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Diabetes Mellitus

Diabetes Mellitus. James W. Mold, M.D., M.P.H. OU-HSC Department of Family and Preventive Medicine. Objective. Attendees should be able to:

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Diabetes Mellitus

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  1. Diabetes Mellitus James W. Mold, M.D., M.P.H. OU-HSC Department of Family and Preventive Medicine

  2. Objective Attendees should be able to: • Construct a rational management plan for an older patient with type 2 DM, taking into account life expectancy, risks for adverse events, and patient goals, preferences, and resources

  3. Format • Lecture (30 minutes) • Small group case-discussions (30 minutes) • Presentations of case discussions in large group (30 minutes)

  4. Type 2 Diabetes Mellitus Insulin resistance plus beta cell failure • Insulin resistance (metabolic syndrome) usually precedes beta cell failure by 10-20 years • Connection between the two is still unclear Beta cell fatigue? Genetically linked? Inflammation? • DM diagnosed when beta cell function insufficient to control blood glucose levels First manifestation is postprandial hyperglycemia

  5. Insulin Resistance/Metabolic Syndrome • Insulin resistance • Hypertension • Lipid abnormalities • Endovascular inflammation • Hypercoagulability Doubles the risk of: Macrovascular events (MI, CVA)

  6. Metabolic SyndromeNCEP ATP III Criteria (3 or more criteria) CriteriaDefining Level Waist circumference Men >40 inches Women >35 inches Triglycerides >150 mg/dL HDL Cholesterol Men <40 mg/dL Women <50 mg/dL Blood Pressure>130/>85 mm Hg Fasting Glucose>110 mg/dL NCEP ATP III. JAMA. 2001;285:2486–2497.

  7. Metabolic Syndrome: Prevalence by ATP III Criteria — NHANES III Population Overall 22% for age 20 and older Prevalence (%)  Age (yr) Adapted from: Ford ES et al. JAMA. 2002;287:356–359.

  8. Why Worry About Insulin Resistance • Twice the risk of MI, CVA, PAD • Eight times the risk of development of type 2 DM • Substantially reduced life expectancy (by approximately 8 years)* *Franco et al. Arch Intern Med 2007;167:1145-1151

  9. Beta Cell Failure Hyperglycemia increases risk for: • Microvascular disease (retinopathy, nephropathy) • Neuropathy • Infection Some small additional risk for: • Macro-vascular disease/events • Hypercoagulability • Endothelial cell dysfunction

  10. UKDPS: Benefits of Glycemic Control vs BP Control With ACEIs or -Blockers 20 Heart Failure Stroke MI Diabetic Death 0 +7 -8 -9 -12 Relative Risk Reduction % -20 -21 -32 -40 Glycemic Control ACEI or BB -44 -60 -56 UKPDS Group. BMJ. 1998;317:703–713. Lancet. 1998;352:837–853.

  11. Early Detection/Screening • USPSTF: Screen all adults with hypertension or hyperlipidemia for type 2 diabetes mellitus.

  12. Prevention In at risk patients: • The onset of beta cell failure (diabetes) can be delayed or prevented with exercise, diet, metformin, glitazones, acarbose, an ACEI or an ARB. • Exercise and diet are much more efficacious than medications. However, • The cost effectiveness of delaying the onset of diabetes has not yet been established.

  13. American Geriatrics Society • Offer individualized therapy that considers • Life expectancy • Cognitive impairment • Patient preferences • Functional status • Social support • Keep therapy as simple and inexpensive as possible

  14. Goals Things you would want to make happen for which it makes very little sense to ask, “so that….?” Examples: A longer life, the ability to communicate through writing, the ability to make decisions for myself.

