Objective. The objective of the present study was to determine if there would be statistically significant differences among apolipoprotein E genotypes in the responsiveness of members of a cluster of seven measures in persons with type 2 diabetes consuming a flaxseed oil supplement (FOS). The cluster of seven are: abdominal obesity, hypertension, platelet hyperaggregability, hyperglycemia, dyslipidemia (decreased serum levels of high-density lipoprotein cholesterol (HDLc) and increased serum levels of triglycerides), increased serum low-density lipoprotein (LDL) oxidation (LDL conjugated dienes) and increased inflammation. All cluster members exacerbate type 2 diabetes. Methods. Thirty-two patients with well-controlled type 2 diabetes participated in this double-blind, placebo (safflower oil supplementation (SOS))-controlled study consisting of three visits. Apolipoprotein E genotyping was done at visit one. The cluster of seven was assessed at each visit. Results. Only platelet aggregability decreased as the result of the FOS relative to placebo while it appeared that there might be some potential for FOS to decrease LDL conjugated dienes. No apolipoprotein E genotype affected any of the cluster of seven responsiveness. Conclusions. Identified apolipoprotein E genotypes played no role in the responsiveness of any member of the cluster of seven to FOS in this study.

Objective. The objective of the study was to determine if there would be statistically significant differences or trends among apolipoprotein E genotypes in the responsiveness of members of a cluster of seven measures in older persons with type 2 diabetes mellitus (T2DM) consuming flaxseed lignan complex (FLC). The cluster of seven are abdominal obesity, hypertension, platelet hyperaggregability, hyperglycemia, dyslipidemia (decreased plasma levels of high-density lipoprotein cholesterol (HDLc), and increased plasma levels of triglycerides), increased low-density lipoprotein (LDL) oxidation and increased inflammation. All cluster members exacerbate T2DM. Methods. Sixteen patients with well-controlled T2DM participated in this double-blind randomized, placebo-controlled crossover study consisting of four visits. Apolipoprotein E genotyping was done at visit one. The cluster of seven, diet, exercise, smoking and medication use were assessed at each visit. Results. The 3/4 genotype showed a stronger downward trend in systolic blood pressure compared to the 3/3 genotype with no trend or significant difference in the 2/4 genotype. There was a downward trend in diastolic blood pressure in genotype 3/3 compared genotype 2/4, which showed no significant difference or trend. Only genotype 3/4 showed a significant drop in diastolic pressure compared to genotypes 2/4 and 3/3. HDLc only showed a downward trend in 3/4 relative to genotypes 2/4 and 3/3. LDL apolipoprotein B oxidation (LDL-Box) only showed an upward trend in 3/3 compared to genotypes 2/4 and 3/4. There were no other significant differences or trends by genotype in the cluster of seven. Conclusions. It appears that those with the 2/4 genotype may not benefit from FLC, those with 3/3 and 3/4 genotypes may benefit only in terms of systolic and diastolic pressures, those with the apo E 3/4 genotype should perhaps avoid FLC to manage HDLc, and those with the 3/3 genotype should perhaps avoid FLC to manage LDL apolipoprotein B oxidation.

The objective of the study was to determine if there would be statistically significant differences or trends among apolipoprotein E genotypes (2/2, 2/3, 2/4, 3/3, 3/4, and 4/4) for each member of the cluster of seven associated with type 2 diabetes (T2D). The cluster of seven includes abdominal obesity, hypertension, platelet hyperaggregability, hyperglycemia, dyslipidemia (decreased plasma levels of high-density lipoprotein cholesterol (HDL-C) and increased plasma levels of triglycerides)), increased low-density lipoprotein (LDL) oxidation, and increased inflammation.

Women with gestational diabetes (GD) have reduced antioxidant capacity; however, the relationship between maternal diet, maternal biochemical capacity, breast milk concentration, and infant intake has not been adequately explored in the literature. An exploration of underlying mechanism(s) is warranted, particularly for nutrient antioxidants impacted by maternal intake. These nutrients may provide a means for modifying maternal and infant antioxidant capacity. Oxygen radical absorbance capacity (ORAC), alpha-tocopherol, ascorbic acid, and beta-carotene concentrations were measured in breast milk of women with and without GD. Plasma, three-day diet records, and breast milk were collected at 6 to 8 weeks postpartum. Student's t-test was used to compare breast milk ORAC, nutrient antioxidant concentration and plasma ORAC between women with and without GD. Pearson correlations were used to determine associations among antioxidant concentrations in breast milk and dietary antioxidant intake. Breast milk antioxidant concentrations were associated with maternal intake of beta-carotene (r = 0.629, p = 0.005). Breast milk and plasma ORAC and antioxidant vitamin concentrations were not significantly different between GD and NG women. Breast milk ORAC associated with breast milk alpha-tocopherol for NG (r = 0.763, p = 0.010), but not GD women (r = 0.385, p = 0.35), and with breast milk ascorbic acid for GD (r = 0.722, p = 0.043) but not NG women (r = 0.141, p = 0.70; interaction p = 0.041). In GD participants, breast milk ORAC was significantly associated with plasma ORAC (r = 0.780, p = 0.039). ORAC and antioxidant vitamin concentrations in breast milk in women with GD were comparable to women with NG; however, the relationships between breast milk ORAC and vitamin concentrations differed in GD versus NG women for alpha-tocopherol and ascorbic acid.

