Nicole Scheuing

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.

Cystic fibrosis-related diabetes compared with type 1 and type 2 diabetes in adults

With increasing life expectancy of patients with cystic fibrosis (CF), secondary diabetes becomes more prevalent. It appears to be the most common co‐morbidity in persons with cystic fibrosis. Therefore, the objective of our study was to describe characteristics of cystic fibrosis‐related diabetes compared with type 1 and 2 diabetes (T1DM/T2DM) in adults.

Vascular risk factors in children, adolescents, and young adults with type 1 diabetes complicated by celiac disease: results from the DPV initiative

Celiac disease (CD) is a common comorbidity of type 1 diabetes (T1D). Long‐term consequences of CD are not completely understood, and adhering to a gluten‐free diet is a burden for many patients. We investigated the effect of CD on vascular risk factors in a large cohort of T1D patients aged <20 yr.

Lower frequency of insulin pump treatment in children and adolescents of Turkish background with type 1 diabetes: analysis of 21,497 patients in Germany.

AIM This study investigated insulin pump therapy in pediatric patients with type 1 diabetes and Turkish origin compared with those without migration background in Germany. SUBJECTS AND METHODS Using a nationwide documentation program, we estimated the prevalence of insulin pump therapy in patients < 20 years of age with Turkish origin and those without migration background. Logistic regression was used to adjust for age, sex, diabetes duration, body mass index SD score (BMI-SDS), glycated hemoglobin, number of outpatient visits, number of daily blood glucose self-measurements, and area-based socioeconomic conditions. RESULTS In 1,695 pediatric type 1 diabetes patients with Turkish background and 19,802 patients without migration background (respectively: 51.2% and 53.0% boys; mean age, 12.4 ± 4.1 and 12.6 ± 4.2 years; mean diabetes duration, 4.7 ± 3.9 and 5.3 ± 4.0 years), fully adjusted prevalences of insulin pump therapy were 18.5% and 30.9%, respectively (odds ratio 0.51, 95% confidence interval 0.43-0.60, P < 0.001). Age, sex, BMI-SDS, outpatient visits, and blood glucose self-control were significantly associated with the prevalence of insulin pump therapy but did not alter the difference substantially. CONCLUSIONS The prevalence of insulin pump therapy is roughly half among pediatric diabetes patients with Turkish background compared with those without migration background. Several covariates could not explain this difference. Individual characteristics or access barriers within the healthcare system may play a role. Further research is needed.

High Variability in Oral Glucose Tolerance among 1,128 Patients with Cystic Fibrosis: A Multicenter Screening Study

Background In cystic fibrosis, highly variable glucose tolerance is suspected. However, no study provided within-patient coefficients of variation. The main objective of this short report was to evaluate within-patient variability of oral glucose tolerance. Methods In total, 4,643 standardized oral glucose tolerance tests of 1,128 cystic fibrosis patients (median age at first test: 15.5 [11.5; 21.5] years, 48.8% females) were studied. Patients included were clinically stable, non-pregnant, and had at least two oral glucose tolerance tests, with no prior lung transplantation or systemic steroid therapy. Transition frequency from any one test to the subsequent test was analyzed and within-patient coefficients of variation were calculated for fasting and two hour blood glucose values. All statistical analysis was implemented with SAS 9.4. Results A diabetic glucose tolerance was confirmed in 41.2% by the subsequent test. A regression to normal glucose tolerance at the subsequent test was observed in 21.7% and to impaired fasting glucose, impaired glucose tolerance or both in 15.2%, 12.0% or 9.9%. The average within-patient coefficient of variation for fasting blood glucose was 11.1% and for two hour blood glucose 25.3%. Conclusion In the cystic fibrosis patients studied, a highly variable glucose tolerance was observed. Compared to the general population, variability of two hour blood glucose was 1.5 to 1.8-fold higher.

Treatment of young patients with HNF1A mutations (HNF1A-MODY).

