Biomedical subjects

A J G Hanley

Publications and source records attributed to A J G Hanley.

8 recordsLinked to original sources

PubMed2006

Clinical and genetic associations with hypertriglyceridemic waist in a Canadian aboriginal population.

OBJECTIVES: To determine the prevalence of 'hypertriglyceridemic waist' (HTGW) in Oji-Cree, to examine its interaction with hepatic nuclear factor-1alpha (HNF1A) in association with type 2 diabetes, and to characterize its putative genetic determinants. METHOD: The presence or absence of HTGW was determined in 522 Oji-Cree subjects (223 males, 299 females), >or=18 years of age, in whom physical measurements and fasting plasma analyte concentrations were gathered, and a 75-g oral glucose tolerance test was administered, as part of a cross-sectional study. Subjects were genotyped for HNF1A codon 319, angiotensinogen (AGT) codons 174 and 235, G-protein beta3-subunit (GNB3) nucleotide 825, fatty acid-binding protein (FABP2) codon 54, nucleotides -455 and -482 of the apolipoprotein (apo) C-III (APOC3) promoter, and a 5-bp insertion/deletion polymorphism within the 3'-untranslated region of protein phosphatase 1 regulatory subunit 3 (PPP1R3). RESULTS: The unadjusted prevalence of HTGW in Oji-Cree adults was 20.5%, with more males affected than females (27.8 vs 15.1%, P=0.0004). Logistic regression analysis, adjusted for age and gender, showed type 2 diabetes was associated with both HNF1A G319S (odds ratio (OR) 4.85, 95% CI 2.45, 9.58) and HTGW (OR 4.96, 95% CI 2.49, 9.88). When the HNF1A mutation and HTGW were present in combination, the OR for type 2 diabetes was markedly increased (OR 43.2, 95% CI 12.4, 150). In women only, both GNB3 825C>T and FABP2 A54T genotypes were significantly associated with HTGW (OR 2.02, 95% CI 1.01, 4.05 and OR 1.95, 95% CI 1.01, 3.74, respectively). CONCLUSIONS: HTGW is prevalent in Oji-Cree, especially in men. The ORs for type 2 diabetes were similar ( approximately 5-fold) for subjects with either the presence of HTGW or the private HNF1A G319S mutation. These two independent risk factors acted synergistically to confer an even greater increased risk of type 2 diabetes.

Abdominal Fat↗

PubMed2006

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↗

PubMed2006

Elevated C-reactive protein in Native Canadian children: an ominous early complication of childhood obesity.

AIM: Subclinical inflammation has been proposed as a pathophysiologic mechanism linking obesity with vascular and metabolic disease. Native North American populations are experiencing high prevalence rates of both (i) childhood obesity and (ii) adult cardiovascular disease (CVD) and type 2 diabetes. Thus, we sought to determine whether subclinical inflammation is an early complication of obesity in Native children. METHODS: Serum concentrations of the inflammatory biomarker C-reactive protein (CRP) were assessed in a population-based, cross-sectional study of the Sandy Lake Oji-Cree community of Northern Ontario, Canada, involving 228 children aged 10-19 years (mean age 14.8). RESULTS: Median CRP in this population was 0.5 mg/l (interquartile range 0.18-1.79 mg/l). CRP levels were higher than age-matched reference data from the Third National Health and Nutrition Examination Survey (NHANES III). Importantly, fully 15.8% of the children of this community had CRP concentrations between 3 and 10 mg/l, a range that identifies adults at high risk of CVD. Moreover, increasing CRP concentration in this paediatric population was associated with an enhanced CV risk profile, consisting of increased adiposity, higher insulin resistance, worsening lipid profile (higher total cholesterol, triglycerides, low-density lipoprotein cholesterol, apolipoprotein B and total cholesterol : high-density-lipoprotein cholesterol ratio), increased leptin and decreased adiponectin. On multivariate analysis, waist circumference and interleukin-6 (IL-6) emerged as independent determinants of CRP concentration. CONCLUSION: Subclinical inflammation is an early complication of childhood obesity in Native children and may foreshadow an increased burden of CVD and type 2 diabetes in the future.

Adolescent↗

PubMed2006

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↗

PubMed2005

Adiponectin and beta cell dysfunction in gestational diabetes: pathophysiological implications.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) identifies a population of young women at high risk of developing type 2 diabetes and thus provides an excellent model for studying early events in the natural history of this disease. Adiponectin, a novel adipocyte-derived protein with insulin-sensitising properties, has been proposed as a factor linking insulin resistance and beta cell dysfunction in the pathogenesis of type 2 diabetes. We conducted the current investigation to determine whether adiponectin is associated with beta cell dysfunction in GDM. METHODS: We studied 180 women undergoing OGTT in late pregnancy. Based on the OGTT results, participants were stratified into three groups: (1) NGT (n=93); (2) IGT (n=39); and (3) GDM (n=48). First-phase insulin secretion was determined using a validated index previously proposed by Stumvoll. Insulin sensitivity was assessed using the validated OGTT insulin sensitivity index of Matsuda and DeFronzo (IS(OGTT)). RESULTS: To evaluate beta cell function in relation to ambient insulin sensitivity, an insulin secretion-sensitivity index (ISSI) was derived from the product of the Stumvoll index and the IS(OGTT), based on the existence of the predicted hyperbolic relationship between these two measures. Mean ISSI was highest in the NGT group (6,731), followed by that in the IGT group (4,976) and then that in the GDM group (3,300) (overall p<0.0001), compatible with the notion of declining beta cell function across these glucose tolerance groups. Importantly, adiponectin was significantly correlated with ISSI (r=0.34, p<0.0001), with a stepwise increase in mean ISSI observed per tertile of adiponectin concentration (trend p<0.0001). In multivariate linear regression analysis, ISSI was positively correlated with adiponectin and negatively correlated with GDM, IGT and C-reactive protein (r(2)=0.54). CONCLUSIONS/INTERPRETATION: Adiponectin concentration is an independent correlate of beta cell function in late pregnancy. As such, adiponectin may play a key role in mediating insulin resistance and beta cell dysfunction in the pathogenesis of diabetes.

