Diabetes Remission Clinical Trial (DiRECT)—Plasma Liver Function Tests Reflect Change in Liver Fat Content in Early Type 2 Diabetes

Abstract

We have evaluated changes in liver function tests and liver fat following 12-month weight change in the Tyneside participants of the prospective, randomised Diabetes Remission Clinical Trial (DiRECT). Complete data were available on 45 of the Intervention group participants. The group was typical of early type 2 diabetes: 53.7±1.2 years; 56% male; weight 99.6±2.6 kg; BMI 34.6±0.7 kg/m2, diabetes duration 3.3±0.2 years. Fasting liver fat content was measured by 3-point Dixon MRI. Baseline fasting plasma glucose was 157±7 mg/dl, with liver fat grossly elevated at 16.2±1.5% (mean±SEM; upper level of normal 5.5%). Mean weight loss was 11.5±1.1 kg (0-37kg) and liver fat was normalised at 4.7±0.9% (p<0.0001). With weight losses of >10kg, 5-10kg, <5kg, liver fat decreased to 1.9±0.3%, 5.9±1.4% and 10.2±2.2% respectively. ALT decreased by 51% (32.5±3.0 to 16.0±1.1 U/l; p<0.0001), 37% (31.8±3.8 to 19.9±3.7U/l; p=0.002), and 35% (24.8±4.7 to16.1±1.6 U/l; p=0.058) respectively. Similar reductions were observed in GGT, by 53% (p<0.0001), 35% (p=0.003), 26% (p= 0.05) respectively. Lesser changes were observed in AST, by 29% (p<0.0001), 20% (p=0.29), and 28% (p=0.012) respectively. There were positive correlations between changes in liver fat and ALT (r=0.6, p<0.0001), GGT (r=0.4, p=0.009) and AST (r=0.4, p=0.016). Change in liver fat correlated with weight change (r=0.5, p<0.0001). Following weight loss in type 2 diabetes, changes in ALT and GGT reflect change in liver fat even within the normal range. Early type 2 diabetes is associated with severe nonalcoholic fatty liver disease, and monitoring change by a simple inexpensive blood test is important in clinical practice. Disclosure S.V. Zhyzhneuskaya: None. A. Al-Mrabeh: None. C. Peters: None. A.C. Barnes: None. K.G. Hollingsworth: None. H. Pilkington: None. P. Welsh: Research Support; Self; Boehringer Ingelheim GmbH, Theracos, Inc. N. Sattar: Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S, Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Mitsubishi Tanabe Pharma Corporation, Medscape, Sanofi-Aventis Deutschland GmbH. M.E. Lean: Advisory Panel; Self; Novo Nordisk Inc., Orexigen Therapeutics, Inc.. Research Support; Self; Cambridge Weight Plan. Consultant; Self; Counterweight Ltd. Stock/Shareholder; Self; Eat Balanced. R. Taylor: None.