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Lay summaryObesity is frequently accompanied by a fatty liver. However, some individuals with high abdominal fat levels nevertheless have low levels of liver fat. Reasons for such discordant phenotypes are unclear. In this paper, we report that among asymptomatic individuals with high levels of visceral fat, low concentrations of IGFBP-2 in the circulation were associated with significantly higher hepatic fat content compared to those with high IGFBP-2 levels. We conclude that quantification of plasma IGFBP-2 concentrations may be useful to identify the early risk for liver fat accumulation in apparently healthy individuals without cardiovascular symptoms.Aim/hypothesisAlthough excess visceral adiposity (VAT) is generally associated with increased liver fat (LF), recent evidence has revealed heterogeneity in LF content among adults with visceral obesity, potentially contributing to specific differences in cardiometabolic outcomes. Reasons for such discordant VAT-LF phenotypes are largely unknown. The present study aimed at assessing whether circulating levels of insulin growth-factor binding protein-2 (IGFBP-2) could be a useful biomarker in the identification of heterogenous and discordant VAT-LF phenotypes.MethodsA sample of 308 middle-aged Caucasian apparently healthy men and women without cardiovascular symptoms were studied for the present cross-sectional analyses. Fasting plasma glucose and lipid levels were assessed and an oral glucose tolerance test was performed. Hepatic fat fraction (HFF) was measured using magnetic resonance spectroscopy whereas VAT was assessed by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants were then classified on the basis of median VAT (81 mL) and IGFBP-2 levels (233 ng/mL).ResultsIndividuals with high levels of VAT were characterized by higher waist circumference, lower insulin sensitivity, as well as by higher plasma triglyceride and lower HDL-cholesterol levels. Plasma IGFBP-2 levels were inversely correlated with HFF (r = -0.39, p < 0.0001). Among men and women with high levels of VAT, those with low levels of IGFBP-2 had significantly higher HFF (7.5 ± 0.7%), compared to participants with high IGFBP-2 concentrations (3.2 ± 0.5%, p < 0.0001).ConclusionIn the presence of excess VAT, high IGFBP-2 concentrations are associated with low levels of LF. Although additional studies will be necessary to establish causality and further clarify the clinical implications of these observations, these findings are concordant with a novel function of IGFBP-2 in modulating susceptibility to non-alcoholic fatty liver disease (NAFLD) in the presence of visceral obesity.

Gagnon et al. perform a Mendelian randomization study to investigate whether excess liver fat underpins adiposity’s effect on cardiometabolic disease risk. They show that abdominal adiposity strongly increases disease risk independently of liver fat, suggesting that targeting liver fat alone may not be sufficient to prevent cardiometabolic disease.

Background The impact of an elevated body mass index (BMI) on atherosclerotic cardiovascular disease (ASCVD) risk in individuals who are metabolically healthy is debated. We investigated the respective contributions of BMI as well as lifestyle and cardiometabolic risk factors combined to ASCVD incidence in 319 866 UK Biobank participants. Methods and Results We developed a cardiovascular health score (CVHS) based on 4 lifestyle and 6 cardiometabolic parameters. The impact of the CVHS on incident ASCVD (15 699 events) alone and in BMI and waist‐to‐hip ratio categories was assessed using Cox proportional hazards in women and men separately. In participants with a high CVHS (8–10), those with a BMI ≥35.0 kg/m2 had a nonsignificantly higher ASCVD risk (hazard ratio [HR], 1.20 [95% CI, 0.84–1.70]; P=0.32) compared with those with a BMI of 18.5 to 24.9 kg/m2. In participants with a BMI of 18.5 to 24.9 kg/m2, those with a lower CVHS (0–2) had a higher ASCVD risk (HR, 4.06 [95% CI, 3.23–5.10]; P

Abstract Translational research aims at reducing gaps between fundamental scientific discoveries and real-world applications. However, the trajectory of most scientific discoveries along the translation research continuum remains highly complex. Logic models are powerful tools that can help reduce this complexity. They are often used to lay out road maps and depict the relationship between activities and their intended effects. Few if any existing tools have been designed to guide the implementation and evaluation of collaborative models between community-based primary health care and biomedical research. To address this gap, we developed a logic model in two stages: 1) a literature review; and 2) the drafting and revision of the model by experts in the field. We describe its components, including objectives, inputs, activities, target groups, outputs, and results for a collaborative model involving fundamental biomedical research and primary health care practices. Our proposed logic model provides a road map that has the potential to reduce the complexity faced by translational research in chronic diseases by providing guidelines for decision-makers. Future work should attempt to validate the model before its broad-based implementation.

