Digestive Diseases and Sciences

, Volume 53, Issue 5, pp 1240–1245

Bone Mineralization in Young Patients with Type 1 Diabetes Mellitus and Screening-identified Evidence of Celiac Disease

  • Daniel R. Diniz-Santos
  • Flávia Brandão
  • Luis Adan
  • Agnaluce Moreira
  • Eliézer J. Vicente
  • Luciana R. Silva
Original Paper

Abstract

The aims of this study were to evaluate bone mineral density (BMD) and bone turnover markers in patients with type 1 diabetes and screening-identified evidence of celiac disease, i.e., celiac autoimmunity. We screened 50 consecutive type 1 diabetic patients for IgA antitissue transglutaminase to identify those with celiac autoimmunity. Eight seropositive patients were identified on this screening, and 12 patients matched for gender and age range were selected as a control group from among the type 1 diabetic patients without celiac autoimmunity. Patients and controls underwent dual-energy X-ray absorptiometry (DEXA) for measurement of bone mineral status and had their blood levels of osteocalcin, carboxy-terminal telopeptide of type I collagen (CTX), calcium, and phosphorus determined. BMD was further adjusted for height, weight, and pubertal stage. Radiographic and blood markers of bone mineralization were compared between patients and controls. BMD (Z-score) at the lumbar spine was −1.44 ± 0.5 SD for patients and 0.04 ± 0.2 SD for controls (= 0.02). Bone mineral content was 37.9 ± 4.5 g for patients and 49.4 ± 2.6 g for controls (= 0.049). Adjusted BMD was −0.62 ± 0.5 SD for patients and 0.81 ± 0.09 SD for controls (= 0.04). After adjustment, four patients and none of the controls presented BMD < −1 SD (P = 0.01). Osteocalcin, CTX, calcium, and phosphorus blood levels were not significantly different between patients and controls. Celiac autoimmunity is associated with reduced bone mineralization in type 1 diabetic patients. The pathophysiological mechanisms and clinical relevance of this finding remain to be further investigated.

