Skip to main content

Advertisement

SpringerLink
Log in

Combination of Obesity with Hyperglycemia is a Risk Factor for the Presence of Vertebral Fractures in Type 2 Diabetic Men

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Although patients with type 2 diabetes show no bone mineral density (BMD) reduction, fracture risks are known to increase. It is unclear why the patients have an increased risk of fracture despite sufficient BMD. We investigated the relationships of body mass index (BMI), HbA1c, and urinary C-peptide (uC-peptide) versus BMD, bone metabolic markers, serum adiponectin, and prevalent vertebral fracture (VF). A total of 163 Japanese type 2 diabetic men were consecutively recruited, and radiographic and biochemical data were collected. BMI was positively correlated with BMD at the whole body, lumbar spine, and femoral neck (P < 0.05) and negatively correlated with osteocalcin and urinary N-terminal cross-linked telopeptide of type-I collagen (uNTX) (P < 0.01). HbA1c was negatively correlated with osteocalcin (P < 0.01) but not BMD at any site. Subjects were classified into four groups based on BMI and HbA1c (group LL BMI < 24 and HbA1c < 9, group LH BMI < 24 and HbA1c ≧ 9, group HL BMI ≧ 24 and HbA1c < 9, group HH BMI ≧ 24 and HbA1c ≧ 9). Serum adiponectin, osteocalcin, and uNTX were lower and the incidence of VF was higher despite sufficient BMD in the HH group. Multivariate logistic regression analysis adjusted for age, duration of diabetes, uC-peptide, and estimated glomerular filtration rate showed that the HH group was associated with the presence of a VF and multiple VFs (odds ratio [OR] = 3.056, 95% confidence interval [CI] 1.031–9.056, P = 0.0439, and OR = 5.415, 95% CI 1.126–26.040, P = 0.0350, respectively). Combination of obesity with hyperglycemia was a risk factor for VF despite sufficient BMD in diabetic men.

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

References

  1. Barrett-Connor E, Holbrook TL (1992) Sex differences in osteoporosis in older adults with non-insulin-dependent diabetes mellitus. JAMA 268:3333–3337

    Article  PubMed  CAS  Google Scholar 

  2. Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA (1999) Mortality after all major types of osteoporotic fracture in men and women an observational study. Lancet 353:878–882

    Article  PubMed  CAS  Google Scholar 

  3. Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D (2000) Risk of mortality following clinical fractures. Osteoporos Int 11:556–561

    Article  PubMed  CAS  Google Scholar 

  4. Center JR, Bliuc D, Nguyen TV, Eisman JA (2007) Risk of subsequent fracture after low-trauma fracture in men and women. JAMA 297:387–394

    Article  PubMed  CAS  Google Scholar 

  5. Ivers RQ, Cumming RG, Mitchell P, Peduto AJ (2001) Diabetes and risk of fracture: the Blue Mountains Eye Study. Diabetes Care 24:1198–1203

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Lipscombe LL, Jamal SA, Booth GL, Hawker GA (2007) The risk of hip fractures in older individuals with diabetes: a population-based study. Diabetes Care 30:835–841

    Article  PubMed  Google Scholar 

  8. Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Bauer DC, Tylavsky FA, de Rekeneire N, Harris TB, Newman AB (2005) Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults: the health, aging, and body composition study. Arch Intern Med 165:1612–1617

    Article  PubMed  Google Scholar 

  9. Ogawa N, Yamaguchi T, Yano S, Yamauchi M, Yamamoto M, Sugimoto T (2007) The combination of high glucose and advanced glycation end-products (AGEs) inhibits the mineralization of osteoblastic MC3T3-E1 cells through glucose-induced increase in the receptor for AGEs. Horm Metab Res 39:871–875

    Article  PubMed  CAS  Google Scholar 

  10. Inaba M, Terada M, Koyama H, Yoshida O, Ishimura E, Kawagishi T, Okuno Y, Nishizawa Y, Otani S, Morii H (1995) Influence of high glucose on 1,25-dihydroxyvitamin D3-induced effect on human osteoblast-like MG–63 cells. J Bone Miner Res 10:1050–1056

    PubMed  CAS  Google Scholar 

  11. Ensrud KE, Lipschutz RC, Cauley JA, Seeley D, Nevitt MC, Scott J, Orwoll ES, Genant HK, Cummings SR (1997) Body size and hip fracture risk in older women: a prospective study. Study of Osteoporotic Fractures Research Group. Am J Med 103:274–280

    Article  PubMed  CAS  Google Scholar 

  12. Johnell O, O’Neill T, Felsenberg D, Kanis J, Cooper C, Silman AJ (1997) Anthropometric measurements and vertebral deformities. European Vertebral Osteoporosis Study (EVOS) Group. Am J Epidemiol 146:287–293

