Estimating glomerular filtration rate in youth with obesity and type 2 diabetes: the iCARE study equation.

BACKGROUND: The validity of pediatric estimated glomerular filtration rate equations (eGFRs) in early stages of CKD including hyperfiltration is unknown. The purpose of this study was to develop an eGFR equation for adolescents with obesity and type 2 diabetes (T2D). METHODS: eGFRs were developed from iohexol-derived GFRs (iGFRs) in 26 overweight/obese (BMI > 85th percentile) youth and 100 with T2D from the iCARE (Improving renal Complications in Adolescents with T2D through REsearch) cohort. Twenty percent of the cohort was withheld as a validation dataset. Linear regression analyses were used to develop the best formula based on body size, sex, creatinine, urea, ± cystatin C. Comparable validity of commonly used eGFR equations was assessed. RESULTS: Mean age 15.4 + 2.4 years, BMI Z-score 2.5 + 1.2, 61% female, and mean iGFR 129.0 + 27.7 ml/min/ 1.73 m2. The best adjusted eGFR formula (ml/min/1.73 m2) was 50.7 × BSA0.816 × (height (cm)/creatinine)0.405 × 0.8994 if sex = female | 1 otherwise. It resulted in 53.8% of eGFRs within 10% of measured iGFR and 96.2% within 30%. Bland-Altman 95% limits of agreement in the external dataset were - 37.6 to 45.5 ml/min/1.73m2 (bias = 3.96), and the correlation was 0.62. This equation performed better than all previously published creatinine-based eGFRs. cystatin C did not significantly improve results; however, some other cystatin C formulas also performed well. CONCLUSIONS: The iCARE equation provides a more accurate creatinine-based eGFR in obese youth with and without T2D. Further studies are warranted to evaluate within-subject variability and applicability to lower GFRs and other populations.

Early-life origins of disparities in chronic diseases among Indigenous youth: pathways to recovering health disparities from intergenerational trauma.

Indigenous women and children experience some of the most profound health disparities globally. These disparities are grounded in historical and contemporary trauma secondary to colonial atrocities perpetuated by settler society. The health disparities that exist for chronic diseases may have their origins in early-life exposures that Indigenous women and children face. Mechanistically, there is evidence that these adverse exposures epigenetically modify genes associated with cardiometabolic disease risk. Interventions designed to support a resilient pregnancy and first 1000 days of life should abrogate disparities in early-life socioeconomic status. Breastfeeding, prenatal care and early child education are key targets for governments and health care providers to start addressing current health disparities in cardiometabolic diseases among Indigenous youth. Programmes grounded in cultural safety and co-developed with communities have successfully reduced health disparities. More works of this kind are needed to reduce inequities in cardiometabolic diseases among Indigenous women and children worldwide.

Intensive gestational glycemic management and childhood obesity: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Hyperglycemia in pregnancy is associated with increased risk of offspring childhood obesity. Treatment reduces macrosomia; however, it is unclear if this effect translates into a reduced risk of childhood obesity. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy and safety of intensive glycemic management in pregnancy in preventing childhood obesity. METHODS: We searched MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov up to February 2016 and conference abstracts from 2010 to 2015. Two reviewers independently identified randomized controlled trials evaluating intensive glycemic management interventions for hyperglycemia in pregnancy and included four of the 383 citations initially identified. Two reviewers independently extracted study data and evaluated internal validity of the studies using the Cochrane Collaboration's Risk of Bias tool. Data were pooled using random-effects models. Statistical heterogeneity was quantified using the I2 test. The primary outcome was age- and sex-adjusted childhood obesity. Secondary outcomes included childhood weight and waist circumference and maternal hypoglycemia during the trial (safety outcome). RESULTS: The four eligible trials (n=767 children) similarly used lifestyle and insulin to manage gestational hyperglycemia, but only two measured offspring obesity and waist circumference and could be pooled for these outcomes. We found no association between intensive gestational glucose management and childhood obesity at 7-10 years of age (relative risk 0.89, 95% confidence interval (CI) 0.65 to 1.22; two trials; n=568 children). Waist circumference also did not differ between treatment and control arms (mean difference, -2.68 cm; 95% CI, -8.17 to 2.81 cm; two trials; n=568 children). CONCLUSIONS: Intensive gestational glycemic management is not associated with reduced childhood obesity in offspring, but randomized data is scarce. Long-term follow-up of trials should be prioritized and comprehensive measures of childhood metabolic risk should be considered as outcomes in future trials.

Diabetes in pregnancy and lung health in offspring: developmental origins of respiratory disease.

