Glucolipotoxicity and Type 2 Diabetes

Type 2 Diabetes Mellitus Clinical Trial

Official title:

The Effects of Experimental Elevation of Plasma Glucose and Lipid on Pancreatic Beta-cell Function in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01375270
• Other study ID #: H-3-2010-127
• Status: Completed
• Phase: N/A
• First received: June 14, 2011
• Last updated: December 2, 2014
• Start date: April 2011
• Est. completion date: December 2014

Study information

• Verified date: December 2014
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Procedure:
• Glucotoxicity
Glucose will be infused intravenously for a 24 hour period to raise blood glucose concentrations 5 mM above basal.
• Lipotoxicity
Intralipid and heparin will be infused intravenously for a 24 hour period to raise blood free fatty acid concentrations to approximately 1 mM.

Locations

Country	Name	City	State
Denmark	Centre of Inflammation and Metabolism, Rigshospitalet	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Insulin Sensitivity	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.	24 hours	No
Secondary	Plasma Cytokines (IL-6, TNF, IL-1beta, IL-1ra)	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.	24 hours	No