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Aim To determine the impact of physical fitness level on hypoglycaemia risk during exercise in people with Type 1 diabetes. Methods A total of 44 patients [34 adults (aged 22-70 years) and 10 adolescents (aged 12-18 years)] with Type 1 diabetes, treated with insulin pump therapy, underwent a standardized exercise session. Cardiorespiratory fitness (maximum oxygen uptake) was measured and classified, based on established norms for age and sex, into either poor (< 25th percentile) or good fitness level (> 25th percentile). Plasma glucose levels were measured every 10 min, each patient performed physical activity at 60% maximum oxygen uptake either on a treadmill for 1 h or on a bicycle for 30 min. Frequency of hypoglycaemia (plasma glucose < 4 mmol/l) and decline in plasma glucose levels during exercise were assessed. Results In all, 23 patients had a good exercise fitness level. Hypoglycaemic events occurred in 17/23 patients (74.0%) in the good fitness level group compared with 8/21 patients (38.0%) in the poor fitness level group ( P = 0.02). Both groups had similar pre-exercise plasma glucose levels. The plasma glucose values during exercise in the good fitness level group compared with the poor fitness level group were: plasma glucose nadir 3.9 ± 1.6 vs 5.5 ± 2.4 mmol/l ( P = 0.01) and plasma glucose change −4.6 ± 3.4 vs. −2.1 ± 3.1 mmol/l ( P = 0.01). The correlation between the plasma glucose nadir and maximum oxygen uptake was r = −0.38 ( P = 0.01). Conclusions Patients with good fitness level seem to be more prone to hypoglycaemia during exercise. This could be the result of better insulin sensitivity and the fact that they tend to exercise at greater work thresholds. These results are a step toward a better understanding of the association between physical fitness and exercise-induced hypoglycaemia. [ABSTRACT FROM AUTHOR]

Background Few children with obesity who are referred for weight management end up enroled in treatment. Factors enabling enrolment are poorly understood. Our purpose was to explore reasons for and facilitators of enrolment in paediatric weight management from the parental perspective. Methods Semi-structured interviews were conducted with parents of 10- to 17-year-olds who were referred to one of four Canadian weight management clinics and enroled in treatment. Interviews were audio-recorded and transcribed verbatim. Manifest/inductive content analysis was used to analyse the data, which included the frequency with which parents referred to reasons for and facilitators of enrolment. Results In total, 65 parents were interviewed. Most had a child with a BMI ≥95th percentile ( n = 59; 91%), were mothers ( n = 55; 85%) and had completed some post-secondary education ( n = 43; 66%). Reasons for enrolment were related to concerns about the child, recommended care and expected benefits. Most common reasons included weight concern, weight loss expectation, lifestyle improvement, health concern and need for external support. Facilitators concerned the referral initiator, treatment motivation and barrier control. Most common facilitators included the absence of major barriers, parental control over the decision to enrol, referring physicians stressing the need for specialized care and parents' ability to overcome enrolment challenges. Conclusions Healthcare providers might optimize enrolment in paediatric weight management by being proactive in referring families, discussing the advantages of the recommended care to meet treatment expectations and providing support to overcome enrolment barriers. [ABSTRACT FROM AUTHOR]

