Reproducibility of plasma glucose responses to moderate-intensity exercise in individuals with type 1 diabetes.

AIM: To examine the within-person variability in plasma glucose responses to moderate-intensity morning exercise in young individuals with type 1 diabetes after overnight fasting and under basal insulin conditions. METHODS: In this pilot study, eight participants completed 40 min of moderate-intensity exercise at 60% V̇O2 peak on three separate days. The within-person standard deviation (SDw) in plasma glucose response was analysed both during and 1 h after exercise using the two visits per participant most closely matched by pre-exercise plasma glucose level. RESULTS: When the two closest matched visits per individual were included for analysis, mean (±SD) change in plasma glucose level was -1.8 ± 1.1 mmoL/L during exercise and -0.6 ± 1.0 mmoL/L during recovery, with the SDw of these changes being 0.5 mmol (95% CI 0.2, 0.8) during exercise and 0.8 mmoL/L (95% CI 0.4, 1.3) during recovery. The median intra-individual difference in plasma glucose level change was 0.3 mmoL/L [IQR 0.1, 0.7] during exercise and 0.8 mmoL/L [IQR 0.4, 1.0] during recovery. CONCLUSION: Within-person plasma glucose responses to moderate-intensity exercise may be reproducible under fasting and basal insulin conditions and similar pre-exercise plasma glucose levels. This finding may assist the design of future studies investigating both the reproducibility of glycaemic responses to exercise and blood glucose management for individuals with type 1 diabetes.

Physical Activity Management for Youth With Type 1 Diabetes: Supporting Active and Inactive Children.

Regular physical activity and exercise are important for youth and essential components of a healthy lifestyle. For youth with type 1 diabetes, regular physical activity can promote cardiovascular fitness, bone health, insulin sensitivity, and glucose management. However, the number of youth with type 1 diabetes who regularly meet minimum physical activity guidelines is low, and many encounter barriers to regular physical activity. Additionally, some health care professionals (HCPs) may be unsure how to approach the topic of exercise with youth and families in a busy clinic setting. This article provides an overview of current physical activity research in youth with type 1 diabetes, a basic description of exercise physiology in type 1 diabetes, and practical strategies for HCPs to conduct effective and individualized exercise consultations for youth with type 1 diabetes.

Questionnaires Measuring Physical Activity in Clinical Pediatric Populations: A Systematic Review.

PURPOSE: Regular physical activity (PA) is a cornerstone therapy for many childhood chronic health conditions, and questionnaires offer a simple method for monitoring PA and identifying children who do not meet clinical practice guidelines. The purpose of this systematic review is to determine which questionnaires are most efficacious for assessing PA in children with chronic health conditions. METHODS: Systematic literature searches were conducted through ProQuest, MEDLINE, Scopus, and SPORTDiscus from January 2010 to August 2020 to identify studies that measured PA with a validated questionnaire in children and adolescents aged 3-18 years old with chronic health conditions. In eligible studies, the validity and reliability of questionnaires were identified, and the modified COnsensus-based Standards for the selection of health status Measurement INstruments checklist and Grading of Recommendations, Assessment, Development, and Evaluations were used to assess the quality and strength of evidence and risk of bias. RESULTS: Four thousand four hundred and seventy-eight references were extracted, and 10 articles were included for review. From 10 eligible studies, 6 questionnaires were identified, none of which adequately measure PA in clinical pediatric populations. CONCLUSION: Questionnaires to adequately measure PA in children with chronic conditions are lacking. This compromises the identification of those who do not meet PA guidelines, limiting the opportunity to identify and address factors contributing to low PA levels.

Transient pseudohypoaldosteronism in infancy secondary to urinary tract infection.

