Twenty years of participation of racialised groups in type 2 diabetes randomised clinical trials: a meta-epidemiological review.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus prevalence is increasing globally and the greatest burden is borne by racialised people. However, there are concerns that the enrolment of racialised people into RCTs is limited, resulting in a lack of ethnic and racial diversity. This may differ depending whether an RCT is government funded or industry funded. The aim of this study was to review the proportions of racialised and white participants included in large RCTs of type 2 diabetes pharmacotherapies relative to the disease burden of type 2 diabetes in these groups. METHODS: The Ovid MEDLINE database was searched from 1 January 2000 to 31 December 2020. English language reports of RCTs of type 2 diabetes pharmacotherapies published in select medical journals were included. Studies were included in this review if they had a sample size of at least 100 participants and all participants were adults with type 2 diabetes. Industry-funded trials must have recruited participants from at least two countries. Government-funded trials were not held to the same standard because they are typically conducted in a single country. Data including the numbers and proportions of participants by ethnicity and race were extracted from trial reports. The participation-to-prevalence ratio (PPR) was calculated for each trial by dividing the percentage of white and racialised participants in each trial by the percentage of white and racialised participants with type 2 diabetes, respectively, for the regions of recruitment. A random-effects meta-analysis was used to generate the pooled PPRs and 95% CIs across study types. A PPR <0.80 indicates under-representation and a PPR >1.20 indicates over-representation. Risk of bias assessments were not conducted for this study as the objective was to examine recruitment of racialised and white participants rather than evaluate the trustworthiness of clinical trial outcomes. RESULTS: A total of 83 trials were included, involving 283,122 participants, of which 15 were government-funded and 68 were industry-funded trials. In government-funded trials, the PPR for white participants was 1.11 (95% CI 0.99, 1.24) and the PPR for racialised participants was 0.72 (95% CI 0.60, 0.86). In industry-funded trials, the PPR for white participants was 1.95 (95% CI 1.74, 2.18) and the PPR for racialised participants was 0.36 (95% CI 0.32, 0.42). The limitations of this study include the reliance on investigator-reported ethnicity and race to classify participants as 'white' or 'racialised', the use of estimates for type 2 diabetes prevalence and demographic data, and the high levels of heterogeneity of pooled estimates. However, despite these limitations, the results were consistent with respect to direction. CONCLUSIONS/INTERPRETATION: Racialised participants are under-represented in government- and industry-funded type 2 diabetes trials. Strategies to improve recruitment and enrolment of racialised participants into RCTs should be developed. REGISTRATION: Open Science Framework registration no. f59mk ( https://osf.io/f59mk ) FUNDING: The authors received no financial support for this research or authorship of the article.

Understanding Newcomer Challenges and Opportunities to Accessing Nature and Greenspace in Riverdale, Hamilton, Ontario: A Neighborhood-Centered Photovoice Study.

BACKGROUND: Access to and engagement with greenspace is related to improved health benefits. We sought to collaborate with community members as partners in research and co-creators in knowledge to better understand which components within a newcomer-dense community help or hinder individual and community efforts to access greenspace and nature-based activities. METHODS: We used photovoice methodology to engage with local residents in focus groups, photowalks, and photo-elicitation interviews. Themes were developed using direct content analysis. RESULTS: A total of 39 participants (ages 11-70 years; median years in Canada of 3.25 years) were engaged in this program of research. From the analysis, we developed four themes: (a) peace and beauty; (b) memories of home; (c) safety and cleanliness; and (d) welcoming strengthened and new opportunities. Participants associated nature with peace, citing it as "under-rated" but "vital" to the neighborhood. Via photographs and stories, participants also shared a multitude of safety concerns that prevent their access to green/outdoor spaces for healthy active living programs or activities (e.g., woodchip-covered playgrounds, ample amounts of garbage littering the park and school grounds, lack of timely ice removal on sidewalks, limited safe biking paths, and unsafe motor vehicle practices at the crosswalks surrounding local parks). CONCLUSION: To translate the key ideas and themes into an informed discussion with policy and decision-makers, we held an in-person exhibition and guided tour where community members, the lead photovoice researcher, and SCORE! principal investigator shared information about each theme in the form of a pseudo-narrative peppered with prepared discussion questions.

Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis.

