Incretins and Metabolism
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.
Type 2 Diabetes
|Study Design:||Observational Model: Case Control
Time Perspective: Cross-Sectional
|Official Title:||The Extrapancreatic Metabolic Effects of Incretin Hormones|
- Glucose turnover [ Time Frame: 0, 1, 2, 3, 4 hours ] [ Designated as safety issue: No ]Rates of appearance and disappearance (g/min) will be measured by examining [6,6-2H2]glucose enrichment in plasma.
- Blood flow and flow-mediated dilation [ Time Frame: 0, 1, 2, 3, 4 hours ] [ Designated as safety issue: No ]
- Palmitate turnover and oxidation [ Time Frame: 0, 1, 2, 3, 4 hours ] [ Designated as safety issue: No ]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.
|Study Start Date:||April 2012|
|Study Completion Date:||December 2014|
|Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
|Normal Glucose Tolerance|
|Type 2 Diabetes|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01607944
|Principal Investigator:||Thomas P Solomon, PhD||Rigshospitalet, Denmark|