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Background Data on the relationship between protein intake and the risk of type 2 diabetes are conflicting. Objective We studied prospective associations between the intake of total, plant-based, and animal protein and the risk of pre-diabetes and diabetes in 4 population-based studies included in the PREVIEW project. Methods Analyses were conducted with the use of data from 3 European cohorts and 1 Canadian cohort, including 78,851 participants. Protein intake was assessed through the use of harmonized data from food-frequency questionnaires or 3-d dietary records. Cohort-specific incidence ratios (IRs) were estimated for pre-diabetes and diabetes, adjusting for general characteristics, lifestyle and dietary factors, disease history, and body mass index (BMI) and waist circumference; results were pooled based on a random-effects meta-analysis. Results Higher total protein intake (g · kg–1 · d–1) was associated with lower incidences of pre-diabetes and diabetes (pooled IRs: 0.84; 95% CI: 0.82, 0.87 and 0.49; 95% CI: 0.28, 0.83, respectively); plant-based protein intake was the main determinant (pooled IRs: 0.83; 95% CI: 0.81, 0.86 and 0.53; 95% CI: 0.36, 0.76, respectively). Substituting 2 energy percentage (E%) protein at the expense of carbohydrates revealed increased risks of pre-diabetes and diabetes (pooled IRs: 1.04; 95% CI: 1.01, 1.07 and 1.09; 95% CI: 1.01, 1.18, respectively). Except for the associations between intakes of total protein and plant-based protein (g · kg–1 · d–1) and diabetes, all other associations became nonsignificant after adjustment for BMI and waist circumference. Conclusions Higher protein intake (g · kg–1 · d–1) was associated with a lower risk of pre-diabetes and diabetes. Associations were substantially attenuated after adjustments for BMI and waist circumference, which demonstrates a crucial role for adiposity and may account for previous conflicting findings. This study was registered at ISRCTN as ISRCTN31174892. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the familial risk of obesity and of an android profile of fat distribution in the general Canadian population. A sample of 15, 245 participants aged 7–69 years from 6, 377 households from the Canada Fitness Survey of 1981 was used. The body mass index (BMI), sum of five skinfolds (SF5), ratio of trunk-to-extremity skinfolds, adjusted for SF5, and waist circumference, adjusted for BMI were used as indicators of obesity and central fat distribution. Age- and sex-standardized risk ratios (SRRs) for spouses and first-degree relatives of obese probands indicate that there is significant familial risk for obesity and an android fat distribution in the Canadian population. SRRs for spouses and first-degree relatives of probands exceeding the 99th percentile are 3.01 and 4.96 for BMI, 7.36 and 4.15 for SF5, 1.41 and 3.18 for ratio of trunk-to-extremity skinfolds, adjusted for SF5, and 1.02 and 2.18 for waist circumference, adjusted for BMI, respectively. The SRRs are smaller for less extreme obesity (lower percentile cutoffs) than for more extreme obesity. The SRRs are greater in spouses than in first-degree relatives for SF5; however, the risk for BMI and an android fat distribution was greater among first-degree relatives than among spouses, suggesting a greater role for genetic factors. Am J Epidemiol 1999; 149:933–42. [ABSTRACT FROM PUBLISHER]

Abstract Metabolites are of great importance for understanding the pathogenesis of several diseases. Understanding the genetic contribution to metabolite concentrations may provide insights into mechanisms of complex diseases. Several studies have investigated heritability of metabolites but none investigated potential influences of genetic and environmental factors on the relationship between metabolites and cardiometabolic (CM) risk factors. Thus, we tested the hypothesis that both genetic and common environmental effects contribute to the variance of plasma metabolite concentrations and that shared genetic and environmental effects explain their phenotypic correlations with CM risk factors. To test this hypothesis, variance component method and bivariate genetic analysis were performed in a family-based sample of 48 French Canadians from 16 families. Familial resemblances were computed for all 147 detected metabolites and 9 (acetylornithine, acylcarnitine C9, arginine, phosphatidylcholine acyl-alkyl C36:4, serotonin, lysophosphatidylcholine acyl C20:4, citrulline, asymmetric dimethylarginine, phosphatidylcholine acyl-alkyl C36:5) showed a significant familial effect (55.7%, 18.7%, and 37.0% for maximal heritability, genetic heritability, and common environmental effect, respectively). Citrulline, phosphatidylcholine acyl-alkyl C36:4, phosphatidylcholine acyl-alkyl C36:5, and serotonin had significant phenotypic correlations with CM risk factors. Citrulline had a positive genetic correlation with apolipoprotein B100, while phosphatidylcholine acyl-alkyl C36:5 had a positive environmental correlation with total cholesterol. In conclusion, familial resemblances in metabolite concentrations were mainly attributable to common environmental effect when considering metabolites with a significant familial effect. Common genetic and environmental factors may also influence the relationship between metabolites and CM risk factors. [ABSTRACT FROM AUTHOR]

