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Medical Overview of Diabetes in Older Adults

Medical Overview of Diabetes in Older Adults. Darin E. Olson, MD, PhD Assistant Professor of Medicine Division of Endocrinology, Metabolism & Lipids Emory University School of Medicine Atlanta VAMC. Case Studies of Diabetes Mellitus in Older Adults.

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Medical Overview of Diabetes in Older Adults

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  1. Medical Overview of Diabetes in Older Adults Darin E. Olson, MD, PhD Assistant Professor of MedicineDivision of Endocrinology, Metabolism & Lipids Emory University School of Medicine Atlanta VAMC

  2. Case Studies of Diabetes Mellitus in Older Adults • Describe a broad spectrum of diabetes in older adults • Illustrate specific points about the approach and management of diabetes in older adults in 3 cases

  3. GeneticsEnvironment aging obesity sedentary lifestyle Onset Natural History - Type 2 Diabetes Complications Disability Prediabetes: IGT, IFG Hyperglycemia Death Insulinresistance Hyperinsulinemia Dyslipidemia Atherosclerosis Hypertension Retinopathy Nephropathy Neuropathy Depression Blindness Renal failureAmputation CVD

  4. New ADA Recommendations for Diagnosing Diabetes

  5. Prevalence of Diabetes in USA Year: Age: CDC Diabetes Data and trends, www.cdc.gov/diabetes/statistics/prev/national/figbyage.htm

  6. Cumulative Incidence of Diabetes According to Study Group Preventing Diabetes in Older Adults All Subjects Older Adults (Cases/100 person-yrs) Adapted from Diabetes Prevention Program Research Group, NEJM 2002;346:393-403

  7. Hemoglobin A1c < 7% Fasting BG 80-120 mg/dL Post-prandial BG 100-150 mg/dL Nutrition Therapy Exercise Anti-platelet agents Blood Pressure Control Lipids Safe use of combination therapy Screen for complications Renal Neural Retinal Cardiovascular Foot Care Education Specifics for older adults addressed 1st time in 2005 ADA Guidelines for Adults with Diabetes

  8. A1C and Relative Risk of Microvascular Complications: DCCT Retinopathy 15 Nephropathy 13 Neuropathy Microalbuminuria 11 9 Relative Risk 7 5 3 1 6 7 8 9 10 11 12 A1C (%) Adapted from Skyler J. EndocrinolMetabClin North Am. 1996;25:243 DCCT Research Group. N Engl J Med. 1993;329:977

  9. CHD Mortality All CHD Events Incidence (%) Incidence (%) A1C (%) A1C (%) 7.0 7.0 <7.0 <7.0 <6 yrs 6 yrs <6 yrs 6 yrs Duration of Diabetes Duration of Diabetes Control of Type 2 Diabetes Predicts Cardiovascular Disease in Older Patients BUT, does epidemiology predict trial results? Adapted from Kuusisto J, et al. Diabetes. 1994;43:960-967.

  10. Multifactorial Intervention Helps STENO-2 Reduced Microvascular Complications: STENO-2 Trial. NEJM 348:393, 2003

  11. American Diabetes Association www.diabetes.org

  12. Individualizing Treatment Goals Position Statement of the ADA & EASD. DIABETES CARE. 2012

  13. Antidiabetic Agents:Major Sites of Action Plasma glucose -GlucosidaseInhibitors GLP-1 agonists TZD’s Carbohydrate Absorption Glucose Uptake (–) (+) Glucose Production GI tract Muscle/Fat (+) InjectedInsulin Metformin Liver (–) (–) Incretins – + X ←DPPIV Insulin Secretion Sulfonylureas Meglitinides GLP-1 agonists Insulin Secretion Pancreas (+) Amylinor analog 4-5

