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Reduced insulin clearance differently relates to increased liver lipid content and worse glycemic control in recent-onset type 2 and type 1 diabetes mellitus

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posted on 2023-10-24, 20:37 authored by Oana-Patricia Zaharia, Sofia Antoniou, Pavel Bobrov, Yanislava Karusheva, Kálmán Bódis, Yuliya Kupriyanova, Vera B. Schrauwen-Hinderling, Amalia Gastaldelli, Julia Szendroedi, Robert Wagner, Volker Burkart, Michael Roden

Objective: Diabetes mellitus may feature impaired insulin kinetics, which could be aggravated by altered hepatic metabolism and glycemic control. Thus, we examined insulin clearance and its possible determinants in persons with recent-onset diabetes. Research design and methods: Participants of the German Diabetes Study (GDS) with type 1 diabetes (T1D; n=306), type 2 diabetes (T2D; n=489) or normal glucose tolerance (CON; n=167) underwent hyperinsulinemic-euglycemic clamps to assess whole-body insulin sensitivity (M-value) and insulin clearance (ICCLAMP). Insulin clearance rates were further calculated during intravenous glucose (ICIVGTT) and mixed meal tolerance tests (ICMMT). Hepatocellular lipid content (HCL) was quantified by 1H-magnetic resonance spectroscopy. Results: Both T1D and T2D had lower ICCLAMP (0.12±0.07 and 0.21±0.06 vs. 0.28±0.14, all p<0.05) and ICMMT than CON (0.71±0.35 and 0.99±0.33 vs. 1.20±0.36, all p<0.05). In T1D, ICCLAMP, ICIVGTT, ICMMT correlated negatively with HbA1c (all p<0.05). M-value correlated positively with ICIVGTT in CON and T2D (r=0.199 and r=0.178, p<0.05) and with ICMMT in CON (r=0.176, p<0.05). HCL negatively associated with ICIVGTT and ICMMT in T2D (r=-0.005 and r=-0.037) and CON (r=-0.127 and r=-0.058, all p<0.05). In line, T2D or CON with steatosis featured lower ICMMT than those without steatosis (both p<0.05). Conclusions: Insulin clearance is reduced in both type 1 and type 2 diabetes already within the first year after diagnosis, but correlates negatively with liver lipid content rather in type 2 diabetes. Moreover, insulin clearance differently associates with glycemic control and insulin sensitivity may suggest specific mechanisms affecting insulin kinetics.

Funding

This study was supported in part by the German Diabetes Center (DDZ), The GDS was initiated and financed by German Diabetes Center (DDZ), which is funded by the Ministry of Culture and Science of the State of Northrhine Westphalia and the German Federal Ministry of Health (BMG), by grants of the Federal Ministry for Research (BMBF) to the German Center for Diabetes Research (DZD e. V., DZD Grant 2016) and the Schmutzler-Stiftung. The research of O.P.Z, is supported by grants from the EFSD (Rising Star Award) and DDG (Adam Heller Prize) and the MODS Initiative (grant PROFILNRW-2020-107-A). The research of M.R. is further supported by grants from the German Research Foundation (DFG, GRK 2576), the German European Community (HORIZON-HLTH-2022-STAYHLTH-02-01: Panel A) to the INTERCEPT-T2D consortium. The sole responsibility for the content of this publication lies with the authors. The funding sources had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

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