Julia M. Hermann

Rates of Diabetic Ketoacidosis: International Comparison With 49,859 Pediatric Patients With Type 1 Diabetes From England, Wales, the U.S., Austria, and Germany

OBJECTIVE Diabetic ketoacidosis (DKA) in children and adolescents with established type 1 diabetes is a major problem with considerable morbidity, mortality, and associated costs to patients, families, and health care systems. We analyzed data from three multinational type 1 diabetes registries/audits with similarly advanced, yet differing, health care systems with an aim to identify factors associated with DKA admissions. RESEARCH DESIGN AND METHODS Data from 49,859 individuals <18 years with type 1 diabetes duration ≥1 year from the Prospective Diabetes Follow-up Registry (DPV) initiative (n = 22,397, Austria and Germany), the National Paediatric Diabetes Audit (NPDA; n = 16,314, England and Wales), and the T1D Exchange (T1DX; n = 11,148, U.S.) were included. DKA was defined as ≥1 hospitalization for hyperglycemia with a pH <7.3 during the prior year. Data were analyzed using multivariable logistic regression models. RESULTS The frequency of DKA was 5.0% in DPV, 6.4% in NPDA, and 7.1% in T1DX, with differences persisting after demographic adjustment (P < 0.0001). In multivariable analyses, higher odds of DKA were found in females (odds ratio [OR] 1.23, 99% CI 1.10–1.37), ethnic minorities (OR 1.27, 99% CI 1.11–1.44), and HbA1c ≥7.5% (≥58 mmol/mol) (OR 2.54, 99% CI 2.09–3.09 for HbA1c from 7.5 to <9% [58 to <75 mmol/mol] and OR 8.74, 99% CI 7.18–10.63 for HbA1c ≥9.0% [≥75 mmol/mol]). CONCLUSIONS These multinational data demonstrate high rates of DKA in childhood type 1 diabetes across three registries/audits and five nations. Females, ethnic minorities, and HbA1c above target were all associated with an increased risk of DKA. Targeted DKA prevention programs could result in substantial health care cost reduction and reduced patient morbidity and mortality.

HbA1c Variability as an Independent Risk Factor for Diabetic Retinopathy in Type 1 Diabetes: A German/Austrian Multicenter Analysis on 35,891 Patients

Objective This study aimed to analyze the effect of HbA1c variability on the occurrence of diabetic retinopathy in type 1 diabetes patients. Patients and Methods 35,891 patients with childhood, adolescent or adult onset of type 1 diabetes from a large multicentre survey, the German/Austrian prospective documentation system (DPV), were analysed. Cox proportional hazard models were used to examine whether intra-individual HbA1c variability expressed as variation coefficient is an independent risk factor for the occurrence of diabetic retinopathy. Results Kaplan-Meier curves stratified by median HbA1c and variation coefficient revealed that retinopathy-free survival probability is lower when both median HbA1c and HbA1c variability are above the 50th percentile. Cox regression models confirmed this finding: After adjustment for age at diabetes onset, gender and median HbA1c, HbA1c variability was independently associated with the occurrence of diabetic retinopathy. Time-covariate interactions used to model non-proportionality indicated an effect decreasing with duration of diabetes for both median HbA1c and HbA1c variability. Predictive accuracy increased significantly when adding HbA1c variability to the Cox regression model. Conclusions In patients with type 1 diabetes, HbA1c variability adds to the risk of diabetic retinopathy independently of average metabolic control.

Longitudinal Trajectories of Metabolic Control From Childhood to Young Adulthood in Type 1 Diabetes From a Large German/Austrian Registry: A Group-Based Modeling Approach

OBJECTIVE Worsening of glycemic control in type 1 diabetes during puberty is a common observation. However, HbA1c remains stable or even improves for some youths. The aim is to identify distinct patterns of glycemic control in type 1 diabetes from childhood to young adulthood. RESEARCH DESIGN AND METHODS A total of 6,433 patients with type 1 diabetes were selected from the prospective, multicenter diabetes patient registry Diabetes-Patienten-Verlaufsdokumentation (DPV) (follow-up from age 8 to 19 years, baseline diabetes duration ≥2 years, HbA1c aggregated per year of life). We used latent class growth modeling as the trajectory approach to determine distinct subgroups following a similar trajectory for HbA1c over time. RESULTS Five distinct longitudinal trajectories of HbA1c were determined, comprising group 1 = 40%, group 2 = 27%, group 3 = 15%, group 4 = 13%, and group 5 = 5% of patients. Groups 1–3 indicated stable glycemic control at different HbA1c levels. At baseline, similar HbA1c was observed in group 1 and group 4, but HbA1c deteriorated in group 4 from age 8 to 19 years. Similar patterns were present in group 3 and group 5. We observed differences in self-monitoring of blood glucose, insulin therapy, daily insulin dose, physical activity, BMI SD score, body-height SD score, and migration background across all HbA1c trajectories (all P ≤ 0.001). No sex differences were present. Comparing groups with similar initial HbA1c but different patterns, groups with higher HbA1c increase were characterized by lower frequency of self-monitoring of blood glucose and physical activity and reduced height (all P < 0.01). CONCLUSIONS Using a trajectory approach, we determined five distinct longitudinal patterns of glycemic control from childhood to early adulthood. Diabetes self-care, treatment differences, and demographics were related to different HbA1c courses.

Severe hypoglycemia rates are not associated with HbA1c: a cross‐sectional analysis of 3 contemporary pediatric diabetes registry databases

To examine the association between glycated hemoglobin (HbA1c) and severe hypoglycemia rates in patients with type 1 diabetes receiving usual care, by analysing data from the US Type 1 Diabetes Exchange (T1DX), German/Austrian Diabetes Patienten Verlaufsdokumenation (DPV), and Western Australian Children Diabetes Database (WACDD) diabetes registries.