Objective. The intent of the present study was to test two hypotheses. The primary hypothesis was that there would be differences between blood serum individual free fatty acids (SIFFA) and serum individual total fatty acids (SITFA) in terms of their different relationships (correlations) to each of homeostatic model assessment-individual insulin resistance (HOMA-IR) and homeostatic model assessment-individual insulin resistance-percentage β-cell function (HOMA-% β) remaining in human type 2 diabetic patients with pre-flaxseed oil (FXO) and pre-safflower oil (SFO) administration. The secondary hypothesis was that FXO (rich in alpha-linolenic acid, ALA) supplementation would alter these correlations differently in the SIFFA and STIFFA pools in comparison with the placebo SFO (poor in ALA). Methods. Patients were recruited via a newspaper advertisement and two physicians. All patients came to visit 1 and three months later to visit 2. At visit 2, the subjects were randomly assigned (double-blind) to flaxseed or safflower oil (placebo) treatment for three months until visit 3. Results. There were pre-intervention differences in the SIFFA and STIFA pool's relationships with each of HOMA-IR and HOMA-% β. These relatioships remained either unchanged or became significant after intervention (treatment or placebo). There was a negative correlation found between HOMA-IR and serum free ALA (SFALA) mol % after FXO. Serum total ALA (STALA) mol % had no significant correlations with HOMA-IR and HOMA- % β before and after flaxseed oil administration. Conclusions. The SIFFA and SITFA pools have different relationships with HOMA-IR and HOMA-% β for each of pre- and post-intervention. It is concluded that the data support both the primary and the secondary hypotheses indicating that they are correct.

Inflammation exacerbates type 2 diabetes (T2D). Decreased inflammation (as measured by plasma C-reactive protein [PCRP]) arises from increased anti-oxidant capacity. Unknown is whether plasma total peroxyl radical-trapping antioxidant potential (PTRAP) contributes to PCRP reduction in older T2D patients (OT2DP) consuming antioxidant-containing flaxseed lignan complex (FLC). The objective was to determine if PTRAP contributes to reduced PCRP in OT2DP consuming FLC.

Objectives. This review assesses the comparative safety and efficacy of selected 3-hydroxy-3-methylglutaric acid coenzyme A inhibitors (statins, cinnamic acids. 3-hydroxy-3-methyl glutaric acid) on the pre-onset type 2 diabetes (PT2D) and post-onset type 2 diabetes (T2D)-related cluster of seven features (central obesity, hyperglycemia, hypertension, dyslipidemia, pro-thrombosis, oxidation and inflammation). Methods. Google scholar and PubMed were searched for statin*, flaxseed lignan complex (FLC), cinnamic acid (CA)*, and 3-hydroxy-3-methylglutaric acid (HMGA) in conjunction with each of PT2D, T2D and the cluster of seven. An introduction was followed by findings or absence thereof on the impacts of each of statins, FLC, CAs and HMGA on each member of the cluster of seven. Results. Pravastatin manages three features in PT2D, while a number of the statins improve five in T2D. FLC is negative in PT2D but controls four in T2D; it is not clear if the CAs and HMGA in FLC play a role in this success. CAs have potential in six and HMGA has potential in three of the cluster of seven though yet CAs and HMGA are untested in PT2D and T2D in humans. There are safety concerns with some statins and HMGA but FLC and CAs appear safe in the doses and durations tested. Conclusions. Selected statins, FLC, CAs and HMGA can manage or have a potential to manage at least three features of the cluster of seven. Most of the literature-stated concerns are with select statins but there are concerns (one actual and two potential) with HMGA.