  15. Goals of Health Care Prevent premature death and disability (QALE) • Increase life expectancy (LOL) • Reduce the risk of disabling complications (future QOL) Improve or maintain current quality of life (QOL) • Maximize ability to function in ways that make life worth living

  16. Clinical Decision-making Strategies in individual cases should depend upon: • Outcomes of importance to the patient • Desire to continue to try to stay alive • Ability to participate in valued life activities • Estimated impact of interventions on those outcomes • Ability and willingness of the patient to adhere to the interventions

  17. DM and Length of Life 75% of Type 2 diabetics die of cardiovascular events (MI, CVA) • 2-4 times more likely to have cardiovascular events • Risk of MI is as high for type 2 diabetics with no prior MI as for non-diabetics with a prior MI • When they have an MI, diabetics are significantly more likely to die or to develop CHF

  18. Lifestyle Modifications Exercise*** • Aerobic: Substantial benefits for both LOL and QOL • Strengthening: Substantial benefits for future QOL, ??LOL • Balance: Reduced falls Diet • Weight reduction: Difficult.** Associated with better QOL. Be more careful in the elderly. • Mediterranean diet: Associated with reduced macrovascular events. Be careful in the elderly.

  19. Low-Dose Aspirin • Reduced risk of MI; greater in men • Reduced risk of CVA; greater in women USPSTF recommends low dose aspirin for men 45 to 79 and women 55 to 79

  20. DM and LOL • ACE inhibitor (ramipril): 24% reduction in overall mortality over 4.5 years (16% after controlling for effects of BP reduction) • Overall mortality reduced in patients with HTN and LVH with ARBs. 42% reduced risk of CVA even if little change in BP. ARBs reduce cardiovascular events more than atenolol. HOPE Study Investigators. Lancet 2000; 355 (9200): 253-259 LIFE Study Investigators. Lancet 2002; 359: 1004-1010

  21. DM and LOL Possible reasons for benefits of ACEIs: • Anti-ischemic • Stimulate endothelial nitric oxide • Decrease myocardial O2 consumption • Anti-atherogenic • Reduce systemic vascular resistance and BP • ?Reduce cardiac remodeling

  22. RRR and ARR Base Risk X RRR = Absolute Risk Reduction If base risk = 10%, and RRR = 50%, then ARR = 5% If base risk = 50%, and RRR = 50%, then ARR = 25% Therefore, the actual benefit of risk reduction is often greater in the elderly assuming equal RRR (because base risk is higher).

  23. Effects of DM on QOL RCT of glipizide XL vs. placebo for 12 weeks • 594 patients; mean age 58.5 (range: 30-85) • Glipizide XL titrated upward as needed • Home glucose monitoring • Final mean A1c’s: 7.5% (glipizide) vs. 9.3% (placebo) • Final average fasting BS’s: 126mg/dl (glipizide) vs. 168 mg/dl (placebo)

  24. Effects of DM on QOL Global QOL directly related to A1c level Glipizide group had significantly (p<0.001) less: • Weakness; fatigue • Urinary frequency; nocturia • Thirst; polydipsia • Dryness of mouth, eyes, or nose • Sweet taste in mouth

  25. Effects of DM on QOL (cont.) Glipizide group also had significantly (p<0.01) less: • Foot cramps; foot pain • Sweating • Numbness of lips or mouth • Blurred or double vision • Crabbiness; short-temperedness

  26. Effects of DM on QOL (cont.) Glipizide group also had (p<0.05) less: • Headaches • Tiredness, drowsiness • Muscle cramps • Vertigo (spinning sensation) • Lightheadedness when standing up • Chest pain with exertion • Confusion

  27. Effects of DM on QOL (cont.) • Glipizide group also had fewer: • Days absent from work • Days spent in bed • Days of restricted activity Testa MA, et al. JAMA 1998; 280 (17): 1490-1496

  28. Micro-vascular Disease • Greater benefit from reduction of A1c from 9 to 8 than from 8 to 7 • It takes 8-10 yrs of glycemic control to realize the benefits for micro-vascular disease

  29. ESRD End Stage Renal Disease (ESRD) by age at diagnosis of DM: Age at Dx A1c Lifetime Risk_ 55 7.0 0.9% 55 9.0 1.6% 65 7.0 0.3% 65 9.0 0.6%

  30. Blindness Blindness from DM Retinopathy by age at diagnosis of DM: Age at Dx A1c Lifetime Risk 55 7.0 0.1% 55 9.0 1.2% 65 7.0 <0.1% 65 9.0 0.5%

