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06-01-2022 | Diabetes | News | Article

Genetic study backs role for liver fat, pancreatic volume in type 2 diabetes risk

Author: Eleanor McDermid

medwireNews: A genetic propensity for increased liver fat and lower pancreatic volume is associated with an increased risk for type 2 diabetes, say researchers.

However, they report that they “did not identify evidence for a causal role of pancreas fat in type 2 diabetes risk or pancreas volume in type 1 diabetes risk.”

As described in Diabetes Care, Hanieh Yaghootkar (Brunel University London, UK) used data from 32,859 people of White British ancestry who underwent a magnetic resonance imaging scan as participants of the UK Biobank study.

Within this study, each standard deviation (5.06%) increase in liver fat was associated with a significant 2.16-fold increase in the risk for type 2 diabetes.

And Mendelian randomization analysis suggested this was a causal association. The team studied 10 genetic variants associated with liver fat, 11 with liver volume, nine with pancreatic fat, and 17 associated with pancreatic volume. These variants were identified in a previous UK Biobank analysis, but the researchers applied them (or proxy single nucleotide polymorphisms) to data from two genome-wide association studies of diabetes risk.

This revealed that each standard deviation increase in genetically determined liver fat was associated with a 27% increase in type 2 diabetes risk.

The other likely causal association was for pancreatic volume, with each observed standard deviation increase associated with a 27% reduction in type 2 diabetes risk and each genetically determined increase associated with a 24% risk reduction.

In sensitivity analyses (but not the main genetic analysis) there was some causal evidence to support the observed association between higher liver volume and increased type 2 diabetes risk, but the researchers note this could “be a reflection of the correlation between greater liver fat and greater liver volume.”

Furthermore, the observed association between pancreatic fat and type 2 diabetes risk was not supported by the genetic analyses.

“Our results may be consistent with the explanation that higher fat in the pancreas observed in people with type 2 diabetes is secondary to disease or a result of a higher general obesity,” say the researchers.

However, they caution that the genetic variant with the strongest effect on pancreatic fat also influences fat deposition in the body and trunk, and that fat distribution can vary within the pancreas, which may produce variable effects on beta-cell function and type 2 diabetes risk.

For type 1 diabetes, the risk declined with higher observed levels of liver fat and of pancreatic volume, but neither of these associations were supported by the Mendelian randomization analysis.

Commenting on the lack of association with pancreatic volume, the team suggests “that de novo lipogenesis in the liver falls when insulin production stops in type 1 diabetes; therefore, liver fat change is a consequence of insulin loss rather than a cause in type 1 diabetes.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

Diabetes Care 2022; doi:10.2337/dc21-1262

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