Keywords

Celiac disease Type 1 diabetes Bone mineral density Osteopenia Osteocalcin 

Abbreviations

BMD

Bone mineral density

BMC

Bone mineral content

CD

Celiac disease

CTX

Carboxy-terminal telopeptide of type I collagen

DEXA

Dual-energy X-ray absorptiometry

NS

Nonsignificant

SD

Standard deviation

SEM

Standard error of the mean

References

  1. 1.
    Green PHR, Jabri B (2003) Celiac disease. Lancet 362:383–391PubMedCrossRefGoogle Scholar
  2. 2.
    Catassi C, Fabiani E, Ratsch IM, Coppa GV, Giorgi PL, Pierdomenico R et al (1996) The celiac iceberg in Italy. A multicentre antigliadin antibodies screening for celiac disease in school-age subjects. Acta Paediatr 85(Suppl 412):29–35CrossRefGoogle Scholar
  3. 3.
    Aktay AN, Lee PC, Kumar V, Parton E, Wyatt DT, Werlin SL (2001) The prevalence and clinical characteristics of celiac disease in juvenile diabetes in Wisconsin. J Pediatr Gastroenterol Nutr 33:462–465PubMedCrossRefGoogle Scholar
  4. 4.
    Shahbazkhani B, Faezi T, Akbari MR, Mohamadnejad M, Sotoudeh M, Rajab A et al (2004) Celiac disease in Iranian type I diabetic patients. Dig Liver Dis 36:191–194PubMedCrossRefGoogle Scholar
  5. 5.
    Hansen D, Bennedbaek FN, Hansen LK, Hoier-Madsen M, Hegedus L, Jacobsen BB, Husby S (2001) High prevalence of celiac disease in Danish children with type I diabetes mellitus. Acta Paediatr 90:1238–1243PubMedCrossRefGoogle Scholar
  6. 6.
    Baptista ML, Koda YKL, Nisihara RM, Ioshii SO (2005) Prevalence of celiac disease in Brazilian children and adolescents with type 1 diabetes mellitus. J Pediatr Gastroenterol Nutr 41:621–624PubMedCrossRefGoogle Scholar
  7. 7.
    Mahmud FH, Murray JA, Kudva YC, Zinsmeister AR, Dierkhising RA, Lahr BD et al (2005) Celiac disease in type 1 diabetes mellitus in a North American community: prevalence, serologic screening, and clinical features. Mayo Clin Proc 80:1429–1434PubMedCrossRefGoogle Scholar
  8. 8.
    Kordonouri O, Dieterich W, Schuppan D, Webert G, Muller C, Sarioglu N et al (2000) Autoantibodies to tissue transglutaminase are sensitive serological parameters for detecting silent celiac disease in patients with type 1 diabetes mellitus. Diabet Med 17:441–444PubMedCrossRefGoogle Scholar
  9. 9.
    Heap J, Murray MA, Miller SC, Jalili T, Moyer-Mileur LJ (2004) Alterations in bone characteristics associated with glycemic control in adolescents with type 1 diabetes mellitus. J Pediatr 144:56–62PubMedCrossRefGoogle Scholar
  10. 10.
    McNair P, Madsbad S, Christiansen C, Christiensen MS, Faber OK, Binder C, Transbol I (1979) Bone loss in diabetes: effects of metabolic state. Diabetologia 17:283–286PubMedCrossRefGoogle Scholar
  11. 11.
    Gunczler P, Lanes R, Paz-Martinez V, Martins R, Esaa S, Colmenares V, Weisinger JR (1998) Decreased lumbar spine bone mass and low bone turnover in children and adolescents with insulin dependent diabetes mellitus followed longitudinally. J Pediatr Endocrinol Metab 11:413–419PubMedGoogle Scholar
  12. 12.
    Hadjidakis DJ, Raptis AE, Sfakianakis M, Mylonakis A, Raptis SA (2006) Bone mineral density of both genders in type 1 diabetes according to bone composition. J Diabetes Complications 20:302–307PubMedCrossRefGoogle Scholar
  13. 13.
    Salvatoni A, Mancassola G, Biasoli R, Cardani R, Salvatore S, Broggini M et al (2004) Bone mineral density in diabetic children and adolescents: a follow-up study. Bone 34:900–904PubMedCrossRefGoogle Scholar
  14. 14.
    Valerio G, del Puente A, Esposito-del Puente AE, Buono P, Mozzillo E, Franzese A (2002) The lumbar bone mineral density is affected by long-term poor metabolic control in adolescents with type 1 diabetes mellitus. Horm Res 58:266–272PubMedCrossRefGoogle Scholar
  15. 15.
    Gunczler P, Lanes R, Paoli M, Martinis R, Villaroel O, Weisinger JR (2001) Decreased bone mineral density and bone formation markers shortly after diagnosis of clinical type 1 diabetes mellitus. J Pediatr Endocrinol Metab 14:525–528PubMedGoogle Scholar
  16. 16.
    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
  17. 17.
    Lunt H, Florkowski CM, Cook HB, Whitehead MR (2001) Bone mineral density, type 1 diabetes and celiac disease. Diabetes Care 24:791–792PubMedCrossRefGoogle Scholar
  18. 18.