The purposes of this study were to derive a new method for identifying resilience (i.e. positive adaptation in spite of serious adversity) among young people in care and to determine the percentage of the latter who experienced resilience on selected outcomes, as conceptualized from within the developmental approach of Looking After Children. The participants comprised two samples of young people who were living in out-of-home care (mainly foster care) in the province of Ontario, Canada, 340 aged 10-15 years and 132 aged 5-9 years. Virtually all had experienced severe adversity in their families of origin, such that in most cases the legal custody, care, and control of the young people had been permanently transferred from their parents to a local Children's Aid Society. Corresponding to each in-care sample was a general-population sample of the same age range that served as a normative comparison group and was drawn from the National Longitudinal Survey of Children and Youth (NLSCY). The NLSCY is an ongoing, long-term social-policy study of the development of a nationally representative sample of Canadian children into adolescence and early adulthood. The general-population samples were composed, respectively, of 5539 young people aged 10-15 years and 11 858 children aged 5-9 years. Resilience among the young people in care was operationally defined, on each outcome variable, as average or above-average functioning relative to that of the general-population sample of the same age range. The percentage experiencing resilience was relatively high on the outcomes of health, self-esteem, and pro-social behaviour, moderate on the outcomes of relationship with friends and anxiety and emotional distress, and low on the outcome of academic performance. The implications of the findings are discussed. [ABSTRACT FROM AUTHOR]

Eighty‐seven patients had a bone marrow transplantation (BMT) at our institution between 1980 and 1992. We wished to study the endocrine complications that accompany this procedure as long‐term survival is now much more common. Forty‐three patients were retrospectively available for review and their records were examined for evidence of thyroid, pubertal, and growth complications. Fifteen per cent of the patients showed evidence of thyroid involvement. Pubertal delay or gonadal damage was almost universal in pubertal‐aged girls treated with busulfan/cyclophosphamide. Gonadal involvement was more frequent in girls than in boys (70% vs. 47%). Sixty per cent of children were shorter or grew at a slower rate. Sixty-five per cent of the children presented with one or more endocrine complications. These are the combined effects of different treatment regimens (chemotherapy, radiotherapy, combined therapy). It is essential to know the natural history of these patients in order to offer proper guidance and treatment as survival rates are increasing. [ABSTRACT FROM AUTHOR]

Our study purpose was to determine the prevalence of metabolically healthy obesity (MHO) and examine factors associated with MHO in children with obesity. This cross-sectional study was a secondary, exploratory analysis of data that included 2-17 years old with a body mass index (BMI) ≥85th percentile from the CANadian Pediatric Weight management Registry. Children were classified as having MHO or metabolically unhealthy obesity (MUO) using consensus-based criteria. Those with MHO had normal triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose. Logistic regression was used to examine factors associated with MHO, which included calculating odds ratios (ORs) and 95% confidence intervals (CIs). In total, 945 children were included (mean age: 12.3 years; 51% female). The prevalence of MHO was 31% (n = 297), with lower levels across increasing age categories (2-5 years [n = 18; 43%], 6-11 years [n = 127; 35%], 12-17 years [n = 152; 28%]). Children with MHO were younger, weighed less, and had lower BMI z-scores than their peers with MUO (all p < 0.01). MHO status was positively associated with physical activity (OR: 1.18; 95% CI: 1.01-1.38), skim milk intake (OR: 1.10; 95% CI: 1.01-1.19), and fruit intake (OR: 1.12; 95% CI: 1.01-1.24) and negatively associated with BMI z-score (OR: 0.69; 95% CI: 0.60-0.79), total screen time in hours (OR: 0.79; 96% CI: 0.68-0.92), and intake of fruit flavoured drinks (OR: 0.91; 95% CI: 0.84-0.99). These findings may help guide clinical decision-making regarding obesity management by focusing on children with MUO who are at relatively high cardiometabolic risk., (© 2021 World Obesity Federation.)