Abstract Background Collaboration between biomedical research and community-based primary health care actors is essential to translate evidence into clinical practice. However, little is known about the characteristics and impacts of implementing collaborative models. Thus, we sought to identify and describe collaboration models that bridge biomedical research and community-based primary health care in chronic disease management. Methods We conducted a scoping review using Medline, Embase, Web of Science, and Cochrane Library from inception to November 2020, to identify studies describing or evaluating collaboration models. We also searched grey literature, screened reference lists, and contacted experts to retrieve further relevant references. The list of studies was then refined using more specific inclusion and exclusion criteria. Two reviewers independently selected studies and extracted relevant data (characteristics of studies, participants, collaborations, and outcomes). No bias assessment was performed. A panel of experts in the field was consulted to interpret the data. Results were presented with descriptive statistics and narrative synthesis. Results Thirteen studies presenting 20 unique collaboration models were included. These studies were conducted in North America (n = 7), Europe (n = 5) and Asia (n = 1). Collaborations were implemented between 1967 and 2014. They involved a variety of profiles including biomedical researchers (n = 20); community-based primary health care actors (n = 20); clinical researchers (n = 15); medical specialists (n = 6); and patients, citizens, or users (n = 5). The main clinical focus was cardiovascular disease (n = 8). Almost half of the collaborations operated at an international level (n = 9) and the majority adopted either a network (n = 7) or hierarchical structure (n = 6). We identified significant implementation barriers (lack of knowledge, financial support, and robust management structure) and collaboration facilitators (partnership, cooperation, multidisciplinary research teams). Out of the 20 included collaboration models, seven reported measurable impact. Conclusion We identified a large variety of collaboration models representing several clinical and research profiles and fields of expertise. As they are all based in high-income countries, further research should aim to identify collaborations in low-income countries, to determine which models and/or characteristics, could better translate evidence into clinical practice in these contexts.

Introduction The COVID-19 pandemic and associated restrictive measures have caused important disruptions in economies and labour markets, changed the way we work and socialise, forced schools to close and healthcare and social services to reorganise. This unprecedented crisis forces individuals to make considerable efforts to adapt and will have psychological and social consequences, mainly on vulnerable individuals, that will remain once the pandemic is contained and will most likely exacerbate existing social and gender health inequalities. This crisis also puts a toll on the capacity of our healthcare and social services structures to provide timely and adequate care. The MAVIPAN (Ma vie et la pandémie/ My Life and the Pandemic) study aims to document how individuals, families, healthcare workers and health organisations are affected by the pandemic and how they adapt.Methods and analysis MAVIPAN is a 5-year longitudinal prospective cohort study launched in April 2020 across the province of Quebec (Canada). Quantitative data will be collected through online questionnaires (4–6 times/year) according to the evolution of the pandemic. Qualitative data will be collected with individual and group interviews and will seek to deepen our understanding of coping strategies. Analysis will be conducted under a mixed-method umbrella, with both sequential and simultaneous analyses of quantitative and qualitative data.Ethics and dissemination MAVIPAN aims to support the healthcare and social services system response by providing high-quality, real-time information needed to identify those who are most affected by the pandemic and by guiding public health authorities’ decision making regarding intervention and resource allocation to mitigate these impacts. MAVIPAN was approved by the Ethics Committees of the Primary Care and Population Health Research Sector of CIUSSS de la Capitale-Nationale (Committee of record) and of the additional participating institutions.Trial registration number NCT04575571.

Abstract In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

A high prevalence of intermediate cardiometabolic risk factors and obesity in chronic obstructive pulmonary disease (COPD) has suggested the existence of pathophysiological links between hypertriglyceridemia, insulin resistance, visceral adiposity, and hypoxia or impaired pulmonary function. However, whether COPD contributes independently to the development of these cardiometabolic risk factors remains unclear. Our objective was to compare ectopic fat and metabolic profiles among representative individuals with COPD and control subjects and to evaluate whether the presence of COPD alters the metabolic risk profile. Study participants were randomly selected from the general population and prospectively classified as non-COPD controls and COPD, according to the Global Initiative for Chronic Obstructive Lung Disease classification. The metabolic phenotype, which consisted of visceral adipose tissue area, metabolic markers including homeostasis model assessment of insulin resistance (HOMA-IR), and blood lipid profile, was obtained in 144 subjects with COPD and 119 non-COPD controls. The metabolic phenotype was similar in COPD and controls. The odds ratios for having pathologic values for HOMA-IR, lipids and visceral adipose tissue area were similar in individuals with COPD and control subjects in multivariate analyses that took into account age, sex, body mass index, tobacco status and current medications. In a population-based cohort, no difference was found in the metabolic phenotype, including visceral adipose tissue accumulation, between COPD and controls. Discrepancies between the present and previous studies as to whether or not COPD is a risk factor for metabolic abnormalities could be related to differences in COPD phenotype or disease severity of the study populations.

