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Introduction: Type 2 diabetes (T2D) is a cardiovascular disease risk equivalent and likely results from broad metabolic changes, which high throughput proteomics have helped to unravel. Prior studies are limited by proteomic coverage, cross sectional design, and lack of physiologic phenotyping. Hypothesis: Complementary proteomic studies of incident T2D and physiologic responses to an intravenous glucose tolerance test (IVGTT) will identify novel proteins with roles in glucose homeostasis and future risk of T2D. Methods: Cardiovascular Health Study (CHS) and HERITAGE study participants without diabetes underwent SomaScan ® profiling of 4,776 plasma proteins. HERITAGE participants underwent IVGTT, from which insulin sensitivity index (S I ), acute insulin response to glucose (AIR G ), and glucose effectiveness (S G ) were derived. We used Cox regression to test protein associations with 18-year incident T2D in CHS, and multivariable linear regression to test protein associations with IVGTT measures in HERITAGE. Results: In CHS (N = 2631, 74 ± 5 years, 62% female, 14% Black), 57 proteins were significantly associated with incident T2D after comprehensive covariate and multiple testing adjustment. Of these, 44, 9, and 8 were associated with S I , AIR G , and S G respectively in HERITAGE (N = 752, 35 ± 14 years, 55% female, 38% Black) (Figure). Notable findings include beta-glucuronidase, which associated with increased T2D risk (HR 1.46 per SD increase in log 2 protein level) and lower S G , suggesting a role in insulin-independent glucose disposal, and thrombospondin-2, which associated with increased T2D risk (HR 1.26 per SD), lower AIR G , and not with S I , indicating that it may be a marker of pancreatic dysfunction. Conclusions: By integrating proteomics from two complementary prospective cohorts using different but related outcomes, we identified 34 novel protein-T2D associations, and characterized their relationship with physiologic axes of glucose metabolism.

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No abstract is provided for this article.

Six pairs of male monozygotic (MZ) twins were submitted to a 22-day overfeeding period during which they ingested a daily surplus of 1,000 kcal above their individual daily energy needs in the form of a mixed diet. Serum lipids, lipoproteins, and apoprotein A and B concentrations were measured before and after the overfeeding period. Percentage of body fat, fasting plasma glucose, and insulin levels as well as plasma glucose and insulin concentrations after a glucose challenge were also measured before and after overfeeding. Results showed that before overfeeding, MZ twins exhibited a significant intrapair resemblance for total serum cholesterol (CHOL), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and for the high density lipoprotein-cholesterol/total cholesterol ratio ( HDL-C CHOL ) (8.2 ≦ F ratios ≦ 32.7, P < .01). The overfeeding experiment induced significant increases only in serum CHOL (P < .01) and in serum LDL-C (P < .05). However, although mean group values of serum TG, HDL-C, and HDL-C CHOL ratio were not significantly modified by overfeeding, there were large interindividual variations in the response of these variables to the experiment. Results suggest that changes in serum TG, HDL-C, and in the HDL-C CHOL ratio were significantly associated with the genotype of the subjects as a significant intrapair resemblance in the response to overfeeding was observed for these variables (0.69 ≦ r ≦ .85, P < .05). Moreover, individual changes in serum HDL-C and in HDL-C CHOL ratio were negatively correlated with changes in serum TG (r = −.64, P < .05 and r = −.84, P < .01; respectively). Finally, subjects that showed an increase in serum TG levels during overfeeding also demonstrated elevated fasting plasma insulin concentrations (r = .67, P < .05) and increased plasma insulin levels during an oral glucose challenge (r = .68; P < .05). These results suggest that the genotype may determine the sensitivity to develop hypertriglyceridemia and a potentially atherogenic lipoprotein-lipid profile (reduced HDL-C CHOL ratio) following a short-term caloric excess. These results also suggest that heredity plays a role in the interindividual variation observed in plasma lipoproteins when chronically overfed.

