Use of remote monitoring with continuous glucose monitoring in young children with Type 1 diabetes: the parents' perspective.

AIM: Remote monitoring with continuous glucose monitoring (CGM) in children with Type 1 diabetes mellitus has recently become available, but little is known about caregivers' experiences of its use, particularly in younger children. The aim of this study was to explore parents' everyday experiences of using this technology. METHODS: The parents of children with Type 1 diabetes diagnosed for > 1 year, aged 2-12 years were invited to participate in a semi-structured interview. Interviews were the second phase of a randomized cross-over study using standard insulin therapy with or without CGM and remote monitoring for two 3-month periods. Open-ended questions were used to explore parents' real-life experiences of the remote monitoring and CGM system. Interviews were analysed using thematic analysis. RESULTS: Five themes related to remote monitoring emerged: (i) impact on sleep quality for the parents, (ii) peace of mind, (iii) impact on anxiety, (iv) freedom and confidence for the parents and children, and (v) impact on relationships. Furthermore, parents reported on themes related to CGM in general, such as better understanding of how to manage and control their child's diabetes and experiences related to physical or technical aspects. CONCLUSION: Overall, parents of primary school children reported that using remote monitoring and CGM was a mostly beneficial experience. However, negative aspects within the themes were also reported. These findings will help to provide a structure to discuss parent and child expectations and provide targeted education at the start of using remote monitoring and CGM.

Effect of combining pre-exercise carbohydrate intake and repeated short sprints on the blood glucose response to moderate-intensity exercise in young individuals with Type 1 diabetes.

AIMS: To determine whether pre-exercise ingestion of carbohydrates to maintain stable glycaemia during moderate-intensity exercise results in excessive hyperglycaemia if combined with repeated sprints in individuals with Type 1 diabetes. METHODS: Eight overnight-fasted people with Type 1 diabetes completed the following four 40-min exercise sessions on separate days in a randomized counterbalanced order under basal insulinaemic conditions: continuous moderate-intensity exercise at 50% V ˙ O 2 peak; intermittent high-intensity exercise (moderate-intensity exercise interspersed with 4-s sprints every 2 min and a final 10-s sprint); continuous moderate-intensity exercise with prior carbohydrate intake (~10 g per person); and intermittent high-intensity exercise with prior carbohydrate intake. Venous blood was sampled during and 2 h after exercise to measure glucose and lactate levels. RESULTS: The difference in marginal mean time-averaged area under the blood glucose curve between continuous moderate-intensity exercise + prior carbohydrate and intermittent high-intensity exercise + prior carbohydrate during exercise and recovery was not significant [0.2 mmol/l (95% CI -0.7, 1.1); P = 0.635], nor was the difference in peak blood glucose level after adjusting for baseline level [0.2 mmol/l (95% CI -0.7, 1.1); P = 0.695]. The difference in marginal mean time-averaged area under the blood glucose curve between continuous moderate-intensity and intermittent high-intensity exercise during exercise and recovery was also not significant [-0.2 mmol/l (95% CI -1.2, 0.8); P = 0.651]. CONCLUSIONS: When carbohydrates are ingested prior to moderate-intensity exercise, adding repeated sprints is not significantly detrimental to glycaemic management in overnight fasted people with Type 1 diabetes under basal insulin conditions.

Dietary protein affects both the dose and pattern of insulin delivery required to achieve postprandial euglycaemia in Type 1 diabetes: a randomized trial.

AIM: To quantify the insulin requirement for a high-protein meal compared with a low-protein meal, controlling for carbohydrate and fat content. METHODS: In this crossover study, young people with Type 1 diabetes were randomized to consume a high- (60 g) or low-protein meal (5 g), each containing 30 g carbohydrate and 8 g fat. A variation of the insulin clamp technique was used to determine the insulin requirements to maintain euglycaemia for the following 5 h. RESULTS: A total of 11 participants (mean ± sd age 16.5 ± 2.7 years, HbA1c 52 ± 8.7 mmol/mol [6.9 ± 0.8%], diabetes duration 6.9±5.1 years) completed the study. The mean insulin requirements for the high-protein meal were higher than for the low-protein meal [10.3 (CI 8.2, 12.57) vs 6.7 units (CI 4.7, 8.8); P=0.001], with inter-individual requirements ranging from 0.9 to six times the low-protein meal requirement. Approximately half the additional insulin [1.1 units/h (CI 0.5, 1.8; P=0.001)] was given in the first 2 h, compared with an additional 0.5 units/h (CI -0.2, 1.2; P=0.148) in the second 2 h and 0.1 units (CI -0.6, 0.8; P=0.769) in the final hour. CONCLUSIONS: A high-protein meal requires ~50% more insulin to maintain euglycaemia than a low-protein meal that contains the same quantity of carbohydrate. The majority is required within the first 2 h. Inter-individual differences exist in insulin requirements for dietary protein.

