Calcified Tissue International

, Volume 83, Issue 5, pp 324–331 | Cite as

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

  • Ippei Kanazawa
  • Toru Yamaguchi
  • Masahiro Yamamoto
  • Mika Yamauchi
  • Shozo Yano
  • Toshitsugu Sugimoto
Article

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.

Keywords

Type 2 diabetes mellitus Body mass index HbA1c Vertebral fracture Bone turnover 

References

  1. 1.
    Barrett-Connor E, Holbrook TL (1992) Sex differences in osteoporosis in older adults with non-insulin-dependent diabetes mellitus. JAMA 268:3333–3337PubMedCrossRefGoogle Scholar
  2. 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 353:878–882PubMedCrossRefGoogle Scholar
  3. 3.
    Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D (2000) Risk of mortality following clinical fractures. Osteoporos Int 11:556–561PubMedCrossRefGoogle Scholar
  4. 4.
    Center JR, Bliuc D, Nguyen TV, Eisman JA (2007) Risk of subsequent fracture after low-trauma fracture in men and women. JAMA 297:387–394PubMedCrossRefGoogle Scholar
  5. 5.
    Ivers RQ, Cumming RG, Mitchell P, Peduto AJ (2001) Diabetes and risk of fracture: the Blue Mountains Eye Study. Diabetes Care 24:1198–1203PubMedCrossRefGoogle Scholar
  6. 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 18:427–444PubMedCrossRefGoogle Scholar
  7. 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 30:835–841PubMedCrossRefGoogle Scholar
  8. 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 165:1612–1617PubMedCrossRefGoogle Scholar
  9. 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 39:871–875PubMedCrossRefGoogle Scholar
  10. 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 10:1050–1056PubMedGoogle Scholar
  11. 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 103:274–280PubMedCrossRefGoogle Scholar
  12. 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 146:287–293PubMedGoogle Scholar
  13. 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 8:567–573PubMedGoogle Scholar
  14. 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 77:683–686PubMedCrossRefGoogle Scholar
  15. 15.
    Hickman J, McElduff A (1989) Insulin promotes growth of the cultured rat osteosarcoma cell line UMR-106–01: an osteoblast-like cell. Endocrinology 124:701–706PubMedGoogle Scholar
  16. 16.
    McCarthy TL, Centrella M, Canalis E (1989) Insulin-like growth factor (IGF) and bone. Connect Tissue Res 20:277–282PubMedCrossRefGoogle Scholar
  17. 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 286:1946–1949PubMedCrossRefGoogle Scholar
  18. 18.
    Cornish J, Callon KE, Reid IR (1996) Insulin increases histomorphometric indices of bone formation in vivo. Calcif Tissue Int 59:492–495PubMedGoogle Scholar
  19. 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–E659Google Scholar
  20. 20.
    Reid IR (2002) Relationships among body mass, its components, and bone. Bone 31:547–555PubMedCrossRefGoogle Scholar
  21. 21.
    Abrahamsen B, Rohold A, Henriksen JE, Beck-Nielsen H (2000) Correlations between insulin sensitivity and bone mineral density in nondiabetic men. Diabet Med 17:124–129PubMedCrossRefGoogle Scholar
  22. 22.
    Leidig-Bruckner G, Ziegler R (2001) Diabetes mellitus a risk for osteoporosis? Exp Clin Endocrinol Diabetes 109:S493–S514PubMedCrossRefGoogle Scholar
  23. 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 11:984–996PubMedCrossRefGoogle Scholar
  24. 24.
    Japanese Society of Nephrology (2007) Clinical practice guidelines for diagnosis and treatment of chronic kidney disease [in Japanese]. Jpn J Nephrol 49:755–870Google Scholar
  25. 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 80:353–358PubMedCrossRefGoogle Scholar
  26. 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 18:1675–1681PubMedCrossRefGoogle Scholar
  27. 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 93:1013–1019PubMedCrossRefGoogle Scholar
  28. 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 124:573–582PubMedGoogle Scholar
  29. 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 16:1506–1512PubMedCrossRefGoogle Scholar
  30. 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 82:2915–2920PubMedCrossRefGoogle Scholar
  31. 31.
    Botolin S, McCabe LR (2006) Chronic hyperglycemia modulates osteoblast gene expression through osmotic and non-osmotic pathways. J Cell Biochem 99:411–424PubMedCrossRefGoogle Scholar
  32. 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 14:1622–1627PubMedCrossRefGoogle Scholar
  33. 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 73:347–352PubMedGoogle Scholar
  34. 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 86:1930–1935PubMedCrossRefGoogle Scholar
  35. 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 147:173–180PubMedCrossRefGoogle Scholar
  36. 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 26:2383–2388PubMedCrossRefGoogle Scholar
  37. 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 8:51–62CrossRefGoogle Scholar
  38. 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 331:520–526PubMedCrossRefGoogle Scholar
  39. 39.
    Richards JB, Valdes AM, Burling K, Perks UC, Spector TD (2007) Serum adiponectin and bone mineral density in women. J Clin Endocrinol Metab 92:1517–1523PubMedCrossRefGoogle Scholar
  40. 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 37:1522–1527PubMedCrossRefGoogle Scholar
  41. 41.
    Kawagishi T, Morii H, Nakatsuka K, Sasao K, Kawasaki K, Miki T, Nishizawa Y (1991) Parathyroid hormone secretion in diabetes mellitus. Contrib Nephrol 90:217–222PubMedGoogle Scholar
  42. 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–S164PubMedCrossRefGoogle Scholar
  43. 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 121:1721–1726PubMedCrossRefGoogle Scholar
  44. 44.
    Pietschmann P, Schernthaner G, Woloszczuk W (1988) Serum osteocalcin levels in diabetes mellitus: analysis of the type of diabetes and microvascular complications. Diabetologia 31:892–895PubMedCrossRefGoogle Scholar
  45. 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 27:181–188PubMedCrossRefGoogle Scholar
  46. 46.
    Fujimoto WY (1996) Overview of non-insulin-dependent diabetes mellitus (NIDDM) in different population groups. Diabet Med 13:S7–S10PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Ippei Kanazawa
    • 1
  • Toru Yamaguchi
    • 1
  • Masahiro Yamamoto
    • 1
  • Mika Yamauchi
    • 1
  • Shozo Yano
    • 1
  • Toshitsugu Sugimoto
    • 1
  1. 1.Department of Internal Medicine 1Shimane University Faculty of MedicineShimaneJapan

Personalised recommendations