Previous diabetic ketoacidosis as a risk factor for recurrence in a large prospective contemporary pediatric cohort: Results from the DPV initiative.

OBJECTIVE: To assess the role of previous episodes of diabetic ketoacidosis (DKA) and their time-lag as risk factors for recurring DKA in youth with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: In a population-based analysis, data from 29,325 children and adolescents with T1D and at least 5 years of continuous follow-up were retrieved from the "Diabetes Prospective Follow-up" (DPV) multi-center registry in March 2020. Statistical analyses included unadjusted comparisons, logistic and negative binomial regression models. RESULTS: Among 29,325 patients with T1D, 86.0% (n = 25,219) reported no DKA, 9.7% (n = 2,833) one, and 4.3% (n = 1,273) more than one episode, corresponding to a DKA rate of 4.4 [95% CI: 4.3-4.6] per 100 patient-years. Female sex, migratory background, higher HbA1c values, higher daily insulin doses, a lower glucose monitoring frequency, and less CGM usage were associated with DKA. In patients with a previous episode, the DKA rate in the most recent year was significantly higher than in patients with no DKA (17.6 [15.9-19.5] vs. 2.8 [2.7-3.1] per 100 patient-years; p < 0.001). Multiple DKAs further increased the recurrence rate. The risk for DKA in the most recent year was higher in patients with an episode in the preceding year than in patients with no previous DKA (OR: 10.0 [95% CI: 8.6-11.8]), and remained significantly elevated 4 years after an episode (OR: 2.3 [1.6-3.1]; p < 0.001). CONCLUSIONS: Each episode of DKA is an independent risk factor for recurrence, even 4 years after an event, underlining the importance of a close follow-up after each episode.

Predictors of diabetic ketoacidosis in children and adolescents with type 1 diabetes. Experience from a large multicentre database.

OBJECTIVE: Diabetic ketoacidosis (DKA) remains a major cause of hospitalization and death in children and adolescents with established type 1 diabetes despite DKA preventing strategies. The aim of the study was to determine incidence and risk factors for DKA in a large cohort of young diabetic patients. METHODS: This investigation uses the dpv-wiss base containing data on 28 770 patients with type 1 diabetes <20yr, from Germany and Austria. For each patient the most recent year of follow-up was evaluated. DKA was defined as pH < 7.3 and/or hospital admission as a result of DKA, excluding onset DKA. RESULTS: Mean age of the study cohort was 13.96 ± 4.0 yr (47.9% females). A total of 94.1% presented with no episode, 4.9% with 1 episode, and 1.0% with recurrent DKA (≥2). When comparing these three groups, age (p < 0.01), HbA1c (p < 0.01), and insulin dose (p < 0.01) were significantly higher in patients with recurre nt DKA. Incidence of DKA was significantly higher in females (7.3 ± 0.5 vs. 5.8 ± 0.2; p = 0.03) and in patients with migration background (7.8 ± 0.6 vs. 6.3 ± 0.3; p = 0.02). No significant association was found with treatment type and diabetes duration. CONCLUSION: In a cohort of European paediatric diabetic patients, the rate of DKA was significantly higher in females and in children with migration background and early teenage years.

Diabetic ketoacidosis in pediatric patients with type 1- and type 2 diabetes during the COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic caused families to stay home and cancel everyday activities. Hospital admissions decreased, affecting changes in diagnoses and management of chronic disease in children. AIMS: We analyzed how the first lockdown influenced clinical presentation and manifestation of children with diabetes mellitus (DM) in a German University Hospital. METHODS: During March 15th and October 11th 2020, data on general patient information, clinical symptoms and on lab results related to diabetic ketoacidosis (DKA) were analyzed in children (0-18 years) who presented with new onset of DM or poor metabolic control of known DM. All data including frequency and severity of DKA were compared to data from patients who presented in 2019. RESULTS: Data from 125 participants with DM were evaluated (2020: n = 52; 2019: n = 73). In 2020, twelve patients (23.1%) were diagnosed with new onset DM, two of them with type2 diabetes, and 66.7% presented with DKA including both patients T2DM. In 2019, 24.5% of patients had new onset DM, and 50% of them presented with DKA. In 2020, patients with new onset DM were younger, presented with more severe symptoms of DKA and had to stay longer in hospital compared to 2019. In 2020, six children (50%) with new onset DM were <6 years, whereas in 2019 most children with new onset DM were adolescents (n = 7, 38.9%). CONCLUSION: COVID-19 lockdown aggravated complications of diabetes onset and therapy management, including severity and frequency of DKA. It underlines the need of health education for early DKA diagnosis to early identify children at risk.

A Comparison of Familial and Sporadic Type 1 Diabetes Among Young Patients.

