Insulin resistance in adipose tissue and fatty liver, but not fat mass, are involved in worsening glycaemic status: The Hiroshima study on glucose metabolism and cardiovascular diseases

Abstract Aims Insulin resistance in adipose tissue causes dysregulation of various adipokine levels and ectopic fat accumulation in other organs, such as the liver. This study investigated the effects of insulin resistance in adipose tissue and concomitant fatty liver on each stage of impaired glucose metabolism compared with visceral fat mass. Materials and Methods This observational study included 3644 individuals who underwent two 75‐g oral glucose tolerance tests at baseline and follow‐up. Adipose insulin resistance index (Adipo‐IR), lipid accumulation product (LAP) and fatty liver index (FLI) were used as indicators of insulin resistance in the adipose tissue, visceral fat mass and fatty liver, respectively. Results Over a mean 2.9‐year follow‐up period, 463 (32.4%) individuals progressed from normoglycaemia to prediabetes, and 198 (10.6%) developed type 2 diabetes from prediabetes. Comparing the highest‐to‐lowest quartiles, baseline levels and changes in Adipo‐IR were associated with an increased odds of progression from normoglycaemia to prediabetes (odds ratio [OR], 2.22; 95% CI, 1.36–3.65, OR, 2.70; 95% CI, 1.83–3.98, respectively) and from prediabetes to the onset of type 2 diabetes (OR, 2.02; 95% CI, 1.04–3.92, OR, 3.09; 95% CI, 1.84–4.19, respectively), after adjusting for possible confounders. Changes in FLI were associated with progression from prediabetes to type 2 diabetes. LAP did not affect the progression of impaired glucose metabolism. Conclusions Adipose tissue insulin resistance, rather than fat mass, is crucial in all stages of deterioration of glycaemic status. Fatty liver plays a decisive role in the eventual development of type 2 diabetes.