BACKGROUND: Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex. METHODS: Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456). RESULTS: In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20-28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated. CONCLUSIONS: Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males.

The Relationship Between Diet, Gut Microbiota, and Serum Metabolome of South Asian Infants at 1 Year.

BACKGROUND: Diet is known to affect the gut microbiota and the serum metabolome in adults, but this has not been fully explored in infants. Infancy is an important developmental period that may influence a person's long-term health. Infant development can be affected by diet, which also interacts with the developing gut microbiota. OBJECTIVES: This study aimed to explore the associations between diet, the gut microbiota, and the serum metabolome of 1-y-old infants with the overarching goal of identifying serum biomarkers of diet and/or the gut microbiota. METHODS: We derived dietary patterns of 1-y-old infants (n = 182) participating in the Canadian South Asian Birth Cohort (START) study. We compared gut microbiota α-diversity and ß-diversity and taxa relative abundance from 16S rRNA gene profiles with dietary patterns (PERMANOVA, Envfit) and investigated diet-serum metabolite associations using a multivariate analysis (partial least squares-discriminant analysis) and univariate analysis (t test). We explored the effect of nondietary factors on diet-serum metabolite relationships by incorporating diet, the gut microbiota, and maternal, perinatal, and infant characteristics in a multivariable forward stepwise regression. We replicated this analysis in White European infants, from the CHILD Cohort Study (n = 81). RESULTS: A dietary pattern characterized by formula consumption and negatively associated with breastfeeding most strongly predicted variation in the gut microbiota (R2 = 0.109) and serum metabolome (R2 = 0.547). Breastfed participants showed higher abundance of microbes from the genera Bifidobacterium (3.29 log2-fold) and Lactobacillus (7.93 log2-fold) and higher median concentrations of the metabolites S-methylcysteine (1.38 µM) and tryptophan betaine (0.43 µM) than nonbreastfed participants. Formula consuming infants showed higher median concentrations of branched-chain/aromatic amino acids (average 48.3 µM) than non-formula-consuming infants. CONCLUSIONS: Formula consumption and breastfeeding most strongly predicted the serum metabolites of 1-y-old infants, even when the gut microbiota, solid food consumption, and other covariates were considered.

Late preterm birth and growth trajectories during childhood: a linked retrospective cohort study.

BACKGROUND: Evidence suggests that accelerated postnatal growth in children is detrimental for adult cardiovascular health. It is unclear whether children born late preterm (34-36 weeks) compared to full term (≥ 39 weeks), have different growth trajectories. Our objective was to evaluate the association between gestational age groups and growth trajectories of children born between 2006-2014 and followed to 2021 in Ontario, Canada. METHODS: We conducted a retrospective cohort study of children from singleton births in TARGet Kids! primary care network with repeated measures of weight and height/length from birth to 14 years, who were linked to health administrative databases. Piecewise linear mixed models were used to model weight (kg/month) and height (cm/month) trajectories with knots at 3, 12, and 84 months. Analyses were conducted based on chronological age. RESULTS: There were 4423 children included with a mean of 11 weight and height measures per child. The mean age at the last visit was 5.9 years (Standard Deviation: 3.1). Generally, the more preterm, the lower the mean value of weight and height until early adolescence. Differences in mean weight and height for very/moderate preterm and late preterm compared to full term were evident until 12 months of age. Weight trajectories were similar between children born late preterm and full term with small differences from 84-168 months (mean difference (MD) -0.04 kg/month, 95% CI -0.06, -0.03). Children born late preterm had faster height gain from 0-3 months (MD 0.70 cm/month, 95% CI 0.42, 0.97) and 3-12 months (MD 0.17 cm/month, 95% CI 0.11, 0.22). CONCLUSIONS: Compared to full term, children born late preterm had lower average weight and height from birth to 14 years, had a slightly slower rate of weight gain after 84 months and a faster rate of height gain from 0-12 months. Follow-up is needed to determine if growth differences are associated with long-term disease risk.

Postsecondary Students' Knowledge of and Adherence to the 2019 Canada's Food Guide: A Cross-sectional Pilot Survey.

