Prevalence of obesity was related to HLA-DQ in 2-4-year-old children at genetic risk for type 1 diabetes.

OBJECTIVES: Body size is postulated to modulate type 1 diabetes as either a trigger of islet autoimmunity or an accelerator to clinical onset after seroconversion. As overweight and obesity continue to rise among children, the aim of this study was to determine whether human leukocyte antigen DQ (HLA-DQ) genotypes may be related to body size among children genetically at risk for type 1 diabetes. METHODS: Repeated measures of weight and height were collected from 5969 children 2-4 years of age enrolled in The Environmental Determinants of Diabetes in the Young prospective study. Overweight and obesity was determined by the International Obesity Task Force cutoff values that correspond to body mass index (BMI) of 25 and 30 kg m(-)(2) at age 18. RESULTS: The average BMI was comparable across specific HLA genotypes at every age point. The proportion of overweight was not different by HL A, but percent obesity varied by age with a decreasing trend among DQ2/8 carriers (P for trend=0.0315). A multivariable regression model suggested DQ2/2 was associated with higher obesity risk at age 4 (odds ratio, 2.41; 95% confidence interval, 1.21-4.80) after adjusting for the development of islet autoantibody and/or type 1 diabetes. CONCLUSIONS: The HLA-DQ2/2 genotype may predispose to obesity among 2-4-year-old children with genetic risk for type 1 diabetes.

Costs of insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) is a prevalent chronic disease that causes marked personal and financial costs for patients, their families and society. Accurate information on costs of the disease is scarce. In this article, we review studies on disease and disease stage-connected costs at the individual and societal levels, and discuss possibilities of decreasing or preventing costs attributable to IDDM. The 3 disease stages are the initial treatment, follow-up after the initial treatment and late treatment. Total costs of IDDM in a given country depend on the incidence of the disease and the efficiency (cost effectiveness) of treatment. Besides everyday treatment costs, the acute and long term complications of the disease cause major additional costs. The lifetime financial costs of IDDM and the amount of human suffering are always substantial. The costs of the 3 clinical stages of IDDM differ markedly. The initial and late periods induce cost peaks, but the costs of follow-up after initial treatment are small. During initial treatment, costs depend mostly on the possible length of hospitalisation. During the late treatment period, costs begin to accumulate rapidly because of long term complications such as diabetic nephropathy, retinopathy, neuropathy and macrovascular disease. Intensive ambulatory care, effective patient education that results in normoglycaemia or near-normoglycaemia in patients and, if needed, shortening of hospitalisations, are the only means to restrict or decrease the costs of IDDM until primary prevention is available. Postponing complications by any length of time will always decrease human suffering and lead to marked savings in healthcare resources.

Excitatory amino acids in cerebrospinal fluid in neonatal asphyxia.

Of the excitatory amino acids, glutamic and aspartic acid were studied in the cerebrospinal fluid of six infants 4-32 hours after a documented episode of severe neonatal asphyxia. Aspartic acid concentration was definitely increased in the cerebrospinal fluid of these patients, whereas glutamic acid concentration varied considerably. Aspartic acid was always increased, even hours after the period of asphyxia, but values were greater in samples taken less than 12 hours after the asphyxial event. The patients with the highest cerebrospinal fluid aspartic acid concentrations had more severe outcomes.

Expression of common familial dyslipidemias in early childhood.