AIM: Hyponatraemia with hyperkalaemia in infancy is a typical presentation of congenital adrenal hyperplasia. In the presence of pyelonephritis, the same biochemical picture can occur with transient type 1 pseudohypoaldosteronism (PHA-1) also termed type 4 renal tubular acidosis. Recognition of PHA-1 enables appropriate management thus avoiding unnecessary investigations and treatment. To improve awareness of this condition, we present a case series to highlight the clinical and biochemical features of PHA-1. METHODS: A retrospective chart review of patients diagnosed with transient PHA-1 at a tertiary children's hospital in Western Australia was conducted. RESULTS: Five male infants (32 days to 6 months) with transient PHA-1 were identified. Failure to thrive was the most common symptom with hyponatraemia on presentation. Two infants had antenatally diagnosed bilateral hydronephrosis and urinary tract infection (UTI) on admission. Two infants were treated for congenital adrenal hyperplasia and received hydrocortisone. All infants had UTI and required parenteral antibiotics. The condition was transient and hyponatraemia corrected by day 4 in all infants. There was no correlation between plasma sodium and aldosterone levels. The severity of PHA-1 was independent of the underlying renal anomaly. Four infants had hydronephrosis and vesicoureteric reflux. Surgical intervention was required in two infants. CONCLUSIONS: PHA-1 may be precipitated by UTI or urinary tract anomalies in early infancy. Urine analysis should be performed in infants with hyponatraemia. Diagnosis of PHA-1 facilitates appropriate renal investigations to reduce long-term morbidity.

Developing type 1 diabetes resources: a qualitative study to identify resources needed to upskill and support community sport coaches.

Introduction: Community sport coaches in Western Australia lack an understanding, the confidence, and knowledge in supporting young people with Type 1 diabetes (T1D). This study aims to identify what T1D educational resources are required to upskill coaches in Western Australia. Methods: Semi-structured online interviews were conducted with i) young people living with T1D, ii) parents of young people living with T1D and iii) community sport coaches. The questions explored i) past experiences of T1D management in community sport ii) the T1D information coaches should be expected to know about and iii) the format of resources to be developed. Thematic analysis of interview transcripts was performed, and the themes identified were used to guide resource development. Results: Thirty-two participants (16 young people living with T1D, 8 parents, 8 coaches) were interviewed. From the interviews, young people wanted coaches to have a better understanding of what T1D is and the effect it has on their sporting performance, parents wanted a resource that explains T1D to coaches, and sports coaches wanted to know the actions to best support a player living with T1D. All groups identified that signs and symptoms of hypoglycaemia and hyperglycaemia needed to be a key component of the resource. Sports coaches wanted a resource that is simple, quick to read and available in a variety of different formats. Conclusion: The interviews resulted in valuable information gained from all groups and have reinforced the need for the development of specific resources to increase community knowledge and provide support for players with T1D, parents and sport coaches.

Ethnic and gender differences in rates of congenital adrenal hyperplasia in Western Australia over a 21 year period.

AIM: To evaluate the incidence, sex distribution, ethnicity, age at diagnosis, clinical presentation and morbidity of all childhood-onset congenital adrenal hyperplasia (CAH) cases in Western Australia (WA) between 1990 and 2010, a state where newborn screening for CAH is not in place. METHODS: The total number of all known CAH cases was identified. Case files were reviewed retrospectively to determine clinical details. Classical CAH (C-CAH) was defined as patients presenting before 6 months of age and non-classical (NC-CAH) as presenting after 6 months. RESULTS: Of the 41 CAH cases (26 female) born in WA, 5(12.2%) were of Aboriginal ethnicity. CAH was due to 21-hydroxylase deficiency in 40 cases. Of those with 21-hydroxylase deficiency, 37 were C-CAH (25 female) and 3 NC-CAH (all male). The incidence of C-CAH in WA was estimated to be 0.67 per 10, 000 live births (1:14, 869). The incidence rate ratio of Aboriginal compared with non-Aboriginal C-CAH was 2.45 (95% confidence interval 0.96-6.29). The mean age of diagnosis of C-CAH cases was lower in females (8.9 ± 2.5 days) compared to males (23.4 ± 9.8 days). Among these males, 72.7% presented initially with adrenal crisis. CONCLUSION: The estimated incidence of classical CAH is similar to composite worldwide data. The increased female-to-male ratio is not in keeping with the expected sex distribution seen in a recessively inherited disease. The delayed diagnosis in males, with a significant proportion presenting with adrenal crisis, could be avoided with newborn screening. The higher rate of CAH in patients with Aboriginal ethnicity is a novel observation.

