Publications

Equations have been developed for the prediction of deep abdominal adipose-tissue (AT) accumulation from anthropometric measurements in a sample of 110 men. An equation including the waist circumference and age could predict 74% of the variance in the amount of deep abdominal AT with an SEE of 29.6 cm2(29.2% of the mean deep abdominal AT value), whereas another equation including the sagittal diameter, the waist-to-hip ratio (WHR), and age explained 76.6% of its variance with an SEE of 28.1 cm2(27.7%). Equations excluding age as an independent variable were also developed. These results indicate that equations in which simple anthropometric measurements are used can provide further information in the assessment of the risk of cardiovascular disease in men. However, we must remember that our ability to predict the amount of deep abdominal AT from anthropometry is limited.

The aim of this report is to evaluate the relationships between baseline levels of adrenal, gonadal and conjugated steroids and baseline cardiorespiratory fitness, as assessed by maximal oxygen uptake (VO2max), as well as its response to a standardized exercise program. To address this aim we used a subset of the HERITAGE Family Study (N = 448). In men, significant positive associations were found between baseline VO2max/kg weight and plasma levels of androsterone glucuronide (ADTG), dihydrotesterone (DHT), 17 hydroxy progesterone (OHPROG), sex hormone binding globulin (SHBG), and testosterone (TESTO), and negative association with aldosterone (ALDO). In women, only the free androgen index (FAI) was negatively associated with baseline VO2max/kg weight. Neither baseline plasma steroid levels nor SHBG concentrations were associated with the gains in VO2max resulting from exposure to the 20-week aerobic exercise program after adjustment for baseline values, age and ethnicity (white or black). We conclude that baseline plasma steroid levels are only weakly associated with individual differences in cardiorespiratory fitness in the sedentary state in men but not in women, whereas no association could be detected with trainability, as defined by the change in VO2max with the exercise program.

Background: Glycine is a non-essential amino acid that has been inversely associated to coronary heart disease (CHD), with recent data suggesting that this relationship may be mediated by lower blo...

To investigate whether genetic variations in the genes encoding the alpha and beta subunits of the Na,K-ATPase are linked with hemodynamic phenotypes.Cross-sectional data based on 533 subjects (no antihypertensive medication) were obtained from 150 families of phase 2 of the Quebec Family Study, together with longitudinal data from 338 subjects (105 families) who had been measured 12 years earlier in phase 1 of the Quebec Family Study.Restriction fragment length polymorphisms were examined at the alpha 2 (exon 1 and exon 21-22 with BglII) and beta 1 (Msp I and Pvu II) loci of Na,K-ATPase. Hemodynamic phenotypes measured included systolic and diastolic blood pressure, heart rate and rate-pressure product at rest and during low-intensity exercise.Sib-pair analysis revealed relatively strong linkages (P = 0.0003-0.002) between the resting heart rate and rate-pressure product and the alpha 2 exon 21-22 marker and alpha 2 haplotype. Moreover, the alpha 2 exon 21-22 marker showed suggestive linkages (P = 0.01 to 0.043) with resting systolic blood pressure and exercise diastolic blood pressure, heart rate and rate-pressure product, and the alpha 2 haplotype with exercise diastolic blood pressure and rate-pressure product and the 12-year change in resting systolic blood pressure (P = 0.03 to 0.05). Both the beta 1 Msp I marker and the beta 1 haplotype were linked with the resting rate-pressure product (P = 0.007 and 0.003, respectively), and all beta 1 markers showed linkage with the change in resting systolic blood pressure (P = 0.00005 to 0.024). In men, there was a significant (P = 0.01) interaction between the alpha 2 exon 21-22 genotype and the postglucose plasma insulin level with regard to resting systolic blood pressure.These data suggest that the alpha 2 and beta 1 genes of Na,K-ATPase contribute to the regulation of hemodynamic phenotypes in healthy subjects.

Background: HDL function has recently been identified as a strong predictor of cardiovascular risk. Exercise is well known to effect HDL metabolism and cardiovascular disease risk, however the effects of exercise on measures of HDL function and composition are less well known. Methods: We examined changes in cholesterol efflux capacity and concomitant changes in the HDL proteome and lipolytic enzymes in 19 white, non-related, individuals from the HERITAGE Family Study. Measurement of the efflux of radiolabeled and BODIPY-labeled cholesterol from J774 macrophages to apoB depleted plasma, along with untargeted HDL proteome profiling and post-heparin hepatic and lipoprotein lipase activities, was performed at baseline and following a 20-week endurance exercise program. Results: There was no effect of regular exercise on cholesterol efflux capacity, but a wide variation in response to exercise was observed (range: -0.28 to 0.40 normalized efflux). Changes in hepatic lipase and lipoprotein lipase activities were moderately positively correlated with changes in radiolabeled ABCA1 and negatively correlated with changes in non-ABCA1 efflux ( Table 1 ). A total of 33 known HDL proteins were identified in all 19 subjects. Only changes in albumin and APOE abundance were nominally (p<0.05) correlated with changes in BODIPY-labeled cholesterol efflux, whereas IGHA1, IGHG2, C6, and SAA4 levels were correlated with global radiolabeled cholesterol efflux ( Table 1 ). Discussion: This pilot study provides limited evidence for a potential role of lipolytic enzymes and select HDL proteins as mediators of changes in cholesterol efflux capacity in response to regular exercise. Future studies with larger sample sizes are needed to further examine how alterations in the HDL proteome are related to HDL function.

