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Abstract

Background

Obesity has been proven to be a risk factor for type 2 diabetes mellitus (T2DM) through numerous pathogenetic mechanisms. Unexpectedly, some studies suggest that subjects with overweight/obesity and T2DM have better clinical outcome than their normal weight peers. This finding is described as “obesity paradox” and calls into question the importance of weight loss in this specific population.

Objective

This article is a narrative overview on the obesity and type 2 diabetes mellitus, particularly regarding the obesity paradox in T2DM patients.

Methods

We used as sources MEDLINE/PubMed, CINAHL, EMBASE, and Cochrane Library, from inception to March 2020; we chose 30 relevant papers regarding the association of obesity with clinical outcome and mortality of patients affected by T2DM.

Results

Many studies report that in patients with T2DM, overweight and obesity are associated with a better prognosis than underweight or normal weight, suggesting the presence of an obesity paradox. However, these studies have numerous limitations due to their mainly retrospective nature and to numerous confounding factors, such as associated pathologies, antidiabetic treatments, smoking habit, lack of data about distribution of body fat or weight history.

Conclusion

Literature data regarding the phenomenon of obesity paradox in T2DM patients are controversial due to the several limitations of the studies; therefore in the management of patients with overweight/obesity and T2DM is recommended referring to the established guidelines, which indicate diet and physical activity as the cornerstone of the treatment.

Level of evidence

Level V: narrative review.

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Data availability

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Code availability

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References

  1. World Health Organization (2016) Global report on diabetes. https://apps.who.int/iris/bitstream/handle/10665/204871/9789241565257_eng.pdf?sequence=1&isAllowed=y. Accessed 12 June 2020.

  2. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, Farzadfar F, Riley LM, Ezzati M, Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Body Mass Index) (2011) National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 377:557–567. https://doi.org/10.1016/S0140-6736(10)62037-5

    Article  PubMed  PubMed Central  Google Scholar 

  3. Frühbeck G, Toplak H, Woodward E, Yumuk V, Maislos M, Oppert JM, Executive Committee of the European Association for the Study of Obesity (2013) Obesity: the gateway to ill health—an EASO position statement on a rising public health, clinical and scientific challenge in Europe. Obes Facts 6:117–120. https://doi.org/10.1159/000350627

    Article  PubMed  PubMed Central  Google Scholar 

  4. World Health Organization. Obesity and Overweight: fact sheet. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed 12 June 2020.

  5. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS (2003) Prevalence of obesity, diabetes, and obesity-related health risk factors. JAMA 289:76–79. https://doi.org/10.1001/jama.289.1.76

    Article  PubMed  Google Scholar 

  6. Hossain P, Kawar B, El Nahas M (2007) Obesity and diabetes in the developing world—a growing challenge. N Engl J Med 356:213–215. https://doi.org/10.1056/NEJMp068177

    Article  CAS  PubMed  Google Scholar 

  7. Centers for Disease Control and Prevention (2004) Prevalence of overweight and obesity among adults with diagnosed diabetes United States, 1988–1994 and 1999–2002. Morb Mortal Wkly Rep 53:1066–1068

    Google Scholar 

  8. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–110. https://doi.org/10.2337/diabetes.52.1.102

    Article  CAS  PubMed  Google Scholar 

  9. Kahn SE, Hull RL, Utzschneider KM (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444:840–846. https://doi.org/10.1038/nature05482

    Article  CAS  PubMed  Google Scholar 

  10. Papaetis GS, Papakyriakou P, Panagiotou TN (2015) Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns. Arch Med Sci 11:463–482. https://doi.org/10.5114/aoms.2015.52350

    Article  PubMed  PubMed Central  Google Scholar 

  11. Meigs JB, Rutter MK, Sullivan LM, Fox CS, D'Agostino RB Sr, Wilson PW (2007) Impact of insulin resistance on risk of type 2 diabetes and cardiovascular disease in people with metabolic syndrome. Diabetes Care 30:1219–1225. https://doi.org/10.2337/dc06-2484

    Article  CAS  PubMed  Google Scholar 

  12. Roden M, Price TB, Perseghin G, Petersen KF, Rothman DL, Cline GW, Shulman GI (1996) Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 97:2859–2865. https://doi.org/10.1172/JCI118742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Shulman GI (2000) Cellular mechanisms of insulin resistance. J Clin Invest 106:171–176. https://doi.org/10.1172/JCI10583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hansen D, Dendale P, Beelen M, Jonkers RA, Mullens A, Corluy L, Meeusen R, van Loon LJ (2010) Plasma adipokine and inflammatory marker concentrations are altered in obese, as opposed to non-obese, type 2 diabetes patients. Eur J Appl Physiol 109:397–404. https://doi.org/10.1007/s00421-010-1362-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Il’yasova D, Wang F, D’AgostinoRBJr, Hanley A, Wagenknecht LE, (2010) Prospective association between fasting NEFA and type 2 diabetes: impact of post-load glucose. Diabetologia 53:866–874. https://doi.org/10.1007/s00125-010-1657-4

