Comparing the bone mineral density among male patients with latent autoimmune diabetes and classical type 1 and type 2 diabetes, and exploring risk factors for osteoporosis



This study aimed to compare the bone mineral densities (BMDs) among male patients with latent autoimmune diabetes in adults (LADA), classical type 1 diabetes (T1DM), and type 2 diabetes (T2DM), and to examine the risk factors for developing low BMD in these patients.

Patients and methods

Between January 2017 and October 2020, a total of 57, 67, and 223 male patients with LADA, classical T1DM, and T2DM, respectively, were recruited from the endocrinology department of Shanghai Tenth People’s Hospital. Hormonal markers of bone metabolism, lipid profiles, uric acid, glycosylated hemoglobin A1c (HbA1c), and beta-cell function were measured using blood samples. BMD was measured at the lumbar spine, femoral neck, and right hip by dual-energy X-ray absorptiometry.


The mean BMD values from all three skeletal sites in male patients with LADA were comparable to those with classical T1DM but were much lower than those with T2DM. After adjusting for confounding factors, multiple linear regression analysis demonstrated that in all male patients with diabetes, body mass index (BMI), uric acid, and fasting C-peptide showed significant positive associations with BMD at all three skeletal sites; however, osteocalcin showed a negative association at all three sites.


Compared with male patients with T2DM, lower BMDs were observed in patients with LADA and T1DM. Low BMI, uric acid, C-peptide levels, and high osteocalcin levels are risk factors for developing low BMD in male patients with diabetes.

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  1. 1.

    Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2diabetes–a meta-analysis. Osteoporos Int 18:427–444

    CAS  Article  Google Scholar 

  2. 2.

    Kurra S, Fink DA, Siris ES (2014a) Osteoporosis-associated fracture and diabetes. Endocrinol Metab Clin N Am 43:233–243

    Article  Google Scholar 

  3. 3.

    Adil C, Aydın T, Taşpınar Ö, Kızıltan H, Eriş AH, Hocaoglu IT, Poşul S, Kepekci M, Denizli E, Güler M (2015) Bone mineral density evaluation of patients with type 2 diabetes mellitus. J Phys Ther Sci 27:179–182

    Article  Google Scholar 

  4. 4.

    Kurra S, Fink DA, Siris ES (2014b) Osteoporosis, Fractures, and Diabetes. Endocrinol Metab Clin N Am 43:233–243

    Article  Google Scholar 

  5. 5.

    Liu B, Xiang Y, Liu Z, Zhou Z (2019) Past, present and future of latent autoimmune diabetes in adults. Diabetes Metab Res Rev 18:e3205

    Google Scholar 

  6. 6.

    Yohena S, Penas-Steinhardt A, Muller C, Faccinetti NI, Cerrone GE, Lovecchio S, Ridner E, Valdez S, Frechtel G (2019) Immunological and clinical characteristics of latent autoimmune diabetes in the elderly. Diabetes Metab Res Rev 35:e3137

    Article  Google Scholar 

  7. 7.

    Hu Y, Li X, Yan X, Huang G, Dai R, Zhou Z (2020) Bone mineral density spectrum in individuals with type 1 diabetes, latent autoimmune diabetes in adults, and type 2 diabetes. Diabetes Metab Res Rev.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Napoli N, Strollo R, Defeudis G, Leto G, Moretti C, Zampetti S, D’Onofrio L, Campagna G, Palermo A, Greto V, Manfrini S, Hawa MI, Leslie RD, Pozzilli P, Buzzetti R, NIRAD (NIRAD 10) and Action LADA Study Group (2018) Serum sclerostin and bone turnover in latent autoimmune diabetes in adults. J Clin Endocrinol Metab 103(5):1921–1928

    Article  Google Scholar 

  9. 9.

    Hamilton EJ, Rakic V, Davis WA, Chubb SA, Kamber N, Prince RL, Davis TM (2009) Prevalence and predictors of osteopenia and osteoporosis in adults with type 1 diabetes. Diabetes Med 26:45–52

    CAS  Article  Google Scholar 

  10. 10.

