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. 2023 Dec 1;46(12):2232-2239.
doi: 10.2337/dc23-1267.

Reduced Insulin Clearance Differently Relates to Increased Liver Lipid Content and Worse Glycemic Control in Recent-Onset Type 2 and Type 1 Diabetes

Oana-Patricia Zaharia  1   2   3 , Sofia Antoniou  2 , Pavel Bobrov  3   4 , Yanislava Karusheva  2   3 , Kálmán Bódis  1   2   3 , Yuliya Kupriyanova  2   3 , Vera Schrauwen-Hinderling  2   3 , Amalia Gastaldelli  5 , Julia Szendroedi  6 , Robert Wagner  1   2   3 , Volker Burkart  2   3 , Michael Roden  1   2   3 ; GDS Group
Collaborators, Affiliations

Reduced Insulin Clearance Differently Relates to Increased Liver Lipid Content and Worse Glycemic Control in Recent-Onset Type 2 and Type 1 Diabetes

Oana-Patricia Zaharia et al. Diabetes Care. .

Abstract

Objective: Diabetes 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 individuals 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 (control [CON]) (n = 167) underwent hyperinsulinemic-euglycemic clamps for assessment of whole-body insulin sensitivity (M value) and insulin clearance (ICCLAMP). Insulin clearance rates were further calculated during intravenous glucose tolerance tests (ICIVGTT) and mixed-meal tests (ICMMT). Hepatocellular lipid content (HCL) was quantified with 1H-MRS.

Results: Both T1D and T2D groups had lower ICCLAMP (0.12 ± 0.07 and 0.21 ± 0.06 vs. 0.28 ± 0.14 arbitrary units [a.u.], respectively, all P < 0.05) and ICMMT (0.71 ± 0.35 and 0.99 ± 0.33 vs. 1.20 ± 0.36 a.u., all P < 0.05) than CON. In T1D, ICCLAMP, ICIVGTT, and 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 subjects with steatosis featured lower ICMMT than those without steatosis (both P < 0.05).

Conclusions: Insulin clearance is reduced in both T1D and T2D within the first year after diagnosis but correlates negatively with liver lipid content rather in T2D. Moreover, insulin clearance differently associates with glycemic control and insulin sensitivity in each diabetes type, which may suggest specific mechanisms affecting insulin kinetics.

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Conflict of interest statement

Duality of Interest. M.R. received fees for lectures and/or advisory boards from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Target RWE and investigator-initiated research support from Boehringer Ingelheim, Nutricia/Danone, and Sanofi. O.-P.Z. and R.W. declare lecture fees from Sanofi. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
Measures of insulin clearance. Scatter plots of serum fasting C-peptide (A), whole-body insulin clearance (ICCLAMP) (B), hepatic ICIVGTT (C), and hepatic ICMMT (D) in CON, T1D, and T2D groups. Black lines depict mean values. *P < 0.05. a.u., arbitrary units.
Figure 2
Figure 2
Impact of hepatic steatosis on insulin sensitivity and insulin clearance. Box plots depicting mean ± SD for insulin sensitivity (A), ICCLAMP (B), ICIVGTT (C), and ICMMT (D) in CON, T1D, and T2D with (+S) and without (-S) steatosis. *P < 0.05. n refers to the number of participants in each group for the respective analysis. a.u., arbitrary units.
Figure 3
Figure 3
Correlation between insulin clearance and metabolic parameters. Associations of ICCLAMP, ICIVGTT, and ICMMT with metabolic parameters (HCL) (A, C, and E) and glycemic control (HbA1c) (B, D, and F) in individuals with T1D and T2D. Statistically significant correlations are depicted with linear regression lines and the respective coefficients (r). a.u., arbitrary units.
See this image and copyright information in PMC

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