Aim: To assess whether a FiASP-and-pramlintide closed-loop system has the potential to replace carbohydrate counting with a simple meal announcement (SMA) strategy (meal priming bolus without carbohydrate counting) without degrading glycaemic control compared with a FiASP closed-loop system., Materials and Methods: We conducted a 24-hour feasibility study comparing a FiASP system with full carbohydrate counting (FCC) with a FiASP-and-pramlintide system with SMA. We conducted a subsequent 12-day outpatient pilot study comparing a FiASP-and-placebo system with FCC, a FiASP-and-pramlintide system with SMA, and a FiASP-and-placebo system with SMA. Basal-bolus FiASP-and-pramlintide were delivered at a fixed ratio (1 U:10 μg). Glycaemic outcomes were measured, surveys evaluated gastrointestinal symptoms and diabetes distress, and participant interviews helped establish a preliminary coding framework to assess user experience., Results: Seven participants were included in the feasibility analysis. Time spent in 3.9-10 mmol/L was similar between both interventions (81%-84%). Four participants were included in the pilot analysis. Time spent in 3.9-10 mmol/L was similar between the FiASP-and-placebo with FCC and FiASP-and-pramlintide with SMA interventions (70%), but was lower in the FiASP-and-placebo with SMA intervention (60%). Time less than 3.9 mmol/L and gastrointestinal symptoms were similar across all interventions. Emotional distress was moderate at baseline, after the FiASP-and-placebo with FCC and SMA interventions, and fell after the FiASP-and-pramlintide with SMA intervention. SMA reportedly afforded participants flexibility and reduced mealtime concerns., Conclusions: The FiASP-and-pramlintide system has the potential to substitute carbohydrate counting with SMA without degrading glucose control., (© 2021 John Wiley & Sons Ltd.)

Conventional bolus calculators apply negative prandial corrections when premeal glucose levels are low. However, no study has evaluated the need for this negative correction with closed-loop systems. We analysed data retrospectively from a cohort study evaluating a closed-loop artificial pancreas system conducted in a diabetes camp over a period of 11 days. Meal boluses with negative correction (n = 98) of 47 participants aged 8 to 22 years were examined. If there was no insulin-on-board from previous boluses at mealtime, the postprandial hyperglycaemia rate increased with increased duration of insulin suspension (P = .03), with odds ratios being exaggerated by 17% per 10 minutes of suspension. However, if there was insulin-on-board from previous boluses, the hyperglycaemia rate did not change with increased duration of insulin suspension (P = .24). When there was no insulin-on-board, the rate of hyperglycaemia after meals preceded by no suspension was 21% (3/14), compared with 52% (12/23) and 64% (9/14) after meals preceded by suspensions of ≥50 and ≥70 minutes, respectively. Meal size did not influence these results. We conclude that, in the absence of insulin-on-board, negative prandial corrections may not be necessary following long insulin suspensions., (© 2020 John Wiley & Sons Ltd.)

Although prolonged engagement in paediatric weight management (PWM) is associated with positive treatment outcomes, little is currently known about enablers of long-term programme attendance. The purpose of our study was to explore families' reasons for and facilitators of their continued attendance at health services for PWM. Semi-structured, individual interviews were conducted with parents of children (10-17 year old; body mass index ≥85th percentile) who completed the active phase of treatment in one of four Canadian multidisciplinary clinics for PWM. Interview data were recorded digitally, transcribed verbatim and analysed thematically. Parents' (n = 40) reasons for continued clinic attendance included ongoing concerns (eg, parental concern about their child's health), actual and expected benefits from treatment (eg, lifestyle improvements) and perceived quality of care (eg, structured, comprehensive, tailored health services). Several logistical and motivational factors contributed to continued attendance, including flexible work schedules, flexible appointment times, financial resources and children's motivation for treatment. Helping families address treatment barriers and ensuring that weight management services meet families' treatment expectations are promising strategies to enhance retention in PWM to optimize health outcomes., (© 2019 World Obesity Federation.)

