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Epidemiology and Population Health

Distinguishing health-related parameters between metabolically healthy and metabolically unhealthy obesity in women

International Journal of Obesity (2024)Cite this article

Subjects

Abstract

Background

Obesity represents a global health crisis, yet a dichotomy is emerging with classification according to the metabolic state into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). This study aimed to identify distinctive systemic clinical/endocrinological parameters between MHO individuals, employing a comprehensive comparative analysis of 50 biomarkers. Our emphasis was on routine analytes, ensuring cost-effectiveness for widespread use in diagnosing metabolic health.

Subjects/methods

The study included 182 women diagnosed with obesity referred for bariatric surgery at the Endocrinology, Diabetes, and Metabolism Service of São João Hospital and University Centre in Portugal. MUO was defined by the presence of at least one of the following metabolic disorders: diabetes, hypertension, or dyslipidemia. Patients were stratified based on the diagnosis of these pathologies.

Results

Significantly divergent health-related parameters were observed between MHO and MUO patients. Notable differences included: albumin (40.1 ± 2.2 vs 40,98 ± 2.6 g/L, p value = 0.017), triglycerides (110.7 ± 51.1 vs 137.57 ± 82.6 mg/dL, p value = 0.008), glucose (99.49 ± 13.0 vs 119.17 ± 38.9 mg/dL, p value < 0.001), glycated hemoglobin (5.58 ± 0.4 vs 6.15 ± 1.0%, p value < 0.001), urea (31.40 ± 10.0 vs 34.61 ± 10.2 mg/dL, p value = 0.014), total calcium (4.64 ± 0.15 vs 4.74 ± 0.17 mEq/L, 1 mEq/L = 1 mg/L, p value < 0.001), ferritin (100.04 ± 129.1 vs 128.55 ± 102.1 ng/mL, p value = 0.005), chloride (104.68 ± 1.5 vs 103.04 ± 2.6 mEq/L, p value < 0.001), prolactin (13.57 ± 6.3 vs 12.47 ± 7.1 ng/mL, p value = 0.041), insulin (20.36 ± 24.4 vs 23.87 ± 19.6 μU/mL, p value = 0.021), c peptide (3.78 ± 1.8 vs 4.28 ± 1.7 ng/mL, p value = 0.003), albumin/creatinine ratio (15.41 ± 31.0 vs 48.12 ± 158.7 mg/g creatinine, p value = 0.015), and whole-body mineral density (1.27 ± 0.1 vs 1.23 ± 0.1 g/cm2, p value = 0.016).

Conclusions

Our findings highlight potential additional parameters that should be taken into consideration alongside the commonly used biomarkers for classifying metabolic health in women. These include albumin, urea, total calcium, ferritin, chloride, prolactin, c-peptide, albumin-creatinine ratio, and whole-body mineral density. Moreover, our results also suggest that MHO may represent a transitional phase preceding the development of the MUO phenotype.

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Fig. 1: Graphic representation of the distribution of metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) according to Body Mass Index (BMI) categories and menopausal status.
Fig. 2: Graphical representation of the statistically significant parameters between MHO and MUO with identification of reference values available.

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Data availability

The datasets generated during and/or analysed during the current study are not publicly available due to privacy or ethical restrictions.

References

  1. Purnell JQ. Definitions, classification, and epidemiology of obesity. Endotext [Internet]. 2023; https://www.ncbi.nlm.nih.gov/books/NBK279167/.

