Muscle Insulin Resistance In Aging
| Status: | Recruiting |
|---|---|
| Conditions: | Healthy Studies, Endocrine |
| Therapuetic Areas: | Endocrinology, Other |
| Healthy: | No |
| Age Range: | 65 - 80 |
| Updated: | 4/2/2016 |
| Start Date: | December 2011 |
| End Date: | September 2016 |
| Contact: | Nicole L Helbling, MS, RN |
| Email: | nlr8@pitt.edu |
| Phone: | 412-692-2285 |
The overall objective of this project is to thoroughly investigate the effects of
diet-induced weight loss in the absence of or in combination with exercise on skeletal
muscle IR, energy metabolism and function. These studies will significantly improve our
understanding of the fundamental biochemical and molecular factors linking
intervention-induced changes in mitochondria, oxidative stress, lipotoxicity, IR, and loss
of muscle function in aging humans.
diet-induced weight loss in the absence of or in combination with exercise on skeletal
muscle IR, energy metabolism and function. These studies will significantly improve our
understanding of the fundamental biochemical and molecular factors linking
intervention-induced changes in mitochondria, oxidative stress, lipotoxicity, IR, and loss
of muscle function in aging humans.
Aging is associated with alterations in skeletal muscle energy metabolism, insulin
resistance and a higher prevalence of type 2 diabetes mellitus (T2DM). Aging is also
associated with a progressive loss of muscle mass and increased adiposity, known as
sarcopenic obesity, which leads to mobility limitations and disability. However, the causes
of insulin resistance and sarcopenia in humans are not known. This project will provide
novel information regarding potential factors underlying both metabolic dysfunction and
sarcopenia in aging muscle - namely, mitochondria and the accumulation of intramyocellular
lipids. Within this conceptual framework we will help elucidate the biological underpinnings
of these two significant health problems related to aging. In addition, we will provide
intervention-based evidence to better understand these complex age-related disorders and
whether mitochondria or intramyocellular lipids are modifiable targets for improved
prevention or treatment strategies for metabolic and muscle dysfunction. Therefore, our
overall objectives are to employ highly innovative methods in muscle biopsy specimens in
order to determine the functional and clinically relevant consequences of these
interventions as well as alterations in several novel biochemical and molecular factors
potentially underlying these intervention effects on human skeletal muscle. Our primary
approach to address all aims of the proposed studies is to conduct a 6-month randomized
controlled trial in obese (BMI ≥ 30 kg/m2) sedentary older men and women 65-80 years of age.
1. Control (health education) group (CON): Subjects will not receive specific exercise or
dietary education or prescription, but will be asked to participate in biweekly health
education sessions.
2. Diet-induced weight loss (DIWL): The goal will be to achieve a goal of 10% weight loss.
3. Weight Loss + Exercise (WLEX): This group will receive exactly the same dietary
intervention as the respective DIWL group. In addition, subjects will be complete a
progressive, moderate intensity supervised This is a single-site randomized controlled
trial. The analysis of each of the aims will involve multiple steps and draw on
statistical methods ranging from simple descriptive statistics to the modeling of
repeated measures outcome data accounting for potential missing observations.
The major outcomes of the study, the muscle biopsy parameters, insulin sensitivity, muscle
mass, strength, power and quality, will be measured at entry into the study and at the end
of the study.
resistance and a higher prevalence of type 2 diabetes mellitus (T2DM). Aging is also
associated with a progressive loss of muscle mass and increased adiposity, known as
sarcopenic obesity, which leads to mobility limitations and disability. However, the causes
of insulin resistance and sarcopenia in humans are not known. This project will provide
novel information regarding potential factors underlying both metabolic dysfunction and
sarcopenia in aging muscle - namely, mitochondria and the accumulation of intramyocellular
lipids. Within this conceptual framework we will help elucidate the biological underpinnings
of these two significant health problems related to aging. In addition, we will provide
intervention-based evidence to better understand these complex age-related disorders and
whether mitochondria or intramyocellular lipids are modifiable targets for improved
prevention or treatment strategies for metabolic and muscle dysfunction. Therefore, our
overall objectives are to employ highly innovative methods in muscle biopsy specimens in
order to determine the functional and clinically relevant consequences of these
interventions as well as alterations in several novel biochemical and molecular factors
potentially underlying these intervention effects on human skeletal muscle. Our primary
approach to address all aims of the proposed studies is to conduct a 6-month randomized
controlled trial in obese (BMI ≥ 30 kg/m2) sedentary older men and women 65-80 years of age.
1. Control (health education) group (CON): Subjects will not receive specific exercise or
dietary education or prescription, but will be asked to participate in biweekly health
education sessions.
2. Diet-induced weight loss (DIWL): The goal will be to achieve a goal of 10% weight loss.
3. Weight Loss + Exercise (WLEX): This group will receive exactly the same dietary
intervention as the respective DIWL group. In addition, subjects will be complete a
progressive, moderate intensity supervised This is a single-site randomized controlled
trial. The analysis of each of the aims will involve multiple steps and draw on
statistical methods ranging from simple descriptive statistics to the modeling of
repeated measures outcome data accounting for potential missing observations.
The major outcomes of the study, the muscle biopsy parameters, insulin sensitivity, muscle
mass, strength, power and quality, will be measured at entry into the study and at the end
of the study.
Inclusion Criteria:
- 65-80 years of age
- Stable weight (No Gain/Loss of > 10 lbs in 6 months)
- Sedentary (≤ 1 continuous exercise/week)
- Non-smoker
- BMI ≥ 30 kg/m2
- Resting Blood Pressure ≤ 150mmHg systolic and ≤ 95 mmHg diastolic
- Note from PCP/Cardiologist for exercise clearance if positive stress test
- Symptoms were observed from exercise test
- Independent in self blood glucose monitoring (those with diabetes only)
Exclusion Criteria:
- Clinically significant CVD including h/o MI
- Peripheral Vascular Disease
- Section: Section 3 - Human Subjects
- Hepatic, renal, muscular/neuromuscular, or active hematologic/oncologic disease
- Clinically diminished pulse
- Presence of bruits in lower extremities
- Previous history of pulmonary emboli
- Peripheral Neuropathy
- Anemia (Hematocrit <34%)
- Any contraindications to moderate exercise (Please specify)
- Inability and/ or willingness to comply with the protocol as written
- Active alcohol or substance abuse (Past 5 Years)
- Total cholesterol >300 mg/dL
- Triglycerides >350 mg/dL
- ALT >80, AST>80, Alk Phos >240
- Proteinuria (defined as > 1+)
- Hypothyroidism (sTSH>8)
- Fasting Glucose > 250 mg/dl
- Hemoglobin A1c > 8.5%
- Currently taking blood thinners such as Coumadin, Lovenox etc
- Currently taking any medications that can alter glucose homeostasis (steroids,
glucocorticoids,nicotinic acid)
- Currently taking thiazolidinediones or insulin
- Females currently on hormone replacement therapy (HRT) less than 6 months
- Claustrophobia
- Previous difficulty with lidocaine or other local anesthetic
- Stress test symptoms:
- Positive ECG (> 2mm ST segment depression) without PCP cardiologist permission
to participate
- Signs or symptoms of cardiovascular decomposition (hypotensive response to
exercise)
- Onset of angina or angina like symptoms, shortness of breath, change in heart
rhythm, signs of poor perfusion (light-headedness), tightness,
- Hypotension
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