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

Diabetes mellitus Heart failure Mortality Obesity paradox Reverse epidemiology

Journal

Clinical research in cardiology : official journal of the German Cardiac Society
ISSN: 1861-0692
Titre abrégé: Clin Res Cardiol
Pays: Germany
ID NLM: 101264123

Informations de publication

Date de publication:
22 Aug 2023
Historique:
received: 21 09 2021
accepted: 13 09 2022
medline: 23 8 2023
pubmed: 23 8 2023
entrez: 22 8 2023
Statut: aheadofprint

Résumé

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. 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. 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%. 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.

Sections du résumé

BACKGROUND 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 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 37608126
doi: 10.1007/s00392-023-02268-3
pii: 10.1007/s00392-023-02268-3
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2023. The Author(s).

Références

Clark AL, Chyu J, Horwich TB (2012) The obesity paradox in men versus women with systolic heart failure. Am J Cardiol 110(1):77–82
pubmed: 22497678 pmcid: 3377856 doi: 10.1016/j.amjcard.2012.02.050
Fonarow GC et al (2007) An obesity paradox in acute heart failure: analysis of body mass index and inhospital mortality for 108,927 patients in the Acute Decompensated Heart Failure National Registry. Am Heart J 153(1):74–81
pubmed: 17174642 doi: 10.1016/j.ahj.2006.09.007
Lavie CJ et al (2016) Update on obesity and obesity paradox in heart failure. Prog Cardiovasc Dis 58(4):393–400
pubmed: 26721180 doi: 10.1016/j.pcad.2015.12.003
Oga EA, Eseyin OR (2016) The obesity paradox and heart failure: a systematic review of a decade of evidence. J Obes 2016:9040248
pubmed: 26904277 pmcid: 4745816 doi: 10.1155/2016/9040248
Shah R et al (2014) Body mass index and mortality in acutely decompensated heart failure across the world: a global obesity paradox. J Am Coll Cardiol 63(8):778–785
pubmed: 24315906 doi: 10.1016/j.jacc.2013.09.072
Tseng CH (2013) Obesity paradox: differential effects on cancer and noncancer mortality in patients with type 2 diabetes mellitus. Atherosclerosis 226(1):186–192
pubmed: 23040832 doi: 10.1016/j.atherosclerosis.2012.09.004
Park J et al (2014) Obesity paradox in end-stage kidney disease patients. Prog Cardiovasc Dis 56(4):415–425
pubmed: 24438733 doi: 10.1016/j.pcad.2013.10.005
Chang HW et al (2016) Association of body mass index with all-cause mortality in patients with diabetes: a systemic review and meta-analysis. Cardiovasc Diagn Ther 6(2):109–119
pubmed: 27054100 pmcid: 4805755 doi: 10.21037/cdt.2015.12.06
Carnethon MR, Rasmussen-Torvik LJ, Palaniappan L (2014) The obesity paradox in diabetes. Curr Cardiol Rep 16(2):446
pubmed: 24408674 doi: 10.1007/s11886-013-0446-3
Blum A et al (2011) “Obesity paradox” in chronic obstructive pulmonary disease. Isr Med Assoc J 13(11):672–675
pubmed: 22279700
Costanzo P et al (2015) The obesity paradox in type 2 diabetes mellitus: relationship of body mass index to prognosis: a cohort study. Ann Intern Med 162(9):610–618
pubmed: 25938991 doi: 10.7326/M14-1551
Brown O et al (2020) Relationship between a single measurement at baseline of body mass index, glycated hemoglobin, and the risk of mortality and cardiovascular morbidity in type 2 diabetes mellitus. Cardiovasc Endocrinol Metab 9(4):177–182
pubmed: 33225234 pmcid: 7673766 doi: 10.1097/XCE.0000000000000202
Goel K et al (2014) Obesity paradox in different populations: evidence and controversies. Future Cardiol 10(1):81–91
pubmed: 24344665 doi: 10.2217/fca.13.84
Adamopoulos C et al (2011) Absence of obesity paradox in patients with chronic heart failure and diabetes mellitus: a propensity-matched study. Eur J Heart Fail 13(2):200–206
pubmed: 20930001 doi: 10.1093/eurjhf/hfq159
Narumi T et al (2014) The obesity paradox is not observed in chronic heart failure patients with metabolic syndrome. EXCLI J 13:516–525
pubmed: 26417279 pmcid: 4464417
Pinho EM et al (2015) Higher BMI in heart failure patients is associated with longer survival only in the absence of diabetes. J Cardiovasc Med (Hagerstown) 16(8):576–582
pubmed: 25118053 doi: 10.2459/JCM.0b013e328364be3c
Zamora E et al (2016) No benefit from the obesity paradox for diabetic patients with heart failure. Eur J Heart Fail 18(7):851–858
pubmed: 27312985 doi: 10.1002/ejhf.576
Lee KS et al (2017) Obesity paradox: comparison of heart failure patients with and without comorbid diabetes. Am J Crit Care 26(2):140–148
pubmed: 28249867 doi: 10.4037/ajcc2017634
Abi Khalil C et al (2017) BMI is inversely correlated to the risk of mortality in patients with type 2 diabetes hospitalized for acute heart failure: findings from the Gulf aCute heArt failuRE (Gulf-CARE) registry. Int J Cardiol 241:262–269
pubmed: 28291623 doi: 10.1016/j.ijcard.2017.02.119
Ballo P et al (2013) Body mass index, gender, and clinical outcome among hypertensive and diabetic patients with stage A/B heart failure. Obesity (Silver Spring) 21(9):E500–E507
