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The Old Paradigm

The Old Paradigm. Type 2 diabetes- Insulin resistance leads to pancreatic decline in insulin secretion. Think “ Adult- Onset Diabetes Mellitus ” . Still produce insulin, but not enough (C-peptide +), not prone to DKA (Ketone -)

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The Old Paradigm

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  1. The Old Paradigm • Type 2 diabetes- Insulin resistance leads to pancreatic decline in insulin secretion. • Think “Adult- Onset Diabetes Mellitus”. Still produce insulin, but not enough (C-peptide +), not prone to DKA (Ketone -) • Type 1 diabetes- Autoimmune attack on pancreatic beta-cell leads to complete loss of insulin secretion and to lifelong insulin-dependence • Think “Juvenile Diabetes”. No insulin production (C- Peptide -), thus prone to DKA (Ketone +).

  2. The New Paradigm The Key Questions: • Phenotype- Non-obese vs. Obese? • Ketones? • C-peptide present? • Auto-antibodies present (GAD-65, Islet Cell Ab)?

  3. Ketones + C-Peptide - Yes: Ketosis-Prone Diabetes AKA “Flatbush Diabetes” Most can be treated with OHA or OHA plus Insulin OR Latent Autoimmune Diabetes of the Adult Or LADA Autoantibodies Present (GAD-65, Islet cell Ab) Treat as Type 2 but test C-peptide periodically As they will become Type 1 C-peptide negative No: Type 1 diabetes 70% have autoantibodies (GAD-65, Islet Cell Ab) ~50% of Type 1 diabetes occurs After age 40 with another peak In the 70’s-80’s. 2 Fasting BG’s >100 mg/dll Two 2 hr GTT >200 mg/dl Classic Poly’s + random BG >200 mg/dl A1c>6.5%???? Obese Phenotype Non-Obese Phenotype Ketosis-Prone? Type 1 diabetes with Type 2 Phenotype Ketones + C-Peptide - Ketones - C-Peptide + No: Non-obese Type 2 (~15% of Type 2’s) Ketones - C-Peptide + Ketones+ C-peptide+ YES Ketones+ C-peptide+ C-peptide ? Type 2 diabetes 85% of Type 2’s

  4. Non-Obese Phenotype • Non-obese Type 2 Diabetes- ~3.5 million Americans • Ketone- • C-peptide+ • treat like other Type 2 diabetes patients • Type 1 Diabetes- 1-1.5 million Americans • Ketone + • C-Peptide - • 70% Auto-antibody + • life-long insulin-dependence • Ketosis-prone Diabetes • Ketone + • C-peptide- • Most can be treated with OHA or OHA+Insulin • Latent Autoimmune Diabetes of the Adult-LADA • Ketones +/- • C-peptide + • Auto-antibodies + • Will likely eventually transition to C-peptide - Type 1 diabetes

  5. Obese Phenotype • Type 2 Diabetes- the vast majority of your patients • Ketone- • C-peptide + • 85% of Type 2’s • D/E, Oral agents, Incretins, Insulin • Type 1 with Type 2 Phenotype • Ketone + • C-Peptide - • Intensively-treated Type 1’s with genetic predispostion to central obesity and insulin resistance • Life-long insulin dependence; consider Pramlintide • Ketosis-Prone Diabetes • Ketone + • C-peptide+

  6. To Confuse the Picture Glucotoxicity- inhibition of insulin secretion due to prolonged exposure to high-levels of glucose; can be Ketone +, C-peptide -. Intensive treatment allows pancreatic insulin secretion to resume. Lipotoxicity- inhibition of insulin secretion due to prolonged exposure to high-levels of circulating fatty acids

  7. Type 1 diabetes 70% have autoantibodies (GAD-65, Islet Cell Ab) ~50% of Type 1 diabetes occurs after age 40 with another peak in the 70’s-80’s. OR Latent Autoimmune Diabetes of the Adult Or LADA Autoantibodies Present (GAD-65, Islet cell Ab) Treat as Type 2, but test C-peptide periodically as they will become Type 1 C-peptide negative

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