BMI is an important driver of ß-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children.

OBJECTIVE: Body weight-related insulin resistance probably plays a role in progression to type 1 diabetes, but has an uncertain impact following diagnosis. In this study, we investigated whether BMI measured at diagnosis was an independent predictor of C-peptide decline 1-year post-diagnosis. DESIGN: Multicentre longitudinal study carried out at diagnosis and up to 1-year follow-up. METHODS: Data on C-peptide were collected from seven diabetes centres in Europe. Patients were grouped according to age at diagnosis (<5 years, n=126; >5 years <10 years, n=295; >10 years <18 years, n=421; >18 years, n=410). Linear regression was used to investigate whether BMI was an independent predictor of change in fasting C-peptide over 1 year. Models were additionally adjusted for baseline insulin dose and HbA1c. RESULTS: In individuals diagnosed between 0 and 5 years, 5 and 10 years and those diagnosed >18 years, we found no association between BMI and C-peptide decline. In patients aged 10-18 years, higher BMI at baseline was associated with a greater decline in fasting C-peptide over 1 year with a decrease (ß 95% CI; P value) of 0.025 (0.010, 0.041) nM/kg per m(2) higher baseline BMI (P=0.001). This association remained significant after adjusting for gender and differences in HbA1c and insulin dose (ß=0.026, 95% CI=0.0097, 0.042; P=0.002). CONCLUSIONS: These observations indicate that increased body weight and increased insulin demand are associated with more rapid disease progression after diagnosis of type 1 diabetes in an age group 10-18 years. This should be considered in studies of ß-cell function in type 1 diabetes.

Age-dependent decline of ß-cell function in type 1 diabetes after diagnosis: a multi-centre longitudinal study.

AIMS: C-peptide secretion is currently the only available clinical biomarker to measure residual ß-cell function in type 1 diabetes. However, the natural history of C-peptide decline after diagnosis can vary considerably dependent upon several variables. We investigated the shape of C-peptide decline over time from type 1 diabetes onset in relation to age at diagnosis, haemoglobin A1c (HbA1c) levels and insulin dose. METHODS: We analysed data from 3929 type 1 diabetes patients recruited from seven European centres representing all age groups at disease onset (childhood, adolescence and adulthood). The influence of the age at onset on ß-cell function was investigated in a longitudinal analysis at diagnosis and up to 5-years follow-up. RESULTS: Fasting C-peptide (FCP) data at diagnosis were available in 3668 patients stratified according to age at diagnosis in four groups (<5 years, n = 344; >5 years < 10 years, n = 668; >10 years < 18 years, n = 991; >18 years, n = 1655). FCP levels were positively correlated with age (p < 0.001); the subsequent decline in FCP over time was log-linear with a greater decline rate in younger age groups (p < 0.0001). CONCLUSIONS: This study reveals a positive correlation between age at diagnosis of type 1 diabetes and FCP with a more rapid decline of ß-cell function in the very young patients. These data can inform the design of clinical trials using C-peptide values as an end-point for the effect of a given treatment.

Update on transcobalamin deficiency: clinical presentation, treatment and outcome.

Transcobalamin (TC) transports cobalamin from blood into cells. TC deficiency is a rare autosomal recessive disorder usually presenting in early infancy with failure to thrive, weakness, diarrhoea, pallor, anemia, and pancytopenia or agammaglobulinemia. It can sometimes resemble neonatal leukemia or severe combined immunodeficiency disease. Diagnosis of TC deficiency is suspected based on megaloblastic anemia, elevation of total plasma homocysteine, and blood or urine methylmalonic acid. It is confirmed by studying the synthesis of TC in cultured fibroblasts, or by molecular analysis of the TCN2 gene. TC deficiency is treatable with supplemental cobalamin, but the optimal type, route and frequency of cobalamin administration and long term patient outcomes are unknown. Here we present a series of 30 patients with TC deficiency, including an update on multiple previously published patients, in order to evaluate the different treatment strategies and provide information about long term outcome. Based on the data presented, current practice appears to favour treatment of individuals with TC deficiency by intramuscular injections of hydroxy- or cyanocobalamin. In most cases presented, at least weekly injections (1 mg IM) were necessary to ensure optimal treatment. Most centres adjusted the treatment regimen based on monitoring CBC, total plasma homocysteine, plasma and urine methylmalonic acid, as well as, clinical status. Finally, continuing IM treatment into adulthood appears to be beneficial.

