Glucolipotoxicity and Type 2 Diabetes

NCT ID: NCT01375270

Last Updated: 2014-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-04-30

Study Completion Date

2014-12-31

Brief Summary

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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

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Conditions

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Type 2 Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Participants

Study Groups

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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.

Group Type EXPERIMENTAL

Glucotoxicity

Intervention Type PROCEDURE

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

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

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.

Group Type EXPERIMENTAL

Lipotoxicity

Intervention Type PROCEDURE

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

Interventions

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Glucotoxicity

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

Intervention Type 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.

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Rigshospitalet, Denmark

OTHER

Sponsor Role lead

Responsible Party

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Thomas Solomon

Group Leader

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Thomas P Solomon, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Locations

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Centre of Inflammation and Metabolism, Rigshospitalet

Copenhagen, , Denmark

Site Status

Countries

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Denmark

Other Identifiers

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H-3-2010-127

Identifier Type: -

Identifier Source: org_study_id