    De Shields SC, Cunningham TD (2018) Comparison of osteoporosis in adults with type 1 and type 2 diabetes mellitus. J Endocrinol Invest 41:1051–1060

    Article  Google Scholar 

  11. 11.

    Hosszúfalusi N, Vatay A, Rajczy K, Prohászka Z, Pozsonyi E, Horváth L, Grosz A, Gerõ L, Madácsy L, Romics L, Karádi I, Füst G, Pánczél P (2003) Similar genetic features and different islet cell autoantibody pattern of latent autoimmune diabetes in adults (LADA) compared with adult-onset type 1 diabetes with rapid progression. Diabetes Care 26:452–457

    Article  Google Scholar 

  12. 12.

    Gielen E, Vanderschueren D, Callewaert F, Boonen S (2011) Osteoporosis in men. Best Pract Res Clin Endocrinol Metab 25:321–335

    CAS  Article  Google Scholar 

  13. 13.

    Huuskonen J, Kröger H, Arnala I, Alhava D (1999) Characteristics of male hip fracture patients. Ann Chir Gynaecol 88:48–53

    CAS  PubMed  Google Scholar 

  14. 14.

    Hadjidakis DJ, Raptis AE, SfakianakisM MA, Raptis SA (2006) Bone mineral density of both genders in type 1 diabetes according to bone composition. J Diabetes Complicat 20:302–307

    Article  Google Scholar 

  15. 15.

    Palermo A, D’Onofrio L, Buzzetti R, Manfrini S, Napoli N (2017) Pathophysiology of bone fragility in patients with diabetes. Calcif Tissue Int 100:122–132

    CAS  Article  Google Scholar 

  16. 16.

    Fourlanos S, Dotta F, Greenbaum CJ, Palmer JP, Rolandsson O, Colman PG, Harrison LC (2005) Latent autoimmune diabetesin adults (LADA) should be less latent. Diabetologia 48:2206–2212

    CAS  Article  Google Scholar 

  17. 17.

    Yang W, Liu J, Shan Z, Tian H, Zhou Z, Ji Q (2014) Acarbose compared with metformin as initial therapy in patients with newly diagnosed type 2 diabetes: an open-label, non-inferiority randomised trial. Lancet Diabetes Endocrinol 2:46–55

    CAS  Article  Google Scholar 

  18. 18.

    Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N (1994) The diagnosis of osteoporosis. J Bone Miner Res 9:1137–1141

    CAS  Article  Google Scholar 

  19. 19.

    Leidig-Bruckner G, Grobholz S, Bruckner T, Scheidt-Nave C, Nawroth P, Schneider JG (2014) Prevalence and determinants of osteoporosis in patients with type 1 and type 2 diabetes mellitus. BMC Endocr Disord 14:33

    Article  Google Scholar 

  20. 20.

    Cree M, Soskolne CL, Belseck E, Hornig J, McElhaney JE, Brant R, Suarez-Almazor M (2000) Mortality and institutionalization following hip fracture. J Am Geriatr Soc 48:283–288

    CAS  Article  Google Scholar 

  21. 21.

    Chen HL, Deng LL, Li JF (2013) Prevalence of osteoporosis and its associated factors among older men with type 2 diabetes. Int J Endocrinol 2013:285729

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Zhou Z, Xiang Y, Ji L, Jia W, Ning G, Huang G, Yang L, Lin J, Liu Z, Hagopian WA, Leslie RD, LADA China Study Group (2013) Frequency, immunogenetics, and clinical characteristics of latent autoimmune diabetes in China (LADA China study): nation-wide, multicenter, clinic-based cross-sectional study. Diabetes 62:543–550

    CAS  Article  Google Scholar 

  23. 23.

    Lu J, Hou X, Zhang L, Hu C, Zhou J, Pang C, Pan X, Bao Y, Jia W (2015) Associations between clinical characteristics and chronic complications in latent autoimmune diabetes in adults and type 2 diabetes. Diabetes Metab Res Rev 31:411–420

    Article  Google Scholar 

  24. 24.