  14. Antidiabetic Agents for Type 2 DM

  15. What would you choose?

  16. Position Statement of the ADA & EASD. DIABETES CARE. 2012

  17. Themes From AGS Guidelines for Older Adults • Individualize care and education • Provide aggressive treatment to prevent and manage cardiovascular risk factors • Help prevent and manage microvascular complications through glycemic control • Screen for and treat geriatric syndromes that are more common in older adults with diabetes California Healthcare Foundation/American Geriatrics Society (AGS) Panel on Improving Care of Elders with Diabetes. Guidelines for Improving the Care of the Older Person with Diabetes Mellitus. J Am Geriatrics Soc 2003; 51:S265-S280

  18. Associated Conditions: Premature death Functional disability Hypertension CAD CVA Depression Cognitive impairment Urinary incontinence Injurious falls Pain Polypharmacy From AGS Guidelines on DM, JAGS, 2003. Accessible at: www.americangeriatricsociety.com Other Adverse Outcomes: Blindness Renal failure Amputations Infections CHF GERD Hospitalization In-hospital complications Disability Conditions Associated with DM in Older Adults

  19. adapted from Norris and Olson. Geriatrics, 2004

  20. Update on Cardio-Vascular Disease in T2DM, 2008 • ACCORD • VADT • ADVANCE • STENO-2 • Nephropathy prevented • Control Risk Factors • Blood Pressure • Lipids • Limited benefit, possibly harm from strict glycemic control • Reasons for lack of benefit unclear

  21. Diabetes in Older Adults: Case 1 Active 68 year old man with cardiovascular risk • Complained of exertional chest pain at work, referred by colleague to seek medical attention • Lifelong overweight, gained 30 lbs. in past 3 years • Remote cigarettes, light alcohol intake • Hypertension controlled with thiazide • Elevated cholesterol (not treated with medications) Contributory Family and Social History • Family history significant for mother with DM d. 85yo from MI, father d. 88yo with dementia, brother with DM and obesity

  22. Diabetes in Older Adults: Case 1 Contributory Medications and Comorbidities • No major comorbid illness Targeted elements of physical exam • MMSE 30/30 • BP 135/90, HR 70, weight 245 lbs., height 5’10”, waist 44” • ECG = NSR, leftward axis Labs • Fasting blood glucose = 164 & 138 mg/dL • HbA1c = 8.0% • Cholesterol 210, LDL 140, HDL 39, TG 160 (mg/dL) • BUN/Cr = 18/1.2, Urine Albumin = 8 mg/day

  23. Diabetes in Older Adults: Case 1Treatment Goals Standard Type 2 DM and major AGS themes guidelines apply for this patient • Aggressively Prevent and Manage Cardiovascular Risk Factors through lifestyle management and medication adherence • Smoking • Lipids • Blood Pressure • Exercise and Diet • Glycemic control: • Nutrition therapy • Lifestyle • Monitoring • HbA1c, fasting and post-prandial goals • Oral or injectable agents all have potential roles

  24. Diabetes in Older Adults: Case 1 Therapeutic Approach Pharmacological goals related to CV risk: • Glycemic Control • Blood Pressure • Lipids • Anti-platelet agents

  25. Diabetes in Older Adults: Case 1Summary • Provide aggressive treatment to prevent and manage cardiovascular risk factors • Help prevent and manage microvascular complications through glycemic control • Follow same DM guidelines as younger adults (unless specific factors need consideration) • Pursue additional conditions associated with DM in older adults • Use multifactorial approach in majority of patients • Individualize approach for every patient…

  26. Position Statement of the ADA & EASD. DIABETES CARE. 2012

  27. Metformin • Generally first choice medication • Reduces hepatic glucose output • Effective in many studies • Mild weight loss • Reduce GI ADE’s by starting low dose • Low risk of hypoglycemia as monotherapy • Prevents DM in younger patients in DPP

  28. Effect of metformin as monotherapy or in combination with glyburide

  29. Metformin • High rate of GI adverse effects • Mild weight loss • Lactic acidosis • Rare (1/40,000) and usually associated with another risk factor • Contraindications: • Renal disease • Hepatic disease • Hypoxic or acidotic conditions