A randomized comparison of three prandial insulin dosing algorithms for children and adolescents with Type 1 diabetes.

AIM: To compare systematically the impact of two novel insulin-dosing algorithms (the Pankowska Equation and the Food Insulin Index) with carbohydrate counting on postprandial glucose excursions following a high fat and a high protein meal. METHODS: A randomized, crossover trial at two Paediatric Diabetes centres was conducted. On each day, participants consumed a high protein or high fat meal with similar carbohydrate amounts. Insulin was delivered according to carbohydrate counting, the Pankowska Equation or the Food Insulin Index. Subjects fasted for 5 h following the test meal and physical activity was standardized. Postprandial glycaemia was measured for 300 min using continuous glucose monitoring. RESULTS: 33 children participated in the study. When compared to carbohydrate counting, the Pankowska Equation resulted in lower glycaemic excursion for 90-240 min after the high protein meal (p < 0.05) and lower peak glycaemic excursion (p < 0.05). The risk of hypoglycaemia was significantly lower for carbohydrate counting and the Food Insulin Index compared to the Pankowska Equation (OR 0.76 carbohydrate counting vs. the Pankowska Equation and 0.81 the Food Insulin Index vs. the Pankowska Equation). There was no significant difference in glycaemic excursions when carbohydrate counting was compared to the Food Insulin Index. CONCLUSION: The Pankowska Equation resulted in reduced postprandial hyperglycaemia at the expense of an increase in hypoglycaemia. There were no significant differences when carbohydrate counting was compared to the Food Insulin Index. Further research is required to optimize prandial insulin dosing.

The time lag prior to the rise in glucose requirements to maintain stable glycaemia during moderate exercise in a fasted insulinaemic state is of short duration and unaffected by the level at which glycaemia is maintained in Type 1 diabetes.

AIMS: To determine the duration of the low hypoglycaemia risk period after the start of moderate-intensity exercise performed under basal insulinaemic conditions and whether this period is affected by the level at which glycaemia is maintained under these conditions. METHODS: This was a prospective, randomized counterbalanced study. Eight participants with Type 1 diabetes (mean ± sd age 21.5 ± 4.0 years) underwent either a euglycaemic (5-6 mmol/l) or hyperglycaemic clamp (9-10 mmol/l) on separate days and were infused with insulin at basal rates and [6,6-2 H]glucose while cycling for 40 min at 50% maximum oxygen consumption rate. The main outcome measures were the glucose infusion rates required to maintain stable glycaemia and glucoregulatory hormone levels, and rates of glucose appearance and disappearance. RESULTS: During the first 20 min of exercise, the glucose infusion rate did not increase significantly, irrespective of the level at which glycaemia was maintained, but increased acutely between 20 and 25 min under both conditions. Maintaining higher glycaemia resulted in higher glucose infusion rate during, but not early post-exercise. With the exception of epinephrine, the glucoregulatory hormone levels and rates of glucose appearance and disappearance were similar between conditions. CONCLUSION: Irrespective of the levels at which glycaemia is maintained, there is a 20-min low exogenous glucose demand period during which the exogenous glucose requirements to maintain stable glycaemia do not increase during moderate exercise performed at basal insulin level.

The glycaemic benefits of a very-low-carbohydrate ketogenic diet in adults with Type 1 diabetes mellitus may be opposed by increased hypoglycaemia risk and dyslipidaemia.

AIMS: To investigate whether very-low-carbohydrate high-fat diets, typical of ketogenic diets, can improve glycaemic control without causing any ill health effects in adults with Type 1 diabetes. METHODS: In this observational study, 11 adults with Type 1 diabetes (seven men, four women, mean ± sd age 36.1± 6.8 years, mean ± sd duration of diabetes 12.8 ± 10.3 years), who followed a ketogenic diet (< 55 g carbohydrate per day) for a mean ± sd of 2.6 ± 3.3 years (ß-hydroxybutyrate 1.6 ± 1.3 mmol/l), underwent sampling and analysis of fasting blood, and were fitted with a blinded continuous glucose monitor for 7 days to measure glycaemic variability. RESULTS: The mean ± sd HbA1c levels were 35±4 mmol/mol (5.3±0.4%), and participants spent 74±20 and 3±8% of their time in the euglycaemic (4-8 mmol/l) and hyperglycaemic (>10 mmol/l) ranges, respectively, with little daily glycaemic variability (sd 1.5±0.7 mmol/l; coefficient of variation 26±8%). Blood glucose levels were <3.0 mmol/l for 3.6% of the time, and participants experienced a median (range) of 0.9 (0.0-2.0) daily episodes of hypoglycaemia. Total cholesterol, LDL cholesterol, total cholesterol/HDL cholesterol ratio, and triglycerides were above the recommended range in 82%, 82%, 64% and 27% of participants, respectively; however, HDL cholesterol levels were within the recommended range for all participants. Participants displayed no or little evidence of hepatic or renal dysfunction. CONCLUSION: This study provides the first evidence that, ketogenic diets in adults with Type 1 diabetes are associated with excellent HbA1c levels and little glycaemic variability, but may also be associated with dyslipidaemia and a high number of hypoglycaemic episodes.