    Lunt H, Florkowski CM, Cundy T, Kendall D, Brown LJ, Elliot JR, Wells JE, Turner JG (1998) A population-based study of bone mineral density in women with longstanding type 1 (insulin dependent) diabetes. Diabetes Res Clin Pract 40:31–38PubMedCrossRefGoogle Scholar
  19. 19.
    Gilsanz V (1998) Bone density in children: a review of the available techniques and indications. Eur J Radiol 26:177–182PubMedCrossRefGoogle Scholar
  20. 20.
    Pagani F, Francucci CM, Moro L (2005) Markers of bone turnover: biochemical and clinical perspectives. J Endocrinol Invest. 28(Suppl 10):8–13PubMedGoogle Scholar
  21. 21.
    Szulc P, Seeman E, Delmas PD (2000) Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int 11:281–294PubMedCrossRefGoogle Scholar
  22. 22.
    Warner JT, Cowan FJ, Dunstan FD, Evans WD, Webb DK, Gregory JW (1998) Measured and predicted bone mineral content in healthy boys and girls aged 6–18 years: adjustment for body size and puberty. Acta Paediatr 87:244–249PubMedCrossRefGoogle Scholar
  23. 23.
    Corazza GR, Di Sario A, Cecchetti L, Torozzi C, Corrao G, Bernardi M, Gasbarrini G (1995) Bone mass and metabolism in patients with celiac disease. Gastroenterology 109:122–128PubMedCrossRefGoogle Scholar
  24. 24.
    Fornari MC, Pedreira S, Niveloni S, Gonzalez D, Diez RA, Vazquez H et al (1998) Pre- and post-treatment serum levels of cytokines IL-1beta, IL-6, and IL-1 receptor antagonist in celiac disease. Are they related to the associated osteopenia? Am J Gastroenterol 93:413–418PubMedGoogle Scholar
  25. 25.
    Mora S, Gilsanz V (2003) Establishment of peak bone mass. Endocrinol Metab Clin North Am 32:39–63PubMedCrossRefGoogle Scholar
  26. 26.
    Barera G, Beccio S, Proverbio MC, Mora S (2004) Longitudinal changes in bone metabolism and bone mineral content in children with celiac disease during consumption of a gluten-free diet. Am J Clin Nutr 79:148–154PubMedGoogle Scholar
  27. 27.
    Kavak US, Yuce A, Kocak N, Demir H, Saltik IN, Gurakan F, Ozen H (2003) Bone mineral density in children with untreated and treated celiac disease. J Pediatr Gastroenterol Nutr 37:434–436PubMedCrossRefGoogle Scholar
  28. 28.
    Meyer D, Stavropolous S, Diamond B, Shane E, Green PHR (2001) Osteoporosis in a North American population with celiac disease. Am J Gastroenterol 96:112–119PubMedGoogle Scholar
  29. 29.
    Miao J, Brismar K, Nyren O, Ugarph-Morawski A, Ye W (2005) Elevated hip fracture risk in type 1 diabetic patients. Diabetes Care 28:2850–2855PubMedCrossRefGoogle Scholar
  30. 30.
    West J, Logan RF, Card TR, Smith C, Hubbard R (2003) Fracture risk in people with celiac disease: a population-based cohort study. Gastroenterology 125:429–436PubMedCrossRefGoogle Scholar
  31. 31.
    Moreno ML, Vazquez H, Maruze R, Smecuol E, Niveloni S, Pedreira S et al (2004) Stratification of bone fracture risk in patients with celiac disease. Clin Gastroenterol Hepatol 2:127–134PubMedCrossRefGoogle Scholar
  32. 32.
    Hill ID, Dirks MH, Liptak GS, Colletti RB, Fasano A, Guandalini S et al (2005) Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 40:1–19PubMedCrossRefGoogle Scholar
  33. 33.
    Rostom A, Murray JA, Kagnoff MF (2006) American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology 131:1981–2002PubMedCrossRefGoogle Scholar
  34. 34.
    Kaukinen K, Maki M, Partanen J, Sievanen H, Collin P (2001) Celiac disease without villous atrophy. Revision of criteria called for. Dig Dis Sci 46:879–887Google Scholar
  35. 35.
    Esteve M, Rosinach M, Fernandez-Banares F et al (2006) Spectrum of glúten-sensitive enteropathy in first-degree relatives of patients with celiac disease: clinical relevance of lymphocytic enteritis. Gut 55:1739–1745PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Daniel R. Diniz-Santos
    • 1
  • Flávia Brandão
    • 2
  • Luis Adan
    • 2
    • 3
  • Agnaluce Moreira
    • 4
  • Eliézer J. Vicente
    • 5
  • Luciana R. Silva
    • 1
    • 3
  1. 1.Division of Pediatric Gastroenterology and Hepatology, Hosannah de Oliveira Pediatric CenterFederal University of BahiaSalvadorBrazil
  2. 2.Pediatric UnitState of Bahia Center for Diabetes and Endocrinology (CEDEBA)SalvadorBrazil
  3. 3.Department of Pediatrics, School of MedicineFederal University of BahiaSalvadorBrazil
  4. 4.LPC Clinical Pathology LaboratorySalvadorBrazil
  5. 5.Bone Densitometry UnitVida ClinicsSalvadorBrazil

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