  2. Kinlen D, Cody D, O’Shea D. Complications of obesity. QJM. 2018;111:437–443.

    Article  CAS  PubMed  Google Scholar 

  3. Blüher M. Metabolically healthy obesity. Endocr Rev. 2020;41:bnaa004.

  4. Phillips CM. Metabolically healthy obesity: definitions, determinants and clinical implications. Rev Endocr Metab Disord. 2013;14:219–27.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  6. Smith GI, Mittendorfer B, Klein S. Metabolically healthy obesity: facts and fantasies. J Clin Investig. 2019;129:3978–89.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Mayoral LP, Andrade GM, Mayoral EP, Huerta TH, Canseco SP, Rodal Canales FJ, et al. Obesity subtypes, related biomarkers & heterogeneity. Indian J Med Res. 2020;151:11–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rey‐López JP, de Rezende LF, Pastor‐Valero M, Tess BH. The prevalence of metabolically healthy obesity: a systematic review and critical evaluation of the definitions used. Obes Rev. 2014;15:781–90.

    Article  PubMed  Google Scholar 

  9. Stefan N. Causes, consequences, and treatment of metabolically unhealthy fat distribution. Lancet Diabetes Endocrinol. 2020;8:616–27.

    Article  PubMed  Google Scholar 

  10. Stefan N, Schulze MB. Metabolic health and cardiometabolic risk clusters: implications for prediction, prevention, and treatment. Lancet Diabetes Endocrinol. 2023;11:426–40.

    Article  CAS  PubMed  Google Scholar 

  11. Jelliffe D, Jelliffe E. Underappreciated pioneers. Quetelet: man and index. Am J Clin Nutr. 1979;32:2519–21.

    Article  CAS  PubMed  Google Scholar 

  12. Lavie CJ, Laddu D, Arena R, Ortega FB, Alpert MA, Kushner RF. Healthy weight and obesity prevention: JACC health promotion series. J Am Coll Cardiol. 2018;72:1506–31.

    Article  PubMed  Google Scholar 

  13. van Vliet-Ostaptchouk JV, Nuotio ML, Slagter SN, Doiron D, Fischer K, Foco L, et al. The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies. BMC Endocr Disord. 2014;14:9.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Liu C, Wang C, Guan S, Liu H, Wu X, Zhang Z, et al. The prevalence of metabolically healthy and unhealthy obesity according to different criteria. Obes Facts. 2019;12:78–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hamer M, Bell JA, Sabia S, Batty GD, Kivimäki M. Stability of metabolically healthy obesity over 8 years: the English longitudinal study of ageing. Eur J Endocrinol. 2015;173:703–08.

    Article  CAS  PubMed  Google Scholar 

  16. Fanali G, Di Masi A, Trezza V, Marino M, Fasano M, Ascenzi P. Human serum albumin: from bench to bedside. Mol Asp Med. 2012;33:209–90.

    Article  CAS  Google Scholar 

  17. Luís C, Baylina P, Soares R, Fernandes R. Metabolic dysfunction biomarkers as predictors of early diabetes. Biomolecules. 2021;11:1589.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kunutsor SK, Apekey TA, Walley J, Kain K. Ferritin levels and risk of type 2 diabetes mellitus: an updated systematic review and meta-analysis of prospective evidence. Diabetes Metab Res Rev. 2013;29:308–18.

    Article  CAS  PubMed  Google Scholar 

  19. Zhang W, Zheng J, Zhang J, Li N, Yang X, Fang ZZ, et al. Associations of serum amino acids related to urea cycle with risk of chronic kidney disease in Chinese with type 2 diabetes. Front Endocrinol (Lausanne). 2023;14:1117308.

    Article  PubMed  Google Scholar 

  20. Kopelman P. Physiopathology of prolactin secretion in obesity. Int J Obes. 2000;24:S104–S108.

    Article  CAS  Google Scholar 

  21. Tanner MJ, Hadlow NC, Wardrop R. Variation of female prolactin levels with menopausal status and phase of menstrual cycle. Aust N Z J Obstet Gynaecol. 2011;51:321–4.

    Article  PubMed  Google Scholar 

  22. Turcotte AF, O’Connor S, Morin SN, Gibbs JC, Willie BM, Jean S, et al. Association between obesity and risk of fracture, bone mineral density and bone quality in adults: a systematic review and meta-analysis. PLoS One. 2021;16:e0252487.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lonardo A, Mantovani A, Lugari S, Targher G. Epidemiology and pathophysiology of the association between NAFLD and metabolically healthy or metabolically unhealthy obesity. Ann Hepatol. 2020;19:359–66.

