Skip to main content
SpringerLink
Log in

Associations between markers of glucose metabolism and bone measures among diabetic and non-diabetic adults

  • Research article
  • Published:
Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Purpose

To investigate the relationships between bone measures, vitamin D status and markers of glucose metabolism among diabetic and non-diabetic adults.

Methods

Cross sectional study with 298 adults (mean age 57.5 years, SD = 14.8; 44.3% male, 16.9% diabetic) participants of the Health Survey–São Paulo (ISA-Capital) 2014–2015. Blood samples were collected to assess serum glucose, insulin and 25 hydroxyvitamin D [25(OH)D] concentrations. Dual-energy x-ray absorptiometry (DXA) was performed to determine total body fat; total lean mass; full body bone mineral density (BMD); lumbar spine BMD and bone mineral content (BMC); and femur BMD and BMC. Fat mass index (FMI), lean mass index (LMI), quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment of insulin resistance (HOMA-IR) and of β-pancreatic cell function (HOMA-β) were calculated. Linear regression analysis were performed.

Results

Multiple bone measures were associated with markers of glucose metabolism in analyses adjusted by age and sex. However, after additional adjustments by LMI, FMI and serum 25(OH)D, only associations of lumbar spine BMC with HOMA-IR (β = 0.167; p = 0.035) and QUICKI (β = -1.879; p = 0.027) persisted, in the subgroup of diabetic participants. Analysis restricted to diabetic subjects revealed stronger correlations between bone parameters and markers of glucose metabolism.

Conclusions

Our study observed positive associations between BMD and markers of insulin resistance among a sample of adults. Correlations were stronger among diabetic subjects, and some associations between bone and glucose metabolism were independent of adiposity. Findings reinforce the need of further research for better understanding the bidirectional and multifactorial crosstalk between glucose homeostasis and bone metabolism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Data availability

Data will be made available on request.

Code availability

Not applicable.

References

  1. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130(3):456–69.

    Article  CAS  Google Scholar 

  2. Wolf G. Function of the bone protein osteocalcin: definitive evidence. Nutr Rev. 1996;54(10):332–3.

    Article  CAS  Google Scholar 

  3. Wood RJ. Vitamin D and adipogenesis: new molecular insights. Nutr Rev. 2008;66(1):40–6.

    Article  Google Scholar 

  4. Díez JJ, Iglesias P. The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol. 2003;148(3):293–300.

    Article  Google Scholar 

  5. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;100(2):197–207.

    Article  CAS  Google Scholar 

  6. Stefan N, Vozarova B, Funahashi T, Matsuzawa Y, Weyer C, Lindsay RS, et al. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes. 2002;51(6):1884–8.

    Article  CAS  Google Scholar 

  7. Ferron M, Hinoi E, Karsenty G, Ducy P. Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci U S A. 2008;105(13):5266–70.

    Article  CAS  Google Scholar 

  8. Kaneko I, Sabir MS, Dussik CM, Whitfield GK, Karrys A, Hsieh J-C, et al. 1,25-Dihydroxyvitamin D regulates expression of the tryptophan hydroxylase 2 and leptin genes: implication for behavioral influences of vitamin D. FASEB J. 2015;29(9):4023–35.

    Article  CAS  Google Scholar 

  9. Maestro B, Molero S, Bajo S, Dávila N, Calle C. Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D(3). Cell Biochem Funct. 2002;20(3):227–32.

    Article  CAS  Google Scholar 

  10. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81.

    Article  CAS  Google Scholar 

  11. Pannu PK, Calton EK, Soares MJ. Calcium and vitamin D in obesity and related chronic disease. Adv Food Nutr Res. 2016;77:57–100.

    Article  CAS  Google Scholar 

  12. Starup-Linde J, Hygum K, Langdahl BL. Skeletal fragility in type 2 diabetes mellitus. Endocrinol Metab (Seoul). 2018;33(3):339–51.

    Article  CAS  Google Scholar 

  13. Poiana C, Capatina C. Fracture risk assessment in patients with diabetes mellitus. J Clin Densitom. 2017;20(3):432–43.

    Article  Google Scholar 

  14. Fulzele K, Riddle RC, DiGirolamo DJ, Cao X, Wan C, Chen D, et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell. 2010;142(2):309–19.