    Article  CAS  Google Scholar 

  16. Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Invest 116:1793–1801. https://doi.org/10.1172/JCI29069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bastard JP, Lagathu C, Caron M, Capeau J (2007) Point-counterpoint:interleukin-6 does/does not have a beneficial role in insulin sensitivity and glucose homeostasis. J Appl Physiol 102:821–822. https://doi.org/10.1152/japplphysiol.01353.2006

    Article  PubMed  Google Scholar 

  18. Kopp HP, Kopp CW, Festa A, Krzyzanowska K, Kriwanek S, Minar E, Roka R, Schernthaner G (2003) Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol 23:1042–1047. https://doi.org/10.1161/01.ATV.0000073313.16135.21

    Article  CAS  PubMed  Google Scholar 

  19. Hrnciar J, Avdicova M, Gabor D, Hrnciarova M, Chamulova M, Jakubikova K, Kaliska G, Kikova V, Kovar F, Kreze A Jr, Lepej J, Okapcova J, Szentivanyi M (2013) Prevalence of metabolic syndrome, insulin resistance, and microvascular angina pectoris in 500 consecutive patients referred to coronarography. Endocr Regul 47:33–38. https://doi.org/10.4149/endo_2013_01_33

    Article  CAS  PubMed  Google Scholar 

  20. Rotter V, Nagaev I, Smith U (2003) Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8and tumor necrosis factor alpha, overexpressed in human fat cells from insulin resistant subjects. J Biol Chem 278:45777–45784. https://doi.org/10.1074/jbc.M301977200

    Article  CAS  PubMed  Google Scholar 

  21. Barnes KM, Miner JL (2009) Role of resistin in insulin sensitivity in rodents and humans. Curr Protein Pept Sci 10:96–107. https://doi.org/10.2174/138920309787315239

    Article  CAS  PubMed  Google Scholar 

  22. Janke J, Engeli S, Boschmann M, Adams F, Böhnke J, Luft FC, Sharma AM, Jordan J (2006) Retinol-binding protein 4 in human obesity. Diabetes 55:2805–2810. https://doi.org/10.2337/db06-0616

    Article  CAS  PubMed  Google Scholar 

  23. Graham TE, Yang Q, Blüher M, Hammarstedt A, Ciaraldi TP, Henry RR, Wason CJ, Oberbach A, Jansson PA, Smith U, Kahn BB (2006) Retinol binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med 354:2552–2563. https://doi.org/10.1056/NEJMoa054862

    Article  CAS  PubMed  Google Scholar 

  24. Askari H, Tykodi G, Liu J, Dagogo-Jack S (2010) Fasting plasmaleptin level is a surrogate measure of insulin sensitivity. J Clin Endocrinol Metab 95:3836–3843. https://doi.org/10.1210/jc.2010-0296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Martin SS, Qasim A, Reilly MP (2008) Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol 52:1201–1210. https://doi.org/10.1016/j.jacc.2008.05.060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Dunmore SJ, Brown JE (2013) The role of adipokines in beta-cell failure of type 2 diabetes. J Endocrinol 216:T37–45. https://doi.org/10.1530/JOE-12-0278

    Article  CAS  PubMed  Google Scholar 

  27. Rhodes CJ (2005) Type 2 diabetes-a matter of β-cell life and death? Science 307:380–384. https://doi.org/10.1126/science.1104345

    Article  CAS  PubMed  Google Scholar 

  28. Leahy JL, Hirsch IB, Peterson KA, Schneider D (2010) Targeting beta-cell function early in the course of therapy for type 2 diabetes mellitus. J Clin Endocrinol Metab 95:4206–4216. https://doi.org/10.1210/jc.2010-0668

    Article  CAS  PubMed  Google Scholar 

  29. Carpentier A, Mittelman SD, Lamarche B, Bergman RN, Giacca A, Lewis GF (1999) Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA elevation. Am J Physiol 276:1055–1066. https://doi.org/10.1152/ajpendo.1999.276.6.E1055

    Article  Google Scholar 

  30. Halban PA, Polonsky KS, Bowden DW, Hawkins MA, Ling C, Mather KJ, Powers AC, Rhodes CJ, Sussel L, Weir GC (2014) β-Cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment. Diabetes Care 37:1751–1758. https://doi.org/10.1210/jc.2014-1425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Prentki M, Nolan CJ (2006) Islet beta cell failure in type 2 diabetes. J Clin Invest 116:1802–1812. https://doi.org/10.1172/JCI29103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kahn SE, Zraika S, Utzschneider KM, Hull RL (2009) The beta cell lesion in type 2 diabetes: there has to be a primary functional abnormality. Diabetologia 52:1003–1012. https://doi.org/10.1007/s00125-009-1321-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wajchenberg BL (2007) beta-cell failure in diabetes and preservation by clinical treatment. Endocr Rev 28:187–218. https://doi.org/10.1210/10.1210/er.2006-0038

