Reduced Bone Mineral Density Is Associated with Celiac Disease Autoimmunity in Children with Type 1 Diabetes

Abstract

Objective To evaluate the association between bone mineral density (BMD), glycemic control (HbA1c) and celiac autoimmunity in children with type one diabetes (T1D) and in an appropriate control population. Study design BMD was assessed cross-sectionally in 252 children with T1D (123 positive for TG and 129 matched children who were negative for transglutaminase [TG]). Additionally, BMD was assessed in 141 children without diabetes who carried T1D-associated HLD-DR,DQ genotypes (71 positive for TG and 70 negative). Results Children with T1D who were positive for TG had significantly worse BMD L1-L4 z-score compared with children with T1D who were negative for TG (−0.45 ± 1.22 vs. 0.09 ± 1.10, p=0.0003). No differences in growth measures, urine N-telopeptides, vitamin D 25OH, ferritin, TSH or HbA1c were found. However, both higher HbA1c (β= −1.25 ± 0.85, p=0.0016) and TG (β= −0.13 ± 0.05, p = 0.0056) were significant and independent predictors of lower BMD in multivariate analyses. No differences in BMD or other variables measured were found between children without diabetes who were positive versus negative for TG. Conclusions The results suggest a synergistic effect of hyperglycemia and celiac autoimmunity on low BMD.

Update on Bone Health in Pediatric Chronic Disease

“…24,26,28,29 Frouda and colleagues 24 as well as the International Society for Clinical Densitometry (ISCD) 11 recommend not evaluating BMD if children are compliant with the diet because data support full recovery. Guidelines from the United Kingdom, however, recommend testing in all patients at time of diagnosis 29 whereas others restrict assessment to those who are not adherent to the diet or have lower BMI, history of irregular menses, anemia, or other risk factors for fracture.…”

“…32–35 Underlying microvasculopathy, decreased vitamin D levels, inflammation, and increased levels of advanced glycation end products further contribute to impaired bone health. 28,32 …”

“…Adults with T1DM have normal to decreased BMD, 4,28,36 with up to 20% of patients over the age of 20 reported as having osteoporosis. 28 Decreased BMD has been reported at the hip and lower BMD in the spine compared with controls.…”

Epidemiology of Skeletal Health in Type 1 Diabetes

“…Similar to the fracture literature, the presence of a T1D-related complication including retinopathy, nephropathy, or other microvascular disease has emerged as a predictor of skeletal deficits in several studies [24, 47•, 49, 59•]. The reported effect of glycemic control on bone outcomes, however, has varied widely, with a negative association seen in some studies [28, 30, 35, 37, 41, 60] but not others [14, 23, 29, 32, 33, 39, 40]. Better glycemic control has been shown to be associated with reduced risk of other T1D-related complications in clinical trials and long-term follow-up studies [22, 61]; so, it is unclear why hyperglycemia has not emerged as a consistent predictor of skeletal deficits.…”

The Association of Celiac Disease With Other Autoimmune Diseases in Children

“…Some studies suggest that patients with newly diagnosed DMT1 and CD have frequent hypoglycemic episodes, higher average value of glycosylated hemoglobin, and reduced bone mineral density [24][25][26]. Conflicting evidence exist as to whether a GFD significantly improves glycemic control in DMT1 patients [24,27,28].…”