OBJECTIVE -Previous reports have predicted greater risk of type 1 diabetes among people who were heavier as young children. The Accelerator Hypothesis predicts earlier onset in heavier people, without necessarily a change in risk, and views type 1 and type 2 diabetes as the same disorder of insulin resistance, set against different genetic backgrounds. Insulin resistance is a function of fat mass, and increasing body weight in the industrialized world has been accompanied by earlier presentation (i.e., acceleration) of type 2 diabetes. We wanted to establish whether increasing body weight was also asociated with the earlier presentation of type 1 diabetes, as the Accelerator Hypothesis would predict.RESEARCH DESIGN AND METHODS -The relationships between fatness and age at diagnosis were examined in context of birth weight, weight change since birth, weight at diagnosis, BMI at diagnosis, and BMI 12 months later in 94 children aged 1-16 years (49 boys and 45 girls) presenting for management of acute-onset type 1 diabetes.RESULTS -BMI standard deviation score (SDS) at diagnosis, weight SDS change since birth, and BMI SDS 12 months later were all inversely related to age at presentation (r ϭ Ϫ0.39 to Ϫ0.40, P Ͻ 0.001). The boys were significantly fatter than the girls (BMI SDS 0.56 vs. Ϫ0.08, respectively; P ϭ 0.006) and presented with diabetes at a significantly younger age (6.74 vs. 8.32 years, respectively; P Ͻ 0.05). The sex difference in age at diagnosis, however, disappeared when corrected for BMI (P ϭ 0.31), suggesting that fatness or something related to it was the responsible factor.CONCLUSIONS -The data are consistent with the hypothesis that the age at presentation of type 1 diabetes is associated with fatness. The implications for prevention of type 1 diabetes may be important. Diabetes Care 26:2865-2870, 2003T he prevalence of diabetes is increasing rapidly in industrialized countries. Although most attention has focused on the increase in type 2 diabetes, there has been a parallel increase in type 1 diabetes, which requires explanation (1). Type 2 diabetes is believed to result from the loss of ␤-cell function in association with insulin resistance (2). The Accelerator Hypothesis regards type 1 diabetes in the same way (3).Awareness of overlap between type 1 and type 2 diabetes is not new. There has long been interest in insulin resistance in type 1 diabetes, although related more to its implications for management and outcome than to its pathogenesis (4 -8). The term "type one-and-a-half" diabetes, referring to the progression in some from type 2 to type 1 diabetes, was coined years ago and remains an area of lively debate (9). In a modern context, the increasing difficulty in distinguishing type 1 from type 2 diabetes in obese young people has given rise to the designation "double diabetes," in which recognition is given to the coexistence of autoimmunity and insulin resistance (10).The insulin resistance that underlies type 2 diabetes seems to result mainly from lifestyle factors: weight increase a...

There are clear gender and ethnic differences in percentage body fat in British schoolchildren which may relate to known differences in the risk of type 2 diabetes in adolescence and adulthood. BMI criteria for defining overweight and obesity do not accurately identify ethnic differences in body fat.

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Metformin therapy has a beneficial treatment effect over placebo for BMI-SDS, fasting glucose, ALT, and ALR ratio at 3 months, with changes in BMI-SDS sustained at 6 months.

Transient neonatal diabetes mellitus (TNDM) is a rare form of childhood diabetes which usually resolves in the first 6 months of life but which predisposes to type 2 diabetes of adult onset. We recently reported paternal uniparental isodisomy of chromosome 6 (UPD6) in two children with TNDM and proposed that there may be an imprinted gene important in the aetiology of diabetes on chromosome 6. We now describe two unrelated families which independently suggest that the gene is imprinted, is paternally expressed and maps to 6q22-q23. One family has a duplication while the other, with familial TNDM, shows linkage to a marker in this region.

