Multitherapy for diabetes.
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Cardiovascular Diseases↗
Biomedical subjects
Stewart B Harris
Publications and source records attributed to Stewart B Harris.
Relationship of the metabolic syndrome to carotid ultrasound traits.
BACKGROUND: The metabolic syndrome is associated with increased vascular disease risk. We evaluated two carotid ultrasound measurements, namely intima media thickness and total plaque volume, in a Canadian Oji-Cree population with a high metabolic syndrome prevalence rate. METHODS: As part of the Sandy Lake Complications Prevalence and Risk Factor Study, 166 Oji-Cree subjects (baseline metabolic syndrome prevalence, 44.0%, according to the National Cholesterol Education Program Adult Treatment Panel III guidelines) were examined using a high-resolution duplex ultrasound scanner. RESULTS: Image analysis showed that mean intima media thickness was elevated in subjects with the metabolic syndrome (818 +/- 18 vs 746 +/- 20 microm), as was total plaque volume (125 +/- 26 vs 77.3 +/- 17.0 mm3). However, after adjustment for age and sex, the differences were significant only for intima media thickness (P = 0.039). Furthermore, a significant trend towards increased intima media thickness was observed with increasing numbers of metabolic syndrome components: mean intima media thickness was highest among individuals with all five metabolic syndrome components compared to those with none (866 +/- 55 vs 619 +/- 23 microm, P = 0.0014). A similar, but non-significant trend was observed for total plaque volume. CONCLUSION: This is the first study of the relationship between the metabolic syndrome and two distinct carotid ultrasound traits measured in the same individuals. The results suggest that standard intima media thickness measurement shows a more consistent and stronger association with the metabolic syndrome than does total plaque volume.
Adult↗
Metabolic syndrome in aboriginal Canadians: prevalence and genetic associations.
OBJECTIVES: The prevalence rates of type 2 diabetes (T2DM) and coronary heart disease (CHD) in Ontario Oji-Cree are among the world's highest. Since metabolic syndrome (MetS) increases risk of T2DM and CHD, we characterized prevalence and putative genetic determinants of MetS in Oji-Cree. METHODS AND RESULTS: In 515 adult (> or = 18 years old) and 115 adolescent (< 18 years old) Oji-Cree subjects, using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, we determined that 29.9% of Oji-Cree adults, and 43.4% of adults > or = 35 years of age, had MetS. Furthermore, 33.9 and 8.7% of female Oji-Cree adults and adolescents, respectively, had MetS. Increased waist girth and depressed HDL cholesterol were the most prevalent individual MetS components, while increased blood pressure was least prevalent. AGT T174M, GNB3 825C>T, and APOC3 -455T>C genotypes were significantly associated with MetS (P = 0.018, 0.0056, and 0.029, respectively) for female adults, whereas FABP2 A54T genotype was associated with MetS (P = 0.040) for female adolescents. CONCLUSIONS: The high MetS prevalence in Oji-Cree adults, especially women, is consistent with their high risk of T2DM and CHD. Functional polymorphisms in three candidate genes for plasma lipoproteins and blood pressure were associated with MetS in adult Oji-Cree. Furthermore, several female adolescents met the adult MetS criteria, suggesting that the genesis of MetS begins in youth, especially among aboriginal females.
Adolescent↗
Nontraditional cardiovascular risk factors in pediatric metabolic syndrome.
OBJECTIVE: To study the relationships between nontraditional cardiovascular (CV) risk factors and components of the metabolic syndrome in Native Canadian children, a population at risk of future CV disease. STUDY DESIGN: CV risk factors were evaluated in a population-based study of a Canadian Oji-Cree community, involving 236 children aged 10 to 19 years. RESULTS: Using an age- and sex-specific case definition, 18.6% of the children met criteria for pediatric metabolic syndrome. As the number of metabolic syndrome component criteria increased, C-reactive protein, leptin, and ratio of apolipoprotein B to apolipoprotein A1 levels rose (all P < .0001) and adiponectin concentration decreased (P = .0006). Principal factor analysis using both traditional and nontraditional CV risk factors revealed 5 underlying core traits, defined as follows: adiposity, lipids/adiponectin, inflammation, blood pressure, and glucose. CONCLUSIONS: Nontraditional CV risk factors accompany the accrual of traditional risk factors early in the progression to pediatric metabolic syndrome. Furthermore, inclusion of these factors in factor analysis suggests that 5 core traits underlie the early development of an enhanced CV risk factor profile in Native children.