Purpose: We conducted a pilot survey among young adults attending a suburban Canadian university to understand: (1) knowledge of the 2019 Canada's Food Guide (CFG); (2) self-reported food choices and eating habits; (3) perceived influence of the CFG on food choices and eating habits; and (4) suggestions to improve engagement with CFG.Methods: Students were recruited, through posts on social media platforms, to complete an online questionnaire between 7 March and 6 April 2020.Results: One-hundred and twenty-one (70% women) students responded. One-third (33%) of women and 8% of men reported consuming the recommended proportion of vegetables and fruits (i.e., 40%-60% of the plate) at their most recent meal (P = 0.001). Men were more likely to report overconsuming protein foods than women (58% vs 32%, P = 0.005). The perceived influence of the CFG on food choices and eating habits was low, with a mean score 2.2 ± 1.4 out of 7, with 7 indicating "highly influential." Over 92% of participants believed awareness of the CFG could be improved through social media platforms.Conclusions: Although half of the participants correctly answered all 8 questions that assessed knowledge of the CFG, there is an opportunity for dietitians and related health professionals to improve engagement with CFG.

The association between late preterm birth and cardiometabolic conditions across the life course: A systematic review and meta-analysis.

BACKGROUND: The effect of being born late preterm (34-36 weeks gestation) on cardiometabolic outcomes across the life course is unclear. OBJECTIVES: To systematically review the association between being born late preterm (spontaneous or indicated), compared to the term and cardiometabolic outcomes in children and adults. DATA SOURCES: EMBASE(Ovid), MEDLINE(Ovid), CINAHL. STUDY SELECTION AND DATA EXTRACTION: Observational studies up to July 2021 were included. Study characteristics, gestational age, cardiometabolic outcomes, risk ratios (RRs), odds ratios (ORs), hazard ratios (HRs), mean differences and 95% confidence intervals (CIs) were extracted. SYNTHESIS: We pooled converted RRs using random-effects meta-analyses for diabetes, hypertension, ischemic heart disease (IHD) and body mass index (BMI) with subgroups for children and adults. The risk of bias was assessed using the Newcastle-Ottawa scale and certainty of the evidence was assessed using the grading of recommendations, assessment, development and evaluation (GRADE) approach. RESULTS: Forty-one studies were included (41,203,468 total participants; median: 5.0% late preterm). Late preterm birth was associated with increased diabetes (RR 1.24, 95% CI 1.17, 1.32; nine studies; n = 6,056,511; incidence 0.9%; I2 51%; low certainty) and hypertension (RR 1.21, 95% CI 1.13, 1.30; 11 studies; n = 3,983,141; incidence 3.4%; I2 64%; low certainty) in children and adults combined. Late preterm birth was associated with decreased BMI z-scores in children (standard mean difference -0.38; 95% CI -0.67, -0.09; five studies; n = 32,602; proportion late preterm 8.3%; I2 96%; very low certainty). There was insufficient evidence that late preterm birth was associated with increased IHD risk in adults (HR 1.20, 95% CI 0.89, 1.62; four studies; n = 2,706,806; incidence 0.3%; I2 87%; very low certainty). CONCLUSIONS: Late preterm birth was associated with an increased risk of diabetes and hypertension. The certainty of the evidence was low or very low. Inconsistencies in late preterm and term definitions, confounding variables and outcome age limited the comparability of studies.

Metabolite profiles and the risk of metabolic syndrome in early childhood: a case-control study.

BACKGROUND: Defining the metabolic syndrome (MetS) in children remains challenging. Furthermore, a dichotomous MetS diagnosis can limit the power to study associations. We sought to characterize the serum metabolite signature of the MetS in early childhood using high-throughput metabolomic technologies that allow comprehensive profiling of metabolic status from a biospecimen. METHODS: In the Family Atherosclerosis Monitoring In earLY life (FAMILY) prospective birth cohort study, we selected 228 cases of MetS and 228 matched controls among children age 5 years. In addition, a continuous MetS risk score was calculated for all 456 participants. Comprehensive metabolite profiling was performed on fasting serum samples using multisegment injection-capillary electrophoresis-mass spectrometry. Multivariable regression models were applied to test metabolite associations with MetS adjusting for covariates of screen time, diet quality, physical activity, night sleep, socioeconomic status, age, and sex. RESULTS: Compared to controls, thirteen serum metabolites were identified in MetS cases when using multivariable regression models, and using the quantitative MetS score, an additional eight metabolites were identified. These included metabolites associated with gluconeogenesis (glucose (odds ratio (OR) 1.55 [95% CI 1.25-1.93]) and glutamine/glutamate ratio (OR 0.82 [95% CI 0.67-1.00])) and the alanine-glucose cycle (alanine (OR 1.41 [95% CI 1.16-1.73])), amino acids metabolism (tyrosine (OR 1.33 [95% CI 1.10-1.63]), threonine (OR 1.24 [95% CI 1.02-1.51]), monomethylarginine (OR 1.33 [95% CI 1.09-1.64]) and lysine (OR 1.23 [95% CI 1.01-1.50])), tryptophan metabolism (tryptophan (OR 0.78 [95% CI 0.64-0.95])), and fatty acids metabolism (carnitine (OR 1.24 [95% CI 1.02-1.51])). The quantitative MetS risk score was more powerful than the dichotomous outcome in consistently detecting this metabolite signature. CONCLUSIONS: A distinct metabolite signature of pediatric MetS is detectable in children as young as 5 years old and may improve risk assessment at early stages of development.

