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GO! Diabetes Program

GO! Diabetes Program. Goals For Today. Review evidence based guidelines and equip you to deliver state of the art care to your diabetic patients Understand tools that support practice performance and improvement Review oral and injectable medicines hypoglycemics

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GO! Diabetes Program

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  1. GO! DiabetesProgram

  2. Goals For Today • Review evidence based guidelines and equip you to deliver state of the art care to your diabetic patients • Understand tools that support practice performance and improvement • Review oral and injectable medicines hypoglycemics • Review multifaceted approach to cardiovascular disease protection

  3. Effect of Tighter Glycemic Control on Progression of Retinopathy DCCT

  4. Effect of Intense Glycemic Control on Nephropathy from DCCT

  5. United Kingdom Prospective Diabetes Study • Study summary – 10 years • Type 2 diabetics – convention vs. intense control • Glycemic control – 7.0 vs. 7.9 • Hypertension control – 144/82 vs. 154/87 • Glycemic control • metformin, sulfonylureas, and insulin • Hypertension • captopril, atenolol

  6. UKPDS Blood Pressure Study:Tight vs. Less Tight Control • 1148 type 2 patients • BP lowered to avg. 144/82 (controls-154/87); 9 yr follow-up Endpoint Risk Reduction(%) P Value______ Any diabetes related endpoint 24 0.0046 Diabetes related deaths 32 0.019 Heart failure 56 0.0043 Stroke 44 0.013 Myocardial infarction 21 NS Microvascular disease 37 0.0092 UKPDS. BMJ. 317: 703-713. 1998.

  7. Glycemic Control Reduces Complications Diabetes Control and Complications Trial (DCCT) Research Group. N Engl J Med 1893:329:977-988 UK Prospective Diabetes Study (UKPDS) Group. Lancet 1993; 352:837-853.

  8. ABCs Of Diabetes Management Diabetes Care 2009;32:S6-12

  9. Control of CV Risk Factors in Diabetic Hypertensive Patients in Academic Medical Centers • A1C <7% • 27% • LDL <100 • 36% • BP <130/85 mmHg • 27% • Daily Aspirin (ASA) Use • 46% • BP, Lipids and A1C • 3% • BP, Lipids, A1C + ASA • 2% McFarlane SI. DiabetesCare 2002;25:718

  10. Type 1 Vs Type 2:How To Tell Them Apart

  11. Diabetes: Early Detection and Lifestyle Monitoring

  12. Metabolic Syndrome • Requires 3 or more: • Triglycerides > 150 • HDL < 40 • Waist size >40” men, >35” women • BP > 130/85 • Fasting glucose > 100 • Caveat: Treatment counts for requirements… (Grundy, Circulation, 2005)

  13. Pre-Diabetes Definition If FBG >100 there is a 10-15% risk of DM within 7 years… or Fasting GTT

  14. Who and When to Screen? • Family history • Overweight (BMI 25) • Dyslipidemia • HTN • High risk ethnicity • Vascular disease • Prior glucose elevation • Hx or exam findings • Starting at age 45, a fasting blood glucose every three years • More frequent screening if:

  15. Role of Obesity in Diabetes • Obesity (specifically abdominal) has one of the highest associations with insulin resistance and glucose intolerance • Numerous studies have tied weight loss to diabetes prevention • A 5-10% weight loss yields a 58% reduction in the incidence of diabetes! • At the end of four years • Diet and exercise regimens average a 4kg loss after two years • Advice alone results in a 1kg gain (Franz, Journal Amer. Diabetes Assoc, 2007)

  16. Quantifying Obesity • Easiest is by waist circumferences. • 40” males, 35” females • Some variation by ethnicity (35” and 31” for Asians) • Measured across iliac crest in the back and the umbilicus in the front

  17. Healthcare Maintenance • Latest ADA guidelines (2009) • Lab surveillance • Diabetic education • Vaccinations/routine healthcare • Smoking cessation • Foot exams • Eye exams

  18. Reasons to Look at Feet • Up to 70% of diabetics eventually develop a neuropathy • Up to 25% develop foot ulcers • Diabetes doubles your risk of LE disease (vascular, neuro, skin) • More than half of the foot ulcers become infected at some point

  19. Foot Surveillance • Examine the feet at every visit • Annual comprehensive evaluation • Sensation • Pulses • Skin condition (ulcers, hair, nails) • Anatomic deformities • Shoe evaluation

  20. Sensory Exam • 10-gram monofilament • Patient should not watch • Five sites per foot • Apply filament perpendicular to skin • Allow slight buckle of filament in one motion • Each site should take 1-2 sec • Do not apply to ulcers or calluses

  21. Eye Care • Diabetic retinopathy is the leading preventable cause of blindness • Prevalence of DR increases with duration of diabetes (100% Type 1, 60% Type 2 after 20 years) • Of all recommendations, eye screening is the least likely to get done

  22. Pathogenesis • Increased circulating glucose leads to weakness of capillary walls • Microaneurysms and leakage occurs causing eventual infarction of the nerve fiber layers (cotton wool spots) • The localized hypoxia then leads to vasoproliferation • Extension into the vitrea (+/- hemorrhage) leads to fibrosis and vision loss

