Atherosclerosis 203 (2009) 291–297 Investigation of hepatic gluconeogenesis pathway in non-diabetic Asian Indians with non-alcoholic fatty liver disease using in vivo ( 31 P) phosphorus magnetic resonance spectroscopy Rajeev Sharma a , Sanjeev Sinha a , K.A. Danishad d , Naval K. Vikram a , Arun Gupta b , Vineet Ahuja c , N.R. Jagannathan d , R.M. Pandey e , Anoop Misra a,f,∗ a Department of Internal Medicine, All India Institute of Medical Sciences, New Delhi, India b Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India c Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India d Department of Nuclear Magnetic Resonance, All India Institute of Medical Sciences, New Delhi, India e Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India f Department of Diabetes and Metabolic Diseases, Fortis Hospitals, New Delhi, and Diabetes Foundation (India), India Received 14 March 2008; received in revised form 9 June 2008; accepted 13 June 2008 Available online 26 June 2008 Abstract Objective: To study hepatic gluconeogenesis pathway in non-diabetic Asian Indian males having non-alcoholic fatty liver disease (NAFLD) using in vivo ( 31 P) phosphorous magnetic resonance spectroscopy (MRS) and correlate these data with anthropometry and insulin resistance. Research design and methods: Forty non-diabetic patients with NAFLD and 20 healthy controls were divided into (i) obese with NAFLD (group I, n = 20), (ii) non-obese with NAFLD (group II, n = 20) and (iii) non-obese without NAFLD (group III, n = 20). Anthropometric and biochemical profiles, short insulin tolerance test (SITT), liver ultrasound, and 31 P MRS (to determine hepatic gluconeogenesis metabolite; phosphomonoesters (PMEs), inorganic phosphate (Pi) and their ratios with respect to ATP) were done. Results: Insulin resistance (Kitt value) was highest in group I (p < 0.05; compared to other two groups), but was also higher in group II as compared to group III (p = ns). The values of PME/Pi, PME/ATP, PME/ATP, PME/tATP ratios were higher (p < 0.05) in group I compared to other two groups. Interestingly, non-obese subjects with NAFLD also showed more derangements of hepatic gluconeogenesis metabolites than non-obese subjects without NAFLD. Positive correlation was observed between PME and other ratios in relation to body mass index, waist circumference, body fat percentage and fasting serum insulin levels in all the three groups. Conclusions: Derangements in hepatic gluconeogenesis as assessed non-invasively using 31 P MRS, was observed in obese and non-obese, non-diabetic Asian Indians with NAFLD. Further research is warranted whether this investigation in NAFLD subjects could be developed as a non-invasive tool to assess those predisposed to develop hyperglycemia. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Non-alcoholic fatty liver; Phosphorus magnetic resonance spectroscopy; Short insulin tolerance test; Phosphomonoesters; Chemical shift imaging 1. Introduction Normal liver contains approximately 5 g of lipids per 100 g of wet weight. Hepatic steatosis (fatty liver) is the term used ∗ Corresponding author at: Department of Diabetes and Metabolic Dis- eases Fortis Flt. Lt. Rajan Dhall Hospital, Sector B, Pocket 1, Vasant Kunj, New Delhi 110070, India. Tel.: +91 11 4277 6222x5030; fax: +91 11 4277 6221. E-mail address: anoopmisra@metabolicresearchindia.com (A. Misra). when lipids, predominantly triglycerides, in liver are more than 5% of liver weight [1,2]. NAFLD is defined as pres- ence of fat in liver with/without presence of inflammation or fibrosis in a person taking less than 20 g of alcohol per day [3]. Data from developed countries indicate prevalence of hepatic steatosis to be 20–25% [4]. It is increasingly becom- ing apparent that NAFLD is another feature of the metabolic syndrome, with insulin resistance being the common fac- tor. The strong association of NAFLD with other features 0021-9150/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2008.06.016