Background and Objective Excess hepatic and pancreatic fat may contribute to hyperglycemia. The objective of this study was to examine the effect of dapagliflozin (SGLT-2 inhibitor) on anthropometric profile, liver, and pancreatic fat in patients with type 2 diabetes mellitus (T2DM). Research Design and Methods This is an observational interventional paired study design without a control group. Patients (n, 30) were given dapagliflozin 10mg/day (on top of stable dose of metformin and/or sulphonylureas) for a period of 120 days. Changes in anthropometry (circumferences and skinfold thickness), surrogate markers of insulin resistance, body composition, liver, and pancreatic fat (as were measured by MRI-derived proton density fat fraction) were evaluated. Result After 120 days of treatment with dapagliflozin, a significant reduction in weight, body mass index (BMI), body fat, circumferences, and all skinfold thickness was seen. A significant reduction in blood glucose, hemoglobin A1c, hepatic transaminases, fasting insulin, homeostatic model assessment –insulin resistance (HOMA-IR), and postprandial C-peptide was noted while HOMA-beta, post parandial insulin sensitivity and fasting adiponectin were significantly increased. There was no change in lean body mass. Compared to baseline there was a significant decrease in mean liver fat fraction (from15.2 to 10.1%, p <0.0001) and mean pancreatic fat fraction (from 7.5 to 5.99%, p <0.0083). Reduction in liver fat was significant after adjustment for change in body weight. Conclusion Dapagliflozin, after 120 days of use, reduced pancreatic and liver fat and increased insulin sensitivity in Asian Indian patients with T2DM.
The Asian-Indian phenotype of type 2 diabetes mellitus is uniquely characterized for cardiometabolic risk. In the context of implementing patient-centric holistic cardio-metabolic risk management as a priority, the choice of various combinations of antidiabetic agents should be individualized. Combined therapy with two classes of antidiabetic agents, namely, dipeptidyl peptidase 4 inhibitors and sodiumglucose co-transporter-2 inhibitors, target several pathophysiological pathways. The wideranging clinical outcomes associated with this combination, including improvement of glycemia and adiposity, reduction of metabolic and vascular risk, safety, and simplicity for sustainable compliance, are extremely relevant to the Asian Indian patient population living with T2DM. In this review we describe the available evidence in detail and present a rational
Background: Genetics of non-alcoholic fatty liver (NAFLD) in Asian Indians has been inadequately investigated. This study aims to determine the association of the 1784G > C polymorphism in the SREBP-2 gene with NAFLD in Asian Indians in north India. Methods: In this study, (n = 335); 162 obese with NAFLD, 91 obese without NAFLD and 82 non-obese without NAFLD subjects were recruited. Abdominal ultrasound, clinical profile, anthropometry, metabolic profile, serum levels of alanine aminotransferase, aspartate aminotransferase, fasting insulin and high sensitivity C-reactive protein (hs-CRP) were analysed. Polymerase chain reaction and restriction fragment length polymorphism were used to identify individual genotypes, and the association of this polymorphism with clinical and biochemical parameters was assessed. Results: The observed frequency of G allele was 0.73 and C allele was 0.27. Frequency of C/C genotype was higher in NAFLD as compared to obese and non-obese subjects (p = 0.003). In NAFLD subjects 57.4% were G/G homozygous, 31.5% G/C heterozygous and 11.1% were C/C homozygous. The SREBP-2 genotype frequencies deviated from the Hardy Weinberg Equilibrium (X2 = 6.39, p = 0.0114). Mean values of TG (p = 0.002), TC (p = 0.002), ALT (p = 0.04) and AST (p =0.03) levels were significantly higher in NAFLD subjects with G/C genotype as compared to G/G genotypes in obese and non-obese groups. Fasting insulin (p = 0.03), HOMA (p = 0.009) and hs-CRP levels were significantly higher in NAFLD subjects with G/C genotype as compared to obese and non obese subjects with G/G genotypes. Conclusion: In this study, conducted for the first time in Asian Indians, SREBP-2 1784 G > C genotype was associated with NAFLD.
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