Obesity without metabolic disorder and silent brain infarcts in aneurologically healthy population

Abstract

Objective

Obesity without metabolic disorder [Ob(+)MD(−)] is a unique subcategory of obesity where individuals are protected from the obesity-related complications. Although conflicting clinical outcomes have been reported, there has been no study of the effects of Ob(+)MD(−) on cerebrovascular disease. In this study, we evaluated the association between the Ob(+)MD(−) phenotype and silent brain infarcts (SBI) in a neurologically healthy population.

Subjects/methods

We evaluated a consecutive series of healthy volunteers recruited between January 2006 and December 2013. MD(−) status was assessed using five clinical markers: blood pressure, triglycerides, high-density lipoprotein, fasting plasma glucose, and waist circumference. Obesity was defined when body mass index ≥ 25 kg/m2. SBI was defined as asymptomatic, well-defined lesions with a diameter ≥ 3 mm with the same signal characteristics as the cerebrospinal fluid on T1- or T2-weighted images.

Results

A total of 3165 subjects were assessed, and 262 (8%) SBI cases were identified. In multivariate analyses, non-obesity with metabolic disorder [Ob(−)MD(+)] (adjusted odds ratio [aOR] = 1.65, 95% confidence interval [CI] = 1.07–2.56, P = 0.025) and obesity with metabolic disorder [Ob(+)MD(+)] (aOR = 1.75, 95% CI = 1.12–2.75, P = 0.014) were closely associated with SBI after adjustment for confounders. Meanwhile, Ob(+)MD(−) did not show any significant association with SBI (aOR = 0.85, 95% CI = 0.20–3.72, P = 0.832). These findings may indicate that metabolic abnormality, irrespective of obesity status, is a main risk factor of SBI. When we compared SBI burdens between the four metabolic phenotypes, the Ob(+)MD(+) and Ob(−)MD(+) groups had higher rates of multiple lesions than the Ob(+)MD(−) and non-obesity without metabolic disorder groups.

Conclusions

The presence of metabolic abnormality, and not obesity per se, is independently associated with the prevalence of SBI in a healthy population.

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References

  1. 1.

    Hinnouho G-M, Czernichow S, Dugravot A, Batty GD, Kivimaki M, Singh-Manoux. A metabolically healthy obesity and risk of mortality: does the definition of metabolic health matter? Diabetes care 2013;36:2294–300.

  2. 2.

    Bradshaw PT, Monda KL, Stevens J. Metabolic syndrome in healthy obese, overweight, and normal weight individuals: the Atherosclerosis Risk in Communities Study. Obesity. 2013;21:203–9.

  3. 3.

    Hinnouho G-M, Czernichow S, Dugravot A, Nabi H, Brunner EJ, Kivimaki M, et al. Metabolically healthy obesity and the risk of cardiovascular disease and type 2 diabetes: the Whitehall II cohort study. Eur Heart J. 2014;36:551–9.

  4. 4.

    Primeau V, Coderre L, Karelis A, Brochu M, Lavoie M, Messier V, et al. Characterizing the profile of obese patients who are metabolically healthy. Int J Obes. 2011;35:971.

  5. 5.

    Chang Y, Ryu S, Suh B, Yun K, Kim C, Cho S. Impact of BMI on the incidence of metabolic abnormalities in metabolically healthy men. Int J Obes. 2012;36:1187.

  6. 6.

    Ortega FB, Lee D-c, Katzmarzyk PT, Ruiz JR, Sui X, Church TS, et al. The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness. Eur Heart J. 2012;34:389–97.

  7. 7.

    Kramer CK, Zinman B, Retnakaran R. Are metabolically healthy overweight and obesity benign conditions? A systematic review and meta-analysis. Ann Intern Med. 2013;159:758–69.

  8. 8.

    Hashimoto Y, Tanaka M, Okada H, Senmaru T, Hamaguchi M, Asano M, et al. Metabolically healthy obesity and risk of incident CKD. Clin J Am Soc Nephrol. 2015;10:578–83.

