Composition & Function of Sarcoplasmic Reticulum in Persons With the Metabolic Syndrome

Washington University School of Medicine27 enrolled

Overview

The investigators previous research has suggested that lipid (fatty) composition in the muscle cells of mice plays a key role in their insulin sensitivity. The purpose of this study is to determine whether these specific fat signatures translate to humans by comparing the muscle of healthy patients to those with pre-diabetes, or "the metabolic syndrome".

The Comp-SR study explores the role of lipid metabolism in key metabolic pathways in skeletal muscle. It is a translation of previous research done in mice studying the effects and functions of certain key enzymes involved in lipid metabolism found to be associated with insulin resistance. These enzymes are fatty acid synthase (FAS), choline/ethanolamine phosphotransferase 1 (CEPT1) and sarcoplasmic-endoplasmic reticulum ATPase (SERCA). Based on the investigators research, it appears that the activity and function of these enzymes determines the ratio of certain phospholipids in the sarcoplasmic reticulum (SR), namely phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Furthermore, the investigators have found that the ratio of these phospholipids correlates with the mouse's sensitivity to insulin. Based on the muscle biopsies of four healthy persons, it was found that human muscle contains similar phospholipids and phospholipid ratios to mice. It is hypothesized that these phospholipid signatures may be predictive of the metabolic status of humans as well. The specific aims of this study are to determine if the composition and function of the sarcoplasmic reticulum is altered in persons with the metabolic syndrome compared to lean controls. This knowledge could provide new understanding of impediments to effective therapy, novel biomarkers of disease progression, and innovative treatment targets for diabetes.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Metabolic Syndrome

Interventions

muscle biopsyPROCEDURE

A member of the study team will obtain a small sample of muscle tissue from the patient's thigh (vastus lateralis muscle).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Control subjects Inclusion: Sedentary: No routine exercise, walking \<10,000 steps per day Age \>18 and \<65 Body Mass Index (BMI) \<32 Healthy by physical exam (patient is devoid of major acute or chronic illness) No significant abnormality in screening labs Exclusion: Currently on any significant prescription medications other than oral contraceptives in women Currently Pregnant Current Tobacco Use Subjects with the Metabolic Syndrome Inclusion: Sedentary: No routine exercise, walking \<10,000 steps per day Age \>18 and \<65 Body Mass Index (BMI) \>30 Meet at least three of the following Adult Treatment Panel (ATP) III criteria for the metabolic syndrome: waist circumference \> or = 40 inches in men, \> or = 35 inches in women blood triglycerides \> or = 150 mg/dL blood HDL cholesterol \<40 mg/dL in men, \<50 in women blood pressure \> or = 130 mmHg systolic, or \> or = 85 mmHg diastolic fasting blood sugar \> or = 100 mg/dL Exclusion: Diagnosed with Type 2 diabetes, coronary artery disease, cancer, liver, lung, or kidney disease or any other major illness Currently on any significant prescription medications other than: oral contraceptives in women More than two standard medication for stage 1 hypertension in men or women (blood pressure 140-159/90-99) Currently Pregnant Current Tobacco Use

Locations (1)

Washington University School of Medicine

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Sarcoplasmic Reticulum Composition

We will take a muscle tissue sample from the subject's thigh (vastus lateralis) to quantify phosphatidylcholine to phosphatidylethanolamine ratio of the sarcoplasmic reticulum.

Time frame: Study Visit Week 4

Secondary Outcomes

Insulin Sensitivity

The homeostatic model assessment for insulin resistance (HOMA-IR) is a calculated value using fasting glucose and insulin levels. It provides a measure of insulin resistance. HOMA-IR values between 0.5 and 1.4 are considered normal and values \>2.9 indicate insulin resistance. The Matsuda Index reflects insulin sensitivity. It is calculated from glucose and insulin levels drawn fasting and during an OGTT. Matsuda Index values of 2.5 or higher are normal and indicate lack of insulin resistance or normal insulin sensitivity. Results of these measures are displayed graphically in the published paper.

Time frame: Study visit week 4

Lean and Fat Body Mass

We will perform a Duel Energy X-ray absorptiometry (DEXA) scan to approximate lean and fat body mass of study subjects.

Time frame: Study Visit week 4

Data from ClinicalTrials.gov

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