Mechanisms of Glucose Counterregulation in Pancreatic Islet Transplantation

Phase 4

Completed

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Procedure: Hypoglycemic and euglycemic glucose clamp

• Registration Number: NCT01668485
• Lead Sponsor: University of Giessen

Brief Summary

Pancreatic islet transplantation improves glucose counterregulation and stabilizes glycemic control in patients with type 1 diabetes mellitus prone to severe hypoglycemia even if insulin independence is not achieved. However, the extent and underlying metabolic pathways of this improvement are unknown. Investigators therefore compare systemic glucose turnover including lactate gluconeogenesis and muscle glucose utilization, between insulin-requiring islet transplant recipients, matched type 1 diabetic subjects who did not receive islet transplantation, and matched healthy non-diabetic subjects.

Detailed Description

Subjects (n=12 each group) undergo a hypoglycemic and a euglycemic hyperinsulinemic clamp in a randomized fashion. Systemic and skeletal muscle glucose and lactate kinetics are assessed using a combination of isotopic and forearm balance techniques.

Study Timeline

• Study Start: 2001-11
• Primary Completion: 2010-11
• Study Completion: 2011-11
• Status Verified: 2012-08
• Study First Submitted: 2012-08-13
• Study First Submitted QC: 2012-08-15
• Last Update Submitted: 2012-08-17
• Study First Posted: 2012-08-20
• Last Update Posted: 2012-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• Type 1 Diabetes
• Pancreatic islet transplantation

Exclusion Criteria

• Type 2 Diabetes

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Islet transplant recipients	Hypoglycemic and euglycemic glucose clamp	Hypoglycemic and euglycemic glucose clamp
Type 1 diabetic subjects	Hypoglycemic and euglycemic glucose clamp	Hypoglycemic and euglycemic glucose clamp.
Non-diabetic subjects	Hypoglycemic and euglycemic glucose clamp	Hypoglycemic and euglycemic glucose clamp

Primary Outcome Measures

Name	Time	Method
Whole body glucose counterregulation	6-8 weeks	Whole body glucose counterregulation is the difference in glucose infusion rates required to maintain the glycemic goal between the hypoglycemic and euglycemic clamp. Clamps were performed at two time points at least two weeks apart. Participants will be followed for the duration of 6-8 weeks to perform the hypoglycemic and euglycemic clamp tests.

Secondary Outcome Measures

Name	Time	Method
Systemic glucose release	6-8 weeks	Systemic glucose release is the amount of glucose released primarily from the liver into the blood compartment during a given time. The unit of measure is μmol/kg/min.; Participants will be followed for the duration of 6-8 weeks to perform the hypoglycemic and euglycemic clamp tests that will yield this parameter.
Skeletal muscle glucose disposal	6-8 weeks	Participants will be followed for the duration of 6-8 weeks to perform the euglycemic and hypoglycemic clamp tests. The unit of measure of this parameters is μmol/kg/min.
Gluconeogenesis from lactate	6-8 weeks	This parameter is determined by labelled lactate infused into the proband. The rate of the de novo synthesis of glucose (gluconeogenesis) is determined by the degree of incorporation of the lactate label into glucose molecules. The unit of measure of this parameter is μmol/kg/min.

Trial Locations

Locations (1)

Justus Liebig University; 🇩🇪 Giessen, Hessia, Germany