    PubMed  CAS  Google Scholar 

  13. Felson DT, Zhang Y, Hannan MT, Anderson JJ (1993) Effects of weight and body mass index on bone mineral density in men and women: the Framingham Study. J Bone Miner Res 8:567–573

    PubMed  CAS  Google Scholar 

  14. Tremollieres FA, Pouilles JM, Ribot C (1993) Vertebral postmenopausal bone loss is reduced in overweight women: a longitudinal study in 155 early postmenopausal women. J Clin Endocrinol Metab 77:683–686

    Article  PubMed  CAS  Google Scholar 

  15. Hickman J, McElduff A (1989) Insulin promotes growth of the cultured rat osteosarcoma cell line UMR-106–01: an osteoblast-like cell. Endocrinology 124:701–706

    PubMed  CAS  Google Scholar 

  16. McCarthy TL, Centrella M, Canalis E (1989) Insulin-like growth factor (IGF) and bone. Connect Tissue Res 20:277–282

    Article  PubMed  CAS  Google Scholar 

  17. Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, Gutierrez G (1999) Stimulation of bone formation in vitro and in rodents by statins. Science 286:1946–1949

    Article  PubMed  CAS  Google Scholar 

  18. Cornish J, Callon KE, Reid IR (1996) Insulin increases histomorphometric indices of bone formation in vivo. Calcif Tissue Int 59:492–495

    PubMed  CAS  Google Scholar 

  19. 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 Endocrinol Metab 265:E655–E659

    CAS  Google Scholar 

  20. Reid IR (2002) Relationships among body mass, its components, and bone. Bone 31:547–555

    Article  PubMed  CAS  Google Scholar 

  21. Abrahamsen B, Rohold A, Henriksen JE, Beck-Nielsen H (2000) Correlations between insulin sensitivity and bone mineral density in nondiabetic men. Diabet Med 17:124–129

    Article  PubMed  CAS  Google Scholar 

  22. Leidig-Bruckner G, Ziegler R (2001) Diabetes mellitus a risk for osteoporosis? Exp Clin Endocrinol Diabetes 109:S493–S514

    Article  PubMed  CAS  Google Scholar 

  23. Genant HK, Jergas M, Palermo L, Nevitt M, Valentin RS, Black D, Cummings SR (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 11:984–996

    Article  PubMed  CAS  Google Scholar 

  24. Japanese Society of Nephrology (2007) Clinical practice guidelines for diagnosis and treatment of chronic kidney disease [in Japanese]. Jpn J Nephrol 49:755–870

    Google Scholar 

  25. Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T (2007) Bone mineral density is not sensitive enough to assess the risk of vertebral fractures in type 2 diabetic women. Calcif Tissue Int 80:353–358

    Article  PubMed  CAS  Google Scholar 

  26. Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T (2007) Serum insulin-like growth factor-I is associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes mellitus. Osteoporos Int 18:1675–1681

    Article  PubMed  CAS  Google Scholar 

  27. Yamamoto M, Yamaguchi T, Yamauchi M, Yano S, Sugimoto T (2008) Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab 93:1013–1019

    Article  PubMed  CAS  Google Scholar 

  28. Verhaeghe J, Suiker AM, Nyomba BL, Visser WJ, Einhorn TA, Dequeker J, Bouillon R (1989) Bone mineral homeostasis in spontaneously diabetic BB rats. II. Impaired bone turnover and decreased osteocalcin synthesis. Endocrinology 124:573–582

    PubMed  CAS  Google Scholar 

  29. Gerdhem P, Isaksson A, Akesson K, Obrant KJ (2005) Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus. Osteoporos Int 16:1506–1512

    Article  PubMed  CAS  Google Scholar 

  30. Okazaki R, Totsuka Y, Hamano K, Ajima M, Miura M, Hirota Y, Hata K, Fukumoto S, Matsumoto T (1997) Metabolic improvement of poorly controlled noninsulin-dependent diabetes mellitus decreases bone turnover. J Clin Endocrinol Metab 82:2915–2920

    Article  PubMed  CAS  Google Scholar 

  31. Botolin S, McCabe LR (2006) Chronic hyperglycemia modulates osteoblast gene expression through osmotic and non-osmotic pathways. J Cell Biochem 99:411–424

    Article  PubMed  CAS  Google Scholar 

  32. Ravn P, Cizza G, Bjarnason NH, Thompson D, Daley M, Wasnich RD, McClung M, Hosking D, Yates AJ, Christiansen C (1999) Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group. J Bone Miner Res 14:1622–1627