Background: Maternal subclinical hypothyroidism is a cause of poor neurodevelopment outcome in the offspring. Although iodine deficiency is the most common cause of hypothyroidism world wide, there are no screening programmes for it in the United Kingdom where the population is assumed to be iodine replete. Objective: To determine the prevalence of reduced iodine intake by measuring urinary iodide concentrations in pregnant and non-pregnant women from the north east of England. Methods: Urinary iodide excretion (UIE) rate was estimated using inductively coupled mass spectrometry in 227 women at 15 weeks gestation and in 227 non-pregnant age matched controls. A reduced intake of iodine is indicated by a concentration in urine of less than 50 mg/l or less than 0.05 mg iodine/mmol creatinine. Results: Eight (3.5%) pregnant women and 13 (5.7%) controls had a reduced iodine/creatinine ratio. These values were higher when UIE was expressed as iodine concentration: 16 (7%) and 20 (8.8%) respectively. Ninety (40%) of the pregnant women had a UIE of 0.05-0.10, which is consistent with borderline deficiency. Conclusion: In this study, 3.5% of pregnant women had evidence of iodine deficiency, and 40% may be borderline deficient. Larger scale studies are required to estimate the true prevalence of iodine deficiency in the United Kingdom.

Symptomatic adrenal insuYciency, presenting as hypoglycaemia or poor weight gain, may occur on withdrawal of corticosteroid treatment but has not previously been reported during inhaled corticosteroid treatment. This case series illustrates the occurence of clinically significant adrenal insuYciency in asthmatic children while patients were on inhaled corticosteroid treatment and the unexpected modes of presentation. General practitioners and paediatricians need to be aware that this unusual but acute serious complication may occur in patients treated with inhaled corticosteroids. (Arch Dis Child 2001;85:330-334)

OBJECTIVE Serum IGF‐I levels are monitored during GH replacement treatment in adults with GH deficiency (GHD) to guide GH dose adjustment and to minimize occurrence of GH‐related side‐effects. This is not routine practice in children treated with GH. The aim of this study was to evaluate changes in (1) serum IGF‐I, IGFBP‐3 and IGF‐I/IGFBP‐3 molar ratio, and (2) serum leptin, an indirect marker of GH response, during the first year of GH treatment in children with disordered growth. DESIGN An observational prospective longitudinal study with serial measurements at five time points during the first year of GH treatment was carried out. Each patient served as his/her own control. PATIENTS The study included 31 patients, grouped as (1) GHD (n = 20) and (2) non‐GHD (Turner syndrome n = 7; Noonan syndrome n = 4), who had not previously received GH treatment. MEASUREMENTS Serum IGF‐I, IGFBP‐3 and leptin levels were measured before treatment and after 6 weeks, 3 months, 6 months and 12 months of GH treatment, with a mean dose of 0.5 IU/kg/wk in GHD and 0.7 IU/kg/wk in non‐GHD groups. IGF‐I, IGFBP‐3 and the calculated IGF‐I/IGFBP‐3 molar ratio were expressed as SD scores using reference values from the local population. RESULTS In the GHD group, IGF‐I SDS before treatment was lower compared with the non‐GHD (−5.4 ± 2.5 vs. −1.8 ± 1.0; P < 0.001). IGF‐I (−1.8 SDS ± 2.2) and IGFBP‐3 (−1.1 SDS ± 0.6) levels and their molar ratios were highest at 6 weeks and remained relatively constant thereafter. In the non‐GHD group, IGF‐I levels increased throughout the year and were maximum at 12 months (0.3 SDS ± 1.4) while IGFBP‐3 (1.1 SDS ± 0.9) and IGF‐I/IGFBP‐3 molar ratio peaked at 6 months. In both groups, IGF‐I SDS and IGF‐I/IGFBP‐3 during treatment correlated with the dose of GH expressed as IU/m2/week (r‐values 0.77 to 0.89; P = 0.005) but not as IU/kg/week. Serum leptin levels decreased significantly during GH treatment in the GHD (median before treatment 4.0 μg/l; median after 12 months treatment 2.4 μg/l; P = 0.02) but not the non‐GHD (median before treatment 3.0 μg/l; median after 12 months treatment 2.6 μg/l). In the GHD group, serum leptin before treatment correlated with 12 month change in height SDS (r = 0.70, P = 0.02). CONCLUSIONS The pattern of IGF‐I, IGFBP‐3 and their molar ratio during the first year of GH treatment differed between the GHD and non‐GHD groups. Calculation of GH dose by surface area may be preferable to calculating by body weight. As a GH dose‐dependent increase in serum IGF‐I and IGF‐I/IGFBP‐3 may be associated with adverse effects, serum IGF‐I and IGFBP‐3 should be monitored routinely during long‐term GH treatment. Serum leptin was the only variable that correlated with first year growth response in GHD.