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Glucolipotoxicity and Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT01375270
Recruitment Status : Completed
First Posted : June 17, 2011
Last Update Posted : December 3, 2014
Sponsor:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment
Type 2 Diabetes Mellitus Procedure: Glucotoxicity Procedure: Lipotoxicity

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: The Effects of Experimental Elevation of Plasma Glucose and Lipid on Pancreatic Beta-cell Function in Humans
Study Start Date : April 2011
Primary Completion Date : May 2014
Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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.


Outcome Measures

Primary Outcome Measures :
  1. Insulin Secretion [ Time Frame: 24 hours ]
    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 :
  1. Insulin Sensitivity [ Time Frame: 24 hours ]
    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.

  2. Plasma Cytokines (IL-6, TNF, IL-1beta, IL-1ra) [ Time Frame: 24 hours ]
    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.


Eligibility Criteria

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
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

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Responsible Party: Thomas Solomon, Group Leader, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01375270     History of Changes
Other Study ID Numbers: H-3-2010-127
First Posted: June 17, 2011    Key Record Dates
Last Update Posted: December 3, 2014
Last Verified: December 2014

Keywords provided by Thomas Solomon, 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
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Gastric Inhibitory Polypeptide
Gastrointestinal Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs