Screening for coeliac disease in 1624 mainly asymptomatic children with type 1 diabetes: is genotyping for coeliac-specific human leucocyte antigen the right approach?

OBJECTIVES: To investigate the frequency of coeliac disease (CD)-specific human leucocyte antigen (HLA) genotypes in paediatric patients with type 1 diabetes (T1D), who are known to have a higher prevalence of CD than the general population, and to evaluate whether HLA genotyping is a suitable first-line screening method for CD. STUDY DESIGN: The study was a multicentre observational analysis of patients with T1D aged <20 years of whom a subgroup had undergone HLA genotyping. Patient data were retrieved from the Diabetes Prospective Follow-up database, a large diabetes follow-up registry. The present analysis included data from 439 centres throughout Germany, Austria, Switzerland and Luxembourg. RESULTS: In March 2017, the database contained 75 202 patients with T1D (53% male, mean age (SD) 14.6 (4.1) years, mean age at diagnosis 8.8 (4.3) years and mean diabetes duration 5.8 (4.3) years). 1624 patients had undergone coeliac-specific HLA genotyping, of whom 1344 (82.8%) were positive for HLA-DQ2, HLA-DQ8 or both, while 17.2% had no coeliac-specific HLA-markers. 26.6% of at-risk patients had a clinical suspected diagnosis of CD, and 3.6% had biopsy-proven CD. CONCLUSIONS: Genotyping for HLA-DQ2, HLA-DQ8 or both is positive in the vast majority (>80%) of patients with T1D. Therefore, screening for coeliac-specific HLA genotypes as a first-line test is not a suitable method to exclude CD in T1D. Regular screening for coeliac-specific antibodies in T1D is still recommended.

Microvascular Complications in Childhood-Onset Type 1 Diabetes and Celiac Disease: A Multicenter Longitudinal Analysis of 56,514 Patients From the German-Austrian DPV Database.

OBJECTIVE: To investigate whether celiac disease (CD) associated with type 1 diabetes increases the risk of microvascular complications. RESEARCH DESIGN AND METHODS: Patients (n = 56,514) aged >10 years with diabetes duration <20 years from 392 centers in Germany and Austria were assigned to one of three categories (n): no CD (50,933), biopsy-confirmed CD (812), or suspected CD (4,769; clinical diagnosis or positive antibodies). The confirmed and suspected groups were combined and analyzed for retinopathy or nephropathy. Cox proportional hazards regression was used to adjust for potential confounders (glycated hemoglobin [HbA1c], age at diabetes onset, sex, smoking, dyslipidemia, and hypertension). RESULTS: Kaplan-Meier analysis revealed that retinopathy and nephropathy occurred earlier in the presence versus absence of CD: retinopathy at age 26.7 years (95% CI 23.7-30.2) in 25% of patients with CD vs. age 33.7 years (33.2-34.4) in 25% without CD and microalbuminuria at age 32.8 years (29.7-42.5) vs. 42.4 years (41.4-43.3). The adjusted risk for both retinopathy (hazard ratio 1.263 [95% CI 1.078-1.481]) and nephropathy (1.359 [1.228-1.504]) was higher in patients with diabetes and CD versus those without CD. Cox regression revealed CD as an independent risk factor for microvascular complications after adjustment for confounders. CONCLUSIONS: CD is an independent risk factor for retinopathy and nephropathy in patients with type 1 diabetes. Our study therefore supports the recommendation for regular serologic testing for CD, even in the absence of clinical CD. Further prospective studies are required to investigate whether a gluten-free diet might reduce the risk of microvascular disorders in patients with diabetes and CD.

Characterization of 33 488 children and adolescents with type 1 diabetes based on the gender-specific increase of cardiovascular risk factors.

OBJECTIVES: Characterization of children with type 1 diabetes (T1DM) regarding number and gender distribution of cardiovascular risk factors (cvRF) and of total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C ratio) for risk assessment. METHODS: 33488 patients 200 mg/dL, >5.17 mmol/L; and/or HDL-C <35 mg/dL, <0.91 mmol/L; and/or LDL-C >130 mg/dL, >3.36 mmol/L), elevated systolic and/or diastolic blood pressure (BP) >or=90th percentile, obesity >97th percentile, active smoking, and HbA1c >or=7.5% were considered as cvRF. RESULTS: 65% had no or 1 cvRF. HbA1c >/=7.5% was the most frequently occurring cvRF followed by BP >or=90th percentile, dyslipidemia, smoking, and BMI >97th percentile. Age at diabetic onset ranged from 7.7 to 9.2 years and diabetes duration from 4.1 to 6.6 years. CvRF showed differences in disfavour of females except smoking and HDL-C <35 mg/dL (0.91 mmol/L). Rate of females was 45% with 0 cvRF and 60% with 4 to 5 cvRF. TC/HDL-C ratio showed no clear association to the number of cvRF. CONCLUSIONS: 35% of a pediatric T1DM population develops 2 or more cvRF thus increasing their cv risk in adulthood. With increasing numbers of cvRF, the percentage of girls is rising from 45% to 60% which might contribute to an assimilation of survival rates in female and male adults. TC/HDL ratio does not predict the extent of cardiovascular risk in pediatric T1DM.

Medical care of obese children and adolescents. APV: a standardised multicentre documentation derived to study initial presentation and cardiovascular risk factors in patients transferred to specialised treatment institutions.

UNLABELLED: So far in Europe, no studies have been published on the structuring of medical care for obese children and adolescents. Besides anthropometric parameters, evaluations of the cardiovascular risk factors hypertension, dyslipidaemia, impaired glucose metabolism and treatment modalities were documented in a standardised multicentre evaluation survey (APV) of 18 primarily outpatient and nine rehabilitation institutions. In total, 3837 children (aged 2-20 years) took part in the years 2000 up to March 2003, of whom 1985 were treated in outpatient institutions and 1852 in rehabilitation institutions. Of these children, 10% were overweight, 37% obese, 49% extremely obese and 4% of normal weight at initial presentation. The frequencies of diagnostic procedures performed and documented were low (measurement of blood pressure 43%, lipids 40%, glucose metabolism 21%). In the subgroup of obese children who were screened for cardiovascular risk factors, 23% suffered from hypertension, 11% displayed increased cholesterol, 9% increased low-density lipoprotein-cholesterol, 29% increased triglycerides, 11% decreased high-density lipoprotein-cholesterol and 6% had impaired glucose metabolism. CONCLUSION: Despite the high prevalence of cardiovascular risk factors in obese children and adolescents confirmed in this report, diagnostic procedures failed in a considerable percentage even in specialised treatment centres for obese children and adolescents. In future, the feedback based on standardised evaluation of diagnostic and treatment procedures should aim to improve the quality of medical care.