  30. Metformin: Use in the elderly? • Age is frequently listed as contraindication • Really Shouldn’t be • Contraindications may be more common in older adults, • remain vigilant

  31. Sulfonyl-Ureas • Previous first choice medication • Increase insulin secretion from beta-cells • glyburide, glipizide, glimeperide • Long history • Efficacy in multiple studies

  32. Sulfonylureas and Hypoglycemia in Older Adults Age was most common associated factor • 80% over 60 yo • Peak age 71-80 Other major factors: • Renal function • Energy intake • Infection Ben-Ami et al, Arch Int Med 1999

  33. Sulfonyl-Ureas • 2nd generation safer than 1st generation • Highest risk of hypoglycemia • Weight gain • High risk of treatment “failure” • Renal metabolism and excretion • Glyburide may be more associated with cardiac arrhythmia risk • Glipizide has shorter half-life • Sulfa allergies

  34. Time Course of Action of Basal Insulin Preparations Effective Duration of Action (h) Maximum Duration of Action (h) Onset of Action (h) Peak Action (h) Insulin Preparation Long acting Glargine (basal analog) 5 None >24 Unknown Detemir (analog) 1 8-10 12-24 18-24 Intermediate acting NPH (isophane) 2-4 6-10 10-16 14-18 Start with a daily dose Advance dose until reaching safe fasting BG goal

  35. 80 80 60 60 40 40 20 20 0 0 Oral glucose load Intravenous (IV) glucose infusion Incretin Effect Diminished in Type 2 Diabetes Control Subjects (n=8) Subjects With Type 2 Diabetes (n=14) Normal Incretin Effect Diminished Incretin Effect IR Insulin, mU/L IR Insulin, mU/L 0 60 120 180 0 60 120 180 Time, min Time, min IR=immunoreactive. Nauck M et al. Diabetologia 1986;29:46–52. Permission requested.

  36. GLP-1 Modulates Numerous Functions in Humans GLP-1: Secreted upon the ingestion of food Promotes satiety and reduces appetite Alpha cells:  Postprandialglucagon secretion Incretins broken down by DPP-IV Liver: Glucagon reduces hepatic glucose output Beta cells:Enhances glucose-dependent insulin secretion Stomach: Helps regulate gastric emptying Data from Flint A, et al. J Clin Invest. 1998;101:515-520;Data from Larsson H, et al.Acta Physiol Scand. 1997;160:413-422Data from Nauck MA, et al. Diabetologia. 1996;39:1546-1553; Data from Drucker DJ. Diabetes. 1998;47:159-169

  37. DPPIV Inhibitors Sitagliptin, saxaglipitin (others in pipeline) • Newest class on the market • DPPIV normally proteolyzes GLP-1,GIP, glucagon to inactivate them • Weight neutral • Enhance insulin secretion • No long-term safety or outcome data • Probably safer in renal disease • Probable additive effect with metformin

  38. GLP-1 Analogs(exenatide, liraglutide) • Incretin mimetic • GLP-1 analog, not recognized by DPPIV • Increases duration and levels • Multiple beneficial effects: • Weight loss • Decreased GI motility • Increased insulin secretion • Suppress glucagon • beta-cell preservation and growth • Suppress appetite

  39. Exenatide, Liraglutide • Modest improvement in glycemia • Weight Loss • Currently expensive • Frequent GI ADE’s • Injected • Exenatide (Byetta™) twice a day before meals • Liraglutide (Victoza™) daily • Exenatide weekly preparation (Bydureon™) just released • Others nearly available or in pipeline • Benefits don’t correlate with physiological effects • Case reports of pancreatitis • No long term or outcome trials

  40. Thiazolidinediones Pioglitazone now 1st (only?) choice • Activates PPARg nuclear receptor • Mostly acts directly on fat and liver cells • Enhances insulin action everywhere • 3-6 weeks for glycemic effects • Best results in preventive trials • Longest duration of oral monotherapy in early diabetes • Purported “pleiotrophic” benefits • Low risk of hypoglycemia as monotherapy

