Julie Robitaille

The PPAR-gamma P12A polymorphism modulates the relationship between dietary fat intake and components of the metabolic syndrome: results from the Québec Family Study

The metabolic syndrome is a complex disorder characterized by an atherogenic dyslipidemia resulting from the interaction between genetic and nutritional factors. The objective of this study was to examine in a cohort of 720 adults participating in the Québec Family Study (QFS) whether dietary fat interacts with the P12A polymorphism in the gene encoding the peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ), a nuclear factor that regulates lipid and glucose homeostasis. Carriers of the A12 allele had a higher body mass index (BMI), waist circumference, fat mass as well as subcutaneous adipose tissue and visceral adipose tissue (VAT) areas both assessed by computed tomography than P12/P12 homozygotes. Total fat and saturated fat intakes estimated from a 3‐day food record were significantly correlated with several components of the metabolic syndrome in P12/P12 homozygotes. None of these expected associations were observed among carriers of the A12 allele. Furthermore, in a model including the PPAR‐γ P12A polymorphism, fat intake, age and gender, PPAR‐γ P12A and its interaction with fat intake were associated with BMI and waist circumference. Similar results were obtained when saturated fat intake replaced total fat intake into the model. When the two genotype groups were further classified into quartiles of total fat or saturated fat intake and their characteristics compared, an increase in fat intake was associated with an increase in waist circumference in P12/P12 homozygotes but not in A12 carriers. There was no difference in the waist circumference in carriers of the A12 allele whether the fat or the saturated fat intake was high or low. These results suggest that the PPAR‐γ P12A polymorphism can modulate the association between dietary fat intake and components of the metabolic syndrome.

Association between the PPARα-L162V polymorphism and components of the metabolic syndrome

AbstractGenetic factors, alone or in interaction with components of the diet, are thought to be involved in the development of the metabolic syndrome. The objective of our study was first to compare the frequency of the peroxisome proliferator-activated receptor (PPAR)α-L162V polymorphism in a sample of men with and without the metabolic syndrome as defined by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) guidelines, and secondly, to evaluate gene-diet interaction effects on features of the metabolic syndrome. The PPARα-L162V genotype was determined in a sample of 632 men by a polymerase chain reaction-restriction length polymorphism (PCR-RFLP)-based method; fat as well as saturated fat intakes were evaluated by a dietitian-administered food frequency questionnaire. The frequency of the V162 allele was similar in men with (n=281) and without (n=351) the metabolic syndrome (χ2=0.03, p=0.84) but was higher in subjects having simultaneously abdominal obesity, hypertriglyceridemia, and low high-density lipoprotein cholesterol (HDL-C) levels (χ2=3.73, p=0.05). Carriers of the V162 were characterized by higher plasma apolipoprotein B and triglyceride (TG) levels (p=0.10, p=0.004). In a model including the PPARα-L162V polymorphism, fat or saturated fat, its interaction, and covariates (smoking habits, and energy and alcohol intake), the interaction explained a significant percentage of the variance observed in waist circumference (p<0.05). In conclusion, the PPARα-L162V polymorphism alone or in interaction with dietary fat intake is associated with components of the metabolic syndrome.

Prevention of gestational diabetes mellitus: a review of studies on weight management.

Entering pregnancy with overweight, obesity or gaining excessive gestational weight could increase the risk of gestational diabetes mellitus (GDM), which is associated with negative consequences for both the mother and the offspring. The objective of this article was to review scientific evidence regarding the association between obesity and GDM, and how weight management through nutritional prevention strategies could prove successful in reducing the risk for GDM. Studies published between January 1975 and January 2009 on the relationship between GDM, pre‐pregnancy body mass index (BMI), gestational weight gain and nutritional prevention strategies were included in this review. Results from these reports suggest that maternal obesity assessed by pre‐pregnancy BMI is associated with an increased risk of GDM. They also show an association between gestational weight gain and increased risk for GDM. Higher dietary fat and lower carbohydrate intakes during pregnancy appear to be associated with a higher risk for GDM, independent of pre‐pregnancy BMI. Some studies showed that restricting energy and carbohydrates could minimize gestational weight gain. However, a firm conclusion on the most effective nutritional intervention for the control of gestational weight gain and glycaemic responses could not be reached based on available studies. In light of the studies reviewed, we conclude that weight management through nutritional prevention strategies could be successful in reducing the risk of GDM. Further studies are required to identify the most effective diet composition to prevent GDM and excessive gestational weight gain. Copyright

