There is growing interest in the potential role of omega-3/fibre-rich seeds in attenuating obesity and other cardiovascular disease (CVD) risk factors in individuals with type 2 diabetes mellitus (T2DM). Preliminary data suggests that consumption of white Salvia hispanica L. (Salba®) seeds prolongs satiety and may aid weight loss. This randomized, double-blind, parallel study assessed the efficacy and safety of Salvia hispanica in overweight/obese individuals with T2DM on weight, body composition, glycemic control and other CVD risk factors. Fifty-eight participants consumed a hypocaloric diet including Salvia hispanica or an energy-and-fibre-matched control over 24 weeks. Greater reductions in weight, waist circumference and inflammation occurred in the Salvia hispanica group versus control. There were no significant between-group differences in safety parameters, glycemic control or other CVD risk factors. Salvia hispanica seeds may support weight loss in overweight/obese individuals with T2DM. Further research is needed to determine whether these effects are maintained.

Breast cancer molecular subtypes, based on expression of estrogen, progesterone and human epidermal growth factor 2 receptors, alter prognosis and treatment options. α-linolenic acid (ALA) is a complementary therapy, however its effectiveness across breast cancer types and estrogen environments is unclear. This research determined the effect of ALA on growth, apoptosis, fatty acid profile, and gene changes in four breast cancer cell lines with varying receptor expression with or without (±) estradiol (E2). ALA (50-200uM) ± E2 reduced growth in all cell lines. 75μM ALA +E2 increased phospholipid % ALA in all cell lines and induced apoptosis in cell lines lacking the three receptors. Cellular % ALA was positively associated with apoptosis and inversely associated with cell growth. ALA altered expression of cell cycle, apoptosis and signal transduction genes. In conclusion, ALA incorporates into breast cancer cells, reduces growth and induces apoptosis regardless of receptor status or E2 level.

The primary objective of this research was to explore the impact of glucose ingestion on 2-back task performance (accuracy, discrimination, and reaction times (RT) to target), its relationship to neural activation, using functional magnetic resonance imaging, and potential modulation by insulin resistance (IR) and low density lipoprotein (LDL) in hypertensive but otherwise healthy older adults. While there was no effect of glucose ingestion on task performance or task-relevant neural activation patterns, this study uniquely observed that IR and LDL associated with all 3 measures of 2-back performance and task-relevant neural activation patterns. The left and right precuneus, left cingulate, and left insula were identified as task-associated regions according to our specific target minus nontarget contrast. Of particular importance was the task activation in the right precuneus as it both showed sensitivity to IR and predicted task RTs to targets, suggesting it plays a modulatory role linking IR to task performance.

This study aims to examine how the migration experience influences newcomer mothers’ young child feeding and care practices and their children’s overall health. The thesis comprises three separate manuscripts, each of which examines one of the three intermediate determinants of the nutritional status of young children (UNICEF 1990): access to healthcare, household food insecurity, and child feeding and care practices. The research was conducted in Toronto’s Jane-Finch neighbourhood, a suburban neighbourhood home to a high density of newcomers. Thirty-two participants (16 Sri Lankan Tamil and 16 Latin American) who had migrated to Canada within the past five years as refugee claimants or family sponsored immigrants participated in the study. Data collection consisted of semi-structured interviews with women from low-income households who had a child between the ages of 1 and 5 years. Spanish and Tamil speaking interviewers interviewed each participant two or three times. Data was analyzed using a mid-level approach in which broad analytical themes are determined prior to analysis and specific themes were then generated based on participants’ perspectives and are grounded in the data. The first manuscript examines newcomer mothers’ experiences accessing physicians for their children and identifies the major gaps between mothers’ expectations and their actual experiences that lead to barriers in communication and overall patient dissatisfaction. The second manuscript demonstrates that mothers’ past experiences with food insecurity affect two aspects of the construct of food insecurity: its managed aspect and its temporal nature. This finding has implications for the measurement of food insecurity in newcomer populations. The third manuscript reveals that newcomer mothers are exposed to several parallel and often conflicting systems of knowledge concerning health and nutrition for their children, and that their utilization of Canada’s Food Guide is impeded by its failure to acknowledge alternate parallel knowledge systems. These findings can be applied to the development of social and health policy aimed at improving cultural competency in healthcare and nutrition education and at ameliorating the income constraints leading to household food insecurity.