    Article  CAS  PubMed  Google Scholar 

  34. Cnop M, Landchild MJ, Vidal J, Havel PJ, Knowles NG, Carr DR, Wang F, Hull RL, Boyko EJ, Retzlaff BM, Walden CE, Knopp RH, Kahn SE (2002) The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations: distinct metabolic effects of two fat compartments. Diabetes 51:1005–1015. https://doi.org/10.2337/diabetes.51.4.1005

    Article  CAS  PubMed  Google Scholar 

  35. Trouwborst I, Bowser SM, Goossens GH, Blaak EE (2018) Ectopic fat accumulation in distinct insulin resistant phenotypes; targets for personalized nutritional interventions. Front Nut 5:77. https://doi.org/10.3389/fnut.2018.00077

    Article  CAS  Google Scholar 

  36. Shulman GI (2014) Ectopic fat in insulin resistance, dyslipidemia and cardiometabolic disease. N Engl J Med 371:1131–1141. https://doi.org/10.1056/NEJMra1011035

    Article  CAS  PubMed  Google Scholar 

  37. Snel M, Jonker JT, Schoones J, Lamb H, de Roos A, Pijl H, Smit JW, Meinders AE, Jazet IM (2012) Ectopic fat and insulin resistance: pathophysiology and effect of diet and lifestyle interventions. Int J Endocrinol. https://doi.org/10.1155/2012/983814

    Article  PubMed  PubMed Central  Google Scholar 

  38. van der Kolk BW, Goossens GH, Jocken JW, Blaak EE (2016) Altered skeletal muscle fatty acid handling is associated with the degree of insulin resistance in overweight and obese humans. Diabetologia 59:2686–2696. https://doi.org/10.1007/s00125-016-4104-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Stinkens R, Goossens GH, Jocken JW, Blaak EE (2015) Targeting fatty acid metabolism to improve glucose metabolism. Obes Rev 16:715–757. https://doi.org/10.1111/obr.12298

    Article  CAS  PubMed  Google Scholar 

  40. Bluher M (2010) The distinction of metabolically 'healthy' from 'unhealthy' obese individuals. Curr Opin Lipidol 21:38–43. https://doi.org/10.1097/MOL.0b013e3283346ccc

    Article  CAS  PubMed  Google Scholar 

  41. Gancheva S, Jelenik T, Álvarez-Hernández E, Roden M (2018) Interorgan metabolic crosstalk in human insulin resistance. Physiol Rev 98:1371–1415. https://doi.org/10.1152/physrev.00015.2017

    Article  CAS  PubMed  Google Scholar 

  42. Neel JV (1962) Diabetes mellitus: a “thrifty” genotype rendered detrimental by "progress"? Am J Hum Genet 14:353–362

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Fuchsberger C, Flannick J, Teslovich TM et al (2016) The genetic architecture of type 2 diabetes. Nature 536:41–47. https://doi.org/10.1038/nature18642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kahn SE, Cooper ME, Del Prato S (2014) Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present and future. Lancet 383:1068–1083. https://doi.org/10.1016/S0140-6736(13)62154-6

    Article  CAS  PubMed  Google Scholar 

  45. Kolb H, Martin S (2017) Environmental/lifestyle factors in the pathogenesis and prevention of type 2 diabetes. BMC Med 15:131. https://doi.org/10.1186/s12916-017-0901-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hamman RF, Wing RR, Edelstein SL, Lachin JM, Bray GA, Delahanty L, Hoskin M, Kriska AM, Mayer-Davis EJ, Pi-Suny-er X, Regensteiner J, Venditti B, Wylie-Rosett J (2006) Effect of weight loss with lifestyle intervention on risk of diabetes. Diabetes Care 29:2102–2107. https://doi.org/10.2337/dc06-0560

    Article  PubMed  Google Scholar 

  47. Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, Rodrigues AM, Rehackova L, Adamson AJ, Sniehotta FF, Mathers JC, Ross HM, McIlvenna Y, Stefanetti R, Trenell M, Welsh P, Kean S, Ford I, McConnachie A, Sattar N, Taylor R (2018) Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet 391:541–551. https://doi.org/10.1016/S0140-6736(17)33102-1

    Article  PubMed  Google Scholar 

  48. Logue J, Walker JJ, Leese G, Lindsay R, McKnight J, Morris A, Philip S, Wild S, Sattar N, on behalf of the Scottish Diabetes Research Network Epidemiology Group (2013) Association between BMI measured within a year after diagnosis of type 2 diabetes and mortality. Diabetes Care 36:887–893. https://doi.org/10.2337/dc12-0944

    Article  PubMed  PubMed Central  Google Scholar 

  49. Thomas G, Khunti K, Curcin V, Molokhia M, Millett C, Majeed A, Paul S (2014) Obesity paradox in people newly diagnosed with type 2 diabetes with and without prior cardiovascular disease. Diabetes Obes Metab 16:317–325. https://doi.org/10.1111/dom.12217