Weight Gain Measures in Women with Gestational Diabetes Mellitus

BACKGROUND Gestational diabetes mellitus (GDM) and excessive gestational weight gain have significant implications for the health of both mother and child. Our objective was to detail gestational weight gain in women in relationship to GDM. METHODS Data were collected by retrospective reviews of medical records in women who delivered between January and December 2007 at the Laval University Medical Center (Quebec, Canada). The analysis included 294 women (55 GDM and 239 controls) for whom gestational weight gain was calculated by the difference between maternal weight measured at delivery, or at the last prenatal visit (≥37th week), and prepregnancy self-reported weight. Gestational weight gain and rate of weight gain were also calculated for each trimester and until GDM screening. Gestational weight gain was compared to the 2009 recommendations by the Institute of Medicine (IOM). Women with GDM were diagnosed and treated according to the Canadian Diabetes Association guidelines. RESULTS Weight gain in the first trimester was significantly higher in GDM patients compared to controls (3.40 ± 0.42 vs. 1.87 ± 0.16 kg, p ≤ 0.01) and was above IOM recommendations, whereas weight gain in the third trimester was significantly lower in GDM patients compared to controls (4.11 ± 0.36 vs. 6.35 ± 0.18 kg, p ≤ 0.0001). Prepregnancy body mass index (BMI) and first trimester weight gain were both significant and independent predictors of GDM (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.17, and OR 1.25, 95% CI 1.10-1.42, respectively). CONCLUSIONS First trimester gestational weight gain may need more clinical attention, as it has been identified as an independent and significant risk factor for GDM independent of traditional risk factors, including preconception obesity.

Circulating interleukin-6 concentrations during and after gestational diabetes mellitus.

Objective. Recent studies have shown that high interleukin‐6 (IL‐6) secretion may aggravate insulin resistance in pregnancy and participate in the pathogenesis of gestational diabetes mellitus (GDM). The aim of this study was to determine whether the presence of GDM is associated with elevated IL‐6 concentrations and whether this association remains after delivery, independent of body mass index. Design. Longitudinal study. Setting. Hospital‐based. Sample. Forty‐seven women were screened for GDM with a 75g oral glucose tolerance test at 26.1±3.7 weeks of pregnancy following the Canadian Diabetes Association guidelines (20 GDM, 27 control subjects). Main outcome measures. Interleukin‐6 levels were measured by ELISA at the time of GDM screening and two months post‐partum. Results. Interleukin‐6 concentrations were significantly higher in women with GDM compared with control women at the time of GDM screening (1.47±0.72 vs. 0.90±0.32pg/mL, p≤0.01). Similar results were obtained two months post‐partum, where IL‐6 levels remained significantly higher in women with GDM compared with control women (1.88±0.85 vs. 1.41±0.87pg/mL, p≤0.05). Interleukin‐6 concentrations were significantly correlated with the Matsuda insulin sensitivity index, measured at the two time points (r=–0.60, p≤0.01 and r=–0.34, p≤0.05). The Matsuda insulin sensitivity index was an independent and significant predictor of IL‐6 concentrations at the time of GDM screening, explaining 35.6% of the variance (p≤0.0001) in this variable. IL‐6 concentration measured at GDM screening was identified as an independent and significant predictor of post‐partum IL‐6 concentrations, explaining 28.6% of the variance (p≤0.001). Conclusions. These results show that GDM is associated with elevated IL‐6 levels independent of obesity levels, both during pregnancy and after delivery.

