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No abstract is provided for this article.

Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants.

The contribution of changes in body fatness and aerobic fitness to changes in blood lipids after aerobic exercise training was investigated. The sample included 295 men (77 black, 218 white) and 355 women (131 black, 224 white), aged 17 to 65 years, from the HERITAGE Family Study. Participants underwent measurements at baseline and after 20 weeks of supervised exercise training on a cycle ergometer. Body fat mass (FM, in kilograms) was determined by underwater weighing, and aerobic fitness (maximal oxygen uptake, Vo 2max, in milliliters per minute) was assessed by cycle ergometry. Blood lipid measurements included fasting plasma levels of high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol (CHOL), CHOL/HDL, and triglycerides (TG). A composite lipid change index (LCI) was derived by subjecting the [Delta ] scores for the individual blood lipids to principal components analysis. The exercise training was accompanied by a mean increase of 17.5% in Vo 2max and a mean decrease of 3.3% in FM. Partial correlations, controlled for age, between absolute changes in Vo 2max and changes in the blood lipids were consistently low and nonsignificant. On the other hand, absolute changes in FM were significantly (P [lt ] .05) associated with changes in HDL-C (r = [minus ].23), HDL2-C (r = [minus ].17), and CHOL/HDL (r = .24) and the LCI (r = [minus ].27) in men and with changes in LDL-C (r = .22), CHOL (r = .19), and CHOL/HDL (r = .15) and the LCI (r = [minus ].19) in women. Forward stepwise regression confirmed that the change in FM was a better predictor of changes in blood lipids than the change in Vo 2max, entering as a predictor in 4 of 8 regressions in both men and women. Change in Vo 2max did not enter as a significant predictor in any regression. Further, there were no differences in LCI between the upper and lower quartiles of Vo 2max change. On the other hand, there were significant differences between the low and high quartiles of FM change. No race effects were observed in any of the relationships, except that race was a significant predictor of changes in TG in both men and women. In conclusion, changes in blood lipids associated with aerobic exercise training do not appear to be related to changes in aerobic fitness per se; rather, they are weakly to moderately associated with changes in body fatness.

<p>High-throughput proteomics allow researchers to simultaneously explore the roles of thousands of biomarkers in the pathophysiology of diabetes. We conducted proteomic association studies of incident type 2 diabetes and physiologic responses to an intravenous glucose tolerance test (IVGTT) to identify novel protein contributors to glucose homeostasis and diabetes risk. We tested 4,776 SomaScan® proteins measured in relation to 18-year incident diabetes risk in participants from the Cardiovascular Health Study (CHS, N=2,631), and IVGTT-derived measures in participants from the HERITAGE Family Study (N=752). We characterize 51 proteins that were associated with longitudinal diabetes risk, using their respective 39, 9, and 8 concurrent associations with insulin sensitivity (SI), acute insulin response to glucose (AIRG), and glucose effectiveness (SG). Twelve of the 51 diabetes associations were novel, including beta-glucuronidase, which associated with increased diabetes risk and lower SG, suggesting an alternative pathway to insulin for glucose disposal; and plexin-B2 which also associated with increased diabetes risk, but with lower AIRG, and not with SI, indicating a mechanism related instead to pancreatic dysfunction. Other novel protein associations included alcohol dehydrogenase-1C, fructose-bisphosphate aldolase-B, and sorbitol dehydrogenase with elevated type 2 diabetes risk, and leucine rich repeat containing protein-15 and myocilin with decreased risk.</p>

In the current prison setting, with the struggle to counter desocialisation, various associations offer psychological and social support to inmates’ families. The present action-research initiative entitled “How children see imprisonment” (Regards d’enfants sur l’incarceration) was conducted by the ciaphs laboratory of the University of Rennes 2 in collaboration with two of these associations and aimed to set up support groups for children who have a parent or relative in prison. The idea was to assess the conditions, means and mechanisms whereby these children may be availed of an opportunity to share their experiences and say what cannot be said to parents and relatives or more widely within their social environment (friends, school, neighbours, etc.). The results show a clear need to strengthen professional practices around families, and above all the children concerned, who turn out to be those who miss out most from what our French social services have to offer.

Evidence of a genetic component for resting heart rate (RHR) has been found. Quantitative trait loci (QTLs) for baseline RHR have been reported, but not for RHR training response. It is of interest to identify QTLs that may harbor genes influencing RHR variation at baseline and in response to regular exercise training. Here, a multipoint variance components linkage scan using 654 markers was performed to search for QTLs that influence RHR adjusted for several covariates at baseline and in response to 20 weeks of endurance training (post-training minus baseline) in 99 White and 127 Black families in the HERITAGE Family Study. Potentially interesting linkages were revealed on 4 q and 11 p for baseline RHR, and on 1 q and 21 q for RHR training response in Whites. The QTLs on 2 q, 6 q, 7 q, 12 q, 14 q, and 15 q for baseline RHR, and on 3 p, 20 p and 21 q for RHR training response were found in Blacks. Promising linkages (lod scores ≥ 1.75, p ≤ 0.0023) involved 11 p for baseline RHR in Whites and 3 p for RHR training response in Blacks, which did not replicate across races. Interestingly in this study, the linkage evidence on 11 p at the SUR locus was somewhat enhanced (lod score went up from 1.7 to 2.0) in a prehypertensive (BP ≥ 135/80 mm Hg) subset of 40 White families suggesting a pleiotropic gene for BP and RHR with interactions. In conclusion, among QTLs on 1 q, 2 p, 3 p, 4 q, and 11 p that replicated across subsamples and studies, 11 p is most promising for dense mapping and association studies in HERITAGE and other cohorts.