  9. 9.

    Jung CH, Lee MJ, Hwang JY, Jang JE, Leem J, Yang DH, et al. Association of metabolically healthy obesity with subclinical coronary atherosclerosis in a Korean population. Obesity. 2014;22:2613–20.

  10. 10.

    Vermeer SE, Longstreth JrWT, Koudstaal PJ. Silent brain infarcts: a systematic review. Lancet Neurol. 2007;6:611–9.

  11. 11.

    Kim BJ, Lee S-H. Prognostic impact of cerebral small vessel disease on stroke outcome. J Stroke. 2015;17:101.

  12. 12.

    Nam K-W, Kwon H-M, Jeong H-Y, Park J-H, Kim SH, Jeong S-M. High neutrophil to lymphocyte ratios predict intracranial atherosclerosis in a healthy population. Atherosclerosis. 2018;269:117–21.

  13. 13.

    Chang Y, Kim B-K, Yun KE, Cho J, Zhang Y, Rampal S, et al. Metabolically-healthy obesity and coronary artery calcification. J Am Collof Cardiology. 2014;63:2679–86.

  14. 14.

    Grundy SM, Becker D, Clark LT, Cooper RS, Denke MA, Howard J, et al. Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Circulation. 2002;106:3143–421.

  15. 15.

    Hamer M, Stamatakis E. Metabolically healthy obesity and risk of all-cause and cardiovascular disease mortality. J Clin Endocrinol Metab. 2012;97:2482–8.

  16. 16.

    Phillips CM, Perry IJ. Does inflammation determine metabolic health status in obese and nonobese adults? J Clin Endocrinol Metab. 2013;98:E1610–E1619.

  17. 17.

    Blüher M. The distinction of metabolically ‘healthy’from ‘unhealthy’obese individuals. Curr Opin Lipidol. 2010;21:38–43.

  18. 18.

    Karelis AD. Metabolically healthy but obese individuals. Lancet. 2008;372:1281–3.

  19. 19.

    Stefan N, Häring H-U, Hu FB, Schulze MB. Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications. Lancet Diabetes Endocrinol. 2013;1:152–62.

  20. 20.

    Aung K, Lorenzo C, Hinojosa MA, Haffner SM. Risk of developing diabetes and cardiovascular disease in metabolically unhealthy normal-weight and metabolically healthy obese individuals. J Clin Endocrinol Metab. 2014;99:462–8.

  21. 21.

    Aguilar-Salinas CA, García EG, Robles L, Riano D, Ruiz-Gomez DG, García-Ulloa AC, et al. High adiponectin concentrations are associated with the metabolically healthy obese phenotype. J Clin Endocrinol Metab. 2008;93:4075–9.

  22. 22.

    Wardlaw J. Blood-brain barrier and cerebral small vessel disease. J Neurol Sci. 2010;299:66–71.

  23. 23.

    Hwang Y, Hayashi T, Fujimoto W, Kahn S, Leonetti D, McNeely M, et al. Visceral abdominal fat accumulation predicts the conversion of metabolically healthy obese subjects to an unhealthy phenotype. Int J Obes. 2015;39:1365.

  24. 24.

    Soriguer F, Gutiérrez-Repiso C, Rubio-Martín E, García-Fuentes E, Almaraz MC, Colomo N, et al. Metabolically healthy but obese, a matter of time? Findings from the prospective Pizarra study. J Clin Endocrinol Metab. 2013;98:2318–25.

  25. 25.

    Eckel N, Meidtner K, Kalle-Uhlmann T, Stefan N, Schulze MB. Metabolically healthy obesity and cardiovascular events: a systematic review and meta-analysis. Eur J Prev Cardiol. 2016;23:956–66.

  26. 26.

    Chang Y, Ryu S, Choi Y, Zhang Y, Cho J, Kwon M-J, et al. Metabolically healthy obesity and development of chronic kidney disease: a cohort study. Ann Intern Med. 2016;164:305–12.

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Correspondence to Hyung-Min Kwon.

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