Children and adolescents with a molecular diagnosis of HNF1A–MODY should be treated with oral sulfonylurea according to current International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines.

Diabetes in Cystic Fibrosis: Multicenter Screening Results Based on Current Guidelines

Background Published estimates on age-dependent frequency of diabetes in cystic fibrosis (CF) vary widely, and are based mostly on older data. However, CF treatment and prevention of comorbidities changed over recent years. In many studies, definition of cystic fibrosis-related diabetes (CFRD) is not in line with current guideline recommendations. Therefore, we evaluated age-dependent occurrence of glucose abnormalities and associated risk factors in CF patients who participated in a multicenter screening program using oral glucose tolerance tests (OGTT). Methods Between 2001 and 2010, 43 specialized CF centers from Germany and Austria serially performed 5,179 standardized OGTTs in 1,658 clinically stable, non-pregnant CF patients with no prior steroid medication or lung transplantation. Age-dependent occurrence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG+IGT, one (DGT) or two consecutive (CFRD) diabetic OGTTs was analyzed, using Kaplan Meier curves. Cox proportional-hazards models were created to elucidate the influence of sex or underweight. Results At baseline/last OGTT, median age was 15.9 years/18.2 years and 30.6%/31.8% of patients were underweight. 25% of patients showed IFG at age 14.3 years; IGT at age 16.3 years; IFG+IGT combined at age 17.7 years. DGT was observed in 25% of patients at age 22.6 years; CFRD at age 34.5 years. Females had a 3.54 [95% CI 1.23–10.18] times higher risk for CFRD; risk for DGT was 2.21 [1.22–3.98] times higher. Underweight was a risk factor for IGT (HR [95% CI]: 1.38 [1.11–1.71]) and IFG+IGT (1.43 [1.11–1.83]), and in males also for DGT (1.49 [1.09–2.04]). Conclusions/Significance If confirmation of diabetes by a second test is required, as recommended in current guidelines, age at CFRD diagnosis was higher compared to most previous studies. However, known risk factors for glucose abnormalities in CF were confirmed. Confirmation of diabetic OGT by a repeat test is important for a consistent diagnosis of CFRD.

Multicentre analysis of 178,992 type 2 diabetes patients revealed better metabolic control despite higher rates of hypertension, stroke, dementia and repeated inpatient care in patients with comorbid Parkinson's disease

BACKGROUND Especially in older people, physicians are faced with the coexistence of type 2 diabetes mellitus (T2DM) and Parkinsons disease (PD). Therefore, this research aimed to compare diabetes endpoints between T2DM with and without PD. METHODS Based on the standardized, multicenter, prospective DPV database, 178,992 T2DM patients (≥40 years) were analyzed. 1579 were diagnosed with PD and/or received specific treatment. Hierarchical multivariable regression models were used for group comparisons; adjusted estimates based on observed marginal frequencies were calculated. RESULTS PD patients were significantly older (77.9 vs. 70.0 years; p < 0.0001) and had a longer diabetes duration (10.3 vs. 8.4 years; p < 0.0001). In young PD patients (<50 years), percentage of females was significantly higher compared to age-matched T2DM patients without PD or people of the German population (66.7 vs. 38.1 vs. 49.0%; p < 0.0001, p < 0.02). After demographic adjustment, T2DM patients with PD showed a significantly lower HbA1c (58.0 vs. 60.3 mmol/mol; p < 0.0001), OAD/GLP-1 treatment (41.9 vs. 45.9%; p < 0.01) and frequency of dyslipidemia (62.0 vs. 64.5%; p < 0.05). In contrast, rates of insulin therapy (57.8 vs. 54.8%; p < 0.05), hypertension (73.3 vs. 68.6%; p < 0.001), antihypertensive medication (60.4 vs. 56.1%; p < 0.01), stroke (12.0 vs. 7.3%; p < 0.0001), dementia (9.2 vs. 2.6%; p < 0.0001) and repeated inpatient care (15.7 vs. 12.0%; p < 0.0001) were significantly higher and duration of hospital stay (6.2 vs. 4.7 days; p < 0.0001) was significantly longer in T2DM with PD. CONCLUSION Clear demographic and clinical differences were observed between T2DM with and without PD. In PD patients, metabolic control is better, potentially due to more intensive medical care.