Different Food Sources of Fructose-Containing Sugars and Fasting Blood Uric Acid Levels: A Systematic Review and Meta-Analysis of Controlled Feeding Trials.

BACKGROUND: Although fructose as a source of excess calories increases uric acid, the effect of the food matrix is unclear. OBJECTIVES: To assess the effects of fructose-containing sugars by food source at different levels of energy control on uric acid, we conducted a systematic review and meta-analysis of controlled trials. METHODS: MEDLINE, Embase, and the Cochrane Library were searched (through 11 January 2021) for trials ≥ 7 days. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars in diets); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced in diets) designs. Independent reviewers (≥2) extracted data and assessed the risk of bias. Grading of Recommendations, Assessment, Development, and Evaluation was used to assess the certainty of evidence. RESULTS: We included 47 trials (85 comparisons; N = 2763) assessing 9 food sources [sugar-sweetened beverages (SSBs), sweetened dairy, fruit drinks, 100% fruit juice, fruit, dried fruit, sweets and desserts, added nutritive sweetener, and mixed sources] across 4 energy control levels in predominantly healthy, mixed-weight adults. Total fructose-containing sugars increased uric acid levels in substitution trials (mean difference, 0.16 mg/dL;  95% CI:  0.06-0.27 mg/dL;  P = 0.003), with no effect across the other energy control levels. There was evidence of an interaction by food source: SSBs and sweets and desserts increased uric acid levels in the substitution design, while SSBs increased and 100% fruit juice decreased uric acid levels in addition trials. The certainty of evidence was high for the increasing effect of SSBs in substitution and addition trials and the decreasing effect of 100% fruit juice in addition trials and was moderate to very low for all other comparisons. CONCLUSIONS: Food source more than energy control appears to mediate the effects of fructose-containing sugars on uric acid. The available evidence provides reliable indications that SSBs increase and 100% fruit juice decreases uric acid levels. More high-quality trials of different food sources are needed. This trial was registered at clinicaltrials.gov as NCT02716870.

Serum nonesterified fatty acids have utility as dietary biomarkers of fat intake from fish, fish oil, and dairy in women.

Nutritional studies rely on various biological specimens for FA determination, yet it is unclear how levels of serum NEFAs correlate with other circulating lipid pools. Here, we used a high-throughput method (<4 min/sample) based on multisegment injection-nonaqueous capillary electrophoresis-mass spectrometry (MSI-NACE-MS) to investigate whether specific serum NEFAs have utility as biomarkers of dietary fat intake in women. We first identified circulating NEFAs correlated with long-term/habitual food intake among pregnant women with contrasting dietary patterns (n = 50). Acute changes in serum NEFA trajectories were also studied in nonpregnant women (n = 18) following high-dose (5 g/day) fish oil (FO) supplementation or isoenergetic sunflower oil placebo over 56 days. In the cross-sectional study, serum ω-3 FAs correlated with self-reported total ω-3 daily intake, notably EPA as its NEFA (r = 0.46; P = 0.001), whereas pentadecanoic acid was associated with full-fat dairy intake (r = 0.43; P = 0.002), outcomes consistent with results from total FA serum hydrolysates. In the intervention cohort, serum ω-3 NEFAs increased 2.5-fold from baseline within 28 days following FO supplementation, and this increase was most pronounced for EPA (P = 0.0004). Unlike for DHA, circulating EPA as its NEFA also strongly correlated to EPA concentrations measured from erythrocyte phospholipid hydrolysates (r = 0.66; P = 4.6 × 10-10) and was better suited to detect dietary nonadherence. We conclude that MSI-NACE-MS offers a rapid method to quantify serum NEFAs and objectively monitor dietary fat intake in women that is complementary to food-frequency questionnaires.

