, Volume 64, Issue 1, pp 82–89 | Cite as

Weight change is associated with increased all-cause mortality and non-cardiac mortality among patients with type 2 diabetes mellitus

  • Zhenhua Xing
  • Junyu Pei
  • Jiabing Huang
  • Xiaofan Peng
  • Pengfei Chen
  • Xinqun Hu
  • Shan GaoEmail author
Original Article



It is unclear whether changes in weight affect subsequent adverse events in patients with type 2 diabetes mellitus (T2DM) already at high risk of cardiovascular disease (CVD).

Methods and results

This is a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study data to examine the relationship between changes in weight and adverse events. Patients were divided into groups based on changes in body mass index (BMI): stable weight, gain or loss of BMI ≤1.5 kg/m2; moderate weight gain, BMI gain of 1.5–5 kg/m2; pronounced weight gain, BMI gain >5 kg/m2; moderate weight loss, BMI loss of 1.5–5 kg/m2; and pronounced weight loss, BMI loss >5 kg/m2. The primary endpoint of the present study was all-cause mortality. Secondary endpoints were cardiac death, non-fatal myocardial infarction (MI), and non-cardiac mortality. A total of 9372 T2DM patients with a mean follow-up of 8.08 ± 3.00 years were included for analysis. The average change in weight across the entire study population was 1.80 ± 9.00%, representing ~0.448 ± 2.98 kg/m2. Patients with pronounced weight loss had the highest risk of all-cause mortality (hazard ratio (HR) 2.07, 95% confidence interval (CI): 1.68–2.55), followed by patients with pronounced weight gain (HR 1.23, 95% CI: 1.02–1.56); patients with stable weight had the lowest risk. An asymmetric V-shaped relationship was observed between changes in BMI and all-cause mortality and non-cardiac mortality. Although no statistical significance was observed in terms of cardiac death and non-fatal MI, a flat V-shaped relationship may exist.


Weight was stable in most T2DM patients with high risk of CVD. Weight loss and gain is associated with increased all-cause mortality and non-cardiac mortality. Pronounced weight loss and weight gain is associated with a slight increase in cardiac death and non-fatal MI incidence, which does not reach statistical significance.


Type 2 diabetes mellitus Body mass index Weight change All-cause mortality Cardiac death 



All authors read, provided critical feedback, and approved the final manuscript.

Authors’ contributions

S.G. and Z.X. designed the study and provided methodological expertise. J.H., X.H. and J.P. drafted the manuscript. P.C., and X.P. drafted the tables and figures.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Consent for publication

All the authors listed have approved the manuscript and agree to publish.


