Investigation of hepatic gluconeogenesis pathway in non-diabetic Asian Indians with non-alcoholic fatty liver disease using in vivo (³¹P) phosphorus magnetic resonance spectroscopy

Abstract

Objective: To study hepatic gluconeogenesis pathway in non-diabetic Asian Indian males having non-alcoholic fatty liver disease (NAFLD) using in vivo (³¹P) 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 ³¹P 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/γATP, PME/βATP, 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 ³¹P 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.