In humans increase in intrapancreatic adipose tissue predicts beta-cell dedifferentiation score before diabetes...

The role of intrapancreatic fat (WAT) in the development of T2D remains debated. In T2D, β-cell dedifferentiation is one of the mechanisms responsible for β-cell failure but its role in prediabetes is unknown. We aimed to investigate the relation between WAT and β-cell dedifferentiation prior to diabetes onset.

We evaluated pancreatic samples from patients without history of diabetes, who had previously undergone an oral glucose tolerance test and hyperglycemic clamp. Subjects were divided into 3 glucose tolerance groups: normal (NGT), altered (IGT) or newly diagnosed diabetes (nDM). Dedifferentiation and WAT% were morphologically assessed.

WAT was higher in nDM patients compared to NGT and IGT (WAT nDM 43.79 ± 20.83 %, IGT 10.67 ± 8.5 %, NGT 4.43 ± 4.37 %). We observed a progressive increase in dedifferentiation score, in parallel with worsening glucose tolerance (from NGT to IGT to nDM; 4.8 ± 3.8; 32.37 ± 7.4; 40.38 ± 19 respectively). A strong linear regression established that WAT could statistically significantly predict dedifferentiated β-cells (R = 0.86, p = 0.005), and that the predicted increase in dedifferentiated β-cells was 1.25 points for every extra one-point change in WAT. Interestingly, the WAT and dedifferentiation score variable pair were significantly related to 1-hour post-load glycemia.

The accumulation of WAT might be responsible for dedifferentiation, making it a potential new target to curb diabetes onset.