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Maple-Brown L.J.,Charles Darwin University | Maple-Brown L.J.,Royal Darwin Hospital | Maple-Brown L.J.,Mt Sinai Hospital | Cunningham J.,Charles Darwin University | And 10 more authors.
Cardiovascular Diabetology | Year: 2012

Background: Indigenous populations of Australia and Canada experience disproportionately high rates of chronic disease. Our goal was to compare cardiovascular (CVD) risk profile and diabetes complications from three recent comprehensive studies of diabetes complications in different Indigenous populations in Australia and Canada.Methods: We compared participants from three recent studies: remote Indigenous Australians (2002-2003, n = 37 known diabetes), urban Indigenous Australians (2003-2005, n = 99 known diabetes), and remote Aboriginal Canadians (2001-2002, n = 188 known diabetes).Results: The three groups were similar for HbA1c, systolic BP, diabetes duration. Although leaner by body-mass-index criteria, remote Indigenous Australians displayed a more adverse CVD risk profile with respect to: waist-hip-ratio (1.03, 0.99, 0.94, remote Indigenous Australians, urban Indigenous Australians, remote Canadians, p < 0.001); HDL-cholesterol (0.82, 0.96, 1.17 mmol/L, p < 0.001); urine albumin-creatinine-ratio (10.3, 2.4, 4.5 mg/mmol); and C-reactive protein. With respect to diabetes complications, microalbuminuria (50%, 25%, 41%, p = 0.001) was more common among both remote groups than urban Indigenous Australians, but there were no differences for peripheral neuropathy, retinopathy or peripheral vascular disease.Conclusions: Although there are many similarities in diabetes phenotype in Indigenous populations, this comparison demonstrates that CVD risk profiles and diabetes complications may differ among groups. Irrespective, management and intervention strategies are required from a young age in Indigenous populations and need to be designed in consultation with communities and tailored to community and individual needs. © 2012 Maple-Brown et al; licensee BioMed Central Ltd.


Maple-Brown L.J.,Charles Darwin University | Maple-Brown L.J.,Royal Darwin Hospital | Maple-Brown L.J.,Mt Sinai Hospital | Brimblecombe J.,Charles Darwin University | And 9 more authors.
Diabetes Research and Clinical Practice | Year: 2013

Aim: Indigenous populations of Australia and Canada experience disproportionately high rates of chronic disease. We hypothesized that despite the common outcome of increased diabetes prevalence, differences in cardiometabolic risk profile may exist between these populations. Methods: We compared community-based data on cardiometabolic risks in Aboriginal Australians (n= 297 without, 45 with diabetes), and Aboriginal Canadians (n= 409 without, 87 with diabetes). Results: Despite strikingly lower weight (62 vs 83kg, p<0.0001) and body mass index (BMI, 22 vs 29kg/m2, p<0.0001), Aboriginal Australians without diabetes had similar waist-hip ratio (WHR, 0.91 vs 0.91, p=0.732), lower HDL-cholesterol (0.97 vs 1.25mmol/L, p<0.0001) and higher HbA1c (5.4 vs 5.2%, p<0.0001) than Aboriginal Canadians without diabetes. Waist was the obesity measure most strongly related to diabetes or cardiometabolic risk in Australians while BMI performed similarly to other obesity measures only in Canadians. Multiple regression of HbA1c revealed age and fasting glucose as independent predictors in each study group, with the addition of WHR in Aboriginal Australians. Conclusion: The notable finding was that waist or WHR are preferred obesity measures to appropriately reflect cardiometabolic risk in Aboriginal Australians, who although leaner by BMI criteria, displayed a similarly adverse risk profile to Aboriginal Canadians. Waist or WHR should be routinely included in clinical assessment in these high-risk populations. © 2013 Elsevier Ireland Ltd.