A 10-second sprint does not blunt hormonal counter-regulation to subsequent hypoglycaemia.

AIM: To investigate whether a 10-second (s) sprint impairs the counter-regulatory response to subsequent hypoglycaemia. METHODS: Nine people (five male, four female) with Type 1 diabetes, aged 21.1 ± 4.5 years, performed a 10-s rest or a 10-s maximum-effort sprint in random order on different days, while subjected to an euinsulinaemic-euglycaemic clamp. This was followed by a hyperinsulinaemic-hypoglycaemic glucose clamp 2.5 h later to induce hypoglycaemia for 40 min. At timed intervals, the counter-regulatory hormonal responses to hypoglycaemia were measured. Blood pressure, heart rate and hypoglycaemic symptoms were also assessed. RESULTS: During the hypoglycaemic clamp, epinephrine, norepinephrine, growth hormone and cortisol levels increased significantly from baseline, and their responses were similar after both rest and sprint conditions. In particular, plasma epinephrine rose eightfold, from 197 ± 103 pmol/l to 1582 ± 1118 pmol/l after the rest condition, and from 219 ± 119 pmol/l to 1900 ± 898 pmol/l after the sprint condition. CONCLUSION: A 10-s sprint is unlikely to blunt the subsequent hormonal counter-regulation to hypoglycaemia in individuals with Type 1 diabetes.

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.

Are low sun exposure and/or vitamin D risk factors for type 1 diabetes?

The global variation in type 1 diabetes (T1D) incidence rates is one of the most significant observed for any non-communicable disease. Geographical patterns in incidence suggest that low sun exposure may contribute to the wide disparity, with incidence rates generally increasing with distance from the Equator. T1D development is associated with hyperactivity of the adaptive immune system leading to autoimmune destruction of insulin-secreting pancreatic ß cells. Both exposure to ultraviolet radiation (UVR) and vitamin D, with their known immunosuppressive effects, have the potential to delay or inhibit the disease. Efforts to confirm the role of UVR by vitamin D dependent and independent pathways in the pathogenesis of T1D have been challenged by inconsistent results among studies. Human observational studies and animal and in vitro experiments indicate that at least some of the benefits of sun exposure come from improved vitamin D status. There is no evidence of benefit for T1D risk of vitamin D supplementation during pregnancy at current recommended levels (400 IU per day); but some evidence supports that higher sun exposure and/or vitamin D sufficiency in pregnancy, or supplementation in early life, decreases T1D risk. Further research is required to confirm an association between UVR exposure and T1D and clarify the mechanisms involved.

Home-based vs inpatient education for children newly diagnosed with type 1 diabetes.

BACKGROUND: Initial management of children diagnosed with type 1 diabetes (T1D) varies worldwide with sparse high quality evidence regarding the impact of different models of care. AIM: To compare the inpatient model of care with a hybrid home-based alternative, examining metabolic and psychosocial outcomes, diabetes knowledge, length of stay, and patient satisfaction. SUBJECTS AND METHODS: The study design was a randomized-controlled trial. Inclusion criteria were: newly diagnosed T1D, aged 3 to 16 years, living within approximately 1 hour of the hospital, English-speaking, access to transport, absence of significant medical or psychosocial comorbidity. Patients were randomized to standard care with a 5 to 6 day initial inpatient stay or discharge after 2 days for home-based management. All patients received practical skills training in the first 48 hours. The intervention group was visited twice/day by a nurse for 2 days to assist with injections, then a multi-disciplinary team made 3 home visits over 2 weeks to complete education. Patients were followed up for 12 months. Clinical outcomes included HbA1c, hypoglycemia, and diabetes-related readmissions. Surveys measured patient satisfaction, diabetes knowledge, family impact, and quality of life. RESULTS: Fifty patients were recruited, 25 to each group. There were no differences in medical or psychosocial outcomes or diabetes knowledge. Average length of admission was 1.9 days shorter for the intervention group. Families indicated that with hindsight, most would choose home- over hospital-based management. CONCLUSIONS: With adequate support, children newly diagnosed with T1D can be safely managed at home following practical skills training.

