Metabolic features of adiposity and glucose homoeostasis among school-aged inuit children from Nunavik (Northern Quebec, Canada).

In contrast to most Indigenous people in Canada, Inuit appeared until recently to have been protected from type 2 diabetes (T2D) related to obesity. We assessed the associations of metabolites (amino acids, acylcarnitines) with adiposity and biomarkers of T2D in school-aged Inuit children of Nunavik (Canada). Concentrations of metabolite were measured in plasma samples from a cross-sectional analysis of 248 children (mean age = 10.8 years). We assessed associations of plasma metabolites with adiposity measures (BMI, skinfold thicknesses) and T2D markers (insulin, glucose, adiponectin). Plasma concentrations of valine and tyrosine were higher in obese and overweight children compared to those of normal weight children (P < 0.05). An increment of 1-SD in BMI (SD = 3.3 kg/m2) was statistically associated with an increment of 0.21 (95% CI: 0.08, 0.33) for valine, 0.15 (95% CI: 0.02, 0.27) for isoleucine and 0.17 (95% CI: 0.04, 0.29) for tyrosine. Insulin concentration increased with concentrations of all amino acids (P < 0.05) except methionine. None of the acylcarnitines measured were statistically significantly associated with adiposity or T2D biomarkers A signature of metabolites, particularly higher levels of branched-chain amino acids, might allow for early detection of T2D among school-aged Inuit children.

Exposure to polychlorinated biphenyls and organochlorine pesticides and risk of dementia, Alzheimer's disease and cognitive decline in an older population: a prospective analysis from the Canadian Study of Health and Aging.

BACKGROUND: Little attention has been paid to neurotoxicants on the risk of dementia. Exposure to known neurotoxicants such as polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides is suspected to have adverse cognitive effects in older populations. OBJECTIVE: To assess whether plasma concentrations of PCBs and OC pesticides are associated with the risk of cognitive decline, Alzheimer's disease (AD) and of all-cause dementia in the Canadian older population. METHODS: Analyses were based on data from the Canadian Study of Health and Aging, a 3-phase, 10-year population-based study of individuals aged 65+ years. Analyses included 669 clinically assessed subjects, of which 156 developed dementia including 108 incident cases of AD. Subjects were screened at each phase with the 100-point Modified Mini-Mental State Examination (3MS), a measurement of global cognitive function. Statistical analyses included Cox proportional hazards model when the outcome was dementia or AD, and a repeated-measure mixed model when the outcome was the 3MS score. RESULTS: No association of PCB and OC pesticides with the risk of dementia and AD was observed. Elevated concentrations of PCB congeners nos 118, 153, 156, 163, and OC pesticides 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its metabolite 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) were significantly associated with cognitive decline as assessed with the 3MS. A posteriori analyses suggested that only p,p'-DDE was significantly related to a higher cognitive decline in time based on the 3MS among incident cases of dementia compared to subjects remaining nondemented. CONCLUSION: PCB and OC pesticide plasma concentrations were not related to the incident diagnosis of neither dementia, nor AD. Using the 3MS scores as the outcome, higher concentrations of four PCB congeners and two OC pesticides were associated with lower cognitive performances in subjects. The association of p,p'-DDE with cognitive decline in time in incident cases of dementia merits further investigation.

Overweight and Obesity Prevalence Among School-Aged Nunavik Inuit Children According to Three Body Mass Index Classification Systems.

PURPOSE: Little is known about the suitability of three commonly used body mass index (BMI) classification system for Indigenous children. This study aims to estimate overweight and obesity prevalence among school-aged Nunavik Inuit children according to International Obesity Task Force (IOTF), Centers for Disease Control and Prevention (CDC), and World Health Organization (WHO) BMI classification systems, to measure agreement between those classification systems, and to investigate whether BMI status as defined by these classification systems is associated with levels of metabolic and inflammatory biomarkers. METHODS: Data were collected on 290 school-aged children (aged 8-14 years; 50.7% girls) from the Nunavik Child Development Study with data collected in 2005-2010. Anthropometric parameters were measured and blood sampled. Participants were classified as normal weight, overweight, and obese according to BMI classification systems. Weighted kappa (κw) statistics assessed agreement between different BMI classification systems, and multivariate analysis of variance ascertained their relationship with metabolic and inflammatory biomarkers. RESULTS: The combined prevalence rate of overweight/obesity was 26.9% (with 6.6% obesity) with IOTF, 24.1% (11.0%) with CDC, and 40.4% (12.8%) with WHO classification systems. Agreement was the highest between IOTF and CDC (κw = .87) classifications, and substantial for IOTF and WHO (κw = .69) and for CDC and WHO (κw = .73). Insulin and high-sensitivity C-reactive protein plasma levels were significantly higher from normal weight to obesity, regardless of classification system. Among obese subjects, higher insulin level was observed with IOTF. CONCLUSIONS: Compared with other systems, IOTF classification appears to be more specific to identify overweight and obesity in Inuit children.