Adiponectin↗
Lifestyle variables, non-traditional cardiovascular risk factors, and the metabolic syndrome in an Aboriginal Canadian population.
OBJECTIVE: To examine lifestyle factors associated with metabolic syndrome (MetS) and to explore the relationships between MetS and non-traditional cardiovascular disease risk factors [adiponectin, leptin, C-reactive protein (CRP), interleukin-6 (IL-6), and serum amyloid A (SAA)] in an isolated Aboriginal Canadian community. RESEARCH METHODS AND PROCEDURES: Data were obtained from 360 non-diabetic adults participating in a population-based study of Aboriginal Canadians. Fasting samples were drawn for glucose, insulin, lipids, adiponectin, leptin, CRP, IL-6, and SAA. Percentage body fat was measured using bioelectrical impedance analysis. Past year physical activity and fitness level were assessed. MetS was diagnosed according to the criteria of the National Cholesterol Education Program, the World Health Organization, and the International Diabetes Federation. RESULTS: The results showed that older age, higher percentage body fat, and lower fitness levels were associated with increased odds of MetS regardless of MetS definition and subject gender. Past year physical activity was independently related with the World Health Organization-MetS in male subjects. Subjects with MetS had significantly higher leptin, CRP, IL-6, and SAA levels and lower adiponectin levels; however, only adiponectin remained significantly low after adjustment for age and percentage body fat. DISCUSSION: The study showed that higher percentage body fat and lower physical activity and fitness were associated with a higher prevalence of MetS in this Aboriginal community and that hypoadiponectinemia was independently associated with MetS.
Adiponectin↗
Implementing practice guidelines: a workshop on guidelines dissemination and implementation with a focus on asthma and COPD.
The present supplement summarizes the proceedings of the symposium "Implementing practice guidelines: A workshop on guidelines dissemination and implementation with a focus on asthma and COPD", which took place in Quebec City, Quebec, from April 14 to 16, 2005. This international symposium was a joint initiative of the Laval University Office of Continuing Medical Education (Bureau de la Formation Médicale Continue), the Canadian Thoracic Society and the Canadian Network for Asthma Care, and was supported by many other organizations and by industrial partners. The objectives of this meeting were to examine the optimal implementation of practice guidelines, review current initiatives for the implementation of asthma and chronic obstructive pulmonary disease (COPD) guidelines in Canada and in the rest of the world, and develop an optimal strategy for future guideline implementation. An impressive group of scientists, physicians and other health care providers, as well as policy makers and representatives of patients' associations, the pharmaceutical industry, research and health networks, and communications specialists, conveyed their perspectives on how to achieve these goals. This important event provided a unique opportunity for all participants to discuss key issues in improving the care of patients with asthma and COPD. These two diseases are responsible for an enormous human and socioeconomic burden around the world. Many reports have indicated that current evidence-based guidelines are underused by physicians and others, and that there are many barriers to an effective translation of recommendations into day-to-day care. There is therefore a need to develop more effective ways to communicate key information to both caregivers and patients, and to promote appropriate health behaviours. This symposium contributed to the initiation of what could become the "Canadian Asthma and COPD Campaign", aimed at improving care and, hence, the quality of life of those suffering from these diseases. It is hoped that this event will be followed by other meetings that focus on how to improve the transfer of key recommendations from evidence-based guidelines into current care, and how to stimulate research to accomplish this.
Asthma↗
Disparate associations of a functional promoter polymorphism in PCK1 with carotid wall ultrasound traits.