  41. Thiazolidinediones ADE’s : • Edema • Macular edema • CHF • Weight Gain • Hepatotoxicity • Decreased bone density • Variable lipid effects • Mild ↑LDL, Idiosyncratic ↑TG New concerns: • increased CAD risk with rosiglitazone • increased Bladder Cancer risk with pioglitazone

  42. SU-Receptor Binding Agents Repaglinide and Nateglinide • Rapid acting, bind to alternate sites of SU receptor • Taken before meals • Somewhat glucose dependent • Decreases hypoglycemia • Less renal clearance than SU • Still some hypoglycemia

  43. SU-like agents and Hypoglycemia in Older Adults Patients over 64 yo in clinical trials for nateglinide Del Prato, Diabetes Care, 2003

  44. Glucosidase Inhibitors Acarbose and miglitol • Blocks breakdown of carbohydrates to prevent absorption at gut • GI ADE’s • Modest glycemic benefit • Take before CHO-rich meals • No risk of hypoglycemia as monotherapy • Benefit in preventive trial

  45. Diabetes in Older Adults: Case 2 Frail woman with microvascular complications • 65 yo woman with type 2 DM for 12 years • Routine follow up • Obesity, family history of DM, signs of gestational diabetes • Home BG measurements: • AM (ave. = 165 mg/dL), rare PM values (all>180) • Multiple complaints • Sedentary lifestyle, limited by complaints Diabetic Complications • Nephropathy, Neuropathy, Retinopathy, Hypertension, Hyperlipidemia Contributory Family and Social History • Remote cigarettes • No EtOH • Daughter shops and cleans. Prepares some meals on her own. • Recently stopped driving

  46. Diabetes in Older Adults: Case 2 Contributing Medications and Comorbidities • Multiple medicines prescribed, not all up-to-date • Inconsistent emptying of bottles (23 bottles of 16 medications) Aspirin, ACE-I, beta-blocker, diuretic, “statin”, SU, metformin, NSAID, opiate, OTC analgesic, OTC sleep aid, PPI, OTC antacid, 2 antidepressants) Targeted elements of physical exam • MMSE 26/30 • BP 140/90, HR 80, Weight 180 lbs, height 5’4”, waist 40” • Unsteady gait • BDR without bleeding • Enlarged liver span • Trace edema, preserved pulses, osteoarthritic changes, fails monofilament, impaired distal vibratory sensation Labs • HbA1c = 8.5% • Cr = 1.3 • LDL = 100, HDL = 38

  47. Diabetes in Older Adults: Case 2 Follow a Multidisciplinary Approach • The group of providers* • Self-management • Caregivers • Geriatric primary care • Diabetes education • Certified Diabetes Educators • Physician Assistants and Nurse Practitioners • Nurses, Directors of Nursing • Pharm.D. and Pharmacists • Nutritionist • Podiatrist • Subspecialty consultants *an example similar to our model at the VA, (Neither all-inclusive nor exclusive)

  48. Diabetes in Older Adults: Case 2Treatment Goals CV risk and Glycemic control • Who benefits according to AGS guidelines • CV risk reduction for all • Glycemic control for: • Symptoms • Avoid progression of established microvascular complications • Greater than 8 years of projected mortality

  49. Diabetes in Older Adults: Case 2 Therapeutic Approach • Choose safest set of medications • Combination Therapy frequently necessary “polypharmacy” vs. Combination therapy: • Hypertension • Glycemic control • Pain control • Psychoactive medications • Avoid contraindicated medications • Metformin • Sulfonylurea • Thiazolidinediones • NSAID’s • Reduce un-necessary medications • Evaluate symptomatic needs judiciously • Reduce psychoactive medications appropriately

  50. Polypharmacy • Definition: “Whenever a drug is not indicated” • R. David Lee, MD • The Triangle (work as a team) • Prescriber • Patient • Others: Nurse, Physician Assistant, Pharmacist, Social workers, Caregiver…. Lee, J Am Board Fam Prac, 1998

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