Endocrine Abstracts

Introduction: It is not known if non-alcoholic fatty liver disease (NAFLD) predates type 2 diabetes. We will study the prevalence of NAFLD in women with previous gestational diabetes (GDM), a population at ≥60% risk for the development of type 2 diabetes, while glucose tolerance is non-diabetic. It is not known if hepatic fat accumulation in NAFLD is disproportionate to fat accumulation in other tissues. We aim to study the association between fat in the liver and in tissues elsewhere and to relate this to insulin sensitivity, secretion and hepatic insulin extraction.

Methods: Sixty women with previous GDM and 65 controls have been recruited and screened for NAFLD using ultra-sound scanning. BMI- and age-matched women been recruited for further in depth metabolic studies: 8 with previous GDM/NAFLD, 10 with previous GDM/no NAFLD, 9 controls/NAFLD and 10 controls/no NAFLD. MR spectroscopy of the liver, muscle and whole body have been done along with an intravenous glucose tolerance test. Studies have local ethical committee approval.

Results: Preliminary results reveal NAFLD in 32 women with previous GDM versus 11 controls. There was more fat in the liver and the tibialis anterior (TA), an oxidative muscle fibre, in the previous GDM/NAFLD versus the control/NAFLD subjects (median(interquartile range): (21 (24–39) vs 9 (5–19) (P=0.01)) and (14 (13–16) vs 9 (8–13) (P=0.02)), respectively. Across the groups intra-hepatic fat correlated negatively with insulin sensitivity (Rho: −0.8; P<0.01), and positively with fat in the TA muscle (Rho: +0.7; P<0.01). There was no difference in fat content in the soleus, a non-oxidative muscle fibre in the previous GDM/NAFLD vs. control/NAFLD subjects: (12 (10–14) vs 12 (8–18) (P=0.9)), respectively. Positive correlations between intra-hepatic fat and subcutaneous and intra-abdominal fat depots were demonstrated.

Conclusions: NAFLD may predate type 2 diabetes. At risk groups may be predisposed to intra-hepatic fat accumulation secondary to greater insulin resistance. Increased fat within oxidative muscle fibres may indicate a mitochondrial defect preceding type 2 diabetes. Intra-hepatic fat does not accumulate disproportionately to fat in other tissues.