Acute Effect of Intensive Insulin Infusion on Intestinal Triglyceride-rich-lipoprotein-apoB48 Metabolism in Type 2 Diabetic Patients

NCT00950209 | Completed

• 2 other identifiers: 2007/172007-002791-33
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Atherosclerotic cardiovascular disease (ASCD) is the first cause of morbidity and mortality at type 2 diabetes. The typical dyslipidemia that is associated with insulin resistance, which includes a postprandial elevation of triglyceride-rich lipoproteins (TRLs) with excess of intestinal triglyceride-rich-lipoprotein-apoB48 (TRL-apoB48), is felt to play an important role in the accelerated ASCD. The investigators' objectives in this study are to determine whether an acute elevation of plasma insulin, secondarily to plasma insulin infusion, modulates the production and the clearance rates of intestinal TRL-apoB48 in type 2 diabetic patients in the fed state and to determine if this is a direct effect of insulin or an indirect effect due to the decrease of plasma FFA or the decrease of plasma glucose.

Conditions

Type 2 Diabetes

Keywords

type 2 diabetic patients in the fed state

Outcome Measures

Primary Outcomes (1)

• To determine whether an acute elevation of plasma insulin, secondarily to plasma insulin infusion, modulates the production and the clearance rates of intestinal TRL-apoB48 in type 2 diabetic patients in the fed state

  3 years

Secondary Outcomes (1)

• To determine if this is a direct effect of insulin or an indirect effect due to the decrease of plasma FFA or the decrease of plasma glucose.

  3 years

Study Arms (3)

euglycaemic hyperinsulinic clamp

ACTIVE COMPARATOR

In the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48. In the second step,the patients of this arm will perform an euglycaemic hyperinsulinic clamp to maintain plasma glucose around 1g/l.

Dietary Supplement: saline infusion; Other: euglycaemic hyperinsulinic clamp

euglycaemic hyperinsulinic clamp with Endolipide and heparin

ACTIVE COMPARATOR

In the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48. In the second step,the patients of this arm will perform an euglycaemic hyperinsulinic clamp to maintain plasma glucose around 1g/l but will be also infused with Endolipide 20 % (12,5 ml/h) and heparin (250 U/h) to prevent the suppressive effect of insulin on plasma free fatty acids.

Dietary Supplement: saline infusion; Other: euglycaemic hyperinsulinic clamp; Dietary Supplement: infusion of Endolipide and heparin

hyperglycaemic hyperinsulinic clamp

ACTIVE COMPARATOR

In the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48. In the second step,the patients of this arm will perform a hyperglycaemic hyperinsulinic clamp to maintain plasma glucose around 2 g/l to prevent the decreasing effect of insulin on plasma glucose.

Dietary Supplement: saline infusion; Other: hyperglycaemic hyperinsulinic clamp

Interventions

saline infusion DIETARY_SUPPLEMENT

In the first step of the protocol, all the patients will have a kinetic study of the TRL-apoB48 in conditions of a saline infusion to measure the "basal" production and clearance rates of the TRL-apoB48

euglycaemic hyperinsulinic clamp; euglycaemic hyperinsulinic clamp with Endolipide and heparin; hyperglycaemic hyperinsulinic clamp

euglycaemic hyperinsulinic clamp OTHER

an euglycaemic hyperinsulinic clamp to maintain plasma glucose around 1g/l

euglycaemic hyperinsulinic clamp; euglycaemic hyperinsulinic clamp with Endolipide and heparin

infusion of Endolipide and heparin DIETARY_SUPPLEMENT

an infusion with Endolipide 20 % (12,5 ml/h) and heparin (250 U/h) to prevent the suppressive effect of insulin on plasma free fatty acids

euglycaemic hyperinsulinic clamp with Endolipide and heparin

hyperglycaemic hyperinsulinic clamp OTHER

a hyperglycaemic hyperinsulinic clamp to maintain plasma glucose around 2 g/l to prevent the decreasing effect of insulin on plasma glucose.

hyperglycaemic hyperinsulinic clamp

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• type 2 diabetic patients according to the criteria of the American Diabetes Association
• body mass index between 25 and 40 kg/m2
• Subject the therapeutic care of which bases only on the oral anti-diabetics excepted of glitazones and inhibitors of alpha-glucosidases
• Subject without cardiovascular event in the previous 6 months or perturbing disease the lipid balance assessment (dysthyroidism, pituitary disease, adrenal disease)
• No anemia, no coagulation disturb, creatinine clearance \> 60 ml/min, fasting triglycerides \< 4g/l

You may not qualify if:

• Hypersensitivity to egg
• Subject with severe disease associated with diabete

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique-Hopitaux de Marseille

Marseille, France

Location

Related Publications (1)

• Nogueira JP, Maraninchi M, Beliard S, Padilla N, Duvillard L, Mancini J, Nicolay A, Xiao C, Vialettes B, Lewis GF, Valero R. Absence of acute inhibitory effect of insulin on chylomicron production in type 2 diabetes. Arterioscler Thromb Vasc Biol. 2012 Apr;32(4):1039-44. doi: 10.1161/ATVBAHA.111.242073. Epub 2012 Feb 2.

  PMID: 22308041 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Heparin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Rene Valero

  Assistance Publique Hopitaux De Marseille

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2009
• First Posted: July 31, 2009
• Study Start: April 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: February 25, 2014

Record last verified: 2014-02

Locations

FR (1)