    Article  CAS  PubMed  Google Scholar 

  50. Flegal KM, Kit BK, Orpana H, Graubard BI (2013) Association for all-cause mortality with overweight and obesity using standard body mass index categories: systematic review and meta-analysis. JAMA 309:71–82. https://doi.org/10.1001/jama.2012.113905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Hainer V, Aldhoon-Hainerova I (2013) Obesity paradox does exist. Diabetes Care 36:276–281. https://doi.org/10.2337/dcS13-2023

    Article  Google Scholar 

  52. Standl E, Erbach M, Schnel O (2013) Defending the con side: obesity paradox does not exist. Diabetes Care 36:282–286. https://doi.org/10.2337/dcS13-2040

    Article  Google Scholar 

  53. Bosello O, Donataccio MP (2013) Obesity paradox. Eat Weight Disord 18:447–448. https://doi.org/10.1007/s40519-013-0080-5

    Article  PubMed  Google Scholar 

  54. Bosello O, Donataccio MP, Cuzzolaro M (2016) Obesity or obesities? Controversies on the association between body mass index and premature mortality. Eat Weight Disord 21:165–174. https://doi.org/10.1007/s40519-016-0278-4

    Article  PubMed  Google Scholar 

  55. Doehner W, Schenkel J, Anke S, Springer J, Audebert H (2013) Overweight and obesity are associated with improved survival, functional outcomes, and stroke recurrence after acute stroke or transient ischaemic attack: observations from the TEMPiS trial. Eur Heart J 34:268–277. https://doi.org/10.1093/eurheartj/ehs340

    Article  PubMed  Google Scholar 

  56. Curtis JP, Selter JG, Wang Y, Rathore SS, Jovin IS, Jadbabaie F, Kosiborod M, Portnay EL, Sokol SI, Bader F, Krumholz HM (2005) The obesity paradox body mass index and outcomes in patients with heart failure. Arch Intern Med 165:55–56. https://doi.org/10.1001/archinte.165.1.55

    Article  PubMed  Google Scholar 

  57. Angerås O, Albertsson P, Karason K, Råmanddal T, Matejka G, James S, Lagervist B, Rosengren A, Omerovis E (2013) Evidence for obesity paradox in patients with acute coronary syndrome: a report from the Swedish Coronary Angiography and Angioplasty Registry. Eur Heart J 34:345–353. https://doi.org/10.1093/eurheartj/ehs217

    Article  PubMed  Google Scholar 

  58. Franz MJ (2013) The obesity paradox and diabetes. Diabetes Spectrum 26:145–151. https://doi.org/10.2337/diaspect.26.3.145

    Article  Google Scholar 

  59. Carnethon MR, Rasmussen-Torvik LJ, Palaniappan L (2014) The obesity paradox in diabetes. Curr Cardiol Rep 16:446. https://doi.org/10.1007/s11886-013-0446-3

    Article  PubMed  Google Scholar 

  60. Forlivesi S, Cappellari M, Bonetti B (2020) Obesity paradox and stroke: a narrative review. Eat Weight Disord. https://doi.org/10.1007/s40519-020-00876-w

    Article  PubMed  Google Scholar 

  61. Anker SD, von Haehling S (2011) The obesity paradox in heart failure: accepting reality and making rational decisions. Clin Pharmacol Ther 90:188–190. https://doi.org/10.1038/clpt.2011.72

    Article  CAS  PubMed  Google Scholar 

  62. Prescott HC, Chang VW (2018) Overweight or obese BMI is associated with earlier, but not later survival after common acute illnesses. BMC Geriatr. https://doi.org/10.1186/s12877-018-0726-2

    Article  PubMed  PubMed Central  Google Scholar 

  63. McEwen LN, Kim C, Karter AJ, Haan MN, Ghosh D, Llantz PM, Mangione CM, Thompson TJ, Herman WH (2007) Risk factors for mortality among patients with diabetes. Diabetes Care 30:1736–1741. https://doi.org/10.2337/dc07-0305

    Article  PubMed  Google Scholar 

  64. Kokkinos P, Myers J, Faselies C, Doumas M, Kheifbek R, Nylen E (2012) BMI-mortality paradox and fitness in African American and Caucasian men with type 2 diabetes. Diabetes Care 35:1021–1027. https://doi.org/10.2337/dc11-2407

    Article  PubMed  PubMed Central  Google Scholar 

  65. Lin CC, Li CI, Liu CS, Lin WY, Lin CH, Chiang JI, Yang SY, Li TC (2019) Obesity paradox in associations between body mass index and diabetes-related hospitalization and mortality in patients with type 2 diabetes: retrospective cohort studies. Diabetes Metab 45:564–572. https://doi.org/10.1016/j.diabet.2019.02.007

    Article  PubMed  Google Scholar 

  66. Kuo JF, Hsieh YT, Mao IC, Lin SD, Tu ST, Hsieh MC (2015) The Association between body mass index and all-cause mortality in patients with type 2 diabetes mellitus. Medicine. https://doi.org/10.1097/MD.0000000000001398

