Incretin Effect in People With Impaired Fasting Glucose

Study Overview
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Brief Summary
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Regulation of endogenous glucose production (EGP) and insulin secretion are major actions of glucagon-like peptide-1 (GLP-1). Determining whether alterations in GLP-1 may contribute to abnormal EGP and insulin secretion in people with impaired fasting glucose (IFG) was the objective of the current study. The investigators hypothesized that defects in GLP-1 may explain the inappropriate basal EGP and diminished insulin secretion in IFG, and, furthermore, that by increasing circulating GLP-1 levels (using a new medicine called sitagliptin) the investigators could reverse these defects.

Official Title
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Exploring the Incretin Effect in People With IFG

Conditions
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Obesity

Intervention / Treatment
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* Drug: Sitagliptin Phosphate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, sedentary, non-smokers, men and women 45-70 years old Subjects were placed into 1 of the 2 groups based on two 2-hour 75g oral glucose tolerance tests (2h OGTT), separated by one week: a control group with normal glucose tolerance (NGT; n=14; fasting glucose <5.6 mmol/l and 2h OGTT <7.8 mmol/l), or IFG (n=10; fasting glucose 5.6-6.9 mmol/l, and 2h OGTT <7.8 mmol/l). Exclusion Criteria: Subjects were excluded for: thyroid stimulating hormone <50 or >500 milliunits/L, fasting triglycerides >10.3 mmol/l, creatinine >130 μmol/l, elevated liver function tests (>2 times normal), hematocrit < 38%, or white blood cell count <3.0 x 103. Use of medications for lipid and/or glucose lowering also excluded enrollees. Women may not have used hormone replacement therapy in the past 1 year. Smokers. BMI <25 or >40 kg/m2. Diabetes or impaired glucose tolerance.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

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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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Impaired Fasting Glucose<br>Treatment of people with impaired fasting glucose with Januvia (sitagliptin phosphate) | Drug: Sitagliptin Phosphate<br>* Januvia 100 mg po qd x 28 days for all subjects after baseline measures made<br>* Other names: brand name: Januvia;|
| Experimental: Normal glucose tolerance<br>Treatment of people with normal glucose tolerance with Januvia (sitagliptin phosphate) | Drug: Sitagliptin Phosphate<br>* Januvia 100 mg po qd x 28 days for all subjects after baseline measures made<br>* Other names: brand name: Januvia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Endogenous Glucose Production |  | Baseline and 28 days | 
| Change in Insulin Secretion |  | Baseline and 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Secretion in Response to Oral vs. IV Glucose |  | Baseline | 
| Baseline and Change in Hormones, Substrates and Insulin Action: C-peptide |  | Baseline and 28 days | 
| Baseline and Change in Hormones, Substrates and Insulin Action: Glucagon |  | Baseline and 28 days | 
| Baseline and Change in Hormones, Substrates and Insulin Action: GLP-1 |  | Baseline and 28 days | 
| Baseline and Change in Hormones, Substrates and Insulin Action: Lactate |  | Baseline and 28 days | 
| Baseline and Change in Hormones, Substrates and Insulin Action: FFA |  | Baseline and 28 days | 
| Baseline and Change in Hormones, Substrates and Insulin Action: Glycerol |  | Baseline and 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pre-diabetes, isotopes, insulin secretion, insulin action, GLP-1, simple obesity, impaired fasting glucose