Prevalence and predictors of severe hypoglycemia in Danish children and adolescents with diabetes.

OBJECTIVE: To investigate the prevalence of severe hypoglycemia in Danish children and adolescents with type 1 diabetes and to pinpoint predictors of this acute complication in children on modern treatment modalities. RESEARCH DESIGN AND METHODS: The study is based on data from DanDiabKids, a national diabetes register for children and adolescents. The register contains data on patients with type 1 diabetes with an ascertainment rate of 99%. Data from 3320 patients aged 0-18 yr was included in the study period from 1998 to 2009 and analyzed using a negative binomial model. RESULTS: One thousand nine hundred and ninety-nine episodes of severe hypoglycemia in 867 patients were registered conferring an overall incidence of severe hypoglycemia of 15.1 [95% confident interval (CI): 13.8; 16.4] per 100 patient years. This remained unchanged during the study period. Duration of diabetes, age and treatment in centers managing less than 100 patients significantly increased the risk of severe hypoglycemia (p < 0.001). Patients on insulin pump therapy had a 42% reduced risk of severe hypoglycemia compared with pen treated patients (p = 0.01). Patients treated with five or more daily insulin injections had a 31% (95% CI: 17; 49) reduced risk of severe hypoglycemia compared to patients on fewer daily injections (p = 0.015). CONCLUSIONS: Despite improvements in metabolic control over a decade the prevalence of severe hypoglycemic events remained unchanged. More intensive treatments such as insulin pump therapy and multiple daily injections on a national level seems to be a protective factor for developing severe hypoglycemia up to 2009.

Diabetic ketoacidosis at the onset of type 1 diabetes is associated with future HbA1c levels.

AIMS/HYPOTHESIS: We investigated the long-term impact of diabetic ketoacidosis (DKA) at onset on metabolic regulation and residual beta cell function in a Danish population with type 1 diabetes. METHODS: The study is based on data from DanDiabKids, a Danish national diabetes register for children. The register provides clinical and biochemical data on patients with type 1 diabetes diagnosed in 1996-2009 and then followed-up until 1 January 2012. Repeated-measurement models were used as statistical methods. RESULTS: The study population comprised 2,964 children <18 years. The prevalence of DKA at diagnosis was 17.9%. Of the total subjects, 8.3% had mild, 7.9% had moderate and 1.7% had severe DKA. DKA (moderate and severe) was associated with increased HbA1c (%) levels (0.24; 95% CI 0.11, 0.36; p = 0.0003) and increased insulin dose-adjusted HbA1c (IDAA1c, 0.51; 95% CI 0.31, 0.70; p < 0.0001) during follow-up, after adjustment for covariates. Children without a family history of diabetes were more likely to present with DKA (19.2% vs 8.8%, p < 0.0001); however, these children had a lower HbA1c (%) level over time (-0.35; 95% CI -0.46, -0.24; p < 0.0001). Continuous subcutaneous insulin infusion (CSII) was associated with a long-term reduction in HbA1c, changing the effect of DKA, after adjustment for covariates (p < 0.0001). CONCLUSIONS/INTERPRETATION: DKA at diagnosis was associated with poor long-term metabolic regulation and residual beta cell function as assessed by HbA1c and IDAA1c, respectively; however, CSII treatment was associated with improvement in glycaemic regulation and residual beta cell function, changing the effect of DKA at onset in our population.

Self-peptides with intermediate capacity to bind and stabilize MHC class I molecules may be immunogenic.

Thirty self-peptides were selected on the basis of their predicted binding to H-2b molecules. The binding of peptides was ascertained experimentally by biochemical (KD measurements) and cellular [major histocompatibility complex class I (MHC-I) stabilization] assays. A weak, but significant, correlation between KD measurements and MHC-I stabilization was observed. Mice (n = 99) were immunized with individual peptides. Twenty-eight peptides were found to induce peptide-specific cytotoxic activity, and a total of 84 mice developed significant cytotoxic T lymphocyte (CTL) responses after immunization. Only one of the 21 mice immunized with high-affinity peptides developed a peptide-specific CTL response of 29 lytic units per 106 splenocytes, whereas 11 of the 42 mice immunized with intermediate-affinity peptides developed peptide-specific CTL responses at this level (P < 0.05). These observations suggest the absence of tolerance towards most MHC-I-restricted self-peptides and that strong antiself immunity can be generated preferentially towards self-peptides with an intermediate affinity for MHC-I. These data should be considered in the design of tumour vaccines based on MHC-I-binding self-peptides.