Nonnutritive sweetener consumption during pregnancy, adiposity, and adipocyte differentiation in offspring: evidence from humans, mice, and cells.

BACKGROUND: Obesity often originates in early life, and is linked to excess sugar intake. Nonnutritive sweeteners (NNS) are widely consumed as "healthier" alternatives to sugar, yet recent evidence suggests NNS may adversely influence weight gain and metabolic health. The impact of NNS during critical periods of early development has rarely been studied. We investigated the effect of prenatal NNS exposure on postnatal adiposity and adipocyte development. METHODS: In the CHILD birth cohort (N = 2298), we assessed maternal NNS beverage intake during pregnancy and child body composition at 3 years, controlling for maternal BMI and other potential confounders. To investigate causal mechanisms, we fed NNS to pregnant C57BL6J mice at doses relevant to human consumption (42 mg/kg/day aspartame or 6.3 mg/kg/day sucralose), and assessed offspring until 12 weeks of age for: body weight, adiposity, adipose tissue morphology and gene expression, glucose and insulin tolerance. We also studied the effect of sucralose on lipid accumulation and gene expression in cultured 3T3-L1 pre-adipocyte cells. RESULTS: In the CHILD cohort, children born to mothers who regularly consumed NNS beverages had elevated body mass index (mean z-score difference +0.23, 95% CI 0.05-0.42 for daily vs. no consumption, adjusted for maternal BMI). In mice, maternal NNS caused elevated body weight, adiposity, and insulin resistance in offspring, especially in males (e.g., 47% and 15% increase in body fat for aspartame and sucralose vs. controls, p < 0.001). In cultured adipocytes, sucralose exposure at early stages of differentiation caused increased lipid accumulation and expression of adipocyte differentiation genes (e.g., C/EBP-α, FABP4, and FASN). These genes were also upregulated in adipose tissue of male mouse offspring born to sucralose-fed dams. CONCLUSION: By triangulating evidence from humans, mice, and cultured adipocytes, this study provides new evidence that maternal NNS consumption during pregnancy may program obesity risk in offspring through effects on adiposity and adipocyte differentiation.

Validity and Reproducibility of a Semi-Quantitative Food-Frequency Questionnaire Designed to Measure the Nutrient Intakes of Canadian South Asian Infants at 12 Months of Age.

Purpose: Validated methods to assess diet of non-European infants are sparse. We assessed the validity and reliability of a semi-quantitative food-frequency questionnaire (FFQ) for South Asian infants in Canada.Methods: We developed an 80-item FFQ to assess infant nutrient intake in the South Asian Birth Cohort study (START). Caregivers completed the FFQ twice along with two 24-hour diet recalls. We measured infant plasma ferritin to cross-validate reported iron intake. We evaluated validity using Spearman's rho (ρ), and reliability using the intraclass correlation coefficient.Results: Seventy-six caregivers provided 2 FFQs and 2 24-hour diet recalls. Energy-adjusted, de-attenuated correlations between the FFQs and 24-hour diet recalls ranged from -0.29 (monounsaturated fat) through 1.00 (cholesterol). The FFQ overestimated energy intake by 128%. Iron intake by 24-hour diet recalls correlated with plasma ferritin (r = 0.41; P = 0.01; n = 37), but iron intake by FFQ did not. The average reproducibility coefficient of the FFQ ranged from 0.24 (macronutrients) to 0.65 (minerals).Conclusions: Among South Asian infants living in Canada, at least 2 days of diet recall completed with the primary caregiver yields more valid and reproducible estimates of nutrient intakes than a semi-quantitative FFQ, and it highlights that careful selection of FFQ portion sizes is important for assessing dietary intake with an FFQ.

Correction to: Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial.

In contrast to statements made in the above paper, measurements of waist and hip circumference were in fact available.

The Effect of Vitamin D Supplementation on Prostate Cancer: A Systematic Review and Meta-Analysis of Clinical Trials.

