<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>
No abstract is provided for this article.
No abstract is provided for this article.
not provided.
Maximal aerobic power (MAP) exhibits considerable variation between individuals within a population. Among all causal sources contributing to variation, heredity is generally thought to exert a rather significant influence. Six hundred and seven subjects (9 to 52 years of age) from 160 families of French descent, living in the greater Quebec city area, have been measured for MAP and several related biological and cultural indicators. Subjects have been submitted to a multistage submaximal ergocycle test. MAP has been estimated by regression of actual measurements of oxygen intake and heart rate (HR) at each work load to mean maximal HR. Age and sex of subjects accounted for more than 50% of the total variation in MAP. Anova procedures revealed the presence of significant familial concentrations from MAP scores adjusted for age, sex, sum of skinfolds, cigarette smoking, current energy expenditure, weekly participation in aerobic activities and socio-economic status. Inter-class correlation analysis indicated a significant spouse resemblance (r = .34), as well as a significant covariation between parents and their children (r = .19) and between children of same sibships (r = .33). These results suggest that heredity is contributing to the variation in MAP, but much less than was previously reported from twin studies. Maximal aerobic power (MAP) is generally considered a valid indicator of the efficiency of aerobic energy production and of the oxygen transporting capacity of the organism. Trainability of MAP easily reaches 10-30% of its initial value, but sometimes training effects well above 40% have been reported (Hickson et al. 1977). Some studies have suggested that MAP phenotype is largely inherited (Klissouras, 1971; Klissouras et al. 1973), while others have found only moderate genetic effects (Weber et al. 1976; Engstrom and Fischbein, 1977) and others have even reported no genetic effects at all (Howald, 1976; Komi et al. 1976). These studies were performed with the classical twin model with sometimes little control over the dimensions that may be associated with an inflated genetic effect (Christian, 1979). On the other hand, Montoye and Gayle (1978) have measured MAP in nuclear families and they have reported only modest resemblance between first degree biological relatives. However, their study was based on a rather modest sample size, for a problem of genetic epidemiology. 'Physical Activity Sciences Laboratory, Laval University, Quebec G1K 7P4. Human Biology , December 1982 , Vol. 54, No. 4, pp. 801-812. © Wayne State University Press, 1982 This content downloaded from 157.55.39.45 on Thu, 01 Sep 2016 05:02:08 UTC All use subject to http://about.jstor.org/terms 802 Gilles Lortie et al. The purpose of this report is to quantify the degree of familial similarity in MAP and to compute covariation between biological relatives with statistic controls over variables known to affect MAP. The study is based on 607 individuals from 160 families. Material and Methods The Subjects Families of this study are of French descent and live in the greater Quebec city area. They were recruited through the media. These families include parents (N = 273) whose ages range from 31.4 to 51.5 years (X = 41.7; SD = 4.2) and at least two of their natural children (N = 334). Ages of the children range from 9.1 to 25.7 years (X = 14.9; SD = 3.3). From this population, it was possible to obtain 119 pairs of spouses, 564 parentchild pairs and 223 pairs of siblings. Maximal Aerobic Power Subjects have been submitted to a progressive submaximal test performed on a Monark bicycle. One electrocardiogram derivation was used to register heart rates (HR) during three 6-minute work loads each separated by a one-minute rest. The test was designed to elicit HR of 150 in parents and 170 in children at the end of the last work load. Expired air was analyzed with a Beckman Measurement Metabolic Cart to obtain oxygen consumption (V02) corrected for standard conditions (STPD). Maximal V02 was estimated by regression analysis from oxygen consumption at the end of each work load and corresponding HR to maximal HR adjusted for age (Astrand and Ryhming, 1954). Maximal oxygen consumption is computed in liters of 02 per minute (V02 max), in ml 02 per kg of body weight per minute (V02 max/kg) and in liters of 02 per squared meter of body surface area (BSA) per minute (V02 max/BSA). V02 max/ cm (ml О 2 per cm of height per minute) and V02 max/cm2 (ml 02 per squared cm of height per minute) have also been studied. Since they produced similar results, these variables are not dealt with in the present report. Body surface area has been computed according to Dubois and Dubois (1916). Biological and Cultural Indicators Because of their potential association with variations in MAP, selected biological and cultural variables were also measured in all subjects. Their effects over MAP were statistically controlled as described below. Six This content downloaded from 157.55.39.45 on Thu, 01 Sep 2016 05:02:08 UTC All use subject to http://about.jstor.org/terms Familial Similarity in Aerobic Power 803 skinfolds (triceps, biceps, subscapular, suprailiac, abdominal and medial calf) measured according to the IBP recommendations (Weiner and Lourie, 1969) were obtained on all subjects. In the present study, the sum of these 6 skinfolds was used as an indicator of body fatness. Data about cigarette smoking were obtained by interview for all subjects and the daily mean number of cigarettes consumed is used in the present report. Energy expenditure was computed from a three-day energy expenditure record. A diary was designed in which each day is divided into 96 periods of 15 minutes. The dominant activity of each of these periods is reported on a scale ranging from 1 to 9. Categorical values 8 and 9, which are equivalent to a median energy expenditure >5.8 times the resting metabolic rate were retained for this study. Thus, energy expenditure was simply the sum of the number of periods 8 and 9 over three days. Furthermore, to go beyond current energy expenditure, the weekly participation in aerobic activities was derived from a detailed questionnaire concerning the two physical activities most practiced during the preceding year. This variable was computed from the mean weekly frequency and the mean session duration in order to estimate the mean weekly time (in min) of participation in aerobic activities. An indication about the socio-economic status (SES) and the associated environmental quality was obtained using the occupation of the father coded following the procedures outlined in Blishen and McRoberts (1976) according to the data of the Canadian census. Statistical Analysis Data were log1() transformed to reduce skewness (gj and kurtosis (g2). Multiple regression analyses were performed in order to quantify the effects of all biological and cultural indicators on MAP. MAP residual scores were computed by subtracting MAP-predicted scores from the original MAP scores. To test for the presence of familial resemblance, an analysis of variance and intra-class correlation were obtained following the procedures outlined in Haggard (1958). Inter-class correlation between pairs of relatives were computed after Donner (1979). Tests for homogeneity between correlation coefficients were applied according to procedures outlined in Snedecor and Cochran (1972). Reliability of Measurements Reliability of the measurements was estimated in a study conducted with 61 subjects from 16 families who repeated all procedures within 10 This content downloaded from 157.55.39.45 on Thu, 01 Sep 2016 05:02:08 UTC All use subject to http://about.jstor.org/terms 804 Gilles Lortie et al.
