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Biomedical subjects

T K Young

Publications and source records attributed to T K Young.

At least 19 recordsLinked to original sources

Characteristics and prevalence of the metabolic syndrome among three ethnic groups in Canada.

OBJECTIVE: To compare the characteristics and prevalence of the metabolic syndrome (MetS) among Native Indians, Inuit, and non-Aboriginal Canadians. METHODS: The study was based on four cross-sectional studies conducted in the late 1980s and early 1990s involving three ethnic groups living in contiguous regions in central Canada: Oji-Cree Indians from several reserves in northern Ontario and Manitoba, Inuit from the Keewatin region of the Northwest Territories, and non-Aboriginal Canadians (predominantly of European heritage) in the province of Manitoba. The MetS was identified among adult subjects according to the National Cholesterol Education Program (NCEP) definition. Prevalence rates were standardized to the 1991 Canadian national population. RESULTS: The age-standardized prevalence of the MetS varied by ethnic group, ranging from as high as 45% among Native Indian women to as low as 8% among Inuit men. Compared with Canadians of European origin, Indians had a worse metabolic profile, while Inuit had a better metabolic profile except for a high rate of abdominal obesity. The NCEP criteria in identifying individuals with the MetS were compared to those of the World Health Organization (WHO) in a subset of subjects with the requisite laboratory data. There was moderate agreement between the NCEP and WHO definitions, with a kappa value of 0.63 (95% confidence interval 0.56-0.70). CONCLUSIONS: The results indicate that the MetS is prevalent in diverse ethnic groups in Canada but varies in the pattern of phenotypic expression. Given the diverse nature of these populations, careful consideration should be given to developing culturally appropriate community-based prevention strategies aimed at reducing the frequency of this syndrome.

Adult↗

Preventing type 2 diabetes using combination therapy: design and methods of the CAnadian Normoglycaemia Outcomes Evaluation (CANOE) trial.

Several studies have demonstrated that type 2 diabetes mellitus (DM) can be prevented/delayed in subjects with impaired glucose tolerance (IGT) by using pharmacologic agents and/or lifestyle interventions. However, a number of challenges remain, including the translation of lifestyle programmes to the general population and the need to achieve greater risk reductions by using pharmacologic approaches. IGT, like DM, is characterized by insulin resistance, beta-cell dysfunction and increased hepatic glucose production. We believe that the use of combination diabetes therapy would be a particularly effective diabetes prevention strategy. In this context, we initiated the Canadian Normoglycemia Outcomes Evaluation (CANOE) study, a moderately sized, randomized, double-blind, controlled trial. The primary objective of CANOE is to determine whether treatment with metformin plus rosiglitazone, in addition to a healthy living lifestyle programme, will prevent the development of DM. The secondary objective of CANOE is to determine whether this treatment approach will improve cardiovascular risk factors associated with IGT. A total of 200 patients will be recruited in Toronto and London, Ontario, and followed for an average of 4 years (range 3-5 years). Active treatment with metformin (500 mg) plus rosiglitazone (2 mg), administered as one capsule twice daily, will be compared to matched placebo. Subjects will be eligible for randomization if they have IGT and are between the ages of 30-75 years. The primary outcome will be the development of new-onset DM, diagnosed by either two fasting plasma glucose values of >or=7 mmol/l or one positive oral glucose tolerance test with a 2-h plasma glucose value of >11.0 mmol/l during the active drug phase of the trial. With a sample size of 100 participants per group, we will be able to detect a relative risk reduction of 45%, with a two-sided log-rank test with a significance level of 0.05 and 80% power, assuming that the median time to progression is 8 years in the control group and that participants will be recruited over 2 years and followed for an average of 4 years. In conclusion, the CANOE study will determine whether combination pharmacological therapy combined with a lifestyle intervention programme can significantly modify the development of diabetes in high-risk Canadians.

Combined Modality Therapy↗

35 years of ICCH: evolution or stagnation of circumpolar health research?