Age at menarche shows a downward secular trend and differs according to socioeconomic conditions, presumably the result of dietary variations. We report two studies conducted in Quebec City in which the relation between diet and menarche was evaluated. In 1978–1980, baseline information for these studies was obtained on girls aged 9 through 15 and included body weight, height, fatfold thickness at six sites, percent of body fat (derived from underwater weighing), and a 3-day dietary record. In a cross-sectional study of 207 girls aged 11 through 15, we compared dietary patterns between premenarcheal and menarcheal girls using logistic regression. In a 6-year follow-up study of 109 girls who had not experienced menarche at the baseline data collection, the relation between time of occurrence of menarche and dietary patterns was assessed using proportional hazards models. The results confirm the association between body weight and age at menarche. Body fat, however, was not strongly related to the onset of menstruation. In both studies, a higher dietary energy intake was associated with an earlier age at menarche. Dietary composition, and dietary fat in particular, was not related to menarche

The present study was performed to further investigate the adaptive component of thermogenesis that appears during prolonged energy restriction. Fifteen obese men and twenty obese women underwent a 15-week weight-loss programme. During this programme, body weight and composition as well as resting energy expenditure (REE) were measured at baseline, after 2 and 8 weeks of energy restriction (-2929 kJ/d) and drug therapy (or placebo), and finally 2–4 weeks after the end of the 15-week drug therapy and energy restriction intervention, when subjects were weight stable. Regression equations were established in a control population of the same age. These equations were then used to predict REE in obese men and women at baseline, after 2 and 8 weeks, as well as after the completion of the programme. In both men and women body weight and fat mass were significantly reduced ( P &lt; 0.05 in all cases) while fat-free mass remained unchanged throughout the programme. At baseline, REE predicted from the regression equation was not significantly different from the measured REE in men, while in women the measured REE was 13 % greater than predicted. After 2 weeks of energy restriction, measured REE had fallen by 469 and 635 kJ/d more than predicted and this difference reached 963 and 614 kJ/d by week 8 of treatment in men and women respectively. Once body-weight stability was recovered at the end of the programme, changes in REE remained below predicted changes in men (-622 kJ/d). However, in women changes in predicted and measured REE were no longer different at this time, even if the women were maintaining a reduced body weight. In summary, the present results confirm the existence of adaptive thermogenesis and give objective measurements of this component during weight loss in obese men and women, while they also emphasize that in women this component seems to be essentially explained by the energy restriction.

The aim of this study was to determine the levels of endocan and other biomarkers of inflammation in the systemic circulation of three groups of patients: 1) biopsy confirmed Stevens Johnson Syndrome, Toxic Epidermal Necrolysis (SJS/TEN) subjects; 2) patients with allergic skin reactions but biopsy negative for SJS/TEN; and 3) normal controls. Besides, this paper aims to investigate the association of endocan levels with the extent of the skin lesions, the presence of purpura, and the degree of acute renal insufficiency, as well as to investigate endocan as a marker of clinical severity by correlating endocan levels with the SCORTEN results (a prognositic score for SJS/TEN).Sixteen patients over the age of 18 years who were referred to Loyola University Medical Center with severe allergic skin reactions were recruited over a two-year period from May 2012 to May 2014. A diagnosis of SJS or TEN was confirmed in 7 subjects by skin biopsy. Citrated plasma samples were assayed for endocan, tumor necrosis factor-α (TNFα), vascular endothelial growth factor (VEGF), and C-reactive protein (CRP). The differences between SJS/TEN subjects, biopsy negative subjects, and normal controls (N.=23) were explored using ANOVA and Tukey's post-hoc test. Associations with other clinical variables were identified using linear and logistic regression.Biopsy positive SJS/TEN subjects and biopsy negative subjects had higher endocan levels than normal controls (SJS/TEN: 3.01 ng/mL [IQR: 2.15-8.11]; biopsy negative: 3.96 ng/mL [IQR: 1.54-4.85]; normal controls: 1.79 ng/mL [IQR: 1.67-1.98]; ANOVA P=0.0038). Endocan levels were more strongly associated with SCORTEN in SJS/TEN subjects than in biopsy negative subjects (R2 SJS/TEN=0.5110; biopsy negative=0.0317). SJS/TEN subjects exhibited significantly higher levels of TNF-α compared to normal controls (P=0.0267). The TNF-α levels were significantly lower compared to biopsy negative subjects (P=0.0052). VEGF levels were also elevated among SJS/TEN and biopsy negative subjects compared to normal controls (SJS/TEN: 12.04 pg/mL: [IQR: 7.64-52.7]; biopsy negative: 10.54 pg/mL [IQR: 4.17-6.46]; normal controls: 4.94 pg/mL [IQR: 4.17-6.46]; ANOVA P<0.0001). There was no significant difference in VEGF levels between SJS/TEN and biopsy negative subjects (P=0.7110). Similarly, CRP levels were elevated among SJS/TEN patients and biopsy negative subjects compared to normal controls (SJS/TEN: 32.09 µg/mL [IQR: 31.49-52.08]; biopsy negative: 83.38 µg/mL [IQR: 44.74-145.38]; healthy normal: 1.08 µg/mL [IQR: 0.73-2.03]; ANOVA P<0.0001). There was no significant difference in CRP levels between SJS/TEN and biopsy negative subjects (P=0.2416).To our knowledge, this is the first study to evaluate enodcan, a marker of endothelial dysfunction, in the systemic circulation of SJS/TEN patients. Elevated endocan levels were more strongly associated with disease severity among SJS/TEN subjects than among less severe allergic reactions with skin involvement.