Abstract Background The Canadian Alliance for Healthy Hearts and Minds (CAHHM) is a pan-Canadian, prospective, multi-ethnic cohort study being conducted in Canada. The overarching objective of the CAHHM is to understand the association of socio-environmental and contextual factors (such as societal structure, activity, nutrition, social and tobacco environments, and access to health services) with cardiovascular risk factors, subclinical vascular disease, and cardiovascular and other chronic disease outcomes. Methods/Design Participants between 35 and 69 years of age are being recruited from existing cohorts and a new First Nations Cohort to undergo a detailed assessment of health behaviours (including diet and physical activity), cognitive function, assessment of their local home and workplace environments, and their health services access and utilization. Physical measures including weight, height, waist/hip circumference, body fat percentage, and blood pressure are collected. In addition, eligible participants undergo magnetic resonance imaging (MRI) of the brain, heart, carotid artery and abdomen to detect early subclinical vascular disease and ectopic fat deposition. Discussion CAHHM is a prospective cohort study designed to investigate the impact of community level factors, individual health behaviours, and access to health services, on cognitive function, subclinical vascular disease, fat distribution, and the development of chronic diseases among adults living in Canada.

BackgroundOur objective was to identify the determinants of high‐density lipoprotein cholesterol efflux capacity (HDL‐CEC) changes in patients with coronary artery disease who participated in a lifestyle modification program aimed at increasing physical activity levels and improving diet quality. Methods and ResultsA total of 86 men with coronary artery disease aged between 35 and 80 years participated in a 1‐year lifestyle modification program that aimed to achieve a minimum of 150 minutes of aerobic physical activity weekly and improve diet quality. HDL‐CECs were measured before and after the 1‐year intervention using 3H‐cholesterol–labeled J774 and HepG2 cells. Visceral, subcutaneous, and cardiac adipose tissue levels were assessed before and after the intervention using magnetic resonance imaging. Lipoprotein particle size and concentrations were measured by proton nuclear magnetic resonance spectroscopy and a complete lipoprotein‐lipid profile was obtained. At baseline, the best correlate of HDL‐CECs were apolipoprotein AI (R2=0.35, P

BackgroundSubclinical atherosclerosis identification remains challenging; abdominal visceral adiposity may improve risk stratification beyond traditional cardiovascular risk factors. Hypertriglyceridemic waist, a visceral adiposity marker combining elevated triglycerides (≥2 mmol/L) and waist circumference (≥90 cm), has been related to carotid atherosclerosis, although associations with high‐risk features, including lipid‐rich necrotic core (LRNC), remain unknown. We tested the hypothesis that hypertriglyceridemic waist is an independent marker of high‐risk atherosclerosis features. Methods and ResultsIn this cross‐sectional study including 467 white men (mean age, 45.9±14.8 years; range 19.4–77.6 years), carotid atherosclerosis characteristics were examined by magnetic resonance imaging and associations with hypertriglyceridemic waist and benefits beyond Framingham Risk Score (FRS) and Pathobiological Determinants of Atherosclerosis in Youth (PDAY) were determined. Subclinical carotid atherosclerosis was present in 61.9% of participants, whereas 50.1% had LRNC. Hypertriglyceridemic waist was associated with carotid maximum wall thickness (P=0.014), wall volume (P=0.025), normalized wall index (P=0.004), and Carotid Atherosclerosis Score (derived from wall thickness and LRNC; P=0.049). Hypertriglyceridemic waist was associated with carotid LRNC volume beyond FRS (P=0.037) or PDAY (P=0.015), contrary to waist circumference alone (both P>0.05). Although 69.7% and 62.0% of participants with carotid atherosclerosis and/or LRNC were not high‐risk by FRS or PDAY, respectively, hypertriglyceridemic waist correctly reclassified 9.7% and 4.5% of them, respectively. Combining hypertriglyceridemic waist with FRS (net reclassification improvement=0.17; P

BackgroundPrevious studies reported that middle‐aged patients with atherogenic lipoprotein‐lipid profile exhibit faster progression of aortic valve stenosis (AS). The ratio of apolipoprotein B/apolipoprotein A‐I (apoB/apoA‐I) reflects the balance between atherogenic and anti‐atherogenic lipoproteins. The aim of this study was to examine the association between apoB/apoA‐I ratio and AS hemodynamic progression and to determine whether this association varies according to age. Methods and ResultsA total of 159 patients (66±13 years, 73% men) with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study. Hemodynamic progression of AS was determined by the change in peak aortic jet velocity (Vpeak) measured by Doppler‐echocardiography between baseline and 2‐year follow‐up. Patients in the top tertile of apoB/apoA‐I ratio (≥0.62) had a faster progression rate of AS compared with those in the bottom/mid tertiles (Vpeak progression: 0.30 [0.09˗0.49] versus 0.16 [0.01˗0.36] m/s, P=0.02). There was a significant interaction (P=0.007) between apoB/apoA‐I ratio and age. Among younger patients (ie, aged