Background and Aim: Little is known about the cardioprotective potential of a healthy lifestyle in familial hypercholesterolemia (FH). The objective of this study was to evaluate the relationship between lifestyle and cardiovascular risk factors in adults with FH., Methods and Results: This cross-sectional study leveraged data from the CARTaGENE Quebec population-based cohort (Canada). Participants with FH were identified using the validated Simplified Canadian Definition for FH. A healthy lifestyle score (HLS), ranging from 0 to 5, was calculated per adherence to 5 lifestyle habits: 1) not smoking; 2) being physically active (≥150 min/week of moderate or vigorous physical activity); 3) eating a healthy diet (Alternate Healthy Eating Index ≥50%); 4) having a light to moderate alcohol consumption (men: 1-30 g/day; women: 1-15 g/day); and 5) sleeping 7-8 h/day. Among the 122 included individuals (women, n = 78; men, n = 44; mean age ± SD: 57.3 ± 6.7 years), 92 (75.4%) had a HLS ≤3/5, while only 5 (4.1%) had a HLS of 5/5. After adjustments for sex, age, body mass index, and lipid-lowering medication use, we found no evidence of an association between the HLS and concentrations of LDL-cholesterol (β = 0.04, 95% CI = -0.08, 0.15 mmol/L; P = 0.54). However, the HLS was favorably associated with HbA1c levels (β = -0.07, 95% CI = -0.13, -0.01%; P = 0.02), and statistical trends suggested favorable associations with HDL-cholesterol (β = 0.06, 95% CI = -0.02, 0.14 mmol/L; P = 0.06) and waist circumference (β = -2.22, 95% CI = -4.62, 0.17 cm; P = 0.07)., Conclusion: This study suggests that a healthy lifestyle is favorably associated with CVD risk factors in adults with FH., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The extent of weight loss among patients undergoing bariatric surgery is highly variable. Herein, we tested the contribution of genetic background to such interindividual variability after biliopancreatic diversion with duodenal switch., Methods: Percentage of excess body weight loss (%EBWL) was monitored in 865 patients over a period of 48 months after bariatric surgery, and two polygenic risk scores were constructed with 186 and 11 (PRS186 and PRS11) single nucleotide polymorphisms previously associated with body mass index (BMI)., Results: The accuracy of the %EBWL logistic prediction model - including initial BMI, age, sex, and surgery modality, and assessed as the area under the receiver operating characteristics (ROC) curve adjusted for optimism (AUCadj = 0.867) - significantly increased after the inclusion of PRS186 (ΔAUCadj = 0.021; 95% CI of the difference [95% CIdiff] = 0.005-0.038) but not PRS11 (ΔAUCadj= 0.008; 95% CIdiff= -0.003-0.019). The overall fit of the longitudinal linear mixed model for %EBWL showed a significant increase after addition of PRS186 (-2 log-likelihood = 12.3; P = 0.002) and PRS11 (-2 log-likelihood = 9.9; P = 0.007). A significant interaction with postsurgery time was found for PRS186 (β = -0.003; P = 0.008) and PRS11 (β = -0.008; P = 0.03). The inclusion of PRS186 and PRS11 in the model improved the cost-effectiveness of bariatric surgery by reducing the percentage of false negatives from 20.4% to 10.9% and 10.2%, respectively., Conclusion: These results revealed that genetic background has a significant impact on weight loss after biliopancreatic diversion with duodenal switch. Likewise, the improvement in weight loss prediction after addition of polygenic risk scores is cost-effective, suggesting that genetic testing could potentially be used in the presurgical assessment of patients with severe obesity., Funding: Heart and Stroke Foundation of Canada (G-17-0016627) and Canada Research Chair in Genomics Applied to Nutrition and Metabolic Health (no. 950-231-580).

Evidence suggests that industrial trans fatty acids (iTFA) impair lipid profiles while ruminant trans fatty acids (rTFA) may lower insulin resistance and blood pressure. The objective of this article was to determine if the plasma phospholipid percentage of rTFA is associated with a favorable cardiometabolic profile. We collected fasting blood samples from 200 individuals from Quebec city (QC, Canada) aged from 18 to 55 years old, including 100 obese (BMI ≥ 30 kg m(-2)) and 100 non-obese (BMI < 30 kg m(-2)) men and women. Fatty acid levels in plasma phospholipids were determined using gas chromatography. After separating the subjects into two groups, according to the median percentage of rTFA in plasma phospholipids, participants in the group with higher percentages of rTFA (0.86 ± 0.24 %) had higher adiponectin levels (p = 0.01) and a lower blood pressure (systolic, p = 0.005; diastolic, p = 0.04). In contrast, concentrations in plasma phospholipids of elaidic acid, a major iTFA, are positively correlated with glycemia in non-obese subjects (p = 0.01) and with both triacylglycerol (TAG) (p = 0.0007) and total cholesterol (TC) (p = 0.009) in obese subjects. These data suggest that rTFA may have beneficial effects on cardiometabolic risk factors conversely to their counterpart iTFA. Dietary sources of TFA should be taken into account in future cardiometabolic studies.