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.

Safety and efficacy of the predictive low glucose management system in the prevention of hypoglycaemia: protocol for randomised controlled home trial to evaluate the Suspend before low function.

INTRODUCTION: Innovations with sensor-augmented pump therapy (SAPT) to reduce hypoglycaemia in patients with type 1 diabetes are an ongoing area of research. The predictive low glucose management (PLGM) system incorporates continuous glucose sensor data into an algorithm and suspends basal insulin before the occurrence of hypoglycaemia. The system was evaluated in in-clinic studies, and has informed the parameters of a larger home trial to study its efficacy and safety in real life. METHODS AND ANALYSIS: The aim of this report is to describe the study design and outcome measures for the trial. This is a 6-month, multicentre, randomised controlled home trial to test the PLGM system in children and adolescents with type 1 diabetes. The system is available in the Medtronic MiniMed 640G pump as the 'Suspend before low' feature. Following a run-in period, participants are randomised to either the control arm with SAPT alone or the intervention arm with SAPT and Suspend before low. The primary aim of this study is to evaluate the time spent hypoglycaemic (sensor glucose <3.5 mmol/L) with and without the system. The secondary aims are to determine the number of hypoglycaemic events, the time spent hyperglycaemic, and to evaluate safety with ketosis and changes in glycated haemoglobin. The study also aims to assess the changes in counter-regulatory hormone responses to hypoglycaemia evaluated by a hyperinsulinaemic hypoglycaemic clamp in a subgroup of patients with impaired awareness. Validated questionnaires are used to measure the fear of hypoglycaemia and the impact on the quality of life to assess burden of the disease. ETHICS AND DISSEMINATION: Ethics committee permissions were gained from respective Institutional Review boards. The findings of the study will provide high quality evidence of the ability of the system in the prevention of hypoglycaemia in real life. TRIAL REGISTRATION NUMBER: ACTRN12614000510640, Pre-results.

Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood.

Childhood obesity is a major public health issue. Here we investigated whether differential DNA methylation was associated with childhood obesity. We studied DNA methylation profiles in whole blood from 78 obese children (mean BMI Z-score: 2.6) and 71 age- and sex-matched controls (mean BMI Z-score: 0.1). DNA samples from obese and control groups were pooled and analyzed using the Infinium HumanMethylation450 BeadChip array. Comparison of the methylation profiles between obese and control subjects revealed 129 differentially methylated CpG (DMCpG) loci associated with 80 unique genes that had a greater than 10% difference in methylation (P-value < 0.05). The top pathways enriched among the DMCpGs included developmental processes, immune system regulation, regulation of cell signaling, and small GTPase-mediated signal transduction. The associations between the methylation of selected DMCpGs with childhood obesity were validated using sodium bisulfite pyrosequencing across loci within the FYN, PIWIL4, and TAOK3 genes in individual subjects. Three CpG loci within FYN were hypermethylated in obese individuals (all P < 0.01), while obesity was associated with lower methylation of CpG loci within PIWIL4 (P = 0.003) and TAOK3 (P = 0.001). After building logistic regression models, we determined that a 1% increase in methylation in TAOK3, multiplicatively decreased the odds of being obese by 0.91 (95% CI: 0.86 - 0.97), and an increase of 1% methylation in FYN CpG3, multiplicatively increased the odds of being obese by 1.03 (95% CI: 0.99 - 1.07). In conclusion, these findings provide evidence that childhood obesity is associated with specific DNA methylation changes in whole blood, which may have utility as biomarkers of obesity risk.

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.

The effect of a short sprint on postexercise whole-body glucose production and utilization rates in individuals with type 1 diabetes mellitus.

