Hepatic Fat in Participants With and Without Incident Diabetes in the Diabetes Prevention Program Outcome Study

Abstract

Purpose To characterize hepatic fat content and fatty liver prevalence, their determinants, and effect of interventions to prevent diabetes using computerized tomography in a cohort with prediabetes, in those developing diabetes versus not. Methods We measured liver fat as liver attenuation (LA) in Hounsfield units in 1876 participants at ~14 years following randomization into the Diabetes Prevention Program, which tested the effects of lifestyle or metformin interventions versus standard care to prevent diabetes. LA was compared among intervention groups and in those with versus without diabetes, and associations with baseline and follow-up measurements of anthropometric and metabolic covariates were assessed. Results There were no differences in liver fat between treatment groups at 14 years of follow-up. Participants with diabetes had lower LA (mean ± SD: 46±16 vs. 51±14HU; p<0.001) and a greater prevalence of fatty liver (LA<40HU) (34% vs 17%; p<0.001). Severity of metabolic abnormalities at the time of LA evaluation were associated with lower LA categories in a graded manner and more strongly in those with diabetes. Averaged annual fasting insulin (an index of insulin resistance [OR, 95% CI 1.76, 1.41-2.20]) waist circumference (1.63, 1.17-2.26), and triglyceride (1.42, 1.13-1.78), but not glucose, were independently associated with LA<40HU prevalence. Conclusions Fatty liver is common in the early phases of diabetes development. The association of LA with insulin resistance, waist circumference and triglyceride levels emphasizes the importance of these markers for hepatic steatosis in this population and that assessment of hepatic fat in early diabetes development is warranted.

Association of Hepatic Steatosis and Fibrosis Indices With Insulin Sensitivity and Inflammation in the POP-ABC Study

“…The prospective Diabetes Prevention Program (DPP) followed individuals with prediabetes for the primary outcome of progression to T2DM. During year 14 of postrandomization follow-up, liver fat was measured as liver attenuation in Hounsfield units in 1876 DPP participants and compared in progressors to T2DM vs nonprogressors [ 20 ]. The investigators reported that progressors to diabetes had a greater prevalence of fatty liver than nonprogressors [ 20 ].…”

“…During year 14 of postrandomization follow-up, liver fat was measured as liver attenuation in Hounsfield units in 1876 DPP participants and compared in progressors to T2DM vs nonprogressors [ 20 ]. The investigators reported that progressors to diabetes had a greater prevalence of fatty liver than nonprogressors [ 20 ]. Furthermore, the DPP investigators observed significant associations between fatty liver and fasting insulin (an index of insulin resistance), waist circumference, and serum triglycerides [ 20 ].…”

“…The investigators reported that progressors to diabetes had a greater prevalence of fatty liver than nonprogressors [ 20 ]. Furthermore, the DPP investigators observed significant associations between fatty liver and fasting insulin (an index of insulin resistance), waist circumference, and serum triglycerides [ 20 ]. The report from the prospective DPP suggests that the well-known cross-sectional association between hepatic steatosis and T2DM probably has an earlier origin, perhaps during the prediabetes stage.…”

“…The report from the prospective DPP suggests that the well-known cross-sectional association between hepatic steatosis and T2DM probably has an earlier origin, perhaps during the prediabetes stage. However, the lack of baseline data on hepatic steatosis, when all DPP participants were at the prediabetes stage, makes it difficult to interpret the longitudinal findings observed after 14 years of follow-up [ 20 ]. Although the DPP participants who developed diabetes during 14 years of follow-up had greater amounts of liver fat than nonprogressors, the direction of the association cannot be ascertained without baseline liver fat data.…”

A Strategic Research Framework for Defeating Diabetes in India: A 21st-Century Agenda

“…[29][30][31] Moreover, Indian diets are low in high-quality protein. 32 Very few studies have examined the association between hepatic fat and the risk of diabetes, 33,34 although the Chennai Urban Rural Epidemiology (CURES) study found that hepatic fat was associated with progression from pre-diabetes to diabetes. 35 As recent data suggest that Indians are at high risk of hepatic fat deposition, and overall visceral adiposity is higher in Indians than in Europeans, 36,37 suitable methods are needed to clearly discriminate between ectopic, visceral, and hepatic fat depositionopening avenues for imaging and artificial intelligence research.…”