Tilman R Rohrer1, Johannes Wolf2, Susanne Liptay3, Klaus-Peter Zimmer4, Elke Fröhlich-Reiterer5, Nicole Scheuing6, Wolfgang Marg7, Martin Stern8, Thomas M Kapellen9, Berthold P Hauffa10, Joachim Wölfle11, Reinhard W Holl6. 1. Division of Pediatric Endocrinology, Department of Pediatric and Adolescent Medicine, Saarland University Medical Center, Homburg/Saar, Germany tilman.rohrer@uks.eu. 2. Department of Pediatric and Adolescent Medicine, St. Vincenz Hospital, Paderborn, Germany. 3. Department of Pediatrics, Technical University Munich, Munich, Germany. 4. Department of General Pediatrics and Neonatology, Children's Hospital, University of Giessen, Giessen, Germany. 5. Department of Pediatrics, Medical University of Graz, Graz, Austria. 6. Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, Ulm, Germany. 7. Center for Pediatrics and Adolescent Medicine, Bremen-Mitte Hospital, Bremen, Germany. 8. University of Tübingen Children's Hospital, Tübingen, Germany. 9. Department of Pediatrics, University of Leipzig, Leipzig, Germany. 10. Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics II, University of Duisburg-Essen, Essen, Germany. 11. Pediatric Endocrinology Division, Children's Hospital, University of Bonn, Bonn, Germany.
Abstract
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.
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.
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