OBJECTIVES:This review assesses the polypharmacy reduction potential of cinnamic acids (CAs) and some related compounds in managing three or more of the cluster of seven, pre- and post-type 2 diabetes mellitus (T2DM)-related features (central obesity, hyperglycemia, hypertension, dyslipidemia, pro-thrombosis, oxidation, and inflammation).METHODS:Google scholar and Pubmed were searched for cinnam*, chlorogenic acid, ferulic acid, and caffeic acid in conjunction with each of pre- and post-onset T2DM, central obesity, hyperglycemia, hypertension, dyslipidemia, pro-thrombosis, oxidation, and inflammation. The study was divided into an introduction followed by findings on the impacts of each of the CAs including trans-CA acid, the E isomer of a CA-based thiazolidinedione and a metabolite of that isomer, as well as p-methoxy CA, various cinnamic amides and some other CA-related compounds (chlorogenic acid, cinnamaldehyde, ferulic and caffeic acid).RESULTS:Trans-CA has a potential to manage three, while each of chlorogenic acid, cinnamalde-hyde, caffeic acid and ferulic acid has a potential to manage all seven members of the cluster. Other CA-related compounds identified may manage only one or two of the cluster of seven.CONCLUSIONS:Much of the work has been done in animal models of pre- and post-onset T2DM and non-pre- or post-onset T2DM humans and animals, along with some cell culture and in vitro work. Very little work has been done with human pre- and post-onset T2DM. While there is potential for managing 3 or more members of the cluster with many of these compounds, a definitive answer awaits large pre- and post-T2DM onset clinical trials with humans.

Hypertension in type 2 diabetes patients (T2DP) contributes significantly to myocardial infarction and stroke. Unknown is the impact of flaxseed lignan complex (FLC) on Diabetes Canada's clinical practice guidelines-defined (DCCPG-D) systolic hypertension (SH) and/or diastolic hypertension (DH) in older T2DP. It was hypothesized that FLC (600 mg secoisolariciresinol diglucoside (SDG)/day) for 3 months would decrease DCCPG-D SH and/or DH in older T2DP. The objective was to test this hypothesis.

Introduction: Type 2 Diabetes (T2D) cases continue to rise dramatically despite efforts to get people to exercise and eat with a view to health and combatting the cluster of 7 issues (central obesity (elevated waist circumference), hyperglycaemia, hypertension, dyslipidemia, pro-thrombotic state, increased oxidation (including Low-density Lipoprotein (LDL)) and the pro-inflammatory state associated with pre- and post-onset T2D. Background: There are numerous medications available to deal with these seven major issues. However, each medication currently available manages a maximum of two cluster members at a time. Consequently, polypharmacy is frequently required to manage the cluster of seven. Polypharmacy brings with it high financial costs for numerous medications, the risk of poor compliance (particularly so in older patients), side effects and drug interactions. Thus, there is a search for new agents that reduce the high costs and risks of polypharmacy while at the same time combatting three or more of the cluster of seven. There is very limited evidence to suggest that one or more lignans may efficaciously and safely, in the short and long term, manage at least three of the cluster of seven, pre- and post-T2D onset, thus reducing polypharmacy. However, multi-centre, large clinical trials are required before any definitive conclusions about these lignans can be reached regarding their safe and efficacious polypharmacy reduction potential, both long and short-term, in pre and post-onset T2D management. Conclusion: It is concluded that some lignans appear to have the potential to manage at least three members of the cluster of seven in pre- or post-T2D onset and hence reduce polypharmacy but much more investigation is required to confirm if such is the case. At the moment, there is not enough evidence that any of the lignans will, in the long or short term, safely and efficaciously manage the cluster of seven via polypharmacy reduction.

Plasma low-density lipoprotein apolipoprotein B oxidation (LDL-Box) contributes significantly to atherosclerosis in type 2 diabetes (T2D) patients. Unknown is the impact of antioxidant-containing flaxseed lignan complex (FLC) on plasma total peroxyl radical-trapping antioxidant potential responsiveness (TRAPR) and, consequently, LDL-Box reduction responsiveness (LDLBoxRR). It was hypothesised that in older T2D patients, TRAPR to FLC consumption would dictate LDLBoxRR. The objective was to test this hypothesis.

