Glucagon-like Peptide 1 (GLP-1) and Endothelial Dysfunction in Metabolic Syndrome

NCT00856700 | Completed DMC

• 1 other identifier: 144/08
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Glucagon-like peptide 1 (GLP-1) is an intestinal peptide hormone secreted in a nutrient-dependent manner that stimulates the pancreatic beta cells to secrete more insulin in response to the same amount of blood glucose. In patients with Type 2 diabetes, GLP-1 secretion is lower than normal, thus suggesting that the hormone may contribute to the pathogenesis of the disease. Whether infusion of GLP-1 affects endothelial function and glucose uptake in humans has never been investigated. In the current proposal, the investigators hypothesize that GLP-1 administration might ameliorate endothelial dysfunction in patients with metabolic syndrome. To test this hypothesis, the investigators will evaluate the acute effects of GLP-1 in the forearm circulation of patients with metabolic syndrome during local hyperinsulinemia by use of the forearm perfusion technique.

Conditions

Metabolic Syndrome

Keywords

GLP-1; Endothelial Function; Metabolic Syndrome

Outcome Measures

Primary Outcomes (1)

• Endothelium-dependent vasodilation capacity

  60 minutes

Secondary Outcomes (1)

• Insulin-mediated glucose uptake

  100 minutes

Study Arms (1)

GLP-1 infusion

EXPERIMENTAL

Patients with metabolic syndrome

Drug: GLP-1 infusion

Interventions

GLP-1 infusion DRUG

Participants will receive intraarterial infusion of GLP-1 (20 pmol/ml solution) for 100 min.

Also known as: Incretins

GLP-1 infusion

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Otherwise healthy individuals aged between 20 and 60 years
• Must satisfy 3 out of the 5 listed criteria for the diagnosis of the metabolic syndrome (ATP III) will be included

You may not qualify if:

• Pregnancy
• Liver disease
• Pulmonary disease
• Renal insufficiency
• Coronary heart disease
• Heart failure
• Peripheral vascular disease
• Coagulopathy
• Any disease predisposing to vasculitis or Raynaud's phenomenon
• Bleeding disorders
• Kidney stones
• Platelet count \< 150,000/ml blood
• Prothrombin time/partial thromboplastin time (PT/PTT) \> 1 second above the normal range, and positive tests for HIV, or hepatitis B or C
• Subjects who are taking any kind of medication will not be included in this study; therefore, antihypertensive and/or lipid-lowering drugs will be discontinued at least 2 weeks before enrollment into this study
• All subjects will be told to refrain from alcohol, beverages containing caffeine, or smoking for at least 24 hours before the study is performed

Sponsors & Collaborators

• University of Rome Tor Vergata: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Tor Vergata University

Rome, 90100, Italy

Location

Related Publications (5)

• Tesauro M, Schinzari F, Rovella V, Melina D, Mores N, Barini A, Mettimano M, Lauro D, Iantorno M, Quon MJ, Cardillo C. Tumor necrosis factor-alpha antagonism improves vasodilation during hyperinsulinemia in metabolic syndrome. Diabetes Care. 2008 Jul;31(7):1439-41. doi: 10.2337/dc08-0219. Epub 2008 Apr 4.

  PMID: 18390795 BACKGROUND

• Tesauro M, Schinzari F, Iantorno M, Rizza S, Melina D, Lauro D, Cardillo C. Ghrelin improves endothelial function in patients with metabolic syndrome. Circulation. 2005 Nov 8;112(19):2986-92. doi: 10.1161/CIRCULATIONAHA.105.553883. Epub 2005 Oct 31.

  PMID: 16260640 BACKGROUND

• Zander M, Madsbad S, Madsen JL, Holst JJ. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet. 2002 Mar 9;359(9309):824-30. doi: 10.1016/S0140-6736(02)07952-7.

  PMID: 11897280 BACKGROUND

• Toft-Nielsen MB, Madsbad S, Holst JJ. Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients. Diabetes Care. 1999 Jul;22(7):1137-43. doi: 10.2337/diacare.22.7.1137.

  PMID: 10388979 BACKGROUND

• Tesauro M, Schinzari F, Adamo A, Rovella V, Martini F, Mores N, Barini A, Pitocco D, Ghirlanda G, Lauro D, Campia U, Cardillo C. Effects of GLP-1 on forearm vasodilator function and glucose disposal during hyperinsulinemia in the metabolic syndrome. Diabetes Care. 2013 Mar;36(3):683-9. doi: 10.2337/dc12-0763. Epub 2012 Oct 15.

  PMID: 23069838 DERIVED

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

Incretins

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Manfredi Tesauro, MD

  Internal Medicine Department, Tor Vergata University, Rome

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Internal Medicine

Study Record Dates

• First Submitted: March 5, 2009
• First Posted: March 6, 2009
• Study Start: November 1, 2008
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: December 11, 2013

Record last verified: 2013-12

Locations

IT (1)