pubmed: 23512886 doi: 10.1002/oby.20420
Khalid U et al (2014) Pre-morbid body mass index and mortality after incident heart failure: the ARIC Study. J Am Coll Cardiol 64(25):2743–2749
pubmed: 25541126 pmcid: 4280076 doi: 10.1016/j.jacc.2014.09.067
Waring ME et al (2011) Weight and mortality following heart failure hospitalization among diabetic patients. Am J Med 124(9):834–840
pubmed: 21854892 pmcid: 3160602 doi: 10.1016/j.amjmed.2011.04.030
Yoshihisa A et al (2019) Heterogeneous impact of body mass index on in-hospital mortality in acute heart failure syndromes: an analysis from the ATTEND Registry. Eur Heart J Acute Cardiovasc Care 8(7):589–598
pubmed: 28361568 doi: 10.1177/2048872617703061
Paniagua JA (2016) Nutrition, insulin resistance and dysfunctional adipose tissue determine the different components of metabolic syndrome. World J Diabetes 7(19):483–514
pubmed: 27895819 pmcid: 5107710 doi: 10.4239/wjd.v7.i19.483
Chadt A et al (2000) Molecular links between obesity and diabetes: “diabesity.” In: De Groot LJ et al (eds) Endotext. MDText.com Inc., South Dartmouth
Ponikowski P et al (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37(27):2129–2200
pubmed: 27206819 doi: 10.1093/eurheartj/ehw128
Association AD (2016) Standards of medical care in diabetes—2016. Diabetes Care 39(suppl. 1):S1–S106
Kerner W, Bruckel J, German Diabetes A (2014) Definition, classification and diagnosis of diabetes mellitus. Exp Clin Endocrinol Diabetes 122(7):384–386
pubmed: 25014088 doi: 10.1055/s-0034-1366278
Organisation WH, Federation ID (2006) Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. WHO, Geneva
Roden M (2016) Diabetes mellitus: definition, classification and diagnosis. Wien Klin Wochenschr 128(Suppl 2):S37-40
pubmed: 27052219 doi: 10.1007/s00508-015-0931-3
Springer J et al (2006) Prognosis and therapy approaches of cardiac cachexia. Curr Opin Cardiol 21(3):229–233
pubmed: 16601462 doi: 10.1097/01.hco.0000221585.94490.09
McDonald MN et al (2019) It’s more than low BMI: prevalence of cachexia and associated mortality in COPD. Respir Res 20(1):100
pubmed: 31118043 pmcid: 6532157 doi: 10.1186/s12931-019-1073-3
Kovesdy CP, Anderson JE, Kalantar-Zadeh K (2007) Inverse association between lipid levels and mortality in men with chronic kidney disease who are not yet on dialysis: effects of case mix and the malnutrition-inflammation-cachexia syndrome. J Am Soc Nephrol 18(1):304–311
pubmed: 17167114 doi: 10.1681/ASN.2006060674
Horwich TB et al (2001) The relationship between obesity and mortality in patients with heart failure. J Am Coll Cardiol 38(3):789–795
pubmed: 11527635 doi: 10.1016/S0735-1097(01)01448-6
Horwich TB, Fonarow GC, Clark AL (2018) Obesity and the obesity paradox in heart failure. Prog Cardiovasc Dis 61(2):151–156
pubmed: 29852198 doi: 10.1016/j.pcad.2018.05.005
Wong ES et al (2011) Examining the BMI-mortality relationship using fractional polynomials. BMC Med Res Methodol 11:175
pubmed: 22204699 pmcid: 3273446 doi: 10.1186/1471-2288-11-175
Clark AL, Fonarow GC, Horwich TB (2015) Impact of cardiorespiratory fitness on the obesity paradox in patients with systolic heart failure. Am J Cardiol 115(2):209–213
pubmed: 25465933 doi: 10.1016/j.amjcard.2014.10.023
Frankenstein L et al (2009) The obesity paradox in stable chronic heart failure does not persist after matching for indicators of disease severity and confounders. Eur J Heart Fail 11(12):1189–1194
pubmed: 19887494 doi: 10.1093/eurjhf/hfp150
Gastelurrutia P et al (2015) Body mass index, body fat, and nutritional status of patients with heart failure: the PLICA study. Clin Nutr 34(6):1233–1238
pubmed: 25573807 doi: 10.1016/j.clnu.2014.12.013
Pozzo J et al (2015) Obesity paradox: origin and best way to assess severity in patients with systolic HF. Obesity (Silver Spring) 23(10):2002–2008
pubmed: 26337500 doi: 10.1002/oby.21216
George AM, Jacob AG, Fogelfeld L (2015) Lean diabetes mellitus: an emerging entity in the era of obesity. World J Diabetes 6(4):613–620
pubmed: 25987958 pmcid: 4434081 doi: 10.4239/wjd.v6.i4.613
Brown A et al (2017) Insulin-associated weight gain in obese type 2 diabetes mellitus patients: what can be done? Diabetes Obes Metab 19(12):1655–1668
pubmed: 28509408 doi: 10.1111/dom.13009
Cosentino F et al (2020) 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 41(2):255–323
pubmed: 31497854 doi: 10.1093/eurheartj/ehz486
Clark AL, Fonarow GC, Horwich TB (2011) Waist circumference, body mass index, and survival in systolic heart failure: the obesity paradox revisited. J Card Fail 17(5):374–380
pubmed: 21549293 doi: 10.1016/j.cardfail.2011.01.009
Sharma A et al (2015) Meta-analysis of the relation of body mass index to all-cause and cardiovascular mortality and hospitalization in patients with chronic heart failure. Am J Cardiol 115(10):1428–1434
pubmed: 25772740 doi: 10.1016/j.amjcard.2015.02.024
Levey AS, Stevens LA (2010) Estimating GFR using the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions. Am J Kidney Dis 55(4):622–627
pubmed: 20338463 pmcid: 2846308 doi: 10.1053/j.ajkd.2010.02.337

