Assessment of Liver Glucose Metabolism in Diabetic Subjects (CLAVA)

Type 2 diabetes is associated with hepatic insulin resistance. One consequence of insulin resistance of the liver is an altered hepatic glucose metabolism. This study investigates whether the whole body (M-value) and hepatic insulin sensitivity obtained by hyperinsulinemic euglycemic clamp is influenced by a preceding intravenous glucose tolerance test (Botnia Clamp) in subjects with type 2 diabetes.

Study Overview

• Status: Completed
• Conditions: Newly Diagnosed Type 2 Diabetes (During the Last 12 Months)
• Intervention / Treatment: Biological: intravenous glucose tolerance test; Biological: hyperinsulinemic euglycemic clamp

Detailed Description

The hyperinsulinemic euglycemic clamp represents the gold standard for measuring peripheral insulin sensitivity. The insulin sensitivity is described by the M-value,which is calculated from glucose infusion rates during the last 30min of the clamp.

Glucose is metabolised in the periphery: 50% by neural tissues, 20% by splanchnic bed and liver, 15% by skeletal muscle, 5% by adipose tissue and 10% by blood cells and other tissues. Under hyperinsulinemic conditions there is a strong shift in glucose utilization: 85% skeletal muscle and 15% by neural tissues, splanchnic bed and liver, adipose tissue, blood cells and other tissues. The contribution of skeletal muscle varies with different insulin sensitivity.

We now want to investigate whether there is a difference in tissue-specific insulin sensitivity measured from a Botnia clamp (intravenous glucose tolerance test (ivGTT) and following clamp) and a single hyperinsulinemic euglycemic clamp? After a 60min ivGTT blood glucose levels in type 2 diabetic subjects are still elevated compared to baseline. High blood glucose levels can influence several parameters and may also affect insulin sensitivity. Until now, it is not proven, that the clamp preceding ivGTT does not have a significant influence on the M-value.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Nordrhein-Westfalen
    • Düsseldorf, Nordrhein-Westfalen, Germany, 40225
      • German Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• newly diagnosed type 2 diabetes (during the last 12 months)or non-diabetic subjects

Exclusion Criteria:

• severe chronic diseases
• hepatitis B, C oder HIV infection
• malignancies
• immune suppressive therapy
• psychiatric illnesses
• drug or alcohol abuse
• anemia
• renal dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Botnia clamp; hyperinsulinemic euglycemic clamp following intravenous glucose tolerance test	Biological: intravenous glucose tolerance test; Administration of a 30% weight-adapted glucose bolus intravenously.; Other Names: ivGTT; Biological: hyperinsulinemic euglycemic clamp; Intravenous administration of 20% glucose and insulin over 3 hours; Other Names: HEC
Active Comparator: hyperinsulinemic euglycemic clamp; hyperinsulinemic euglycemic clamp without previous intravenous glucose tolerance test	Biological: hyperinsulinemic euglycemic clamp; Intravenous administration of 20% glucose and insulin over 3 hours; Other Names: HEC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
M Value in hyperinsulinemic euglycemic clamp	measurement of whole body insulin sensitivity with hyperinsulinamic euglicamic clamp	3h

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin-suppressed endogenous glucose production (liver insulin sensitivity)	Insulin-suppressed endogenous glucose production (liver insulin sensitivity)	3h

Collaborators and Investigators

• Sponsor: German Diabetes Center
• Investigators: Study Director: Michael Roden, Prof., MD, Director German Diabetes Center; Principal Investigator: Michael Roden, Prof., MD, Director German Diabetes Center

Publications and helpful links

General Publications

• Kahl S, Nowotny B, Piepel S, Nowotny PJ, Strassburger K, Herder C, Pacini G, Roden M. Estimates of insulin sensitivity from the intravenous-glucose-modified-clamp test depend on suppression of lipolysis in type 2 diabetes: a randomised controlled trial. Diabetologia. 2014 Oct;57(10):2094-102. doi: 10.1007/s00125-014-3328-3. Epub 2014 Jul 22.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2011
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: July 18, 2011
• First Submitted That Met QC Criteria: July 18, 2011
• First Posted (Estimated): July 19, 2011

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: June 2, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: insulin sensitivity; type 2 diabetes; hyperinsulinemic euglycemic clamp
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: CLAVA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No