CONTEXT: Recently we showed that a 10-sec maximal sprint effort performed before or after moderate intensity exercise can prevent early hypoglycemia during recovery in individuals with type 1 diabetes mellitus (T1DM). However, the mechanisms underlying this protective effect of sprinting are still unknown. OBJECTIVE: The objective of the study was to test the hypothesis that short duration sprinting increases blood glucose levels via a disproportionate increase in glucose rate of appearance (Ra) relative to glucose rate of disappearance (Rd). SUBJECTS AND EXPERIMENTAL DESIGN: Eight T1DM participants were subjected to a euglycemic-euinsulinemic clamp and, together with nondiabetic participants, were infused with [6,6-(2)H]glucose before sprinting for 10 sec and allowed to recover for 2 h. RESULTS: In response to sprinting, blood glucose levels increased by 1.2 ± 0.2 mmol/liter (P < 0.05) within 30 min of recovery in T1DM participants and remained stable afterward, whereas glycemia rose by only 0.40 ± 0.05 mmol/liter in the nondiabetic group. During recovery, glucose Ra did not change in both groups (P > 0.05), but glucose Rd in the nondiabetic and diabetic participants fell rapidly after exercise before returning within 30 min to preexercise levels. After sprinting, the levels of plasma epinephrine, norepinephrine, and GH rose transiently in both experimental groups (P < 0.05). CONCLUSION: A sprint as short as 10 sec can increase plasma glucose levels in nondiabetic and T1DM individuals, with this rise resulting from a transient decline in glucose Rd rather than from a disproportionate rise in glucose Ra relative to glucose Rd as reported with intense aerobic exercise.

Lower cardiorespiratory fitness in children with Type 1 diabetes.

AIMS: The present study aimed to compare cardiorespiratory fitness levels in children with and without Type 1 diabetes. In addition, the relationship between cardiorespiratory fitness and a range of physical and clinical factors was investigated. METHODS: Eighty-eight children with Type 1 diabetes aged 5-14 years completed a submaximal step test of cardiorespiratory fitness. Sixty-two of these children were successfully matched to control subjects without diabetes based on age, sex and anthropometrics for comparison. In addition, the relationship between cardiorespiratory fitness and a range of physical and clinical variables was assessed in the children with diabetes. RESULTS: The heart rate response to exercise was higher in children with Type 1 diabetes, indicating reduced cardiorespiratory fitness levels compared with control subjects. Both gender and glycaemic control (HbA(1c) ) were significantly associated with cardiorespiratory fitness, with female sex and poorer glycaemic control associated with reduced fitness. CONCLUSIONS: Future research should investigate whether the reduced fitness in children with Type 1 diabetes is attributable to lower physical activity levels, or physiological changes resulting from the diabetes pathology itself.

Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data.

AIMS/HYPOTHESIS: We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. METHODS: Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders.Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. RESULTS: Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p=0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p=0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p=0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. CONCLUSIONS/INTERPRETATION: Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.

Glycaemic impact of patient-led use of sensor-guided pump therapy in type 1 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: The objective of this study was to assess the impact of patient-led sensor-guided pump management on glycaemic control, and compare the effect with that of standard insulin pump therapy. METHODS: An open multicentre parallel randomised controlled trial was conducted at five tertiary diabetes centres. Participants aged 13.0-40.0 years with well-controlled type 1 diabetes were randomised 1:1 to either study group for 3 months. Randomisation was carried out using a central computer-generated schedule. Participants in the intervention group used sensor-guided pump management; no instructive guidelines in interpreting real-time data were provided ('patient-led' use). Participants in the control group continued their original insulin pump regimen. Continuous glucose monitoring (CGM) and HbA(1c) level were used to assess outcomes. The primary outcome was the difference in the proportion of time in the target glycaemic range during the 3 month study period (derived from CGM, target range 4-10 mmol/l). Secondary outcomes were difference in HbA(1c), time in hypoglycaemic (< or =3.9 mmol/l) and hyperglycaemic (> or =10.1 mmol/l) ranges and glycaemic variability. RESULTS: Sixty-two participants were recruited and randomised; 5/31 and 2/31 withdrew from intervention and control groups, respectively, leaving 26/31 and 29/31 for the intention-to-treat analyses. When adjusted for baseline values, the mean end-of-study HbA(1c) was 0.43% lower in the intervention group compared with the control group (95% CI 0.19 to 0.75%; p = 0.009). No difference was observed in CGM-derived time in target (measured difference 1.72; 95% CI -5.37 to 8.81), hypoglycaemic (0.54; 95% CI -3.48 to 4.55) or hyperglycaemic (-2.18; 95% CI -10.0 to 5.69) range or in glycaemic variability (-0.29; 95% CI -0.34 to 0.28). Within the intervention group, HbA(1c) was 0.51% lower in participants with sensor use > or =70% compared with participants with sensor use <70% (95% CI -0.98 to -0.04, p = 0.04). Five episodes of device malfunction occurred. CONCLUSIONS/INTERPRETATION: Individuals established on insulin pump therapy can employ sensor-guided pump management to improve glycaemic control. An apparent dose-dependent effect of sensor usage was noted; however, frequent use of this technology (> or =70%) was not universally acceptable. TRIAL REGISTRATION: ACTRN12606000049572