Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients.

In first-degree relatives of type 1 diabetic patients, we investigated whether diabetes risk assessment solely based on insulinoma antigen 2 (IA-2) and zinc transporter 8 (ZnT8) antibody status (IA-2A, respectively, ZnT8A) is as effective as screening for three or four autoantibodies [antibodies against insulin (IAA), glutamate decarboxylase 65 kDa (GAD) glutamate decarboxylase autoantibodies (GADA) and IA-2A with or without ZnT8A] in identifying children, adolescents and adults who progress rapidly to diabetes (within 5 years). Antibodies were determined by radiobinding assays during follow-up of 6444 siblings and offspring aged 0-39 years at inclusion and recruited consecutively by the Belgian Diabetes Registry. We identified 394 persistently IAA(+) , GADA(+) , IA-2A(+) and/or ZnT8A(+) relatives (6·1%). After a median follow-up time of 52 months, 132 relatives developed type 1 diabetes. In each age category tested (0-9, 10-19 and 20-39 years) progression to diabetes was significantly quicker in the presence of IA-2A and/or ZnT8A than in their joint absence (P < 0·001). Progression rate was age-independent in IA-2A(+) and/or ZnT8A(+) relatives but decreased with age if only GADA and/or IAA were present (P = 0·008). In the age group mainly considered for immune interventions until now (10-39 years), screening for IA-2A and ZnT8A alone identified 78% of the rapid progressors (versus 75% if positive for ≥ 2 antibodies among IAA, GADA, IA-2A and ZnT8A or versus 62% without testing for ZnT8A). Screening for IA-2A and ZnT8A alone allows identification of the majority of rapidly progressing prediabetic siblings and offspring regardless of age and is more cost-effective to select participants for intervention trials than conventional screening.

Care delivery and outcomes among Belgian children and adolescents with type 1 diabetes.

UNLABELLED: We aimed to investigate care processes and outcomes among children and adolescents with type 1 diabetes treated in hospital-based multidisciplinary paediatric diabetes centres. Our retrospective cross-sectional study among 12 Belgian centres included data from 974 patients with type 1 diabetes, aged 0-18 years. Questionnaires were used to collect data on demographic and clinical characteristics, as well as process of care completion and outcomes of care in 2008. Most patients lived with both biological or adoption parents (77 %) and had at least one parent of Belgian origin (78 %). Nearly all patients (≥95 %) underwent determination of HbA(1c) and BMI. Screening for retinopathy (55 %) and microalbuminuria (73 %) was less frequent, but rates increased with age and diabetes duration. Median HbA(1c) was 61 mmol/mol (7.7 %) [interquartile range 54-68 mmol/mol (7.1-8.4 %)] and increased with age and insulin dose. HbA(1c) was higher among patients on insulin pump therapy. Median HbA(1c) significantly differed between centres [from 56 mmol/mol (7.3 %) to 66 mmol/mol (8.2 %)]. Incidence of severe hypoglycaemia was 30 per 100 patient-years. Admissions for ketoacidosis had a rate of 3.2 per 100 patient-years. Patients not living with both biological or adoption parents had higher HbA(1c) and more admissions for ketoacidosis. Parents' country of origin was not associated with processes and outcomes of care. CONCLUSION: Outcomes of care ranked well compared to other European countries, while complication screening rates were intermediate. The observed centre variation in HbA(1c) remained unexplained. Outcomes were associated with family structure, highlighting the continuing need for strategies to cope with this emerging challenge.

[Weight of obesity in (pre)type 2 diabetes in children and adolescents: how and when to screen for?]. / Le poids de l'obésité dans le (pré)diabète de type 2 chez les enfants et adolescents : quand et comment le rechercher ?

There has been wide recognition in the past decade of the increasing frequency of type 2 diabetes in youth, largely but not exclusively in North America. In some American locations and populations, incidence and prevalence of type 2 diabetes are much higher than those of type 1 diabetes, because of increased calorie and fat intake, and decreased exercise. The increasing prevalence of type 2 diabetes in the United States has closely paralleled the increase in childhood obesity noted there, but now across the Western world. Besides obesity, the other youth risk factors for type 2 diabetes are: ethnicity, puberty, family history, metabolic syndrome, polycystic ovary syndrome, acanthosis nigricans. Any feature or condition associated with insulin resistance/hyperinsulinemia should alert to screen youth at increased risk for (pre)type 2 diabetes. Treatment goals are to decrease weight and increase exercise, to normalize insulinemia, glycemia and HbA1c, to control hypertension and hyperlipidemia. The aim of the pharmacological therapy is to decrease insulin resistance, namely by metformin. Sometimes, insulin therapy is necessary.

Complete remission following donor leukocyte infusion in ALL relapsing after haploidentical bone marrow transplantation.

A 7-month-old boy with a high risk ALL harbouring the translocation (4;11) was grafted with an haploidentical bone marrow from paternal origin. At time of relapse, 11 months after BMT, he received donor leukocyte infusions (DLI) which put him in second CR. GVHD and pancytopenia occurred 2 weeks after DLI and were fully reversed with CsA + prednisolone. Six months later, the child continues to be in second CR, off steroid therapy, without any signs of GVHD. Our limited experience indicates that a second CR can be obtained with acceptable toxicity by DLI in very high risk ALL children who have been previously grafted with haploidentical bone marrow cells.

Congenital absence of insulin cells in a neonate with diabetes mellitus and mutase-deficient methylmalonic acidaemia.

We report on a female neonate with diabetes mellitus and methylmalonic acidaemia, who died at age 16 days. Using immunocytochemistry, electron microscopy and in situ hybridisation, we were unable to demonstrate any insulin cells in the pancreatic islets. Methylmalonic acidaemia was caused by a methylmalonyl coenzyme A mutase apoenzyme defect. The metabolic crisis of the methylmalonic acidaemia aggravated the diabetes and may explain the failure of insulin therapy. Our results suggest that the infant suffered from a congenital absence of beta cells associated with a genetically transmitted mutase apoenzyme defect.