OBJECTIVE: To investigate natural course, treatment, and outcomes in familial versus sporadic type 1 diabetes. RESEARCH DESIGN AND METHODS: In a population-based study, we compared patients with onset of type 1 diabetes before the age of 20 years who had a first-degree relative with type 1 diabetes (familial diabetes) with patients with type 1 diabetes who had no first-degree relative with type 1 diabetes (sporadic diabetes) at diagnosis and over the first 10 treatment years, using multivariable regression and proportional hazards models. Patients were identified from the Diabetes Prospective Follow-up Registry (DPV) between 1995 and 2018. RESULTS: Of 57,371 patients with type 1 diabetes, 53,606 (93.4%) had sporadic diabetes and 3,765 (6.6%) had familial diabetes. Familial diabetes, compared with sporadic diabetes, was associated with younger age (median 7.9 vs. 9.7 years, P < 0.001), lower prevalence of ketoacidosis (11.9% vs. 20.4%, P < 0.001), and lower HbA1c levels (9.7% vs. 11.1%, P < 0.001) at onset and higher prevalence of associated autoimmune disease (16.7% vs. 13.6%, P < 0.001). Over 10 years, patients with familial diabetes, in comparison with sporadic diabetes, more often used insulin pumps (P < 0.001) and had a lower rate of severe hypoglycemia (12.97 vs. 14.44 per 100 patient-years, P < 0.001) but similar HbA1c levels (P ≥ 0.08) and ketoacidosis rates (1.85 vs. 2.06 per 100 patient-years, P = 0.11). In familial and sporadic diabetes, absence of ketoacidosis at onset predicted fewer events of severe hypoglycemia (hazard ratio [HR] 0.67, P < 0.001, and 0.91, P < 0.001, respectively) and of ketoacidosis (HR 0.64, P = 0.007, and 0.66, P < 0.001, respectively) after 10 years. CONCLUSIONS: Familial type 1 diabetes, compared with sporadic type 1 diabetes, is characterized by earlier disease manifestation and higher autoimmune comorbidity as well as less metabolic decompensation at onset, likely related to higher disease awareness in affected families, while the course of disease is similar. These findings may have implications for the generalizability of results of diabetes prevention trials from patients with familial type 1 diabetes to patients with sporadic type 1 diabetes.

Area Deprivation and Regional Disparities in Treatment and Outcome Quality of 29,284 Pediatric Patients With Type 1 Diabetes in Germany: A Cross-sectional Multicenter DPV Analysis.

OBJECTIVE: This study analyzed whether area deprivation is associated with disparities in health care of pediatric type 1 diabetes in Germany. RESEARCH DESIGN AND METHODS: We selected patients <20 years of age with type 1 diabetes and German residence documented in the "diabetes patient follow-up" (Diabetes-Patienten-Verlaufsdokumentation [DPV]) registry for 2015/2016. Area deprivation was assessed by quintiles of the German Index of Multiple Deprivation (GIMD 2010) at the district level and was assigned to patients. To investigate associations between GIMD 2010 and indicators of diabetes care, we used multivariable regression models (linear, logistic, and Poisson) adjusting for sex, age, migration background, diabetes duration, and German federal state. RESULTS: We analyzed data from 29,284 patients. From the least to the most deprived quintile, use of continuous glucose monitoring systems (CGMS) decreased from 6.3 to 3.4% and use of long-acting insulin analogs from 80.8 to 64.3%, whereas use of rapid-acting insulin analogs increased from 74.7 to 79.0%; average HbA1c increased from 7.84 to 8.07% (62 to 65 mmol/mol), and the prevalence of overweight from 11.8 to 15.5%, but the rate of severe hypoglycemia decreased from 12.1 to 6.9 events/100 patient-years. Associations with other parameters showed a more complex pattern (use of continuous subcutaneous insulin infusion [CSII]) or were not significant. CONCLUSIONS: Area deprivation was associated not only with key outcomes in pediatric type 1 diabetes but also with treatment modalities. Our results show, in particular, that the access to CGMS and CSII could be improved in the most deprived regions in Germany.

Direct diabetes-related costs in young patients with early-onset, long-lasting type 1 diabetes.

OBJECTIVE: To estimate diabetes-related direct health care costs in pediatric patients with early-onset type 1 diabetes of long duration in Germany. RESEARCH DESIGN AND METHODS: Data of a population-based cohort of 1,473 subjects with type 1 diabetes onset at 0-4 years of age within the years 1993-1999 were included (mean age 13.9 (SD 2.2) years, mean diabetes duration 10.9 (SD 1.9) years, as of 31.12.2007). Diabetes-related health care services utilized in 2007 were derived from a nationwide prospective documentation system (DPV). Health care utilization was valued in monetary terms based on inpatient and outpatient medical fees and retail prices (perspective of statutory health insurance). Multiple regression models were applied to assess associations between direct diabetes-related health care costs per patient-year and demographic and clinical predictors. RESULTS: Mean direct diabetes-related health care costs per patient-year were €3,745 (inter-quartile range: 1,943-4,881). Costs for glucose self-monitoring were the main cost category (28.5%), followed by costs for continuous subcutaneous insulin infusion (25.0%), diabetes-related hospitalizations (22.1%) and insulin (18.4%). Female gender, pubertal age and poor glycemic control were associated with higher and migration background with lower total costs. CONCLUSIONS: Main cost categories in patients with on average 11 years of diabetes duration were costs for glucose self-monitoring, insulin pump therapy, hospitalization and insulin. Optimization of glycemic control in particular in pubertal age through intensified care with improved diabetes education and tailored insulin regimen, can contribute to the reduction of direct diabetes-related costs in this patient group.