Diabetes is an increasingly common complication of pregnancy. In parallel with this trend, a rise in chronic lung disease in children has been observed in recent decades. While several adverse health outcomes associated with exposure to diabetes in utero have been documented in epidemiological and experimental studies, few have examined the impact of diabetes in pregnancy on offspring lung health and respiratory disease. We provide a comprehensive overview of current literature on this topic, finding suggestive evidence that exposure to diabetes in utero may have adverse effects on lung development. Delayed lung maturation and increased risk of respiratory distress syndrome have been consistently observed among infants born to mothers with diabetes and these findings are also observed in some rodent models of diabetes in pregnancy. Further research is needed to confirm and characterize epidemiologic observations that diabetes in pregnancy may predispose offspring to childhood wheezing illness and asthma. Parallel translational studies in human pregnancy cohorts and experimental models are needed to explore the role of fetal programming and other potential biological mechanisms in this context.

Does First Nations ancestry modify the association between gestational diabetes and subsequent diabetes: a historical prospective cohort study among women in Manitoba, Canada.

BACKGROUND: Over the past 30 years, the prevalence of diabetes has steadily increased among Canadians, and is particularly evident among First Nations (FN) women. The interplay between FN ancestry, gestational diabetes and the development of subsequent diabetes among mothers remains unclear. METHODS: After excluding known pre-existing diabetes, we explored whether FN ancestry may modify the association between gestational diabetes and post-partum diabetes among women in Manitoba (1981-2011) via a historical prospective cohort database study. We analysed administrative data in the Population Health Research Data Repository using Kaplan-Meier survival analysis and Cox proportional hazards regression. RESULTS: Gestational diabetes was diagnosed in 11 906 of 404 736 deliveries (2.9%), 6.7% of FN and 2.2% of non-FN pregnant women (P < 0.0001). Post-partum diabetes during ≤ 30 years follow-up was more than three times higher among FN women than among non-FN women (P < 0.0001). Diabetes developed in 76.0% of FN and 56.2% of non-FN women with gestational diabetes within the follow-up period. The hazard ratio of gestational diabetes for post-partum diabetes was 10.6 among non-FN women and 5.4 among FN women. Other factors associated with a higher risk of diabetes included lower family income among FN and non-FN women and rural/remote residences among FN women. Among non-FN women, urban residence was associated with a higher risk of diabetes. CONCLUSION: Gestational diabetes increases post-partum diabetes in FN and non-FN women. FN women had substantially more gestational diabetes or post-partum diabetes than non-FN women, partially due to socio-economic and environmental barriers. Reductions in gestational diabetes and socio-economic inequalities are required to prevent diabetes in women, particularly in FN population.

Physical activity intensity and type 2 diabetes risk in overweight youth: a randomized trial.

BACKGROUND: The chronic effects of high-intensity endurance training on metabolic health outcomes in overweight adolescents remains poorly understood. OBJECTIVE: To test the hypothesis that high-intensity endurance training (ET) is superior to moderate-intensity ET for improving risk factors for type 2 diabetes in overweight adolescents. DESIGN AND METHODS: In this randomized trial, 106 overweight and obese adolescents (15.2 years; 76% female; 62% Caucasian) were randomly assigned to high-intensity ET (70-85% of heart rate reserve, n=38), moderate-intensity ET (40-55% heart rate reserve; n=32) or control for 6 months (n=36). The primary and secondary outcome measures were insulin sensitivity assessed using a frequently sampled intravenous glucose tolerance test and hepatic triglyceride content with magnetic resonance spectroscopy. Exploratory outcomes were cardiorespiratory fitness, physical activity and MRI and dual x-ray absorptiometry-derived measures of adiposity. RESULTS: The study had 96% retention and attendance was 61±21% and 55±24% in the high- and moderate-intensity ET arms. Intention-to-treat analyses revealed that, at follow-up, insulin sensitivity was not different between high-intensity (-1.0 mU kg(-1) min(-1); 95% confidence interval (CI): -1.6, +1.4 mU kg(-1) min(-1)) and moderate-intensity (+0.26 mU kg(-1) min(-1); 95% CI: -1.3, +1.8 mU kg(-1) min(-1)) ET arms compared with controls (interaction, P=0.97). Similarly, hepatic triglyceride at follow-up was not different in high-intensity (-1.7% fat/water (F/W); 95% CI: -7.0, +3.6% F/W) and moderate-intensity (-0.40% FW; 95% CI: -6.0, +5.3% F/W) ET compared with controls. Both high intensity (+4.4 ml per kg-FFM (fat-free mass) per minute; 95% CI: 1.7, 7.1 ml kg-FFM(-1) min(-1)) and moderate intensity (+4.4 ml kg-FFM(-1) min(-1); 95% CI: 1.6, 7.3 ml kg-FFM(-1) min(-1)) increased cardiorespiratory fitness, relative to controls (interaction P<0.001). CONCLUSIONS: ET improves cardiorespiratory fitness among obese adolescents; however, owing to lack of compliance, the influence of exercise intensity on insulin sensitivity and hepatic triglycerides remains unclear.

