Role of Physical Activity and Sedentary Behaviors on Vascular and Myocardial Structure and Function in Type 1 Diabetes.

OBJECTIVE: To estimate associations between physical activity and sedentary behaviors and early markers of cardiovascular diseases (CVD) in adolescents with and without type 1 diabetes. STUDY DESIGN: Cross-sectional data stem from CARDEA, a study investigating early CVD development in 100 adolescents with type 1 diabetes recruited at Sainte-Justine University Hospital Diabetes Clinic and 97 healthy adolescents without diabetes (14-18 years), in Montréal, Canada. Outcomes included arterial stiffness by pulse-wave velocity, endothelial function (VTI) by flow-mediated dilation test, and cardiac magnetic resonance imaging markers. Moderate-to-vigorous physical activity (MVPA) and sedentary time were estimated by accelerometry and leisure screen time by questionnaire. We estimated multivariable linear regression models stratified by group. RESULTS: In adolescents with type 1 diabetes, 10-minutes daily increase in MVPA was associated with 3.69 g/m (95% CI: -1.16; 8.54) higher left ventricular (LV) mass/height and 1-h increase in device-measured sedentary time with 0.68 mm (0.20; 1.16) higher wall thickness but only in those with glycated hemoglobin ≤7.5%. In healthy adolescents, a 10-minute increase in MVPA was associated with 1.32 g/m (-0.03; 2.66) higher LV mass/height. Every 1-hour increase in sedentary time was associated with -1.82 cm (-3.25; -0.39) lower VTI, -2.99 g/m (-5.03; -0.95) lower LV mass/height, and -0.47 mm (-0.82; -0.12) lower wall thickness. CONCLUSIONS: Being active and limiting sedentary time appears beneficial for cardiac structure and endothelial function in healthy adolescents; however adequate glycemic control combined with higher levels of MVPA may be required for adolescents with type 1 diabetes to overcome the impact of diabetes.

Associations of Abnormal Maternal Glucose Regulation in Pregnancy with Offspring Adiposity, Insulin Resistance, and Adipokine Markers During Childhood and Adolescence.

OBJECTIVE: To examine the associations of abnormal maternal glucose regulation in pregnancy with offspring adiposity, insulin resistance, adipokine, and inflammatory markers during childhood and adolescence. STUDY DESIGN: Project Viva is a prospective prebirth cohort (n = 2128 live births) initiated from 1999 through 2002 in Eastern Massachusetts, US. During the second trimester of pregnancy, clinicians used 2-step oral glucose challenge testing to screen for gestational diabetes mellitus. In the offspring, we measured anthropometry, insulin resistance, adipokines, lipids, and inflammatory markers in mid-childhood (n = 1107), early adolescence (n = 1027), and mid-adolescence (n = 693). We used multivariable linear regression models and generalized estimating equations adjusted for child age and sex, and for maternal age, race/ethnicity, education, parity, and smoking during pregnancy; we further adjusted for prepregnancy body mass index (BMI). RESULTS: In mid-adolescence (17.1 [0.8] years of age), offspring of mothers with gestational diabetes mellitus (n = 27) had a higher BMI z-score (ß; 95% Cl; 0.41 SD; 0.00, 0.82), sum of skinfolds (8.15 mm; 2.48, 13.82), homeostatic model assessment for insulin resistance (0.81 units; 0.13, 1.50), leptin z-score (0.40 SD; 0.01, 0.78), and leptin/adiponectin ratio z-score (0.51 SD; CI 0.09, 0.93) compared with offspring of mothers with normoglycemia (multivariable-adjusted models). The associations with BMI, homeostatic model assessment for insulin resistance, and adiponectin seemed stronger in mid-adolescence compared with earlier time points. The associations were attenuated toward the null after adjustment for maternal prepregnancy BMI. CONCLUSION: Exposure to gestational diabetes mellitus is associated with higher adiposity, insulin resistance, and altered adipokines in mid-adolescence. Our findings suggest that the peripubertal period could be a key time for the emergence of prenatally programmed metabolic abnormalities.

