1. Prevalence of Diabetes in Race & Ethnic Groups

2. Increase in diabetes in 1990’s

3. The Prevalence of Diabetes in Native American Populations

6. Insulin comes from the Pancreas $-Cells Produce and Secrete Insulin Primary target tissue cites include: hepatic cells (liver) muscle cells adipocytes (fat) Insulin primarily released in response to a rise in blood glucose levels Elongated tissue nestled within intestines and between kidneys/adrenals

8. Insulin Insulin Receptor Glucose

10. IRS-1 IRS-2 IRS-3 IRS-4 Glucose Insulin Insulin Receptor PI 3 K PIP 3 AKT-1 AKT-2 AKT-3

11. IRS-1 IRS-2 IRS-3 IRS-4 Tyrosine Phosphorylation Hyperinsulinemia Protein tyrosine phosphatases (PTPs) Serine Phosphorylation Ligand-induced downregulation Glucose

12. IRS-1 IRS-2 IRS-3 IRS-4 Hyperinsulinemia Hyperinsulinemia → decreases expressionof IRS-1 and IRS-2 Protein tyrosine phosphatases (PTPs) Protein tyrosine phosphatases (PTPs) → dephophorylates important tyrosine residues → reducing activity Serine Phosphorylation Serine Phosphorylation → interaction with IRS Proteins → downregulates IR function →modifies kinase activity of IRS protein Ligand-induced downregulation Ligand-induced downregulation → internalization and degradation IR Glucose

13. IRS-1 IRS-2 IRS-3 IRS-4 PI 3 K PIP 3 PhosphatasePTENSHIP2 Glucose

14. IRS-1 IRS-2 IRS-3 IRS-4 PI 3 K PIP 3 Phosphatase Phosphatase → dephosphrylates PIP 3 PTEN PTEN → dephosphrylates PIP 3 SHIP2 SHIP2 → dephosphrylates PIP 3 Glucose

15. IRS-1 IRS-2 IRS-3 IRS-4 PI 3 K PIP 3 AKT-1 AKT-2 AKT-3 Glucose Uptake Cell Differentiation ↑Protein Synthesis ↓Gluconeogenesis ↑Glucose Synthesis GLUT4 Glucose

16. IRS-1 IRS-2 IRS-3 IRS-4 PI 3 K PIP 3 AKT-1 AKT-2 AKT-3 Glucose Uptake Cell Differentiation ↑Protein Synthesis ↓Gluconeogenesis ↑Glucose Synthesis GLUT4 Glucose

17. IRS-1 IRS-2 IRS-3 IRS-4 PI 3 K PIP 3 AKT-1 AKT-2 AKT-3 Glucose Uptake Cell Differentiation Protein Synthesis Gluconeogenesis Glucose Synthesis

20. IRS-1 IRS-2 IRS-3 IRS-4 PI 3 K PIP 3 AKT-1 AKT-2 AKT-3 Glucose Uptake Cell Differentiation Protein Synthesis Gluconeogenesis Glucose Synthesis TNFαIL-6 FFA

21. CARBOHYDRATE METABOLISM Liver & Muscle Glycogenolysis Hyperglycemia Glucoseurea-Osmotic Diuresis Fluid & Electrolyte Loss Dehydration Liver & Muscle Glycogenolysis Hyperglycemia Glucoseurea-Osmotic Diuresis Fluid & Electrolyte Loss Dehydration

22. CARBOHYDRATE METABOLISM Hemoconcentration Peripheral Circulatory Failure Hypotension Renal Blood Flow Renal Failure Coma Death Hemoconcentration Peripheral Circulatory Failure Hypotension Renal Blood Flow Renal Failure Coma Death

23. LIPID METABOLISM Lipogenesis Lypolysis Lipemia Ketogenesis Ketonemia Metablic AcidosisKetonuria Hyperpena Dehydration

24. LIPID METABOLISM Hemoconcentration Peripheral Circulatory Failure Hypotension Renal Blood Flow Renal Failure Coma Death Hemoconcentration Peripheral Circulatory Failure Hypotension Renal Blood Flow Renal Failure Coma Death

