Effect of l-arginine on energy metabolism, skeletal muscle and brown adipose tissue in South Asian and Europid prediabetic men: a randomised double-blinded crossover study

Aims/hypothesis Individuals of South Asian origin are at increased risk of developing type 2 diabetes mellitus and associated comorbidities compared with Europids. Disturbances in energy metabolism may contribute to this increased risk. Skeletal muscle and possibly also brown adipose tissue (BAT) ar...

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Bibliographic Details
Published in:Diabetologia 2019-01, Vol.62 (1), p.112-122
Main Authors: Boon, Mariëtte R., Hanssen, Mark J. W., Brans, Boudewijn, Hülsman, Cindy J. M., Hoeks, Joris, Nahon, Kimberly J., Bakker, Charlotte, van Klinken, Jan B., Havekes, Bas, Schaart, Gert, Jazet, Ingrid M., Rensen, Patrick C. N., van Marken Lichtenbelt, Wouter D.
Format: Article
Language:English
Subjects:
Adipose tissue
Adipose tissue (brown)
Adipose Tissue, Brown - drug effects
Adipose Tissue, Brown - metabolism
Adult
Arginine
Arginine - therapeutic use
Biopsy
Blood Glucose
Body Mass Index
Body weight
Calorimetry
Computed tomography
Cross-Over Studies
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Double-Blind Method
Electron transport
Energy metabolism
Energy Metabolism - drug effects
Ethnicity
Fasting
Glucose
Glucose metabolism
Glucose tolerance
Human Physiology
Humans
Insulin
Internal Medicine
Laboratory testing
Male
Medicine
Medicine & Public Health
Mens health
Metabolic Diseases
Metabolic rate
Metabolism
Middle Aged
Minority & ethnic groups
Mitochondria
Muscle, Skeletal - drug effects
Muscle, Skeletal - metabolism
Musculoskeletal system
Nitric oxide
Overweight
Oxidation
Positron emission tomography
Prediabetic State
Respiration
Skeletal muscle
Supplements
Thermogenesis - drug effects
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Summary:Aims/hypothesis Individuals of South Asian origin are at increased risk of developing type 2 diabetes mellitus and associated comorbidities compared with Europids. Disturbances in energy metabolism may contribute to this increased risk. Skeletal muscle and possibly also brown adipose tissue (BAT) are involved in human energy metabolism and nitric oxide (NO) is suggested to play a pivotal role in regulating mitochondrial biogenesis in both tissues. We aimed to investigate the effects of 6 weeks of supplementation with l -arginine, a precursor of NO, on energy metabolism by BAT and skeletal muscle, as well as glucose metabolism in South Asian men compared with men of European descent. Methods We included ten Dutch South Asian men (age 46.5 ± 2.8 years, BMI 30.1 ± 1.1 kg/m 2 ) and ten Dutch men of European descent, that were similar with respect to age and BMI, with prediabetes (fasting plasma glucose level 5.6–6.9 mmol/l or plasma glucose levels 2 h after an OGTT 7.8–11.1 mmol/l). Participants took either l -arginine (9 g/day) or placebo orally for 6 weeks in a randomised double-blind crossover study. Participants were eligible to participate in the study when they were aged between 40 and 55 years, had a BMI between 25 and 35 kg/m 2 and did not have type 2 diabetes. Furthermore, ethnicity was defined as having four grandparents of South Asian or white European origin, respectively. Blinding of treatment was done by the pharmacy (Hankintatukku) and an independent researcher from Leiden University Medical Center randomly assigned treatments by providing a coded list. All people involved in the study as well as participants were blinded to group assignment. After each intervention, glucose tolerance was determined by OGTT and basal metabolic rate (BMR) was determined by indirect calorimetry; BAT activity was assessed by cold-induced [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography–computed tomography scanning. In addition, a fasting skeletal muscle biopsy was taken and analysed ex vivo for respiratory capacity using a multisubstrate protocol. The primary study endpoint was the effect of l -arginine on BAT volume and activity. Results l -Arginine did not affect BMR, [ 18 F]FDG uptake by BAT or skeletal muscle respiration in either ethnicity. During OGTT, l -arginine lowered plasma glucose concentrations (AUC 0–2 h  − 9%, p  
ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-018-4752-6