    Article  CAS  PubMed  Google Scholar 

  24. Pfortmueller CA, Uehlinger D, von Haehling S, Schefold JC. Serum chloride levels in critical illness—the hidden story. Intensive Care Med Exp. 2018;6:10.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wahren J, Ekberg K, Johansson J, Henriksson M, Pramanik A, Johansson BL, et al. Role of C-peptide in human physiology. Am J Physiol Endocrinol Metab. 2000;278:E759–E768.

    Article  CAS  PubMed  Google Scholar 

  26. Hills CE, Brunskill NJ. Cellular and physiological effects of C-peptide. Clin Sci. 2009;116:565–74.

    Article  CAS  Google Scholar 

  27. Rossi MCE, Nicolucci A, Pellegrini F, Comaschi M, Ceriello A, Cucinotta D, et al. Obesity and changes in urine albumin/creatinine ratio in patients with type 2 diabetes: the DEMAND Study. Nutr Metab Cardiovasc Dis. 2010;20:110–16.

    Article  CAS  PubMed  Google Scholar 

  28. Du N, Peng H, Chao X, Zhang Q, Tian H, Li H. Interaction of obesity and central obesity on elevated urinary albumin-to-creatinine ratio. PLoS One. 2014;9:98926.

    Article  Google Scholar 

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Acknowledgements

The authors would like to acknowledge the patients enrolled in this study. Carla Luís acknowledges FCT—Fundação para a Ciência e Tecnologia by a doctoral scholarship (SFRH/BD/146489/2019).

Author information

Authors and Affiliations

  1. Endocrinology, Diabetes and Metabolism Service, São João Hospital and University Centre, 4200-319, Porto, Portugal

    Fernando Mendonça, Telma Moreno, Diana Festas, Jorge Pedro & Ana Varela

  2. CRIO group—Centro de Responsabilidade Integrado de Obesidade, São João Hospital and University Centre, 4200-319, Porto, Portugal

    Fernando Mendonça, Paula Freitas, Diana Festas, Jorge Pedro, Ana Varela & Eduardo Lima Costa

  3. Biochemistry Unit, Biomedicine Department, FMUP—Faculty of Medicine, University of Porto, 4200-450, Porto, Portugal

    Pietra Soares, Ilda Rodrigues, Raquel Soares & Carla Luís

  4. i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135, Porto, Portugal

    Paula Freitas, Raquel Soares & Carla Luís

  5. Nuclear Medicine Department, São João Hospital and University Centre, 4200-319, Porto, Portugal

    Ana Fernandes

  6. Faculty of Health Sciences, University Fernando Pessoa, Fernando Pessoa Hospital-School (FCS/HEFP/UFP), Porto, Portugal

    Rúben Fernandes

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  1. Fernando Mendonça
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Consortia

CRIO group

  • Fernando Mendonça
  • , Paula Freitas
  • , Diana Festas
  • , Jorge Pedro
  • , Ana Varela
  •  & Eduardo Lima Costa

Contributions

Conceptualization: FM, CL; methodology: FM, CL; validation: RF, RS, ELC; formal analysis: FM, CL; resources and methodology: PS, TM, PF, IR, DF, JP, AV, AR; supervision: PF, RF, RS, ELC; Writing—original draft preparation: CL; writing—review, editing, and validation: FM; PS, TM, PF, IR, DF, JP, AV, AR, RF, RS, ELC, CL. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Carla Luís.

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Informed consent was obtained from all subjects involved in the study.

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Mendonça, F., Soares, P., Moreno, T. et al. Distinguishing health-related parameters between metabolically healthy and metabolically unhealthy obesity in women. Int J Obes (2024). https://doi.org/10.1038/s41366-024-01519-1

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