Antidiuretic hormone and the activation of glucose production during high intensity aerobic exercise.

OBJECTIVE: This study aimed to investigate the role that antidiuretic hormone (ADH) may play in the activation of glucose production during high intensity aerobic exercise. MATERIALS/METHODS: This study was part of larger study based on a repeated measures cross-over study design and involved ten adult participants who exercised in the morning at 80 % V̇O2peak for up to 40 min or until exhaustion. During and after exercise, the participants were subjected to a morning euglycaemic/euinsulinaemic clamp while [6,6-2H2]glucose was infused and blood sampled to measure the endogenous rate of glucose appearance (Ra) and ADH levels. RESULTS: The levels of plasma ADH were 1.8 ± 0.2 pmol/L (mean ± SEM) at rest and increased to 10.5 ± 2.1 pmol/L at the end of exercise (mean ± SEM), which lasted 8.5-40 min. In response to exercise, glucose Ra also rose significantly (p < 0.05), but there was no significant association between changes in ADH levels and glucose Ra (r = 0.49; p = 0.150). CONCLUSIONS: Although the significant increase in glucose Ra and ADH levels during high intensity aerobic exercise suggest for the first time that these processes may be causally related, there was no significant association between these variables, maybe because of the small sample size and varying exercise durations. Hence, the importance of the causal role that ADH may play in the exercise-mediated activation of hepatic glucose production warrants further in depth investigations.

Effect of Exercise Intensity on Exogenous Glucose Requirements to Maintain Stable Glycemia At High Insulin Levels in Type 1 Diabetes.

CONTEXT: Under basal insulin levels, there is an inverted U relationship between exercise intensity and exogenous glucose requirements to maintain stable blood glucose levels in type 1 diabetes (T1D), with no glucose required for intense exercise (80% V̇O2 peak), implying that high-intensity exercise is not conducive to hypoglycemia. OBJECTIVE: This work aimed to test the hypothesis that a similar inverted U relationship exists under hyperinsulinemic conditions, with high-intensity aerobic exercise not being conducive to hypoglycemia. METHODS: Nine young adults with T1D (mean ±â€…SD age, 22.6 ±â€…4.7 years; glycated hemoglobin, 61 ±â€…14 mmol/mol; body mass index, 24.0 ±â€…3.3 kg/m2, V̇O2 peak, 36.6 ±â€…8.0 mL·kg-1 min-1) underwent a hyperinsulinemic-euglycemic clamp to maintain stable glycemia (5-6 mmol·L-1), and exercised for 40 minutes at 4 intensities (35%, 50%, 65%, and 80% V̇O2peak) on separate days following a randomized counterbalanced study design. MAIN OUTCOME MEASURES: Glucose infusion rates (GIR) and glucoregulatory hormones levels were measured. RESULTS: The GIR (±â€…SEM) to maintain euglycemia was 4.4 ±â€…0.4 mg·kg-1 min-1 prior to exercise, and increased significantly by 1.8 ±â€…0.4, 3.0 ±â€…0.4, 4.2 ±â€…0.7, and 3.5 ±â€…0.7 mg·kg-1 min-1 during exercise at 35%, 50%, 65%, and 80% V̇O2 peak, respectively, with no significant differences between the 2 highest exercise intensities (P > .05), despite differences in catecholamine levels (P < .05). During the 2-hour period after exercise at 65% and 80% V̇O2 peak, GIRs did not differ from those during exercise (P > .05). CONCLUSIONS: Under hyperinsulinemic conditions, the exogenous glucose requirements to maintain stable glycemia during and after exercise increase with exercise intensity then plateau with exercise performed at above moderate intensity ( > 65% V̇O2 peak). High-intensity exercise confers no protection against hypoglycemia.

