Natural History of Type 2 Diabetes Progressive Pancreatic

Natural History of Type 2 Diabetes Progressive Pancreatic Failure Years from -10 diagnosis Pancreas function -5 Onset Insulin “efficiency” Insulin secretion Post-Meal glucose Fasting glucose Pre-diabetes 0 10 5 15 Diagnosis “Pre-diabetes” “Metabolic Syndrome” PLASMA GLUCOSE Normal: 99 mg/dl or less Pre-Diabetes: 100 -125 mg/dl) Diabetes > 126 mg/dl fasting); > 200 mg/dl )(Post. Prandial) Type 2 diabetes Ramlo-Halsted BA, Edelman SV. Prim Care. 1999; 26: 771 -789 Nathan DM. N Engl J Med. 2002; 347: 1342 -1349

Cardiovascular Risk in Pre-diabetes Non-Diabetic Diabetes Relative Risk of MI or Stroke 7 5. 02 6 3. 64 5 3. 19 4 2. 4 3 2 1. 0 1 0 Nondiabetic Throughout >15 Yr Before Dx 10 -14. 9 Yr Before Dx Pre-Diabetes Hu FB, et al. Diabetes Care. 2002; 25: 1129 -1134. <10 Yr Before Dx Diabetic Throughout

Pre-diabetes Plasma membrane Insulin receptor Chemical Signals Insulin “Efficiency” Glucose (“sugar”) carriers Insulin Glucose carriers move to the surface Carriers insert into cell surface Blood Sugar GLUT 4=glucose transporter 4 Blood Sugar enters body

“Metabolic” Syndrome Physical Inactivity Obesity Aging Insulin Efficient (“resistance”) High Cholesterol Elevated Blood Pressure Modified from S. Grundy MD Heart Disease High Blood Sugar Blood Vessel Dysfunction

Body Shape Matters!!! “Central” obesity An Index of Abdominal vs Peripheral Obesity High Waist/Hip ( 0. 95 in men) ( 0. 80 in women) Low Waist/Hip (<0. 95 in men) (<0. 80 in women)

Waist Measurement and Diabetes Risk 25 Risk (%) 20 Upper 10% WHR Lower 10% WHR 15 10 5 0 54 55 56 57 58 59 60 61 62 63 64 65 66 67 Age Risk of diabetes mellitus during 13 years in relation to WHR at baseline. Comparison between these in upper and lower 10% of WHR distribution. Larsson. Acta Med Scand Suppl. 1988; 723: 45 -51.

Waist/Hip Ratio and Risk • Men: waist size >40 vs <37 inches • Women: waist size >34 vs <31 inches ~4 -fold greater risk for type 2 diabetes ~3 - to 4 -fold greater risk for major cardiovascular event Lean et al. Lancet. 1998; 351: 853 -856.

Cumulative hazard (%) Death Increases with Metabolic Syndrome Heart Disease Deaths 15 YES 10 Metabolic Syndrome: 5 0 NO 0 2 4 6 8 Follow-up (y) 10 12

Visceral Fat Distribution: Normal vs Type 2 Diabetes Normal Type 2 Diabetes

bteestes a i e d b a o i TD R. Heine MD Metabolic Syndrome ?

Type 2 Diabetes Predicted Treatment Paradigm Years from -10 diagnosis -5 0 10 5 15 Onset Diagnosis Insulin Nutritional Preventive Strategies Increased Heart Disease Other Injected meds Single Medication Combination (two) Medications Diet and exercise Pre-diabetes Type 2 diabetes

NIH Funded Botanical Research Centers “Your Tax Dollars at work” • Botanical Center for Age-Related Disease Purdue University/UAB • Botanical Dietary Supplements for Women’s Health University of Illinois at Chicago • Botanical and Lipids (Cholesterol) Harvard and Wake Forest Universities • Botanicals and Cancer Memorial Sloan-Kettering Cancer Center/ Rockefeller University • Botanicals and Metabolic Syndrome PBRC-LSU/Rutgers

Tarragon and Diabetes Russian tarragon • Extract of Artemisia dracunculus with antidiabetic properties • Produced from hydroponically grown plants under controlled conditions

Clinical Research: BENCH to BEDSIDE! Years 1 -4 Animal Testing to monitor Safety and effectiveness Years 1 -3 Human Testing in Several Phases Years 3 -5 Cells tested with Experimental Intervention

Are Claims for “over the counter” supplements real?

Botanicals Studied “Eat and Drink the Rainbow”