Ann Pediatr Endocrinol Metab.  2017 Dec;22(4):247-252. 10.6065/apem.2017.22.4.247.

A lack of association between vitamin D-binding protein and 25-hydroxyvitamin D concentrations in pediatric type 1 diabetes without microalbuminuria

• Kim HY
• Lee YA
• Jung HW
• Gu MJ
• Kim JY
• Lee GM
• Lee J
• Yoon JY
• Yang SW
• Shin CH

• KMID: 2400781
• DOI: http://doi.org/10.6065/apem.2017.22.4.247

Abstract

PURPOSE
Vitamin D deficiency is reported to be more common in type 1 diabetes patients and might be associated with the increased urinary loss of vitamin D binding protein (VDBP) consequent to impaired 25-hydroxyvitamin D (25(OH)D) circulation. We aimed to evaluate the possible increased urinary loss of VDBP, a correlation between VDBP and circulating 25(OH)D level, and risk factors influencing low vitamin D level in pediatric type 1 diabetes patients without microalbuminuria.
METHODS
This is a cross-sectional study of subjects who visited Seoul National University Children's Hospital between January and March 2013. Forty-two type 1 diabetes patients and 29 healthy controls were included. Biochemical parameters including serum and urine VDBP concentrations were analyzed.
RESULTS
There was no significant difference in the frequency of vitamin D deficiency or serum 25(OH)D level between the 2 groups. The serum and urine VDBP concentrations did not show any difference between the 2 groups. Serum 25(OH) D level did not correlate with serum or urine VDBP. Multivariate regression analysis revealed that daylight outdoor hours (β=2.948, P=0.003) and vitamin D intake (β=2.865, P=0.003) affected the 25(OH)D level; the presence of type 1 diabetes or urinary VDBP excretion was not significant.
CONCLUSIONS
In pediatric type 1 diabetes patients, urinary VDBP excretion did not contribute to low serum 25(OH)D level in the setting of normoalbuminuria. The factors associated with 25(OH)D level during winter periods were daylight outdoor hours and vitamin D intake. Further studies including both micro- and macroalbuminuria patients with type 1 diabetes are warranted.

Keyword

Vitamin D-binding protein; Ergocalciferols; Type 1 diabetes mellitus; Child; Albuminuria

MeSH Terms

Albuminuria
Child
Cross-Sectional Studies
Diabetes Mellitus, Type 1
Ergocalciferols
Humans
Risk Factors
Seoul
Vitamin D
Vitamin D Deficiency
Vitamin D-Binding Protein*
Vitamins*
Ergocalciferols
Vitamin D
Vitamin D-Binding Protein
Vitamins

Reference

References

1. Svoren BM, Volkening LK, Wood JR, Laffel LM. Significant vitamin D deficiency in youth with type 1 diabetes mellitus. J Pediatr. 2009; 154:132–4.

2. Littorin B, Blom P, Schölin A, Arnqvist HJ, Blohmé G, Bolinder J, et al. Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS). Diabetologia. 2006; 49:2847–52.

3. Thrailkill KM, Jo CH, Cockrell GE, Moreau CS, Fowlkes JL. Enhanced excretion of vitamin D binding protein in type 1 diabetes: a role in vitamin D deficiency? J Clin Endocrinol Metab. 2011; 96:142–9.

4. Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008; 29:726–76.

5. Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab. 2009; 94:26–34.

6. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96:1911–30.

7. Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J, et al. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell. 1999; 96:507–15.

8. Dusso AS, Tokumoto M. Defective renal maintenance of the vitamin D endocrine system impairs vitamin D renoprotection: a downward spiral in kidney disease. Kidney Int. 2011; 79:715–29.

9. Korea Centers for Disease Control and Prevention; Division of Chronic Disease Surveillance; Committee for the Development of Growth Standard for Korean Children and Adolescents; Korean Pediatric Society; Committee for School Health and Public Health Statistics. 2007 Korean children and adolescents growth standard (commentary for the development of 2007 growth chart). Cheongju: Korea Centers for Disease Control and Prevention, Division of Chronic Disease Surveillance;2007.

10. National Rural Resources Development Institute. Korean standard food composition table. 8th revision [Internet]. Wanju: National Institute of Agricultural Sciences;2011. [cited 2014 Dec 10]. Available from: http://koreanfood.rda.go.kr/eng/fctFoodSrchEng/engMain.

