Siri Fredheim

Remission without insulin therapy on gluten-free diet in a 6-year old boy with type 1 diabetes mellitus.

A 5-year and 10-month old boy was diagnosed with classical type 1 diabetes mellitus (T1DM) without celiac disease. He started on a gluten-free diet after 2–3 week without need of insulin treatment. At the initiation of gluten-free diet, HbA1c was 7.8% and was stabilised at 5.8%–6.0% without insulin therapy. Fasting blood glucose was maintained at 4.0–5.0 mmol/l. At 16 months after diagnosis the fasting blood glucose was 4.1 mmol/l and after 20 months he is still without daily insulin therapy. There was no alteration in glutamic acid decarboxylase positivity. The gluten-free diet was safe and without side effects. The authors propose that the gluten-free diet has prolonged remission in this patient with T1DM and that further trials are indicated.

Insulin pump treatment; increasing prevalence, and predictors for better metabolic outcome in Danish children and adolescents with type 1 diabetes.

Few studies have looked at nationwide data for insulin pump treatment. Since 1996 the Danish Childhood Diabetes Registry (DanDiabKids) has collected data on all Danish diabetic patients aged 0–15 yr. The purpose of this study is to evaluate the prevalence of continuous subcutaneous insulin infusion (CSII) use among Danish children with diabetes and to compare metabolic control in CSII‐treated children and adolescents to those treated with MDI.

The PTPN22 C1858T gene variant is associated with proinsulin in new-onset type 1 diabetes.

BackgroundThe protein tyrosine phosphatase nonreceptor type 2 (PTPN22) has been established as a type 1 diabetes susceptibility gene. A recent study found the C1858T variant of this gene to be associated with lower residual fasting C-peptide levels and poorer glycemic control in patients with type 1 diabetes. We investigated the association of the C1858T variant with residual beta-cell function (as assessed by stimulated C-peptide, proinsulin and insulin dose-adjusted HbA1c), glycemic control, daily insulin requirements, diabetic ketoacidosis (DKA) and diabetes-related autoantibodies (IA-2A, GADA, ICA, ZnT8Ab) in children during the first year after diagnosis of type 1 diabetes.MethodsThe C1858T variant was genotyped in an international cohort of children (n = 257 patients) with newly diagnosed type 1 diabetes during 12 months after onset. We investigated the association of this variant with liquid-meal stimulated beta-cell function (proinsulin and C-peptide) and antibody status 1, 6 and 12 months after onset. In addition HbA1c and daily insulin requirements were determined 1, 3, 6, 9 and 12 months after diagnosis. DKA was defined at disease onset.ResultsA repeated measurement model of all time points showed the stimulated proinsulin level is significantly higher (22%, p = 0.03) for the T allele carriers the first year after onset. We also found a significant positive association between proinsulin and IA levels (est.: 1.12, p = 0.002), which did not influence the association between PTPN22 and proinsulin (est.: 1.28, p = 0.03).ConclusionsThe T allele of the C1858T variant is positively associated with proinsulin levels during the first 12 months in newly diagnosed type 1 diabetes children.

Partial Remission Definition: Validation based on the insulin dose-adjusted HbA1c (IDAA1C) in 129 Danish Children with New-Onset Type 1 Diabetes †

To validate the partial remission (PR) definition based on insulin dose‐adjusted HbA1c (IDAA1c).

Proinsulin, GLP-1, and glucagon are associated with partial remission in children and adolescents with newly diagnosed type 1 diabetes

Kaas A, Max Andersen ML, Fredheim S, Hougaard P, Buschard K, Petersen JS, de Beaufort C, Robertson KJ, Hansen L, Mortensen HB, Nielsen LB, On behalf of The Hvidoere Study Group on childhood diabetes. Proinsulin, GLP‐1, and glucagon are associated with partial remission in children and adolescents with newly diagnosed type 1 diabetes.

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

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.

Equal access to health care may diminish the differences in outcome between native and immigrant patients with type 1 diabetes.

Previous studies have found that ethnicity influences glycemic control. We hypothesized that differences between Nordic and non‐Nordic patients are less pronounced for children with type 1 diabetes in high incidence countries in Northern Europe.

Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-Sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes

OBJECTIVE International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA1c levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA1c across and within eight high-income countries to best inform international benchmarking and policy recommendations. RESEARCH DESIGN AND METHODS Data were collected between 2013 and 2014 from 64,666 children with T1D who were <18 years of age across 528 centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway. We used fixed- and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA1c levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and children’s glycemic control. RESULTS Sweden had the lowest mean HbA1c (59 mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC ≤4%). Germany and Austria had the next lowest mean HbA1c (61–62 mmol/mol [7.7–7.8%]) but showed the largest center variations (ICC ∼15%). Centers in England, Wales, and the U.S. showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value <0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA1c levels (5.6 mmol/mol [0.5%] per 5 mmol/mol [0.5%] increase in center SD of HbA1c values of all children attending a specific center). CONCLUSIONS At similar average levels of HbA1c, countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.

Intrafamilial Variability of Early-Onset Diabetes due to an INS Mutation

Aim. The objective of this study was to describe the clinical characteristics of two siblings and their father carrying a C95Y mutation in the insulin (INS) gene. Methods/Results. A Danish patient, his sister, and his father were identified to carry the C95Y mutation in the preproinsulin molecule causing permanent neonatal diabetes. All three were diagnosed before 29 weeks of age, were born at term with near-normal birth weight, and were negative for GAD, ICA, IA-2, and IAA autoantibodies. The daily insulin requirement the first six months after diagnosis was <0.5  U kg−1 day−1 for both children. The father, insulin treated for over 40 years, has bilateral preproliferative retinopathy. Conclusions. These three cases further confirm the essential features of diabetes caused by INS mutations with proteotoxic effect. We conclude that patients with similar features must be investigated for mutations of INS gene.