Background There is a significant deficiency of national health information for Indigenous peoples in Canada. This manuscript describes the Community Profile Survey (CPS), a community-based, national-level survey designed to identify and describe existing healthcare delivery, funding models, and diabetes specific infrastructure and programs in Indigenous communities. Methods The CPS was developed collaboratively through FORGE AHEAD and the First Nations and Inuit Health Branch of Health Canada. Regional and federal engagement and partnerships were built with Indigenous organizations to establish regionally-tailored distribution of the 8-page CPS to 440 First Nations communities. Results were collected (one survey per community) and reported in strata by region, with descriptive analyses performed on all variables. Results were shared with participating communities and regional/federal partners through tailored reports. Results A total of 84 communities completed the survey (19% response rate). The majority of communities had a health centre/office to provide service to their patients with diabetes, with limited on-reserve hospitals for ambulatory or case-sensitive conditions. Few healthcare specialists were located on-site, with patients frequently travelling off-site (> 40 km) for diabetes-related complications. The majority of healthcare professionals on-site were Health Directors, Community Health Nurses, and Home Care Nurses. Many communities had a diabetes registry but few reported a diabetes surveillance system. Regional variation in healthcare services, diabetes programs, and funding models were noted, with most communities engaging in some type of innovative strategy to improve care for patients with diabetes. Conclusions The CPS is the first community-based, national-level survey of its kind in Canada. Although the response rate was low, the CPS was distributed and successfully administered across a broad range of First Nations communities, and future considerations would benefit from a governance structure and leadership that strengthens community engagement, and a longitudinal research approach to increase the representativeness of the data. This type of information is important for communities and regions to inform decision making (maintain successes, and identify areas for improvement), strengthen health service delivery and infrastructure, increase accessibility to healthcare personnel, and allocate funding and/or resources to build capacity and foster a proactive chronic disease prevention and management approach for Indigenous communities across Canada. Trial registration Current ClinicalTrial.gov protocol ID NCT02234973 . Registered: September 9, 2014.

Background: Increased inflammation (as measured by elevated plasma C-reactive protein (CRP) concentrations and elevated HbA1C are linked in type 2 diabetes (T2D) progression. The objective was to test the novel hypothesis that in older T2D patients, flaxseed lignan complex (FLC; containing secoisolariciresinol diglucoside [SDG]) consumption would decrease HbA1C and plasma CRP, resulting in plasma CRP and HbA1C being significantly negatively correlated with elevated plasma enterolactone (ENL; an intestinal bacterial metabolite of SDG). ENL, but not SDG, undergoes intestinal absorption.

Biotransformation of L-tyrosine methyl ester (L-TM) to the methyl ester of para- hydroxycinnamic acid (p-HCAM) using Rhodotorula glutinis yeast phenylalanine/tyrosine ammonia lyase (PTAL; EC 4.3.1.26) enzyme was successfully demonstrated for the first time; progress of the reaction was followed by spectrophotometric determination at 315 nm. The following conditions were optimized for maximal formation of p-HCAM: pH (8.5), temperature (37°C), speed of agitation (50 rpm), enzyme concentration (0.080 μM), and substrate concentration (0.50 mM). Under these conditions, the yield of the reaction was ∼15% in 1 h incubation period and ∼63% after an overnight (∼18 h) incubation period. The product (p-HCAM) of the reaction of PTAL with L-TM was confirmed using Nuclear Magnetic Resonance spectroscopy (NMR). Fourier Transform Infra-Red spectroscopy (FTIR) was carried out to rule out potential hydrolysis of p-HCAM during overnight incubation. Potential antibacterial activity of p-HCAM was tested against several strains of Gram-positive and Gram-negative bacteria. This study describes a synthetically useful transformation, and could have future clinical and industrial applications.

Abstract Objectives. Elevated total serum free fatty acids (FFAs) concentrations have been suggested, controversially, to enhance insulin resistance and decrease percent remaining β-cell function. However, concentrations of individual serum FFAs have never been published in terms of their relationship (correlation) to homeostatic model assessment-insulin resistance (HOMA-IR) and percent remaining β-cell function (HOMA-%β) in the type 2 diabetics (T2Ds). Alpha-linolenic acid consumption has a negative correlation with the insulin resistance, which in turn is negatively correlated with the remaining β-cell function. The primary objective was to test the hypothesis that there would be different relationship (correlation) between the blood serum individual free FFA mol % levels and HOMA-IR and/or HOMA-%β in T2D. The secondary objective was to test the hypothesis that flaxseed oil, previously being shown to be ineffective in the glycemic control in T2Ds, may alter these correlations in a statistically significant manner as well as HOMA-IR and/or HOMA-%β. Methods. Patients were recruited via a newspaper advertisement and two physicians have been employed. All the patients came to visit one and three months later for a second visit. At the second visit, the subjects were randomly assigned (double blind) to flaxseed or safflower oil treatment for three months, until the third visit. Results. Different statistically significant correlations or trends towards among some serum individual free FFA mol % levels and HOMA-IR and HOMA-%β, pre- and post-flaxseed and safflower oil supplementation were found. However, flaxseed oil had no impact on HOMA-IR or HOMA-%β despite statistically significant alterations in correlations compared to baseline HOMA-IR. Conclusions. The obtained data indicate that high doses of flaxseed oil have no statistically significant effect on HOMA-IR or HOMA-%β in T2Ds, probably due to the additive effects of negative and positive correlations.

