Skip to main content

Advertisement

SpringerLink
Log in

Low serum osteoprotegerin levels in normoalbuminuric type 1 diabetes mellitus

  • Original Article
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

The aim of this study is to establish whether abnormal mineral metabolism is present in patients with type 1 DM with normal renal function and in the absence of microalbuminuria. Serum levels of 1,25-dihydroxyvitamin D, osteoprotegerin (OPG) and receptor activator for nuclear factor kappa β ligand (RANKL) and other determinants of bone metabolism were measured in 35 patients with type 1 DM and in 25 age-, sex- and ethnicity-matched healthy controls. Serum OPG (1.98 vs. 2.98 pmol/l: P = 0.001), 1,25-dihydroxyvitamin D (41.1 vs. 48.2 pmol/l: P = 0.035) and magnesium (0.84 vs. 0.89 mmol/l P = 0.029) levels were significantly lower in patients with type 1 DM compared to normal controls. RANKL levels were similar in both groups. The groups did not differ with respect to calcium, phosphate, PTH, 25-hydroxyvitamin D, tubular reabsorption of phosphate and cross-linked N-telopeptides of type 1-collagen levels. Abnormalities of mineral metabolism including low serum OPG and 1,25-dihydroxyvitamin D levels occur in patients with type 1 DM with normal renal function and in the absence of microalbuminuria. These abnormalities may promote altered bone metabolism and vascular pathology.

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.

Fig. 1

Similar content being viewed by others

References

  1. Chen NX, Moe SM (2003) Arterial calcification in diabetes. Curr Diab Rep 3(1):28–32

    Article  PubMed  Google Scholar 

  2. Vattikuti R, Towler DA (2004) Osteogenic regulation of vascular calcification: an early perspective. Am J Physiol Endocrinol Metab 286(5):E686–E696

    Article  CAS  PubMed  Google Scholar 

  3. Collin-Osdoby P (2004) Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin. Circ Res 95(11):1046–1057

    Article  CAS  PubMed  Google Scholar 

  4. Khosla S (2001) Minireview: the OPG/RANKL/RANK system. Endocrinology 142(12):5050–5055

    Article  CAS  PubMed  Google Scholar 

  5. Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL (2007) Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 71(1):31–38

    Article  CAS  PubMed  Google Scholar 

  6. Vanholder R (2006) Chronic kidney disease in adults—UK guidelines for identification, management and referral. Nephrol Dial Transplant 21(7):1776–1777

    Article  PubMed  Google Scholar 

  7. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1):31–41

    Article  CAS  PubMed  Google Scholar 

  8. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med 130(6):461–470

    CAS  PubMed  Google Scholar 

  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. Diabet Med 26(1):45–52

    Article  CAS  PubMed  Google Scholar 

  10. Botolin S, McCabe LR (2006) Chronic hyperglycemia modulates osteoblast gene expression through osmotic and non-osmotic pathways. J Cell Biochem 99(2):411–424

    Article  CAS  PubMed  Google Scholar 

  11. Brandao FR, Vicente EJ, Daltro CH, Sacramento M, Moreira A, Adan L (2007) Bone metabolism is linked to disease duration and metabolic control in type 1 diabetes mellitus. Diabetes Res Clin Pract 78(3):334–339

    Article  CAS  PubMed  Google Scholar 

  12. Verhaeghe J, Suiker AM, Visser WJ, Van HE, Van BR, Bouillon R (1992) The effects of systemic insulin, insulin-like growth factor-I and growth hormone on bone growth and turnover in spontaneously diabetic BB rats. J Endocrinol 134(3):485–492

    Article  CAS  PubMed  Google Scholar 

  13. Schoppet M, Preissner KT, Hofbauer LC (2002) RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol 22(4):549–553

    Article  CAS  PubMed  Google Scholar 

  14. Rasmussen LM, Tarnow L, Hansen TK, Parving HH, Flyvbjerg A (2006) Plasma osteoprotegerin levels are associated with glycaemic status, systolic blood pressure, kidney function and cardiovascular morbidity in type 1 diabetic patients. Eur J Endocrinol 154(1):75–81