Ley S.H.,University of Toronto | Harris S.B.,University of Western Ontario | Connelly P.W.,University of Toronto | Connelly P.W.,Li Ka Shing Knowledge Institute | And 10 more authors.
Clinical Chemistry | Year: 2010

BACKGROUND: Expanding evidence indicates that apolipoprotein B (apo B) is superior to LDL cholesterol as a marker of vascular disease. Although traditional lipid measures are known to predict type 2 diabetes, limited data are available regarding apo B. We assessed the association of apo B with incident type 2 diabetes and compared it with traditional lipid variables as a risk predictor in aboriginal Canadians. METHODS: Of an initial cohort of 606 individuals without diabetes in 1993-1995, 540 were contacted for the 10-year follow-up evaluation in 2003-2005. Fasting and 2-h postload glucose concentrations were obtained at baseline and follow-up to determine incident type 2 diabetes. Baseline fasting serum lipids were measured with standard laboratory procedures. RESULTS: The cumulative 10-year incidence of type 2 diabetes was 17.5%. High concentrations of apo B, triglycerides, triglycerides, and LDL cholesterol, and low concentrations of HDL cholesterol were individually associated with incident type 2 diabetes in univariate analyses. Comparing C statistics of univariate models showed apo B to be a superior determinant of incident diabetes compared with LDL (P = 0.026) or HDL (P = 0.004) cholesterol. With multivariate adjustment including waist circumference, apo B (odds ratio, 1.50; 95% CI, 1.11-2.02) and triglycerides (odds ratio, 1.49; 95% CI, 1.12-1.98) remained associated with incident diabetes, whereas LDL and HDL cholesterol became nonsignificant. CONCLUSIONS: The association of plasma apo B with incident type 2 diabetes and its better prediction of risk compared with LDL or HDL cholesterol suggest the potential for the use of apo B in type 2 diabetes risk communication and prevention.


Mansuri S.,University of Toronto | Badawi A.,Public Health Agency of Canada | Kayaniyil S.,University of Toronto | Cole D.E.,Sunnybrook Research Institute | And 9 more authors.
Diabetes Research and Clinical Practice | Year: 2015

Aims: To investigate the associations of 25-hydroxyvitamin D (25(OH)D) with insulin resistance (IR), beta-cell function and metabolic syndrome (MetS) in a First Nations population. Methods: We conducted a cross-sectional analysis using data from the Sandy Lake Health and Diabetes Project (2003-2005). A total of 390 participants (>12y) were assessed for 25(OH)D, fasting glucose, insulin, lipids, blood pressure, inflammatory markers, anthropometric and lifestyle variables and a 75-g oral glucose tolerance test was administered. IR was calculated using the Matsuda insulin sensitivity index (ISOGTT) and the computational homeostasis model assessment of IR (HOMA2-IR). Beta-cell function was calculated using the insulinogenic index (IGI) divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2). The 2009 harmonized criteria were used to define MetS. Results: Higher 25(OH)D was associated with a decreased prevalence of dysglycemia (OR=0.71 95% CI, 0.51-0.97 per SD increase). In addition, there were significant associations of 25(OH)D with measures of insulin action (ISOGTT; beta=0.31; 95% CI, 0.12, 0.49; HOMA2-IR; beta=-29; 95% CI -0.46, -0.11 and beta-cell function (ISSI-2; beta=0.15; 95% CI, 0.02, 0.28). The prevalence of MetS was 41%. There was a decreased risk (OR=0.73, 95% CI 0.56, 0.94) of MetS per SD increase in baseline 25(OH)D. Finally, there was a significant positive association of 25(OH)D with adiponectin (beta=0.16; 95% CI=0.01, 0.31). Conclusions: These results support a potential role for vitamin D metabolism in the natural history of T2DM among Aboriginal Canadians, although carefully designed randomized trials will be required to establish causality. © 2015 Elsevier Ireland Ltd.


