Longitudinal association of fatty pancreas with the incidence of type-2 diabetes in lean individuals: a 6-year computed tomography-based cohort study

Background: Only a few studies have longitudinally evaluated whether fatty pancreas increases the risk of type-2 diabetes (T2D), and their results were inconsistent. Fatty pancreas is closely linked to overweight and obesity, but previous studies did not exclude overweight or obese individuals. Therefore, in this cohort study, we investigated the association between fatty pancreas and T2D incidence in lean individuals. Methods: Between 2008 and 2013, 1478 nondiabetic lean individuals (i.e. body-mass index < 25 kg/m²) underwent health examinations including computed tomography (CT) and were followed for a median of 6.19 years. Fatty pancreas was evaluated by a histologically-validated method using pancreas attenuation (Hounsfield units [HU]) on CT at baseline; lower pancreas attenuation indicates more pancreatic fat. To detect incident T2D, we used fasting plasma glucose, HbA1c, and self-reports of prescribed anti-diabetes medications. Odds ratios (OR) for the association between pancreas attenuation and incident T2D were estimated using logistic regression models adjusted for likely confounders. Results: T2D occurred in 61 participants (4.13%) during the follow-up period. Lower pancreas attenuation (i.e. more pancreatic fat) at baseline was associated with incident T2D (unadjusted OR per 10 HU lower attenuation: 1.56 [95% CI 1.28–1.91], p < 0.001). The multivariable-adjusted analysis revealed a similar association (adjusted OR per 10 HU lower attenuation: 1.32 [95% CI 1.06–1.63], p = 0.012). Conclusions: T2D was likely to develop in lean individuals with the fatty pancreas. Among people who are neither obese nor overweight, the fatty pancreas can be used to define a group at high risk for T2D.