For patients with type 1 diabetes, closed-loop delivery systems (CLS) combining an insulin pump, a glucose sensor and a dosing algorithm allowing a dynamic hormonal infusion have been shown to improve glucose control when compared with conventional therapy. Yet, reducing glucose excursion and simplification of prandial insulin doses remain a challenge. The objective of this literature review is to examine current meal-time strategies in the context of automated delivery systems in adults and children with type 1 diabetes. Current challenges and considerations for post-meal glucose control will also be discussed. Despite promising results with meal detection, the fully automated CLS has yet failed to provide comparable glucose control to CLS with carbohydrate-matched bolus in the post-meal period. The latter strategy has been efficient in controlling post-meal glucose using different algorithms and in various settings, but at the cost of a meal carbohydrate counting burden for patients. Further improvements in meal detection algorithms or simplified meal-priming boluses may represent interesting avenues. The greatest challenges remain in regards to the pharmacokinetic and dynamic profiles of available rapid insulins as well as sensor accuracy and lag-time. New and upcoming faster acting insulins could provide important benefits. Multi-hormone CLS (eg, dual-hormone combining insulin with glucagon or pramlintide) and adjunctive therapy (eg, GLP-1 and SGLT2 inhibitors) also represent promising options. Meal glucose control with the artificial pancreas remains an important challenge for which the optimal strategy is still to be determined., (© 2017 John Wiley & Sons Ltd.)

GH plays an essential role in the growing child by binding to the growth hormone receptor (GHR) on target cells and regulating multiple growth promoting and metabolic effects. Mutations in the GHR gene coding regions result in GH insensitivity (dwarfism) due to a dysfunctional receptor protein. However, children with idiopathic short stature (ISS) show growth impairment without GH or GHR defects. We hypothesized that decreased expression of the GHR gene may be involved. To test this, we investigated whether common genetic variants (microsatellites, SNPs) in regulatory regions of the GHR gene region were associated with the ISS phenotype. Genotyping of a GT-repeat microsatellite in the GHR 5'UTR in a Montreal ISS cohort (n = 37 ISS, n = 105 controls) revealed that the incidence of the long/short (L/S) genotype was 3.3× higher in ISS children than controls (P = 0.04, OR = 3.85). In an Italian replication cohort (n = 143 ISS, n = 282 controls), the medium/short (M/S) genotype was 1.9× more frequent in the male ISS than controls (P = 0.017, OR = 2.26). In both ISS cohorts, logistic regression analysis of 27 SNPs showed an association of ISS with rs4292454, while haplotype analysis revealed specific risk haplotypes in the 3' haploblocks. In contrast, there were no differences in GT genotype frequencies in a cohort of short stature (SS) adults versus controls (CARTaGENE: n = 168 SS, n = 207 controls) and the risk haplotype in the SS cohort was located in the most 5' haploblock. These data suggest that the variants identified are potentially genetic markers specifically associated with the ISS phenotype., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Aims: To assess whether the dual-hormone (insulin and glucagon) artificial pancreas reduces hypoglycaemia compared to the single-hormone (insulin alone) artificial pancreas in outpatient settings during the day and night., Material and Methods: In a randomized, three-way, crossover trial we compared the dual-hormone artificial pancreas, the single-hormone artificial pancreas and sensor-augmented pump therapy (control) in 23 adults with type 1 diabetes. Each intervention was applied from 8 AM Day 1 to 8 PM Day 3 (60 hours) in outpatient free-living conditions. The primary outcome was time spent with sensor glucose levels below 4.0 mmol/L. A P value of less than .017 was regarded as significant., Results: The median difference between the dual-hormone system and the single-hormone system was -2.3% (P = .072) for time spent below 4.0 mmol/L, -1.3% (P = .017) for time below 3.5 mmol/L, and -0.7% (P = .031) for time below 3.3 mmol/L. Both systems reduced (P < .017) hypoglycaemia below 4.0, 3.5 and 3.3 mmol/L compared to control therapy, but reductions were larger with the dual-hormone system than with the single-hormone system (medians -4.0% vs -3.4% for 4.0 mmol/L; -2.7% vs -2.2% for 3.5 mmol/L; and -2.2% vs -1.2% for 3.3 mmol/L). There were 34 hypoglycaemic events (<3.0 mmol/L for 20 minutes) with control therapy, 14 with the single-hormone system and 6 with the dual-hormone system. These differences in hypoglycaemia were observed while mean glucose level was low and comparable in all interventions (P = NS)., Conclusions: The dual-hormone artificial pancreas had the lowest risk of hypoglycaemia, but the differences were not statistically significant. Larger studies are needed., (© 2017 John Wiley & Sons Ltd.)

