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Glucose-stimulated insulin and proinsulin responses, and insulin sensitivity, were studied in 30 HLA identical, 38 HLA haplo-identical, and 25 HLA non-identical, healthy islet-cell-antibody negative siblings of Type 1 diabetic patients. The results were compared with 41 age- and sex-matched healthy subjects with no diabetes in the family. The proinsulin-corrected insulin response to an intravenous glucose infusion test was significantly lower among siblings when insulin sensitivity was taken into account (1.65 (inter-quartile range 1.20-2.64) vs 2.18 (1.65-3.28) nmol mmol-1 min, p = 0.04). Proinsulin values were consistently higher among siblings than among control subjects (peak values 50.0 vs 38.0 pmol l-1 (p = 0.004)). When proinsulin release was corrected for individual insulin sensitivity this difference remained. The results suggest disturbed islet B-cell function, unrelated to HLA identity or the presence of circulating islet cell antibodies.

To assess the total insulin secretion in children in different nutritional states we have analysed the 24 h urinary C-peptide excretion in 32 obese children (16 boys and 16 girls) 8-15 years of age as well as in 7 girls with anorexia nervosa 11-16 years of age. Obese children had a median urinary C-peptide excretion rate of 0.27 nmol/kg/24 h, which was not different from that of a group of normal-weight children. In the group of anorectic girls, on the other hand, the median value 0.47 nmol/kg/24 h was significantly (p less than 0.05) higher than for normal-weight girls of the same age (median = 0.26 nmol/kg/24 h). These results indicate that in obese children insulin secretion, measured as the 24 h urinary C-peptide excretion per kg body weight, is the same as in normal-weight children. Total insulin secretion is consequently increased. In anorexia nervosa, on the other hand, the higher C-peptide excretion per kg body weight compared with normal-weight children, indicates that insulin secretion is increased in relation to body weight.

Recently we reported that insulin resistance and glucose induced insulin release are inversely correlated to age in young healthy siblings of diabetic patients. To confirm this pattern of change with age, the subjects were reexamined after two years. The study was limited to the age groups with the lowest insulin sensitivity, i.e. 14.0-15.9 years for females and 16.0-17.9 years for males. All five girls and four of five boys showed an increased insulin sensitivity as measured by the somatostatin-insulin-glucose infusion test (p = 0.02). All subjects showed a decrease in fasting levels of insulin-like growth factor 1 (IGF-1) (p less than 0.01) during the observation period. All except one showed an increase in the levels of dehydroepiandrosterone sulphate (DHEA-S) (p less than 0.01). These data confirm that insulin sensitivity increases in the late teenage period. The parallelism to the changes of IGF-1 indicate that the pubertal changes in insulin sensitivity may partly be caused by growth hormone. Our data contradict the hypothesis that the low insulin sensitivity of puberty is due to the increased levels of DHEA-S.

Glycosylated hemoglobin A (HbA1c), considered to reflect long-term metabolic control of diabetes, was analyzed in 131 patients, aged 2 5/12-19 6/12 yr, with juvenile-onset diabetes. Using stepwise multiple regression HbA1c, fasting blood glucose and plasma 3-hydroxybutyrate were analyzed as dependent variables versus independent variables such as age of the patients, duration of the disease, level of plasma immunoreactive C-peptide (IRCP), insulin dose, and number of insulin injections (one or two) per day. HbA1c was inversely related only to IRCP concentration. A low but significant, positive correlation was found between HbA1c and the duration of diabetes. Stepwise addition of the other independent variables did not further increase the fraction of explained variance. HbA1c was also correlated with a subjective rating score of the metabolic control performed by the treating physician. Fasting plasma glucose was significantly related to HbA1c but not to any of the independent variables. Fasting 3-hydroxybutyrate showed an inverse correlation to the age of the patient. The present study showed that in juvenile-onset diabetic patients, endogenous insulin secretion as reflected by IRCP was the factor best correlated with a low level of HbA1c. After the cessation of endogenous insulin secretion, there is a progressive deterioration of metabolic control and multiple injections of insulin rather than one or two per day may be needed to reach optimal control in the patients.