PubMed | University of Western Ontario, Li Ka Shing Knowledge Institute, Sandy Lake Health and Diabetes Project, Johns Hopkins University and 4 more.
Type: | Journal: International journal of circumpolar health | Year: 2016

Sub-optimal vitamin D status is common worldwide and the condition may be associated with increased risk for various chronic diseases. In particular, low vitamin D status is highly prevalent in indigenous communities in Canada, although limited data are available on the determinants of serum 25-hydroxyvitamin D (25(OH)D) concentrations in this population. The relationship between traditional food consumption and vitamin D status has not been well documented.To investigate the determinants of serum 25(OH)D status in a First Nations community in Ontario, Canada, with a focus on the role of traditional food consumption and activities.A cross-sectional analysis was conducted within the Sandy Lake Health and Diabetes Project (2003-2005). A total of 445 participants (>12 years of age) were assessed for serum 25(OH)D status, anthropometric and lifestyle variables, including traditional and non-traditional dietary practices and activities. Diet patterns were identified using factor analysis, and multivariate linear regression analysis was used to analyse the determinants of 25(OH)D concentrations.Mean serum 25(OH)D concentrations were 22.1 nmol/L (16.9, 29.9 nmol/L) in men and 20.5 nmol/L (16.0, 27.3 nmol/L) in women. Multivariate determinants of higher serum 25(OH)D included higher consumption of traditional and healthier market foods, higher wild fish consumption, male gender, spring/summer season of blood collection and more frequent physical activity. Significant negative determinants included hours of TV/day, higher BMI and higher consumption of unhealthy market foods.Traditional food consumption contributed independently to higher 25(OH)D concentrations in a First Nations community with a high prevalence of sub-optimal vitamin D status.


Reeds J.,University of Toronto | Mansuri S.,University of Toronto | Mamakeesick M.,Sandy Lake Health and Diabetes Project | Harris S.B.,University of Western Ontario | And 7 more authors.
Canadian Journal of Diabetes | Year: 2016

Background: Type 2 diabetes mellitus is a growing concern worldwide, particularly in Indigenous communities, which have undergone a marked nutrition transition characterized by reduced intakes of traditional foods and increased intakes of market foods. Few studies have assessed the relationships between differing dietary patterns and risk for type 2 diabetes in Indigenous communities in Canada. The objective of the study was to characterize dietary patterns using factor analysis (FA) and to relate these patterns to the incidence of type 2 diabetes after 10 years of follow up in a First Nations community in Ontario, Canada. Methods: We conducted a prospective analysis of 492 participants in the SLHDP who did not have diabetes at baseline (1993 to 1995) and were followed for 10 years. A food-frequency questionnaire was administered, and FA was used to identify patterns of food consumption. Multivariate logistic regression analyses determined associations of food patterns with incident type 2 diabetes, adjusting for sociodemographic and lifestyle confounders. Results: At follow up, 86 participants had developed incident type 2 diabetes. FA revealed 3 prominent dietary patterns: Balanced Market Foods, Beef and Processed Foods and Traditional Foods. After adjustment for age, sex, waist circumference, interleukin-6 and adiponectin, the Beef and Processed Foods pattern was associated with increased risk for incident type 2 diabetes (OR=1.38; 95% CI 1.02, 1.86). In contrast, the Balanced Market Foods and Traditional Foods Patterns were not significantly associated with type 2 diabetes. Conclusions: Dietary interventions should encourage reduced consumption of unhealthful market foods, in combination with improvements in local food environments so as to increase access to healthful foods and reduce food insecurity in Indigenous communities. © 2016 Canadian Diabetes Association.