Variants within the muscle and liver isoforms of the carnitine palmitoyltransferase I (CPT1) gene interact with fat intake to modulate indices of obesity in French-Canadians

Obesity is under the influence of genetic and nutritional factors. The objective was to verify whether variants in the gene encoding the carnitine palmitoyltransferase I (CPT1), a key enzyme in β-oxidation of fatty acids, are associated with obesity phenotypes, alone or in interaction with fat intake. Sequencing of CPT1 was performed in 40 overweight subjects and 4 controls. Genotypes were determined in 351 French-Canadians. Fat intake was evaluated by a food frequency questionnaire. We identified 14 genetic variations in CPT1A and 26 in CPT1B. Nine variants within CPT1B and one variant within CPT1A were selected for further analyses based on the minor allele frequency (>10%) or on potential functional impact. A significant association between obesity phenotypes (BMI, weight, and waist girth) and CPT1B c.282-18C > T and p.E531K variants was observed (p < 0.05) No other association was found with variants in CPT1A and CPT1B. When subjects were divided into six groups according to p.E531K genotypes and further on the basis of fat using the median value as a cutoff point (34.4% of energy), BMI, weight, and waist girth were higher in E531/K531 on a high-fat diet compared to E531/K531 subjects under a low-fat diet (p = 0.004, p = 0.006, p = 0.003, respectively). There was no difference among E531/E531 and K531/K531. Similar results were obtained with the CPT1A p.A275T variant as BMI and waist girth were higher in A275/A275 on a high fat compared to A275/A275 subjects on a low-fat diet. Among carriers of the T275 allele, obesity indices were not affected by fat intake (p = 0.05 and p = 0.008 for BMI and waist girth, respectively). Among variants within the CPT1B gene, 13 haplotypes were inferred and the two most frequent haplotypes, H7 (38.0%) and H5 (27.7%), were kept for diplotype analysis. These haplotypes were not associated with indices of obesity, but as observed with the CPT1B E531K variant fat intake modulated this association. In conclusion, this finding suggests that indices of obesity might be modulated by an interaction between CPT1 variants and fat intake.

Effect of an Oat Bran-Rich Supplement on the Metabolic Profile of Overweight Premenopausal Women

Background/Aims: A healthy diet is a key factor in the prevention of cardiovascular disease, the leading cause of death for women in industrialized countries. In this regard, soluble fibers may have beneficial effects on the plasma lipoprotein/lipid profile. The objective of the present study was to investigate the plasma lipoprotein/lipid response to dietary fibers in overweight premenopausal women within a randomized controlled trial. Methods: Following a 2-week run-in phase, 34 premenopausal women (age: 22–53 years) were randomly assigned either to the control group (no supplement) or to the treatment group, which received 2 oat bran-enriched muffins per day (28 g/day of oat bran) during 4 weeks. Results: Supplementation with oat bran had a beneficial effect on plasma HDL-C levels. Indeed, compared to the control group (n = 16), a mean increase in plasma HDL-C levels of 11.2% was observed in women eating the oat bran supplement (n = 18) (p = 0.01), whereas the total cholesterol/HDL-C ratio decreased by 7.0% (p = 0.002). Results were similar after adjustment for age, apo E genotype and weight change. Conclusion: These results suggest that oat bran-rich foods have beneficial effect on the metabolic profile of overweight women. Integration of these foods as part of a healthy diet may, therefore, improve the cardiovascular risk profile of women.

