Incretin Effect in People With Impaired Fasting Glucose (1651)

Exploring the Incretin Effect in People With IFG

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Sitagliptin Phosphate

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Leigh Perreault, MD, University of Colorado, Denver

Publications and helpful links

General Publications

• Perreault L, Man CD, Hunerdosse DM, Cobelli C, Bergman BC. Incretin action maintains insulin secretion, but not hepatic insulin action, in people with impaired fasting glucose. Diabetes Res Clin Pract. 2010 Oct;90(1):87-94. doi: 10.1016/j.diabres.2010.06.012. Epub 2010 Aug 13.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: November 20, 2008
• First Submitted That Met QC Criteria: November 20, 2008
• First Posted (Estimate): November 21, 2008

Study Record Updates

• Last Update Posted (Actual): April 5, 2021
• Last Update Submitted That Met QC Criteria: March 9, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: GLP-1; insulin secretion; pre-diabetes; impaired fasting glucose; insulin action; simple obesity; isotopes
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: 07-0749

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO