International Diabetes Center International Diabetes Center Diabetes: Pathophysiology, Natural History and Treatment International Diabetes Center International Diabetes Center Glucose Metabolism and the Natural History of Diabetes • Normal Glucose Metabolism • Type 1 Diabetes (IDDM) Autoimmune • Type 2 Diabetes (NIDDM) Insulin Resistant and Insulin Deficient • Gestational Diabetes Mellitus (GDM) Diabetes in Pregnancy International Diabetes Center International Diabetes Center Normal Glucose Metabolism Normal Glucose Metabolism Peripheral Tissues (Muscle and Fat) Glucose Liver Insulin and glucagon secretion Glucose (glycogen) storage and production-Liver and Kidneys Pancreas Nutrition (carbohydrates) Glucose (glycogen) storage and metabolism International Diabetes Center International Diabetes Center Abnormal Glucose Metabolism Abnormal Glucose Metabolism Peripheral Tissues (Muscle and Fat) Glucose Liver Relative Insulin deficiency (type 2, GDM) or no insulin (type 1) Improper regulation of gluconeogenesis (type 1 and type 2) Pancreas Nutrition (carbohydrates) Insulin resistance (type 2, GDM) International Diabetes Center International Diabetes Center Diabetes Pathophysiology: Defects Associated with Type 1, Type 2 and GDM International Diabetes Center International Diabetes Center Natural History of Type 1 Diabetes 0 20 40 60 80 100 120 -6 -4 -2 0 2 4 6 8 10 12 Time (Age dependent) Time (Age dependent) Insulin Level Autoimmune B Cell destruction begins Genetic background At risk for Type 1 diabetes Islet cell antibodies appear % of Normal Function % of Normal Function International Diabetes Center International Diabetes Center Natural History of Type 1 Diabetes 0 20 40 60 80 100 120 -6 -4 -2 0 2 4 6 8 10 12 50 100 150 200 250 300 350 Time (Age Time (Age dependent ) ) Insulin Level Fasting Glucose Autoimmune B Cell destruction begins Genetic background Genetic background At risk for Type 1 diabetes At risk for Type 1 diabetes Islet cell antibodies appear Glucose (mg/dL) % of Normal Function DM DX DM DX (11.1 mmol/L) (7.0 mmol/L) DM DM ONSET ONSET International Diabetes Center International Diabetes Center Natural History of Type 2 Diabetes ©2004 International Diabetes Center. All rights reserved 0 50 100 150 200 250 -10 -5 0 5 10 15 20 25 30 Years of Diabetes Insulin Resistance Insulin Level Beta cell dysfunction At risk for Diabetes % of Normal Function International Diabetes Center International Diabetes Center Natural History of Type 2 Diabetes 0 50 100 150 200 250 -10 -5 0 5 10 15 20 25 30 50 100 150 200 250 300 350 Years of Diabetes Insulin Resistance Insulin Level Fasting Glucose Post Meal Glucose Developing Diabetes ©2004 International Diabetes Center. All rights reserved Glucose (mg/dL) % of Normal Function (11.1 mmol/L) (7.0 mmol/L) Beta cell dysfunction International Diabetes Center International Diabetes Center Nucleus Insulin Glucose Insulin Receptor Glucose Transporter (GLUT 4) G G G G G G G G G G G G G Adipose and muscle tissues require insulin for 90-95% of glucose uptake. Liver, pancreas and brain do not require insulin for glucose uptake. G G G G G G G G G G Insulin Signaling Pathway in Insulin Sensitive Cells ©2004 International Diabetes Center. All rights reserved [...]... ©2004 International Diabetes Center All rights reserved International Diabetes Center Common to all Forms of Diabetes • Hyperglycemia • Hyperglycemia is related to microvascular and macrovascular complications in Type 1 and Type 2; and to excess fetal growth and complications of delivery in GDM • Treatment of hyperglycemia results in improved outcomes International Diabetes Center Treatment MNT Type... Inhibitors - Acarbose, Miglitol Insulin – Bolus/pre-meal insulin (Regular and Rapid Acting – Lispro and Aspart) – Basal/background insulin (NPH, Lente, Glargine) International Diabetes Center Treatment MNT Type 1 ©2004 International Diabetes Center All rights reserved X ORAL AGENTS INSULIN X International Diabetes Center