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

Abstract

OBJECTIVETo investigate whether celiac disease (CD) associated with type 1 diabetes increases the risk of microvascular complications. RESEARCH DESIGN AND METHODSPatients (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 [HbA 1c ], age at diabetes onset, sex, smoking, dyslipidemia, and hypertension). RESULTSKaplan-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. CONCLUSIONSCD 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.

Microvascular complications in T1DM and coeliac disease

“…Patients were assigned to three different groups: no coeliac disease (n = 50,933), suspected coeliac disease (n = 4,769) and biopsy-confirmed coeliac disease (n = 812). 3 The low prevalence of biopsy-confirmed coeliac disease in this study (1.4%) 3 is consistent with reports of a fairly low occurrence of the disease in the general population in Germany (0.3% in the general population). 4 In patients with T1DM and concomitant suspected or biopsy-confirmed coeliac disease, both retinopathy and nephro pathy developed earlier than in patients with only T1DM.…”

“…4 In patients with T1DM and concomitant suspected or biopsy-confirmed coeliac disease, both retinopathy and nephro pathy developed earlier than in patients with only T1DM. 3 In patients with suspected or biopsyconfirmed coeliac disease and T1DM, 25% developed retinopathy by age 27 years (34 years in patients with T1DM but without coeliac disease). Similarly, nephropathy developed in 25% of patients with coeliac disease by age 33 years (42 years in patients without coeliac disease).…”

“…In a new study, Rohrer and colleagues have assessed the risk of retinopathy and nephropathy in patients who have both T1DM and coeliac disease. 3 In this large multicentre prospective study, the investigators collected data from 56,514 patients with T1DM at 392 clinical centres in Germany and Austria. All the participants were <20 years old at T1DM onset and were aged >10 years at their latest follow-up visit.…”

Coeliac patients detected during type 1 diabetes surveillance had similar issues to those diagnosed on a clinical basis

“…Similar results have previously been reported by Tsouka et al (15), and it is evident that these patients are at risk of progressing towards an even more severe disease if not diagnosed and placed on dietary treatment. This issue is of particular importance in diabetic children, as it is known that concomitant type 1 diabetes further predisposes coeliac disease patients to a complicated disease course (24,25). In general, a delay in diagnosis could lead to various consequences of untreated coeliac disease, and screening has been proved to constitute a significant protective factor against the delay and subsequent unnecessary burden of the disease.…”

The Association of Celiac Disease With Other Autoimmune Diseases in Children

“…CD is regarded as an independent risk factor for retinopathy and nephropathy in patients with DMT1 [29].…”