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Observational Study
. 2017 Dec;105:184-190.
doi: 10.1016/j.bone.2017.09.001. Epub 2017 Sep 4.

Evidence of Disordered Calcium Metabolism in Adolescent Girls With Type 1 Diabetes: An Observational Study Using a Dual-Stable Calcium Isotope Technique

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Observational Study

Evidence of Disordered Calcium Metabolism in Adolescent Girls With Type 1 Diabetes: An Observational Study Using a Dual-Stable Calcium Isotope Technique

David R Weber et al. Bone. .
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Abstract

Type 1 diabetes (T1D) is associated with skeletal abnormalities including low bone density and increased fracture risk. The pathophysiology underlying T1D related skeletal fragility remains unknown. The objective of this study was to use a dual-stable calcium isotope method to investigate the effects of T1D on calcium absorption and estimated calcium retention in adolescent females. Twenty adolescent females with T1D were admitted for a 24-h calcium absorption study using oral (44Ca) and intravenous (42Ca) stable isotopes for determination of percent gastrointestinal calcium absorption and estimated calcium retention. Five out of twenty participants were found to have negative estimated calcium retention. Participants with negative calcium retention had greater urinary calcium excretion [202mg/d (IQR: 178-213)] compared to those with positive calcium retention [101.5mg/d (IQR: 82-122)], p=0.01, but similar calcium intake and percent calcium absorption. With the exception of one outlier, 24-h urine calcium was significantly associated with hemoglobin A1c (Pearson's r=0.55, p=0.02). 50% of participants consumed less than the RDA for calcium; fractional calcium absorption was inversely correlated with calcium intake in participants not meeting the RDA (Spearman's rho -0.65, p=0.04). In conclusion, one-quarter of adolescent girls with T1D were found to have negative estimated calcium retention at a time when bone mineral accrual should be ongoing. This appeared to be the result of excess urinary calcium excretion as opposed to diminished gastrointestinal calcium absorption. Insufficient calcium availability for bone deposition during adolescence could impair bone mineral accrual and contribute to skeletal fragility. Trial registered: ClinicalTrials.gov Reg No. NCT03156179.

Keywords: Bone mineral content; Calcium; Hypercalciuria; Hyperglycemia; Stable isotopes; Type 1 diabetes.

Conflict of interest statement

Conflict of Interest Statement: None of the authors has a conflict of interest to declare.

Figures

Figure 1
Figure 1
Comparison of calcium outcomes including (A) 24-hour urine calcium excretion, (B) dietary calcium intake, (C) percent calcium absorption, and (D) true calcium absorbed between female T1D participants with negative estimated calcium retention (n=5) versus those with positive estimated calcium retention (n=15). Only 24-hour urine calcium excretion differed significantly between the groups. Wilcoxon rank sum test used to compare calcium outcomes between groups; statistical significance was defined as two-sided p-value <0.05. Solid circle in 1C is an outside data point (>1.5*interquartile range)
Figure 2
Figure 2
Scatter plot showing the relationship between 24-hour urine calcium excretion and hemoglobin A1c in 20 female T1D participants. Dashed line represents the estimated regression line including all data points (R2=0.23, p=0.34). Solid line represents the estimated regression line excluding data point in lower right corner as an outlier (R2=0.55, p=0.02), outlier determineation based upon studentized residual = −2.8, leverage = 0.43 (where 2k=2/n=0.3), Cook’s D = 2.1 (where 4/n=0.2), DFBETA = −2.3 (where 2/Sqrt(n)=0.45). Pearson’s product-moment coefficient used to determine strength of relationship between variables; statistical significance was defined as two-sided p-value <0.05.

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