The aim of the present study was to compare the immunogenicity of monocomponent human insulin with that of monocomponent porcine insulin in newly diagnosed Type 1 (insulin-dependent) diabetic children. One hundred and thirty-five patients at diagnosis of diabetes (age 1-18 years, mean age 9.3 years) were randomly allocated to treatment with either Monotard MC + Actrapid MC or Monotard HM + Actrapid HM in a double-blind trial conducted in Sweden, Finland, Norway and Denmark. The human and porcine insulin groups were identical at diagnosis with respect to age, sex and measures of metabolic control. At all times the mean insulin antibody levels and the percentage of antibody-positive patients were lower in the human group compared with the porcine group. At 3 and 12 months, the insulin antibody values were significantly lower in the human group than in the porcine group (p less than 0.05, Wilcoxon's rank sum test). At 12 months, antibody values in the human group ranged from 0 to 1.2 U/l (mean 0.14 U/l) and in the porcine insulin group from 0-5.2 U/l (mean 0.63 U/l). It is therefore concluded that human monocomponent insulin has a lower immunogenicity than porcine insulin of the same purity in newly diagnosed diabetic children during the first year of insulin treatment.

Glucose-induced insulin response and insulin sensitivity were studied in 32 HLA-identical, 38 haplo-identical and 24 non-identical, islet-cell-antibody-negative, healthy siblings of young Type 1 (insulin-dependent) diabetic patients (age range 10-28 years). No significant differences were obtained between HLA-identical, HLA-haplo-identical siblings and HLA-non-identical siblings in insulin response using an i.v. glucose infusion test even when the insulin sensitivity as estimated by the somatostatin-insulin-glucose infusion test was taken into account. A significant inverse correlation to age was found for both insulin response (r = -0.24, p = 0.02) and insulin sensitivity (r = -0.36, p less than 0.01) in the young siblings studied.

One hundred and thirty eight patients participated in a two-year randomized, double-blind multicentre trial to compare monocomponent human insulin and porcine insulin in the treatment of newly diagnosed insulin dependent diabetic children with respect to development of insulin antibodies, metabolic control and B-cell function. There was no difference between the two patient groups throughout treatment either in the level of IgG insulin binding or the percentage of patients with insulin antibodies (IgG-insulin greater than 0.012 U/l). However, the estimated mean of log insulin binding values in the antibody positive patients alone was significantly lower (p less than 0.05) in the human insulin treated group at all times apart from 1 and 18 months (e.g., human insulin group at one and two years: 0.104 and 0.152 U/l, porcine insulin group at one and two years: 0.162 and 0.212 U/l). The insulin antibodies in both patient groups bound equivalent amounts of human and porcine insulin tracer. Metabolic control, insulin dosage and B-cell function in the two treatment groups were similar throughout the treatment period. It is concluded that in newly diagnosed insulin dependent diabetic children monocomponent human insulin is slightly less immunogenic than monocomponent porcine insulin, and equally effective in overall metabolic control.

The effect of fetal insulin injection on body weight and carcass lipid and nitrogen content was studied in four groups of rat fetuses. In each litter, one fetus in each horn was randomly chosen for treatment with either insulin injection, saline injection, insulin solvent injection or sham operation. Injections were given subcutaneously to the fetuses on days 18 1/2, 19 1/2, and 20 1/2 of gestation. The experimental model and the statistical evaluation took into consideration the influence of the fetal position in the uterine horn as well as the variability of fetal size between different litters. Using this experimental model we found that insulin injections to the fetal rat had no effect on body weight and body composition.

Aims/hypothesis. To analyse the incidence of Type I (insulin-dependent) diabetes mellitus in the 0–34 years age group in Sweden 1983–1998. Methods. Incidence and cumulative incidence per 100 000 and Poisson regression analysis of age-period effects was carried out using 11 751 cases from two nation-wide prospective registers. Results. Incidence (95%-CI) was 21.4 (20.8–21.9) in men and 17.1 (16.6–17.5) in women between 0 and 34 years of age. In boys aged 0–14 and girls aged 0–12 years the incidence increased over time, but it tended to decrease at older age groups, especially in men. Average cumulative incidence at 35 years was 748 in men and 598 in women. Cumulative incidence in men was rather stable during four 4-year periods (736, 732, 762, 756), while in women it varied more (592, 542, 617, 631). In males aged 0–34 years, the incidence did not vary between the 4-year periods (p=0.63), but time changes among the 3-year age groups differed (p<0.001). In females the incidence between the periods varied (p<0.001), being lower in 1987–1990 compared to 1983–1986, but time changes in the age groups did not differ (p=0.08). For both sexes median age at diagnosis was higher in 1983–1986 than in 1995–1998 (p<0.001) (15.0 and 12.5 years in males; 11.9 and 10.4 in females, respectively). Conclusion/interpretation. During a 16-year period the incidence of Type I diabetes did not increase in the 0–34 years age group in Sweden, while median age at diagnosis decreased. A shift to younger age at diagnosis seems to explain the increasing incidence of childhood Type I diabetes. [ABSTRACT FROM AUTHOR]