The UDP-glucuronosyltransferase UGT1 locus is composed of nine exon 1s, each flanked by a unique promoter region, and common exons (2, 3, 4, and the alternatively spliced exons 5a and 5b). Here, we characterized the genetic architecture of the UGT1 gene in a Caucasian sample. Overall, 98 variations in regulatory domains, exons and exon-intron boundaries were genotyped in 254 unrelated subjects, including 12 unreported UGT1 polymorphisms. We determined allele frequencies, computed pairwise linkage disequilibrium (LD), and inferred haplotypes; this thorough analysis yielding a limited number of common UGT1 haplotypes. Moreover, only 17 haplotype tagging single nucleotide polymorphisms (htSNPs) are required to capture most of the allelic diversity of the locus. Four haplotype blocks were inferred: Block 9/6 (UGT1A9, UGT1A7 and UGT1A6), Block 4 (UGT1A4), Block 3/1 (UGT1A3 and UGT1A1), and Block C (3'UTR). A high level of linkage exists between Blocks 9/6 and 3/1, while the 3'UTR SNPs are genetically isolated. The most common haplotype (16.5%) presents multiple deleterious alleles, mainly 1A1*28, 1A3*2, 1A6*2, and 1A7*4. More interestingly, we reveal the co-occurrences of multiple deleterious variations, some of which could be associated with interindividual differences in glucuronidation. Comparison with the HapMap data set demonstrated differences in haplotypic diversity between ethnic samples, but similarity between Caucasian cohorts, as observed previously. This report provides relevant data for further pharmacogenomic studies., ((c) 2009 Wiley-Liss, Inc.)

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 beta-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.

Objective: To investigate the familial resemblance of 7-year changes in body mass and adiposity among Canadian families., Research Methods and Procedures: The sample consisted of 655 women and 660 men from 521 families who participated in the Canada Fitness Survey in 1981 and the follow-up Campbell's Survey in 1988. Indicators of baseline and 7-year changes in body mass and adiposity included body mass (kilograms), body mass index (BMI; kilograms per square meter), sum of five skinfolds (SF5; millimeters), and waist circumference (WC; millimeters). The data were adjusted for the effects of age and sex, and the change scores were adjusted for baseline levels. A familial correlation model was used to determine the heritability of each phenotype using maximum likelihood techniques., Results: Significant familial resemblance was observed at baseline and for 7-year changes in all phenotypes. At baseline, moderate heritabilities were observed [body mass: heritability coefficient (h(2)) = 56%; BMI, h(2) = 39%; SF5, h(2) = 41%; and WC, h(2) = 39%], whereas values were attenuated for each change score except for WC (Deltabody mass, h(2) = 23%; DeltaBMI, h(2) = 14%; DeltaSF5, h(2) = 12%; and DeltaWC, h(2) = 45%)., Discussion: Changes in body mass and adiposity significantly aggregate within families over 7 years. However, baseline values are characterized by higher heritability levels except WC. The significant heritabilities observed for change scores suggest that lifestyle, transient environmental factors, and possibly age-related gene effects are important determinants of changes in body mass and adiposity.

Background: Among adrenergic receptor subtypes that regulate lipid mobilization, the alpha2-adrenergic receptor is involved in the inhibition of fatty acid mobilization from adipose tissue. A C-1291G polymorphism is located in the alpha2-adrenergic receptor gene (ADRA2A) but no association with body fat accumulation has been reported yet., Materials and Methods: Body mass index (BMI), fat mass (FAT), percentage body fat (%FAT), trunk-to-extremity skinfold ratio (TER), sum of eight skinfolds (SF8), and abdominal subcutaneous (ASF), visceral (AVF), and total (ATF) fat areas assessed by CT scan have been measured in adult sedentary white (n = 503) and black (n = 276) subjects participating in the HERITAGE Family Study. Association between the C-1291G polymorphism and each phenotype was tested separately in men and women of each race using ANCOVA with the effects of age as covariate in addition to the effects of BMI for TER and of FAT for AVF, ASF, and ATF., Results: The allele frequencies of the ADRA2A C-1291G polymorphism differed between races. No association was observed in white subjects, except for a moderate effect of the polymorphism accounting for less than 1% of the variance in AVF and ATF in women. In black subjects, however, the G-1291 allele was found to be associated with an increase of TER in men (3.8% of variance accounted for by the polymorphism), while in black women it was associated with a decrease in TER (2.9%) and in AVF (2.5%)., Conclusion: These results suggest a role for the ADRA2A gene in determining the propensity to store fat in the abdominal area, independently of total body fatness.