Association between leptin, lipid metabolism, and bone remodeling markers in men with type 2 diabetes mellitus

Authors

DOI:

https://doi.org/10.14739/2310-1210.2026.2.331070

Keywords:

type 2 diabetes mellitus, leptin, dyslipidemia, bone turnover markers, P1NP, β-CTX, bone mineral density, men’s health

Abstract

Type 2 diabetes mellitus (T2DM) is associated with disturbances in bone metabolism that may increase fracture risk, even in the presence of normal or high bone mineral density (BMD). Dyslipidemia and elevated leptin levels, both common in T2DM, considered potential contributors to impaired bone remodeling, particularly in men, where skeletal responses to metabolic disturbances remain insufficiently understood.

Aim. To evaluate associations between serum leptin levels, lipid metabolism parameters, and markers of bone turnover in men with T2DM.

Materials and methods. A cross-sectional study included 62 men with T2DM (aged 50–65 years) and 58 age-matched non-diabetic controls. Laboratory assessments included HbA1c, insulin, leptin, testosterone, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone, lipid profile, and bone turnover markers (P1NP, β-CTX). BMD at the lumbar spine and proximal femur was measured by dual X-ray absorptiometry (DXA). Insulin resistance was evaluated using HOMA-IR. Correlations were analyzed using Spearman’s rank test.

Results. Men with T2DM had higher BMI (29.8 kg/m2 vs. 26.7 kg/m2, p = 0.006), elevated leptin (15.2 ng/mL vs. 11.2 ng/mL, p = 0.003), dyslipidemia (increased triglycerides and LDL-C, decreased HDL-C), and lower 25(OH)D levels (16.8 ng/mL vs. 21.6 ng/mL, p = 0.007) compared to controls. Bone formation marker P1NP was significantly reduced (35.4 ng/mL vs. 43.9 ng/mL, p = 0.009), while resorption marker β-CTX was increased (0.44 ng/mL vs. 0.37 ng/mL, p = 0.042) in T2DM group. BMD was significantly lower at the lumbar spine and total hip (p < 0.05). Leptin levels were correlated positively with BMI and HOMA-IR, while triglycerides were negatively correlated with P1NP (r = -0.218, p = 0.023).

Conclusions. This study demonstrates that men with T2DM exhibited significant associations between dyslipidemia, hyperleptinemia, and altered bone metabolism. These metabolic abnormalities were linked to reduced bone mineral density, most notably at the lumbar spine and proximal femur. The results suggest that lipid and hormonal imbalances may contribute to poor bone health in T2DM, highlighting the need for careful skeletal assessment and targeted preventive approaches in this group.

Author Biographies

Sain Safarova, Azerbaijan Medical University, Baku

MD, PhD, DSc, Professor of the Department of Internal Medicine No. 2

Saadet Safarova, Azerbaijan Medical University, Baku

MD, PhD, Associate Professor of the Department of Obstetrics and Gynecology No. 1

Aydan Taghiyeva, University of York

BSc Student (Year 3), Department of Biomedical Science

References

Faienza M, Pontrelli P, Brunetti G. Type 2 diabetes and bone fragility in children and adults. World J Diabetes. 2022; 15;13(11):900-11. doi: https://doi.org/10.4239/wjd.v13.i11.900

Hofbauer LC, Busse B, Eastell R, Ferrari S, Frost M, Müller R, et al. Bone fragility in diabetes: novel concepts and clinical implications. Lancet Diabetes Endocrinol. 2022;10(3):207-20. doi: https://doi.org/10.1016/S2213-8587(21)00347-8

Zhao C, Kan J, Xu Z, Zhao D, Lu A, Liu Y, et al. Higher BMI and lower femoral neck strength in males with type 2 diabetes mellitus and normal bone mineral density. Am J Med Sci. 2022;364(5):631-7. doi: https://doi.org/10.1016/j.amjms.2022.06.007

Lecka-Czernik B, Rosen CJ. Skeletal integration of energy homeostasis: Translational implications. Bone. 2016;82:35-41. doi: https://doi.org/10.1016/j.bone.2015.07.026

Upadhyay J, Farr OM, Mantzoros CS. The role of leptin in regulating bone metabolism. Metabolism. 2015;64(1):105-13. doi: https://doi.org/10.1016/j.metabol.2014.10.021

Obradovic M, Sudar-Milovanovic E, Soskic S, Essack M, Arya S, Stewart AJ, et al. Leptin and obesity: role and clinical implication. Front Endocrinol (Lausanne). 2021;12:585887. doi: https://doi.org/10.3389/fendo.2021.585887

Cosme D, Gomes AC. Leptin Levels and Bone Mineral Density: A Friend or a Foe for Bone Loss? A Systematic Review of the Association Between Leptin Levels and Low Bone Mineral Density. Int J Mol Sci. 2025;26(5):2066. doi: https://doi.org/10.3390/ijms26052066