Associations Between Weight-Loss Attempts, Weight-Related Stress, and Body Image During Childhood and Adolescence in Children With Parental Obesity.

Background: Few longitudinal studies have investigated the role of weight-loss attempts or weight-related stress on body image during childhood. We examined whether weight-loss attempts and weight-related stress are associated with weight misperception and body dissatisfaction across childhood and adolescence. Methods: Data were drawn from the Quebec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort of Canadian children with parental obesity (8-10 years: n = 630; 10-12 years: n = 564; 15-17 years: n = 377). We assessed weight-loss attempts and weight-related stress at baseline and first follow-up, and perceived and desired silhouettes at first and second follow-up with questionnaires. Weight misperception consisted of the difference in BMI z-score (zBMI) from the perceived silhouette and the measured zBMI. Body dissatisfaction consisted of the discordance between perceived and desired silhouettes. We estimated multivariable mixed-effects regression models adjusting for age, sex, pubertal stage, parental BMI and education, and sport-based teasing. Results: Weight loss attempts were associated with a higher weight misperception score (ever tried, beta [95% confidence intervals; CI]: 0.13 [0.01-0.24]) and with 2.13 times higher desire to be thinner (95% CI: 1.39-3.26) at the subsequent follow-up. Similarly, children stressed by their weight had a higher misperception score (beta [95% CI]: 0.15 [0.02-0.27]) and greater desire to be thinner at the next follow-up (odds ratio [95% CI]: 1.73 [0.999-3.00]). Conclusions: Weight-loss attempts and weight-related stress in children and adolescents are associated with weight misperception and body dissatisfaction, supporting empowerment and counseling focusing on healthy eating behaviors and a positive body image. Clinical Trial Registration Number: NCT03356262.

Proactive Contact Tracing.

The COVID-19 pandemic has spurred an unprecedented demand for interventions that can reduce disease spread without excessively restricting daily activity, given negative impacts on mental health and economic outcomes. Digital contact tracing (DCT) apps have emerged as a component of the epidemic management toolkit. Existing DCT apps typically recommend quarantine to all digitally-recorded contacts of test-confirmed cases. Over-reliance on testing may, however, impede the effectiveness of such apps, since by the time cases are confirmed through testing, onward transmissions are likely to have occurred. Furthermore, most cases are infectious over a short period; only a subset of their contacts are likely to become infected. These apps do not fully utilize data sources to base their predictions of transmission risk during an encounter, leading to recommendations of quarantine to many uninfected people and associated slowdowns in economic activity. This phenomenon, commonly termed as "pingdemic," may additionally contribute to reduced compliance to public health measures. In this work, we propose a novel DCT framework, Proactive Contact Tracing (PCT), which uses multiple sources of information (e.g. self-reported symptoms, received messages from contacts) to estimate app users' infectiousness histories and provide behavioral recommendations. PCT methods are by design proactive, predicting spread before it occurs. We present an interpretable instance of this framework, the Rule-based PCT algorithm, designed via a multi-disciplinary collaboration among epidemiologists, computer scientists, and behavior experts. Finally, we develop an agent-based model that allows us to compare different DCT methods and evaluate their performance in negotiating the trade-off between epidemic control and restricting population mobility. Performing extensive sensitivity analysis across user behavior, public health policy, and virological parameters, we compare Rule-based PCT to i) binary contact tracing (BCT), which exclusively relies on test results and recommends a fixed-duration quarantine, and ii) household quarantine (HQ). Our results suggest that both BCT and Rule-based PCT improve upon HQ, however, Rule-based PCT is more efficient at controlling spread of disease than BCT across a range of scenarios. In terms of cost-effectiveness, we show that Rule-based PCT pareto-dominates BCT, as demonstrated by a decrease in Disability Adjusted Life Years, as well as Temporary Productivity Loss. Overall, we find that Rule-based PCT outperforms existing approaches across a varying range of parameters. By leveraging anonymized infectiousness estimates received from digitally-recorded contacts, PCT is able to notify potentially infected users earlier than BCT methods and prevent onward transmissions. Our results suggest that PCT-based applications could be a useful tool in managing future epidemics.