BACKGROUND AND PURPOSE: Cytosolic phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32), encoded by PCK1, catalyzes the first committed step in gluconeogenesis. We previously showed that a -232C>G promoter polymorphism within a cis-acting element required for basal and cAMP-mediated PCK1 gene transcription results in loss of negative regulation by insulin, contributing to worsened metabolic control in the context of insulin resistance. We hypothesized that this polymorphism would be associated with carotid atherosclerosis in a sample of 150 aboriginal Canadians. METHODS: Dependent variables were 2 distinct carotid traits, namely intima-media thickness (IMT) assessed using B-mode ultrasound and total carotid plaque volume (TPV) assessed using 3D ultrasound. RESULTS: Multivariate analysis showed significant but opposite associations of PCK1 genotype with these traits. Specifically, subjects with the PCK1-232G/G genotype had more carotid IMT (0.80+/-0.02 versus 0.73+/-0.03 mm; P=0.007) but less TPV (0.10+/-0.09 versus 0.38+/-0.13; P=0.03) than subjects with other genotypes. CONCLUSIONS: The findings connect the key enzyme in gluconeogenesis with atherosclerosis. The meaning of the opposing associations of PCK1 genotype with IMT and TPV is unclear; more work is required to confirm whether these might be distinct quantitative traits with different biological determinants.
Adolescent↗
Methylenetetrahydrofolate reductase polymorphism 677C>T is associated with peripheral arterial disease in type 2 diabetes.
BACKGROUND: Individuals with diabetes are twice as likely to develop peripheral arterial disease (PAD), the manifestation of extensive atherosclerosis throughout the lower extremities. One putative determinant of PAD is the 677C>T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR), which has previously been found to associate with various diabetic complications including retinopathy, nephropathy, atherosclerosis and coronary heart disease. The objective of this study was to investigate a possible role for the MTHFR 677C>T gene polymorphism with PAD in subjects with type 2 diabetes from an isolated aboriginal Canadian population. METHODS: The 677C>T MTHFR gene polymorphism was genotyped in 138 subjects of Oji-Cree descent. Participants were selected from a community-wide survey that included PAD assessment by ankle-brachial index (ABI) measurement, and also intermittent claudication assessment by the Rose questionnaire. RESULTS: MTHFR 677T allele carriers had an increased risk of PAD with an odds ratio of 3.54 (95% CI 1.01, 12.4), P = 0.049, after adjustment for age, sex, duration of diabetes, hypertension, current smoking habits, and use of insulin or oral treatment for diabetes. None of these additional co-variables was significantly associated with PAD. No association was found between MTHFR genotype and intermittent claudication. CONCLUSION: The genetic influence of the MTHFR 677C>T genotype on diabetic PAD is modest, yet for the Oji-Cree it is a major risk factor in comparison to other traditional risk factors.
Brachial Artery↗
Cigarette smoking and cardiovascular risk factors among Aboriginal Canadian youths.
BACKGROUND: Aboriginal populations in North America are exhibiting an increased prevalence of cardiovascular disease and associated traditional and nontraditional cardiovascular risk factors, trends believed to be due to the influence of Western lifestyle habits. Because these influences are present at an early age, we sought to study the patterns of one such habit, cigarette smoking, among Aboriginal Canadian youths and to assess the associated accrual of cardiovascular risk factors at an early age. METHODS: Patterns of cigarette smoking were assessed in a population-based, cross-sectional study involving 236 youths aged 10-19 (mean 14.9) years in the Oji-Cree community of Sandy lake, in northwestern Ontario. Participants underwent clinical and metabolic evaluation with assessment of cardiovascular risk factors. RESULTS: The prevalence of cigarette smoking among the study participants was considerably higher than age-specific national averages, with fully 50% of the participants overall and 82% of the adolescent participants (aged 15-19) being current smokers. Compared with their peers, children smoking 6 or more cigarettes per day had an enhanced cardiovascular risk profile consisting of a higher mean systolic blood pressure (111 v. 107.5 mm Hg, p = 0.036), a higher mean plasma homocysteine level (8.7 v. 7.6 micromol/L, p = 0.008) and a lower mean serum folate level (4.5 v. 5.4 mmol/L, p = 0.007), after adjustment for age, sex and body mass index. In separate multiple linear regression analyses, current cigarette exposure (number of cigarettes smoked per day) emerged as an independent determinant of both systolic blood pressure and plasma homocysteine level. INTERPRETATION: In this Aboriginal community with remarkably high rates of cigarette smoking among its youth, an independent dose-response relation was found between current smoking exposure and both traditional (systolic blood pressure) and nontraditional (homocysteine level) cardiovascular risk factors. The association of cigarette smoking with an enhanced cardiovascular risk profile at an early age may be a factor contributing to the high prevalence of cardiovascular disease in this Aboriginal population.
