1657-P: Patatin-Like Phospholipase Domain-Containing 3 Gene Indirectly Modulates Hepatocellular Lipid Content in Severe Insulin Resistant Diabetes

The G-allele in the single-nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase domain containing 3 (PNPLA3) gene associates with increased risk of nonalcoholic fatty liver disease (NAFLD) and its progression. As the recently-described severe insulin resistant diabetes (SIRD) cluster specifically relates to NAFLD, the present study examined whether this SNP differently associates with insulin sensitivity and hepatic lipid content (HCL) in clusters of new-onset diabetes patients. Participants (n=917) of the prospective German Diabetes Study underwent genotyping, hyperinsulinemic-euglycemic clamps and magnetic resonance spectroscopy. SIRD had the lowest whole-body insulin sensitivity compared to severe insulin deficient (SIDD), moderate obesity-related (MOD), moderate age-related (MARD) and severe autoimmune diabetes clusters (SAID; all p