Glucolipotoxicity and Type 2 Diabetes

Not Applicable

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Procedure: Glucotoxicity; Procedure: Lipotoxicity

• Registration Number: NCT01375270
• Lead Sponsor: Rigshospitalet, Denmark

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-04
• Study First Submitted: 2011-06-14
• Study First Submitted QC: 2011-06-16
• Study First Posted: 2011-06-17
• Primary Completion: 2014-05
• Status Verified: 2014-12
• Study Completion: 2014-12
• Last Update Submitted: 2014-12-02
• Last Update Posted: 2014-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Glucotoxicity Trial	Glucotoxicity	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.
Lipotoxicity Trial	Lipotoxicity	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.

Primary Outcome Measures

Name	Time	Method
Insulin Secretion	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

Name	Time	Method
Plasma Cytokines (IL-6, TNF, IL-1beta, IL-1ra)	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.
Insulin Sensitivity	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.

Trial Locations

Locations (1)

Centre of Inflammation and Metabolism, Rigshospitalet; 🇩🇰 Copenhagen, Denmark