Diurnal Variability in the Regulation of Beta-cell Function and Insulin Sensitivity in Overweight People

Study Overview
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Brief Summary
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The purpose of this research study is to learn more about how our body produces sugar, breaks down fat for fuel, and makes insulin (the major hormone that controls the production of blood sugar and fat breakdown) during a 24-hour day and how body fat and muscle are involved in these processes.

Detailed Description
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The purpose of this study is to determine whether there are diurnal differences in postprandial beta-cell function and hepatic insulin sensitivity and the factors that influence these metabolic functions, including insulin signaling, adipose tissue and systemic inflammation, nicotinamide phosphoribosyltransferase (NAMPT)-mediated nicotinamide adenine dinucleotide(NAD) biosynthesis, and sirtuin (silent mating type information regulation 2 homolog 1 (SIRT1)) in overweight human subjects.

Official Title
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Diurnal Variability in the Regulation of Beta-cell Function and Insulin Sensitivity in Overweight People

Conditions
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Overweight

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females 18-55 years old BMI between 25.0-29.9 kg/m2 Must be sedentary (regular exercise <1hour/week or <2 times/week Exclusion Criteria: Regular exercise (>1hour/week or >2 times/week) Diabetes Severe organ dysfunction Smokers Severe hypertriglyceridemia (>300 mg/dl) Medications that may alter the results of the study Pregnant Breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine postprandial beta-cell function (insulin secretion) after ingesting breakfast and dinner meals. | Postprandial pancreatic beta-cell function will be evaluated by using a mixed meal labelled with stable isotope tracers, in conjunction with stable isotope tracer infusion. Metabolic outcomes from the breakfast meal will be compared with values obtained after dinner. | 24 hours | 
| Determine postprandial hepatic insulin sensitivity (suppression of endogenous glucose production) after ingesting breakfast and dinner meals. | Postprandial pancreatic hepatic insulin sensitivity will be evaluated by using a mixed meal labelled with stable isotope tracers, in conjunction with stable isotope tracer infusion. Metabolic outcomes from the breakfast meal will be compared with values obtained after dinner. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine whether there is diurnal variability in muscle insulin signaling | This muscle samples will be obtained two times (every 12 hours for 24 hours)to assess NAMPT and NAD+ concentrations, SIRT1 activity, and factors involved in insulin signaling. | 24 hours | 
| Determine whether there is diurnal variability in adipose tissue and systemic inflammation. | Subcutaneous adipose tissue samples will be obtained four times (every 6 hours for 24 hours) to evaluate NAMPT and NAD+ concentrations, SIRT1 activity, and markers of inflammation. | 24 hours | 
| Determine whether there is diurnal variability in NAMPT-mediated NAD+ biosynthesis and SIRT1. | Blood samples will be obtained at regular intervals for 24 hours to evaluate; 1)plasma free fatty acids (FFA), glucose and insulin concentrations, 2)NAMPT and NAD+ concentrations, 3)SIRT1 activity,and 4)systemic markers of inflammation (C-reactive protein and interleukin (IL) -6). | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Overweight