Vitamin D has received attention for its potential to disrupt cancer processes. However, its effect in the treatment of prostate cancer is controversial. This study aimed to assess the effect of vitamin D supplementation on patients with prostate cancer. In the present study, PubMed, Scopus, ISI Web of Science, and Google Scholar were searched up to September 2017 for trials that evaluated the effect of vitamin D supplementation on prostate specific antigen (PSA) response, mortality, and its possible side effects in participants with prostate cancer. The DerSimonian and Laird inverse-weighted random-effects model was used to pool the effect estimates. Twenty-two studies (16 before-after and 6 randomized controlled trials) were found and included in the meta-analysis. The analysis of controlled clinical trials revealed that PSA change from baseline [weighted mean difference (WMD)=-1.66 ng/ml, 95% CI: -0.69, 0.36, p=0.543)], PSA response proportion (RP=1.18, 95% CI: 0.97, 1.45, p=0.104) and mortality rate (risk ratio (RR)=1.05, 95% CI: 0.81-1.36; p=0.713) were not significantly different between vitamin D supplementation and placebo groups. Single arm trials revealed that vitamin D supplementation had a modest effect on PSA response proportion: 19% of those enrolled had at least a 50% reduction in PSA by the end of treatment (95% CI: 7% to 31%; p=0.002). Although before-after studies showed that vitamin D increases the PSA response proportion, it does not seem that patients with prostate cancer benefit from high dose vitamin D supplementation and it should not be recommended for the treatment.

Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial.

AIMS/HYPOTHESIS: In line with current advice, we assessed the effect of replacing carbohydrate consumption with mixed nut consumption, as a source of unsaturated fat, on cardiovascular risk factors and HbA1c in type 2 diabetes. The data presented here are from a paper that was retracted at the authors' request ( https://doi.org/10.2337/dc16-rt02 ) owing to lack of adjustment for repeated measures in the same individual. Our aim, therefore, was to fix the error and add new complementary data of interest, including information on clotting factors and LDL particle size. METHODS: A total of 117 men and postmenopausal women with type 2 diabetes who were taking oral glucose-lowering agents and with HbA1c between 47.5 and 63.9 mmol/mol (6.5-8.0%) were randomised after stratification by sex and baseline HbA1c in a parallel design to one of three diets for 3 months: (1) 'full-dose nut diet' (n = 40): a diet with 2.0 MJ (477 kcal) per 8.4 MJ (2000 kcal) energy provided as mixed nuts (75 g/day); (2) 'full-dose muffin diet' (n = 39): a diet with 1.97 MJ (471 kcal) per 8.4 MJ (2000 kcal) energy provided as three whole-wheat muffins (188 g/day), with a similar protein content to the nuts, and the same carbohydrate-derived energy content as the monounsaturated fatty acid-derived energy content in the nuts; or (3) 'half-dose nut diet' (n = 38): a diet with 1.98 MJ (474 kcal) per 8.4 MJ (2000 kcal) energy provided as half portions of both the nuts and muffins. The primary outcome was change in HbA1c. The study was carried out in a hospital clinical research centre and concluded in 2008. Only the statistician, study physicians and analytical technicians could be blinded to the group assessment. RESULTS: A total of 108 participants had post-intervention data available for analysis (full-dose nut group, n = 40; full-dose muffin group, n = 35; half-dose nut group, n = 33). Compared with the full-dose muffin diet, the full-dose nut diet provided 9.2% (95% CI 7.1, 11.3) greater total energy intake from monounsaturated fat. The full-dose nut diet (median intake, 75 g/day) also reduced HbA1c compared with the full-dose muffin diet by -2.0 mmol/mol (95% CI -3.8, -0.3 mmol/mol) (-0.19% [95% CI -0.35%, -0.02%]), (p = 0.026). Estimated cholesterol levels in LDL particles with a diameter <255 ångström [LDL-c<255Å]) and apolipoprotein B were also significantly decreased after the full-dose nut diet compared with the full-dose muffin diet. According to the dose response, the full-dose nut diet is predicted to reduce HbA1c (-2.0 mmol/mol [-0.18%]; p = 0.044), cholesterol (-0.25 mmol/l; p = 0.022), LDL-cholesterol (-0.23 mmol/l; p = 0.019), non-HDL-cholesterol (-0.26 mmol/l; p = 0.020), apolipoprotein B (-0.06 g/l, p = 0.013) and LDL-c<255Å (-0.42 mmol/l; p < 0.001). No serious study-related adverse events occurred, but one participant on the half-dose nut diet was hospitalised for atrial fibrillation after shovelling snow. CONCLUSIONS/INTERPRETATION: Nut intake as a replacement for carbohydrate consumption improves glycaemic control and lipid risk factors in individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00410722 FUNDING: The study was funded by the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Loblaw Companies and the Canada Research Chairs Program of the Government of Canada.

