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Glucolipotoxicity and Type 2 Diabetes

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Thomas Solomon, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01375270
First received: June 14, 2011
Last updated: March 14, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention
Type 2 Diabetes Mellitus
Procedure: Glucotoxicity
Procedure: Lipotoxicity

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: The Effects of Experimental Elevation of Plasma Glucose and Lipid on Pancreatic Beta-cell Function in Humans

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Insulin Secretion [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Insulin secretion will be assessed in response to intravenous infusions of glucose, GLP-1, GIP, and arginine, and in response to meal ingestion.


Secondary Outcome Measures:
  • Insulin Sensitivity [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Glucose kinetics will be assesed using [6,6-2H2]glucose. Rate of glucose disappearance during glucose infusion will be quantified per unit of plasma insulin to derive an estimate of insulin sensitivity.

  • Plasma Cytokines (IL-6, TNF, IL-1beta, IL-1ra) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Cytokines will be measured in plasma: IL-6, TNF-alpha, IL-1beta, IL-1 receptor antagonist, IL-8, IL-10, Interferon gamma. Peripheral blood mononuclear cells will be isolated.


Estimated Enrollment: 36
Study Start Date: April 2011
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Glucotoxicity Trial

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
Glucose will be infused intravenously for a 24 hour period to raise blood glucose concentrations 5 mM above basal.
No Intervention: Control Trial

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.

Experimental: Lipotoxicity Trial

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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01375270

Locations
Denmark
Centre of Inflammation and Metabolism, Rigshospitalet
Copenhagen, Denmark, 2100
Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
Principal Investigator: Thomas P Solomon, Ph.D. Rigshospitalet, Denmark
  More Information

No publications provided

Responsible Party: Thomas Solomon, Group Leader, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01375270     History of Changes
Other Study ID Numbers: H-3-2010-127
Study First Received: June 14, 2011
Last Updated: March 14, 2013
Health Authority: Denmark: Ethics Committee

Keywords provided by Rigshospitalet, Denmark:
diabetes
incretin
beta-cell function
glucolipotoxicity
glucagon-like peptide 1
glucose-dependent insulinotropic polypeptide

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on November 25, 2014