Markedly increased incidence of critical illness in adults with Type 1 diabetes.

AIMS: To compare the incidence of and mortality after intensive care unit admission in adults with paediatric-onset Type 1 diabetes vs the general population. METHODS: Using population-based administrative data from Manitoba, Canada, we identified 814 cases of paediatric-onset Type 1 diabetes, and 3579 general population controls matched on age, sex and region of residence. We estimated the incidence of intensive care unit admission in adulthood, and compared the findings between populations using incidence rate ratios and multivariable Cox proportional hazards regression, adjusting for age, sex, comorbidity and socio-economic status. We estimated age- and sex-standardized mortality rates after intensive care unit admission. RESULTS: Between January 2000 and October 2009, the average annual incidence of intensive care unit admission among prevalent cohorts was 910 per 100 000 in the Type 1 diabetes population, and 106 per 100 000 in matched controls, an eightfold increased risk (incidence rate ratio 8.6; 95% CI 5.5, 14.0). The adjusted risk of intensive care unit admission was elevated to a greater extent among women with Type 1 diabetes compared with matched women (hazard ratio 14.7; 95% CI 7.2, 29.4) than among men with Type 1 diabetes compared with matched men (hazard ratio 4.92; 95% CI 10.3, 2.36) The most common reasons for admission in the diabetes cohort were diabetic ketoacidosis, infection and ischaemic heart disease. At 30%, 5-year mortality was higher in the diabetes cohort than in the matched cohort (relative risk 5.7; 95% CI 1.2, 8.9). CONCLUSIONS: Compared with the general population, the risk of intensive care unit admission was higher in adults with paediatric-onset Type 1 diabetes, and mortality after admission was also higher.

Comparison of anthropometric measurements in children to predict metabolic syndrome in adolescence: analysis of prospective cohort data.

OBJECTIVES: The optimal screening measures for obesity in children remain controversial. Our study aimed to determine the anthropometric measurement at age 10 years that most strongly predicts the incidence of cardio-metabolic risk factors at age 13 years. SUBJECTS/METHODS: This was a prospective cohort study of a population-based cohort of 438 children followed between age 7 and 13 years of age. The main exposure variables were adiposity at age 10 years determined from body mass index (BMI) Z-score, waist circumference (WC) Z-score, waist-to-hip ratio and waist-to-height ratio. Outcome measures included systolic (SBP) and diastolic blood pressure (DBP), fasting high-density (HDL-c) and low-density lipoprotein cholesterol (LDL-c), triglycerides, insulin and glucose (homeostasis model of assessment, HOMA), and the presence of metabolic syndrome (MetS). RESULTS: WC Z-score at age 10 years was a stronger predictor of SBP (ß 0.21, R(2) 0.38, P<0.001 vs ß 0.30, R(2) 0.20, P<0.001) and HOMA (ß 0.51, R(2) 0.25, P<0.001 vs 0.40, R(2) 0.19, P<0.001) at age 13 years compared with BMI Z-score. WC relative to height and hip was stronger predictors of cardio- metabolic risk than BMI Z-score or WC Z-score. The relative risk (RR) of incident MetS was greater for an elevated BMI Z-score than for an elevated WC (girls: RR 2.52, 95% confidence interval (CI): 1.46-4.34 vs RR 1.56, 95% CI 1.18-2.07) and (boys: RR 2.86, 95% CI 1.79-4.62 vs RR 2.09, 95% CI 1.59-2.77). CONCLUSIONS: WC was a better predictor of SBP and HOMA compared with BMI or WC expressed relative to height or hip circumference. BMI was associated with higher odds of MetS compared with WC. Thus, BMI and WC may each be clinically relevant markers of different cardio-metabolic risk factors, and important in informing obesity-related prevention and treatment strategies.

Maternal distress in early life predicts the waist-to-hip ratio in schoolchildren.