    Pánczél P, Hosszúfalusi N, Bornemisza B, Hudes M, Flegal KM, Crawford PB (2001) Latent autoimmune diabetes in adults (LADA): part of the clinical spectrum of type-1 diabetes mellitus of autoimmune origin. Orv Hetil 142:2571–2578

    PubMed  Google Scholar 

  25. 25.

    Wang MC, Bachrach LK, Van Loan M, Yamwong S, Ratanachaiwong W, Sritara P (2005) The relative contributions of lean tissue mass and fat mass to bone density in young women. Bone 37:4744–4781

    Google Scholar 

  26. 26.

    Barrera G, Bunout D, Gattás V, de la Maza MP, Leiva L, Hirsch S (2004) A high body mass index protects against femoral neck osteoporosis in healthy elderly subjects. Nutrition 20:769–771

    Article  Google Scholar 

  27. 27.

    Ahn SH, Lee SH, Kim BJ, Lim KH, Bae SJ, Kim EH, Kim HK, Choe JW, Koh JM, Kim GS (2013) Higher serum uric acid is associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in healthy postmenopausal women. Osteoporos Int 24:2961–2970

    CAS  Article  Google Scholar 

  28. 28.

    Wu ZQ, Zhang Y, Xie E, Song WJ, Yang RX, Yan CJ, Zhang BF, Xu HG (2016) High uric acid (UA) negatively affects serumtartrate-resistant acid phosphatase 5b (TRACP 5b) immunoassay. PLoS ONE 11e:0147554

    Google Scholar 

  29. 29.

    Li HZ, Chen Z, Hou CL, Tang YX, Wang F, Fu QG (2015) Uric acid promotes osteogenic differentiation and inhibits adipogenic differentiation of human bone mesenchymal stem cells. J Biochem Mol Toxicol 29:382–387

    Article  Google Scholar 

  30. 30.

    Reid IR, Evans MC, Cooper GJ, Ames RW, Stapleton J (1993) Circulating insulin levels are related to bone density in normal postmenopausal women. Am J Physiol 265:E655-659

    CAS  PubMed  Google Scholar 

  31. 31.

    Stolk RP, van Daele PL, Pols HA, Burger H, Hofman A, Birkenhäger JC, Lamberts SW, Grobbee D (1996) Hyperinsulinemia and bone mineral density in an elderly population: the Rotterdam study. Bone 18:545–549

    CAS  Article  Google Scholar 

  32. 32.

    Barrett-Connor E, Kritz-Silverstein D (1996) Does hyperinsulinemia preserve bone? Diabetes Care 19:1388–1392

    CAS  Article  Google Scholar 

  33. 33.

    Zhou Y, Li Y, Zhang D, Wang J, Yang H (2010) Prevalence and predictors of osteopenia and osteoporosis in postmenopausal Chinese women with type 2 diabetes. Diabetes Res Clin Pract 90:261–269

    Article  Google Scholar 

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This study was supported by grants from the National Key R&D Program of China (No. 2018YFC1314100) and the National Nature Science Foundation (No. 81601269 and No.81700752).

Author information




Manna Zhang performed the study and wrote the manuscript; CS and HY collected the data and performed the statistical analysis; MC helped us collect data in terms of expanding sample size and improving the data information; JG, XC and HS participated in recruiting the patients; SQ designed the study and edited the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to M. Zhang.

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Conflict of interest

The authors have no conflicts of interest.

Ethical approval

All procedures performed in our study involving human participants were in accordance with the ethical standards of the institutional human subjects review board of the shanghai Tenth people’s hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Zhang, M., Sheng, C., You, H. et al. Comparing the bone mineral density among male patients with latent autoimmune diabetes and classical type 1 and type 2 diabetes, and exploring risk factors for osteoporosis. J Endocrinol Invest (2021).

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  • Latent autoimmune diabetes in adults
  • Classical type 1 diabetes
  • Type 2 diabetes
  • Bone mineral density
  • Osteoporosis