes Care 2015;38(suppl 1):S43. Figure 7.1; adapted with permission from Inzucchi SE, et al. Diabetes Care, 2015;38:140-149

Approach To Starting and Adjusting Insulin in Type 2 Diabetes ADA. 7. Approaches to Glycemic Treatment. Diabetes Care 2015;38(suppl 1):S46. Figure 7.2; adapted with permission from Inzucchi SE, et al. Diabetes Care, 2015;38:140-149

Case 58 yo M has had DM2 for 16 yrs, poorly controlled. Current regimen below. [+] MI and CHF. [+] retinopathy and gastroparesis. No hypoglycemia. Nonsmoker. [+] family history. BP 138/90, BMI 34. Lungs clear. [+] BLE edema. Metformin 1000mg BID Glipizide 10mg BID Atorvastatin 40 mg daily

Case - continued Hemoglobin A 1c = 8.4% Creatinine = 0.67 mg/dl TSH = 2.83 miu/l LDL cholesterol = 92 mg/dl

Case - continued Addition of which medication below will improve glucose control and minimize side effects? A. Exenetide B. Pioglitazone C. Saxagliptin D. Canagliflozin E. Insulin glargine

Thiazolidinediones Pioglitazone, Rosiglitazone Activates nuclear transcription factor PPAR-γ, increasing insulin sensitivity Pros: Cons: No hypoglycemia,? Decreased CVD (pio), generic Wt increase, edema, CHF,? MI (rosi)

Glucagon-like-peptide-1 agonists Exenetide, exenetide extended release, liraglutide, albiglutide, dulaglutide Increases glucose dependent insulin secretion, increases satiety, slows gastric emptying Pros: No hypoglycemia, Dec wt, Dec postprand gluc Cons: GI side effects,?pancreatitis, medullary thyroid cancer, cost

Dipeptidyl peptidase-4 inhibitors Sitagliptin, saxagliptin, linagliptin, alogliptin DPP-4 breaks down GLP-1 Results in increased glucose dependent insulin secretion Pros: No hypoglycemia, oral Cons:?increased CHF,?acute pancreatitis, angioedema, cost

Sodium-glucose Cotransporter 2 inhibitors Canagliflozin, dapagliflozin, empagliflozin Inihibits SGLT-2 in the proximal nephron, leading to glucosuria Pros: Cons: No hypoglycemia, wt loss, decreased BP GU infections, polyuria, hypotension, dehydration, increased LDL, cost

Insulins (onset / duration) Rapid acting (15 / 3-5h) Lispro Aspart Glulisine Inhaled insulin (15 / 2h) Short acting (30-60 / 4-8h) Human regular Intermediate Human NPH (2-4h / 10-18h) U-500 regular (30-60 / 10-18h)

Insulins (onset / duration) Basal insulin analogs Lantus (Glargine U-100) (4-6h / 24h) Detemir (2-3h / 6-24h) Toujeo (Glargine U-300) (6h / 24h) Pre-mixed insulins 70/30 75/25 50/50

Case 58 yo M has had DM2 for 2 yrs, poorly controlled. Current regimen below. No complications. No hypoglycemia. Nonsmoker. [+] family history. BP 128/60, BMI 31. Exam otherwise normal. Metformin 1000mg BID Glipizide 10mg BID Atorvastatin 40 mg daily

Case - continued Hemoglobin A 1c = 11.4% Creatinine = 0.67 mg/dl LDL cholesterol = 92 mg/dl

Case - continued Addition of which medication below will improve glucose control and minimize side effects? A. Liraglutide B. Pioglitazone C. Linagliptin D. Canagliflozin E. Insulin detemir

CARDIOVASCULAR DISEASE AND RISK MANAGEMENT

Cardiovascular Disease CVD is the major cause of morbidity, mortality for those with diabetes Largest contributor to direct/indirect costs Common conditions coexisting with type 2 diabetes (e.g., hypertension, dyslipidemia) are clear risk factors for CVD Diabetes itself confers independent risk Benefits observed when individual cardiovascular risk factors are controlled to prevent/slow CVD in people with diabetes ADA. 8. Cardiovascular Disease and Risk Management. Diabetes Care 2015;38(suppl 1):S49