Relation of total sugars, fructose and sucrose with incident type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Sugar-sweetened beverages are associated with type 2 diabetes. To assess whether this association holds for the fructose-containing sugars they contain, we conducted a systematic review and meta-analysis of prospective cohort studies. METHODS: We searched MEDLINE, Embase, CINAHL and the Cochrane Library (through June 2016). We included prospective cohort studies that assessed the relation of fructose-containing sugars with incident type 2 diabetes. Two independent reviewers extracted relevant data and assessed risk of bias. We pooled risk ratios (RRs) using random effects meta-analyses. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Fiffeen prospective cohort studies (251 261 unique participants, 16 416 cases) met the eligibility criteria, comparing the highest intake (median 137, 35.2 and 78 g/d) with the lowest intake (median 65, 9.7 and 25.8 g/d) of total sugars, fructose and sucrose, respectively. Although there was no association of total sugars (RR 0.91, 95% confidence interval [CI] 0.76-1.09) or fructose (RR 1.04, 95% CI 0.84-1.29) with type 2 diabetes, sucrose was associated with a decreased risk of type 2 diabetes (RR 0.89, 95% CI 0.80-0.98). Our confidence in the estimates was limited by evidence of serious inconsistency between studies for total sugars and fructose, and serious imprecision in the pooled estimates for all 3 sugar categories. INTERPRETATION: Current evidence does not allow us to conclude that fructose-containing sugars independent of food form are associated with increased risk of type 2 diabetes. Further research is likely to affect our estimates. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01608620.

Harmonization of Food-Frequency Questionnaires and Dietary Pattern Analysis in 4 Ethnically Diverse Birth Cohorts.

BACKGROUND: Canada is an ethnically diverse nation, which introduces challenges for health care providers tasked with providing evidence-based dietary advice. OBJECTIVES: We aimed to harmonize food-frequency questionnaires (FFQs) across 4 birth cohorts of ethnically diverse pregnant women to derive robust dietary patterns to investigate maternal and newborn outcomes. METHODS: The NutriGen Alliance comprises 4 prospective birth cohorts and includes 4880 Canadian mother-infant pairs of predominantly white European [CHILD (Canadian Healthy Infant Longitudinal Development) and FAMILY (Family Atherosclerosis Monitoring In earLY life)], South Asian [START (SouTh Asian birth cohoRT)-Canada], or Aboriginal [ABC (Aboriginal Birth Cohort)] origins. CHILD used a multiethnic FFQ based on a previously validated instrument designed by the Fred Hutchinson Cancer Research Center, whereas FAMILY, START, and ABC used questionnaires specifically designed for use in white European, South Asian, and Aboriginal people, respectively. The serving sizes and consumption frequencies of individual food items within the 4 FFQs were harmonized and aggregated into 36 common food groups. Principal components analysis was used to identify dietary patterns that were internally validated against self-reported vegetarian status and externally validated against a modified Alternative Healthy Eating Index (mAHEI). RESULTS: Three maternal dietary patterns were identified-"plant-based," "Western," and "health-conscious"-which collectively explained 29% of the total variability in eating habits observed in the NutriGen Alliance. These patterns were strongly associated with self-reported vegetarian status (OR: 3.85; 95% CI: 3.47, 4.29; r2 = 0.30, P < 0.001; for a plant-based diet), and average adherence to the plant-based diet was higher in participants in the fourth quartile of the mAHEI than in the first quartile (mean difference: 46.1%; r2 = 0.81, P < 0.001). CONCLUSION: Dietary data collected by using FFQs from ethnically diverse pregnant women can be harmonized to identify common dietary patterns to investigate associations between maternal dietary intake and health outcomes.

