Metabolic Syndrome
Conditions
Keywords
Metabolic Syndrome, Pre-diabetes, impaired glucose tolerance, Phospholipids
Brief summary
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.
Detailed description
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.
Interventions
PROCEDUREmuscle biopsy
A member of the study team will obtain a small sample of muscle tissue from the patient's thigh (vastus lateralis muscle).
Sponsors
Washington University School of Medicine
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sarcoplasmic Reticulum Composition | Study Visit Week 4 | We will take a muscle tissue sample from the subject's thigh (vastus lateralis) to quantify phosphatidylcholine to phosphatidylethanolamine ratio of the sarcoplasmic reticulum. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity | Study visit week 4 | 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. |
| Lean and Fat Body Mass | Study Visit week 4 | We will perform a Duel Energy X-ray absorptiometry (DEXA) scan to approximate lean and fat body mass of study subjects. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metabolic Syndrome Muscle biopsy to determine sarcoplasmic reticulum composition and function, Oral Glucose tolerance test with insulin levels at time points to determine Insulin sensitivity, DEXA scan to determine lean muscle and fat mass
muscle biopsy: A member of the study team will obtain a small sample of muscle tissue from the patient's thigh (vastus lateralis muscle). | 12 |
| Control Muscle biopsy to determine sarcoplasmic reticulum composition and function, Oral Glucose tolerance test with insulin levels at time points to determine Insulin sensitivity, DEXA scan to determine lean muscle and fat mass
muscle biopsy: A member of the study team will obtain a small sample of muscle tissue from the patient's thigh (vastus lateralis muscle). | 15 |
| Total | 27 |
Baseline characteristics
| Characteristic | Metabolic Syndrome | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 15 Participants | 27 Participants |
| Age, Continuous | 51.3 years STANDARD_DEVIATION 8.4 | 39.5 years STANDARD_DEVIATION 16.4 | 44.8 years STANDARD_DEVIATION 14.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 13 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 12 Participants | 20 Participants |
| Region of Enrollment United States | 12 participants | 15 participants | 27 participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 15 |
| other Total, other adverse events | 0 / 12 | 0 / 15 |
| serious Total, serious adverse events | 0 / 12 | 0 / 15 |
Outcome results
Primary
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
Population: Samples not included were lost during tissue processing. Metabolic syndrome (n=10); Control (n=13)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metabolic Syndrome | Sarcoplasmic Reticulum Composition | 2.0 PC:PE ratio | Standard Error 0.2 |
| Control | Sarcoplasmic Reticulum Composition | 2.2 PC:PE ratio | Standard Error 0.2 |
Secondary
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
Population: Oral glucose tolerance tests were performed on 15 controls and 11 metabolic syndrome participants. The insulin data was lost for one metabolic syndrome participant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metabolic Syndrome | Insulin Sensitivity | 2.5 Matsuda Index | Standard Deviation 1.9 |
| Control | Insulin Sensitivity | 5.6 Matsuda Index | Standard Deviation 2.2 |
Secondary
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
Population: All study participants received DEXAs and data were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metabolic Syndrome | Lean and Fat Body Mass | 43.7 Total body fat (%) | Standard Deviation 5 |
| Control | Lean and Fat Body Mass | 30.6 Total body fat (%) | Standard Deviation 7.5 |