Natural History of Type 2 Diabetes
Progressive Pancreatic Failure
Years from
diagnosis
-10
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 )(PostPrandial)
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
Insulin “Efficiency”
Plasma membrane
Insulin
receptor
Chemical
Signals
Glucose (“sugar”)
carriers
Insulin
Glucose carriers move
to the surface
Carriers insert into
cell surface
Blood
Sugar
GLUT4=glucose transporter 4
Blood Sugar enters body
“Metabolic” Syndrome
Obesity
Physical
Inactivity
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.
Death Increases with Metabolic Syndrome
Cumulative hazard (%)
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
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
Other Injected meds
Combination (two)
Medications
Increased Heart
Disease
Single
Medication
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”