Insulin and Sarcopenia in the Elderly

Sponsor

The University of Texas Medical Branch, Galveston (Other)

Overall Status

Completed

CT.gov ID

NCT00690534

Collaborator

National Institute on Aging (NIA) (NIH)

Enrollment

Location

Arms

Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Muscle loss with aging is a significant contributor to disability in older people. Our general hypothesis is that loss of muscle with aging, known as sarcopenia, may be due to inability of muscle to grow in response to insulin. Our goal is to determine the mechanisms underlying this age-related insulin resistance of muscle proteins, which will allow us to define in the future specific interventions to target this defect and provide the scientific basis for the prevention and treatment of sarcopenia.

Condition or Disease	Intervention/Treatment	Phase
Sarcopenia	Drug: Insulin Regular Drug: L-NMMA Drug: Sodium Nitroprusside Other: mixed meal	Phase 1

Detailed Description

Our general hypothesis is that a reduced response of muscle protein anabolism to insulin plays an important role in the loss of muscle mass with aging. Our goal is to determine the mechanisms underlying the age-related insulin resistance of muscle proteins, which will allow us to define specific interventions to target this defect and provide the scientific basis for the prevention and treatment of sarcopenia.

Our previous studies indicate that the response of muscle proteins to the anabolic action of insulin is impaired in healthy older adults as compared to younger controls, which hampers the anabolic effect of mixed feeding on muscle proteins. These changes are associated with an age-related reduction in the vasodilatory response to insulin, which, from our data, appears to be a potentially important mediator of the physiological anabolic effect of insulin on muscle proteins. Preliminary data from our laboratory also suggest that in older subjects a single bout of aerobic exercise may restore the normal response of blood flow, muscle protein synthesis and anabolism to insulin.

Therefore, we will test in healthy subjects the following specific hypotheses:

Insulin-induced increases in blood flow and muscle perfusion are necessary for the physiological stimulation of muscle protein synthesis and anabolism by insulin.
Aging reduces the vascular sensitivity to insulin, which prevents the physiological increase in blood flow and muscle perfusion in response to insulin, thereby decreasing the response of muscle protein synthesis and net balance to the anabolic action of insulin and mixed feeding.
Aerobic exercise can restore, in older subjects, the insulin-induced increase in blood flow and muscle perfusion to youthful levels, thus normalizing the anabolic effect of insulin and mixed feeding on muscle protein synthesis and net muscle protein balance.

We will use state-of the art stable isotope tracer techniques to measure muscle protein turnover, and a newly developed method to measure muscle perfusion in young and older subjects. The results of these studies will allow us to better define the physiological mechanisms of action of insulin on muscle protein anabolism, advance our knowledge on the pathophysiology of sarcopenia, and provide the scientific basis for the behavioral and/or pharmacological treatment of muscle loss with aging.

Study Design

Study Type:

Interventional

Actual Enrollment :

88 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Insulin and Sarcopenia in the Elderly

Study Start Date :

Sep 1, 2005

Actual Primary Completion Date :

Aug 1, 2012

Actual Study Completion Date :

Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: CMAY Insulin in young	Drug: Insulin Regular insulin, 0.2 mU/kg/min for 3 hours
Experimental: IMAY L-NMMA + insulin in young	Drug: Insulin Regular insulin, 0.2 mU/kg/min for 3 hours Drug: L-NMMA variable rate for 3 hours
Experimental: SNPY SNP in young	Drug: Sodium Nitroprusside variable rate for 3 hours
Active Comparator: CSNP Insulin in elderly	Drug: Insulin Regular insulin, 0.2 mU/kg/min for 3 hours
Experimental: ISNP SNP in elderly	Drug: Insulin Regular insulin, 0.2 mU/kg/min for 3 hours Drug: Sodium Nitroprusside variable rate for 3 hours
Experimental: SNPE SNP in elderly	Drug: Sodium Nitroprusside variable rate for 3 hours
Active Comparator: CMealO Meal in elderly	Other: mixed meal mixed meal
Experimental: SMealO SNP+meal in elderly	Drug: Sodium Nitroprusside variable rate for 3 hours Other: mixed meal mixed meal
Active Comparator: MealY meal in young	Other: mixed meal mixed meal
Experimental: ExIns insulin+exercise in elderly	Drug: Insulin Regular insulin, 0.2 mU/kg/min for 3 hours
Experimental: ExMeal meal+exercise in elderly	Other: mixed meal mixed meal

Outcome Measures

Primary Outcome Measures

muscle protein synthesis [5 and 8 hours]

Secondary Outcome Measures

blood flow [5 and 8 hours]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age 18-40 yrs, and 65-85 yrs.
Ability to sign consent form (score >23 on the 30-item Mini Mental State Examination, MMSE)
Stable body weight for at least 3 months

Exclusion Criteria:

Physical dependence or frailty (impairment in any of the Activities of Daily Living (ADL), history of falls (>2/year) or significant weight loss in the past year)
Exercise training (>2 weekly sessions of moderate to high intensity aerobic or resistance exercise)
Pregnancy or nursing women.
Significant heart, liver, kidney, blood or respiratory disease
Peripheral vascular disease
Diabetes mellitus or other untreated endocrine disease
Active cancer
Recent (within 6 months) treatment with anabolic steroids, or corticosteroids.
Alcohol or drug abuse
Severe depression (>5 on the 15-item Geriatric Depression Scale, GDS)
Potential subjects who have recently donated blood in the past 60 days will be excluded from participating in the study.