Estimating causal effects of physical activity and sedentary behaviours on the development of type 2 diabetes in at-risk children from childhood to late adolescence: an analysis of the QUALITY cohort.

BACKGROUND: Uncertainty remains regarding the causal effect of physical activity and sedentary behaviours on the development of type 2 diabetes in children. We aimed to estimate average treatment effects of physical activity and sedentary behaviours on risk of type 2 diabetes in individuals who are at risk during childhood and adolescence. METHODS: We used data from the Quebec Adipose and Lifestyle Investigation in Youth (QUALITY) cohort of children of western European descent (white non-Hispanic race or ethnicity) with a parental history of obesity (defined as a BMI of 30 kg/m2 or more, or a waist circumference of more than 102 cm in men and 88 cm in women) evaluated at the ages of 8-10 years (baseline), 10-12 years (first follow-up cycle), and 15-17 years (second follow-up cycle) in Québec, Canada. We measured moderate-to-vigorous physical activity (MVPA) and sedentary time by accelerometry, and leisure screen time by questionnaire at each cycle. Outcomes included fasting and 2 h post-load glycaemia and validated indices of insulin sensitivity and insulin secretion. We estimated average treatment effects of MVPA, sedentary time, and screen time on markers of type 2 diabetes using longitudinal marginal structural models with time-varying exposures, outcomes, and confounders from the ages of 8-10 to 15-17 years and inverse probability of treatment and censoring weighting. We considered both the current and cumulative effects of exposures on outcomes. FINDINGS: 630 children were evaluated at baseline (age 8-10 years) between July, 2005, and December, 2008, 564 were evaluated at the first follow-up (age 10-12 years) between July, 2007, and March, 2011, and 377 were evaluated at the second follow-up (age 15-17 years) between September, 2012, and May, 2016. Based on cumulative exposure results, estimated average treatment effects for MVPA were 5·6% (95% CI 2·8 to 8·5) on insulin sensitivity and -3·8% (-7·1 to -0·5) on second-phase insulin secretion per 10 min daily increment from the ages of 8-10 years to age 15-17 years. Average treatment effects for sedentary time and reported screen time resulted in reduced insulin sensitivity (-8·2% [-12·3 to -3·9] and -6·4% [-10·1 to -2·5], respectively), increased second-phase insulin secretion (5·9% [1·9 to 10·1] and 7·0% [-0·1 to 14·7], respectively), and higher fasting glycaemia (0·03 mmol/L [0·003 to 0·05] and 0·02 mmol/L [0·01 to 0·03], respectively) per additional daily hour from the ages of 8-10 years to 15-17 years. INTERPRETATION: Using modern causal inference approaches strengthened the evidence of MVPA and sedentary behaviours as key drivers of development of type 2 diabetes in at-risk children and adolescents, and should be considered as key targets for prevention. FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and Fonds de Recherche du Québec-Santé. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Natural history and determinants of dysglycemia in Canadian children with parental obesity from ages 8-10 to 15-17 years: The QUALITY cohort.

