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Multicenter Study
. 2024 Jun;113(6):822-830.
doi: 10.1007/s00392-023-02268-3. Epub 2023 Aug 22.

Glycaemic control and insulin therapy are significant confounders of the obesity paradox in patients with heart failure and diabetes mellitus

Hanna Fröhlich  1 , Anna Bossmeyer  1 , Syed Kazmi  2 , Kevin M Goode  2 , Stefan Agewall  3 , Dan Atar  3 , Morten Grundtvig  4 , Norbert Frey  1 , John G F Cleland  5   6 , Lutz Frankenstein  7 , Andrew L Clark  2 , Tobias Täger  1
Affiliations
Multicenter Study

Glycaemic control and insulin therapy are significant confounders of the obesity paradox in patients with heart failure and diabetes mellitus

Hanna Fröhlich et al. Clin Res Cardiol. 2024 Jun.

Abstract

Background: A high body mass index (BMI) confers a paradoxical survival benefit in patients with heart failure (HF) or diabetes mellitus (DM). There is, however, controversy whether an obesity paradox is also present in patients with HF and concomitant DM. In addition, the influence of glycaemic control and diabetes treatment on the presence or absence of the obesity paradox in patients with HF and DM is unknown.

Methods: We identified 2936 patients with HF with reduced ejection fraction (HFrEF) in the HF registries of the universities of Heidelberg, Germany, and Hull, UK (general sample). Of these, 598 (20%) were treated for concomitant DM (DM subgroup). The relationship between BMI and all-cause mortality was analysed in both the general sample and the DM subgroup. Patients with concomitant DM were stratified according to HbA1c levels or type of diabetes treatment and analyses were repeated.

Results: We found an inverse BMI-mortality relationship in both the general sample and the DM subgroup. However, the obesity paradox was less pronounced in patients with diabetes treated with insulin and it disappeared in those with poor glycaemic control as defined by HbA1c levels > 7.5%.

Conclusion: In patients with HFrEF, a higher BMI is associated with better survival irrespective of concomitant DM. However, insulin treatment and poor glycaemic control make the relationship much weaker.

Keywords: Diabetes mellitus; Heart failure; Mortality; Obesity paradox; Reverse epidemiology.

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Conflict of interest statement

Prof. Atar reports personal fees from Astra-Zeneca, personal fees from Boehringer-Ingelheim, personal fees from Novartis and personal fees from MSD (outside the submitted work). Prof. Cleland reports personal fees from Abbott, personal fees from Amgen, grants and personal fees from Bayer, grants and personal fees from Bristol Myers Squibb, personal fees from Novartis, personal fees from Medtronic, personal fees from Idorsia, grants and personal fees from Vifor, grants and personal fees from Pharmacosmos, grants and personal fees from Cytokinetics, personal fees from Servier, non-financial support from Boehringer-Ingelheim, personal fees from Astra-Zeneca, personal fees from Innolife, personal fees from Torrent, grants and personal fees from Johnson & Johnson, grants and personal fees from Myokardia, personal fees from Respicardia, grants and personal fees from Stealth Biopharmaceuticals, and grants and personal fees from Viscardia (outside the submitted work). Prof. Frankenstein reports personal fees from Astra-Zeneca, grants and personal fees from Bayer, personal fees from Boehringer (outside the submitted work). Prof. Frey reports personal fees from Boehringer and personal fees from AstraZeneca (outside the submitted work).

Figures

Fig. 1
Fig. 1
Relationship between BMI and 5-year all-cause mortality in ambulatory patients with chronic stable HFrEF (general sample). BMI body mass index (kg/m2), HFrEF heart failure with reduced ejection fraction
Fig. 2
Fig. 2
Relationship between BMI and 5-year all-cause mortality in ambulatory patients with chronic stable HFrEF with or without concomitant DM. BMI body mass index (kg/m2), DM type 2 diabetes mellitus, HFrEF heart failure with reduced ejection fraction
Fig. 3
Fig. 3
Relationship between BMI and 5-year all-cause mortality in ambulatory patients with chronic stable HFrEF and concomitant DM (diabetes subgroup) stratified by type of diabetes treatment. BMI body mass index (kg/m2), DM type 2 diabetes mellitus, HFrEF heart failure with reduced ejection fraction, IDDM insulin dependent diabetes mellitus, NIDDM non insulin dependent diabetes mellitus
Fig. 4
Fig. 4
Relationship between BMI and 5-year all-cause mortality in ambulatory patients with chronic stable HFrEF and concomitant DM (diabetes subgroup) stratified by HbA1c. BMI body mass index (kg/m2), DM type 2 diabetes mellitus, HFrEF heart failure with reduced ejection fraction
Fig. 5
Fig. 5
Relationship between HbA1c (%) and 5-year all-cause mortality in ambulatory patients with chronic stable HFrEF and concomitant DM (diabetes subgroup). DM type 2 diabetes mellitus, HFrEF heart failure with reduced ejection fraction
Fig. 6
Fig. 6
Relationship between HbA1c (%) and 5-year all-cause mortality in ambulatory patients with chronic stable HFrEF and concomitant DM (diabetes subgroup) stratified by BMI. BMI body mass index (kg/m2), DM type 2 diabetes mellitus, HFrEF heart failure with reduced ejection fraction
See this image and copyright information in PMC

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