@article{75388ca02a104812a2f3883146b722b3,
title = "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",
abstract = "Aims/hypothesisIndividuals 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 6weeks 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.MethodsWe included ten Dutch South Asian men (age 46.52.8years, BMI 30.11.1kg/m(2)) and ten Dutch men of European descent, that were similar with respect to age and BMI, with prediabetes (fasting plasma glucose level 5.6-6.9mmol/l or plasma glucose levels 2h after an OGTT 7.8-11.1mmol/l). Participants took either l-arginine (9g/day) or placebo orally for 6weeks in a randomised double-blind crossover study. Participants were eligible to participate in the study when they were aged between 40 and 55years, had a BMI between 25 and 35kg/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 [F-18]fluorodeoxyglucose ([F-18]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.Resultsl-Arginine did not affect BMR, [F-18]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",
keywords = "Brown adipose tissue, l-Arginine, Nitric oxide, Skeletal muscle, South Asian, INSULIN SENSITIVITY, MITOCHONDRIAL DYSFUNCTION, GLUCOSE-UPTAKE, WEIGHT-LOSS, OBESE, PREVALENCE, DIET, FAT, SUPPLEMENTATION, BIOGENESIS",
author = "Boon, {Mariette R.} and Hanssen, {Mark J. W.} and Boudewijn Brans and Hulsman, {Cindy J. M.} and Joris Hoeks and Nahon, {Kimberly J.} and Charlotte Bakker and {van Klinken}, {Jan B.} and Bas Havekes and Gert Schaart and Jazet, {Ingrid M.} and Rensen, {Patrick C. N.} and {van Marken Lichtenbelt}, {Wouter D.}",
note = "Funding Information: Funding WDvML receives funding from the EU FP7 project DIABAT (HEALTH-F2-2011-278373) and the Netherlands Organization for Scientific Research (TOP 91209037). MRB is supported by the Netherlands Organization for Scientific Research (Rubicon 825.13.021) and the Dutch Diabetes Research Foundation (junior postdoc fellowship; 2015.81.1808). JH is supported by a Vidi grant (917.14.358) for innovative research from the Netherlands Organization for Scientific Research. PCNR is Established Investigator of the Dutch Heart Foundation (2009T038). Funding Information: cold-induced glucose oxidation (+44%, p < 0.05) in Europids only. Of note, in skeletal muscle biopsies several respiration states were consistently lower in South Asian men compared with Europid men. Conclusions/interpretation L-Arginine supplementation does not affect BMR, [18F]FDG uptake by BAT, or skeletal muscle mitochondrial respiration in Europid and South Asian overweight and prediabetic men. However, L-arginine improves glucose tolerance in Europids but not in South Asians. Furthermore, South Asian men have lower skeletal muscle oxidative capacity than men of European descent. Funding This study was funded by the EU FP7 project DIABAT, the Netherlands Organization for Scientific Research, the Dutch Diabetes Research Foundation and the Dutch Heart Foundation. Trial registration: ClinicalTrials.gov NCT02291458. Funding Information: l -Arginine (Argimax [l -arginine hydrochloride]) and placebo supplements were kindly provided by Hankintatukku (Karkkila, Finland), who had no further role in the conduct of the study and the interpretation of data. The technical assistance of H. Sips (Department of Medicine, Leiden University Medical Center) is highly appreciated. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. WDvML receives funding from the EU FP7 project DIABAT (HEALTH-F2-2011-278373) and the Netherlands Organization for Scientific Research (TOP 91209037). MRB is supported by the Netherlands Organization for Scientific Research (Rubicon 825.13.021) and the Dutch Diabetes Research Foundation (junior postdoc fellowship; 2015.81.1808). JH is supported by a Vidi grant (917.14.358) for innovative research from the Netherlands Organization for Scientific Research. PCNR is Established Investigator of the Dutch Heart Foundation (2009T038). Mari?tte R. Boon and Mark J. W. Hanssen are joint first authors. The authors declare that there is no duality of interest associated with this manuscript. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2019",
month = jan,
doi = "10.1007/s00125-018-4752-6",
language = "English",
volume = "62",
pages = "112--122",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer, Cham",
number = "1",
}