11. U.S. Department of Health and Human Services. 2008 Physical activity guidelines for Americans [Internet]. Washington, DC: U.S. Department of Health and Human Services;c2008. [cited 2016 Jun 1]. Available from: http://www.health.gov/paguidelines/guidelines.

12. Weaver CM. Vitamin D, calcium homeostasis, and skeleton accretion in children. J Bone Miner Res. 2007; 22 Suppl 2:V45–9.

13. Kumar J, Muntner P, Kaskel FJ, Hailpern SM, Melamed ML. Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001-2004. Pediatrics. 2009; 124:e362–70.

14. Prytuła A, Wells D, McLean T, Balona F, Gullett A, Knott C, et al. Urinary and dialysate losses of vitamin D-binding protein in children on chronic peritoneal dialysis. Pediatr Nephrol. 2012; 27:643–9.

15. Tojo A, Kinugasa S. Mechanisms of glomerular albumin filtration and tubular reabsorption. Int J Nephrol. 2012; 2012:481520.

16. Cooke NE, David EV. Serum vitamin D-binding protein is a third member of the albumin and alpha fetoprotein gene family. J Clin Invest. 1985; 76:2420–4.

17. Christensen EI, Birn H. Megalin and cubilin: multifunctional endocytic receptors. Nat Rev Mol Cell Biol. 2002; 3:256–66.

18. Nyomba BL, Verhaeghe J, Thomasset M, Lissens W, Bouillon R. Bone mineral homeostasis in spontaneously diabetic BB rats. I. Abnormal vitamin D metabolism and impaired active intestinal calcium absorption. Endocrinology. 1989; 124:565–72.

19. Blanton D, Han Z, Bierschenk L, Linga-Reddy MV, Wang H, Clare-Salzler M, et al. Reduced serum vitamin D-binding protein levels are associated with type 1 diabetes. Diabetes. 2011; 60:2566–70.

20. Alon US. Vitamin D metabolites in childhood nephrotic syndrome. Pediatr Nephrol. 1995; 9:791–2.

21. Fowlkes JL, Bunn RC, Cockrell GE, Clark LM, Wahl EC, Lumpkin CK, et al. Dysregulation of the intrarenal vitamin D endocytic pathway in a nephropathy-prone mouse model of type 1 diabetes. Exp Diabetes Res. 2011; 2011:269378.

22. Thrailkill KM, Nimmo T, Bunn RC, Cockrell GE, Moreau CS, Mackintosh S, et al. Microalbuminuria in type 1 diabetes is associated with enhanced excretion of the endocytic multiligand receptors megalin and cubilin. Diabetes Care. 2009; 32:1266–8.

23. Bolland MJ, Grey AB, Ames RW, Horne AM, Mason BH, Wattie DJ, et al. Age-, gender-, and weight-related effects on levels of 25-hydroxyvitamin D are not mediated by vitamin D binding protein. Clin Endocrinol (Oxf). 2007; 67:259–64.

24. Winters SJ, Chennubhatla R, Wang C, Miller JJ. Influence of obesity on vitamin D-binding protein and 25-hydroxy vitamin D levels in African American and white women. Metabolism. 2009; 58:438–42.

25. Carpenter TO, Zhang JH, Parra E, Ellis BK, Simpson C, Lee WM, et al. Vitamin D binding protein is a key determinant of 25-hydroxyvitamin D levels in infants and toddlers. J Bone Miner Res. 2013; 28:213–21.

26. Speeckaert M, Huang G, Delanghe JR, Taes YE. Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism. Clin Chim Acta. 2006; 372:33–42.

27. Hamed EA, Faddan NH, Elhafeez HA, Sayed D. Parathormone--25(OH)-vitamin D axis and bone status in children and adolescents with type 1 diabetes mellitus. Pediatr Diabetes. 2011; 12:536–46.

28. Chakhtoura M, Azar ST. The role of vitamin d deficiency in the incidence, progression, and complications of type 1 diabetes mellitus. Int J Endocrinol. 2013; 2013:148673.

29. Greer RM, Portelli SL, Hung BS, Cleghorn GJ, McMahon SK, Batch JA, et al. Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes. Pediatr Diabetes. 2013; 14:31–41.

30. Lee YA, Kim HY, Hong H, Kim JY, Kwon HJ, Shin CH, et al. Risk factors for low vitamin D status in Korean adolescents: the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2009. Public Health Nutr. 2014; 17:764–71.