Impact of Maternal Country of Birth on Type-1-Diabetes Therapy and Outcome in 27,643 Children and Adolescents from the DPV Registry

Objective To study the impact of maternal country of birth on type-1-diabetes (T1D) therapy and outcome. Study Design and Methods 27,643 T1D patients aged ≤20 years with documented maternal country of birth from the multicenter German/Austrian diabetes patient registry (DPV) were analyzed. Patients were categorized based on their mother’s origin: Germany/Austria (reference), Turkey, Southern Europe, and Eastern Europe. To compare BMI standard deviation score (BMI-SDS), diabetes therapy and outcome between groups, multivariable regression was applied with adjustments for age, sex and duration of diabetes. Based on observed marginal frequencies, adjusted estimates were calculated. Linear regression was used for continuous data, logistic regression for binary data and Poisson regression for count data. All statistical analyses were performed using SAS 9.4. Significance was set at a two-tailed p<0.05. Results 83.3% of patients were offspring of native mothers. A Turkish, Southern or Eastern European background was documented in 2.4%, 1.7% and 4.3% of individuals. After demographic adjustment, patients with migration background had a higher mean BMI-SDS (Turkey, Southern Europe or Eastern Europe vs. Germany/Austria: 0.58±0.03, 0.40±0.04, or 0.37±0.02 vs. 0.31±0.01; ±SE) and a lower use of insulin pumps (26.8%, 27.9%, or 32.6% vs. 37.9%) compared to offspring of native mothers. Mean HbA1c was worst in individuals of Turkish mothers (Turkey vs. Germany/Austria: 69.7±0.7 vs. 66.6±0.1 mmol/mol; ±SE). Patients of Eastern European descent had an increased rate of severe hypoglycemia (22.09±0.13 vs. 16.13±0.02 events per 100 patient-years) and ketoacidosis was more prevalent in offspring of Turkish or Southern European mothers (7.50±0.10, or 7.13±0.11 vs. 6.54±0.02 events per 100 patient-years). Patients of Turkish descent were more often hospitalized (57.2±2.7 vs. 48.5±0.4 per 100 patient-years). All differences were significant. Conclusion The differences in diabetes therapy and outcome among patients with distinct migration background suggest that specific challenges have to be considered in clinical care.

Adherence to clinical care guidelines for cystic fibrosis-related diabetes in 659 German/Austrian patients

BACKGROUND In Germany/Austria, data on medical care for cystic fibrosis-related diabetes (CFRD) is limited. METHODS Anonymized data from 659 CFRD patients were analyzed and compared to the latest ADA/CFF guidelines. RESULTS Specialized diabetes clinics were attended less frequently than recommended (3.1 vs. 4.0 times yearly). 7.9% of patients had a complete profile of examinations: diabetes education (44.9%), HbA1c (88.8%), blood pressure (79.5%), BMI (86.5%), lipid status (37.5%), retinopathy (29.9%), microalbuminuria (33.2%), and self-monitoring of blood glucose (71.6%). HbA1c and blood pressure were measured less frequently than recommended (2.3 and 2.0 vs. 4.0 times yearly). Overall, guidelines were followed more frequently in children than adults. Contrary to recommendations, not all patients were treated with insulin (77.2 vs. 100.0%). Insulin therapy was initiated earlier in children than adults, but there was still a substantial delay (0.9 vs. 2.7years after diagnosis, p<0.001). CONCLUSION In CFRD patients studied, adherence to care guidelines was suboptimal.