The first Circumpolar Health symposium took place in Fairbanks in 1967. Approximately every three years since, an increasing number of researchers have met to present and discuss the health conditions of the North. We analysed the proceedings from the 11 congresses and the abstracts from the 12th congress in 2003 and found a shift of focus from biology to sociology of health. Today, circumpolar health research is primarily focused on three major topics: 1. epidemiology of indigenous peoples of the North; 2. health care delivery in the North; and 3. the effect of physical factors on human physiology and health. Despite the diverse research interests, it is remarkable how a community of circumpolar scientists and practitioners has emerged over the past 35 years.

Antarctic Regions↗

Gastric emptying and intestinal transit of liquid and solid markers in rats with chronic uremia.

Gastrointestinal motor abnormalities may account for dyspeptic symptoms of chronic uremia patients. However, the data on gastric emptying are conflicting in human studies. We, therefore, assessed gastric emptying and gastrointestinal transit in a rat uremia model. Chronic uremia was induced by five-sixths nephrectomy in the rats. After 20-hour fasting, the rats were loaded with 70 glass beads as solid markers through a gastric catheter. Two hours later, the stomach was exposed and the small intestine was equally divided into 10 segments. The glass beads in the stomach and in each intestinal segment were counted. The gastric emptying was expressed as the ratio of the number of glass beads in the small intestine to that counted from the entire gastrointestinal tract. The intestinal transit was assessed by analyzing the geometric center of the distribution of glass beads in the intestinal segments. Two conventional nonabsorbable markers, radioactive chromate and charcoal, were also used to evaluate gastric emptying and intestinal transit in the fasted state. Additionally, similar experiments of glass beads were performed in the fed state. It was found that, in the fasted state, the gastric emptying and the intestinal transit of liquid or solid markers were little affected by uremia. In the fed state, however, chronic uremia significantly decreased the intestinal transit but hardly affected the gastric emptying. We conclude that the postprandial intestinal transit, but not the gastric emptying, of solid markers may be decreased in the fed state by chronic uremia in a severity-dependent manner of a rat model, which resembles the findings in uremic patients.

Animals↗

Variable association between genetic variation in the CYP7 gene promoter and plasma lipoproteins in three Canadian populations.

The promoter sequence variant -278A in the CYP7 gene, which encodes cholesterol 7-alpha hydroxylase, was previously reported to be associated with reduced plasma low density lipoprotein (LDL) cholesterol concentration. We tested for association of CYP7-278A with plasma lipoprotein traits in samples taken from three distinct Canadian populations: 594 Alberta Hutterites, 325 Ontario Oji-Cree and 190 Keewatin Inuit. The CYP7-278A allele frequencies in these three groups were 0.708, 0.466 and 0.490, respectively. The frequencies of CYP7-278A/A homozygotes were 0.481, 0.215 and 0.247, respectively. In the Hutterites, CYP7-278A was associated with reduced plasma HDL-cholesterol and apolipoprotein AI concentration. In the Oji-Cree, CYP7-278A was not significantly associated with any plasma lipoprotein trait. In the Inuit CYP7-278A was associated with elevated plasma total and LDL-cholesterol. There was no consistent relationship between the population mean plasma LDL-cholesterol concentration and the population CYP7-278A frequency. Our findings suggest that the common -278A promoter variant of CYP7 was inconsistently associated with variation in plasma LDL- and HDL-cholesterol in samples from three independent populations. The inconsistencies could be due to differences in genetic background or to unspecified environmental or genetic factors.

Adult↗

Undiagnosed diabetes: does it matter?

