L-arginine and Brown Adipose Tissue

• Status: Unknown status
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: Male

Summary

The South Asian population is facing an epidemic of type 2 diabetes, of which the underlying cause is still unknown. It is currently hypothesized that an ethnic susceptibility towards a disturbed energy metabolism may underlie this disadvantageous metabolic phenotype. In line with this, the investigators recently discovered that Dutch South Asian subjects have 32% lower resting energy expenditure (REE) and 34% lower energy-combusting brown adipose tissue (BAT) compared to matched white Caucasians. Nitric oxide (NO) was recently shown to be crucial for BAT development and, interestingly, South Asians have diminished NO bioavailability. Thus, the disadvantageous metabolic phenotype in South Asians may be caused by diminished NO bioavailability resulting in lower BAT volume. Therefore, the investigators hypothesize that increasing NO generation in the body by administration of L-arginine, the precursor of NO, will improve their metabolic phenotype by increasing BAT volume, thereby increasing REE and clearance of triglycerides and glucose by BAT. To investigate this, the investigators will perform a randomized placebo-controlled multicenter cross-over study in moderately obese Dutch South Asians and matched white Caucasians. Subjects will receive L-arginine (9 gram/day) or placebo for 6 weeks, followed by a wash-out period of 4 weeks and then again 6 weeks of one of either treatments. At the end of both treatment periods, a cold-induced PET-CT scan will be performed. Furthermore, muscle and fat biopsies will be obtained and thermoregulation will be assessed.

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Maastricht University Medical Center
• Collaborator: Leiden University Medical Center

Criteria

Inclusion Criteria:

• Caucasian or South Asian ethnicity

• Age: 35-50 years

• Gender: male

• BMI: 25-30 kg/m2

• Plasma glucose levels 2 h after OGTT between 7.8 and 11 mM (e.g. impaired glucose tolerance) or Fasting plasma glucose levels > 5.5 mM

• Good general health

Exclusion Criteria:

• Type 2 diabetes (determined on basis of oral glucose tolerance test (OGTT))

• BMI > 30 kg/m2

• Plasma glucose levels 2 h after OGTT < 7.8 mM

• Plasma L-arginine levels < 41 or > 114 uM

• Use of beta-blockers (these inhibit BAT activity) < 1 month before start of study or during study

• Systolic blood pressure < 90 mmHg

• Haematocrit < 0.41 or > 0.51 l/l

• Haemoglobin < 8.5 or > 11.0

• Creatinine (enzymatic method) < 45 or > 100 μmol/L

• ASAT > 45 U/L

• ALAT > 50 U/L

• Alkaline phosphatase > 125 U/L

• Gamma GT > 45 U/L

• Participation in an intensive weight-loss program or vigorous exercise program during the last year before the start of the study

• Abuse of drugs and/or alcohol

• Hyperthyroidism or hypothyroidism

• Participation in earlier research or medical examinations that included PET-CT scanning

• Psychologically unstable subjects (as judged by the treating medical specialist)

• Subjects with mental retardation (as judged by the treating medical specialist)

• Subjects with severe behaviour disorders (as judged by the treating medical specialist)