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Type II Diabetes

Type II Diabetes. Matthew Love, M.D. Case 1. Fred Banting, a 52 year-old man, complains of polyuria and polydypsia for three weeks. On questioning, he also admits to dizziness on standing. On exam, his BP is 135/80, Pulse 95. He is 5’8” tall, weighs 220# and has acanthosis nigricans.

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Type II Diabetes

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  1. Type II Diabetes Matthew Love, M.D.

  2. Case 1 Fred Banting, a 52 year-old man, complains of polyuria and polydypsia for three weeks. On questioning, he also admits to dizziness on standing. On exam, his BP is 135/80, Pulse 95. He is 5’8” tall, weighs 220# and has acanthosis nigricans. Urine dipstick is ++ for glucose. Fingerstick glucose is 188. Point of Care Hemoglobin A1c is 8.3%. Does this patient have Diabetes?

  3. Diagnosis

  4. Prediabetes • Impaired fasting glucose: 100 < FPG < 126 • Impaired glucose tolerance: OGTT result at 2h between 140-199. • Hemoglobin A1c of 6.0% – 6.4%

  5. Remember the Pathogenesis

  6. Remember the Pathophysiology

  7. Case 2 Dulce Diente is a 37 year-old female with a family history of diabetes. She wants to be checked for diabetes because she has gained a lot of weight, she keeps getting yeast infections and her urine tastes sweet. Physical exam is normal except for a BMI of 29. FPG checked by fingerstick on her father’s glucometer has been 110-120. Point of Care HbA1c comes back at 6.8% Should she be started on medicine? Is there anything that can be done to prevent the progression of her diabetes?

  8. Diabetes Prevention ProgramResults

  9. Diabetes Prevention ProgramChange in weight & Physical Activity

  10. PREVENTION TRIALS

  11. Case 3 Isabel Fadiman is a 41 year-old African-American female who presents for a check-up. She has no complaints. Past medical history includes gestational diabetes during her last pregnancy five years ago. Family history is positive for two brothers and both parents with Type 2 DM. She does not smoke. On exam, her BP is 120/80 and her BMI is 27. There is no acanthosis nigracans or any other abnormality. Should she be screened for diabetes?

  12. Diabetes Screening Recommendations

  13. Risk Factors for Type 2 Diabetes • Age > 45 y • First-degree relative with type 2 Diabetes • African-American, Hispanic, Asian, Pacific Islander, or Native American ethnicity • History of gestational diabetes or delivery of infant weighing ≥9 lbs • Polycystic ovary syndrome • Overweight, especially abdominal obesity • Cardiovascular disease,hypertension, dyslipidemia, or other • metabolic syndrome features

  14. Initial Evaluation • Symptoms • Exam – BP, BMI, Feet • Labs • HbA1c • Ualb/cr • Chemistry (Cr, LFTs) • EKG • Referrals • Dietician • Glucometer Teaching • Ophthalmology • Podiatry

  15. Blood Glucose Monitoring

  16. Glucometer Operation

  17. Case 4 Matt Forman is a 54 year-old man with newly diagnosed Type II Diabetes. His FPG is 148 and his HbA1c is 7.8% . Physical is normal except for BMI of 28. Except for the glucose values, his laboratory exams are normal. How should he be treated?

  18. Treatment non-pharmacologicDiet • Carbohydrates • Should comprise 45%-65% of total calories • No concentrated sweets (soda, juice, desserts) • No white starches (especially rice and pasta) • Fresh vegetables and fruits rather than canned • Fats • Should comprise < 30% of total calories • Saturated fats should be < 7%

  19. Treatment non-pharmacologicExercise

  20. Treatment pharmacologicOral Agents

  21. Metformin • No weight gain • No hypoglycemia • Cheap, generic, old • GI side effects frequent • Rare but serious lactic acidosis • Start at 500 bid with meals • Titrate up quickly to 1000 bid or 850 tid

  22. Sulfonylurea • Cheap, generic, old • Equally effective • May cause hypoglycemia • Weight gain • Start at low dose, increase gradually

  23. Thiazolidinediones TZD • Increase glucose uptake and decrease glucose production • Equally effective • May preserve beta-cell function • Newer, more expensive • Fluid retention • May cause xs MIs

  24. Incretin mimetics

  25. Incretin-based therapies

  26. Alpha-glucosidase Inhibitors • Lower postprandial glucose and A1c • Less potent • No weight gain • Cause flatulence • Contraindicated in cirrhosis • Take with first bite of meal

  27. Case 4 Matt Forman is a 54 year-old man with newly diagnosed Type II Diabetes. His FPG is 148 and his HbA1c is 7.8% . Physical is normal except for BMI of 28. Except for the glucose values, his laboratory exams are normal. After 6 months of a diabetic diet and increased exercise, his HbA1c is 8.1% How should he be treated?

  28. Case 4 Matt Forman is a 54 year-old man with newly diagnosed Type II Diabetes. His FPG is 148 and his HbA1c is 7.8% . Physical is normal except for BMI of 28. Except for the glucose values, his laboratory exams are normal. After 6 months of a diabetic diet and increased exercise, his HbA1c is 8.1% After 6 months of Metformin at a dose of 1000 mg bid, his HbA1c is 7.1% How should he be treated? What is the glycemic control target?