We report on life course stress determinants of overweight in children, using data from the longitudinal follow-up of the nested case-control arm of the SAGE (study of asthma genes and the environment) birth cohort in Manitoba, Canada. Waist and hip measurements were obtained during a clinic visit at age 9-11 years. Multiple linear regression was conducted to determine the relationship between the waist-to-hip ratio and maternal smoking during pregnancy, postpartum maternal distress and stress reactivity in children (cortisol, cortisol-DHEA [dihydroepiandrostrenone] ratio quartiles) following a clinic stressor at age 8-10 years. We found waist-to-hip risk at age 9-11 years to be elevated among boys and girls whose mothers had experienced distress in the postnatal period. This association varied by gender and asthma status. In healthy girls, postpartum distress increased waist-to-hip ratio by a factor of 0.034 (P < 0.01), independent of the child's stage of puberty and adrenarche, cortisol-DHEA ratio and duration of exclusive breastfeeding. Among girls with asthma, maternal smoking during pregnancy was associated with an increased waist-to-hip ratio, if the mother also experienced distress in the postpartum period (0.072, P = 0.038). Among asthmatic boys, an association between maternal distress and waist-to-hip ratio was evident at the highest cortisol-DHEA ratios. Stress-induced changes to leptin and infant over-eating pathways were proposed to explain the postnatal maternal distress effects. Drawing on the theories of evolutionary biology, our findings underscore the significance of postnatal stress in disrupting hypothalamic-pituitary-adrenal axis function in infants and increasing risk for child overweight.

Infrequent milk consumption plus being overweight may have great risk for asthma in girls.

BACKGROUND: Inadequate milk consumption and being overweight are each associated with asthma symptoms in children. Milk consumption has been inversely related to childhood overweight. Thus, being overweight may be a pathway or a confounder in milk-asthma relationship. A combination of both factors may be associated with greater risk of asthma than one factor alone. METHODS: This study included 246 children with allergist-diagnosed asthma and 477 nonasthmatic controls at the age of 8-10 years. Information on milk consumption during the last 12 months was obtained from questionnaires. Being overweight was defined as body mass index > or =85th percentile. Being overweight as a possible pathway or confounder was formally tested. The odds ratio (OR) for combined infrequent milk consumption and being overweight in asthmatic vs nonasthmatic children was determined in multivariate logistic regression analyses. RESULTS: There was a significant interaction between milk consumption and sex of the child in relation to asthma. Asthma was significantly associated with infrequent milk consumption in girls (crude OR 2.11, 95% CI 1.05-4.24) but not in boys. The asthma-milk relation in girls was neither mediated by being overweight (p(mediation tests) = 0.27) nor was the relationship confounded by being overweight (a 9% change in coefficient). Asthmatic girls had 3.6 times increased odds of having combination of infrequent milk consumption and being overweight than nonasthmatic girls (adjusted OR 3.64, 95% CI 1.18-11.24). Asthma was not associated with either factor or with absence of the other in girls. CONCLUSION: Infrequent milk consumption plus being overweight may have great risk for asthma in girls.

Short-term insulin therapy in adolescents with type 2 diabetes mellitus.

The optimum pharmacological treatment of type 2 diabetes mellitus (DM2) in youth for those who fail to achieve adequate glycemic control (HbA1c <7%) with lifestyle intervention is unknown. The aim of this pilot study was to observe the effect of short-term insulin therapy (<16 weeks duration) on glycemic control in youth with DM2. A pre-mix 30/70 insulin was given twice daily to 18 youth aged 10-18 years with DM2 for 8.7+/-4.3 weeks with a starting dose of 0.5 U/kg/day. HbA1c, body mass index (BMI) and episodes of hypoglycemia were monitored during the treatment period and for a 12-month period after insulin was stopped. Mean HbA1c decreased from 12.81% to 7.59% (95% CI 6.54, 8.64). This improvement persisted for 12 months without any further drug therapy. There was no significant change in mean BMI and there were no episodes of moderate or severe hypoglycemia. Decreasing beta-cell glucose toxicity with rapid improvement of blood glucose may play an important role in treatment of DM2 in adolescents. Early success in achieving target blood glucose levels is an important aspect of adolescent DM2 care.