No abstract is provided for this article.

Weight loss protects against type 2 diabetes but is hard to maintain with behavioral modification alone. In an analysis of data from a nonrandomized, prospective, controlled study, we examined the effects of bariatric surgery on the prevention of type 2 diabetes.In this analysis, we included 1658 patients who underwent bariatric surgery and 1771 obese matched controls (with matching performed on a group, rather than individual, level). None of the participants had diabetes at baseline. Patients in the bariatric-surgery cohort underwent banding (19%), vertical banded gastroplasty (69%), or gastric bypass (12%); nonrandomized, matched, prospective controls received usual care. Participants were 37 to 60 years of age, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was 34 or more in men and 38 or more in women. This analysis focused on the rate of incident type 2 diabetes, which was a prespecified secondary end point in the main study. At the time of this analysis (January 1, 2012), participants had been followed for up to 15 years. Despite matching, some baseline characteristics differed significantly between the groups; the baseline body weight was higher and risk factors were more pronounced in the bariatric-surgery group than in the control group. At 15 years, 36.2% of the original participants had dropped out of the study, and 30.9% had not yet reached the time for their 15-year follow-up examination.During the follow-up period, type 2 diabetes developed in 392 participants in the control group and in 110 in the bariatric-surgery group, corresponding to incidence rates of 28.4 cases per 1000 person-years and 6.8 cases per 1000 person-years, respectively (adjusted hazard ratio with bariatric surgery, 0.17; 95% confidence interval, 0.13 to 0.21; P<0.001). The effect of bariatric surgery was influenced by the presence or absence of impaired fasting glucose (P=0.002 for the interaction) but not by BMI (P=0.54). Sensitivity analyses, including end-point imputations, did not change the overall conclusions. The postoperative mortality was 0.2%, and 2.8% of patients who underwent bariatric surgery required reoperation within 90 days owing to complications.Bariatric surgery appears to be markedly more efficient than usual care in the prevention of type 2 diabetes in obese persons. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01479452.).

Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia, is a complex disease primarily caused by impairment in insulin sensitivity (S I ) and insulin secretion. While a strong genetic component for T2DM is well established, there are few reports on racial differences in the magnitude of the genetic effects of T2DM and indices of glucose and insulin metabolism. We report here on the familial resemblance for traits related to glucose metabolism at pre‐exercise training levels in 492 members from 99 sedentary White families and 259 members from 108 Black families participating in the multicenter HERITAGE Family Study. All these traits were obtained from the frequently sampled intravenous glucose tolerance test (IVGTT). They include glucose disappearance index (K g ), an overall index for glucose tolerance, acute insulin response to glucose (AIR Glucose ) which is an index for insulin secretion, and those derived from the minimal model including S I and the disposition index (DI). DI, derived as the product of S I and AIR Glucose , is a measure of the activity of the B‐cells adjusted for insulin resistance. After adjustment for age, sex, and body mass index, the maximal heritability estimates in Blacks (Whites) are 48±14% (25±8%) for K g , 44±14% (46±8%) for AIR Glucose , 38±12% (44±8%) for S I and 32±14% (24±8%) for DI. Interestingly, Blacks have higher heritability for overall glucose tolerance than Whites but there is no race difference in heritability estimates for insulin sensitivity or insulin secretion.

<i>Background/Aims:</i> Genome-wide association studies have led to the identification of several susceptibility genes for type 2 diabetes mellitus (T2DM). The objective of this study was to test the hypothesis that the associations between single nucleotide polymorphisms (SNPs) in these genes and adiposity and glucose homeostasis-related phenotypes are influenced by dietary fat intake. <i>Methods:</i> Thirty-three SNPs in 9 T2DM genes <i>(CDKAL1, CDKN2A/B, HHEX, HNF1B, IGF2BP2, KCNJ11, SLC30A8, TCF7L2</i> and <i>WFS1)</i> were tested in a maximum of 669 subjects from the Quebec Family Study. Subjects were measured for several adiposity indices and underwent a 75-gram oral glucose tolerance test. Total fat intake was estimated from a 3-day dietary record. <i>Results:</i> We observed 13 significant (p ≤ 0.01) SNP-dietary fat interactions. Among them, <i>IGF2BP2</i> rs4402960, alone or in interaction with dietary fat intake, influenced abdominal total fat (ATF: SNP effect, p = 0.006, interaction effect, p = 0.009) and abdominal visceral fat (AVF: SNP effect, p = 0.007, interaction effect, p = 0.01). Similarly, <i>TCF7L2</i> rs12573128 alone or in interaction with dietary fat intake, influenced insulin sensitivity (SNP effect and interaction effect, p ≤ 0.008) and glucose tolerance (SNP effect p ≤ 0.009 and interaction effect, p ≤ 0.01). <i>Conclusion:</i> These results suggest that gene-dietary fat interactions may influence glucose homeostasis-related phenotypes and play an important role in determining the increased risk of diabetes associated with the T2DM susceptibility genes.