Over 12% of households were food insecure in Canada in 2011. Despite recognition of this problem, there remains no targeted public policy to address it. To inform interventions, examined in this thesis were how changes in financial resources related to changes in severity of food insecurity, the needs of food insecure households, and the effectiveness of current interventions. Studies 1, 2, 4, and 5 utilized data from a sample of 485 low income families living in high poverty neighbourhoods in Toronto, and Study 3 used data from the Canadian Community Health Survey (CCHS) 2009-2011. In Study 1, the sensitivity of severity of food insecurity to changes in employment and income was observed. In Study 2, it was found that severity of food insecurity was associated with increasing probability of experiencing hardships in other domains such as delayed bill payments and giving up household services. The relationship between food insecurity and obesity among women was examined in Study 3, and it was shown that diagnoses of mood disorder partially explained the association. Patterns of association also varied by family status and severity of experiences. In Studies 4 and 5, use and non-use of current interventions focused on alleviating hunger (i.e. food banks) and improving healthy food access in communities (i.e. community gardens, Good Food Box) were examined among food insecure families. There was a low prevalence of use of all types of programs. Programs were not used because programs were not accessible or were not viewed as appropriate supports to meet needs. Taken together, findings suggest that interventions focused on potential manifestations and consequences of food insecurity are misplaced, and reinforce the urgent need for interventions to alleviate the financial insufficiency and insecurity that underpins food insecurity.

The effect of exercise (EXR) on food intake (FI), subjective appetite and net energy balance was investigated in normal weight (NW), overweight (OW) and obese (OB) boys. Each boy received in random order either a non-caloric sweetened control (CON) or glucose (GLU) drink after either EXR or sedentary activity. Normal weight and OW/OB boys exercised at their ventilation threshold (VeT) in experiment 1 and NW boys exercised at 25% above their VeT in experiment 2. Overweight/OB boys ate significantly more total food than NW boys but not when adjusted for body weight. Food intake was lower after the GLU drink. Although EXR increased average appetite it did not affect FI. However, net energy balance was reduced by EXR in OW/OB boys, but not in NW boys. Thus, while EXR increases subjective appetite, apparent intake compensation occurred only in NW, but not in OW/OB boys, resulting in reduced net energy balance in OW/OB boys.

The effect of exercise (EXR) on food intake (FI), subjective appetite and net energy balance was investigated in normal weight (NW), overweight (OW) and obese (OB) boys. Each boy received in random order either a non-caloric sweetened control (CON) or glucose (GLU) drink after either EXR or sedentary activity. Normal weight and OW/OB boys exercised at their ventilation threshold (VeT) in experiment 1 and NW boys exercised at 25% above their VeT in experiment 2. Overweight/OB boys ate significantly more total food than NW boys but not when adjusted for body weight. Food intake was lower after the GLU drink. Although EXR increased average appetite it did not affect FI. However, net energy balance was reduced by EXR in OW/OB boys, but not in NW boys. Thus, while EXR increases subjective appetite, apparent intake compensation occurred only in NW, but not in OW/OB boys, resulting in reduced net energy balance in OW/OB boys.

Fatty acid synthase (FAS) is over-expressed in many human cancers and its activity is required for cancer cell survival. To understand why FAS is over-expressed, we compared in breast cancer cells the utilization of fatty acids synthesized endogenously by FAS to those supplied exogenously in the culture medium. We found that endogenously synthesized fatty acids are esterified to the same lipid and phospholipid classes in the same proportions as those derived exogenously and that some endogenous fatty acids are excreted. Thus, FAS over-expression in cancer does not fulfill a specific requirement for endogenously synthesized fatty acids. We next investigated whether lipogenic activity mediated by FAS was, instead, involved in the maintenance of high glycolytic activity in cancer cells. By culturing breast cancer and non-cancer cells in anoxic conditions, we increased glycolysis 2-3 fold but observed no concomitant increase in lipogenesis. More research is needed to understand why FAS is over-expressed in cancer.

