Plasma concentrations of vitamin D metabolites during puberty of diabetic children

Abstract

Plasma concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D and vitamin D binding protein were determined in 87 serum samples from 46 Type 1 (insulin-dependent) diabetic children and adolescents at the various stages of puberty. The results were compared with data similarly obtained from healthy pubertal children. The diabetic patients had lower mean 1,25-dihydroxyvitamin D concentrations (p less than 0.05) and higher molar ratios of 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D (p less than 0.05) than their healthy counter parts. In contrast to the reference group, the diabetic patients failed to attain the increase in 1,25-dihydroxyvitamin D normally seen during the pubertal stages of maximal growth velocity. The mean plasma levels of vitamin-D binding protein did not differ between the two groups, and a calculated 'free' 1,25-dihydroxyvitamin D value followed a pattern similar to that of total 1,25-dihydroxyvitamin D throughout puberty for both groups. The results suggest that the regulatory mechanisms of the vitamin D endocrine system are altered in diabetic children at puberty, resulting in a relative decrease in 1,25-dihydroxyvitamin D plasma concentration and increased 24,25-dihydroxyvitamin D levels.

Vitamin D homeostasis is compromised due to increased urinary excretion of the 25-hydroxycholecalciferol-vitamin D-binding protein complex in the Zucker diabetic fatty rat

“…Although we and others have found that vitamin D metabolism can be dramatically altered under diabetic conditions (1,27,29), exploration of the role of megalin and its endocytic partners in maintaining optimal vitamin status is a new concept. Hence, these studies may offer new insight into whether vitamin D supplementation and monitoring urinary and serum vitamin D levels can help prevent or alleviate secondary complications stemming from compromised kidney function in diabetes.…”

“…It is well documented that non-insulin-dependent diabetics are at a disproportionately high risk for the development of breast, prostate, and colorectal cancer, cancers that are arguably the most sensitive to the actions of vitamin D. The naturally occurring active form of vitamin D (1,25D 3 ) has well-documented antiproliferative actions, including cell cycle arrest, differentiation, and induction of apoptosis (4,5,12,24,37). Because low serum levels of 1,25D 3 and its precursors are often present in diabetes (1,14,27,29), there may be a substantially larger dietary vitamin D requirement for these individuals. Numerous animal studies have outlined the potential role of increased vitamin D status with respect to the inhibition of tumor formation and promotion.…”

Vitamin D 1alpha-hydroxylase (CYP1alpha) polymorphism in Graves' disease, Hashimoto's thyroiditis and type 1 diabetes mellitus

“…The vitamin D endocrine system has important immunomodulatory properties and 1,25(OH) 2 D 3 can prevent autoimmune diabetes (1) and autoimmune thyroiditis (2) in animal models. Also, 1,25(OH) 2 D 3 serum levels were reported to be reduced in type 1 diabetes -even at disease onset (18,19) -and in autoimmune hyperthyroidism compared with nonautoimmune hyperthyroidism (20). A recent study investigating various parameters of vitamin D metabolism in mono-and dizygotic twins found 65% of the 1,25(OH) 2 D 3 serum levels to be genetically determined (21).…”

Calciotrophic hormones during experimental hypocalcaemia and hypercalcaemia in spontaneously diabetic rats

“…Yet, PTH concentrations increased normally during a citrateinduced hypocalcaemic clamp in diabetic adults (Schwarz et al 1992). 1,25(OH) 2 D 3 concentrations were normal in insulin-treated diabetic adults (Storm et al 1983, Nyomba et al 1986, Auwerx et al 1988, Gallacher et al 1993; however, decreased levels of both total and free 1,25(OH) 2 D 3 have been reported in diabetic children and adolescents (Frazer et al 1981, Rødland et al 1985, Saggese et al 1988 during diabetic ketoacidosis -reversible after treatment (Storm et al 1983), and in severely insulin-deficient adult diabetics in central Africa (Nyomba et al 1986). …”

“…In those studies in which ionised calcium (Ca 2+ ) was measured, a small but significant decrease has been documented in both diabetic children and adults (Fogh-Andersen et al 1983, Saggese et al 1988, Schwarz et al 1992; this decrease persisted during a calcium infusion (Amado et al 1987). Serum P concentrations were reported to be normal (Saggese et al 1988, Schwarz et al 1992, increased (Rødland et al 1985) or decreased (Auwerx et al 1988); intensifying the insulin therapy raised serum P levels (Raskin & Pak 1981). PTH concentrations, measured by immunoassays that detect the intact hormone, were found to be within the normal range in diabetic adults (Schwarz et al 1992, Gallacher et al 1993, but a rise in PTH levels was noted after improvement of glycaemic control (Thalassinos et al 1993); decreased levels of intact PTH were reported in diabetic children, with a sluggish response to a low-Ca diet (Saggese et al 1988).…”