Glucose and lipids stimulate the gut-hormones glucagon-like peptide (GLP)-1, GLP-2 and glucose-dependent insulinotropic polypeptide (GIP) but the effect of these on human postprandial lipid metabolism is not fully clarified.To explore the responses of GLP-1, GLP-2 and GIP after a fat-rich meal compared to the same responses after an oral glucose tolerance test (OGTT) and to investigate possible relationships between incretin response and triglyceride-rich lipoprotein (TRL) response to a fat-rich meal.Glucose, insulin, GLP-1, GLP-2 and GIP were measured after an OGTT and after a fat-rich meal in 65 healthy obese (BMI 26.5-40.2 kg/m(2)) male subjects. Triglycerides (TG), apoB48 and apoB100 in TG-rich lipoproteins (chylomicrons, VLDL1 and VLDL2) were measured after the fat-rich meal.Postprandial responses (area under the curve, AUC) for glucose, insulin, GLP-1, GLP-2, GIP in plasma, and TG, apoB48 and apoB100 in plasma and TG-rich lipoproteins.The GLP-1, GLP-2 and GIP responses after the fat-rich meal and after the OGTT correlated strongly (r = 0.73, p

Patrick Mathieu1, Philippe Pibarot2, Jean-Pierre Després31Department of Surgery, Centre de Recherche de l’Hôpital Laval/Institut de Cardiologie de Québec, Québec, Canada; 2Department of Medicine, Centre de Recherche de l’Hôpital Laval/Institut de Cardiologie de Québec, Québec, Canada; 3Department of Social and Preventive Medicine, Centre de Recherche de l’Hôpital Laval/Institut de Cardiologie de Québec, Québec, CanadaAbstract: Atherosclerosis is a chronic inflammatory disease characterized by infiltration of blood vessels by lipids and leukocytes. There is a growing body of evidence that among risk factors that promote atherosclerosis, the metabolic syndrome is a powerful and prevalent predictor of cardiovascular events. The systemic inflammatory process associated with the metabolic syndrome has numerous deleterious effects that promote plaque activation, which is responsible for clinical events. Interactions between the innate immune system with lipidderived products seem to play a major role in the pathophysiology of atherosclerosis in relation with the metabolic syndrome. The multiple links among adipose tissue, the vascular wall, and the immune system are the topics of this review, which examines the roles of oxidized low density lipoprotein, inflammatory cytokines, and adipokines in triggering and perpetuating a danger signal response that promotes the development of atherosclerosis. Furthermore, therapeutic options that specifically target the metabolic syndrome components are reviewed in light of recent developments. Keywords: atherosclerosis, inflammation, metabolic syndrome, innate immune system, danger signal theory

The aim of this study was first to examine the relationships between adiponectin gene (Apm1) polymorphisms and anthropometric indices as well as plasma adiponectin and lipoprotein/lipid levels, and then to investigate whether the presence of visceral obesity or insulin resistance may modulate the impact of these polymorphisms on metabolic risk variables. Molecular screening of the Apm1 gene was achieved, and a sample of 270 unrelated men recruited from the greater Quebec City area and selected to cover a wide range of body fatness values was genotyped. Sequencing of the Apm1 gene revealed two previously reported polymorphisms (c.45T>G and c.276G>T) as well as two newly identified genetic variations (−13752delT and −13702G>C). Carriers of the c.276T allele had higher LDL-cholesterol and lower HDL-triglyceride concentrations than did 276G/G homozygotes (P = 0.02 and P = 0.01, respectively). Carriers of the c.45G allele exhibited higher plasma adiponectin concentrations than did 45T/T homozygotes (P = 0.04). After dividing each genotype group into subgroups for visceral AT, homozygotes for the normal allele at position −13752delT, carriers of the c.45G allele, and carriers of the c.276T allele had similar total apolipoprotein B (apoB) concentrations, whether they were viscerally obese or not.These results suggest that some Apm1 gene polymorphisms influence plasma adiponectin concentrations and lipoprotein/lipid levels. In addition, the impact of these polymorphisms is modulated by the presence of visceral obesity.

Genome-wide multipoint linkage analyses were performed to identify chromosomal regions harboring genes influencing LDL-cholesterol, total apolipoprotein B (apoB), and LDL-apoB levels using 654 markers. They were assessed in a sedentary state (baseline) and after a 20 week endurance training program. Strong evidence for two quantitative trait loci (QTLs) for baseline levels was found. There is linkage evidence in black families on chromosomes 1q41-q44 [at marker D1S2860, 238 centimorgan (cM), with a maximum log of the odds (LOD) score of 3.7 for LDL-apoB] and in white families on chromosome 8q24 (at marker D8S1774, 142 cM, with LOD scores of 3.6, 3.3, and 2.5 for baseline LDL-cholesterol, LDL-apoB, and apoB, respectively). There were no strong signals for the lipoprotein training responses (as computed as the difference in posttraining minus baseline levels).In conclusion, QTLs for baseline apoB and LDL-cholesterol levels on chromosomes 1q41-q44 (in blacks) and 8q24 (in whites) were found. As there are no known strong candidate genes in these regions for lipids, follow-up studies to determine the source of those signals are needed.