    Article  CAS  PubMed  Google Scholar 

  15. Xiang GD, Sun HL, Zhao LS (2007) Changes of osteoprotegerin before and after insulin therapy in type 1 diabetic patients. Diabetes Res Clin Pract 76(2):199–206

    Article  CAS  PubMed  Google Scholar 

  16. Szulc P, Hofbauer LC, Heufelder AE, Roth S, Delmas PD (2001) Osteoprotegerin serum levels in men: correlation with age, estrogen, and testosterone status. J Clin Endocrinol Metab 86(7):3162–3165

    Article  CAS  PubMed  Google Scholar 

  17. Dovio A, Sartori ML, Angeli A (2003) Correspondence re: A. Lipton et al., Serum osteoprotegerin levels in healthy controls and cancer patients. Clin. Cancer Res., 8: 2306-2310, 2002. Clin Cancer Res 9(6):2384–2385

    CAS  PubMed  Google Scholar 

  18. Singh DK, Winocour P, Farrington K (2008) Mechanisms of disease: the hypoxic tubular hypothesis of diabetic nephropathy. Nat Clin Pract Nephrol 4(4):216–226

    Article  CAS  PubMed  Google Scholar 

  19. Sjogren A, Floren CH, Nilsson A (1986) Magnesium deficiency in IDDM related to level of glycosylated hemoglobin. Diabetes 35(4):459–463

    Article  CAS  PubMed  Google Scholar 

  20. Fatemi S, Ryzen E, Flores J, Endres DB, Rude RK (1991) Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. J Clin Endocrinol Metab 73(5):1067–1072

    Article  CAS  PubMed  Google Scholar 

  21. Al-Badr W, Martin KJ (2008) Vitamin D and kidney disease. Clin J Am Soc Nephrol 3(5):1555–1560

    Article  CAS  PubMed  Google Scholar 

  22. Schoppet M, Al-Fakhri N, Franke FE, Katz N, Barth PJ, Maisch B, Preissner KT, Hofbauer LC (2004) Localization of osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, and receptor activator of nuclear factor-kappaB ligand in Monckeberg’s sclerosis and atherosclerosis. J Clin Endocrinol Metab 89(8):4104–4112

    Article  CAS  PubMed  Google Scholar 

  23. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89(2):309–319

    Article  CAS  PubMed  Google Scholar 

  24. Malyankar UM, Scatena M, Suchland KL, Yun TJ, Clark EA, Giachelli CM (2000) Osteoprotegerin is an alpha vbeta 3-induced, NF-kappa B-dependent survival factor for endothelial cells. J Biol Chem 275(28):20959–20962

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded by Renal Research Unit, Lister Hospital, Stevenage, UK, and partly supported by an unrestricted grant from Eli Lily.

Conflict of interest statement

All authors have no conflicts of interest.

Author information

Authors and Affiliations

  1. Renal Unit, Lister Hospital, East and North Herts NHS Trust, Stevenage, SG1 4AB, UK

    Dhruv K. Singh & Ken Farrington

  2. Diabetes and Endocrinology, East and North Herts NHS Trust, Stevenage, SG1 4AB, UK

    Peter Winocour & Bev Summerhayes

  3. Department of Clinical Chemistry, East and North Herts NHS Trust, Stevenage, SG1 4AB, UK

    Adie Viljoen & G. Sivakumar

Authors
  1. Dhruv K. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Winocour
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bev Summerhayes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adie Viljoen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Sivakumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ken Farrington
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dhruv K. Singh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Singh, D.K., Winocour, P., Summerhayes, B. et al. Low serum osteoprotegerin levels in normoalbuminuric type 1 diabetes mellitus. Acta Diabetol 47 (Suppl 1), 105–110 (2010). https://doi.org/10.1007/s00592-009-0146-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00592-009-0146-z

Keywords

Search

Navigation