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. 2025 Dec 1;48(12):2031-2035.
doi: 10.2337/dc24-2023.

Role of Adipose Tissue Compartments for Cardiovascular Risk in Diabetes Endotypes

Oana-Patricia Zaharia  1   2   3 , Yuliya Kupriyanova  2   3 , Pavel Bobrov  2   4 , Christian Binsch  1   2   3 , Birgit Knebel  2   5 , Tim Mori  2   4 , Iryna Yurchenko  2   3 , Dania Marel Mendez Cardenas  2   3 , Theresa Kössler  1   2   3 , Nina Trinks  2   3 , Martin Schön  1   2   3 , Kálmán B Bódis  1   2   3 , Robert Wagner  1   2   3 , Vera Schrauwen-Hinderling  2   3 , Michael Roden  1   2   3 ; GDS Group*
Collaborators, Affiliations

Role of Adipose Tissue Compartments for Cardiovascular Risk in Diabetes Endotypes

Oana-Patricia Zaharia et al. Diabetes Care. .

Abstract

Objective: The severe insulin-resistant diabetes (SIRD) endotype is associated with metabolic dysfunction-associated steatotic liver disease and higher cardiovascular risk. We investigated whether skeletal muscle or adipose tissue lipids are elevated in SIRD.

Research design and methods: Participants (N = 420) of the German Diabetes Study (GDS) were assigned to diabetes clusters using a validated algorithm. 1H-magnetic resonance methods were used to quantify intramyocellular lipids (IMCLs), intrahepatic lipids (IHLs), and visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes.

Results: Aside from elevated IHLs (P < 0.01), SIRD showed higher VAT and SAT than other endotypes after adjustment for BMI (all P < 0.05) but not for multiple comparisons. All endotypes featured comparable IMCLs. VAT volume and IHLs correlated with cardiovascular risk scores (Framingham r = 0.661 and 0.548, respectively, P < 0.05). Polygenic risk scores for VAT were associated with higher cardiovascular risk.

Conclusions: SIRD features higher IHLs and nominally higher VAT volume, which likely contribute to increased cardiovascular risk, highlighting implications for tailored prevention and treatment.

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Conflict of interest statement

Duality of Interest. O.-P.Z. reported receiving lecture fees from Sanofi and Chiesi. R.W. reported receiving lecture fees from Novo Nordisk, Sanofi, and Eli Lilly and served on advisory boards for Akcea Therapeutics, Daiichi Sankyo, Sanofi, Eli Lilly, and Novo Nordisk. M.R. reported receiving fees for lecturing and/or advisory board activities from AstraZeneca, Boehringer Ingelheim Pharma, Echosens, Eli Lilly, Madrigal, MSD, Novo Nordisk, and Synlab and investigator-initiated studies from Boehringer Ingelheim, Novo Nordisk, and Sanofi. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
Lipid content and adipose tissue volumes stratified by cluster. Violin plots showing minimum, maximum, median, and interquartile range. A: IHLs. B: IMCLs. C: VAT. D: SAT. E: PGS_VAT_adj. F: PGS_ASAT_adj. *P < 0.05, **P < 0.05 after adjustment for multiple comparisons. a.u., arbitrary units.
See this image and copyright information in PMC

Comment in

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