Glucolipotoxicity and Type 2 Diabetes

NCT01375270 | Completed

• 1 other identifier: H-3-2010-127
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Elevations of blood glucose and lipid are thought to be deleterious to the insulin secretory function of the pancreas. This is known as glucolipotoxicity. However, few studies have examined this in detail. This investigation will examine pancreatic insulin secretory function in physiological models of glucolipotoxicity such as obese and type 2 diabetic individuals. Furthermore, healthy subjects will undergo 24 hour infusion of glucose or Intralipid to induce experimental models of glucolipotoxicity. Insulin secretion in response to intravenous infusions of glucose, GLP-1, GIP, and arginine and in response to meal ingestion, will be examined. the investigators hypothesize that experimental glucolipotoxicity will impairs pancreatic insulin secretory function to levels akin to that seen in type 2 diabetics.

Conditions

Type 2 Diabetes Mellitus

Keywords

diabetes; incretin; beta-cell function; glucolipotoxicity; glucagon-like peptide 1; glucose-dependent insulinotropic polypeptide

Outcome Measures

Primary Outcomes (1)

• Insulin Secretion

  Insulin secretion will be assessed in response to intravenous infusions of glucose, GLP-1, GIP, and arginine, and in response to meal ingestion.

  24 hours

Secondary Outcomes (2)

• Insulin Sensitivity

  24 hours

• Plasma Cytokines (IL-6, TNF, IL-1beta, IL-1ra)

  24 hours

Study Arms (3)

Glucotoxicity Trial

EXPERIMENTAL

Insulin secretion will be assessed using a hyperglycemic clamp combined with GLP-1, GIP, and arginine infusions. The clamp will be performed before and after 24 hours of bed rest, isocaloric meal feeding, and experimental elevation of blood glucose.

Procedure: Glucotoxicity

Control Trial

NO INTERVENTION

Insulin secretion will be assessed using a hyperglycemic clamp combined with GLP-1, GIP, and arginine infusions. The clamp will be performed before and after 24 hours of bed rest and isocaloric meal feeding.

Lipotoxicity Trial

EXPERIMENTAL

Insulin secretion will be assessed using a hyperglycemic clamp combined with GLP-1, GIP, and arginine infusions. The clamp will be performed before and after 24 hours of bed rest, isocaloric meal feeding, and experimental elevation of blood free fatty acids.

Procedure: Lipotoxicity

Interventions

Glucotoxicity PROCEDURE

Glucose will be infused intravenously for a 24 hour period to raise blood glucose concentrations 5 mM above basal.

Glucotoxicity Trial

Lipotoxicity PROCEDURE

Intralipid and heparin will be infused intravenously for a 24 hour period to raise blood free fatty acid concentrations to approximately 1 mM.

Lipotoxicity Trial

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• normal glucose tolerance based on screening OGTT or
• diagnosed type 2 diabetic (confirmed with OGTT)

You may not qualify if:

• insulin dependent diabetes
• age \<18 or \>65 years
• BMI \<20 or \> 35 kg/m2
• evidence of hematological, pulmonary, hepatic, renal, or cardiovascular disease
• actively undergoing weight-loss (\>2kg change in last 6 months)
• bariatric surgery (gastric by-pass or banding)
• pregnancy
• smoking

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Centre of Inflammation and Metabolism, Rigshospitalet

Copenhagen, 2100, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Thomas P Solomon, Ph.D.

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Group Leader

Study Record Dates

• First Submitted: June 14, 2011
• First Posted: June 17, 2011
• Study Start: April 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: December 1, 2014
• Last Updated: December 3, 2014

Record last verified: 2014-12

Locations

DK (1)