Treatment: Type 1 Diabetes % of Normal Function Glucose (mg/dL) Insulin + Medical Nutrition... Level At risk for Diabetes -10 -5 Beta cell dysfunction 0 5 Adapted from: UKPDS 33: Lancet 1998; 352, 837-853 DeFronzo RA Diabetes 37:667, 1988 Saltiel J Diabetes 45:1661-1669, 1996 Robertson RP Diabetes 43:1085, 1994 Tokuyama Y Diabetes 44:1447, 1995 Polonsky KS N Engl J Med 1996;334:777 ©2004 International Diabetes Center All rights reserved 10 15 20 25 30 Years of Diabetes International Diabetes Center... International Diabetes Center All rights reserved International Diabetes Center % of Normal Function Glucose (mg/dL) Natural History of Type 2 Diabetes 350 300 250 200 150 100 50 250 200 150 100 50 0 Relative Insulin Deficiency Post Meal Glucose Fasting Glucose (11.1 mmol/L) (7.0 mmol/L) Insulin Resistance At risk for Diabetes -10 -5 0 Insulin Level Beta cell dysfunction 5 10 15 20 25 30 Years of Diabetes. .. Basal/Bolus Insulin RA(G) - RA - RA - G > 4% Insulin Stage INFUSION PUMP ©2004 International Diabetes Center All rights reserved International Diabetes Center Treatment MNT Type 2 ©2004 International Diabetes Center All rights reserved X ORAL AGENTS X INSULIN X International Diabetes Center Medical Nutrition Therapy (Food Plan and Exercise) • Action – Appropriate distribution of carbohydrate intake (carb counting)... muscle proliferation function Nucleus Inside Cell and migration • Reduced inflammation Lipid Profile • Pioglitazone: Triglyceride, HDL Homeostatic • Rosiglitazone: LDL, HDL • PAI-1 and Fibrinogen • Platelet aggregation BENEFITS BEYOND DIABETES: INSULIN RESISTANCE SYNDROME ESPECIALLY LIPIDS AND HTN International Diabetes Center α-Glucosidase Inhibitor: Acarbose and Miglitol • Action – Delays carbohydrates... Glucose toxicity occurs when there is chronic exposure to high glucose levels ©2004 International Diabetes Center All rights reserved Voltage-gated Calcium Channel* G GG Pyruvate ATP ADP K+ Ca++ G Potassium Channel G G G G K+ International Diabetes Center Glucose (mg/dL) Natural History of Gestational Diabetes 150 Post Meal Glucose (8.3 mmol/L) 100 (5.3 mmol/L) Fasting Glucose % of Normal Function... Type 2 X ORAL AGENTS GDM ©2004 International Diabetes Center All rights reserved INSULIN X X X International Diabetes Center Diabetes Therapies Medical Nutrition Therapy (Food Plan & Exercise) Oral Agents – Insulin Secretagogues • Sulfonylureas- 1st, 2nd and 3rd generation • Repaglinide • Nateglinide – Biguanides - Metformin – Thiazolidinediones - Rosiglitazone and Pioglitazone α-Glucosidase Inhibitors... choices/meal (if needed) ©2004 International Diabetes Center All rights reserved International Diabetes Center Exercise • Increase level of physical fitness – cardiovascular endurance – muscle strength/endurance – lean body mass – flexibility • 30 minutes of exercise per day, cumulative • Age and lifestyle appropriate e.g walking, bicycling, swimming, running International Diabetes Center Glucose (mg/dL) % of... monotherapy – High post prandial blood glucose (180-225 mg/dL or 10.0-12.5 mmol/L) • • Precautions and Contraindications – Kidney Disease: Serum creatinine >2.0 mg/dL – Liver Disease: Evidence of severe disease – Heart Disease: none – Inflammatory bowel disease • Pregnancy – passes placental barrier, initiate insulin therapy Side effects – Flatulence, abdominal pain and diarrhea International Diabetes Center . International Diabetes Center International Diabetes Center Diabetes: Pathophysiology, Natural History and Treatment International Diabetes Center International Diabetes Center Glucose Metabolism and. and the Natural History of Diabetes • Normal Glucose Metabolism • Type 1 Diabetes (IDDM) Autoimmune • Type 2 Diabetes (NIDDM) Insulin Resistant and Insulin Deficient • Gestational Diabetes. Pathophysiology: Defects Associated with Type 1, Type 2 and GDM International Diabetes Center International Diabetes Center Natural History of Type 1 Diabetes 0 20 40 60 80 100 120 -6 -4 -2 0 2 4 6 8