No abstract is provided for this article.

Thirty-three untrained subjects of both sexes, 18-31 years of age, performed several tests on cycle ergometers. Maximal aerobic power (MAP) was obtained in a progressive work test. Maximal aerobic capacity (MAC) was measured in a 90-min maximal test and was computed as the total work output during that period. Two all-out cycle ergometer work tests lasting 10 s and 90 s were used to estimate the anaerobic alactic capacity (AAC) and lactic capacity (ALC). Anaerobic alactic power (AAP) was computed as the highest output in 1 s in the AAC test and anaerobic lactic power (ALP) was obtained as the mean output during the last 5 s in an all-out test of 30 s. Correlation coefficients were computed between all measurements of capacity and power expressed per kg of body weight as well as with scores adjusted for sex differences. Common variances (r2 X 100) between measurements of power were either low (MAP-AAP, 40%) or moderate (MAP-ALP, 61%; AAP-ALP, 62%) while common variances between measurements of capacity were sometimes low (MAC-AAC, 49%) or higher (MAC-ALC, 76%; AAC-ALC, 77%). The common variances between tests of power and capacity reached high values when calculated with metabolic criteria of the same class (MAP-MAC, 81%; AAP-AAC, 92%). These results provide quantitative evidence to support the notion of specificity between the aerobic and the anaerobic work performances and support the distinction between capacity and power of the three energy systems.

Lipogenesis from glucose and lipoprotein lipase activity were investigated in humans. The reliability of measurements was quantified and correlations with fat cell weight were assessed. Twenty-four subjects (7 women, 17 men) were studied twice within a 2-week period, along with 17 additional male subjects who were studied once and used only in the correlation analyses. All subjects were not regularly involved in an exercise-training program and were between 18 and 30 years of age. Following an overnight fast, adipose tissue specimens were obtained by suprailiac biopsy and fat cells were collagenase isolated. Mean fat cell weight was obtained from 400 to 500 cell diameter determinations per subject. Basal and insulin-stimulated fat cell lipogenesis from glucose were determined using D-[U- 14 C]glucose and were reported in nanomoles of glucose per hour per 10 6 cells. Adipose tissue heparin-releasable lipoprotein lipase activity was also determined and expressed in micromoles of free fatty acids per hour per gram of tissue and per 10 6 cells. Fat cell weight, basal and insulin-stimulated lipogenesis and lipoprotein lipase activity per gram showed high reliability of measurement, interclass and intraclass coefficients being 0.83 and over. Lipoprotein lipase activity per 10 6 cells showed a somewhat lower degree of reliability, interclass and intraclass coefficients being, respectively, 0.69 and 0.81. On the other hand, fat cell weight was positively correlated with lipoprotein lipase activity (r = 0.80), while no significant correlation was observed between basal lipogenesis and fat cell weight. Moreover, basal lipogenesis presented no significant correlation with lipoprotein lipase activity. These results suggest that, under standardized conditions, and from a single tissue sample, human adipose tissue lipoprotein lipase activity and fat cell lipogenesis can be measured with a satisfactory level of reliability. They also suggest that lipoprotein lipase activity is highly related with adipocyte lipid content.