Adolescent↗
A comparison of ultrasound measurements to assess carotid atherosclerosis development in subjects with and without type 2 diabetes.
BACKGROUND: Subjects with type 2 diabetes are at an increased risk of vascular complications. The use of carotid ultrasound remains an attractive, non-invasive method to monitor atherosclerotic disease progression and/or response to treatment in patients with type 2 diabetes, with intima-media thickness routinely used as the gold standard to detect pathology. However, alternative measurements, such as plaque area or volume, may represent a potentially more powerful approach. Thus, the objective of this study was to compare the traditional intima-media thickness measurement against the novel total plaque volume measurement in analyzing carotid atherosclerosis development in individuals with type 2 diabetes. METHODS: The case-control study included 49 Oji-Cree adults with diabetes or impaired glucose tolerance, aged 21-69, and 49 sex- and age-matched normoglycemic subjects. At baseline, metabolic variables were measured, including body mass index, waist circumference, total cholesterol: high density lipoprotein ratio, plasma triglycerides, plasma glucose, and serum insulin. Carotid ultrasound measurements, 7 years later, assessed carotid arterial intima-media thickness and total plaque volume. RESULTS: At baseline, the two groups were well matched for smoking habits, hypertension, body mass index, and waist circumference. Differences were noted in baseline measurements of total cholesterol:high density lipoprotein (P = 0.0006), plasma triglycerides (P < 0.0001) and fasting glucose (P < 0.0001). After seven years, carotid ultrasound scans revealed that total plaque volume measurements (P = 0.037), but not intima-media thickness measurements, were higher in subjects with diabetes/impaired glucose tolerance compared to the normoglycemic controls. Correlation between intima-media thickness and total plaque volume was moderate. Based on our study findings, to achieve power levels > 0.70 when comparing intima-media thickness measurements for diabetics versus non-diabetics, thousands of study subjects are required. For comparing total plaque volume measurements, only hundreds of study subjects are required. CONCLUSION: The development of atherosclerotic plaque is greater in subjects with diabetes/impaired glucose tolerance. Total plaque volume appears to capture the atherosclerotic disease burden more effectively in subjects with type 2 diabetes, and would be an appropriate outcome measure for studies aimed at changing the diabetic milieu.
Adult↗
Teleconferenced educational detailing: diabetes education for primary care physicians.
INTRODUCTION: Formal didactic continuing medical education (CME) is relatively ineffective for changing physician behaviour. Diabetes mellitus is an increasingly prevalent disease, and interventions to improve adherence to clinical practice guidelines (CPGs) are needed. METHODS: A stratified, cluster-randomized, controlled trial design was used to evaluate the effects of a teleconferenced educational detailing (TED) CME on glycemic control (hemoglobin [Hb] A1c) and family physician adherence to national diabetes guidelines. TED employed sequential, small-group, case-based education using CPGs delivered by a diabetes specialist. Medical record audit data from baseline through the end of a 12-month postintervention period were compared for the control and intervention groups. Satisfaction with the intervention was evaluated. RESULTS: Sixty-one physicians provided 660 medical records. The intervention did not affect mean Hb A1c levels but did significantly (p = .04) alter the distribution of patients by category of glycemic control, with fewer in the intervention group in inadequate control (15.8% versus 23.9%). More patients took insulin (alone or with oral agents) in the intervention group (21.2% versus 12.0%, p = .03), and more took oral agents only in the control group (89.0% versus 82.9%, p = .005). More patients in the intervention group had documentation of body mass index (7.8% versus 1.9%, p < .02), eye exam (12.1% versus 5.1%, p = .02), and treatment plan (43.5% versus 23.6%, p = .01) and used a flow sheet (14.6% versus 7.7%, p < .03). Although there was general satisfaction with the teleconferencing format, specialist educators found the format more challenging than the family physicians. DISCUSSION: CME delivered by teleconference was feasible, well attended, well received by participants, and improved some key diabetes management practices and outcomes.