Declining incidence of severe retinopathy and persisting decrease of nephropathy in an unselected population of Type 1 diabetes-the Linköping Diabetes Complications Study.

AIMS/HYPOTHESIS: In a previous study conducted over the last decades we found a decreased incidence of nephropathy but unchanged incidence of severe retinopathy among patients with Type 1 diabetes diagnosed in childhood and with 20 years duration of diabetes. The aim of our current study was to investigate the incidence 5 to 10 years later in the same population. METHODS: We studied all 269 patients in whom Type 1 diabetes was diagnosed in childhood between 1961 and 1985 in a district in southeastern Sweden. Ninety-one percent were monitored for retinopathy until at least 1997 and 95% were monitored for nephropathy. Severe retinopathy was defined as laser-treated retinopathy and nephropathy as persistent proteinuria. Survival analysis was used and the patients divided into five cohorts according to the time of onset of diabetes. RESULTS: The cumulative proportion of severe retinopathy had declined ( p=0.006). After 25 years it was 47% (95% CI 34-61), 28% (15-40) and 24% (12-36) in the cohorts 1961 to 1965, 1966 to 1970 and 1971 to 1975 respectively. After 30 years it was 53% (40-66) and 44% (28-59) in the oldest cohorts. The cumulative proportion of nephropathy after 25 years duration was 30% (18-42), 8% (1-16) and 13% (4-23) in the cohorts 1961 to 1965, 1966 to 1970 and 1971 to 1975 respectively. After 30 years, it was 32% (20-44) and 11% (2-20) for the oldest cohorts ( p<0.0001). CONCLUSIONS/INTERPRETATION: In an unselected population with Type 1 diabetes diagnosed in childhood, modern diabetes care markedly reduced the incidence of severe retinopathy and nephropathy.

One thousand small-bowel biopsies in children. A single-port versus a double-port capsule.

BACKGROUND: Small-bowel biopsy is a well-established technique in the evaluation of children with intestinal malabsorption, e.g. coeliac disease. The biopsy is performed endoscopically or with a peroral capsule instrument. The aim of the present retrospective study was to compare the single-port Watson capsule with the double-port Storz capsule with regard to procedure and fluoroscopy time, complications and failure rate. METHODS: All 1,078 peroral small-bowel biopsies performed at our department during 1989-99 were studied. In 387 of these, the Watson capsule was used and in the remaining 691 the Storz capsule. Median age of the children was 2.5 years. About one-third of the children were premedicated with the prokinetic drug cisapride and as sedatives alimemazine or diazepam orally. Two-thirds of the children were given metoclopramide along with midazolam intravenously. The biopsies were performed under intermittent fluoroscopy. RESULTS: The median biopsy procedure time was significantly shorter with the Storz capsule (7 min) compared to the Watson capsule (10 min) (P < 0.05). The median fluoroscopy time was 5 sec with the Storz capsule and 8 sec with the Watson capsule (P < 0.01). The failure rate did not differ significantly between the two capsule types: 10.3% (Watson) and 7.7% (Storz). One potential but no serious complication occurred. CONCLUSIONS: Providing that effective sedation is available, small-bowel biopsy with a peroral capsule, and the Storz double-port multibiopsy capsule in particular, is a safe and fast method exposing the child to a minimal radiation dose.

Small bowel capsule biopsy in children: parents' opinions on children's discomfort.

UNLABELLED: This questionnaire study asked the parents of 62 children undergoing small bowel capsule biopsy for their reactions to the discomfort experienced by their children. The children were randomized to receive sedation with midazolam either intravenously or intranasally. With regard to the biopsy procedure the parents of 94% of the children had no objections. The parents of 3% of the children found the biopsy very unpleasant and another 3% suggested that the biopsy should be performed under general anaesthesia. The proportion of parents with negative reactions to the biopsy procedure did not differ significantly between the intravenously and intranasally sedated children. With regard to the sedation given, the parents of 79% of the children did not think that their children were in any discomfort at all. Ten percent of the children had obvious signs of nasal discomfort using the intranasal administration. In the remaining 11% of the children the parents reported various symptoms. CONCLUSION: The vast majority of parents of children undergoing small bowel capsule biopsy found the procedure satisfactory providing that the sedative medication was given intravenously rather than intranasally.