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.

Factors contributing to partial remission in type 1 diabetes: analysis based on the insulin dose‐adjusted HbA1c in 3657 children and adolescents from Germany and Austria

Insulin dose‐adjusted hemoglobin A1c (HbA1C, IDAA1c) correlates well with stimulated C‐peptide levels, but has not yet been evaluated in a large cohort of patients with Type 1 diabetes (T1D).

Type 1 diabetes in older adults: Comparing treatments and chronic complications in the United States T1D Exchange and the German/Austrian DPV registries

AIMS Compare characteristics, therapies and clinical outcomes in older adults with type 1 diabetes in the United States T1D Exchange (T1DX) and German/Austrian Diabetes Patienten Verlaufsdokumentation (DPV) registries. METHODS Cross-sectional study of adults ≥60years old with type 1 diabetes seen in 2011-2012 in the T1DX (n=1283) and DPV (n=2014) registries. Wilcoxon rank-sum test was used for continuous variables and chi-square test for categorical variables. Adjusted analyses used generalized linear models. RESULTS Individuals in both registries were similar in body mass index (mean 27kg/m2), percent with obesity (25%) and gender (48% male). In T1DX there was longer diabetes duration (32.3 vs. 28.8years), greater use of antihypertensive medications (including ACE-I and ARBs; 85% vs. 62%), statins (68% vs. 40%), aspirin (77% vs. 21%), insulin pumps (58% vs. 18%), and less smoking (7% vs. 10%); lower adjusted mean LDL-cholesterol (84 vs. 109mg/dL), and lower adjusted mean systolic and diastolic blood pressures (128 vs. 136 and 68 vs. 74mmHg); fewer myocardial infarctions (6% vs. 9% [99% CI of difference, 1% to 5%]), strokes (2% vs. 8% [3% to 7%]), microvascular complications including microalbuminuria (17% vs. 44% [22% to 32%]) but increased depression (16.1% vs. 8.7%). Adjusted mean HbA1c levels were similar (7.5%, 58mmol/mol). CONCLUSIONS Differences between the registries included greater use of antihypertensives, statins and insulin pumps, and fewer chronic complications in the T1DX. Further research is needed to better understand the role of intensive therapy in improving outcomes in older adults with type 1 diabetes.

Use of Adjuvant Pharmacotherapy in Type 1 Diabetes: International Comparison of 49,996 Individuals in the Prospective Diabetes Follow-up and T1D Exchange Registries

The majority of those with type 1 diabetes (T1D) have suboptimal glycemic control (1–4); therefore, use of adjunctive pharmacotherapy to improve control has been of clinical interest. While noninsulin medications approved for type 2 diabetes have been reported in T1D research and clinical practice (5), little is known about their frequency of use. The T1D Exchange (T1DX) registry in the U.S. and the Prospective Diabetes Follow-up (DPV) registry in Germany and Austria are two large consortia of diabetes centers; thus, they provide a rich data set to address this question. For the analysis, 49,996 pediatric and adult patients with diabetes duration ≥1 year and a registry update from 1 April 2015 to 1 July 2016 were included (19,298 individuals from 73 T1DX sites and 30,698 individuals from 354 DPV sites). Adjuvant medication use (metformin, glucagon-like peptide 1 [GLP-1] receptor agonists, dipeptidyl peptidase 4 [DPP-4] inhibitors, sodium–glucose cotransporter 2 [SGLT2] inhibitors, and other noninsulin diabetes medications including pramlintide) was extracted from …

No adverse effect of outdoor air pollution on HbA1c in children and young adults with type 1 diabetes.

BACKGROUND Evidence is growing that air pollutants deteriorate glucose metabolism and insulin sensitivity by oxidative stress and inflammation. This might affect HbA1c levels and insulin requirements in type 1 diabetes. There are no data available on this association. METHODS Air pollution values of respirable particulate matter (PM10), nitrogen dioxides (NO2), and accumulated ozone (O3-AOT40) were obtained from the federal environmental agency (Umweltbundesamt II) and assigned to place of residence of 840 participants from a nation-wide population-based type 1 diabetes registry (German Diabetes Center, Düsseldorf, Germany). Information on HbA1c, social status, treatment and co-morbidities was collected by self-administered questionnaires. Complete information was available for 771 patients aged 11-21 years at the time of study. RESULTS In linear regression models, no adverse effects of air pollutants (PM10, NO2 or O3-AOT40 on HbA1c level were found, but O3-AOT40 was inversely associated with HbA1c (mmol/mol) in the crude (estimate per IQR: -1.86; 95% CI: (-3.27; -0.44); p=0.01) and the best model adjusting for lifestyle, socioeconomic factors, clinical information, and season (-1.50; (-2.82; -0.17); 0.034). After adding area of residency as random effect to the crude and the best model, the association was no longer significant (-1.64; (-3.84; 0.56); 0.14); (-1.56; (-3.67; 0.55); 0.14). Adjustment for further possible confounders did not affect the estimates seriously. None of the pollutants was associated with insulin dose (IU/kg body weight). CONCLUSIONS Investigated pollutants had no adverse effect on metabolic control in children and young adults with type 1 diabetes in this cross-sectional study. The weak inverse association of accumulated ozone with HbA1c might be due to confounding by regional characteristics or regional aspects of care.

Self‐reported regular alcohol consumption in adolescents and emerging adults with type 1 diabetes: A neglected risk factor for diabetic ketoacidosis? Multicenter analysis of 29 630 patients from the DPV registry

The risk of hypoglycemia increases after alcohol consumption in patients with type 1 diabetes. This study aimed to investigate the association between metabolic control and self‐reported alcohol consumption in young patients with type 1 diabetes.