Social determinants of health on glycemic control in pediatric type 1 diabetes.

OBJECTIVE: To evaluate the relationship between the social determinants of health (SDH) and glycemic control in a large pediatric type 1 diabetes (T1D) population. STUDY DESIGN: Deprivation Indices (DI) were used to ascertain population-level measures of socioeconomic status, family structure, and ethnicity in patients with T1D followed at The Hospital for Sick Children August 2010-2011 (n = 854). DI quintile scores were determined for individual patients based on de-identified postal codes, and linked to mean patient A1Cs as a measure of glycemic control. We compared mean A1C between the most and least deprived DI quintiles. Associations were estimated controlling for age and sex, and repeated for insulin pump use. RESULTS: The T1D population evaluated in this study was most concentrated in the least and most deprived quintiles of the Material DI. A1C levels were highest in patients with the greatest degree of deprivation (fifth vs first quintile) on the Material DI (9.2% vs 8.3%, P < .0001), Social DI (9.1% vs 8.3%, P < .0001), and Ethnic Concentration Index (8.9% vs 8.4%, P = .03). These relationships between measures of the SDH and A1C were not evident for patients on insulin pumps. On regression analysis, higher A1C was predicted by older age, female sex, not using pump therapy, and being in the most deprived quintile for Material and Social Deprivation, but not Ethnic Concentration. CONCLUSIONS: Measures of the SDH comprising Material and Social Deprivation were significantly associated with suboptimal glycemic control in our pediatric T1D cohort. Use of insulin pump therapy also predicted A1C and may have a moderating effect on these relationships.

CYP24A1 and SLC34A1 Pathogenic Variants Are Uncommon in a Canadian Cohort of Children with Hypercalcemia or Hypercalciuria.

OBJECTIVES: Biallelic pathogenic variants in CYPA24A1 and SLC34A1 are causes of idiopathic infantile hypercalcemia. Pathogenic variants in both may also give rise to hypercalciuria with nephrocalcinosis or nephrolithiasis without previous hypercalcemia (renal group). Our objective was to examine the frequency of CYP24A1 or SLC34A1 variants in children with early hypercalcemia or late-onset hypercalciuria. METHOD: Forty-one children from 7 centers across Canada were recruited. Local investigations were undertaken. The serum was evaluated by liquid chromatography tandem-mass spectrometry for the ratio of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3, (25-OH-D3:24,25-(OH)2D3), an elevation pathognomonic for the loss of function of the CYP24A1 enzyme. Mutational analyses were undertaken. Family cascade screening was performed if pathogenic variants were detected in probands. RESULTS: Twenty-nine children had early-onset hypercalcemia; none had elevated 25-OH-D3:24,25-(OH)2D3 or variants. Interestingly, 2 of 12 in the renal group had elevated 25-OH-D3:24,25-(OH)2D3 and presented as preadolescents. In case 1, cascade testing revealed a sibling and parent with asymptomatic pathogenic variants in CYP24A1. Four CYP24A1 pathogenic variants were identified in these 2 probands: 3 have been described in European populations, and 1 is a rare variant in exon 7 (c931delC) that is likely pathogenic. No SLC34A1 pathogenic variants were detected. CONCLUSION: In Canada, pathogenic variants in CYP24A1 appear to manifest with late-onset hypercalciuria and its sequelae. The 25-OH-D3:24,25-(OH)2D3 ratio is an excellent tool for screening for biallelic pathogenic variants in CYP24A1. We confirm that cascade testing is important for these variants.

Screening and Treatment Outcomes in Adults and Children With Type 1 Diabetes and Asymptomatic Celiac Disease: The CD-DIET Study.

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD. RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA1c and continuous glucose monitoring over 12 months. RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%, N = 1,298] vs. 4.7% [95% CI 3.4-5.9%, N = 1,089], P = 0.035) with lower rates of prior CD screening (6.9% vs. 44.2%, P < 0.0001). Fifty-one participants were randomized to a GFD (N = 27) or GCD (N = 24). No HbA1c differences were seen between the groups (+0.14%, 1.5 mmol/mol; 95% CI -0.79 to 1.08; P = 0.76), although greater postprandial glucose increases (4-h +1.5 mmol/L; 95% CI 0.4-2.7; P = 0.014) emerged with a GFD. CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.