Auteurs

Hanna Fröhlich (H)

Department of Cardiology, Angiology, and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.

Anna Bossmeyer (A)

Department of Cardiology, Angiology, and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.

Syed Kazmi (S)

Hull University Teaching Hospitals NHS Trust, Hull, UK.

Kevin M Goode (KM)

Hull University Teaching Hospitals NHS Trust, Hull, UK.

Stefan Agewall (S)

Department of Cardiology, and Institute of Clinical Medicine, Oslo University Hospital Ulleval, University of Oslo, Oslo, Norway.

Dan Atar (D)

Department of Cardiology, and Institute of Clinical Medicine, Oslo University Hospital Ulleval, University of Oslo, Oslo, Norway.

Morten Grundtvig (M)

Medical Department, Innlandet Hospital Trust Division Lillehammer, Lillehammer, Norway.

Norbert Frey (N)

Department of Cardiology, Angiology, and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.

John G F Cleland (JGF)

National Heart and Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, UK.
Robertson Centre for Biostatistics and Clinical Trials, Glasgow, UK.

Lutz Frankenstein (L)

Department of Cardiology, Angiology, and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany. lutz.frankenstein@med.uni-heidelberg.de.

Andrew L Clark (AL)

Hull University Teaching Hospitals NHS Trust, Hull, UK.

Tobias Täger (T)

Department of Cardiology, Angiology, and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.

Classifications MeSH