Ortona E, Pagano MT, Capossela L, Malorni W. The Role of Sex Differences in Bone Health and Healing. Biology (Basel). 2023;12(7):993. doi: https://doi.org/10.3390/biology12070993

Li H, Wen Y, Liu P, Zhang L, Zhang X, Liu Y, et al. Characteristics of bone metabolism in postmenopausal women with newly diagnosed type 2 diabetes mellitus. Clin Endocrinol (Oxf). 2021;95(3):430-8. doi: https://doi.org/10.1111/cen.14501

Tomasiuk JM, Nowakowska-Płaza A, Wisłowska M, Głuszko P. Osteoporosis and diabetes - possible links and diagnostic difficulties. Reumatologia. 2023;61(4):294-304. doi: https://doi.org/10.5114/reum/170048

Faraj M, Schwartz AV, Burghardt AJ, Black D, Orwoll E, Strotmeyer ES, et al. Risk factors for bone microarchitecture impairments in older men with type 2 diabetes-The MrOS Study. J Clin Endocrinol Metab. 2025;110(5):e1660-9. doi: https://doi.org/10.1210/clinem/dgae452

Napoli N, Chandran M, Pierroz DD, Abrahamsen B, Schwartz AV, Ferrari SL. IOF Bone and Diabetes Working Group. Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol. 2017;13(4):208-19. doi: https://doi.org/10.1038/nrendo.2016.153

Xiao H, Li W, Qin Y, Lin Z, Qian C, Wu M, Xia Y, Bai J, Geng D. Crosstalk between Lipid Metabolism and Bone Homeostasis: Exploring Intricate Signaling Relationships. Research (Wash D C). 2024;7:0447. doi: https://doi.org/10.34133/research.0447

Anagnostis P, Florentin M, Livadas S, Lambrinoudaki I, Goulis DG. Bone Health in Patients with Dyslipidemias: An Underestimated Aspect. Int J Mol Sci. 2022;23(3):1639. doi: https://doi.org/10.3390/ijms23031639

Salmón-Gómez L, Catalán V, Frühbeck G, Gómez-Ambrosi J. Relevance of body composition in phenotyping the obesities. Rev Endocr Metab Disord. 2023;24(5):809-23. doi: https://doi.org/10.1007/s11154-023-09796-3

Whipple T, Sharkey N, Demers L, Williams N. Leptin and the skeleton. Clin Endocrinol (Oxf). 2002;57(6):701-11. doi: https://doi.org/10.1046/j.1365-2265.2002.01630.x.

Khosla S. Leptin-central or peripheral to the regulation of bone metabolism? Endocrinology. 2002;143(11):4161-4. doi: https://doi.org/10.1210/en.2002-220843

Szeliga A, Grymowicz M, Kostrzak A, Smolarczyk R, Bala G, Smolarczyk K, Meczekalski B, Suchta K. Bone: A Neglected Endocrine Organ? J Clin Med. 2024;13(13):3889. doi: https://doi.org/10.3390/jcm13133889

Mostafa SM, Elebrashy I, Haddad HE, Shaker O, Razek NA, Fayed A. Association between bone turnover markers, bone mineral density, and serum osteoglycine in middle-aged men with Type 2 Diabetes mellitus. Diabetol Metab Syndr. 2024;16(1):155. doi: https://doi.org/10.1186/s13098-024-01388-8

Bouillon R, LeBoff MS, Neale RE. Health effects of vitamin D supplementation: lessons learned from randomized controlled trials and mendelian randomization studies. J Bone Miner Res. 2023;38(10):1391-403. doi: https://doi.org/10.1002/jbmr.4888

Li J, Xie Y, Sun S, Xue C, Xu W, Xu C, et al. Regional differences in bone mineral density biomechanically induce a higher risk of adjacent vertebral fracture after percutaneous vertebroplasty: a case-comparative study. Int J Surg. 2023;109(3):352-363. doi: https://doi.org/10.1097/JS9.0000000000000273

Ojo O, Onilude Y, Brooke J, Apau V, Kazangarare I, Ojo O. The Effect of Type 2 Diabetes on Bone Quality: A Systematic Review and Meta-Analysis of Cohort Studies. Int J Environ Res Public Health. 2025;22(6):910. doi: https://doi.org/10.3390/ijerph22060910

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Published

2026-04-23

How to Cite

1.
Safarova S, Safarova S, Taghiyeva A. Association between leptin, lipid metabolism, and bone remodeling markers in men with type 2 diabetes mellitus. Zaporozhye Medical Journal [Internet]. 2026Apr.23 [cited 2026Apr.23];28(2):130-3. Available from: https://zmj.zsmu.edu.ua/article/view/331070