The genetic dissection of complex inherited diseases is a major challenge. Despite limited success in finding genes, substantial data based on genome-wide scan strategies is now available for a variety of diseases and related phenotypes. This can perhaps best be appreciated in the field of lipid and lipoprotein levels, where the amount of information generated is becoming overwhelming. We have created a database containing the results from whole-genome scans of lipid-related phenotypes undertaken to date. The usefulness of this database is demonstrated by performing a new autosomal genomic scan on apolipoprotein B (apoB), LDL-apoB, and apoA-I levels, measured in 679 subjects of 243 nuclear families. Linkage was tested using both allele-sharing and variance-component methods. Only two loci provided support for linkage with both methods: a LDL-apoB locus on 18q21.32 and an apoA-I locus on 3p25.2.Adding those findings to the database highlighted the fact that the former is reported as a lipid-related locus for the first time, whereas the latter has been observed before. However, concerns arise when displaying all data on the same map, because a large portion of the genome is now covered with loci supported by at least suggestive evidence of linkage.

Small, dense LDL particles have been associated with an increased risk of coronary artery disease, and cholesteryl ester transfer protein (CETP) has been suggested to play a role in LDL particle remodeling. We examined the relationship between LDL heterogeneity and plasma CETP mass in familial hypercholesterolemia (FH). LDL particles were characterized by polyacrylamide gradient gel electrophoresis in a total of 259 FH heterozygotes and 208 nonFH controls. CETP mass was measured by enzyme-linked immunosorbent assay in a subgroup of 240 participants, which included 120 FH patients matched with 120 controls. As compared with controls, FH subjects had an 11% higher CETP mass. Moreover, LDL-peak particle diameter (LDL-PPD) was significantly smaller in FH heterozygotes than in controls (258.1 ± 4.8 vs. 259.2 ± 4.1 Å; P = 0.01) after adjustment for covariates. There was also an inverse relationship between LDL-PPD and CETP mass (R = −0.15; P = 0.02), and this relationship was abolished by adjustment for the FH/control status, indicating that LDL-PPD changes in FH are mediated, at least in part, by an increase in plasma CETP mass concentrations.These results suggest that increased plasma CETP mass concentrations could lead to significant LDL particle remodeling in FH heterozygotes and could contribute to the pathogenesis of atherosclerosis.

The objective of the present study was to examine the impact of the T111I missense mutation in exon 3 of the endothelial lipase (EL) gene on HDL and its potential interaction effect with dietary fat. The study sample included 281 women and 216 men aged between 17 and 76 years from the Québec Family Study. Plasma HDL3-C levels of I111I homozygote women were higher compared with those of women carrying the wild-type allele (P = 0.03). These differences were not attenuated when adjusted for levels of obesity and were not observed among men. Dietary PUFA interacted with the T111I mutation to modulate apolipoprotein A-I (apoA-I) and HDL3-C levels among women. Specifically, a diet rich in PUFA was associated with increased apoA-I levels among women carriers of the I111 allele and with decreased apoA-I among women homozygotes for the wild-type allele (P = 0.002). A similar interaction was observed with plasma HDL3-C levels (P = 0.003). These interactions were not observed among men.In conclusion, the EL T111I mutation appears to have a modest effect on plasma HDL levels. The gene-diet interaction among women, however, suggests that the T111I missense mutation may confer protection against the lowering effect of a high dietary PUFA intake on plasma apoA-I and HDL3-C levels.

Abdominal visceral adipose tissue (AT) accumulation is associated with an atherogenic metabolic profile that includes increased plasma triglyceride (TG), low HDL cholesterol levels, and an insulin-resistant hyperinsulinemic state. Whereas the apolipoprotein (apo) C-III C3238G gene variant, often referred to as the SstI polymorphism, has been related to variations in plasma TG concentrations, another variation within the insulin responsive element (C-482T) of the apoC-III gene has been associated with greater glucose and insulin responses to an oral glucose tolerance test (OGTT); however, these results were obtained in nonobese individuals. We therefore investigated the effects of three apoC-III gene polymorphisms, namely SstI, C-482T, and T-455C, on fasting plasma lipoprotein-lipid levels and response to a 75 g OGTT in a sample of 122 viscerally obese men (abdominal visceral AT area ≥130 cm2). Among the three gene variants that were examined, the SstI variation was the only one found to be associated with hypertriglyceridemia. Indeed, S1/S2 heterozygotes (n = 24) were characterized by increased fasting plasma TG concentrations compared with S1/S1 homozygotes (n = 98) (mean ± SD: 3.03 ± 1.58 vs. 2.34 ± 0.95 mmol/l respectively, P < 0.05). The higher TG concentrations in S1/S2 were associated with the presence of smaller, denser LDL particles compared with S1/S1 subjects (LDL peak particle diameter: 24.8 ± 0.5 nm vs. 25.1 ± 0.5 nm respectively, P < 0.05). Furthermore, there was no association between the response to the OGTT and any of the apoC-III gene variants (SstI, T-455C, or C-482T) examined.Results of the present study support the notion of a hypertriglyceridemic effect associated with the apoC-III SstI polymorphism that could modulate the magnitude of the dyslipidemic state in abdominally obese patients.

