Mitochondrial Impairment in Muscle Insulin Resistance

NCT ID: NCT00222924

Last Updated: 2007-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-12-31
• Study Completion Date: 2006-12-31

Brief Summary

This investigation is being carried out to learn more about research findings from a study that was completed last year. Those findings revealed that within the skeletal muscle cells of individuals with type 2 diabetes, there was often damage to the mitochondria (the muscle cell's power source or the machinery of the muscle cell that produces energy). In individuals with type 2 diabetes, the liver continues to release sugar even when sugar levels are normal; the pancreas is not able to produce and release insulin normally; and the muscle and fat cells no longer respond as effectively to insulin. These defects lead to an abnormal rise of sugar in the blood. In this study, we want both to look more closely at the mitochondria and see if there is potential for improving mitochondrial functioning (improving the machinery of the muscle cell that produces energy) and reversing mitochondrial damage through a weight loss or a combined exercise/weight loss program. The program you get assigned to will be determined by a process called randomization (like a flip of a coin).

Detailed Description

Recent research from our laboratory has detected novel findings concerning damage to mitochondria within skeletal muscle in type 2 diabetes (type 2 DM), damage that is evident morphologically and by functional criteria. In this project, we propose, firstly, to more fully test this hypothesis of an impaired bio-energetic capacity, and to begin to examine the pathogenesis of damage to mitochondria in type 2 DM. We are also interested in assessing the potential for reversing damage, and improving functional capacity of mitochondria through a weight loss or a combined exercise and weight loss intervention.

The first specific aim is to measure the functional capacity of mitochondria in human skeletal muscle in type 2 DM and in those at apparent risk for type 2 DM (obese, sedentary, non-diabetic adults with the Metabolic Syndrome and/or impaired glucose tolerance). The second specific aim is to examine the morphology of mitochondria in human skeletal muscle in type 2 DM and in those at apparent risk for type 2 DM. The third specific aim is to examine the pathogenesis of mitochondrial damage in type 2 DM and in those at apparent risk for type 2 DM. The fourth specific aim is to assess whether exercise and diet can improve mitochondrial function and morphology in type 2 DM and in those at apparent risk for type 2 DM.

Conditions

Diabetes; Obesity

Keywords

Mitochondria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

weight loss/ exercise

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• AGE 30 to 55 years old BMI 28 to 38 kg/m2 BLOOD PRESSURE Systolic < 150 ; Diastolic < 95 SEDENTARY Currently not engaged in a regular exercise program and a VO2 max pre-training value < 55 ml/kg-fat free mass-min HEALTH (Group 1) Type 2 diabetes mellitus for < 10 years and independent in SBGM HEALTH (Group 2) Non-diabetic with impaired glucose tolerance (as per ADA) or with Metabolic Syndrome (as per NCEP-ATP III)

HEALTH Must be in good general health with no known h/o the following:

liver disease, kidney disease, PVD (including diminished pulses, or H/O thrombophlebitis), heart disease (including any h/o MI), neuromuscular disease, neurological disease (including peripheral neuropathy or muscle wasting), paresis, edema , current malignancy, or any drug or alcohol abuse, LAB VALUES Enroll if: No Proteinuria (defined as < 1+ protein on routine dipstick) Hct > 34% ALT < 80, AST < 80, Alk Phos < 240 sTSH < 8 (Group 2) 2 hr glucose on OGTT >140mg/dl but < 200mg/dl or NCEP-ATP III criteria) Triglyceride < 450 Cholesterol < 300 Negative Urine Pregnancy

Exclusion Criteria

• (Group 1) anti-hypertensives, "statin" hypolipemics, and diabetic medications okay but exclude if taking: insulin, or a hypolipemic that is not a "statin" (Group 2) "statin" hypolipemic medications are okay. A hypolipemic that is not a "statin" will exclude.

Inability and / or unwillingness to comply with the protocol as written Previous difficulty with lidocaine or other local anesthetic Claustrophobia Wt gain or loss of > 3 kg during past 4 weeks

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: lead

Principal Investigators

David E. Kelley, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

R01DK049200

Identifier Type: NIH

Identifier Source: secondary_id

View Link

021165

Identifier Type: -

Identifier Source: org_study_id