Age, Lifestyle, Muscle Mechanisms in Insulin Resistance

National Institutes of Health (NIH)

Status

Completed

Conditions

Exercise Capacity

Obesity

Glucose Intolerance

Treatments

Behavioral: AEX

Behavioral: Dietary counseling

Study type

Interventional

Funder types

NIH

Identifiers

NCT00971594

AG0120

K01AG021457 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The purpose of this study is to investigate the mechanisms by which physical inactivity and obesity alter skeletal muscle insulin signaling to cause insulin resistance and increase the development of impaired glucose tolerance (IGT).

Full description

Aging is associated with a progressive development of impaired glucose tolerance (IGT), due to an increased peripheral tissue resistance to the action of insulin. Insulin resistance, a common state in both obese and sedentary individuals, eventually leads to the development of glucose intolerance, and type 2 diabetes with aging. Even in the absence of diabetes, insulin resistance is a key feature in various metabolic abnormalities that increase the risk for developing cardiovascular disease (CVD). Previous studies demonstrate improvements in glucose tolerance and glucose utilization following moderate energy restriction coupled with moderate intensity AEX. WL, through behavioral modification of diet and aerobic exercise (AEX), is perhaps the most effective way to treat as well as prevent insulin resistance and its associated metabolic complications of IGT and type 2 diabetes. Although these studies demonstrate the beneficial effect of weight loss (WL) and AEX on glucose tolerance and insulin action, not much is known about the cellular and molecular mechanisms by which these nonpharmacologic treatments improve glucose utilization in high-risk obese older individuals.

This study seeks to determine the cellular mechanisms by which aerobic exercise and weight loss alter skeletal muscle insulin signaling to improve insulin action in older glucose intolerant individuals. A second purpose is to determine whether certain genes (hereditary information) affect the way the body utilizes glucose in response to exercise and weight loss. In addition, adipose tissue is increasingly recognized as more than an inert depot serving not only to accept and store excess energy in the form of triglycerides, but also to secrete hormones and adipokines that have substantial effects on lipid and glucose metabolism. Furthermore, there are depot differences in metabolic function, as well as adipokine content. However, the physiology both underlying and consequential to these observations remains unknown. Thus, a third aim is to examine the effects of obesity on regional adipokine secretion and expression, and the relationship of adipokines to insulin resistance and the metabolic syndrome.

Enrollment

15 patients

Sex

Male

Ages

50+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Men older than 50 yrs of age
Non-smoking (more than 5 years)
BMI greater than 25 kg/m2 and less than 50 kg/m2

Exclusion criteria

CAD, CHF, Myocardial infarction within 6 months or other symptomatic heart disease
History of stroke, peripheral arterial disease
Currently being treated for active cancer
On oral agents or insulin therapy for diabetes
Poorly controlled Dyslipidemia (abnormal concentration of lipids or lipoproteins in the blood)
Poorly controlled hypertension (BP > 180/95)
Other systematic disorders that are not medically treated and stable
Physical impairment limiting normal activity and other contraindications to exercise
Aerobically conditioned
Abnormal response to exercise (chest pain, significant arrhythmias, extreme shortness of breath, cyanosis, exercising BP > 240/120)
Taking warfarin/coumadin
Taking oral steroids
Abnormal renal function or liver function
Chronic pulmonary disease severe enough to require oxygen
Anemia
MMSE < 24, dementia