Age, Lifestyle, Muscle Mechanisms in Insulin Resistance

Obesity Clinical Trial

Official title:

Age, Lifestyle, Muscle Mechanisms in Insulin Resistance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00971594
• Other study ID #: AG0120
• Secondary ID: K01AG021457
• Status: Completed
• Phase: N/A
• First received: September 2, 2009
• Last updated: September 2, 2009
• Start date: June 2004
• Est. completion date: May 2008

Study information

• Verified date: September 2009
• Source: National Institute on Aging (NIA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 50 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Exercise Capacity
• Glucose Intolerance
• Insulin Resistance
• Obesity

Intervention

Behavioral:
• Dietary counseling
1 hour sessions, once per week, with a registered dietitian on the American Heart Association Step I diet with caloric intake for each volunteer adjusted by the dietitian to elicit a WL of ~0.2-0.4 kg/wk
• AEX
Moderate aerobic exercise (75-80% HRR for 45 min) at the Baltimore GRECC exercise facility using treadmills 3 times per week for 6 months.

Locations

Country	Name	City	State
United States	Baltimore VA Medical Center	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Catenacci VA, Hill JO, Wyatt HR. The obesity epidemic. Clin Chest Med. 2009 Sep;30(3):415-44, vii. doi: 10.1016/j.ccm.2009.05.001. Review. — View Citation

Deshmukh AS, Hawley JA, Zierath JR. Exercise-induced phospho-proteins in skeletal muscle. Int J Obes (Lond). 2008 Sep;32 Suppl 4:S18-23. doi: 10.1038/ijo.2008.118. Review. — View Citation

Houmard JA, Tanner CJ, Slentz CA, Duscha BD, McCartney JS, Kraus WE. Effect of the volume and intensity of exercise training on insulin sensitivity. J Appl Physiol (1985). 2004 Jan;96(1):101-6. Epub 2003 Sep 12. — View Citation

Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin stimulated glucose disposal		Baseline and 6 months	Yes
Primary	Content and activity of insulin signaling proteins from muscle biopsies		Baseline and 6 months	Yes
Primary	Glucose tolerance		Baseline and 6 months	Yes
Secondary	Aerobic capacity		Baseline and 6 months	Yes
Secondary	Body weight/Composition		Baseline and 6 months	Yes
Secondary	Cytokines		Baseline and 6 months	Yes
Secondary	Other biomarkers (such as glucose, insulin etc)		Baseline and 6 months	Yes