This study compared the effects of 3 short-term maximal exercise tests lasting 10, 30, and 90 sec upon blood volume, plasma electrolytes, glucose, glycerol, lactate and skeletal muscle ATP, PC, glycogen, and lactate concentrations. Seven sedentary male subjects were recruited and 5 of them were randomly assigned to each of the 3 protocols. The tests were performed on a modified ergocycle at workloads of 0.9, 0.075, and 0.05 kp∙kg −1 body mass, respectively. Muscle biopsies were taken from the vastus lateralis before and immediately after each exercise. Venous blood samples were collected before, immediately after, and during the recovery (5, 20, 60, and 120 min). Plasma volume decreased during the 30- and 90-sec tests and was increased in all tests after 60 min of recovery. Plasma K + increased during all tests and returned to normal values 5 min postexercise, except after the 90-sec test where it fell below resting values. Plasma Na + and Cl − were unaffected. Blood lactate increased in all tests, glucose increased after the 90-sec test, and glycerol increased after the 30- and 90-sec tests. All 3 tests brought relatively similar changes in muscle ATP, PC, and glycogen while muscle lactate changes were related to exercise duration. These results suggest that a normal hydration status is important for a subject undergoing short training bouts, and that high-intensity tests of short duration do not require a special nutritional regimen to enhance glycogen reserves. Key words: skeletal muscle, hemoconcentration, hypervolemia, hyperkalemia

Background Genome-wide association studies (GWASs) have identified several genes associated with obesity. The mechanisms through which these genes affect body weight are not fully characterized. Recent studies suggest that eating behavior (EB) traits could be involved, but only a few EB traits were investigated. Objective This study aimed to investigate whether genetic susceptibility to obesity is mediated by EB traits (cognitive restraint, disinhibition, hunger) and their subscales. We hypothesized that EB traits, and their subscales, partly mediate this association. Design Adult individuals (n = 768) who participated in the Quebec Family Study were included in this cross-sectional study. A genetic risk score (GRS) of obesity was calculated based on the 97 genetic variants recently identified in a GWAS meta-analysis of body mass index (BMI). EB traits and their subscales were assessed with the use of the Three-Factor Eating Questionnaire. Regression analyses with age and sex as covariates were used to investigate the associations between GRS, EB traits, BMI, and WC and whether the association between GRS and obesity is mediated by EB traits, which represents the indirect effect of GRS on obesity. Results The GRS of obesity was positively associated with BMI (β = 0.19 ± 0.04, P < 0.0001) and WC (β = 0.46 ± 0.10, P < 0.0001). Regression analyses also revealed that the association between GRS of obesity and BMI was partly mediated by disinhibition and susceptibility to hunger (βindirect = 0.09 ± 0.03, P = 0.0007, and βindirect = 0.04 ± 0.02, P = 0.02, respectively). Habitual and situational susceptibility to disinhibition (βindirect = 0.08 ± 0.03, P = 0.002 and βindirect = 0.05 ± 0.02, P = 0.003, respectively) as well as internal and external locus of hunger (βindirect = 0.03 ± 0.02, P = 0.03 for both) were also found to mediate the association between GRS of obesity and BMI. The same trends were observed with WC. Conclusions The results of this study indicate that the genetic susceptibility to obesity is partly mediated through undesirable EB traits, which suggests that they could be targeted in obesity treatment and prevention. This trial was registered at clinicaltrials.gov as NCT03355729.