    Article  CAS  Google Scholar 

  15. Kanazawa I, Sugimoto T. Diabetes mellitus-induced bone fragility. Intern Med. 2018;57(19):2773–85.

    Article  CAS  Google Scholar 

  16. World Health Organization. Physical Status: the use and interpretation of anthropometry: Report of a WHO expert committee. (WHO technical report series; 854). Geneva; 1995.

  17. Organización Panamericana de la Salud. División de Promoción y Protección de la Salud (HPP). Encuesta multicentrica salud bienestar y envejecimiento (SABE) en América Latina: informe preliminar. Multicenter survey aging, health and wellbeing in Latin América and the Caribbean (SABE): preliminary report. Reunión del Comité Asesor de Investigaciónes en Salud. Washington D.C.; 2001.

  18. Kelly TL, Wilson KE, Heymsfield SB. Dual energy X-Ray absorptiometry body composition reference values from NHANES. PloS One. 2009;4(9):e7038.

    Article  Google Scholar 

  19. Kanis JA, McCloskey EV, Johansson H, Oden A, Melton LJ, Khaltaev N. A reference standard for the description of osteoporosis. Bone. 2008;42(3):467–75.

    Article  CAS  Google Scholar 

  20. Schousboe JT, Shepherd JA, Bilezikian JP, Baim S. Executive summary of the 2013 ISCD position development conference on bone densitometry. JCD 2013;16(4):455–7.

  21. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.

    Article  CAS  Google Scholar 

  22. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85(7):2402–10.

    Article  CAS  Google Scholar 

  23. Sempos CT, Heijboer AC, Bikle DD, Bollerslev J, Bouillon R, Brannon PM, DeLuca HF, Jones G, Munns CF, Bilezikian JP, Giustina A, Binkley N. Vitamin D assays and the definition of hypovitaminosis D: results from the first international conference on controversies in vitamin D: vitamin D assays and defining hypovitaminosis D. Br J Clin Pharmacol. 2018;84(10):2194–207. https://doi.org/10.1111/bcp.13652.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes–a meta-analysis. Osteoporos Int. 2007;18(4):427–44.

    Article  CAS  Google Scholar 

  25. Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Zmuda JM, et al. Diabetes is associated independently of body composition with BMD and bone volume in older white and black men and women: the Health, Aging, and Body Composition Study. J Bone Miner Res. 2004;19(7):1084–91.

    Article  Google Scholar 

  26. Ma L, Oei L, Jiang L, Estrada K, Chen H, Wang Z, et al. Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol. 2012;27(5):319–32.

    Article  CAS  Google Scholar 

  27. Dennison EM, Syddall HE, Aihie Sayer A, Craighead S, Phillips DIW, Cooper C. Type 2 diabetes mellitus is associated with increased axial bone density in men and women from the Hertfordshire Cohort Study: evidence for an indirect effect of insulin resistance? Diabetologia. 2004;47(11):1963–8.

    Article  CAS  Google Scholar 

  28. Haffner SM, Bauer RL. The association of obesity and glucose and insulin concentrations with bone density in premenopausal and postmenopausal women. Metabolism. 1993;42(6):735–8.

    Article  CAS  Google Scholar 

  29. Schwartz AV, Vittinghoff E, Bauer DC, Hillier TA, Strotmeyer ES, Ensrud KE, et al. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA. 2011;305(21):2184–92.

    Article  CAS  Google Scholar 

  30. Wongdee K, Charoenphandhu N. Update on type 2 diabetes-related osteoporosis. World J Diabetes. 2015;6(5):673–8.

    Article  Google Scholar 

  31. Ho-Pham LT, Chau PMN, Do AT, Nguyen HC, Nguyen TV. Type 2 diabetes is associated with higher trabecular bone density but lower cortical bone density: the Vietnam Osteoporosis Study. Int. 2018;29(9):2059–67.

    CAS  Google Scholar 

  32. Gan W, Clarke RJ, Mahajan A, Kulohoma B, Kitajima H, Robertson NR, et al. Bone mineral density and risk of type 2 diabetes and coronary heart disease: a Mendelian randomization study. Wellcome Open Res. 2017;2:68.

    Article  Google Scholar 

  33. Hardy OT, Czech MP, Corvera S. What causes the insulin resistance underlying obesity? Curr Opin Endocrinol Diabetes Obes. 2012;19(2):81–7.