Recommendations: Hypertension/Blood Pressure Control Goals People with diabetes and hypertension should be treated to a systolic blood pressure goal of <140 mmhg A Lower systolic targets, such as <130 mmhg, may be appropriate for certain individuals, such as younger patients, if it can be achieved without undue treatment burden C Patients with diabetes should be treated to a diastolic blood pressure <90 mmhg A Lower diastolic targets, such as <80 mmhg, may be appropriate for certain individuals, such as younger patients, if it can be achieved without undue treatment burden B ADA. 8. Cardiovascular Disease and Risk Management. Diabetes Care 2015;38(suppl 1):S49

Recommendations: Hypertension/Blood Pressure Control Treatment Pharmacological therapy for patients with diabetes and hypertension comprise a regimen that includes either an ACE inhibitor or angiotensin II receptor blocker B; if one class is not tolerated, substitute the other C An ACE inhibitor or ARB is not recommended for the primary prevention of diabetic kidney disease in patients who have normal blood pressure and a normal urine-albumin-tocreatinine ratio (UACR) (<30 mg/g) B ADA. 8. Cardiovascular Disease and Risk Management. Diabetes Care 2015;38(suppl 1):S50

Recommendations: Dyslipidemia/Lipid Management Screening In adults, a screening lipid profile is reasonable E At first diagnosis At the initial medical evaluation And/or at age 40 years and periodically (e.g., every 1-2 years) thereafter ADA. 8. Cardiovascular Disease and Risk Management. Diabetes Care 2015;38(suppl 1):S51

Case 19 yo M has had DM1 for 8 yrs, reasonable control managed on MDI insulin regimen. No complications. Rare hypoglycemia. Nonsmoker. [-] family history. BP 128/78, BMI 32 otherwise normal exam.

Case - continued Hemoglobin A 1c = 7.8% Creatinine = 0.77 mg/dl TSH = 2.83 miu/l Total cholesterol = 224 mg/dl HDL cholesterol = 26 mg/dl LDL cholesterol = 150 mg/dl Triglycerides = 229 mg/dl

Case - continued Initiation of which of the following would lead to greatest reduction in lifetime cardiovascular risk? A. Intensify glucose control B. Statin C. Fibrate D. Niacin E. Low fat diet

Recommendations for Statin Treatment in People with Diabetes Age Risk factors Recommended statin dose * Monitoring with lipid panel <40 years None None Annually or as CVD risk factor(s) ** Moderate or high needed to monitor for Overt CVD *** High adherence 40 75 years >75 years None Moderate As needed to CVD risk factors High monitor Overt CVD High adherence None CVD risk factors Overt CVD Moderate Moderate or high High As needed to monitor adherence * In addition to lifestyle therapy. ** CVD risk factors include LDL cholesterol 100 mg/dl (2.6 mmol/l), high blood pressure, smoking, and overweight and obesity. *** Overt CVD includes those with previous cardiovascular events or acute coronary syndromes. ADA. 8. Cardiovascular Disease and Risk Management. Diabetes Care 2015;38(suppl 1):S52, Table 8.1

What is moderate / high intensity statin? Circulation. June 24, 2014 vol. 129 no. 25 suppl 2 S1-S45

Recommendations: Dyslipidemia/Lipid Management Treatment recommendations and goals Combination therapy has been shown not to provide additional cardiovascular benefit above statin therapy alone and is not generally recommended A Statin therapy is contraindicated in pregnancy B In clinical practice, providers may need to adjust intensity of statin therapy based on individual patient response to medication (e.g. side effects, tolerability, LDL cholesterol levels.) E Cholesterol laboratory testing may be helpful in monitoring adherence to therapy but may not be needed once the patient is stable on therapy E ADA. 8. Cardiovascular Disease and Risk Management. Diabetes Care 2015;38(suppl 1):S52

Questions?