The relations of regional adipose tissue (AT) distribution measured by computed tomography (CT) to plasma insulin-glucose homeostasis and lipoprotein-lipid levels were studied in 58 obese and 29 lean control men. In the group of obese men, the visceral AT area measured by CT was positively correlated with fasting plasma triglyceride and insulin levels and with glucose and insulin areas under the curves measured during a 75-g oral glucose tolerance test. Visceral AT area was also negatively associated with plasma high-density lipoprotein (HDL) and HDL2 cholesterol levels. The relative accumulation of abdominal fat, estimated by the ratio of abdominal to femoral AT areas obtained by CT, was also a significant correlate of indices of carbohydrate metabolism and was the best univariate correlate of plasma lipoprotein levels. No significant associations were observed between the visceral AT area, the ratio of abdominal to femoral AT areas, and indices of carbohydrate and lipoprotein metabolism in the group of lean men. On the other hand, the subcutaneous abdominal AT area was a significant correlate of the glucose area under the curve in both groups of men, but this association was not independent from the percentage of total body fat. No relationship was observed between the femoral AT area and indices of carbohydrate metabolism in either lean or obese groups. In obese men, however, the femoral AT area was negatively correlated with plasma triglyceride concentration and positively correlated with plasma HDL and HDL2 cholesterol levels. Comparison between two subgroups of equally obese men showing either low or high levels of visceral AT and a group of lean men generally revealed that only obese men with high levels of visceral AT showed significant metabolic alterations compared with lean men. These results demonstrate that the amount of visceral AT and the ratio of abdominal to femoral AT measured by CT are important correlates of the alterations in carbohydrate and lipoprotein metabolism observed in obese men. In addition, our results suggest that obesity is required to observe significant associations between body fat distribution measured by CT and metabolic variables. Finally, we suggest that, in men, a high accumulation of femoral fat may be protective against the adverse effects of obesity, particularly abdominal obesity, on plasma lipoprotein levels.

Protein tyrosine phosphatase 1B (PTPN1) affects the regulation of insulin signaling and energy metabolism. We studied whether polymorphisms in the PTPN1 gene impact body fat distribution in the HERITAGE Family Study cohort in 502 white and 276 black subjects. Insulin sensitivity index, glucose disappearance index, acute insulin response to glucose (AIR glucose ), and the disposition index (DI) were obtained from the frequently sampled intravenous glucose tolerance test. White subjects with the G82G at the PTPN1 IVS6+G82A polymorphism had higher body fat levels ( p = 0.031) and sum of eight skinfolds ( p = 0.003) and highest subcutaneous fat on the limbs ( p = 0.002). G82A subjects had the lowest AIR glucose ( p = 0.005) and disposition index ( p = 0.040). Interaction effects between PTPN1 and leptin receptor gene variants influenced insulin sensitivity index and AIR glucose ( p from 0.006 to 0.010). The variant PTPN1 Pro387Leu was associated with lower fasting insulin level ( p = 0.035) and glucose disappearance index ( p = 0.038). In summary, PTPN1 IVS6+G82G homozygotes showed higher levels of all measures of adiposity. G82 allele heterozygotes are potentially at higher risk for type 2 diabetes. Gene‐gene interactions between the PTPN1 and leptin receptor genes contributed to the phenotypic variability of insulin sensitivity. The PTPN1 Pro387Leu variant was associated with lower glucose tolerance.

It has been suggested recently that molecules expressed both in the pancreas and hypothalamus, such as mu-opioid receptor 1 (OPRM1), could form an integrated brain-liver system, which may sense glucose levels and therefore contribute to the development of type 2 diabetes mellitus (T2DM). In the present study, we tested associations between OPRM1 gene polymorphisms (rs1799971, 102T/C and rs0648007G/A) and indices of glucose tolerance, insulin sensitivity (IS) and insulin secretion derived from plasma measures obtained in a fasting state and following a 75 g oral glucose tolerance test (OGTT) in 749 subjects from the Quebec Family Study (QFS). Polymorphisms were tested for association with glucose tolerance (normal vs IFG and T2DM combined) by calculating a chi(2) statistic and corresponding P values, whereas associations with quantitative measures of glucose tolerance, IS and insulin secretion were tested using mixed linear models implemented in the MIXED procedure of sas (SAS Institute, Cary, NC, USA). Associations were found between 102T/C OPRM1 and indices of glucose tolerance and IS. Compared with T/T homozygotes, carriers of the OPRM1 C-102 variant exhibited a better glucose tolerance with a lower (P = 0.006) glucose area under the curve (AUC) following the OGTT and a better IS with a higher (P = 0.03) value of the Cederholm index, a numerical index of the curve relating glucose uptake to the log(10) plasma insulin levels during the OGTT. The results of the present study reveal that the 102T/C OPRM1 gene polymorphism is associated with a better glucose tolerance and improved IS, both of which suggest a potential protective effect of this variant on T2DM risk.

We aimed to determine the associations of waist circumference (WC) and BMI with all-cause mortality among patients with diabetes.The sample included 847 white and 553 African American patients (18-69 years of age) with diabetes. Height, weight, and WC were measured, and the BMI (kg/m2) was calculated. Cox regression was used to analyze the associations of BMI and WC with mortality, adjusting for age, sex, race, examination year, smoking status, alcohol consumption, and physical activity. Hazard ratios (HRs) are expressed per standard deviation of each independent variable.A total of 86 deaths occurred during 6.7 years of follow-up. After adjustment for covariates, WC (HR 1.40 [95% CI 1.14-1.72]) and BMI (1.29 [1.04-1.61]) demonstrated significant relationships with mortality.The results indicate that maintaining a healthy WC and BMI are both important for individuals living with diabetes.

No abstract is provided for this article.