The role of glucagon in the pathophysiology of diabetes has long been recognized, although its approved clinical use has so far been limited to the emergency treatment of severe hypoglycaemia. A novel use of glucagon as intermittent mini-boluses is proposed in the dual-hormone version (insulin and glucagon) of the external artificial pancreas. Short-term studies suggest that the incorporation of glucagon into artificial pancreas systems has the potential to further decrease hypoglycaemic risk and improve overall glucose control; however, the potential long-term safety and benefits also need to be investigated given the recognized systemic effects of glucagon. In the present report, we review the available animal and human data on the physiological functions of glucagon, as well as its pharmacological use, according to dosing and duration (acute and chronic). Along with its main role in hepatic glucose metabolism, glucagon affects the cardiovascular, renal, pulmonary and gastrointestinal systems. It has a potential role in weight reduction through its central satiety function and its role in increasing energy expenditure. Most of the pharmacological studies investigating the effects of glucagon have used doses exceeding 1 mg, in contrast to the mini-boluses used in the artificial pancreas. The available data are reassuring but comprehensive human studies using small but chronic glucagon doses that are close to the physiological ranges are lacking. We propose a list of variables that could be monitored during long-term trials of the artificial pancreas. Such trials should address the questions about the risk-benefit ratio of chronic glucagon use., (© 2016 John Wiley & Sons Ltd.)

Background: In a previously published randomized controlled trial (Brown et al. Alcohol Clin Exp Res 2010; 34, 292-301), our research team showed that a 30-minute brief motivational interviewing (BMI) session was more effective in reducing percentages of risky drinking days in drunk driving recidivists than a control information-advice intervention at 12-month follow-up. In this sequel to the initial study, 2 main hypotheses were tested: (i) exposure to BMI increases the time to further arrests and crashes compared with exposure to the control intervention (CTL) and (ii) characteristics, such as age, moderate the benefit of BMI., Methods: A sample of 180 community-recruited recidivists who had drinking problems participated in the study. Participants gave access to their provincial driving records at baseline and were followed up for a mean of 1,684.5 days (SD = 155.7) after randomization to a 30-minute BMI or CTL session. Measured outcomes were driving arrests followed by convictions including driving while impaired (DWI), speeding, or other moving violations as well as crashes. Age, readiness to change alcohol consumption, alcohol misuse severity, and number of previous DWI convictions were included as potential moderators of the effect of the interventions., Results: For arrests, Cox proportional hazards modeling revealed no significant differences between the BMI and the CTL group. When analyses were adjusted to age tertile categories, a significant effect of BMI in the youngest age tertile (<43 years old) emerged. For crashes, no between-group differences were detected., Conclusions: BMI was better at delaying DWI and other dangerous traffic violations in at-risk younger drivers compared with a CTL similar to that provided in many remedial programs. BMI may be useful as an opportunistic intervention for DWI recidivism prevention in settings such as DWI courts. Treatment effectiveness studies are needed to ascertain how the present findings generalize to the real-world conditions of mandated relicensing programs., (Copyright © 2013 by the Research Society on Alcoholism.)

