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Type 1 Diabetes Treatment Options

Type 1 Diabetes Treatment Options. Part 1. Stanley Schwartz Mark Stolar Emeritus, Univ of Pa. Type 1 Diabetes. Diabetes mellitus type 1 (IDDM)

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Type 1 Diabetes Treatment Options

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  1. Type 1 Diabetes Treatment Options Part 1 Stanley Schwartz Mark Stolar Emeritus, Univ of Pa

  2. Type 1 Diabetes • Diabetes mellitus type 1 (IDDM) Hyperglycemia resulting from the autoimmune destruction of the insulin-producing beta cells in the pancreas- insulin therapy is essential for survival= insulin dependent unlike type 2 diabetes where insulin use defines insulin treated not dependent

  3. Pathogenesis of Type 1 Diabetes Environmentaltriggers andregulators Immunedysregulation Loss of first-phase insulin response Interactions betweengenes impartingsusceptibility and resistance May be relapsing/remitting Glucose intolerance β-cell Mass Variable insulitisβ-cell sensitivity to injury Overt diabetes Pre-diabetes Time Adapted with permission from Atkinson MA, Eisenbarth GS. Lancet. 2001;358:221

  4. Type 1 Diabetes • Insulin-deficient state • Therapeutic goal: replace insulin • Strategy: provide replacement insulin in manner that mimics normal fasting/prandial physiology • This cannot always be done with current insulin analogues • Goal to reduce microvascular complications. Is postprandial hyperglycemia more pathogenic?

  5. 76% 59% 39% 54% 64% DCCTMicrovascular Complication Event Rates and Risk Reductions Cumulative Incidence (%) 1 2 3 2 1 1. DCCT Research Group. Ophthalmology. 1995;102:647 2. DCCT Research Group. Kidney Int. 1995;47:1703 3. DCCT Research Group. AnnIntern Med. 1995;122:561

  6. :1. Hypoglycemia2. Weight gain3. Glycemic, including daytime, variability4. Doesn’t address non-insulin mediated causes of hyperglycemia in type 1 diabetes The Downside to Intensive Insulin Management

  7. DCCT RESULTS Severe Hypoglycemia 100 • Persistent three-fold increase in INT • Increased risk of multiple episodes within same patient (INT = 22%, CON = 4%) • Number of prior episodes was strongest predictor of future risk • Current A1C not solely predictive of risk 80 60 Intensive Rate/100 Patient Years 40 20 Conventional 0 5 6 7 8 9 10 11 12 13 14 HbA1c (%) During Study DCCT Research Group, Diabetes 1997;46:271-286

  8. Hypoglycemia Unawareness Is a Dangerous Complication of T1DM • Each episode of hypoglycemia reduces counterregulatory response to low glucose even after one episode • Reduction in catecholamine response decreases awareness/symptoms even after a single episode • Nocturnal hypoglycemia is most pathogenic and unrecognized. Hypoglycemic awareness decreases significantly in the elderly

  9. CV Consequences of Hypoglycemia • Prolonged QT- intervals- Diabetologia 52:42,2009 • Can be of pronged duration IJCP Sup 129, 7/02 • Greater with higher catecholamine levels Europace 10,860 • Associated with Angina Diabetes Care 26, 1485, 2003 / Ischemic EKG changes Porcellati, ADA2010 • Associated with Arrhythmias • Associated with Sudden Death Endocrine Practice 16,¾ 2010 • Increased Glycemic Variabilty- Adverse ICU outcomes/Increased vascular inflammation Hirsch ADA2010

  10. :1. Hypoglycemia2. Weight gain3.Glycemic, including daytime, variability4. Doesn’t address non-insulin mediated causes of hyperglycemia in type 1 diabetes The Downside to Intensive Insulin Management

  11. 30 10.0 25 7.5 20 15 Δ Weight (kg) 5.0 Δ Weight (kg) 10 5 2.5 0 0 -5 1 2 3 4 0 3 6 9 12 15 Quartile of Weight Gain Time (y) Consequences of Intensive Insulin Therapy Weight Gain UKPDS (Type 2) DCCT (Type 1) Intensive Conventional Data from Purnell J, et al. JAMA 1998; 280:140-146 Data from UKPDS Group (UKPDS 33). Lancet 1998; 352:837-853

  12. +8.7 kg +4.6 kg -2.2% -2.6% Yki-Jarvinen 1999 Henry 1993 Weight Gain MEALTIME INSULIN THERAPY 10 8 6 Δ Weight (kg) 4 2 0 BID Insulin Intensive BID Insulin 12 11 10 9 8 A1C (%) ADA Goal 7 6 5 4

  13. :1. Hypoglycemia2. Weight gain3. Glycemic, including daytime, variability4. Doesn’t address non-insulin mediated causes of hyperglycemia in type 1 diabetes The Downside to Intensive Insulin Management

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