  1. 1.
    P. Ambery, V.E. Parker, M. Stumvoll et al. MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study. Lancet 391(10140), 2607–2618 (2018)CrossRefGoogle Scholar
  2. 2.
  3. 3.
    E.W. Gregg, N. Sattar, M.K. Ali, The changing face of diabetes complications. Lancet Diabetes Endocrinol. 4(6), 537–547 (2016)CrossRefGoogle Scholar
  4. 4.
    K.S.S. Rao, S. Kaptoge, A. Thompson et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N. Engl. J. Med. 364(9), 829–841 (2011)CrossRefGoogle Scholar
  5. 5.
    D. Mozaffarian, E.J. Benjamin, A.S. Go et al. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation 133(4), e38–e360 (2016)Google Scholar
  6. 6.
    F.B. Ortega, C.J. Lavie, S.N. Blair, Obesity and cardiovascular disease. Circ. Res. 118(11), 1752–1770 (2016)CrossRefGoogle Scholar
  7. 7.
    E.E. Calle, M.J. Thun, J.M. Petrelli, C. Rodriguez, C.W. Heath, Body-mass index and mortality in a prospective cohort of U.S. adults. N. Engl. J. Med. 341(15), 1097–1105 (1999)CrossRefGoogle Scholar
  8. 8.
    S. Maru, Y.T. van der Schouw, C.H. Gimbrère, D.E. Grobbee, P.H. Peeters, Body mass index and short-term weight change in relation to mortality in Dutch women after age 50 y. Am. J. Clin. Nutr. 80(1), 231–236 (2004)CrossRefGoogle Scholar
  9. 9.
    X. Pi-Sunyer, G. Blackburn, F.L. Brancati et al. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 30(6), 1374–1383 (2007)CrossRefGoogle Scholar
  10. 10.
    C. Sauvaget, K. Ramadas, G. Thomas, J. Vinoda, S. Thara, R. Sankaranarayanan, Body mass index, weight change and mortality risk in a prospective study in India. Int. J. Epidemiol. 37(5), 990–1004 (2008)CrossRefGoogle Scholar
  11. 11.
    W.B. Drøyvold, N.T.I. Lund, S. Lydersen et al. Weight change and mortality: the Nord-Trøndelag Health Study. J. Intern. Med. 257(4), 338–345 (2005)CrossRefGoogle Scholar
  12. 12.
    I.M. Lee, R.S. Paffenbarger, Change in body weight and longevity. JAMA 268(15), 2045–2049 (1992)CrossRefGoogle Scholar
  13. 13.
    H.C. Gerstein, M.C. Riddle, D.M. Kendall et al. Glycemia treatment strategies in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am. J. Cardiol. 99(12A), 34i–43i (2007)CrossRefGoogle Scholar
  14. 14.
    H.C. Gerstein, M.E. Miller, R.P. Byington et al. Effects of intensive glucose lowering in type 2 diabetes. N. Engl. J. Med. 358(24), 2545–2559 (2008)CrossRefGoogle Scholar
  15. 15.
    S. Durrleman, R. Simon, Flexible regression models with cubic splines. Stat. Med. 8(5), 551–561 (1989)CrossRefGoogle Scholar
  16. 16.
    I. Kunz, U. Schorr, S. Klaus, A.M. Sharma, Resting metabolic rate and substrate use in obesity hypertension. Hypertension 36(1), 26–32 (2000)CrossRefGoogle Scholar
  17. 17.
    Y.Y. Fadl, H.M. Krumholz, M. Kosiborod et al. Predictors of weight change in overweight patients with myocardial infarction. Am. Heart J. 154(4), 711–717 (2007)CrossRefGoogle Scholar
  18. 18.
    L.F. Amador, S.S. Al, K.S. Markides, J.S. Goodwin, Weight change and mortality among older Mexican Americans. Aging Clin. Exp. Res. 18(3), 196–204 (2006)CrossRefGoogle Scholar
  19. 19.
    R. Andres, D.C. Muller, J.D. Sorkin, Long-term effects of change in body weight on all-cause mortality. A review. Ann. Intern. Med. 119(7 Pt 2), 737–743 (1993)CrossRefGoogle Scholar
  20. 20.
    D.K. Dey, E. Rothenberg, V. Sundh, I. Bosaeus, B. Steen, Body mass index, weight change and mortality in the elderly. A 15 y longitudinal population study of 70 y olds. Eur. J. Clin. Nutr. 55(6), 482–492 (2001)CrossRefGoogle Scholar
  21. 21.
    S.G. Wannamethee, A.G. Shaper, M. Walker, Weight change, body weight and mortality: the impact of smoking and ill health. Int. J. Epidemiol. 30(4), 777–786 (2001)CrossRefGoogle Scholar
  22. 22.
    C. Iribarren, D.S. Sharp, C.M. Burchfiel, H. Petrovitch, Association of weight loss and weight fluctuation with mortality among Japanese American men. N. Engl. J. Med. 333(11), 686–692 (1995)CrossRefGoogle Scholar
  23. 23.
    A.B. Newman, D. Yanez, T. Harris, A. Duxbury, P.L. Enright, L.P. Fried, Weight change in old age and its association with mortality. J. Am. Geriatr. Soc. 49(10), 1309–1318 (2001)CrossRefGoogle Scholar
  24. 24.
    E.R. Pamuk, D.F. Williamson, M.K. Serdula, J. Madans, T.E. Byers, Weight loss and subsequent death in a cohort of U.S. adults. Ann. Intern. Med. 119(7 Pt 2), 744–748 (1993)CrossRefGoogle Scholar
  25. 25.
    A.A. Meltzer, J.E. Everhart, Unintentional weight loss in the United States. Am. J. Epidemiol. 142(10), 1039–1046 (1995)CrossRefGoogle Scholar
  26. 26.
    D.F. Williamson, T.J. Thompson, M. Thun, D. Flanders, E. Pamuk, T. Byers, Intentional weight loss and mortality among overweight individuals with diabetes. Diabetes Care 23(10), 1499–1504 (2000)CrossRefGoogle Scholar
  27. 27.
    F.W. Cheng, X. Gao, G.L. Jensen, Weight change and all-cause mortality in older adults: a meta-analysis. J. Nutr. Gerontol. Geriatr. 34(4), 343–368 (2015)CrossRefGoogle Scholar
  28. 28.
    J.P. Wilding, The importance of weight management in type 2 diabetes mellitus. Int. J. Clin. Pract. 68(6), 682–691 (2014)CrossRefGoogle Scholar
  29. 29.
    S. Choi, K. Kim, S.M. Kim et al. Association of obesity or weight change with coronary heart disease among young adults in South Korea. JAMA Intern. Med. 178(8), 1060–1068 (2018)CrossRefGoogle Scholar
  30. 30.
    R. Selmer, A. Tverdal, Body mass index and cardiovascular mortality at different levels of blood pressure: a prospective study of Norwegian men and women. J. Epidemiol. Community Health 49(3), 265–270 (1995)CrossRefGoogle Scholar
  31. 31.
    Y. Zheng, J.E. Manson, C. Yuan et al. Associations of weight gain from early to middle adulthood with major health outcomes later in life. JAMA 318(3), 255–269 (2017)CrossRefGoogle Scholar
  32. 32.
    A. Nanri, T. Mizoue, Y. Takahashi, M. Noda, M. Inoue, S. Tsugane, Weight change and all-cause, cancer and cardiovascular disease mortality in Japanese men and women: the Japan Public Health Center-Based Prospective Study. Int. J. Obes. (Lond.). 34(2), 348–356 (2010)CrossRefGoogle Scholar
  33. 33.
    Z. Xing, J. Pei, J. Huang, X. Peng, P. Chen, X. Hu, Relationship of obesity to adverse events among patients with mean 10-year history of type 2 diabetes mellitus: results of the ACCORD study. J. Am. Heart Assoc. 7(22), e010512 (2018)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Cardiovascular Medicine, The Second Xiangya HospitalCentral South UniversityChangshaChina
  2. 2.Department of Geriatrics, The Second Xiangya HospitalCentral South UniversityChangshaChina

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