  29. Glycemic Control Target: Good Control Reduces Microvascular Complications

  30. Glycemic Control Target: The UKDPS – the largest and longest study in Type II DM • Microvascular complications were reduced 25% in the intensive- therapy group • Epidemiologic analysis showed that for every 1% reduction of HbA1c: • 35% reduction in microvascular complications • 25% reduction in diabetes related deaths • 7% reduction in all cause mortality • 18% reduction in myocardial infarction • No lower threshold

  31. Glycemic Control Target: Macrovascular Complications ACCORD trial – Action to Control Cardiovascular Risk in Diabetes

  32. Glycemic Control Target: Current Recommendations from the ADA: • The Benefits of Intensive Glycemic Control on Macrovascular Complications vary based on the population being treated • Those most likely to benefit from intensive control are those with shorter duration of DM, no known vascular disease, and without severe hypoglycemia • The risk of intensive glycemic control may outweigh the benefits in those with a long duration of DM, known vascular disease, or symptomatic severe hypoglycemia

  33. Case 4 Matt Forman is a 54 year-old man with newly diagnosed Type II Diabetes. His FPG is 148 and his HbA1c is 7.8% . Physical is normal except for BMI of 28. Except for the glucose values, his laboratory exams are normal. After 6 months of a diabetic diet and increased exercise, his HbA1c is 8.1% After 6 months of Metformin at a dose of 1000 mg bid, his HbA1c is 7.1% How should he be treated? A second agent should be added

  34. Case 4 – Algorithm

  35. Case 5 Norman P. Hagedorn is a 64 year-old man with Type II Diabetes for 12 years. He also has CAD, s/p MI and CABG, HTN, gout, and BPH. Medications include metformin, glyburide, pioglitazone, and sitagliptin at maximal doses. Previously, his HbA1c were always in the 7.0-7.9% range, however his last two HbA1cs, three months apart, are 9.8% and 10.9%. Previous attempts to introduce insulin injections have met with adamant refusals. What might have happened to his glycemic control?

  36. Case 5 Norman P. Hagedorn is a 64 year-old man with Type II Diabetes for 12 years. He also has CAD, s/p MI and CABG, HTN, gout, and BPH. Medications include metformin, glyburide, pioglitazone, and sitagliptin at maximal doses. Previously, his HbA1c were always in the 7.0-7.9% range, however his last two HbA1cs, three months apart, are 9.8% and 10.9%. Bedtime NPH 10 Units is added to his metformin. Glyburide , pioglitazone, and sitagliptin are discontinued. After following the titration schedule for six weeks, he is on 25 units NPH and morning fingersticks are 95-125.

  37. Case 5 Norman P. Hagedorn is a 64 year-old man with Type II Diabetes for 12 years. He also has CAD, s/p MI and CABG, HTN, gout, and BPH. Medications include metformin, glyburide, pioglitazone, and sitagliptin at maximal doses. Previously, his HbA1c were always in the 7.0-7.9% range, however his last two HbA1cs, three months apart, are 9.8% and 10.9%. Bedtime NPH 10 Units is added to his metformin. Glyburide , pioglitazone, and sitagliptin are discontinued. After following the titration schedule for six weeks, he is on 25 units NPH and morning fingersticks are 95-125. After 3 months with continued good am fingersticks, HbA1c is 8.5%. What would you do now? Pre-dinner fsg are 160-180, so NPH is switched to glargine and eventually titrated up to a dose of 35 U daily. Now am fsg are 80-110 and pre-dinner are 95-120. 3 months later HbA1c is 8.0%. What would you do now?

  38. Diabetes Treatment Algorithm

  39. Diabetes and Hypertension - UKDPS For each 10 mm decrease in SBP: • Microvascular complications ↓ 13% • Death ↓ 15% • MI ↓ 11%

  40. Diabetes & Lipids - Heart Protection Study • Primary prevention with risk factors (hypertension, diabetes, and CVA) • 2x2 factorial design simvastatin 40 mg/day, antioxidant cocktail (600 mg vitamin E, 250 mg vitamin C, 20 mg beta carotene) • N = 20,000; subgroups include: Women (n ~ 5,000) Elderly (>65, n ~ 10,000) Diabetics (n ~ 6,000) Stroke (n ~ 3,000) Hypertension (n ~ 8,000) Noncoronary vascular disease (n ~ 7,000) Low to average blood cholesterol (n ~ 8,000)

  41. Heart Protection Study: Vascular Events by Baseline Disease Risk ratio and 95% CI Statin better Statin worse  24 ± 2.6% (2P <0.00001) 0.4 0.6 0.8 1.0 1.2 1.4

  42. Diabetes/HTN & Lipids – Steno-2 Intervention was intensive lowering of BP, lipids, and A1c Macrovascular complications reduced 50% in intensive treatment group over 13 years

  43. Diabetes & HTN & Lipids

  44. The Routine Followup Visit • Glycemic Control • Fingersticks • Daily if previously at target and on orals or glargine • More frequently if not at target or more complicated regimen • Symptoms of hypoglycemia & hyperglycemia • Adherence to Diet, Exercise, & Medication • Ongoing Education • Ongoing Screening for longterm microsvascular complications (at least yearly) • Nephropathy (Ualb/cr), Neuropathy (monofilament) , retinopathy • Control of other macrovascular risk factors • LDL < 100 • BP < 130/80

  45. Question 1 – What are the symptoms of diabetes? • Hyperglycemia • Tm of kidney for reabsorption of glucose > 160, sugar pulls water, leading to polyuria; the dehydration stimulates thirst • Polyphagia and weight loss • Blurry vision – glucose deposits in cornea • Yeast infections • Volume Depletion - Orthostatic dizziness • Nonspecific symptoms • Headaches, weakness

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