The purpose of this paper is 1) to describe maximal anaerobic alactacid (AAC) and lactacid (ALC) capacity test and 2) to determine their reliabilities in men and women. The subjects were submitted to either a 10-s (2 trials) or a 90-s (1 trial) all-out ergocycle test for AAC and ALC respectively. Thirty-four male and 24 female subjects were tested for AAC, while 21 males and 19 females took part in the ALC test. A modified bicycle ergometer allowed the exact measurement of the distance and the work load for the computation of the work performed. load for the computation of the work performed. Each subject was tested and retested within 7 days. In both AAC and ALC, male subjects performed more work than women. AAC was 108 +/- 16 (mean +/- SD) and 90 +/- 14 J/kg for males and females respectively while ALC was 486 +/- 50 and 377 +/- 34 J/kg. Although the work load was designed to be 0.09 kp/kg for the AAC and 0.05 kp/kg for the ALC tests, there were wide variations between subjects with respect to the optimal load (AAC: from 0.05 to 0.11; ALC: from 0.03 to 0.06 kp/kg). Reproducibility was consistently high, with intraclass correlations of 0.98 and 0.99 for AAC (AAC-Max) and ALC respectively, with no difference between the male and female subgroups. It is concluded that these AAC and ALC tests, designed under assumptions of face validity, allow for differences between males and females and are highly repeatable.

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The aim of the study was to investigate the possible interactions among the glucocorticoid receptor (GRL), lipoprotein lipase (LPL), and adrenergic receptor (ADR) genes on plasma insulin and lipid levels. The study was cross-sectional and based on 742 individuals from phase 2 of the Quebec Family Study (QFS) cohort. Gene markers were identified by Southern blot analysis or polymerase chain reaction (PCR). Plasma glucose and insulin in the fasted state and during an oral glucose tolerance test (OGTT) were determined and insulin and glucose areas were computed. Triglyceride (TG) and cholesterol concentrations in plasma and lipoprotein fractions were determined enzymatically. The results show that GRL and LPL variants had independent effects on plasma high-density lipoprotein cholesterol (HDL-C) and two β2-ADR variants were related to total cholesterol concentrations. The α2-ADR gene Dral polymorphism was the only variant that had an independent effect on the plasma insulin area. Gene-gene interaction effects were found between GRL and α2-ADR genes for low-density lipoprotein cholesterol ([LDL-C] P = .013) and between GRL and LPL genes for HDL-C (P = .045). Higher-order interaction effects involving GRL, LPL, and ADR markers were observed for the plasma insulin area (P = .001 to .025) but not the glucose area. After correction for multiple tests, the findings remained essentially unchanged for the insulin area but became nonsignificant for the lipid phenotypes. In conclusion, multiple interactions among GRL, LPL, and ADR gene markers contribute to insulin metabolism and perhaps to lipid levels, while no significant effect is found for each gene separately. The LPL locus appears to determine the pattern of interactions with ADR and GRL loci. These results suggest that gene-gene interaction effects could play a role in the etiology of risk factors for common chronic diseases.

Twin resemblance in somatotype components was considered in 28 male and 34 female monozygotic (MZ) twin pairs and 19 male and 21 female dizygotic (DZ) twin pairs, 9.3-23.5 years of age. The Heath-Carter anthropometric somatotype method was used. Mean somatotypes of male twins and female twins did not differ, whereas male twins were significantly more mesomorphic than female twins. Twin resemblance was evaluated in two ways: first, treating each somatotype component independently of the other two (as in earlier twin studies), and, second, looking at resemblance in each somatotype component after statistically controlling for the other two components (thus treating the somatotype as a composite). Intraclass correlations were consistently higher in MZ than in DZ twins of both sexes, and within-pair variances were consistently lower in MZ than in DZ twins of both sexes. However, after controlling for the effects of the other two somatotype components, within-pair variances of male MZ and DZ twins for each somatotype component did not differ. In general, Heath-Carter anthropometric somatotype components show (1) significant resemblance in MZ and DZ twins within each sex, although the degree of resemblance is altered in male twins when a different analytic strategy is used, (2) no sex difference in degree of resemblance, and (3) greater resemblance within MZ twin pairs than within DZ twin pairs. These results are compatible with the presence of genetic variation affecting physique in adolescents and young adults.