BACKGROUND: The 1998 Canadian clinical practice guidelines for the management of diabetes lowered the cutoff point for diagnosing diabetes mellitus from a fasting plasma glucose (FPG) level of 7.8 to 7.0 mmol/L. We studied the prevalence and clinical outcomes of undiagnosed and diagnosed diabetes within specific ranges of FPG among a cohort of subjects recruited in 1990. METHODS: In 1990 a representative sample of 2792 adult residents of Manitoba participated in the Manitoba Heart Health Survey, which included measurement of FPG and a question about each participant's past history of diabetes. Individuals who would now be classified as having undiagnosed diabetes under the new criteria were not considered as such in 1990. Through data linkage with the provincial health care utilization database, the use of health care by these individuals was tracked and compared with that of individuals whose diabetes had been diagnosed and with that of normoglycemic individuals over an 8-year period subsequent to the survey. RESULTS: The prevalence of undiagnosed diabetes in the adult population of Manitoba was 2.2%. Undiagnosed cases accounted for about one-third of all diabetes cases. Individuals with undiagnosed diabetes had an unfavourable lipid profile and higher blood pressure and obesity indices than normoglycemic individuals. Individuals who satisfied the new criteria for diabetes but remained undiagnosed had an additional 1.35 physician visits per year (95% confidence interval [95% CI] 0.93-1.96) and were more likely to be admitted to hospital at least once (odds ratio 1.23, 95% CI 0.40-3.79), compared with normoglycemic individuals. INTERPRETATION: Undiagnosed cases represent the unseen but clinically important burden of diabetes, with significant concurrent metabolic derangements and a long-term impact on health care use.

Adult↗

Possible site of decreased intestinal zinc absorption in chronic uremic rats.

BACKGROUND/AIMS: Previous zinc tolerance tests in uremic patients indicated decreased intestinal zinc absorption. In the present study, a zinc tolerance test was initially applied to a uremic rat model and subsequently the possible site of malabsorption investigated. METHODS: Chronic uremia was induced by five-sixths nephrectomy. Both control and nephrectomized rats were divided into three groups including animals with intact intestine, removal of the jejunum, and removal of the ileum. Each rat was orally loaded with zinc sulfate (80 mg/kg) in conscious state. Blood samples were drawn before and after zinc load at different intervals during 6 h for zinc analysis. The area under the plasma zinc curve (AUC) and the maximal increase of plasma zinc level (C(max)) were calculated. RESULTS: Jejunectomy decreased both AUC and C(max) in control and nephrectomized rats, whereas ilectomized animals remained, interestingly, unchanged with regard to these two parameters. Significant decreases in both AUC and C(max) were observed in nephrectomized rats as compared with the control rats. CONCLUSIONS: The jejunum is the main site of zinc absorption in response to a large oral load of zinc sulfate in both normal and uremic rats. The data further suggest that five-sixths nephrectomy reduces gastrointestinal zinc absorption in rats predominantly by the ileum.

Animals↗

Common genomic variation in LMNA modulates indexes of obesity in Inuit.

We discovered that rare mutations in LMNA, which encodes lamins A and C, underlie autosomal dominant Dunnigan-type familial partial lipodystrophy. Because familial partial lipodystrophy is an extreme example of genetically disturbed adipocyte differentiation, it is possible that common variation in LMNA is associated with obesity-related phenotypes. We subsequently discovered a common single nucleotide polymorphism (SNP) in LMNA, namely 1908C/T, which was associated with obesity-related traits in Canadian Oji-Cree. We now report association of this LMNA SNP with anthropometric indexes in 186 nondiabetic Canadian Inuit. We found that physical indexes of obesity, such as body mass index, waist circumference, waist to hip circumference ratio, subscapular skinfold thickness, and subscapular to triceps skinfold thickness ratio were each significantly higher among Inuit subjects with the LMNA 1908T allele than in subjects with the 1908C/1908C genotype. For each significantly associated obesity-related trait, the LMNA 1908C/T SNP genotype accounted for between approximately 10--100% of the attributable variation. The results indicate that common genetic variation in LMNA is an important determinant of obesity-related quantitative traits.

Adult↗

The evaluation of transferred health care services in Wunnimin Lake, Wapekeka and Kingfisher Lake First Nations: a nursing perspective.

The Canadian federal government initiated the policy to transfer administrative control of health services to First Nations communities in the late 1980s. While there are outstanding issues concerning the implementation of the policy, many communities consider this an opportunity to improve the health of First Nations people and the work environment of health care providers. This paper reports on the evaluation of the process of transfer of health services experienced by three communities in northwestern Ontario, Canada, focusing on nursing services. Based on interviews with health care providers and community members, the overall assessment was that transfer had successfully addressed chronic issues relating to the working conditions of nurses and problems of recruitment and retention.