Diabetes Mellitus↗
Differences between carotid wall morphological phenotypes measured by ultrasound in one, two and three dimensions.
Ultrasound measurements are both surrogate markers and risk factors for atherosclerosis end points. Carotid intima-media thickness (IMT) is most commonly used, but ultrasound can also define structures in higher spatial dimensions, such as total plaque area (TPA) and total plaque volume (TPV). Because there are minimal data regarding the relationship between IMT, TPA and TPV, we measured these variables in 272 Oji-Cree subjects. We found pairwise correlations for IMT:TPA, IMT:TPV and TPA:TPV of 0.507, 0.588 and 0.846, respectively (transformed variables, all P <0.0001). In a subset of 168 subjects with complete cardiovascular risk factor data, we performed multivariate regression analysis to identify sources of variation for IMT, TPA and TPV. We found that the ultrasound traits showed different correlations with individual cardiovascular risk factors. In particular, IMT was significantly associated with hypertension, TPA with smoking and plasma cholesterol, and TPV with diabetes. Therefore, these ultrasound measures of carotid artery morphology, while somewhat correlated, likely represent distinctive quantitative traits with different biological determinants, as underscored by different risk factor associations in the multivariate regression analysis. Because the measurements have different implications and determinants, investigators might need to be selective about the particular measurements they choose for specific applications.
Adult↗
Glycemic control and morbidity in the Canadian primary care setting (results of the diabetes in Canada evaluation study).
The objective of this national, cross-sectional study was to provide insight into the care and treatment of type 2 diabetes (T2DM) in the Canadian primary care setting. Specifically, the study examines glycemic control, management and morbidity load among T2DM patients, and investigates the relationship of glycemic control and morbidity load with duration of diabetes. Participating primary care physicians (PCPs) (N=243) completed a chart audit for the first 10 patients with T2DM attending their clinics (2473 eligible patient records). The mean A1C was 7.3% with 49% of patients not at target (A1C>or=7.0%). Glycemic control eroded significantly with increasing duration of diabetes in spite of increasing therapeutic intervention. T2DM patients experienced a high morbidity load (hypertension 63%; dyslipidemia 59%; macrovascular complications 28%; microvascular complications 38%) each of which increased significantly with duration of diabetes. For 79% of patients not at target, PCPs identified lifestyle intervention as the strategy for achieving glycemic targets while more aggressive treatment plans were identified for only 56%. These results underscore the complexity of primary care management of T2DM and suggest that current treatment approaches are not intensive enough for a large proportion of patients especially those with longer duration of disease.
Blood Glucose↗
A pilot school-based healthy eating and physical activity intervention improves diet, food knowledge, and self-efficacy for native Canadian children.