In children, the mechanisms implicated in deterioration of glucose homeostasis versus reversion to normal glucose tolerance (NGT) remain uncertain. We aimed to describe the natural history of dysglycemia from childhood to late adolescence and to identify its early determinants. We used baseline (8-10 years, n = 630), 1st follow-up (10-12 years, n = 564) and 2nd follow-up (15-17 years, n = 377) data from the QUALITY cohort of White Canadian children with parental obesity. Children underwent a 2-h oral glucose tolerance test at each cycle with plasma glucose and insulin measured at 0/30/60/90/120 min. American Diabetes Association criteria defined dysglycemia (impaired fasting glucose, impaired glucose tolerance or type 2 diabetes). Longitudinal patterns of insulin sensitivity and beta-cell function were estimated using generalized additive mixed models. Model averaging identified biological, sociodemographic and lifestyle-related determinants of dysglycemia. Of the children NGT at baseline, 66 (21%) developed dysglycemia without reverting to NGT. Among children with dysglycemia at baseline, 24 (73%) reverted to NGT. In children with dysglycemia at 1st follow-up, 18 (53%) later reverted to NGT. Among biological, sociodemographic and lifestyle determinants at 8-10 years, only fasting and 2-h glucose were associated with developing dysglycemia (odds ratio [95% CI] per 1 mmol/L increase: 4.50 [1.06; 19.02] and 1.74 [1.11; 2.73], respectively). Beta-cell function decreased by 40% in children with overweight or obesity. In conclusion, up to 75% of children with dysglycemia reverted to NGT during puberty. Children with higher fasting and 2-h glucose were at higher risk for progression to dysglycemia, while no demographic/lifestyle determinants were identified.

Profile of Daughters and Sisters of Women With Polycystic Ovary Syndrome: The Role of Proband's Glucose Tolerance.

CONTEXT: First-degree relatives of women with polycystic ovary syndrome (PCOS) present hormonal and metabolic alterations compared to girls unrelated to PCOS. It is unknown whether glucose intolerance in the PCOS proband confers a more severe metabolic predisposition on their first-degree relatives. OBJECTIVE: To determine whether glucose tolerance status in women with PCOS is associated with worsened glucose metabolism and sex hormone levels in their peripubertal daughters or sisters. DESIGN: Cross-sectional study. SETTING: Seven academic centers in North America, South America, and Europe. PATIENTS: Sixty-four pairs of women with PCOS and their daughters or younger sisters aged between 8 and 14 years were recruited. Twenty-five mothers or older sisters with PCOS were glucose intolerant (GI) and 39 were normal glucose tolerant (NGT). MAIN OUTCOME MEASURES: Beta-cell function estimated by the insulin secretion-sensitivity index-2 (ISSI-2) during an oral glucose tolerance test and by the disposition index during a frequently sampled IV glucose tolerance test. Free testosterone and 17-hydroxyprogesterone (17-OHP) levels. RESULTS: Being related to a GI PCOS proband was associated with a lower ISSI-2 (P-value = 0.032) after adjusting for ethnicity, body mass index z-score, and pubertal stage. They also had higher free testosterone (P-value = 0.011) and 17-OHP levels compared to girls with an NGT proband, the latter becoming significant after adjusting for confounders (P-value = 0.040). CONCLUSIONS: Compared to first-degree female relatives of women with PCOS and NGT, first-degree relatives of women with PCOS and GI display lower beta-cell function and hyperandrogenemia, putting them at higher risk of GI and PCOS development.

Body Mass Index Z Score vs Weight-for-Length Z Score in Infancy and Cardiometabolic Outcomes at Age 8-10 Years.

OBJECTIVES: To confirm that World Health Organization weight-for-length z scores (zWFL) and World Health Organization body mass index z scores (zBMI) in infancy are associated with adiposity and cardiometabolic measures at 8-10 years old and to compare the predictive ability of the 2 methods. STUDY DESIGN: zWFL and zBMI at 6, 12, and 18 months of age were computed using data extracted from health booklets, among participants in the Québec Adipose and Lifestyle InvesTigation in Youth prospective cohort (n = 464). Outcome measures at 8-10 years included adiposity, lipid profile, blood pressure, and insulin dynamics. The relationships between zWFL, zBMI, and each outcome were estimated using multivariable linear regression models. Outcome prediction at 8-10 years was compared between the 2 methods using eta-squared and the Lin concordance correlation coefficient. RESULTS: zWFL and zBMI were associated with all measures of adiposity at 8-10 years. Associations with other cardiometabolic measures were less consistent. For both zWFL and zBMI across infancy, eta-squared were highly similar and the Lin coefficients were markedly high (≥0.991) for all outcomes. CONCLUSIONS: There was no evidence that zBMI and zWFL in infancy differed in their ability to predict adiposity and cardiometabolic measures in childhood. This lends support to the sole use of zBMI for growth monitoring and screening of overweight and obesity from birth to 18 years. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03356262.

