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• W3035880881 abstract "OBJECTIVE The rs738409(G) single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain–containing 3 (PNPLA3) gene associates with increased risk and progression of nonalcoholic fatty liver disease (NAFLD). As the recently described severe insulin-resistant diabetes (SIRD) cluster specifically relates to NAFLD, this study examined whether this SNP differently associates with hepatic lipid content (hepatocellular lipids [HCL]) and insulin sensitivity in recent-onset diabetes. RESEARCH DESIGN AND METHODS A total of 917 participants in the German Diabetes Study (GDS) underwent genotyping, hyperinsulinemic-euglycemic clamps with stable isotopic tracer dilution, and MRS. RESULTS The G allele associated positively with HCL (β = 0.36, P &lt; 0.01), independent of age, sex, and BMI across the whole cohort, but not in the individual clusters. Those with SIRD exhibited lowest whole-body insulin sensitivity compared with those with severe insulin-deficient (SIDD), moderate obesity-related (MOD), moderate age-related (MARD), and severe autoimmune diabetes (SAID) clusters (all P &lt; 0.001). Interestingly, the SIRD group presented with higher prevalence of the rs738409(G) SNP compared with other clusters and the glucose-tolerant control group (P &lt; 0.05). HCL was higher in the SIRD group (median 13.6% [1st quartile 5.8; 3rd quartile 19.1] compared with the MOD (6.4 % [2.1; 12.4], P &lt; 0.05), MARD (3.0% [1.0; 7.9], P &lt; 0.001), SAID (0.4% [0.0; 1.5], P &lt; 0.001), and glucose-tolerant (0.9% [0.4; 4.9), P &lt; 0.001) group. Although the PNPLA3 polymorphism did not directly associate with whole-body insulin sensitivity in SIRD, the G-allele carriers had higher circulating free fatty acid concentrations and greater adipose tissue insulin resistance compared with noncarriers (both P &lt; 0.001). CONCLUSIONS Members of the SIRD cluster are more frequently carriers of the rs738409(G) variant. The SNP-associated adipose tissue insulin resistance and excessive lipolysis may contribute to their NAFLD." @default.
• W3035880881 created "2020-06-25" @default.
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• W3035880881 date "2020-06-19" @default.
• W3035880881 modified "2023-10-18" @default.
• W3035880881 title "Role of Patatin-Like Phospholipase Domain–Containing 3 Gene for Hepatic Lipid Content and Insulin Resistance in Diabetes" @default.
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• W3035880881 doi "https://doi.org/10.2337/dc20-0329" @default.
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