25. PROTEIN METABOLISM Aminoacidemia Gluconeogenesis Urinary Nitrogen Aminoacidemia Gluconeogenesis Urinary Nitrogen Loss of cellular K + Net loss of K + Loss of cellular K + Net loss of K + Protein Catabolism

31. Fong, D.S., et al. Diabetes Care 27:S84, 2004 Prevalence of Diabetic Retinopathy after Diagnosis of Diabetes

39. heart and blood vessels digestive system urinary tract sex organs sweat glands eyes AUTONOMIC NEUROPATHY

40. Unawareness of Hypoglycemia Postural Hypotension Unresponsive Heart Rate Maldistribution of Blood Flow Alternating Constipation and Uncontrolled diarrhea Gastroparesis (stomach to empty too slowly) persistent nausea and vomiting, bloating, and loss of appetite. fluctuations in blood glucose levels Swallowing difficulties Incomplete bladder emptying bacteria to grow in the bladder and kidneys and causing urinary tract infections. Urinary incontinence Decrease sexual response in men and women Lack of or perfuse sweating pupils less responsive to changes in light AUTONOMIC NEUROPATHY

41. toes feet legs hands arms PERIPHERAL NEUROPATHY

42. numbness or insensitivity to pain or temperature a tingling, burning, or prickling sensation sharp pains or cramps extreme sensitivity to touch, even a light touch loss of balance and coordination PERIPHERAL NEUROPATHY

43. eyes facial muscles ears pelvis and lower back thighs abdomen FOCAL NEUROPATHY

44. inability to focus the eye double vision aching behind one eye paralysis on one side of the face (Bell's palsy) severe pain in the lower back or pelvis pain in the front of a thigh pain in the chest, stomach, or flank pain on the outside of the shin or inside the foot chest or abdominal pain that is sometimes mistaken for heart disease, heart attack, or appendicitis FOCAL NEUROPATHY

45. thighs hips buttocks PROXIMAL NEUROPATHY

46. pain in either the thighs, hips, buttocks, or legs, usually on one side of the body weakness in the legs, manifested by an inability to go from a sitting to a standing position without help PROXIMAL NEUROPATHY

47. ANHYDROSIS

48. EXERCISE PREVENTION Helmich, S.P. et al. New England J Medicine 325:147-152, 199 Incidence Rates of type 2 (/ 10,000 man-years

49. Regular Walking Decreases Morbidity Rates by 50% in Diabetics Gregg, E.W., Arch Intern Med 163:1440-1447, 2003

51. Boule, N.G. et al JAMA 286:1218-1227, 2001. Exercise Groups Control Groups

52. Boule, N.G. et al JAMA 286:1218-1227, 2001. Exercise GroupsControl Groups

53. INSULIN SENSITIVITY Glucose Uptake (mg/m 2 /min) * Landt, et al, Diabetes Care 8:461-465, 1985 Wallberg-Henriksson et al., Am J Clinical Nutrition 249:C233-C237, 1985 Yki-Jarvinen et al, Diabetes Care 7:520-527, 1984.

54. MUSCLE BLOOD FLOW Katz, M. and N. Janjan. Diabetes 27:726-731, 1978 Resistance (mmHg/ml min/100 g Filtration (dl/min mmHg/100 g Capacity (ml/100g)

55. MUSCLE BLOOD FLOW Wallberg-Henriksson et al., Am J Clinical Nutrition 249:C233- C237, 1985 Wallberg-Henriksson, et al, Diabetes 33:851-857, 1984 Capillaries/Fiber

58. SIGNS AND SYMPTOMS OF HYPOGLYCEMIA Apathy SweatingExcessive Hunger DrowsyFainting Convulsions Dizziness FatigueCrying Hand Tremors IrritabilityBlurred Vision Confusion DelusionDouble Vision Headache Slurred SpeechUnsteady Gait Nervousness Poor Coordination Inability to concentrate Loss of Consciousness SIGNS AND SYMPTOMS OF HYPOGLYCEMIA Apathy SweatingExcessive Hunger DrowsyFainting Convulsions Dizziness FatigueCrying Hand Tremors IrritabilityBlurred Vision Confusion DelusionDouble Vision Headache Slurred SpeechUnsteady Gait Nervousness Poor Coordination Inability to concentrate Loss of Consciousness