Self-reported weight loss attempts and weight-related stress in childhood: Heightening the risk of obesity in early adolescence.

OBJECTIVE: Weight loss attempts occur as early as childhood. The impacts of weight loss attempts and weight-related stress on the occurrence of obesity during childhood remain unknown. We aimed to: (a) assess the prevalence of self-reported weight loss attempts and weight-related stress in 8-10 year-old children and (b) determine associations with adiposity 2 years later. METHOD: Data were collected from a cohort study of 564 Canadian children aged 8-10 years, having one or both biological parents with obesity (Quebec Adipose and Lifestyle Investigation in Youth cohort). Self-reported weight loss attempts and weight-related stress were assessed at baseline in the child's questionnaire. Adiposity was measured at baseline and 2 years later using body mass index z-scores (zBMI), waist-to-height ratio (WHtR), and percentage of body fat (%BF) obtained from dual-energy x-ray absorptiometry. Linear and logistic regression analyses were used while adjusting for potential confounders. RESULTS: Forty-eight percent of children reported previous weight loss attempts and 20% reported weight-related stress. Self-reported weight loss attempts and weight-related stress were associated with higher zBMI, WHtR, and %BF 2 years later in adjusted models, although estimates were attenuated when including baseline adiposity measures. Self-reported weight loss attempts, but not weight-related stress, increased the risk of becoming overweight among children who were normal weight at baseline. DISCUSSION: Weight loss attempts are prevalent in children with parental obesity. Children reporting weight loss attempts and weight-related stress tend to have higher adiposity 2 years later and are more likely to become overweight.

Tune out and turn in: the influence of television viewing and sleep on lipid profiles in children.

BACKGROUND/OBJECTIVES: Physical activity is beneficial to lipid profiles; however, the association between sedentary behavior and sleep and pediatric dyslipidemia remains unclear. We aimed to investigate whether sedentary behavior or sleep predicted lipid profiles in children over a 2-year period. SUBJECTS/METHODS: Six hundered and thirty children from the QUALITY cohort, with at least one obese parent, were assessed prospectively at ages 8-10 and 10-12 years. Measures of sedentary behavior included self-reported TV viewing and computer/video game use. Seven-day accelerometry was used to derive sedentary behavior and sleep duration. Adiposity was assessed using DEXA scans. Twenty-four-hour dietary recalls yielded estimates of carbohydrate and fat intake. Outcomes included fasting total cholesterol, triglycerides, HDL and LDL-cholesterol. Multivariable models were adjusted for adiposity and diet. RESULTS: At both Visit 1 (median age 9.6 year) and Visit 2 (median age 11.6 year), children were of normal weight (55%), overweight (22%), or obese (22%). Every additional hour of TV viewing at Visit 1 was associated with a 7.0% triglyceride increase (95% CI: 3.5, 10.6; P < 0.01) and 2.6% HDL decrease (95% CI: -4.2, -0.9; P < 0.01) at Visit 2; findings remained significant after adjusting for adiposity and diet. Every additional hour of sleep at Visit 1 predicted a 4.8% LDL decrease (95% CI: -9.0, -0.5; P = 0.03) at Visit 2, after adjusting for fat intake; this association became nonsignificant once controlling for adiposity. CONCLUSIONS: Longer screen time during childhood appears to deteriorate lipid profiles in early adolescence, even after accounting for other major lifestyle habits. There is preliminary evidence of a deleterious effect of shorter sleep duration, which should be considered in further studies.