A systematic review and meta-analysis of nut consumption and incident risk of CVD and all-cause mortality.

Dietary patterns containing nuts are associated with a lower risk of CVD mortality, and increased nut consumption has been shown to have beneficial effects on CVD risk factors including serum lipid levels. Recent studies have reported on the relationship between nut intake and CVD outcomes and mortality. Our objective was to systematically review the literature and quantify associations between nut consumption and CVD outcomes and all-cause mortality. Five electronic databases (through July 2015), previous reviews and bibliographies of qualifying articles were searched. In the twenty included prospective cohort studies (n 467 389), nut consumption was significantly associated with a lower risk of all-cause mortality (ten studies; risk ratio (RR) 0·81; 95 % CI 0·77, 0·85 for highest v. lowest quantile of intake, P het=0·04, I 2=43 %), CVD mortality (five studies; RR 0·73; 95 % CI 0·68, 0·78; P het=0·31, I 2=16 %), all CHD (three studies; RR 0·66; 95 % CI 0·48, 0·91; P het=0·0002, I 2=88 %) and CHD mortality (seven studies; RR 0·70; 95 % CI 0·64, 0·76; P het=0·65, I 2=0 %), as well as a statistically non-significant reduction in the risk of non-fatal CHD (three studies; RR 0·71; 95 % CI 0·49, 1·03; P het=0·03, I 2=72 %) and stroke mortality (three studies; RR 0·83; 95 % CI 0·69, 1·00; P het=0·54, I 2=0 %). No evidence of association was found for total stroke (two studies; RR 1·05; 95 % CI 0·69, 1·61; P het=0·04, I 2=77 %). Data on total CVD and sudden cardiac death were available from one cohort study, and they were significantly inversely associated with nut consumption. In conclusion, we found that higher nut consumption is associated with a lower risk of all-cause mortality, total CVD, CVD mortality, total CHD, CHD mortality and sudden cardiac death.

Rationale, design, and methods for Canadian alliance for healthy hearts and minds cohort study (CAHHM) - a Pan Canadian cohort study.

BACKGROUND: The Canadian Alliance for Healthy Hearts and Minds (CAHHM) is a pan-Canadian, prospective, multi-ethnic cohort study being conducted in Canada. The overarching objective of the CAHHM is to understand the association of socio-environmental and contextual factors (such as societal structure, activity, nutrition, social and tobacco environments, and access to health services) with cardiovascular risk factors, subclinical vascular disease, and cardiovascular and other chronic disease outcomes. METHODS/DESIGN: Participants between 35 and 69 years of age are being recruited from existing cohorts and a new First Nations Cohort to undergo a detailed assessment of health behaviours (including diet and physical activity), cognitive function, assessment of their local home and workplace environments, and their health services access and utilization. Physical measures including weight, height, waist/hip circumference, body fat percentage, and blood pressure are collected. In addition, eligible participants undergo magnetic resonance imaging (MRI) of the brain, heart, carotid artery and abdomen to detect early subclinical vascular disease and ectopic fat deposition. DISCUSSION: CAHHM is a prospective cohort study designed to investigate the impact of community level factors, individual health behaviours, and access to health services, on cognitive function, subclinical vascular disease, fat distribution, and the development of chronic diseases among adults living in Canada.

Assessing the quality of published genetic association studies in meta-analyses: the quality of genetic studies (Q-Genie) tool.

BACKGROUND: Advances in genomics technology have led to a dramatic increase in the number of published genetic association studies. Systematic reviews and meta-analyses are a common method of synthesizing findings and providing reliable estimates of the effect of a genetic variant on a trait of interest. However, summary estimates are subject to bias due to the varying methodological quality of individual studies. We embarked on an effort to develop and evaluate a tool that assesses the quality of published genetic association studies. Performance characteristics (i.e. validity, reliability, and item discrimination) were evaluated using a sample of thirty studies randomly selected from a previously conducted systematic review. RESULTS: The tool demonstrates excellent psychometric properties and generates a quality score for each study with corresponding ratings of 'low', 'moderate', or 'high' quality. We applied our tool to a published systematic review to exclude studies of low quality, and found a decrease in heterogeneity and an increase in precision of summary estimates. CONCLUSION: This tool can be used in systematic reviews to inform the selection of studies for inclusion, to conduct sensitivity analyses, and to perform meta-regressions.