The Transcultural Diabetes Nutrition Algorithm (tDNA) is a clinical tool designed to facilitate implementation of therapeutic lifestyle recommendations for people with or at risk for type 2 diabetes. Cultural adaptation of evidence-based clinical practice guidelines (CPG) recommendations is essential to address varied patient populations within and among diverse regions worldwide. The Canadian version of tDNA supports and targets behavioural changes to improve nutritional quality and to promote regular daily physical activity consistent with Canadian Diabetes Association CPG, as well as channelling the concomitant management of obesity, hypertension, dyslipidemia, and dysglycaemia in primary care. Assessing glycaemic index (GI) (the ranking of foods by effects on postprandial blood glucose levels) and glycaemic load (GL) (the product of mean GI and the total carbohydrate content of a meal) will be a central part of the Canadian tDNA and complement nutrition therapy by facilitating glycaemic control using specific food selections. This component can also enhance other metabolic interventions, such as reducing the need for antihyperglycaemic medication and improving the effectiveness of weight loss programs. This tDNA strategy will be adapted to the cultural specificities of the Canadian population and incorporated into the tDNA validation methodology.

Reduced plasma HDL cholesterol concentration has been associated with an increased risk of coronary heart disease. However, a low HDL cholesterol concentration is usually not observed as an isolated disorder because this condition is often accompanied by additional metabolic alterations. The objective of this study was to document the relevance of assessing HDL particle size as another feature of the atherogenic dyslipidemia found among subjects with visceral obesity and insulin resistance. For that purpose, an average HDL particle size was computed by calculating an integrated HDL particle size using nondenaturing 4–30% gradient gel electrophoresis. Potential associations between this average HDL particle size versus morphometric and metabolic features of visceral obesity were examined in a sample of 238 men. Results of this study indicated that HDL particle size was a significant correlate of several features of an atherogenic dyslipidemic profile such as increased plasma TG, decreased HDL cholesterol, high apolipoprotein B, elevated cholesterol/HDL cholesterol ratio, and small LDL particles as well as increased levels of visceral adipose tissue (AT) (0.33 ≤ |r| ≤ 0.61, P < 0.0001). Thus, men with large HDL particles had a more favorable plasma lipoprotein-lipid profile compared with those with smaller HDL particles. Furthermore, men with large HDL particles were also characterized by reduced overall adiposity and lower levels of visceral AT as well as reduced insulinemic-glycemic responses to an oral glucose load. In conclusion, small HDL particle size appears to represent another feature of the high TG-low HDL cholesterol dyslipidemia found in viscerally obese subjects characterized by hyperinsulinemia.—Pascot, A., I. Lemieux, D. Prud'homme, A. Tremblay, A. Nadeau, C. Couillard, J. Bergeron, B. Lamarche, and J-P. Després. Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity. J. Lipid Res. 2001. 42: 2007–2014.

Low plasma levels of HDL cholesterol have been associated with an increased risk of coronary heart disease. HDL particles are heterogeneous with respect to size and apolipoprotein content. The objective of the present study was to develop a method to generate lipid-stainable calibrators that would allow the assessment of HDL particle size from whole plasma, using polyacrylamide gradient gel electrophoresis (PAGGE). Lipid-stainable HDL calibrators were obtained by subjecting isolated red blood cells to hemolysis either by freezing at −20 or −80°C overnight or by rapid exposure to liquid nitrogen and mixing of the hemolysis products with plasma aliquots. All three methods were highly reproducible in producing Sudan black lipid-stainable HDL calibrators ranging from 75 to 200 Å. The assessment of HDL particle size with these lipid-stainable HDL calibrators was also highly reproducible, with a coefficient of variation below 5.5%. These lipid-stainable HDL calibrators simplify the assessment of HDL particle size by PAGGE using whole plasma, without the need for costly, time-consuming ultracentrifugation procedures. —Pérusse, M., A. Pascot, J-P. Després, C. Couillard, and B. Lamarche. A new method for HDL particle sizing by polyacrylamide gradient gel electrophoresis using whole plasma.

Peroxisome proliferator-activated receptor alpha (PPARα) is a member of the steroid hormone receptor super family involved in the control of cellular lipid utilization. This makes PPARα a candidate gene for type 2 diabetes and dyslipidemia. The aim of this study was to investigate whether genetic variation in the human PPARα gene can influence the risk of type 2 diabetes and dyslipidemia among French Canadians. We therefore first determined the genomic structure of human PPARα, and then designed intronic primers to sequence the coding region and the exon–intron boundaries of the gene in 12 patients with type 2 diabetes and in 2 nondiabetic subjects. Sequence analysis revealed the presence of a L162V missense mutation in exon 5 of one diabetic patient. Leucine 162 is contained within the DNA binding domain of the human PPARα gene, and is conserved among humans, mice, rats, and guinea pigs. We subsequently screened a sample of 121 patients newly diagnosed with type 2 diabetes and their age and sex-matched nondiabetic controls, recruited from the Saguenay-Lac-St-Jean region of Northeastern Quebec, for the presence of the L162V mutation by a PCR-RFLP based method. There was no difference in L162 homozygote or V162 carrier frequencies between diabetics and nondiabetics. However, whether diabetic or not, carriers of the V162 allele had higher plasma apolipoprotein B levels compared to noncarriers (P = =0.05). To further this association, we screened another sample of 193 nondiabetic subjects recruited in the greater Quebec City area.Carriers of the V162 allele compared with homozygotes of the L162 allele had significantly higher concentrations of plasma total and LDL-apolipoprotein B as well as LDL cholesterol (P ≤ 0.02). These results suggest an association between the PPARα V162 allele and the atherogenic/hyperapolipoprotein B dyslipidemia.