Attitude of Health Personnel↗

Type 2 diabetes mellitus in Canada's first nations: status of an epidemic in progress.

This review provides a status report on the epidemic of type 2 diabetes mellitus that is affecting many of Canada's First Nations. We focus on the published literature, especially reports published in the past 2 decades, and incorporate data from the Aboriginal Peoples Survey and the First Nations and Inuit Regional Health Survey. We look at the extent and magnitude of the problem, the causes and risk factors, primary prevention and screening, clinical care and education, and cultural concepts and traditional knowledge. The epidemic of type 2 diabetes is still on the upswing, with a trend toward earlier age at onset. Genetic-environmental interactions are the likely cause. Scattered intervention projects have been implemented and evaluated, and some show promise. The current health and social repercussions of the disease are considerable, and the long-term outlook remains guarded. A national Aboriginal diabetes strategy is urgently needed.

American Indian or Alaska Native↗

Diabetes-associated autoantibodies in aboriginal children.

Type-2 diabetes is increasing in aboriginal children and adolescents and must be distinguished from type-1 diabetes in this population. The absence of diabetes-associated autoantibodies supports the clinical impression of type-2 diabetes in the affected members of this population.

Adolescent↗

Health care seeking behavior following a health survey: impact on prevalence estimates of chronic diseases.

This article addresses the time sequence between a population health survey and subsequent health care use and how this changes the incidence estimates of selected chronic diseases. A cardiovascular survey of a representative sample of the adult population of Manitoba, Canada was linked with the health insurance claims database. Of the 2792 subjects in the survey, 98% were linked successfully, using an encrypted personal health insurance number. Five years of physician claims data for the survey participants were reviewed including 18 months prior to and 42 months following the survey. Survey participants started seeking confirmation of possible hypertension as soon as they received blood pressure information at the interview. Confirmation of diabetes and elevated cholesterol were not completed until 3-4 months after participants had received the laboratory test results. As many as 4.6 times more new cases of hypertension per month, 5.1 times more cases of elevated cholesterol, and 3.3 times more cases of diabetes were diagnosed following the survey. Surveys designed to determine the prevalence of specific chronic diseases generate new cases within a short time afterwards, thus affecting the original prevalence estimates. The process of assessing the burden of disease in a population is dynamic rather than static, and comparisons across populations need to take into account the frequency and recency of past surveys.

Adult↗

Childhood obesity in a population at high risk for type 2 diabetes.

OBJECTIVES: To determine the prevalence of obesity and investigate its association with fasting glucose and insulin among children and adolescents in a population at high risk for type 2 diabetes. DESIGN: A cross-sectional screening survey involving anthropometry and fasting serum levels of glucose and insulin. SETTING: A remote aboriginal (Ojibwa-Cree) community in northern Manitoba, Canada. PARTICIPANTS: All children aged 4 to 19 years in the community were invited to participate, with a response rate of 82% (n = 719). MAIN OUTCOME MEASURES: Obesity is defined as body mass index exceeding the 85th percentile of the National Center for Health Statistics reference data. The diagnosis of diabetes and impaired fasting glucose is based on the new criteria of the American Diabetes Association. RESULTS: There is a high prevalence of obesity, with 64% (female) and 60% (male) exceeding the 85th percentile and 40% (female) and 34% (male) exceeding the 95th percentile. Body mass index is a significant predictor of both glucose and insulin in both sexes, independent of age. Obese children are at increased risk of being classified as having diabetes or impaired fasting glucose (odds ratio 5.1, 95% CI 1.51, 17.0). CONCLUSIONS: The early onset of type 2 diabetes in childhood is increasingly observed in many populations. Childhood obesity is a strong risk factor. Early detection and intervention directed at obesity are potential strategies to avert the long-term consequences of type 2 diabetes.

Adolescent↗

Association between PON1 L/M55 polymorphism and plasma lipoproteins in two Canadian aboriginal populations.