A Novel Mobile Health App to Educate and Empower Young People With Type 1 Diabetes to Exercise Safely: Prospective Single-Arm Mixed Methods Pilot Study.

BACKGROUND: Empowering young people with type 1 diabetes (T1D) to manage their blood glucose levels during exercise is a complex challenge faced by health care professionals due to the unpredictable nature of exercise and its effect on blood glucose levels. Mobile health (mHealth) apps would be useful as a decision-support aid to effectively contextualize a blood glucose result and take appropriate action to optimize glucose levels during and after exercise. A novel mHealth app acT1ve was recently developed, based on expert consensus exercise guidelines, to provide real-time support for young people with T1D during exercise. OBJECTIVE: Our aim was to pilot acT1ve in a free-living setting to assess its acceptability and functionality, and gather feedback on the user experience before testing it in a larger clinical trial. METHODS: A prospective single-arm mixed method design was used. Ten participants with T1D (mean age 17.7 years, SD 4.2 years; mean HbA1c, 54 mmol/mol, SD 5.5 mmol/mol [7.1%, SD 0.5%]) had acT1ve installed on their phones, and were asked to use the app to guide their exercise management for 6 weeks. At the end of 6 weeks, participants completed both a semistructured interview and the user Mobile Application Rating Scale (uMARS). All semistructured interviews were transcribed. Thematic analysis was conducted whereby interview transcripts were independently analyzed by 2 researchers to uncover important and relevant themes. The uMARS was scored for 4 quality subscales (engagement, functionality, esthetics, and information), and a total quality score was obtained from the weighted average of the 4 subscales. Scores for the 4 objective subscales were determined by the mean score of each of its individual questions. The perceived impact and subjective quality of acT1ve for each participant were calculated by averaging the scores of their related questions, but were not considered in the total quality score. All scores have a maximal possible value of 5, and they are presented as medians, IQRs, and ranges. RESULTS: The main themes arising from the interview analysis were "increased knowledge," "increased confidence to exercise," and "suitability" for people who were less engaged in exercise. The uMARS scores for acT1ve were high (out of 5) for its total quality (median 4.3, IQR 4.2-4.6), engagement (median 3.9, IQR 3.6-4.2), functionality (median 4.8, IQR 4.5-4.8), information (median 4.6, IQR 4.5-4.8), esthetics (median 4.3, IQR 4.0-4.7), subjective quality (median 4.0, IQR 3.8-4.2), and perceived impact (median 4.3, IQR 3.6-4.5). CONCLUSIONS: The acT1ve app is functional and acceptable, with a high user satisfaction. The efficacy and safety of this app will be tested in a randomized controlled trial in the next phase of this study. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12619001414101; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378373.

X-linked Congenital Adrenal Hypoplasia with a Novel NR0B1/DAX Gene Mutation.

BACKGROUND: The etiology of primary adrenal insufficiency has implications for further management of the condition. CASE CHARACTERISTICS: A 5-year-old boy presented in adrenal crisis with glucocorticoid and mineralocorticoid deficiency. OBSERVATION: Investigations confirmed primary adrenal insufficiency and ruled out the common etiologies. Genetic testing identified a novel NR0B1/DAX gene mutation. MESSAGE: A genetic diagnosis in children with primary adrenal insufficiency is useful to provide genetic counselling.

Effect of Exercise Intensity on Glucose Requirements to Maintain Euglycemia During Exercise in Type 1 Diabetes.