Adiponectin↗

PubMed2005

Abdominal obesity predicts declining insulin sensitivity in non-obese normoglycaemics: the Insulin Resistance Atherosclerosis Study (IRAS).

AIM: Cross-sectional studies have demonstrated a relationship between obesity and insulin sensitivity (S(I)); however, there is a lack of evidence from longitudinal studies. METHODS: The Insulin Resistance Atherosclerosis Study (IRAS) estimated S(I) (x10(-4)/min.microU/ml) directly using a frequently sampled intravenous glucose tolerance test with minimal model analysis in 504 normoglycaemic subjects. Partial correlation coefficients (r) were calculated to compare the relationship of change in S(I) from baseline to 5 years later (DeltaS(I)) with baseline waist circumference (waist) as a measure of abdominal obesity and body mass index (BMI) as a measure of overall obesity. Mean DeltaS(I) was -1.06 (SD = 1.85). RESULTS: Higher baseline waist (r = -0.16; p = 0.0005), but not BMI (r = -0.005; p = 0.91), was associated with (-) DeltaS(I) in models including sex, ethnicity, clinical centre and baseline S(I), BMI, waist, age and physical activity. The waist-DeltaS(I) relationship differed across the levels of baseline BMI, being significant only in normal weight (r = -0.21) and overweight subjects (r = -0.16), but not in obese subjects. DeltaS(I) was correlated with a 5-year change in either obesity measure (Deltawaist: r = -0.22 and DeltaBMI: r = -0.20; p = 0.0001). CONCLUSIONS: Among non-diabetics, waist circumference was a strong predictor of declining S(I) among lean subjects, a modest predictor among overweight subjects, but was not predictive among obese individuals. Waist circumference should be considered, in addition to BMI, when identifying individuals at high risk of diabetes or the insulin resistance syndrome.

Abdomen↗

PubMed2005

Synergism between mutant HNF1A and the metabolic syndrome in Oji-Cree Type 2 diabetes.

AIMS: To determine the prevalence of the metabolic syndrome in the Sandy Lake Oji-Cree and to examine its interaction with HNF1A in association with impaired glucose tolerance and Type 2 diabetes. METHODS: Using data collected from the Sandy Lake Health and Diabetes Project (1993-1995), the presence or absence of the metabolic syndrome was determined in 515 Oji-Cree subjects, > or = 18 years of age. In the original study, fasting plasma analytes were measured, a 75-g oral glucose tolerance test was administered, and subjects were genotyped for HNF1A G319S. RESULTS: The unadjusted prevalence of the metabolic syndrome in the Oji-Cree adults was 29.9%. The adjusted odds ratio (OR) and 95% confidence interval for Type 2 diabetes among subjects who carried the HNF1A G319S mutation and had the modified metabolic syndrome (excluding hyperglycaemia) was 20.3 (6.94, 59.6). Adjusted ORs for Type 2 diabetes for subjects with either the HNF1A G319S mutation alone or the modified metabolic syndrome alone were 5.56 (2.85, 10.9) and 4.84 (2.53, 9.27), respectively. The risk of having impaired glucose tolerance was not influenced by the presence of either factor. CONCLUSIONS: The risk of Type 2 diabetes was similar (approximately five-fold increased) for subjects with either the presence of the modified metabolic syndrome or the private HNF1A G319S mutation. Interestingly, when present in combination, the two independent risk factors appeared to act synergistically to confer an even greater increased risk of Type 2 diabetes.

Adult↗

PubMed2004

Hypoadiponectinaemia in South Asian women during pregnancy: evidence of ethnic variation in adiponectin concentration.

AIMS: People of South Asian descent face an increased risk of Type 2 diabetes mellitus (DM) and coronary artery disease (CAD) compared with other ethnic groups. One candidate factor underlying this risk may be adiponectin, as circulating levels of this adipocyte-derived protein are reduced in both Type 2 DM and CAD. In a recent study, we assessed the relationship between adiponectin and gestational diabetes (GDM), a potential model of early events in the natural history of Type 2 DM. Here, we report the impact of ethnicity on plasma adiponectin concentration in that study. METHODS: A cross-sectional study was performed in 180 women undergoing oral glucose tolerance testing in late second or early third trimester to investigate the relationship between adiponectin and glucose tolerance in pregnancy. Based on self-reported ethnicity, participants were stratified into three groups: (i) Caucasian (n = 116), (ii) South Asian (n = 31), and (iii) Asian (n = 28). RESULTS: Median adiponectin concentration was much lower in the South Asian group (9.7 micro g/ml) than in Caucasians (15.8 micro g/ml) or Asians (16.1 micro g/ml) (overall P < 0.0001). With adjustment for age, prepregnancy body mass index, weight gain in pregnancy, previous history of GDM, family history of DM, fasting insulin and glucose intolerance, mean adiponectin remained significantly lower among South Asians compared with either Caucasians (P < 0.0001) or Asians (P = 0.0034). CONCLUSIONS: Women of South Asian descent exhibit significantly reduced plasma concentrations of adiponectin in pregnancy compared with Caucasian and Asian counterparts. This observation raises the possibility of hypoadiponectinaemia as a potential factor contributing to the increased risk of diabetes and cardiovascular disease in South Asians.

Adiponectin↗