    Article  PubMed  PubMed Central  Google Scholar 

  67. Doehner W, Erdman E, Cairns R, Clark AL, Dormandy JA, Ferrannini E, Anker SD (2012) Inverse relation of body weight and weight change with mortality and morbidity in patients with type 2 diabetes and cardio-vascular co-morbidity: an analysis of the PROactive study population. Int J Cardiol 162:20–26. https://doi.org/10.1016/j.ijcard.2011.09.039

    Article  PubMed  Google Scholar 

  68. Pagidipati NJ, Zheng Y, Green JB, McGuire DK, Mentz RJ, Shah S, Aschner P, Delibasi T, Rodbard HW, Westerhout CM, Holman RR, Peterson ED, on behalf of the TECOS Study Group (2019) Association of obesity with cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease: Insights from TECOS. Am Heart J 219:47–57. https://doi.org/10.1016/j.ahj.2019.09.016

    Article  PubMed  Google Scholar 

  69. Park H, Lee HW, Yoo J, Lee HS, Nam HS, Kim YD, Heo JH (2019) Body mass index and prognosis in ischemic stroke patients with type 2 diabetes mellitus. Front Neurol 10:563. https://doi.org/10.3389/fneur.2019.00563

    Article  PubMed  PubMed Central  Google Scholar 

  70. Mulnier HE, Seaman HE, Raleigh VS, Soedamah-Muthu SS, Colhoun HM, Lawrenson RA (2006) Mortality in people with type 2 diabetes in the UK. Diabet Med 23:516–521. https://doi.org/10.1111/j.1464-5491.2006.01838.x

    Article  CAS  PubMed  Google Scholar 

  71. Costanzo P, Cleland JG, Pellicori P, Clark AL, Hepburn D, Kilpatrick ES, Perrone-Filardi P, Zhang J, Atkin SL (2015) The obesity paradox in type 2 diabetes mellitus: relationship of body mass index to prognosis: a cohort study. Ann Intern Med 162:610–618. https://doi.org/10.7326/M14-1551

    Article  PubMed  Google Scholar 

  72. Zhao W, Katzmarzyk PT, Horswell R, Wang Y, Li W, Johnson J, Heymseld SB, Cefalu WT, Ryan DH, Hu G (2014) Body mass index and the risk of all-cause mortality among patients with type 2 diabetes mellitus. Circulation 130:2143–2151. https://doi.org/10.1161/CIRCULATIONAHA.114.009098

    Article  PubMed  PubMed Central  Google Scholar 

  73. Lee EY, Lee YH, Yi SW, Shin SA, Yi JJ (2017) BMI and all-cause mortality in normoglycemia, impaired fasting glucose, newly diagnosed diabetes, and prevalent diabetes: a cohort study. Diabetes Care 40:1026–1033. https://doi.org/10.2337/dc16-1458

    Article  PubMed  Google Scholar 

  74. Tobias DK, Pan A, Jackson CL, O’Reilly EJ, Ding EL, Willett WC, Manson JE, Hu FB (2014) Body-mass index and mortality among adults with incident type-2 diabetes. N Engl J Med 370:233–244. https://doi.org/10.1056/NEJMoa1304501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Badrick E, Sperrin M, Buchan IE, Renehan AG (2017) Obesity paradox and mortality in adults with and without incident type 2 diabetes: a matched population-level cohort study. BMJ Open Diabetes Res Care 10:5. https://doi.org/10.1136/bmjdrc-2016-000369

    Article  Google Scholar 

  76. Zahir SF, Griffin A, Veerman JL, MaglianoDJ SJE, Cao KL, Mehdi AM (2019) Exploring the association between BMI and mortality in australian women and men with and without diabetes: the ausdiab study. Diabetologia 62:754–758. https://doi.org/10.1007/s00125-019-4830-4

    Article  PubMed  PubMed Central  Google Scholar 

  77. Tate J, Knuiman M, Davis WA, Davis TME, Bruce DG (2019) A comparison of obesity indices in relation to mortality in type 2 diabetes: the Fremantle Diabetes Study. Diabetologia 63:528–536. https://doi.org/10.1007/s00125-019-05057-8

    Article  CAS  PubMed  Google Scholar 

  78. Eeg-Olofsson K, Cederholm J, Nilsson PM, Zethelius B, Nunez L, Gudbjörnsdóttir S, Eliasson B (2009) Overweight, obesity and cardiovascular diseases and mortality in type 2 diabetes: an observational study in 13,087 patients. Diabetologia 52:65–73. https://doi.org/10.1007/s00125-008-1190-x

    Article  CAS  PubMed  Google Scholar 

  79. Adamopoulos C, Meyer P, Desai RV, Karatzidou K, Ovalle F, White M, Aban I, Love TE, Deedwania P, Anker SD, Ahmed A (2011) Absence of obesity paradox in patients with chronic hearth failure and diabetes mellitus: a propensity-matched study. Eur J Hearth Fail 13:200–206. https://doi.org/10.1093/eurjhf/hfq159