Ley S.H.,University of Toronto | Hegele R.A.,University of Western Ontario | Connelly P.W.,University of Toronto | Connelly P.W.,Li Ka Shing Knowledge Institute | And 11 more authors.
Cardiovascular Diabetology | Year: 2010

Background: C-reactive protein (CRP), a biomarker of inflammation, has been associated with increased risk of developing cardiovascular disease. Common variants of the hepatocyte nuclear factor 1A (HNF1A) gene encoding HNF-1α have been associated with plasma CRP in predominantly European Caucasian samples. HNF1A might therefore have an impact on vascular disease and diabetes risk that is mediated by CRP. In an Aboriginal Canadian population, a private polymorphism, HNF1A G319S, was associated with increased prevalence of type 2 diabetes. However, it has not been investigated whether this association is mediated by CRP. We aimed to investigate whether CRP was mediating the association between HNF1A G319S and type 2 diabetes in an Aboriginal Canadian population with a high prevalence of diabetes.Methods: A total of 718 individuals who participated in a diabetes prevalence and risk factor survey were included in the current analysis. Participants were genotyped for HNF1A G319S. Fasting plasma samples were analyzed for CRP. Fasting plasma glucose and a 75-g oral glucose tolerance test were obtained to determine type 2 diabetes.Results: The prevalence rate of type 2 diabetes was 17.4% (125/718) using the 1999 World Health Organization definition and was higher among S319 allele carriers compared to G/G homozygotes (p < 0.0001). Among participants without type 2 diabetes, CRP levels were higher among G/G homozygotes (1.64 [95% confidence interval 1.35-2.00] mg/l) than in S319 carriers (1.26 [1.04-1.54] mg/l) (p = 0.009) after adjustment for age, sex, 2-h post-load glucose, waist circumference, and serum amyloid A. CRP levels were elevated among those with diabetes after similar adjustment (4.39 [95% confidence interval 3.09-6.23] and 4.44 [3.13-6.30] mg/L, respectively), and no significant difference in CRP was observed between S319 carriers and non-carriers (p = 0.95).Conclusions: CRP levels were lower in S319 allele carriers of the HNF1A gene compared to non-carriers among individuals without diabetes, but this difference was not present among those with diabetes, who uniformly had elevated CRP levels. Therefore, while HNF1A appears to influence CRP concentrations in the non-diabetic state, chronic elevation of CRP is unlikely mediating the association between the HNF1A polymorphism and the high prevalence of type 2 diabetes in this Aboriginal population. © 2010 Ley et al; licensee BioMed Central Ltd.


Lahiry P.,University of Western Ontario | Cao H.,University of Western Ontario | Ban M.R.,University of Western Ontario | Pollex R.L.,University of Western Ontario | And 7 more authors.
Journal of Lipid Research | Year: 2010

Apolipoprotein (apo) C-I is a constituent of chylomicrons, very low density lipoprotein, and high density lipoprotein. The role of apo C-I in human metabolism is incompletely defi ned. We took advantage of a naturally occurring amino acid polymorphism that is present in aboriginal North Americans, namely apo C-I T45S. We assessed the hypothesis that metabolic traits, including obesity-related and lipoprotein-related traits, would differ between carriers and noncarriers of apo C-I T45S. A genotyping assay was developed for APOC1 T45S and genotypes were determined in a sample of 410 Canadian Oji-Cree subjects. The allele frequency of the apo C-I S45 allele was ∼ 8% in this sample. We observed the apo C-I S45 allele was signifi cantly associated with 1) lower percent body fat (P < 0.05), 2) lower waist circumference (P = 0.058), 3) lower serum leptin levels (P < 0.05), and 4) lower plasma apo C-I levels (P < 0.0001), using a newly developed ELISA-based method. Taken together, these results suggest that at the whole human phenotype level, apo C-I is associated with the complex metabolic trait of obesity as well as with serum leptin levels. Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc.


