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Observational Study
. 2024 Sep 3;23(1):326.
doi: 10.1186/s12933-024-02420-x.

Metabolically "extremely unhealthy" obese and non-obese people with diabetes and the risk of cardiovascular adverse events: the Silesia Diabetes - Heart Project

Oliwia Janota  1   2   3 , Marta Mantovani  4   5 , Hanna Kwiendacz  6 , Krzysztof Irlik  7   8 , Tommaso Bucci  4   9 , Steven H M Lam  4 , Bi Huang  4   10 , Uazman Alam  4   11   12 , Giuseppe Boriani  5 , Mirela Hendel  8 , Julia Piaśnik  8 , Anna Olejarz  8 , Aleksandra Włosowicz  8 , Patrycja Pabis  8 , Wiktoria Wójcik  8 , Janusz Gumprecht  6 , Gregory Y H Lip  4   13 , Katarzyna Nabrdalik  6   4
Affiliations
Observational Study

Metabolically "extremely unhealthy" obese and non-obese people with diabetes and the risk of cardiovascular adverse events: the Silesia Diabetes - Heart Project

Oliwia Janota et al. Cardiovasc Diabetol. .

Abstract

Background: There is a growing burden of non-obese people with diabetes mellitus (DM). However, their cardiovascular risk (CV), especially in the presence of cardiovascular-kidney-metabolic (CKM) comorbidities is poorly characterised. The aim of this study was to analyse the risk of major CV adverse events in people with DM according to the presence of obesity and comorbidities (hypertension, chronic kidney disease, and dyslipidaemia).

Methods: We analysed persons who were enrolled in the prospective Silesia Diabetes Heart Project (NCT05626413). Individuals were divided into 6 categories according to the presence of different clinical risk factors (obesity and CKM comorbidities): (i) Group 1: non-obese with 0 CKM comorbidities; (ii) Group 2: non-obese with 1-2 CKM comorbidities; (iii) Group 3: non-obese with 3 CKM comorbidities (non-obese "extremely unhealthy"); (iv) Group 4: obese with 0 CKM comorbidities; (v) Group 5: obese with 1-2 CKM comorbidities; and (vi) Group 6: obese with 3 CKM comorbidities (obese "extremely unhealthy"). The primary outcome was a composite of CV death, myocardial infarction (MI), new onset of heart failure (HF), and ischemic stroke.

Results: 2105 people with DM were included [median age 60 (IQR 45-70), 48.8% females]. Both Group 1 and Group 6 were associated with a higher risk of events of the primary composite outcome (aHR 4.50, 95% CI 1.20-16.88; and aHR 3.78, 95% CI 1.06-13.47, respectively). On interaction analysis, in "extremely unhealthy" persons the impact of CKM comorbidities in determining the risk of adverse events was consistent in obese and non-obese ones (Pint=0.824), but more pronounced in individuals aged < 65 years compared to older adults (Pint= 0.028).

Conclusion: Both non-obese and obese people with DM and 3 associated CKM comorbidities represent an "extremely unhealthy" phenotype which are at the highest risk of CV adverse events. These results highlight the importance of risk stratification of people with DM for risk factor management utilising an interdisciplinary approach.

Keywords: Cardiovascular events; Comorbidities; Diabetes mellitus; Metabolically unhealthy; Obesity.

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Conflict of interest statement

G.Y.H.L. is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Anthos and Daiichi-Sankyo. No fees are received personally. G.Y.H..L is a NIHR Senior Investigator and co-PI of the AFFIRMO project on multimorbidity in AF (grant agreement No 899871), TARGET project on digital twins for personalised management of atrial fibrillation and stroke (grant agreement No 101136244) and ARISTOTELES project on artificial intelligence for management of chronic long term conditions (grant agreement No 101080189), which are all funded by the EU’s Horizon Europe Research & Innovation programme. G.B. is Study Coordinator of ARISTOTELES (Applying ARtificial Intelligence to define clinical trajectorieS for personalized predicTiOn and early deTEction of comorbidity and muLtimorbidity pattErnS) Grant from Horizon Europe (HORIZON-HLTH-2022-STAYHLTH-01- Grant 101080189). G.B. received small speaker’s fee from Bayer, Boston, Boehringer Ingelheim, Brystol Myers Squibb, Janssen, and Sanofi. UA has received honoraria from Eli Lilly, Procter & Gamble, Viatris, Grunenthal and Sanofi for educational meetings and funding for attendance to an educational meeting from Diiachi Sankyo. UA has also received investigator-led funding by Procter & Gamble and is a council member of the Royal Society of Medicine's Vascular, Lipid & Metabolic Medicine Section. HK received remunerations/fees for activities on behalf of Sanofi-Aventis, Eli Lilly, Novo Nordisk, Servier, Astra-Zeneca, Boehringer-Ingelheim. JG received remunerations/fees for activities on behalf of Sanofi-Aventis, Eli Lilly, Novo Nordisk, Servier, Astra-Zeneca, Boehringer-Ingelheim, Bioton, Polfa Tarchomin, Medtronic, Roche, and Abbott. KN received remunerations/fees for activities on behalf of Sanofi-Aventis, Eli Lilly, Novo Nordisk, Servier, Astra-Zeneca, Boehringer-Ingelheim, Bioton, Polfa Tarchomin, Roche, and Abbott. All other authors report no disclosures.

Figures

Fig. 1
Fig. 1
Flowchart of the study. BMI, body mass index; CKM cardiovascular-kidney-metabolic
Fig. 2
Fig. 2
Kaplan Meier curve for the primary outcome according to the different clinical risk groups. CKM, cardiovascular-kidney-metabolic; Group 1, non-obese with 0 CKM comorbidities; Group 2, non-obese with 1-2 CKM comorbidities; Group 3, non-obese with 3 CKM comorbidities; Group 4, obese with 0 CKM comorbidities; Group 5, obese with 1-2 CKM comorbidities; Group 6, obese with 3 CKM comorbidities
Fig. 3
Fig. 3
Interaction analysis on the risk of the primary outcome according to the “extremely unhealthy” status. CI, confidence interval; DM, diabetes mellitus; HR, hazard ratio. Adjusted for age, sex, duration of diabetes, current smoking, previous CAD
See this image and copyright information in PMC

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