The lipoprotein/lipid profile is modulated by a gene–diet interaction effect between polymorphisms in the liver X receptor-α and dietary cholesterol intake in French-Canadians

Genetic and nutritional factors interact together and modulate the plasma lipid profile. We identified variations in the gene encoding the liver X receptor alpha (LXRalpha) and investigated their effects on the plasma lipoprotein/lipid profile. We also examined whether the association between cholesterol intake and plasma lipid profile was modulated by LXRalpha variants. The LXRalpha gene was sequenced in thirty-five French-Canadian men with high plasma total cholesterol (>5.0 mmol/l) and LDL-cholesterol (>3.5 mmol/l) concentrations. dietary cholesterol was obtained from a food-frequency questionnaire. The LXRalpha c.-115G>A, c.-840C>A and c.-1830T>C genotypes were determined by direct sequencing in 732 subjects. Molecular screening of the LXRalpha gene revealed sixteen variants. Genotypes c.-115G>A, c.-840C>A and c.-1830T>C (rare allele frequency of 14.3%, 14.2% and 11.0%, respectively) were analysed further. Plasma total cholesterol concentrations were higher in carriers of the -115A, -840A and -1830C allele, compared with the -115G/G, -840C/C and -1830T/T homozygotes (P< or =0.05). In a model including the c.-115G>A polymorphism, cholesterol intake, the interaction term c.-115G>A x cholesterol intake (mg/d) and covariates, LXRalpha-115G>A explained 1.8% and 2.1% of the variance in total cholesterol and LDL-cholesterol concentrations (P=0.02 and P=0.01), whereas the interaction term explained 2.9% (P=0.002) and 2.8% (P=0.005), respectively. When subjects were divided into four groups according to the median of cholesterol (290.8 mg) and -115G>A genotypes, high cholesterol intake was associated with higher cholesterol levels in -115A carriers. Similar results were observed for c.-840C>A and c.-1830T>C. These results suggest that cholesterol intake interacts with LXRalpha variants to modulate the plasma lipid profile.

Relationship between lactation duration and insulin and glucose response among women with prior gestational diabetes

BACKGROUND Few studies have investigated whether favorable effects of lactation persist after weaning and protect women with prior gestational diabetes mellitus (GDM) against later development of insulin resistance and insulin secretion defects. OBJECTIVE To investigate the impact of lactation duration on insulin and glucose response among women with prior GDM. DESIGN/METHODS The study group comprised 144 women with a history of GDM between 2003 and 2010. Plasma insulin and glucose concentrations were obtained from a 75 g oral glucose tolerance test (OGTT). Total lactation duration (exclusive breastfeeding and breast and bottle-feeding) for all infants was self-reported in months. RESULTS Mean age was 36.5±5.0 years. Time between delivery and metabolic testing was 4.0±1.9 years. Women breastfed for an average of 13.9±16.8 months. Most women (80.6%) reported a history of lactation. Women who lactated had higher homeostasis model assessment for insulin sensitivity (HOMA-IS) and Matsuda indices and lower fasting and 2-h post-OGTT insulin concentrations as well as area under the curve (AUC) for insulin (P≤0.01 for all). Compared with women who lactated for <10 months, women who lactated for ≥10 months had improved insulin sensitivity-secretion index, higher HOMA-IS and Matsuda indices, lower fasting and 2-h post-OGTT insulin concentrations as well as AUC for insulin, and lower incidence of impaired glucose intolerance (P≤0.05 for all). In multiple linear regression analyses, lactation duration emerged as an independent predictor of fasting insulin concentrations (β=-0.02) and insulin sensitivity indices (β=0.02) (P≤0.05 for all). CONCLUSIONS These results suggest that longer duration of lactation is associated with improved insulin and glucose response among women with prior GDM.

Genes, fat intake, and cardiovascular disease risk factors in the Quebec Family Study.

Objective: The aim of this study was to assess gene‐diet interaction effects on cardiovascular disease (CVD) risk factors (waist circumference, plasma triacylglycerol, high‐density lipoprotein‐cholesterol and fasting glucose concentrations, and diastolic and systolic blood pressure) in the Quebec Family Study cohort.