Exercise Training and Glucose Metabolism in Aging

Diabetes and its associated complications affect more than 20 million Americans, and the prevalence of type 2 diabetes and impaired glucose tolerance rises dramatically with age such that 40% of Americans over age 60 are affected. In older adults, glucose metabolism may be affected by reduced skeletal muscle capillary supply, which limits insulin, glucose, and oxygen delivery to skeletal muscle. Reduced capillary supply to skeletal muscle is found in older individuals with impaired glucose tolerance and we hypothesize that this is due to reduced vascular growth factor expression, and chronic inflammation. Further, we hypothesize that reversal of a sedentary lifestyle through aerobic exercise training will increase insulin signaling and vascular growth factor expression, as well as decrease inflammation, to increase capillary supply to skeletal muscle, which contributes to improved glucose metabolism in older adults. This study will: 1) Determine the mechanisms underlying reduced skeletal muscle capillarization in older adults with impaired glucose tolerance; and 2) Determine the effect of aerobic exercise training-induced increases in skeletal muscle capillarization on glucose metabolism in older adults.

24 weeks of aerobic exercise training: 3 times per week, 60 minutes per session, at 70% of maximal aerobic capacity

Inclusion Criteria: Age 50-75 years Non-smoker >2 years Body mass index = 18-35 kg/m2 Exclusion Criteria: History of CAD or cerebrovascular disease that would preclude exercise Implantable defibrillator Active cancer Chronic pulmonary, thyroid, renal, liver, or hematological disease HIV positive or prone to malnutrition Sickle cell anemia Type 1 diabetes, or currently on medication to treat type 2 diabetes Poorly-controlled type 2 diabetes Poorly-controlled hypertension Taking medications including: beta-blockers, oral steroids, warfarin, certain statins, hormone replacement therapy (HRT), oral contraceptives (OCP), thiazolidinediones (TZD), or chronic steroids or nonsteroidal analgesics (NSAIDS) that may not be safely discontinued temporarily for specific procedures (i.e. for 72 hours prior) Allergic to lidocaine or heparin Recent weight change (>5kg in 3 months) Currently pregnant or nursing Physical impairment limiting exercise Dementia or unstable clinical depression

Prior SJ, Goldberg AP, Ortmeyer HK, Chin ER, Chen D, Blumenthal JB, Ryan AS. Increased Skeletal Muscle Capillarization Independently Enhances Insulin Sensitivity in Older Adults After Exercise Training and Detraining. Diabetes. 2015 Oct;64(10):3386-95. doi: 10.2337/db14-1771. Epub 2015 Jun 11.