    Article  Google Scholar 

  80. Zamora E, Lupón J, Enjuanes C, Pascual-Figal D, de Antonio M, Domingo M, Comín-Colet J, Vila J, Peñafiel J, Farré N, Alonso N, Santesmases J, Troya M, Bayés-Genís A (2016) No benefit from the obesity paradox for diabetic patients with hearth failure. Eur J Hearth Fail 18:851–858. https://doi.org/10.1002/ejhf.576

    Article  Google Scholar 

  81. Kwon Y, Kim HJ, Park S, Park YG, Cho KH (2017) Body mass index-related mortality in patients with type 2 diabetes and heterogeneity in obesity paradox studies: a dose-response meta-analysis. PLoS ONE 3:12. https://doi.org/10.1371/journal.pone.0168247

    Article  CAS  Google Scholar 

  82. Han SJ, Boyko EJ (2018) The evidence for an obesity paradox in type 2 diabetes mellitus. Diabetes Metab J 42:179–187. https://doi.org/10.4093/dmj.2018.0055

    Article  PubMed  PubMed Central  Google Scholar 

  83. Jong CB, Li HY, Pan SL, Hsieh MY, Su FY, Chen KC, Yin WH, Chan SH, Wu YW, Wang KY, Chang KC, Hwang JJ, Wu CC (2019) Relationship between body mass index, antidiabetic agents and midterm mortality in patients with both type 2 diabetes mellitus and acute coronary syndrome. J Am Heart Assoc. https://doi.org/10.1161/JAHA.118.011215

    Article  PubMed  PubMed Central  Google Scholar 

  84. Yu E, Ley SH, Manson JE, Willett W, Satija A, Hu FB, Stokes A (2017) Weight history and all cause and cause-specific mortality in three prospective cohort studies. Ann Intern Med 166:613–620. https://doi.org/10.7326/M16-1390

    Article  PubMed  PubMed Central  Google Scholar 

  85. Neeland IJ, TurerAT ACR, Berry JD, Rohatgi A, Das SR, Khera A, Vega GL, McGuire DK, Grundy SM, de Lemos JA (2015) Body fat distribution and incident cardiovascular disease in obese adults. J Am Coll Cardiol 65:2150–2151. https://doi.org/10.1016/j.jacc.2015.01.061

    Article  PubMed  PubMed Central  Google Scholar 

  86. Hayashi T, Boyko EJ, McNeely MJ, Leonetti DL, Kahn SE, Fujimoto WY (2008) Visceral adiposity, not abdominal subcutaneous fat area, is associated with an increase in future insulin resistance in Japanese Americans. Diabetes 57:1269–1275. https://doi.org/10.2337/db07-1378

    Article  CAS  PubMed  Google Scholar 

  87. Bozorgmanesh M, Arshi B, Sheikholeslami F, Azizi F, Hadaegh F (2014) No obesity paradox-BMI incapable of adequately capturing the relation of obesity with all-cause mortality: an inception diabetes cohort study. Int J Endocrinol. https://doi.org/10.1155/2014/282089

    Article  PubMed  PubMed Central  Google Scholar 

  88. Lim S, Meigs JB (2013) Ectopic fat and cardiometabolic and vascular risk. Int J Cardiol 169:166–176. https://doi.org/10.1016/j.ijcard.2013.08.077

    Article  PubMed  Google Scholar 

  89. Kim JH, Lim S, Choi SH, Kim KM, Yoon JW, Kim KW, Lim JY, Park KS, Jang HC (2014) Sarcopenia: an independent predictor of mortality in community-dwelling older Korean men. J Gerontol A Biol Sci Med Sci 69:1244–1252. https://doi.org/10.1093/gerona/glu050

    Article  PubMed  Google Scholar 

  90. Marzetti E, Calvani R, Tosato M, Cesari M, Di Bari M, Cherubini A, Collamati A, D'Angelo E, Pahor M, Bernabei R, Landi F, SPRINTT Consortium (2017) Sarcopenia: an overview. Aging Clin Exp Res 29:11–17. https://doi.org/10.1007/s40520-016-0704-5

    Article  PubMed  Google Scholar 

  91. Batsis JA, Mackenzie TA, Emeny RT, Lopez-Jimenez F, Bartels SJ (2017) Low lean mass with and without obesity, and mortality: results from the 1999–2004 National Health and Nutrition Ex-amination Survey. J Gerontol A Biol Sci Med Sci 72:1445–1451. https://doi.org/10.1093/gerona/glx002

    Article  PubMed  PubMed Central  Google Scholar 

  92. Rantanen T, Harris T, Leveille SG, Visser M, Foley D, Masaki K, Guralnik JM (2000) Muscle strength and body mass index as long-term predictors of mortality in initially healthy men. J Gerontol A Biol Sci Med Sci 55:M168–M173. https://doi.org/10.1093/gerona/55.3.m168