  23. Diabetic Retinopathy Normal Retina (left) contrasted with Proliferative Diabetic Retinopathy (right) Refer patients for ophthalmologist evaluation

  24. Glycemic Control – Oral Agents

  25. General RulesHypoglycemic Therapy • Normalize fasting glucose levels first (90-130 mg/dl) • Many patients will achieve A1C < 7% • When to target postprandial glucose levels? • Fasting and preprandial values are at goal • A1C levels are not met • Measure 1-2 hours after beginning of the meal • Glucose are generally at their peak

  26. Glycemic Goals of Therapy Verbal Target ~100 <<200 As low as possible w/o unacceptable adverse effects Goal Premeal plasma glucose (mg/dL) 2-h postprandial plasma glucose A1C ADA 90-130 <180* <7%** * Evaluation and treatment of postprandial glucose may be useful in the setting of suspected postprandial hyperglycemia, with the use of agents targeting postprandial hyperglycemia and for suspected hypoglycemia ** More stringent glycemic goals (i.e. a normal A1C, <6%) may further reduce complications at the cost of increased risk of hypoglycemia Diabetes Care 2009;32:S6-12

  27. Biguanides: Metformin Mechanism of action • Reduces hepatic glucose production • Depends upon presence of insulin Safety and efficacy • Decreases A1C 1-2% • Adverse effects: diarrhea and nausea; main risk: lactic acidosis • Discontinuation rate 5% • Contraindications: renal, cardiac, hepatic insufficiency; IV contrast • No direct effect on kidney Dosing • Initial dose: 500 mg once a day; dosing: usually BID • Maximum effective dose: 2,000 mg per day • Titration frequency: week(s) to months • Alternate formulations: “XR” and combinations

  28. Metformin Outperformed Other Meds in Obese Patients (UKPDS) Lancet 1998 Sep 12;352(9131):854-65.

  29. Insulin Secretagogues: Sulfonylureas (SFU) and “Glinides” • Mechanism of action • Stimulate basal and postprandial insulin secretion • Require functioning beta cells (no effect on beta cell dysfunction) • Work quickly • Safety and efficacy • Decrease A1Capproximately1-2% • Lower fasting glucose 20% • Adverse events: weight gain, allergy (rare); main risk, hypoglycemia • Dosing • Initial dose: 1/8 to 1/4 maximum dose; dosing: 1-2 times/day (SFU), 3 times/day (glinides) • Maximum effective dose: 1/2 maximum(full dose with nateglinide) • Titration frequency: day(s) to weeks

  30. Preferred Sulfonylureas • All available as generic agents Glipizide ER 5-20 mg once per day • Once daily, flat profile, low plasma levels resulting in a low risk of weight gain and hypoglycemia Glipizide 2.5 to 20 mg twice a day • Twice daily. Half-life 2-4 hours, peaks in 2-3 hours. By taking it once a day at low dose it stimulates insulin secretion for 6-12 hours Glimepiride 1-8 mg per day • Once daily. Half-life 9 hours, peak action for 4 hours. Special utility like with glipizide but with longer half-life Buse J. Personal Opinion Melander A. Diabetes 2004;53 Suppl 3:S151

  31. Thiazolidinediones (TZD’s or Glitazones): Pioglitazone and Rosiglitazone Mechanism of action • Enhance insulin sensitivity in muscle, adipose tissue • Inhibit hepatic gluconeogenesis • Reduced rate of beta cell dysfunction Safety and efficacy • Decrease A1C1-2% • Adverse events: edema, weight gain, anemia; rare serious risk: liver failure Dosing • Initial dose (monotherapy): 1/2 to 2/3 maximum; dosing,1-2 x/day • Maximum effective dose: maximum dose • Titration frequency: weeks to month(s)

  32. Oral Hypoglycemics TZD Lipid Effects • Rosiglitazone(Avandia) • +LDL • +HDL • +Triglycerides • Pioglitazone (Actos) • +LDL • +HDL • -Triglycerides • Rosiglitazone – Black box warning for CHF and ischemic heart disease; warnings about increased fracture risk in women • Pioglitzaone – Black box warning for CHF and warning about increase fracture risk. No evidence to suggest increased ischemic heart disease.

  33. AHA/ADA Consensus Statement for TZDs • Not recommended for patients with NY Heart Association class III or IV heart failure • TZDs alone, or particularly in combination with insulin, may cause fluid retention which can lead to heart failure • Incidence of CHF <1% with TZD monotherapy • Increased to 2%-3% in combination with insulin • Patients should be observed for signs and symptoms of heart failure • TZDs should be discontinued if any deterioration in cardiac status occurs Nesto RW et al. Diabetes Care 2004;27:256

  34. Alpha-Glucosidase Inhibitors: Acarbose And Miglitol • Mechanism of action • Delay absorption of carbohydrates • Depend upon postprandial hyperglycemia • Safety and efficacy • Decrease A1C0.5-1% • Adverse events: flatulence; main risk: rare liver enzyme elevation • Dosing • Initial dose: 1/4 maximum once daily; dosing: 3 times daily • Maximum effective dose: 1/2 maximum dose • Titration frequency: week(s) to months • Used infrequently by most clinicians