Elevated waist circumference (WC) and decreased antioxidant capacity are associated with increased low-density lipoprotein (LDL) oxidation. Elevated LDL apolipoprotein B oxidation (LDLBox) and LDL fatty acid oxidation (conjugated dienes [LDL-CD]) contribute to the major causes of death (myocardial infarction and stroke) in type 2 diabetes (T2D). Dietary lignans may alter body fat distribution and have antioxidant potential. The purpose was to test the hypothesis that flaxseed lignan complex (FLC) consumption would significantly better manage WC, increase LDL apolipoprotein B concentration-adjusted total peroxyl radical trapping antioxidant potential (TRAP) and consequently decrease similarly adjusted LDLBox and LDL-CD levels in older type 2 diabetes patients. Such adjustment controls for LDL particle number, hence permitting more informative “per capita” comparisons.

Objectives: To carry out a systematic review of interventions that have aimed at improving screening, treatment, prevention and management of type 2 diabetes and obesity-related chronic disease in Indigenous communities in Canada from 2008 to 2014, with the aim of identifying current best practices.Methods: A comprehensive literature review was carried out through an electronic database search using Medline, EMBASE, PubMED and Google scholar.Results: We identified 17 publications, comprising 13 evaluated interventions. Of them, 7 were school-based programs focused on children, 5 focused on adults, and 1 included both adults and children. Most interventions aimed at encouraging behaviour change, especially dietary change, but did little to address the underlying context of systemic marginalization and colonialism experienced in many Indigenous communities. Interventions focused on improving fitness were more effective than those aimed at dietary change. Overall, we found a range of successes among these interventions. Those that met with limited success reported that complex social issues and poverty presented challenges to effective intervention work in these communities. Participatory action research methods and community ownership of the intervention were found to be essential for project success.Conclusions: Diabetes-focused intervention research in Indigenous communities appears to be a low priority for Canadian funders and policymakers. More intervention research is urgently needed in these communities. To be effective, this work must take an approach that is historically deep and sufficiently broad as to enable the ideologic, policy and institutional changes necessary in order to achieve true equity. This will involve addressing colonialism, racism and social exclusion as broader determinants of health. (C) 2015 Canadian Diabetes Association.

Plasma low-density lipoprotein(LDL) oxidation substantially exacerbates atherosclerosis in type 2 diabetes(T2D). The impact of antioxidant-containing flaxseed lignan complex (FLC) consumption on LDL fatty acid conjugated diene (LDL-CD), oxidized low-density lipoprotein protein (LDLox) and total peroxyl radical-trapping antioxidant potential (TRAP) levels has never been examined in persons with T2D. It was hypothesized that FLC relative to placebo would decrease LDL-CD and LDLox via increased TRAP levels. The objective was to test this hypothesis.

The variables examined are a waist circumference-associated clinically significant cluster not yet examined for changes due to flaxseed lignan complex ( FLC) administration in people with type 2 diabetes. It was hypothesized that FLC relative to placebo would increase (or better manage) percent pancreatic beta-cell function and plasma HDL2-cholesterol concentration and decrease (or better manage) the waist:height ratio (WHTR), body weight, BMI, waist:hip ratio, insulin resistance, total plasma free fatty acid, Lp(a), HDL3- and non-HDL-cholesterol concentrations. The objective was to test this hypothesis. Sixteen (11 male, 5 female) people with type 2 diabetes (mean age 66 years, mean BMI 31.2 kg/m2) completed this double-blind, randomized, crossover placebo-controlled study. Patients consumed 4 capsules/day of FLC (600 mg secoisolariciresinol diglucoside/day) or placebo for 3 months followed by a 3-month washout period (no exposure to FLC or placebo) followed by 3 months on that (FLC or placebo) to which they had not been previously exposed in this study. All data is reported as mean (SEM). Only WHTR was better FLC managed (60.1 [2.8] [start] – 60.5 [2.8] [finish] [FLC] vs. 60.1 [2.7] [start] – 61.4 [2.7] [finish] [placebo]) (p=0.04) with no other significant differences due to FLC. Diet (including alcohol), smoking, medication (dose and type) and exercise patterns did not change over the course of the study. Better WHTR management has been suggested by some to be an even more powerful indicator of improved metabolic control in type 2 diabetics (compared to waist circumference). However, while it is concluded that FLC significantly better managed the WHTR, it did not affect significantly the other aforementioned dependent variables. The clinical significance, if any, of these findings awaits elucidation.