    Article  CAS  Google Scholar 

  34. Ye J. Mechanisms of insulin resistance in obesity. Front Med. 2013;7(1):14–24.

    Article  Google Scholar 

  35. Shapses SA, Pop LC, Wang Y. Obesity is a concern for bone health with aging. Nutr Res N Y N. 2017;39:1–13.

    Article  CAS  Google Scholar 

  36. Park K-Y, Hwang H-S, Park H-K. Modifiable lifestyle factors associated with osteoporosis in Korean men: a case-control study. Arch Osteoporos. 2017;12(1):56.

    Article  Google Scholar 

  37. da Silva AP, Matos A, Ribeiro R, Gil Â, Valente A, Bicho M, et al. Sarcopenia and osteoporosis in Portuguese centenarians. Eur J Clin Nutr. 2017;71(1):56–63.

    Article  Google Scholar 

  38. Sutton ALM, MacDonald PN. Vitamin D: more than a “bone-a-fide” hormone. Mol Endocrinol Baltim Md. 2003;17(5):777–91.

    Article  CAS  Google Scholar 

  39. Neve A, Corrado A, Cantatore FP. Osteocalcin: skeletal and extra-skeletal effects. J Cell Physiol. 2013;228(6):1149–53.

    Article  CAS  Google Scholar 

  40. Meehan M, Penckofer S. The role of vitamin D in the aging adult. J Aging Gerontol. 2014;2(2):60–71.

    Article  Google Scholar 

  41. Barrett-Connor E, Kritz-Silverstein D. Does hyperinsulinemia preserve bone? Diabetes Care. 1996;19(12):1388–92.

    Article  CAS  Google Scholar 

  42. Barroso LN, Farias DR, Soares-Mota M, Bettiol H, Barbieri MA, Foss MC, Silva AAMD, Kac G. Waist circumference is an effect modifier of the association between bone mineral density and glucose metabolism. Arch Endocrinol Metab. 2018;62(3):285–95.

    PubMed  Google Scholar 

Download references

Funding

This study was supported by the Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq) 150754/2017-5 (KVG’s postdoctoral scholarship) and by São Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP) 15/07971-7 (project funding), 14/26787-0 (NAGF’s PhD scholarship). CNPq and FAPESP had no role in the design, analysis or writing of this article.

Author information

Author notes

  1. Kelly Virecoulon Giudici

    Present address: Institute of Aging (Gerontopole), Toulouse University Hospital (CHU), Université Toulouse III Paul Sabatier, Toulouse, France

Authors and Affiliations

  1. Nutrition Department, School of Public Health, University of São Paulo, Avenida Doutor Arnaldo, 715, Cerqueira César, São Paulo, SP, Zip Code 01246-904, Brazil

    Kelly Virecoulon Giudici, Natasha Aparecida Grande de França, Bárbara Santarosa Emo Peters, Regina Mara Fisberg & Lígia Araújo Martini

Authors
  1. Kelly Virecoulon Giudici
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Natasha Aparecida Grande de França
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bárbara Santarosa Emo Peters
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Regina Mara Fisberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lígia Araújo Martini
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Kelly Virecoulon Giudici: Conceptualization, Methodology, Formal Analysis, Writing- Original draft preparation. Natasha Aparecida Grande de França: Investigation, Data curation, Writing – Review & Editing. Barbara Santarosa Emo Peters: Investigation, Data curation, Writing – Review & Editing. Regina Mara Fisberg: Project Administration, Supervision, Writing- Reviewing and Editing. Lígia Araújo Martini: Conceptualization, Methodology, Supervision, Funding Acquisition, Writing- Reviewing and Editing.

Corresponding author

Correspondence to Kelly Virecoulon Giudici.

Ethics declarations

Ethics approval

The study was approved by the Ethics in Research Committee from the School of Public Health of the University of São Paulo (FSP/USP) (ISA-Capital 2014–2015 general protocol number: 32344014.3.0000.5421; blood collection: 36607614.5.0000.5421; DXA: 44552815.0.0000.5421).

Consent to participate

All participants were informed about the objectives of research and signed an informed consent form.

Consent for publication

Not applicable.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Giudici, K.V., de França, N.A.G., Peters, B.S.E. et al. Associations between markers of glucose metabolism and bone measures among diabetic and non-diabetic adults. J Diabetes Metab Disord 20, 1247–1255 (2021). https://doi.org/10.1007/s40200-021-00849-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40200-021-00849-5

Keywords

Search

Navigation