Early identification of common familial dyslipidemias may prevent premature atherosclerotic disease. This study estimated the diagnostic values of few early childhood repeatedly deviant lipid samples by the knowledge of the parent's dyslipidemia. The first 7 years of age data of 353 children with their parents were evaluated from atherosclerosis risk-factor intervention study controls. Parents' low high-density-lipoprotein-cholesterol concentration (hypo-HDL-C), and high total cholesterol concentration-HDL-C (hyper-non-HDL-C) were defined. True hypo-HDL-C and hyper-non-HDL-C children were defined when their respective individual longitudinal means were beyond the appropriate lipid quintiles. Sensitivities, specificities, positive and negative predictive values of the early lipid samples were estimated with individual standard deviation models and bootstrap confidence. Hypo-HDL-C children proportions were 15.3% of all, and 20.9% of the children from the hypo-HDL-C parents (p=0.26). Hyper-non-HDL-C children were 16.7% of all and 31.8% of the children from the hyper-non-HDL-C parents (p=0.008). One early non-HDL-C sample in the highest quintile predicted 56% of the hyper-non-HDL-C children from healthy parents, but 83% of the hyper-non-HDL-C children from the hyper-non-HDL-C parents. Mean of three samples improved the latter prediction to 91%. This showed that if hypercholesterolemic parent's child expressed repeatedly hyper-non-HDL-C, it predicts true dyslipidemia of the child.

Tracking of serum lipoprotein (a) concentration and its contribution to serum cholesterol values in children from 7 to 36 months of age in the STRIP Baby Study. Special Turku Coronary Risk Factor Intervention Project for Babies.

We investigated the tracking phenomenon of serum lipoprotein (a) concentrations and assessed the impact of serum concentration of lipoprotein (a) cholesterol on total cholesterol concentrations in children from 7 to 36 months of age. Serum samples for lipoprotein (a) and cholesterol determinations at 7, 13, 24 and 36 months were prospectively obtained from 430 children. Serum lipoprotein (a) was determined using immunoradiometric assay. A strong correlation was observed between lipoprotein (a) concentrations at 7 and 36 months of age (r = 0.88, P < 0.001). Seventy-eight per cent to 86% of the children in the lowest and highest lipoprotein (a) quintiles at 13 months remained in the respective quintiles at 36 months. The average contribution of lipoprotein (a) cholesterol to total cholesterol varied from 0.5% to 3.2% (individual variation 0.13-32.39%) depending on the type of milk received and the age of the children. At 7 months the contribution was 0.44% in breast-fed and 0.93% in formula-fed infants (P < 0.0001). The tracking phenomenon of serum lipoprotein (a) concentrations is strong already in early childhood. The contribution of lipoprotein (a) cholesterol to serum total cholesterol concentration should be taken into account when the changes in serum cholesterol levels are interpreted in the first year of life.

Pharmacokinetics of aminoguanidine administration and effects on the diabetes frequency in nonobese diabetic mice.

In vitro studies suggest that intra-islet nitric oxide production may contribute to the pathogenesis of autoimmune insulin-dependent diabetes mellitus. We tested whether aminoguanidine (AG), a competitive inhibitor of inducible nitric oxide synthase, might block beta cell destruction and prevent insulin-dependent diabetes mellitus in vivo. A total of 50 female nonobese diabetic mice, from the time of weaning until 32 wk of age, received injections (i.p.) twice daily with 50 mg AG/kg body weight and received AG in drinking water (350 mg/liter). A total of 50 littermates treated with vehicle alone served as controls. A 24-hr pharmacokinetic analysis showed that AG was readily absorbed after i.p. administration, peaked in plasma (9.0 micrograms/ml) at 0.5 hr and had a half-life of 1.88 hr. Steady-state values for the area under the curve for the therapeutic regimen were 20.51 and 16.35 (micrograms)(hr)/ml for the 0000 to 1600 and 1600 to 2400 hr, respectively. In terms of therapy, life-table analysis indicated the frequency of insulin-dependent diabetes mellitus (6/30 AG-treated vs. 11/31 vehicle-treated, P = .25) and insulitis scores (2.0 +/- 1.1 vs. 2.4 +/- 1.2 in nondiabetic AG- and vehicle-treated mice at 32 wk, respectively, P = .20) were similar in both groups. Flow cytometric analysis revealed no quantitative differences in islet infiltrating macrophages, CD4+ or CD8+ T lymphocytes between groups of animals randomly killed at 8, 16 and 32 wk. Although not eliminating a role for nitric oxide in the pathogenesis of insulin-dependent diabetes mellitus, prophylactic treatment with AG did not significantly impact the onset of insulitis or diabetes in nonobese diabetic mice.