Serum paraoxonase circulates on a subfraction of high density lipoproteins and appears to use phospholipids on both low and high density lipoprotein particles as a physiological substrate. This functional relationship could explain the reported associations between common variation in the PON1 gene--at codons 55 and 192--and phenotypes related to atherosclerosis and lipoprotein metabolism. We evaluated associations between plasma lipoproteins and PON1 L/M55, PON1 Q/R192 and PON2 A/G148 polymorphisms in samples from two Canadian aboriginal populations, namely the Oji-Cree and the Inuit. In diabetic Oji-Cree, we found that carriers of PON1 M55 had a higher mean plasma triglyceride concentration than non-carriers. In non-diabetic Oji-Cree, we found that carriers of PON1 M55 had higher mean plasma concentrations of total and low density lipoporetein cholesterol and apo B than non-carriers. In Inuit, we found that carriers of PON1 M55 had higher mean plasma concentrations of total and low density lipoprotein cholesterol than non-carriers. The other polymorphic markers were not associated with variation in any plasma lipoprotein trait. Thus, the PON1 M55 allele appeared to be associated with deleterious changes in the plasma lipoprotein profile from two independent Canadian aboriginal samples. These results suggest that common variation in PON1 codon 55 is associated with variation of intermediate traits in plasma lipoprotein metabolism in aboriginal Canadians.

Adolescent↗

Monitoring disease burden and preventive behavior with data linkage: cervical cancer among aboriginal people in Manitoba, Canada.

OBJECTIVES: This study sought to estimate rates of cervical cancer and Papanicolaou testing among Aboriginal and non-Aboriginal women in Manitoba, Canada. METHODS: Data were derived through linking of administrative databases. RESULTS: In comparison with non-Aboriginal women, Aboriginal women had 1.8 and 3.6 times the age-standardized incidence rates of in situ and invasive cervical cancer, respectively. With the exception of those aged 15 to 19 years, Aboriginal women were less likely to have had at least 1 Papanicolaou test in the preceding 3 years. CONCLUSIONS: Data linkage provides a rapid and inexpensive means to estimate disease burden and preventive behavior in the absence of registries. There is an urgent need for an organized Papanicolaou test screening program in the Aboriginal population.

Adolescent↗

Plasma phospholipid fatty acids in the central Canadian arctic: biocultural explanations for ethnic differences.

As part of the Keewatin Health Assessment Study, a comprehensive health interview and examination survey of Inuit and non-Inuit in the central Canadian Arctic during 1990-91, plasma samples were analyzed for phospholipid fatty acid composition. Compared to non-Inuit, the Inuit have reduced levels of dihomo-gamma-linoleic (DGLA) and arachidonic acid (ratios of 0.41 and 0.46) and the sum of all n-6 fatty acids (ratio of 0.65), but increased level of eicosapentaenoic (EPA) acid (ratio of 1.37). These trends are consistent with those reported from other circumpolar Inuit populations, especially the reduced arachidonic acid and increased EPA, although the Inuit excess in EPA is much less pronounced due to the greater importance of caribou rather than sea mammals in most of the Keewatin communities. The high linoleic/arachidonic acid ratio suggests increased inhibition of the metabolic pathway regulated by the enzyme delta-5 desaturase, which can be explained by the presence of high levels of highly unsaturated fatty acids of dietary origin, and/or a genetic deficiency. In multiple linear regression models with the independent variable list consisting of Inuit status, age, sex, education, physical activity, spending time on the land and consumption of wild meat and local fish, Inuit status is independently associated with lower levels of the n-6 acids but not the n-3 acids. This indicates that factors other than diet and lifestyle, perhaps genetic ones, may account for the observed "ethnic" differences. However, for those fatty acids in which Inuit differ from non-Inuit, there is no dose-response relationship in terms of self-reported degree ofnon-Inuit admixture. Dietary fatty acids play an important role in the risk of cardiovascular diseases and diabetes, diseases of increasing importance in the health transition experienced by the Inuit. Association studies of plasma fatty acids and DNA markers of candidate genes for atherosclerosis and insulin resistance may provide a clearer picture of the genetic basis for the observed differences in plasma fatty acid composition between Inuit and non-Inuit.

Adult↗