Plasma polychlorinated biphenyl and organochlorine pesticide concentrations in dementia: the Canadian Study of Health and Aging.

BACKGROUND: Even though polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides are recognized as neurotoxicants, few studies have investigated their associations with dementia. Here, we assess associations of plasma PCB and OC pesticide concentrations with all-cause dementia and Alzheimer's disease (AD). METHODS: Analyses are based on data from the Canadian Study of Health and Aging, a population-based study of men and women aged 65+ years at baseline. PCB and OC pesticide concentrations were measured in 2023 participants who had complete clinical evaluations and blood samples; 574 had dementia, including 399 cases of AD. Concentrations were log-transformed and used as continuous variables in logistic regression models to assess their individual associations with dementia and AD. RESULTS: After adjustment for blood collection period, total plasma lipids, age, sex, education, apolipoprotein E e4 allele (ApoE4), tobacco and alcohol use, rural/urban residence, and comorbidities, elevated plasma PCB concentrations were not associated with increased prevalence of dementia and AD. Elevated concentrations of some OC pesticides and metabolites such as hexachlorobenzene, cis-nonachlor and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane were significantly associated with a reduced prevalence of dementia. A significant reduced prevalence of AD was also observed with elevated hexachlorobenzene concentrations. Other OC pesticides and metabolites were not associated with the prevalence of dementia or AD. No effect modification by sex and ApoE4 was observed for either dementia or AD. CONCLUSIONS: Elevated plasma PCB and OC pesticide concentrations were not associated with higher prevalence of all-cause dementia and AD. The possibility of modest reductions in prevalence with specific OC pesticides remains to be further investigated given the cross-sectional design of this study.

Polychlorinated biphenyls and organochlorine pesticides in plasma of older Canadians.

No nationwide study has ever measured polychlorinated biphenyl (PCB) and organochlorine pesticide (OCP) body burden in Canadians aged 65 years and over. The objective of this study was to determine plasma concentrations of PCB congeners and OCPs in participants from a sub-cohort of the Canadian Study of Health and Aging and to examine the effects of socio-demographic, anthropometric and lifestyle characteristics on selected organochlorine concentrations. Archived plasma samples collected from 2023 subjects were analyzed by gas chromatography-mass spectrometry using negative chemical ionization for 15 PCB congeners and 11 OCPs. Descriptive statistics were used to report PCB congeners and OCP plasma concentrations. Multivariate models were used to study whether age at blood collection, sex, education, body mass index, rural residence, geographic region, smoking status and alcohol intake influences PCB 153, the most abundant congener, and the major OCP (beta-hexachlorocyclohexane, hexachlorobenzene, trans-nonachlor, p,p'-DDE) plasma concentrations. Statistical analyses were restricted to 1979 subjects and 17 organochlorine compounds for which at least 50% of the samples had concentrations above the limit of detection. Of these, 775 were men (mean age: 82.2 years) and 1204 were women (mean age: 84.6 years). The median concentrations (ng/g lipid) of PCB 153 in the plasma of men and women were 70.9 and 75.4, respectively. The levels of the sum of PCBs and the sum of dioxin-like PCBs were 276 and 31.3 for men, and 300 and 45.5 for women, respectively. The median concentrations (ng/g lipid) of p,p'-DDE, the most abundant OCP, were 565 for men and 828 for women. All compounds were positively and significantly intercorrelated (rs=0.39-0.99; p<0.001). Except for trans-nonachlor, the multivariate models revealed that age and male sex were the determining characteristics that showed, respectively, strongly positive and negative associations with selected organochlorine concentrations. These plasma concentrations from a large population based study can be considered as baseline data for body burdens of older Canadians.