  31. Diabetic Peripheral and Autonomic Neuropathies • Proposed mechanisms: sorbitol, myoinosital, ischemia, glycosylation, osmotic • Improved glucose control probably slows progression, but size of effect is unknown • Some evidence of minor benefits from: C-peptide, Vitamin E, other antioxidants, nerve growth factors

  32. Why Not Control Everything? • Law of diminishing returns • Less benefit from successive interventions • Diminishing ability to correctly adhere to more complicated regimens • Increased side effects and drug interactions from more meds (exponential increase above 4-5) • Impact of testing and interventions on lifestyle

  33. Math ARR = RRR (baseline risk) Most interventions that can reduce risk of heart attack have RRR of about 25%. If 10-yr base = 20%, then the first intervention results in an ARR of 5%, the second in an ARR of 3.75% (25% of 15%), and so on (diminishing returns)

  34. RRR = Relative Risk Reduction; ARR = Absolute Risk Reduction Diminishing Returns Equal RRRs

  35. RRR = Relative Risk Reduction; ARR = Absolute Risk Reduction Diminishing ReturnsTreatments Chosen from Best RRR to Worst

  36. Problems with Hypoglycemia • Case-control study involving 111 community-dwelling adults >75 years of age • Strong correlation between A1c<7 and increased risk of falls • NHLBI-funded ACCORD study, a RCT with 10,251 participants • Intensive treatment group had an excess number of deaths

  37. Simulation Fictitious 79 year-old woman with DM, COPD, HTN, OA, and osteoporosis. Researchers applied relevant clinical practice guidelines using a conservative approach and generics. • Required 12 medications • $406 per month (pre-Medicare D) • Taken at 5 different times per day • Multiple potential interactions Boyd CM, et al. JAMA 2005; 294(6): 716-724.

  38. Case Mr. M is a 65 yo man with type 2 diabetes mellitus diagnosed a yr. ago. Sedentary lifestyle; no cigarettes or alcohol. Recent onset of fatigue, decreased libido, polyuria and polydipsia, and increasing pain in his joints. He currently takes no medications. Past and family history are unremarkable. His primary care physician finds: body mass index (BMI) of 30.5, BP 200/100 mmHg, osteoarthritis involving fingers and knees, hemoglobin A1c 10%, LDL cholesterol 140 mg/dl, HDL cholesterol 40 mg/dl, total cholesterol 260 mg/dl, ALT and AST slightly elevated, and serum testosterone low.

  39. Diabetes Personal Health Decisions (PHD) Engine Archimedes program • Attempts to model diabetes by including >100 biological variables, symptoms, signs, tests, treatments, and outcomes • Uses differential equations and object-oriented programming to model the links between variables • Keeps all continuous variables continuous

  40. Diabetes Personal Health Decisions (PHD) Engine • Addresses co-morbidities and treatments with multiple effects • Includes not only individual patients, but also aspects of the helath care delivery system (facilities, equipment, policies and procedures, costs, and utilities) • Data based upon knowledge of pathophysiology, clinical trials, and data from Kaiser Permanente

  41. PHD Validation • Subjected to a series of 74 validation exercises involving 18 clinical trials, 10 of which were not used in the construction of the engine • Correlation between results of PHD simulations and clinical trials overall was astounding (r=0.99) • Correlation between absolute differences in outcomes also amazing (r=0.97)

  42. Mr. Waldman (Diabetes PHD Risk Engine) Life expectancy is about 7 years. 7-yr. Risk MI CVA 40% 17% ARRSumARRSum Aspirin 11% 2% Moderate Exercise 10% 20% 5% 6% BP to 130 with ACEI 7% 24% 3% 9% Lower LDL to 100 5% 27% 0% 9% Lower A1c to 6.5% 1% 28% 0% 9% Reduce BMI to 26 9% 31% 3% 11% www.diabetes.org

  43. Objective Attendees should be able to: • Construct a rational management plan for an older patient with DM, taking into account goals and preferences, life expectancy, abilities, and resources

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