    Article  CAS  PubMed  Google Scholar 

  93. Leong DP, Teo KK, Rangarajan S, Lopez-Jaramillo P, Avezum A Jr, Orlandini A, Seron P, Ahmed SH, Rosengren A, Kelishadi R, Rahman O, Swaminathan S, Iqbal R, Gupta R, Lear SA, OguzA YK, Zatonska K, Chifamba J, Igumbor E, Mohan V, Anjana RM, Gu H, Li W, Yusuf S, Prospective Urban Rural Epidemiology (PURE) Study investigators (2015) Prognostic value of grip strength: findings from the prospective urban rural epidemiology (PURE) study. Lancet 386:266–273. https://doi.org/10.1016/S0140-6736(14)62000-6

    Article  PubMed  Google Scholar 

  94. Hamasaki H, Kawashima Y, Katsuyama H, Sako A, Goto A, Yanai H (2017) Association of handgrip strength with hospitalization, cardiovascular events, and mortality in Japanese patients with type 2 diabetes. Sci Rep 7:7041. https://doi.org/10.1038/s41598-017-07438-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Church TS, Cheng YJ, Earnest CP, Barlow CE, Gibbons LW, Priest EL, Blair SN (2004) Exercise capacity and body composition as predictors of mortality among men with diabetes. Diabetes Care 27:83–88. https://doi.org/10.2337/diacare.27.1.83

    Article  PubMed  Google Scholar 

  96. McAuley PA, Myers JN, Abella JP, Tan SY, Froelicher VF (2007) Exercise capacity and body mass as predictors of mortality among male veterans with type 2 diabetes. Diabetes Care 30:1539–1543. https://doi.org/10.2337/dc06-2397

    Article  PubMed  Google Scholar 

  97. McAuley PA, Kokkinos PF, Oliveira RB, Emerson BT, Myers JN (2010) Obesity paradox and cardiorespiratory fitness in 12,417 male veterans aged 40 to 70 years. Mayo Clin Proc 85:115–121

    Article  PubMed  PubMed Central  Google Scholar 

  98. Whelton SP, McAuley PA, Dardari Z, Orimoloye OA, Brawner CA, Ehrman JK, Keteyian SJ, Al-Mallah M, Blaha MJ (2020) Association of BMI, fitness, and mortality in patients with diabetes: evaluating the obesity paradox in the Henry Ford Exercise Testing Project (FIT Project) cohort. Diabetes Care 43:677–682. https://doi.org/10.2337/dc19-1673

    Article  PubMed  Google Scholar 

  99. Preston SH, Stokes A (2014) Obesity paradox: conditioning on disease enhances biases in estimating the mortality risks of obesity. Epidemiology 25:454–461. https://doi.org/10.1097/EDE.0000000000000075

    Article  PubMed  PubMed Central  Google Scholar 

  100. Yano Y, Kario K, Ishikawa S, Ojima T, Gotoh T, Kayaba K, Tsutsumi A, Shimada K, Nakamura Y, Kjii E (2013) Associations between diabetes, leanness, and the risk of death in the Japanese general population: the Jichi Medical School Cohort Study. Diabetes Care 36:1186–1192. https://doi.org/10.2337/dc12-1736

    Article  PubMed  PubMed Central  Google Scholar 

  101. Zoppini G, Verlato G, Leuzinger C, Zamboni C, Brun E, Bonora E, Muggeo M (2003) Body mass index and the risk of mortality in type II diabetic patients from Verona. Int J Obes Relat Metab Disord 27:281–285. https://doi.org/10.1038/sj.ijo.802199

    Article  CAS  PubMed  Google Scholar 

  102. Femminò S, Pagliaro P, Penna C (2020) Obesity and cardioprotection. Curr Med Chem 27:230–239. https://doi.org/10.2174/0929867326666190325094453

    Article  CAS  PubMed  Google Scholar 

  103. Jamieson A, Finer N (2017) Can we reconcile 'the obesity paradox' with recent cardiovascular outcome trials in diabetes? Clin Obes 7:255–259. https://doi.org/10.1111/cob.12217

    Article  CAS  PubMed  Google Scholar 

  104. Tobias DK, Manson JE (2018) The obesity paradox in type 2 diabetes and mortality. Am J Lifestyle Med 12:244–251. https://doi.org/10.1177/1559827616650415

    Article  PubMed  Google Scholar 

  105. Lajous M, Bijon A, Fagherazzi G, Boutron-Ruault MC, Balkau B, Clavel-Chapelon F, Hernán MA (2014) Body mass index, diabetes, and mortality in French women: explaining away a “paradox”. Epidemiology 25:10–14. https://doi.org/10.1097/EDE.0000000000000031

