Reproducibility of the plasma glucose response to moderate-intensity exercise in adolescents with Type 1 diabetes.

AIMS: The aim of the study was to evaluate the reproducibility of the plasma glucose response to moderate-intensity exercise performed on different days under controlled conditions in adolescents with Type 1 diabetes. METHODS: Eight adolescents with Type 1 diabetes on continuous subcutaneous insulin infusion completed two exercise sessions, each on two separate days, under basal insulin and fasting conditions. On each day, participants cycled twice for 30 min at 55% of their peak rate of oxygen consumption, with each exercise session separated by a 30-min rest. RESULTS: Plasma insulin levels were similar between testing days and exercise sessions. The mean absolute drop in plasma glucose from the commencement to the end of exercise was 1.6 ± 0.5 mmol/l on day 1 and 1.9 ± 0.7 mmol/l on day 2 (P = 0.3). In response to the first exercise session, plasma glucose levels relative to baseline did not change significantly (0.2 ± 0.6 and -0.2 ± 0.5 mmol/l on days 1 and 2). By contrast, the change in plasma glucose during the second exercise session was -1.1 ± 0.7 and -1.3 ± 0.7mmol/l on days 1 and 2, respectively. The mean absolute intra-individual difference in the change in plasma glucose between testing days were 0.7 ± 0.5 [95% confidence interval (CI) 0.4-1.0] and 0.7 ± 0.4 (95% CI 0.4-1.0) mmol/l, at the end of the first and second exercise sessions respectively. CONCLUSIONS: The plasma glucose response to moderate-intensity exercise under similar glycaemic and basal insulin conditions can be reproducible in adolescents with Type 1 diabetes.

Psychiatric disorders during early adulthood in those with childhood onset type 1 diabetes: Rates and clinical risk factors from population-based follow-up.

AIM: To determine the incidence of and risk factors for psychiatric disorders in early adulthood in patients with childhood onset type 1 diabetes (T1D). METHODS: In this retrospective-cohort study, we identified a population-based childhood onset T1D cohort and an age and sex matched (5:1) non-diabetic comparison cohort. Data linkage was used to access inpatient hospitalization data, mental health support service data, and mortality data to follow-up both cohorts into early adulthood. RESULTS: The mean age of T1D diagnosis was 9.5 years (SD 4.1), with a mean age at end of follow-up of 26.4 years (SD 5.2, max 37.7). The diagnosis of any psychiatric disorder was observed for 187 of 1302 (14.3%) in the T1D cohort and 400 of 6422 (6.2%) in the comparison cohort [adjusted hazard ratio (HR) 2.3; 95% CI 1.9, 2.7]. Anxiety, eating, mood, and personality and behaviour disorders were observed at higher rates within the T1D cohort. Comorbid psychiatric disorders were more frequent, at the cohort level, within the T1D cohort (2-3 disorders 3.76% vs 1.56%) and service utilization was higher (15+ contacts 6.8% vs 2.8%); though these differences did not remain when restricted to only those individuals diagnosed during follow-up. A history of poor glycaemic control was associated with an increased risk of anxiety, mood, and 'any' disorder (HR ranging from 1.35 to 1.42 for each 1% increase in mean paediatric HbA1c). CONCLUSION: Our findings highlight the need for access to mental health support services as part of routine patient care for young adults with T1D, and for better predictive tools to facilitate targeting at-risk patients with early intervention programs.

Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison.

AIMS: Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries. METHODS: Data were obtained for children and/or adults with Type 1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173 880. Proportions with HbA1c < 58 mmol/mol (< 7.5%) and ≥ 75 mmol/mol (≥ 9.0%) were compared by age and sex. RESULTS: Data were available for 324 501 people. The proportions with HbA1c 58 mmol/mol (< 7.5%) varied from 15.7% to 46.4% among 44 058 people aged < 15 years, from 8.9% to 49.5% among 50 766 people aged 15-24 years and from 20.5% to 53.6% among 229 677 people aged ≥ 25 years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available. CONCLUSION: These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.