Background: Driving while impaired (DWI) recidivists with unresolved alcohol use problems pose an ongoing risk for traffic safety. Following conviction, many do not participate in mandated alcohol evaluation and intervention programs, or continue to drink problematically after being relicensed. This study investigated if, in DWI recidivists with alcohol problems and not currently involved in DWI intervention, Brief Motivational Interviewing (BMI) produced greater reductions in risky drinking at 6- and 12-month follow-up compared to an information-advice control condition. Additional analyses explored whether BMI was associated with greater readiness to change, subsequent substance abuse treatment service utilization, and satisfaction compared to the control condition., Methods: Male and female recidivists with drinking problems and not currently engaged in DWI intervention were recruited, evaluated, and then randomly assigned to receive 1 of 2 manualized interventions: 30-minute BMI session or information-advice. Participants, interviewers, researchers, and statisticians were blind to assignment. Outcomes were changed in: percent of risky drinking days (i.e., > or =3 standard drinks/d for males; > or =2 for females) in the previous 6 months derived from the Timeline Followback, biomarkers of alcohol abuse (GGT, AST, ALT, MCV) by blood assay, and alcohol abuse-related behaviors using the MMPI-Mac scale. Data from the Readiness to Change Questionnaire, a substance abuse service utilization questionnaire, and the Client Satisfaction Scale were also collected., Results: Analyses revealed significant declines in risky drinking with both interventions. BMI (n = 92) resulted in a 25% reduction in risky drinking days at 12-month follow-up, which compared to the control intervention (n = 92) represented a significant decline from 6-month levels. Exposure to BMI also produced significantly greater improvement at 6-month follow-up in a biomarker of alcohol abuse and a behavioral measure related to recidivism risk. Exploration of readiness to change, substance abuse service utilization, and satisfaction with intervention indicated a perception of BMI being more useful in coping with problems., Conclusions: Brief MI approaches warrant further implementation and effectiveness research as an opportunistic DWI intervention strategy to reduce risks associated with alcohol use outside of clinical and DWI relicensing settings.

We report on three patients with Costello syndrome and isolated growth hormone (GH) deficiency treated with biosynthetic GH. To our knowledge, these are the only patients with Costello syndrome who have been successfully treated for GH deficiency. We review the pathophysiology of Costello syndrome and highlight the recent recommendations of tumor screening and cardiac surveillance in this population, of particular relevance to those receiving GH therapy., (Copyright 2004 Wiley-Liss, Inc.)

Background: An earlier latent class analysis (LCA) of the symptoms of antisocial personality disorder in alcohol-dependent subjects enrolled in the Montreal sample of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence suggested a three-class qualitative solution. The present analysis of a larger, international WHO/ISBRA sample provides evidence of a four-class solution with expanded symptomatic differentiation., Methods: An unrestricted LCA of 15 antisocial behaviors expressed after 15 years of age was performed in 465 males with DSM-IV diagnosis of alcohol dependence, from the Montreal center (n = 120, overlapping the previous LCA), Helsinki (n = 80), São Paolo (n = 145), Sapporo (n = 22), and Sydney (n = 98); subjects were of various races, were ascertained from various sources, and showed a wide range of social adjustment., Results: Four latent classes that appeared to differ qualitatively were identified. For descriptive purposes, the classes are termed socially adjusted adults (SAA, n = 197), antisocial work-adjusted adults (AWAA, n = 126), antisocial work-maladjusted adults (AWMA, n = 120), and antisocial aggressive adults (AAA, n = 23). The AAA class had the earliest age of onset for alcohol dependence, which decreased across classes. Proportion of alcohol-dependent first-degree relatives was low in the SAA class (13.6%), moderate in the AWAA and the AWMA classes (20.8% and 18.7% respectively), and high in the AAA class (33.3%)., Conclusions: It is unknown if and to what extent racial, cultural, and ascertainment heterogeneity between collaborating centers might have influenced these analyses. The results presented here show qualitative differences among antisocial alcohol-dependent individuals in job adjustment and aggressive behavior, but only the latter distinction was relevant to familial alcohol dependence. Moreover, both the aggressive class and socially adjusted class differed in familial loading for alcohol dependence from the remaining two antisocial classes. These data provide improved empirical support for qualitative differentiation of aggressive from nonaggressive antisocial alcohol-dependent individuals and might also have nosological implications for antisocial personality disorder.