    Article  PubMed  PubMed Central  Google Scholar 

  106. Carnethon MR, de Chavez PJ, Biggs ML, Lewis CE, Pankow JS, Bertoni AG, Golden SH, Liu K, Mukamal KJ, Campbell-Jenkins B, Dyer AR (2012) Association of weight status with mortality in adults with incident diabetes. JAMA 308:581–590. https://doi.org/10.1001/jama.2012.928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Monami M, Cremasco F, Lamanna C, Colombi C, Desideri CM, Iacomelli I, Marchionni N, Mannucci E (2011) Glucagon-like peptide-1 receptor agonists and cardiovascular events: a meta-analysis of randomized clinical trials. Exp Diabetes Res. https://doi.org/10.1155/2011/215764

    Article  PubMed  PubMed Central  Google Scholar 

  108. Look AHEAD Research Group1, Pi-Sunyer X, Blackburn G, Brancati FL, Bray GA, Bright R, Clark JM, Curtis JM, Espeland MA, Foreyt JP, Graves K, Haffner SM, Harrison B, Hill JO, Horton ES, Jakicic J, Jeffery RW, Johnson KC, Kahn S, Kelley DE, Kitabchi AE, Knowler WC, Lewis CE, Maschak-Carey BJ, Montgomery B, Nathan DM, Patricio J, Peters A, Redmon JB, Reeves RS, Ryan DH, Safford M, Van Dorsten B, Wadden TA, Wagenknecht L, Wesche-Thobaben J, Wing RR, Yanovski SZ (2007) Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 30:1374–1383. https://doi.org/10.2337/dc07-0048

    Article  Google Scholar 

  109. Chen Y, Yang X, Wang J, Li Y, Ying D, Yuan H (2018) Weight loss increases all cause mortality in overweight or obese patients with diabetes. Medicine. https://doi.org/10.1097/MD.0000000000012075

    Article  PubMed  PubMed Central  Google Scholar 

  110. Aucott LS, Philip S, Avenell A, Afolabi E, Sattar N, Wild S, on behalf of the Scottish Diabetes Research Network Epidemiology Group (2018) Patterns of weight change after the diagnosis of type 2 diabetes in Scotland and their relationship with glycaemic control, mortality and cardiovascular outcomes: a retrospective cohort study. BMJ. https://doi.org/10.1136/bmjopen-2015-010836

    Article  Google Scholar 

  111. Look AHEAD Research Group, Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, Crow RS, Curtis JM, Egan CM, Espeland MA, Evans M, Foreyt JP, Ghazarian S, Gregg EW, Harrison B, Hazuda HP, Hill JO, Horton ES, Hubbard VS, Jakicic JM, Jeffery RW, Johnson KC, Kahn SE, Kitabchi AE, Knowler WC, Lewis CE, Maschak-Carey BJ, Montez MG, Murillo A, Nathan DM, Patricio J, Peters A, Pi-Sunyer X, Pownall H, Reboussin D, Regensteiner JG, Rickman AD, Ryan DH, Safford M, Wadden TA, Wagenknecht LE, West DS, Williamson DF, Yanovski SZ (2013) Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 369:145–154. https://doi.org/10.1056/NEJMoa1212914

    Article  CAS  Google Scholar 

  112. Ma C, Avenell A, Bolland M, Hudson J, Stewart F, Robertson C, Sharma P, Fraser C, MacLennan G (2017) Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis. BMJ. https://doi.org/10.1136/bmj.j4849

    Article  PubMed  PubMed Central  Google Scholar 

  113. Lean MEJ, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, Rodrigues AM, Rehackova L, Adamson AJ, Sniehotta FF, Mathers JC, Ross HM, McIlvenna Y, Welsh P, Kean S, Ford I, McConnachie A, Messow CM, Sattar N, Taylor R (2019) Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol 7:344–355. https://doi.org/10.1016/S2213-8587(19)30068-3

    Article  PubMed  Google Scholar 

  114. Lajous M, Banack HR, Kaufman JS, Hernan MA (2015) Should patients with chronic disease be told to gain weight? The obesity paradox and selection bias. Am J Med 128:334–336. https://doi.org/10.1016/j.amjmed.2014.10.043

    Article  PubMed  Google Scholar 

  115. Sjöström L (2013) Review of the key results from the Swedish Obese Subjects (SOS) trial—a prospective controlled intervention study of bariatric surgery. J Intern Med 273:219–234. https://doi.org/10.1111/joim.12012

    Article  PubMed  Google Scholar 

  116. Fried M, Yumuk V, Oppert JM, Scopinaro N, Torres A, Weiner R, Yashkov Y, Frühbeck G, International Federation for Surgery of Obesity and Metabolic Disorders-European Chapter (IFSO-EC), European Association for the Study of Obesity (EASO), European Association for the Study of Obesity Obesity Management Task Force (EASO OMTF) (2014) Interdisciplinary European guidelines on metabolic and bariatric surgery. Obes Surg 24:42–55. https://doi.org/10.1007/s11695-013-1079-8

    Article  CAS  PubMed  Google Scholar 

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Gravina, G., Ferrari, F. & Nebbiai, G. The obesity paradox and diabetes. Eat Weight Disord 26, 1057–1068 (2021). https://doi.org/10.1007/s40519-020-01015-1

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