Incretins and Metabolism

Completed

• Conditions: Type 2 Diabetes

• Registration Number: NCT01607944
• Lead Sponsor: Rigshospitalet, Denmark

Brief Summary

Incretin hormones (GLP-1 and GIP) have insulin secretory effects on the pancreas that are glucose dependent. Extrapancreatic effects of incretin hormones are reported, however the glucose dependency of these effects have not been examined. In type 2 diabetes, pancreatic endocrine function and incretin metabolism are impaired. The investigators hypothesize that extrapancreatic effects of incretin hormones are glucose depedent and dysregulated in subjects with type 2 diabetes.

Healthy control subjects and type 2 diabetics will undergo pancreatic clamps. In brief, somatostatin will be infused to inhibit pancreatic endocrine function and basal levels of insulin, glucagon, and growth hormone will be replace via infusion. Metabolic flux will be studied during euglycemic and hyperglycemic stages of the pancreatic clamp. Each subject will undergo 3 trials involving the co-infusion of either saline(Control Trial), GLP-1, or GIP. Glucose metabolism will be assessed using 13C-glucose stable isotope methodology combined with indirect calorimetry and expired breath isotope ratio analysis. Blood flow and flow-mediated dilation will be measured using ultrasound Doppler. Skeletal muscle and abdominal adipose biopsies will be taken to examine intracellular signalling.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-04
• Study First Submitted: 2012-05-23
• Study First Submitted QC: 2012-05-25
• Study First Posted: 2012-05-30
• Primary Completion: 2014-09
• Status Verified: 2014-12
• Study Completion: 2014-12
• Last Update Submitted: 2014-12-02
• Last Update Posted: 2014-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 20

Inclusion Criteria

• age 18-60 years
• BMI 18-35 kg/m2
• NGT or T2DM as classified by ADA criteria

Exclusion Criteria

• Insulin dependency
• Smokers
• History of or presentation with cardiovascular disease, cancer, and chronic hematological, renal, hepatic, pulmonary disease
• Weight loss (>2 kg in previous 6 months)
• Physical activity (>150 mins/week)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Glucose turnover	0, 1, 2, 3, 4 hours	Rates of appearance and disappearance (g/min) will be measured by examining \[6,6-2H2\]glucose enrichment in plasma.

Secondary Outcome Measures

Name	Time	Method
Palmitate turnover and oxidation	0, 1, 2, 3, 4 hours	Rates of appearance and disappearance (g/min) will be measured by examining \[U13C\]palmitate enrichment in plasma. Rate of oxidation (g/min) will also be measured by examining 13C incorporation into CO2 in expired breath.
Blood flow and flow-mediated dilation	0, 1, 2, 3, 4 hours

Trial Locations

Locations (1)

Rigshospitalet; 🇩🇰 Copenhagen, Denmark