ObjectivesTo determine whether for a given waist circumference (WC), a larger hip circumference (HC) was associated with a reduced risk of insulin resistance, type 2 diabetes (T2D), hypertension and cardiovascular disease (CVD) in HIV-infected patients. A second objective was to determine whether, for a given WC, the addition of HC improved upon estimates of abdominal adiposity, in particular visceral adipose tissue (VAT), compared to those obtained by WC alone.MethodsHIV-infected men (N = 1481) and women (N = 841) were recruited between 2005 and 2009. WC and HC were obtained using standard techniques and abdominal adiposity was measured using computed tomography.ResultsAfter control for WC and covariates, HC was negatively associated with risk of insulin resistance (pConclusionsThe identification of HIV-infected individuals at increased health risk by WC alone is substantially improved by the addition of HC. Estimates of visceral adipose tissue by WC are not substantially improved by the addition of HC and thus variation in visceral adiposity may not be the conduit by which HC identifies increased health risk.

Sedentary behaviour has recently emerged as a unique risk factor for chronic disease morbidity and mortality. One factor that may explain this relationship is visceral adiposity, which is prospectively associated with increased cardiometabolic risk and mortality. The objective of the present study was to determine whether sedentary behaviour was associated with increased accumulation of visceral fat or other deleterious changes in cardiometabolic risk over a 6-year follow-up period among adult participants in the Quebec Family Study.The current study included 123 men and 153 women between the ages of 18 and 65. Total sedentary time and physical activity were assessed by self-report questionnaire. Cross-sectional areas of visceral and subcutaneous abdominal adipose tissue were assessed using computed tomography. Cardiometabolic biomarkers including fasting insulin, glucose, blood lipids, HOMA-Insulin Resistance, and oral glucose tolerance were also measured. All variables of interest were collected at both baseline and follow-up.After adjustment for age, sex, baseline BMI, physical activity, energy intake, smoking, education, income and menopausal status, baseline sedentary behaviour was not associated with changes in visceral adiposity or any other marker of cardiometabolic risk. In the longitudinal model which adjusted for all studied covariates, every 15-minute increase in sedentary behaviour from baseline to follow-up was associated with a 0.13 cm increase in waist circumference (95% CI = 0.02, 0.25). However, there was no association between changes in sedentary behaviour and changes in visceral adiposity or other markers of cardiometabolic risk.These results suggest that neither baseline sedentary behaviour nor changes in sedentary behaviour are associated with longitudinal changes in visceral adiposity in adult men and women. With the exception of waist circumference, the present study did not find evidence of a relationship between sedentary behaviour and any marker of cardiometabolic risk in this population.

Previous studies looking at the relationship between sleep duration and the metabolic syndrome have only used a dichotomous approach (presence/absence) and failed to adjust for important confounding factors. The objective of the present study was to examine the association between self-reported sleep duration and features of the metabolic syndrome in adults.A cross-sectional analysis from the Quebec Family Study (Canada) was conducted on 810 participants aged 18 to 65 years. Participants were categorized as short (≤6 h), adequate (7-8 h) or long (≥9 h) sleepers. The metabolic syndrome was defined according to the American Heart Association/National Heart, Lung, and Blood Institute's criteria.Overall, 24.6% of the sample had the metabolic syndrome. A U-shaped relationship between sleep duration and the prevalence of metabolic syndrome (33.3%, 22.0% and 28.8% in short, adequate and long sleepers, respectively) was observed (P

Objective. To examine the effect of acute and short-term (~1 week) aerobic exercise training on plasma adiponectin levels in inactive, abdominally obese men. Materials and Methods. Inactive and abdominally obese men (n=38, waist circumference ≥102 cm) recruited from Kingston, Canada were randomly allocated to perform three bouts of aerobic treadmill exercise at either low (50% VO2 peak) or high (75% VO2 peak) intensity during a 1-week period. Blood samples were taken before and after the first exercise session and 24–72 hours following the completion of the final exercise session. Results. Adiponectin levels were elevated immediately following an acute bout of exercise at both high and low intensities (High: 5.79±0.42 versus 5.05±0.41 ug/mL; Low: 5.24±0.44 versus 4.37±0.44 ug/mL, P