CONTEXT: No recommendations exist to inform the carbohydrate amount required to prevent hypoglycemia associated with exercise of different intensities in individuals with type 1 diabetes (T1D). OBJECTIVE: The relationship between exercise intensity and carbohydrate requirements to maintain stable euglycemia in individuals with T1D remains to be determined. It was predicted that an "inverted-U" relationship exists between exercise intensity and the amount of glucose required to prevent hypoglycemia during exercise at basal insulinemia. Our objective was to investigate this relationship and elucidate the underlying glucoregulatory mechanisms. DESIGN, PARTICIPANTS, AND INTERVENTION: We subjected nine individuals (mean ± SD age, 21.5 ± 4.0 years; duration of disease, 11.4 ± 6.4 years; glycated hemoglobin, 7.9 ± 0.8% [60 mmol/mol]; body mass index, 25.4 ± 5.5 kg/m(2); VO2peak, 34.8 ± 5.1 mL·kg(-1)·min(-1); and lactate threshold, 59.9 ± 5.9% VO2peak) with T1D to a euglycemic clamp, whereby euglycemia was maintained by infusing basal insulin rates with concomitant infusion of [6,6-(2)H2]glucose for determining glucose kinetics. Glucose was infused to maintain euglycemia during and for 2 hours after exercise of different intensities (35, 50, 65, and 80% VO2peak). MAIN OUTCOME MEASURES: The glucose infusion rate (GIR), levels of glucoregulatory hormones, and rates of endogenous glucose appearance and disappearance were compared between conditions. RESULTS: The mean GIR to maintain euglycemia during exercise increased with intensity up to 50% (4.0 ± 1.6 g/h; P < .05) and 65% (4.1 ± 1.7 g/h), but no glucose was required at 80% VO2peak. Glucose rate of appearance and disappearance increased with intensity and, together with plasma catecholamines, reached higher levels at 80% VO2peak. CONCLUSION: Our findings support the predicted inverted-U relationship between exercise intensity and glucose requirement. However, the relationship between iv and oral glucose requirements needs to be investigated to translate these GIR data to clinical practice.

Efficacy and safety of sirolimus in a neonate with persistent hypoglycaemia following near-total pancreatectomy for hyperinsulinaemic hypoglycaemia.

Hyperinsulinaemic hypoglycaemia (HH) is characterised by inappropriate insulin secretion and is the most common cause for persistent neonatal hypoglycaemia. The only treatment available for medically unresponsive hypoglycaemia is a near-total pancreatectomy. A neonate with severe HH, due to a homozygous ABCC8 mutation, was not responsive to treatment with maximal doses of diazoxide and subcutaneous daily octreotide, and underwent a near-total pancreatectomy; however, hypoglycaemia persisted. Introduction of sirolimus, an mTOR (mammalian target of rapamycin) inhibitor, obviated the requirement for glucose infusion. Euglycaemia was achieved with no significant adverse events from the drug. Sirolimus therapy was ceased at 13 months of age. No episodes of persistent hypoglycaemia were observed after cessation of sirolimus. This report demonstrates the successful use of sirolimus for persistent hypoglycaemia in the critically ill infant post pancreatectomy. Sirolimus could be considered in patients with severe HH not responsive to conventional medical and surgical therapy. However, the long-term efficacy and safety with this immunosuppressive drug in very young patients are not assured.

NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients.

Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea is caused by thyroid transcription factor 1 (NKX2-1/TTF1) mutations. We report the clinical and molecular characteristics of four cases presenting with primary hypothyroidism, respiratory distress, and neurological disorder. Two of the four patients presenting with the triad of BLTS had NKX2-1 mutations, and one of these NKX2-1 [c.890_896del (p.Ala327Glyfs*52)] is a novel variant. The third patient without any identified NKX2-1 mutations was a carrier of mitochondrial mutation; this raises the possibility of mitochondrial mutations contributing to thyroid dysgenesis. Although rare, the triad of congenital hypothyroidism, neurological, and respiratory signs is highly suggestive of NKX2-1 anomalies. Screening for NKX2-1 mutations in patients with thyroid, lung, and neurological abnormalities will enable a unifying diagnosis and genetic counseling for the affected families. In addition, identification of an NKX2-1 defect would be helpful in allaying the concerns about inadequate thyroxine supplementation as the cause of neurological defects observed in some children with congenital hypothyroidism.