  35. INCRETINSRole of Glucagon Like Peptide (GLP-1) in Glucose Homeostasis

  36. Incretin Drugs Exenatide (Byetta) – GLP-1 analog • Injection twice daily • 5mcg bid AC x 1 month, then 10mcg bid AC • Beneficial effects described previously • Expensive • Weight loss • Reduction in HgBA1C Sitagliptin (Januvia)– DPP4 inhibitor • Technically not an incretin but similar effects • Oral administration • 100mg daily • Weight neutral

  37. Key Points to Consider for Therapy Maximal benefits of metformin are observed at the recommended daily dose of 2000 mg (1 g BID)1 Thiazolidinediones should be started at low doses and slowly increased to minimize side effects2 Glucose-lowering effects of a sulfonylurea plateau at half the maximum recommended dose3 Garber AJ et al. Am J Med 1997;103:491 Nesto RW et al. Diabetes Care 2004;27:256 Stenman S et al. Ann Intern Med 1993;118:169

  38. Glycemic Control - Injected Therapies

  39. 12.4% 37.2% >8% 7.8% 63% 7% 17.0% 25.8% 37.0% 63% Of Patients with DiabetesAre Not at ADA A1CGoal <7% Adults aged 20-74 years with previously diagnosed diabetes who participated in the interview and examination components of the National Health And Nutrition Examination Survey (NHANES), 1999-2000 A1C % of Subjects n=404 Saydah SH et al. JAMA 2004;291:335

  40. Difficulties In AchievingTarget A1C Values • Challenges • Late diagnosis and initiation of therapy • Therapeutic inertia • Lack of effective lifestyle intervention • Secondary failure • Adverse events associated with antihyperglycemic therapies • Complexity of care • Role of postprandial glucose in failure

  41. Common Concerns When Transitioning To Insulin • Fear of needles or pain from injections • Fear of hypoglycemia • Weight gain Funnel M. Self-management Support for Insulin Therapy in Type 2 Diabetes. The Diabetes Educator 2004;30:274

  42. Common Concerns When Transitioning To Insulin • Adverse impact on lifestyle; inconvenient; loss of personal freedom and independence • Belief that insulin means diabetes is worse or more serious disease • Insulin as a personal failure • Insulin causes complications • Treated differently by family members Funnel M. Self-management support for insulin therapy in type 2 diabetes. The Diabetes Educator 2004;30:274

  43. Potential Insulin Regimens • Insulin pump Physiologic/COMPLEX/Flexible • Multiple daily injections • Free mixing - twice daily • Pre-mixed - twice daily • Basal only SIMPLE/Inflexible How do we balance simplicity and flexibility to achieve glycemic control?

  44. Indications for Insulin • Not contraindicated at anytime • Consider as initial therapy • HgbA1C > 10% • Fasting glucose > 250mg/dl • Random glucose > 300 • Recommended as initial therapy • Polyuria, polydipsia, weight loss, ketones

  45. Insulin InitiationAnswers to Provider Concerns • Normalize the fasting glucose • Fasting FSBS 70-130 • Once Daily Options • Start 10 units or 0.2 u/kg • Basal Insulin (glargine or detemir) • NPH (bedtime) • Premixed before dinner • Increase 2-3 units every 3 days prn to reach target of 70-130 fasting • Decrease 3 units for fasting < 70

  46. Once Daily Insulin OptionsBasals vs. NPH vs. Premixed

  47. Rapid (Glulisine,Lispro, Aspart,) Long (Glargine) Insulin ActionEffect Of Various Formulations 140 120 100 Short (Regular) Insulin Level (U/ml) 80 Intermediate (NPH) 60 40 Detimir 20 0 0 2 4 8 10 12 14 16 6 Hours

  48. Fasting Glucose at TargetHgbA1C Not at Goal • Must Normalize Post Prandial Glucose • Options • Change HS NPH to BID NPH • Change Pre-mixed Insulin from QD to BID • Add Mealtime Insulin to Basal Insulins

  49. Monomeric Insulin Analogs • How to switch or start • Insulin immediately before the meal (or after) • Review signs, symptoms and management of hypoglycemia • Safety • Arguably, glulisine, aspart, lispro and are safer than regular human insulin • Patient preference • Significant patient preference for monomeric analog versus regular human insulin • Duration of action • Covers postprandial glucose surge well • In type 1 diabetes, will need an additional injection of basal or NPH

  50. Carbohydrate Counting • Technique based on the concept that most meal-related glucose increase is due to the carbohydrate content • Patients count either • Carbohydrate choices (milk, fruit, breads, sweets, starchy vegetables) • Grams of “total carbohydrates” on food label • Providers prescribe insulin-to-carbohydrate ratio • Start with 1 unit per choice or 1 unit per 15 grams • Typical dose is 2-4 units per choice in type 2 diabetes • Titrate based on postprandial glucose monitoring • Generally, start with glulisine/lispro/aspart administered just after meals

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