Glucolipotoxicity and Type 2 Diabetes

Rigshospitalet

Status: Completed

Conditions: Type 2 Diabetes Mellitus

Treatments: Procedure: Lipotoxicity; Procedure: Glucotoxicity

Study type: Interventional

Funder types: Other

Identifiers

NCT01375270

H-3-2010-127

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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30 participants in 3 patient groups

Glucotoxicity Trial

Experimental group

Description:

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.

Treatment:

Procedure: Glucotoxicity

Control Trial

No Intervention group

Description:

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.

Lipotoxicity Trial

Experimental group

Description:

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.

Treatment:

Procedure: Lipotoxicity