Ley S.H.,University of Toronto | Harris S.B.,University of Western Ontario | Connelly P.W.,University of Toronto | Connelly P.W.,Li Ka Shing Knowledge Institute | And 9 more authors.
Diabetes, Obesity and Metabolism | Year: 2012

Aims: Traditional lipid indices have been associated with type 2 diabetes, but limited data are available regarding non-high-density lipoprotein (non-HDL) cholesterol. In view of recent guidelines for the clinical management of dyslipidemia recommending the monitoring of non-HDL cholesterol as a secondary target after achieving the low-density lipoprotein (LDL) cholesterol goal, we aimed to assess the association of non-HDL cholesterol with incident type 2 diabetes and compare its utility as a risk predictor with traditional lipid variables in Aboriginal Canadians. Methods: Of 606 diabetes-free participants at baseline, 540 (89.1%) returned for 10-year follow-up assessments. Baseline anthropometry, blood pressure, fasting insulin and serum lipids were measured. Fasting and 2-h postload glucose were obtained at baseline and follow-up to determine the incidence of type 2 diabetes. Results: The cumulative incidence of type 2 diabetes was 17.5%. Higher non-HDL cholesterol, total-to-HDL cholesterol ratio, apolipoprotein B, triglyceride and LDL cholesterol and lower HDL cholesterol concentrations were individually associated with incident type 2 diabetes in univariate analyses (all p < 0.05). Non-HDL cholesterol was a superior determinant of incident diabetes compared with LDL cholesterol (comparing C-statistics of univariate models p = 0.01) or HDL cholesterol (p = 0.004). With multivariate adjustment including waist circumference, non-HDL cholesterol remained associated with incident diabetes [odds ratio (OR) 1.42 (95% confidence interval, CI 1.07-1.88)], while LDL cholesterol and HDL cholesterol became non-significant. Conclusions: Non-HDL cholesterol was associated with incident type 2 diabetes and was superior to LDL cholesterol as a risk predictor in this population. Further studies are required to establish the utility of non-HDL cholesterol in non-Aboriginal populations. © 2012 Blackwell Publishing Ltd.


Ley S.H.,University of Toronto | Hegele R.A.,University of Western Ontario | Harris S.B.,University of Western Ontario | Mamakeesick M.,Sandy Lake Health and Diabetes Project | And 11 more authors.
BMC Medical Genetics | Year: 2011

Background: In a recent report of large-scale association analysis, a type 2 diabetes susceptibility locus near HNF1A was identified in predominantly European descent populations. A population-specific G319S polymorphism in HNF1A was previously identified in Aboriginal Canadians who have a high prevalence of type 2 diabetes. We aimed to investigate the association of the HNF1A G319S polymorphism with incident type 2 diabetes and to assess whether clinical risk variables for type 2 diabetes influence the association in an Aboriginal population.Methods: Of 606 participants who were free of diabetes at baseline in 1993-1995, 540 (89.1%) participated in 10-year follow-up assessments in 2003-2005. Fasting glucose and a 75-g oral glucose tolerance test were obtained to determine incident type 2 diabetes. Participants were genotyped for the HNF1A G319S polymorphism. Interviewers administered questionnaires on smoking behavior.Results: The incidence rates of type 2 diabetes were 14.2% (55/388) in major allele homozygotes and 31.2% (29/93) in minor allele carriers (p < 0.001). The HNF1A G319S carrier status was associated with incident type 2 diabetes (odds ratio [OR] 3.78 [95% CI 2.13-6.69]) after adjustment for age, sex, hypertension, triglyceride, HDL cholesterol, and waist circumference. A statistical interaction was observed between HNF1A G319S and baseline active cigarette smoking on the development of type 2 diabetes with similar adjustment (p = 0.006). When participants were stratified by baseline smoking status, HNF1A G319S carriers who were active smokers had increased risk of developing diabetes (OR 6.91 [95% CI 3.38-14.12]), while the association was attenuated to non-significance among non-smokers (1.11 [0.40-3.08]).Conclusions: The HNF1A G319S variant is associated with incident type 2 diabetes in Aboriginal Canadians. Furthermore, cigarette smoking appears to amplify incident diabetes risk in carriers of HNF1A G319S. © 2011 Ley et al; licensee BioMed Central Ltd.

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