The Sandy Lake school-based diabetes prevention program is a culturally appropriate intervention for Ojibway-Cree students in the 3rd, 4th, and 5th grades. This paper reports the results of the program in changing dietary intake behaviors and related psychosocial factors. Physical activity results are not included. The study was a pretest/post-test, single-sample design conducted during the 1998-1999 school year. A total of 122 students completed all 4 measurements (anthropometry, 24-h dietary recall, and 2 questionnaires), at baseline and follow-up. There were significant increases (P < 0.0001) in dietary intention, dietary preference, knowledge, and dietary self-efficacy, and in the curriculum knowledge scale between baseline and follow-up. Intervention exposure was significantly associated with being in the highest category for knowledge about foods that were low in dietary fat [Medium Exposure odds ratio (OR): 3.4; P < 0.05; High Exposure OR: 6.4; P < 0.05], being in the highest category for dietary self-efficacy (Medium Exposure OR: 3.7; P < 0.05; High Exposure OR: 3.9; P < 0.1), being in the highest category for knowledge about curriculum concepts (Medium Exposure OR: 3.4; P < 0.05; High Exposure OR: 9.4: P < 0.01), and for having met the age + 5 g dietary fiber intake/d (Medium Exposure OR: 2.9; P < 0.1; High Exposure OR: 11.0; P < 0.01). Exposure to the intervention was not associated with dietary intent or the percentage of energy from dietary fat. This program was associated with improved knowledge and the psychosocial factors related to healthy eating and dietary fiber intake of students in a remote First Nations community.
Adolescent↗
Complications of Type 2 Diabetes Among Aboriginal Canadians: prevalence and associated risk factors.
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Albuminuria↗
Genetic variation in PPARG encoding peroxisome proliferator-activated receptor gamma associated with carotid atherosclerosis.
BACKGROUND AND PURPOSE: Peroxisome proliferator-activated receptor gamma is a crucial molecule in atherogenesis because it is associated with metabolic risk factors such as obesity and diabetes and also plays a key role in subcellular metabolism of arterial wall macrophage foam cells. Genetic variation in PPARG has been associated with metabolic and cardiovascular end points. METHODS: We investigated the relationship between 2 common PPARG polymorphisms, namely P12A and c.1431C>T, and carotid atherosclerosis in a sample of 161 Canadian aboriginal people. Dependent variables were carotid intima media thickness (IMT), assessed using B-mode ultrasonography, and total carotid plaque volume (TPV), assessed using 3D ultrasound. RESULTS: Using multivariate analysis, we found that subjects with > or =1 PPARG A12 allele had less carotid IMT than others (0.72+/-0.03 versus 0.80+/-0.02 mm; P=0.0045), with no between-genotype difference in TPV. In contrast, subjects with the PPARG c.1431T allele had greater TPV than others (124+/-18.4 versus 65.1+/-23.7 mm3; P=0.0079), with no between-genotype difference in IMT. CONCLUSIONS: The findings show an association between PPARG genotypes and carotid arterial phenotypes, and further reflect the prevailing view that the PPARG A12 allele protects against deleterious phenotypes. Also, whereas IMT and TPV are somewhat correlated with each other, they might also represent distinct traits with discrete determinants representing different stages of atherogenesis.
Adult↗
Promoter polymorphism in PCK1 (phosphoenolpyruvate carboxykinase gene) associated with type 2 diabetes mellitus.
We sequenced the promoter and coding regions of PCK1 encoding cytosolic phosphoenolpyruvate carboxykinase from genomic DNA of subjects with type 2 diabetes mellitus (DM). We found nine single nucleotide polymorphisms (SNPs) that were present with varying allele frequencies and pairwise linkage disequilibrium relationships in different ethnic groups. The -232C-->G promoter SNP was within a cis-acting element required for basal and cAMP-mediated PCK1 gene transcription. The expression of a luciferase reporter construct containing -232G in three different cell lines showed significantly increased basal expression with no down-regulation by insulin compared with a construct containing -232C. The odds ratios for type 2 DM among subjects with one or two copies of -232G compared with -232C/C homozygotes were 1.9 (95% confidence interval, 1.2-3.0) in a Canadian aboriginal sample and 2.8 (95% confidence interval, 1.7-4.7) in a Caucasian sample. Thus, we report a promoter SNP in PCK1 that was resistant to down-regulation by insulin in vitro and was associated with type 2 DM in two independent study samples.
Adult↗
Recommendations from the Canadian Diabetes Association. 2003 guidelines for prevention and management of diabetes and related cardiovascular risk factors.
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Algorithms↗