Hyperglycemia and the Extra-pancreatic Effect of Incretins

Not Applicable

Completed

• Conditions: Extra-pancreatic Incretin Effect; Glucose Effectiveness
• Interventions: Biological: Saline; Biological: GIP; Biological: GLP-1

• Registration Number: NCT01749163
• Lead Sponsor: Rigshospitalet, Denmark

Brief Summary

Incretin hormones (GLP-1 and GIP) released from the intestine in response to meal ingestion augment insulin secretion from the pancreas to help maintain glycemic control. Studies in vitro and in vivo have shown that these incretin hormones also have functional effects in other tissues independent of the insulin secretory response. Both GLP-1 and GIP stimulate insulin secretion in a glucose-dependent manner, however the glucose-dependency of their extra-pancreatic effects has not been examined in vivo. By using pancreatic clamp methodology during euglycemic and hyperglycemic conditions we will test the hypothesis that extra-pancreatic effects of GLP-1 and GIP are glucose-dependent.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-09
• Study First Submitted: 2012-12-11
• Study First Submitted QC: 2012-12-12
• Study First Posted: 2012-12-13
• Primary Completion: 2013-12
• Study Completion: 2014-03
• Status Verified: 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 18-30 kg/m2
• Male
• Normal glycemic control (fasting glucose <5.6 mM)

Exclusion Criteria

• Evidence of chronic disease
• Smoking
• Active weight loss (>2 kg in previous 6 months)
• Treatment with drugs known to affect our outcome varaibles

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Control	Saline	Saline will be coninfused during the pancreatic clamp
GIP	GIP	GIP will be infused intravenously during the pancreatic clamp at 1.5 pmol/kg/min
GLP-1	GLP-1	GLP-1 will be infused intravenously during the pancreatic clamp at 0.5 pmol/kg/min

Primary Outcome Measures

Name	Time	Method
Glucose metabolism	up to 4 hours	Pancreatic clamp will be performed including infusion of somatostatin and replacement of basal insulin, glucagon, and growth hormone. During pancreatic clamps, euglycemia (5 mM) will be maintained via exogenous glucose infusion for the first 2-hours, followed by hyperglycemia (+5 mM) for the final 2-hours. An infusion of the stable isotope \[U13C\]glucose will be performed to assess glucose kinetics. Expired air will be collected for the analysis of \[U13C\]glucose into 13CO2.
Lipid metabolism	up to 4 hours	An infusion of the stable isotope \[D5\]glycerol will be performed to assess glycerol kinetics.

Secondary Outcome Measures

Name	Time	Method
Endothelial function	Baseline, 2 hours, and 4 hours	Ultrasound Doppler will be used to examine lower and upper limb blood flow and flow-mediated dilation
Signaling	Baseline, 2 hours, and 4 hours	Skeletal muscle (vastus lateralis) and subcutaneous abdominal adipose biopsies will be obtained under local anaesthetic by the Bergstrom needle technique. Intracellular signalling related to glucose and lipid metabolism will be measured.

Trial Locations

Locations (1)

Rigshospitalet; 🇩🇰 Copenhagen, Capital Region, Denmark