La obesidad visceral se asocia a anormalidades metabólicas aumentando el riesgo de diabetes de tipo 2 y de coronariopatía (CP). El Estudio Cardiovascular de Québec demostró que la tríada metabólica aterogénica (TMA) presente en hombres visceralmente obesos (VO), incrementa 20 veces el riesgo de CP durante un período de 5 años. Fue desarrollado un algoritmo de detección precoz a fin de identificar individuos que podrían ser portadores de estas anormalidades aterogénicas. Fue descubierto que la presencia simultánea de una circunferencia de la cintura elevada y una hipertrigliceridemia moderada ("cintura hipertrigliceridémica" - CH) podrían identificar adecuadamente a una proporción significativa de portadores de la TMA. Es importante dejar claro, que incluso en ausencia de los clásicos factores de riesgo los pacientes VO pueden tener un riesgo elevado de CP si presentan la CH. Finalmente, se ha sugerido que el riesgo de desarrollar un síndrome coronario agudo en pacientes VO no está siempre relacionado al grado de estenosis coronaria y debería considerarse el perfil aterotrombótico/inflamatorio del paciente en la valoración del riesgo. La estabilización de la placa aterosclerótica se convertiría en un objetivo terapéutico legítimo y más factible para la prevención de la CP en los pacientes VO.Abdominal obesity is associated with metabolic abnormalities, increasing the risk of type 2 diabetes and coronary artery disease (CAD). The Quebec Cardiovascular Survey demonstrated that the atherogenic metabolic triad (AMT) present in abdominally obese (AO) males increases the risk of CAD 20-fold over the course of 5 years. An early detection algorithm was developed to identify individuals presenting these atherogenic abnormalities. It was found that the association of large waist circumference (WC) and moderate hypertriglyceridemia (the "hypertriglyceridemic waist", or HW) could adequately identify a significant portion of individuals with the AMT. It is important to note that even in the absence of classic risk factors, abdominally obese patients can present increased risk of CAD if they have HW. Finally, it has been suggested that the risk of developing an acute coronary syndrome in AO patients is not always related to the degree of coronary stenosis, and the patient’s atherothrombotic/inflammatory profile should be taken into account in evaluating risk. Stabilization of the atherosclerotic plaque would become a legitimate therapeutic objective, and more feasible for prevention of CAD, in AO patients.

La obesidad visceral se asocia a anormalidades metabólicas aumentando el riesgo de diabetes de tipo 2 y de coronariopatía (CP). El Estudio Cardiovascular de Québec demostró que la tríada metabólica aterogénica (TMA) presente en hombres visceralmente obesos (VO), incrementa 20 veces el riesgo de CP durante un período de 5 años. Fue desarrollado un algoritmo de detección precoz a fin de identificar individuos que podrían ser portadores de estas anormalidades aterogénicas. Fue descubierto que la presencia simultánea de una circunferencia de la cintura elevada y una hipertrigliceridemia moderada ("cintura hipertrigliceridémica" - CH) podrían identificar adecuadamente a una proporción significativa de portadores de la TMA. Es importante dejar claro, que incluso en ausencia de los clásicos factores de riesgo los pacientes VO pueden tener un riesgo elevado de CP si presentan la CH. Finalmente, se ha sugerido que el riesgo de desarrollar un síndrome coronario agudo en pacientes VO no está siempre relacionado al grado de estenosis coronaria y debería considerarse el perfil aterotrombótico/inflamatorio del paciente en la valoración del riesgo. La estabilización de la placa aterosclerótica se convertiría en un objetivo terapéutico legítimo y más factible para la prevención de la CP en los pacientes VO.

La obesidad visceral se asocia a anormalidades metabólicas aumentando el riesgo de diabetes de tipo 2 y de coronariopatía (CP). El Estudio Cardiovascular de Québec demostró que la tríada metabólica aterogénica (TMA) presente en hombres visceralmente obesos (VO), incrementa 20 veces el riesgo de CP durante un período de 5 años. Fue desarrollado un algoritmo de detección precoz a fin de identificar individuos que podrían ser portadores de estas anormalidades aterogénicas. Fue descubierto que la presencia simultánea de una circunferencia de la cintura elevada y una hipertrigliceridemia moderada ("cintura hipertrigliceridémica" - CH) podrían identificar adecuadamente a una proporción significativa de portadores de la TMA. Es importante dejar claro, que incluso en ausencia de los clásicos factores de riesgo los pacientes VO pueden tener un riesgo elevado de CP si presentan la CH. Finalmente, se ha sugerido que el riesgo de desarrollar un síndrome coronario agudo en pacientes VO no está siempre relacionado al grado de estenosis coronaria y debería considerarse el perfil aterotrombótico/inflamatorio del paciente en la valoración del riesgo. La estabilización de la placa aterosclerótica se convertiría en un objetivo terapéutico legítimo y más factible para la prevención de la CP en los pacientes VO.