Influence of cold exposure and thyroid hormones on regulation of adrenal catecholamines.

Since thyroid hormones influence urinary excretion of catecholamines after exposure to cold, the effects of hyper- and hypo-thyroidism on adrenal tyrosine hydroxylase (TH) (EC 1.14.16.2), phenylethanolamine-N-methyl transferase (PNMT) (EC 2.1.1.28), and serum dopamine-beta-hydroxylase (DbetaH) (EC 1.14.17.1) of rats of 23 and 4 degrees C were studied. TH changes resembled the urinary excretion pattern at 4 degrees C in being higher after 8 days than after 1 day of exposure, and in declining as acclimation occurred. At 23 degrees C, TH activity of hypothyroid rats was significantly higher than in euthyroid or hyperthyroid animals, and after 1 day at 4 degrees C the value increased even more. While in the hypothyroid animals at 4 degrees C the concentration of adrenal catecholamines was less, the epinephrine to norepinephrine ratio was higher than at 23 degrees C. Very high TH activity with a decline in catecholamine concentration suggests that the capacity of TH had been exceeded. PNMT activity was significantly elevated in this group. TH activity was not decreased in the hyperthyroid group at 23 degrees C, and was increased after 8 days at 4 degrees C, suggesting that circulating thyroid hormones have no direct inhibitory effect on TH. Serum DbetaH was elevated after exposure to 4 degrees C, regardless of thyroid hormonal status. The activation of adrenal TH in hypothyroid rats at 23 degrees C and of TH, PNMT, and serum DbetaH at 4 degrees C is probably the result of increased activity of the sympathetic nervous system.

Effects of hypophysectomy and short- aing electron-microscopic study.

The follicular architecture of the thyroid gland of the rat following experimentally induced states of hypo- and hyperactivity was investigated by scanning electron microscopy and the findings correlated with both light and transmission electron-microscopic observations. By scanning electron microscopy, the microvilli on the apical surfaces of the follicular cells showed the most striking changes; following hypophysectomy, the cells were flattened and the microvilli had decreased in both size and number, whereas following propylthiouracil (PTU) administration the epithelial cells were enlarged, and marked hyperplasia and hypertrophy of the microvilli was present. Of particular interest is that the changes observed following PTU appeared to be identical in short- and long-term PTU-treated rats. Similarly, the heterogeneity of the follicular cells observed within the follicles was maintained under the various experimental conditions. Although the functional significance of these observations is not quite clear, it appears justifiable to assume that a reduction of luminal surface area of the follicular epithelial cell may hinder, whereas an increase may facilitate transport process across the apical cell membrane.

Ethanol metabolism and liver oxidative capacity in cold acclimation.

Exposure of rats to an ambient temperature of 5 degrees C for 4 to 6 weeks led to a 30 to 80 percent increase in the rate of oxygen consumption and a 50 percent increase in the rate of ethanol oxidation by liver slices, a 50 percent increase in mitochondrial alpha-glycerophosphate oxidase activity of liver, and a 100 percent increase in Na++K+-activated adenosine-triphosphatase, activity. Ouabain, an inhibitor of the Na++K+-activated adenosine-triphosphatase, completely blocked the extra respiration and ethanol oxidation. Dinitrophenol, which increases oxygen consumption and ethanol oxidation by liver slices from normal rats, was ineffective with slices from cold-exposed animals. Ethanol disappearance rate in vivo was also increased by cold acclimation, even though liver alcohol dehydrogenase activity was reduced. It is suggested that increased hydrolysis of ATP by the sodium pump system is responsible for the increased oxygen consumption and ethanol metabolism in the livers of cold-acclimated animals.