Vigorous physical activity and longitudinal associations with cardiometabolic risk factors in youth.

OBJECTIVE: To examine the longitudinal associations between different physical activity (PA) intensities and cardiometabolic risk factors among a sample of Canadian youth. METHODS: The findings are based on a 2-year prospective cohort study in a convenience sample of 315 youth aged 9-15 years at baseline from rural and urban schools in Alberta, Canada. Different intensities (light, moderate and vigorous) of PA were objectively assessed with Actical accelerometers. The main outcome measures were body mass index (BMI) z-score, waist circumference, cardiorespiratory fitness and systolic blood pressure at 2-year-follow-up and conditional BMI z-score velocity. A series of linear regression models were conducted to investigate the associations after adjusting for potential confounders. RESULTS: At follow-up, cardiorespiratory fitness increased (quartile 1 vs quartile 4=43.3 vs 50.2; P(trend)<0.01) and waist circumference decreased (quartile 1 vs quartile 4=79.0 vs 72.6; P(trend)=0.04; boys only) in a dose-response manner across quartiles of baseline vigorous-intensity PA. A similar trend was observed for systolic blood pressure (quartile 1 vs quartile 4=121.8 vs 115.3; P(trend)=0.07; boys only). Compared with quartile 1 of vigorous-intensity PA, BMI z-score at follow-up and conditional BMI z-score velocity were significantly lower in the quartile 2 and 3 (P<0.05). Waist circumference at follow-up also decreased (quartile 1 vs quartile 4=75.3 vs 73.8; P(trend)=0.04) across quartiles of baseline moderate-intensity PA. CONCLUSIONS: Time spent in vigorous-intensity PA was associated with several positive health outcomes 2 years later. These findings suggest that high-intensity activities in youth help to reduce the risk for several chronic diseases.

Lifestyle intervention on diet and exercise reduced excessive gestational weight gain in pregnant women under a randomised controlled trial.

OBJECTIVE: To examine the effect of an exercise and dietary intervention during pregnancy on excessive gestational weight gain (EGWG), dietary habit and physical activity in pregnant women. DESIGN: Randomised controlled trial. SETTING: Community-based study. POPULATION: Nondiabetic urban-living pregnant women (<26 weeks of gestation). METHODS: Participants in the intervention group were provided with community-based group exercise sessions, instructed home exercise and dietary counselling between 20 and 36 weeks of gestation. Participants in both groups received physical activity and food intake surveys at enrolment and 2 months after the enrolment. MAIN OUTCOME MEASURES: Prevalence of EGWG and measures of physical activity and food intakes between the two groups. RESULTS: A total of 190 pregnant women, 88 in the control group and 102 in the intervention group, completed the study. Decreased daily intakes of calorie, fat, saturated fat and cholesterol were detected in participants in the intervention group at 2 months after enrolment compared with the control group (P<0.01). Participants in the intervention group had higher physical activity 2 months after enrolment compared with the control group (P<0.01). The lifestyle intervention during pregnancy reduced the prevalence of EGWG in the intervention group compared with the control group (P<0.01) according to the guidelines of the Institute of Medicine. CONCLUSION: The findings suggest that lifestyle intervention during pregnancy increased physical activity, improved dietary habits and reduced EGWG in urban-living pregnant women.

Effects of hyperbaric oxygen on aerobic performance in a normobaric environment.

The purpose was to examine the acute effects of a hyperbaric oxygen (HBO2) treatment on a) recovery following prolonged exercise and b) aerobic performance in a trained population. Subjects were six male and six female, trained runners with mean Vo2max values of 64.6 +/- 5.6 and 51.9 +/- 6.6 ml x kg(-1) x min(-1), respectively. Subjects performed four exercise-HBO2 conditions in random order: a) control, b) exercise-no HBO2, c) no exercise-HBO2; and d) exercise-HBO2. Exercise was a 90-min run at 75-80% of Vo2max x HBO2 treatments consisted of breathing 95% O2 at 2.5 atm abs for 90 min. At the end of each condition, aerobic performance was assessed with a VO2max test and by the oxygen cost of running on a treadmill at three submaximal velocities. Recovery was not enhanced following a single HBO2 treatment at 2.5 atm abs for 90 min, nor did it alter submaximal or maximal running performance.