    Article  PubMed  CAS  Google Scholar 

  33. Ricci TA, Heymsfield SB, Pierson RN, Stahl T, Chowdhury HA, Shapses SA (2001) Moderate energy restriction increases bone resorption in obese postmenopausal women. Am J Clin Nutr 73:347–352

    PubMed  CAS  Google Scholar 

  34. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA (2001) Hypoadiponectemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935

    Article  PubMed  CAS  Google Scholar 

  35. Matsubara M, Maruoka S, Katayose S (2002) Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur J Endocrinol 147:173–180

    Article  PubMed  CAS  Google Scholar 

  36. Ryan AS, Berman DM, Nicklas BJ, Shiha M, Gingerich RL, Meneilly GS, Egan JM, Elahi D (2003) Plasma adiponectin and leptin levels, body composition, and glucose utilization in adult women with wide ranges of age and obesity. Diabetes Care 26:2383–2388

    Article  PubMed  CAS  Google Scholar 

  37. Kanazawa I, Yamaguchi T, Yano S, Yamauchi M, Yamamoto M, Sugimoto T (2008) Adiponectin and AMP kinase activator stimulate proliferation, differentiation, and mineralization of osteoblastic MC3T3–E1 cells. BMC Cell Biol 8:51–62

    Article  CAS  Google Scholar 

  38. Oshima K, Nampei A, Matsuda M, Iwaki M, Fukuhara A, Hashimoto J, Yoshikawa H, Shimomura I (2005) Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun 331:520–526

    Article  PubMed  CAS  Google Scholar 

  39. Richards JB, Valdes AM, Burling K, Perks UC, Spector TD (2007) Serum adiponectin and bone mineral density in women. J Clin Endocrinol Metab 92:1517–1523

    Article  PubMed  CAS  Google Scholar 

  40. Sugimoto T, Ritter C, Morrissey J, Hayes C, Slatopolsky E (1990) Effects of high concentrations of glucose on PTH secretion in parathyroid cells. Kidney Int 37:1522–1527

    Article  PubMed  CAS  Google Scholar 

  41. Kawagishi T, Morii H, Nakatsuka K, Sasao K, Kawasaki K, Miki T, Nishizawa Y (1991) Parathyroid hormone secretion in diabetes mellitus. Contrib Nephrol 90:217–222

    PubMed  CAS  Google Scholar 

  42. Yamamoto T, Ozono K, Miyauchi A, Kasayama S, Kojima Y, Shima M, Okada S (2001) Role of advanced glycation end products in adynamic bone disease in patients with diabetic nephropathy. Am J Kidney Dis 38:S161–S164

    Article  PubMed  CAS  Google Scholar 

  43. Ikeda K, Matsumoto T, Morita K, Yamato H, Takahashi H, Ezawa I, Ogata E (1987) The role of insulin in the stimulation of renal 1,25-dihydroxyvitamin D synthesis by parathyroid hormone in rats. Endocrinology 121:1721–1726

    Article  PubMed  CAS  Google Scholar 

  44. Pietschmann P, Schernthaner G, Woloszczuk W (1988) Serum osteocalcin levels in diabetes mellitus: analysis of the type of diabetes and microvascular complications. Diabetologia 31:892–895

    Article  PubMed  CAS  Google Scholar 

  45. Scragg R, Holdaway I, Singh V, Metcalf P, Baker J, Dryson E (1995) Serum 25-hydroxyvitamin D3 levels decreased in impaired glucose tolerance and diabetes mellitus. Diabetes Res Clin Pract 27:181–188

    Article  PubMed  CAS  Google Scholar 

  46. Fujimoto WY (1996) Overview of non-insulin-dependent diabetes mellitus (NIDDM) in different population groups. Diabet Med 13:S7–S10

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine 1, Shimane University Faculty of Medicine, 89-1, Enya-cho, Izumo, Shimane, 693-8501, Japan

    Ippei Kanazawa, Toru Yamaguchi, Masahiro Yamamoto, Mika Yamauchi, Shozo Yano & Toshitsugu Sugimoto

Authors
  1. Ippei Kanazawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toru Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masahiro Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mika Yamauchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shozo Yano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Toshitsugu Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toru Yamaguchi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kanazawa, I., Yamaguchi, T., Yamamoto, M. et al. Combination of Obesity with Hyperglycemia is a Risk Factor for the Presence of Vertebral Fractures in Type 2 Diabetic Men. Calcif Tissue Int 83, 324–331 (2008). https://doi.org/10.1007/s00223-008-9178-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-008-9178-6

Keywords

Search

Navigation