Diabetes Metab J.  2020 Aug;44(4):592-601. 10.4093/dmj.2019.0104.

Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults

• Rhee EJ
• Kwon H
• Park SE
• Han KD
• Park YG
• Kim YH
• Lee WY

• KMID: 2513018
• DOI: http://doi.org/10.4093/dmj.2019.0104

Abstract

Recent studies suggest an association between diabetes and increased risk of heart failure (HF). However, the associations among obesity status, glycemic status, and risk of HF are not known. In this study, we analyzed whether the risk of HF increases in participants according to baseline glycemic status and whether this increased risk is associated with obesity status.

We analyzed the risk of HF according to baseline glycemic status (normoglycemia, impaired fasting glucose [IFG], and diabetes) in 9,720,220 Koreans who underwent Korean National Health Screening in 2009 without HF at baseline with a median follow-up period of 6.3 years. The participants were divided into five and six groups according to baseline body mass index (BMI) and waist circumference, respectively.

Participants with IFG and those with diabetes showed a 1.08- and 1.86-fold increased risk of HF, respectively, compared to normoglycemic participants. Compared to the normal weight group (BMI, 18.5 to 22.9 kg/m²), the underweight group (BMI <18.5 kg/m²) showed a 1.7-fold increased risk of HF, and those with BMI ≥30 kg/m² showed a 1.1-fold increased risk of HF, suggesting a J-shaped association with BMI. When similar analyses were performed for different glycemic statuses, the J-shaped association between BMI and HF risk was consistently observed in both groups with and without diabetes.

Participants with IFG and diabetes showed a significantly increased HF risk compared to normoglycemic participants. This increased risk of HF was mostly prominent in underweight and class II obese participants than in participants with normal weight.

Keyword

Body mass index; Diabetes mellitus; Heart failure; Obesity; Prediabetic state

Figure

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  Fig. 1 Risk for heart failure in different glycemic status and obesity degree with normoglycemia and normal body weight as the reference. IR, incidence rate; HR, hazard ratio; CI, confidence interval.

Reference

1. Won JC, Lee JH, Kim JH, Kang ES, Won KC, Kim DJ, Lee MK. Diabetes fact sheet in Korea, 2016: an appraisal of current status. Diabetes Metab J. 2018; 42:415–424. PMID: 30113146.

2. Diabetes Control and Complications Trial Research Group. Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329:977–986. PMID: 8366922.

3. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352:837–853. PMID: 9742976.

4. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003; 348:383–393. PMID: 12556541.

5. Lehrke M, Marx N. Diabetes mellitus and heart failure. Am J Cardiol. 2017; 120:S37–S47. PMID: 28606342.

6. MacDonald MR, Petrie MC, Varyani F, Ostergren J, Michelson EL, Young JB, Solomon SD, Granger CB, Swedberg K, Yusuf S, Pfeffer MA, McMurray JJ. CHARM Investigators. Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J. 2008; 29:1377–1385. PMID: 18413309.

7. Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974; 34:29–34. PMID: 4835750.

8. Aronow WS, Ahn C. Incidence of heart failure in 2,737 older persons with and without diabetes mellitus. Chest. 1999; 115:867–868. PMID: 10084505.

9. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE. EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373:2117–2128. PMID: 26378978.

10. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR. CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017; 377:644–657. PMID: 28605608.

11. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Silverman MG, Zelniker TA, Kuder JF, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Ruff CT, Gause-Nilsson IAM, Fredriksson M, Johansson PA, Langkilde AM, Sabatine MS. DECLARE-TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019; 380:347–357. PMID: 30415602.

12. Kinlen D, Cody D, O'Shea D. Complications of obesity. QJM. 2018; 111:437–443. PMID: 29025162.

13. Park J, Lee ES, Lee DY, Kim J, Park SE, Park CY, Lee WY, Oh KW, Park SW, Rhee EJ. Waist circumference as a marker of obesity is more predictive of coronary artery calcification than body mass index in apparently healthy Korean adults: the Kangbuk Samsung health study. Endocrinol Metab (Seoul). 2016; 31:559–566. PMID: 28029026.

14. Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ, Larson MG, Kannel WB, Vasan RS. Obesity and the risk of heart failure. N Engl J Med. 2002; 347:305–313. PMID: 12151467.

15. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006; 355:251–259. PMID: 16855265.

16. Thrainsdottir IS, Aspelund T, Hardarson T, Malmberg K, Sigurdsson G, Thorgeirsson G, Gudnason V, Ryden L. Glucose abnormalities and heart failure predict poor prognosis in the population-based Reykjavík Study. Eur J Cardiovasc Prev Rehabil. 2005; 12:465–471. PMID: 16210933.

17. Thrainsdottir IS, Aspelund T, Thorgeirsson G, Gudnason V, Hardarson T, Malmberg K, Sigurdsson G, Ryden L. The association between glucose abnormalities and heart failure in the population-based Reykjavik study. Diabetes Care. 2005; 28:612–616. PMID: 15735197.

18. Bahrami H, Bluemke DA, Kronmal R, Bertoni AG, Lloyd-Jones DM, Shahar E, Szklo M, Lima JA. Novel metabolic risk factors for incident heart failure and their relationship with obesity: the MESA (Multi-Ethnic Study of Atherosclerosis) study. J Am Coll Cardiol. 2008; 51:1775–1783. PMID: 18452784.

19. Kristensen SL, Jhund PS, Lee MMY, Kober L, Solomon SD, Granger CB, Yusuf S, Pfeffer MA, Swedberg K, McMurray JJV. CHARM Investigators and Committees. Prevalence of prediabetes and undiagnosed diabetes in patients with HFpEF and HFrEF and associated clinical outcomes. Cardiovasc Drugs Ther. 2017; 31:545–549. PMID: 28948430.

20. Matsue Y, Suzuki M, Nakamura R, Abe M, Ono M, Yoshida S, Seya M, Iwatsuka R, Mizukami A, Setoguchi M, Nagahori W, Ohno M, Matsumura A, Hashimoto Y. Prevalence and prognostic implications of pre-diabetic state in patients with heart failure. Circ J. 2011; 75:2833–2839. PMID: 22008319.

21. Song SO, Jung CH, Song YD, Park CY, Kwon HS, Cha BS, Park JY, Lee KU, Ko KS, Lee BW. Background and data configuration process of a nationwide population-based study using the Korean national health insurance system. Diabetes Metab J. 2014; 38:395–403. PMID: 25349827.

22. American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2019. Diabetes Care. 2019; 42:S13–S28. PMID: 30559228.

23. Seo MH, Lee WY, Kim SS, Kang JH, Kang JH, Kim KK, Kim BY, Kim YH, Kim WJ, Kim EM, Kim HS, Shin YA, Shin HJ, Lee KR, Lee KY, Lee SY, Lee SK, Lee JH, Lee CB, Chung S, Cho YH, Choi KM, Han JS, Yoo SJ. Committee of Clinical Practice Guidelines, Korean Society for the Study of Obesity (KSSO). 2018 Korean Society for the Study of Obesity guideline for the management of obesity in Korea. J Obes Metab Syndr. 2019; 28:40–45. PMID: 31089578.

24. World Health Organization. Regional Office for the Western Pacific. The Asia-Pacific perspective: redefining obesity and its treatment. Sydney: Health Communications Australia;2000.

25. Lee SY, Park HS, Kim DJ, Han JH, Kim SM, Cho GJ, Kim DY, Kwon HS, Kim SR, Lee CB, Oh SJ, Park CY, Yoo HJ. Appropriate waist circumference cutoff points for central obesity in Korean adults. Diabetes Res Clin Pract. 2007; 75:72–80. PMID: 16735075.

26. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999; 130:461–470. PMID: 10075613.

27. Nichols GA, Gullion CM, Koro CE, Ephross SA, Brown JB. The incidence of congestive heart failure in type 2 diabetes: an update. Diabetes Care. 2004; 27:1879–1884. PMID: 15277411.