Clinical and demographic risk factors associated with mortality during early adulthood in a population-based cohort of childhood-onset type 1 diabetes.

AIMS: To calculate standardized mortality ratios and to assess the association between paediatric clinical factors and higher risk of mortality during early adulthood in a population-based cohort of subjects with Type 1 diabetes. METHODS: Subjects with Type 1 diabetes were identified through the Western Australian Children's Diabetes Database and clinical data for those who reached 18 years of age (n = 1309) were extracted. An age- and sex-matched (without diabetes) comparison cohort (n = 6451) was obtained from the birth registry. Mortality records were obtained from the death registry. Participants were followed up until 31 January 2012. Associations of clinical factors (from clinic visits before 18 years of age) with mortality were assessed using Cox proportional hazard models. RESULTS: The standardized mortality ratio for all-cause mortality was 1.7 (95% CI 0.7-3.3) for male and 10.1 (95% CI 5.2-17.7) for female subjects with Type 1 diabetes (median age at end of study 25.6 years). The adjusted hazard ratio was 1.5 (95% CI 1.1-2.1) for a 1% increase in mean paediatric HbA1c level, 3.8 (95% CI 0.9-15.3) for four episodes of severe hypoglycaemia relative to zero episodes, and 6.21 (95% CI 1.4-28.4) for a low-level socio-economic background relative to a high-level background. CONCLUSIONS: People with childhood-onset Type 1 diabetes have higher mortality rates in early adulthood. At particularly high risk are women, those with a history of poor HbA1c levels, those with recurrent severe hypoglycaemia during paediatric management, and those from a low socio-economic background. These groups may benefit from intensified management during transition from paediatric to adult care facilities.

Hypoglycaemia, fear of hypoglycaemia and quality of life in children with Type 1 diabetes and their parents.

AIM: To evaluate the association between fear of hypoglycaemia, episodes of hypoglycaemia and quality of life in children with Type 1 diabetes and their parents. METHODS: This was a cross-sectional, population-based study of 325 children with Type 1 diabetes and their parents. The children were aged 2-18 years. A total of 325 parents of the patients aged 2-18 years and 196 of the patients themselves (aged 8-18 years) completed questionnaires including the PedsQL Diabetes Module, the Hypoglycaemia Fear Survey and Clarke's hypoglycaemia awareness questionnaire. Data were compared with HbA1c results and the history of severe hypoglycaemia episodes. RESULTS: Parents with the highest levels of fear of hypoglycaemia reported that their children had a reduced quality of life (P < 0.001). Similarly children with the greatest fear also reported a reduced quality of life (P < 0.001); however a history of severe hypoglycaemia was not associated with the child's quality of life as perceived by the child or parent. Episodes of severe hypoglycaemia were associated with an increased fear of hypoglycaemia for the parents (P = 0.004) but not the children. Children in the highest fear quartile also had a higher HbA(1c) concentration compared with those in the lowest fear quartile [increase in HbA(1c) 7 mmol/mol (0.6%), P < 0.01]. CONCLUSIONS: Fear of hypoglycaemia and not episodes of hypoglycaemia per se is associated with increased psychological burden for children with Type 1 diabetes. Interventions to reduce fear of hypoglycaemia in these families may improve their quality of life.

Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Children of preschool age often have episodes of virus-associated wheeze, and research assessing efficacy of corticosteroids for paediatric wheeze exacerbations is inconclusive. METHODS: This non-inferiority, randomised, double-blind, placebo-controlled trial was to compare the efficacy of placebo versus oral prednisolone in children aged 24-72 months presenting with virus-associated wheeze at the paediatric emergency department of Princess Margaret Hospital in Perth, WA, Australia. Eligible participants were randomly assigned (1:1) using a computer-generated random number program to receive placebo or prednisolone (1 mg/kg per day) for 3 days. The primary outcome was total length of stay in hospital until ready for discharge. Following an analysis to test the hypothesis that placebo is non-inferior to prednisolone, a post-hoc superiority analysis was done to test the hypothesis that prednisolone was superior to placebo. A non-inferiority margin of 10% was used to establish non-inferiority. Efficacy analyses were on a modified intention-to-treat basis, whereby patients were excluded from the final efficacy analysis if consent was withdrawn, two doses of study drug were vomited, or paperwork was lost. All participants were included in safety analyses. This study is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12612000394842. FINDINGS: Between June 11, 2012, and June 10, 2015, we screened 3727 patients for eligibility. 624 eligible patients were randomly assigned to treatment, and 605 patients were included in the modified intention-to-treat analysis (300 patients from the placebo group, 305 patients from the prednisolone group). The median length of stay until ready for discharge was longer in the placebo group (540 min [IQR 124-971]) than in the prednisolone group (370 min [121-709]); placebo was inferior to prednisolone. In the post-hoc superiority analysis of 605 patients, the unadjusted ratio of geometric mean for length of stay was 0·79 (95% CI 0·64-0·97; p=0·0227) for the prednisolone group relative to the placebo group. No serious adverse events were reported during the study or follow-up period. One child in the placebo group had a non-specific maculopapular rash, which resolved spontaneously. Two children (one from each group) were reported to be hyperactive during follow-up assessments. INTERPRETATION: Oral prednisolone had a clear benefit over placebo at reducing the length of stay in children presenting to a paediatric emergency department with virus-associated wheeze and was well tolerated. FUNDING: Western Australian Department of Health.

Long-term cholesterol-lowering effects of 4 fat-restricted diets in hypercholesterolemic and combined hyperlipidemic men. The Dietary Alternatives Study.

CONTEXT: The long-term effect of aggressively vs moderately fat-restricted diets has not been studied extensively in free-living subjects with different types of hyperlipidemia. OBJECTIVE: To compare the cholesterol-lowering effects of 4 levels of dietary fat intake restriction after 1 year. DESIGN: Randomized, parallel, comparison trial. SETTING: Male employees of a large industry. PARTICIPANTS: A total of 444 men had low-density lipoprotein cholesterol (LDL-C) levels above the 75th age-specific percentile. Subjects with triglyceride (TG) levels less than the 75th age-specific percentile were defined as hypercholesterolemic (HC) and those with TG levels at or above the 75th age-specific percentile were defined as combined hyperlipidemic (CHL). INTERVENTIONS: Hypercholesterolemic subjects were randomized to diets 1, 2, 3, and 4 taught to contain 30%, 26%, 22%, and 18% fat, and the CHL subjects were randomized to diets 1, 2, and 3. All 4 diets were taught to subjects and spouses or partners in 8 weekly 2-hour classes. MAIN OUTCOME MEASURES: Plasma lipoprotein levels after 1 year. RESULTS: Fat intake after 1 year declined from a mean of 34% to 36% of energy to 27%, 26%, 25%, and 22% in the 4 HC diet groups and 28%, 26%, and 25% in the 3 CHL diet groups. Mean+/-SD percent LDL-C reductions were 5.3%+/-16.2%, 13.4%+/-12.6%, 8.4%+/-11.2%, and 13.0%+/-15.7% in the HC diet groups and 7.0%+/-16.2%, 2.8%+/-15.8%, and 4.6%+/-13.5% in the CHL diet groups (P<.01 in all but 1 instance). Apoprotein B levels decreased 8.6%, 10.7%, 4.3%, and 5.3% in the HC groups and 14.6%, 11.4%, and 9.9% in the CHL groups (P<.05-.01 in each instance). Triglyceride levels increased significantly in subjects following HC diets 3 and 4, 21.7% and 38.7% (P<.05 and .01), but not in any CHL subjects. High-density lipoprotein cholesterol decreased 2.8% and 3.2% in subjects on HC diets 3 and 4, respectively (P<.05 in both cases). CONCLUSIONS: After 1 year, moderate restriction of dietary fat intake attains meaningful and sustained LDL-C reductions in HC subjects and apoprotein B reductions in both HC and CHL subjects. More extreme restriction of fat intake offers little further advantage in HC or CHL subjects and potentially undesirable effects in HC subjects.