Prevention of Type 2 Diabetes Mellitus by L-Arginine in Patients With Metabolic Syndrome
Status:
Completed
Trial end date:
2009-06-01
Target enrollment:
Participant gender:
Summary
Aim
The principal objective of this project is:
• To evaluate the efficacy of long term (18 months) L-Arginine therapy in preventing or
delaying clinical onset of type 2 diabetes mellitus in subjects with impaired glucose
tolerance (IGT) and Metabolic Syndrome.
Secondary end points are:
1. To define if a long term treatment with L-arginine is able to ameliorate insulin
sensitivity and endothelial dysfunction in this population.
2. To find new risk profiles and candidate genes able to define the sub-group of patients
at higher risk to develop type 2 diabetes mellitus.
Methodology This is a double blind, parallel, one centre study to determine if long term oral
L-arginine administration is able to delay or prevent type 2 diabetes mellitus in patients
with Metabolic Syndrome. Two hundred and ninety four subjects were recruited at the
Cardio-Metabolic and Clinical Trials Unit of the San Raffaele Scientific Institute. One
hundred and forty two patients were randomized to enter the study and assigned to two arms:
oral L-arginine (6.4 g/die) or placebo, in addition to diet and physical exercise. The
treatment were maintained for 18 months. Visits were performed every 3 months for clinical
evaluation, blood samples, treatment supply and collection of data on adverse events.
Furthermore, patients were contacted every month by telephone to evaluate the accurate
continuation of the study and they were instructed to phone to the centre in case of possible
adverse events.
An OGTT were performed before the enter into the study and at the end of the study period. An
additional OGTT were performed at an intermediate visit if fasting glucose levels were more
than 126 mg/dl. A diabetic response caused the end-point of the patient. Metabolic, hormonal
and endothelial activation and inflammation parameters were measured. Evaluation of
endothelium-mediated and non-endothelium-mediated vasodilatation were performed by strain
gauche plethysmography evaluating forearm blood at the basal state. in post-ischemic
conditions and after nitroglycerine administration.
Before the enter into the study, an additional blood sample were drawn for DNA extraction and
candidate genes variants evaluation. Before the enter into the study and at the end of the
study period, gene expression for inflammation were measured on mRNA extraction on
endothelial progenitor cells.