Substantial evidence supports a role of diet in glucose metabolism, but only a few reports have investigated the impact of diet during pregnancy on risk of gestational diabetes (GDM). Although metabolic hormones have been detected in milk, no studies have investigated the impact of maternal metabolic status assessed during pregnancy on insulin and adiponectin concentrations in human milk. The purpose of this thesis was to investigate the association of maternal macronutrient intakes with metabolic status during pregnancy and its subsequent impact on human milk hormones. Participating women (n=216) underwent a 3-hour oral glucose tolerance test at 30 (95% confidence interval [CI] 25, 33) weeks gestation, recalled their second trimester dietary intake, and donated early (the first week) and mature (3 months postpartum) milk. Higher vegetable and fruit fiber intake was associated with reduced insulin resistance (beta±SE -0.100±0.029, p=0.0008) and increased insulin sensitivity (0.029±0.012, p=0.01) among those with a family history of type 2 diabetes. Lower % carbohydrate and higher % total fat were associated with increased GDM risk (odds ratio 0.60 [95% CI 0.40, 0.90] and 1.61 [1.06, 2.44], respectively). Prenatal metabolic abnormalities including higher pregravid body mass index (beta±SE 0.053±0.014, p=0.0003), in addition to gravid hyperglycemia (0.218±0.087, p=0.01), insulin resistance (0.255±0.047, p<0.0001), lower insulin sensitivity (-0.521±0.108, p<0.0001), and higher serum adiponectin (0.116±0.029, p<0.0001) were associated with higher insulin in mature milk. Obstetrical measures including nulliparity (0.171±0.058, p=0.004), longer duration of gestation (0.546±0.146, p=0.0002), and unscheduled caesarean section (0.387±0.162, p=0.02) were associated with higher adiponectin in early milk. Holder pasteurization, a process recommended by the Human Milk Bank Association of North America before distributing human donor milk, reduced milk adiponectin and insulin concentrations by 32.8% and 46.1%, respectively (both p<0.0001). In conclusion, the distribution of macronutrient intakes during pregnancy was associated with risk for abnormal glucose metabolism later in pregnancy. In addition, maternal prenatal metabolic abnormalities were associated with high insulin concentrations in mature milk, while only obstetrical parameters were associated adiponectin concentrations in early milk. Our findings support the need for continued work to determine optimal prenatal nutritional strategies to prevent GDM and subsequently to improve infant nutrition.

Emerging evidence suggests that vitamin D may be associated with type 2 diabetes (T2DM), however current data are inconsistent regarding metabolic disorders underlying T2DM. The objectives of this thesis were to investigate the association of vitamin D with the primary pathophysiological disorders of type 2 diabetes: namely insulin resistance (IR) and beta (β)-cell dysfunction, and the metabolic syndrome (MetS). All studies included individuals participating in the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study, comprising 712 subjects 30 years and older, and at risk of T2DM at baseline. Serum 25-hydroxyvitamin D [25(OH)D] was measured to assess vitamin D nutritional status. Validated oral glucose tolerance test derived indices for IR and β-cell function were calculated. In the first cross-sectional study, multivariate linear regression analyses indicated a significant inverse association of serum 25(OH)D with IR (β=-0.003, p=0.007) and a significant positive association of 25(OH)D with β-cell function (β=0.004, p=0.03) at the baseline PROMISE clinic visit (n=712). In another cross-sectional study also conducted using data from the baseline PROMISE clinic visit, higher 25(OH)D was found to be significantly associated with a reduced presence of the MetS after multivariate adjustment (OR=0.76, 95% CI 0.62-0.93). Low serum 25(OH)D was also significantly associated with various MetS components. In light of the findings in the first cross-sectional study, the third study examined prospective associations of baseline 25(OH)D with 3-year follow-up IR and β-cell function (n=489). Although baseline 25(OH)D was not significantly associated with follow-up IR, a significant positive association of baseline 25(OH)D with β-cell function at follow-up was observed (β=0.005, p=0.015). Lastly, in a longitudinal substudy (n=127), seasonal changes in 25(OH)D over 2.5 years did not significantly affect changes in IR and β-cell function. In conclusion, results indicated that baseline serum 25(OH)D was cross-sectionally related to IR, β-cell function and the MetS, and was prospectively related to β-cell function at the 3-year follow-up. In addition, seasonal changes in 25(OH)D do not adversely affect IR and β-cell function over time. These findings suggest a potential role for higher 25(OH)D levels in reducing diabetes risk, although additional longitudinal studies are warranted.