Lowering Saturated Fat and Increasing Vegetable and Fruit Intake May Increase Insulin Sensitivity 2 Years Later in Children with a Family History of Obesity.

Background: Identifying dietary factors that determine insulin sensitivity and secretion in children entering puberty may provide valuable information for the early prevention of type 2 diabetes. Objectives: We assessed whether macronutrients and food groups are longitudinally associated with insulin sensitivity and secretion over a 2-y period in children with a family history of obesity, and whether associations differ by level of adiposity. Methods: Data were derived from the Quebec Adipose and Lifestyle Investigation in Youth (QUALITY) Study, an ongoing prospective cohort including 630 children recruited at ages 8-10 y, with ≥1 obese parent, and followed 2 y later (n = 564). The intake of macronutrients and foods was assessed at baseline using three 24-h dietary recalls. At age 10-12 y, insulin sensitivity was assessed by the Matsuda Insulin Sensitivity Index (ISI) and the homeostatic model assessment of insulin resistance. Insulin secretion was assessed by the ratio of the area under the curve of insulin to the area under the curve of glucose at 30 min and at 120 min of an oral-glucose-tolerance test. Multivariable linear regression models were fitted for each dietary factor while adjusting for age, sex, puberty, physical activity, screen time, total energy intake, and percentage of body fat; and interaction terms between dietary factors and percentage of body fat were tested. Results: Saturated fat intake was associated with a 1.95% lower (95% CI: -3.74%, -0.16%) Matsuda ISI, whereas vegetable and fruit intake was associated with a 2.35% higher (95% CI: 0.18%, 4.52%) Matsuda ISI 2 y later. The association of saturated fat intake with insulin sensitivity was most deleterious among children with a higher percentage of body fat (P-interaction = 0.023). Other than fiber intake, no longitudinal associations between dietary intake and insulin secretion were found. Conclusions: Lowering saturated fat and increasing vegetable and fruit intakes during childhood may improve insulin sensitivity as children enter puberty. This study was registered at www.clinicaltrials.gov as NCT03356262.

Evolution of metabolic alterations 5 Years after early puberty in a cohort of girls predisposed to polycystic ovary syndrome.

BACKGROUND: We and others have observed that young girls predisposed to polycystic ovary syndrome (PCOS) display defective insulin sensitivity, beta-cell function and non-esterified fatty acids (NEFA) suppressibility during early pubertal years, compared to controls. Our objective is to assess whether these differences in glucose and NEFA metabolisms persist after 5 years in late/post-puberty. METHODS: We conducted a prospective cohort study between 2007 and 2015 with 4-6 years of follow-up in an academic institution research center. We compared 8 daughters and sisters of PCOS women (PCOSr) to 8 age-matched girls unrelated to PCOS (±1.5 years). Girls were assessed initially at 8-14 years old and re-assessed after a median follow-up of 5.4 years, at 13-21 years old. Our main measures were a frequently sampled intravenous glucose tolerance test (FSivGTT)-derived insulin sensitivity (IS) and beta-cell function (disposition index, DIFSivGTT); and indices of NEFA suppression during FSivGTT (logn-linear slope of NEFA and T50 of NEFA suppression). RESULTS: At follow-up, both PCOSr and controls had similar results: IS = 3.2 vs 3.4 (p = 0.88), DIFSivGTT = 1926 vs 1380 (p = 0.44), logn-linear slope = -0.032 vs -0.032 (p = 0.88) and T50NEFA = 18.1 vs 20.8 min (p = 0.57). IS, DIFSivGTT and NEFA suppressibility were stable in PCOSr after 5 years, but decreased significantly in controls (all p < 0.05). CONCLUSIONS: Impaired metabolism observed during early puberty in girls predisposed to PCOS remains stable after 5 years whereas control girls deteriorated their metabolic parameters. Therefore, both groups become comparable in late/post-puberty. Early puberty may thus represent a window during which metabolic alterations are transiently apparent in girls at risk of PCOS.