Physical inactivity and obesity

underlie the insulin

resistance of aging

Amati F, Dubé JJ, Coen PM, Stefanovic-Racic M, Toledo FGS,

Goodpaster BH

Diabetes Care, 2009

 Physical Insulin
Obesity
Aging
Inactivity Resistance
 Physical
Inactivity

Insulin
Aging
Resistance

Obesity
Is insulin resistance characteristic of aging
or does physical inactivity and obesity
underlie this aging effect?
Study Design
Younger Older
(24 - 47 yr) (60 - 75 yr)

Athletes 7 12

Normal
11 10
Sedentary

weight

Obese 15 15
 Insulin sensitivity
“Hyperinsulinemic Euglycemic clamp”

insulin infusion blood samples glucose infusion

 Insulin sensitivity
Plasma insulin (uU/mL) Plasma glucose (mg/dL)

200 100

150 75

100 50

50 25

Baseline
0 0
0 30 60 90 120 0 30 60 90 120
Time (min) Time (min)
 Insulin sensitivity

10 Rate of glucose disposal (Rd)

Glucose infusion rate (mg/kg/min)

0
0 30 60 90 120
Time (min)
Hepatic glucose production
“Stable isotope dilution”

Hepatic Tracer Exogenous

glucose = disposal - glucose
production rate infusion rate
 Younger Older

14

12
Insulin Sensitivity (Rd)

10

0
Athletes Normal Weight Obese
 Conclusions
• IR was not a feature of old age
• Obesity and Physical inactivity underlie
• Hepatic glucose was not a confound
• No mechanisms revealed
• Consistent with literature showing
improved IS with physical activity