28. van Melle JP, Bot M, de Jonge P, de Boer RA, van Veldhuisen DJ, Whooley MA. Diabetes, glycemic control, and new-onset heart failure in patients with stable coronary artery disease: data from the heart and soul study. Diabetes Care. 2010; 33:2084–2089. PMID: 20805280.

29. Levelt E, Mahmod M, Piechnik SK, Ariga R, Francis JM, Rodgers CT, Clarke WT, Sabharwal N, Schneider JE, Karamitsos TD, Clarke K, Rider OJ, Neubauer S. Relationship between left ventricular structural and metabolic remodeling in type 2 diabetes. Diabetes. 2016; 65:44–52. PMID: 26438611.

30. Shimizu I, Minamino T, Toko H, Okada S, Ikeda H, Yasuda N, Tateno K, Moriya J, Yokoyama M, Nojima A, Koh GY, Akazawa H, Shiojima I, Kahn CR, Abel ED, Komuro I. Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents. J Clin Invest. 2010; 120:1506–1514. PMID: 20407209.

31. Kwak SH, Park KS. Pathophysiology of type 2 diabetes in Koreans. Endocrinol Metab (Seoul). 2018; 33:9–16. PMID: 29589384.

32. Falcao-Pires I, Hamdani N, Borbely A, Gavina C, Schalkwijk CG, van der Velden J, van Heerebeek L, Stienen GJ, Niessen HW, Leite-Moreira AF, Paulus WJ. Diabetes mellitus worsens diastolic left ventricular dysfunction in aortic stenosis through altered myocardial structure and cardiomyocyte stiffness. Circulation. 2011; 124:1151–1159. PMID: 21844073.

33. Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res. 2004; 63:582–592. PMID: 15306213.

34. Rijzewijk LJ, Jonker JT, van der Meer RW, Lubberink M, de Jong HW, Romijn JA, Bax JJ, de Roos A, Heine RJ, Twisk JW, Windhorst AD, Lammertsma AA, Smit JW, Diamant M, Lamb HJ. Effects of hepatic triglyceride content on myocardial metabolism in type 2 diabetes. J Am Coll Cardiol. 2010; 56:225–233. PMID: 20620743.

35. Neubauer S. The failing heart: an engine out of fuel. N Engl J Med. 2007; 356:1140–1151. PMID: 17360992.

36. Carbone S, Lavie CJ, Arena R. Obesity and heart failure: focus on the obesity paradox. Mayo Clin Proc. 2017; 92:266–279. PMID: 28109619.

37. Padwal R, McAlister FA, McMurray JJ, Cowie MR, Rich M, Pocock S, Swedberg K, Maggioni A, Gamble G, Ariti C, Earle N, Whalley G, Poppe KK, Doughty RN, Bayes-Genis A. Meta-analysis Global Group in Chronic Heart Failure (MAGGIC). The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data. Int J Obes (Lond). 2014; 38:1110–1114. PMID: 24173404.

38. Lee DH, Ha KH, Kim HC, Kim DJ. Association of body mass index with risk of major adverse cardiovascular events and mortality in people with diabetes. J Obes Metab Syndr. 2018; 27:61–70. PMID: 31089542.

39. De Schutter A, Lavie CJ, Kachur S, Patel DA, Milani RV. Body composition and mortality in a large cohort with preserved ejection fraction: untangling the obesity paradox. Mayo Clin Proc. 2014; 89:1072–1079. PMID: 25039037.

40. Aune D, Sen A, Norat T, Janszky I, Romundstad P, Tonstad S, Vatten LJ. Body mass index, abdominal fatness, and heart failure incidence and mortality: a systematic review and dose-response meta-analysis of prospective studies. Circulation. 2016; 133:639–649. PMID: 26746176.

41. Jia G, Whaley-Connell A, Sowers JR. Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced heart disease. Diabetologia. 2018; 61:21–28. PMID: 28776083.

42. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the Heart Failure Society of America. J Card Fail. 2017; 23:628–651. PMID: 28461259.

43. Shearer F, Lang CC, Struthers AD. Renin-angiotensin-aldosterone system inhibitors in heart failure. Clin Pharmacol Ther. 2013; 94:459–467. PMID: 23852393.