Rico-Sanz et al. (1) reported familial data on muscle phenotypes in the pages of this journal. Unfortunately, due to a data management error that occurred during file merger and transfer from one laboratory to another, some of the published results require amendment. The error affected the muscle enzyme data of 11 subjects. In these cases, pre- and posttraining values of creatine kinase (CK), phosphorylase (PHOS), hexokinase (HK), phosphofructokinase (PFK), glyceraldehyde phosphate dehydrogenase (GAPDH), 3-beta-hydroxyacyl CoA dehydrogenase (HADH), carnitine palmitoyl transferase (CPT), citrate synthase (CS), and cytochrome c oxidase (COX) were inadvertently transposed. However, the histochemical (muscle fiber types and capillary data) and lipoprotein lipase activity data for these subjects were correct in the original report. The data were reanalyzed using the corrected enzyme data file, and the results are summarized in Table 1 (Table 2 of the original report) and Table 2 (Table 5 of the original report). Overall, the qualitative findings remain unchanged although the numerical values changed to some extent. In particular, the endurance training-induced increases in the muscle enzyme activities became larger. The borderline significant increases of CK, PHOS, and PFK in the original report became highly significant. However, the GAPDH training response remained statistically nonsignificant. Additionally, we noted a trend for the familial aggregation results based on the corrected data file. Since the between-family variance was slightly reduced in the corrected enzyme data set while the within-family variance remained almost unchanged, the new F-values tended to be somewhat lower than in the original report. Thus, the revised familial aggregation estimates remain significant, although somewhat smaller.TABLE 1: Descriptive statistics of the vastus lateralis muscle maximal enzyme activities (corrigendum).TABLE 2: Familial aggregation of maximal enzyme activities in the vastus lateralis muscle (corrigendum).In summary, the reanalysis based on the corrected data set shows that the effects of a 20-wk endurance training program on skeletal muscle enzyme activities is even more pronounced than was originally reported. Moreover, familial aggregation for the muscle enzyme phenotypes was confirmed both in the sedentary state and in response to endurance training.
Accumulation of adipose tissue is associated with cardiometabolic risks. Although visceral adipose tissue (VAT) has been strongly implicated in this relationship, there is still some debate regarding the contribution of abdominal subcutaneous adipose tissue (SAT). The purpose of this study was to determine the contribution of abdominal SAT to cardiometabolic risk factors, independent of total and visceral adiposity. These relationships were assessed in Caucasian and African Americans. It is a cross-sectional analysis of the Pennington Center Longitudinal Study. Data were extracted from 1246 participants. Total body fat mass (FM) was measured by dual-energy X-ray absorptiometry, whereas abdominal VAT and SAT areas (cm2) were measured with computed tomography. The cardiometabolic risk factors included resting blood pressure (BP), fasting blood glucose and triglyceride concentrations and high-density lipoprotein cholesterol (HDL-C). Positive relationships across tertiles of VAT were seen for the participants with high glucose, high BP and low HDL-C (P<0.043). There was also a significant increase in the percentage of participants with two or more cardiometabolic risk factors across most tertiles of abdominal SAT (P<0.042). Logistic regression analysis showed that in univariate models, all adiposity measures were significantly associated with increased odds of having all risk factors in men and women. In multivariate models, VAT was significantly associated with most risk factors across gender. Abdominal SAT and FM (odds ratios (ORs) 1.3–2.1; all P<0.05) were associated with fewer risk factors after accounting for VAT. VAT (OR=5.9 and 5.3) and SAT (OR=2.0 and 1.8) were both associated with higher odds of the presence of two or more cardiometabolic risk factors in both males and females (P<0.001). The data suggest that abdominal SAT is not protective against unfavorable cardiometabolic risk profiles. These conclusions were consistent across ethnic groups.
No abstract is provided for this article.
Variations in human energy expenditure are partly because of an influence of the genotype, even after control for the well‐established concomitants of energy expenditure. Using the techniques of genetic epidemiology, we have found that about 40% of the variance in resting metabolic rate, thermic effect of food, and energy cost of low‐to‐moderate intensity exercise (≤5 times the resting metabolic rate) is explained by inherited characteristics. A significant genetic effect has also been reported for the level of habitual physical activity. The existence of a genotype‐environment interaction has also been investigated. Thus, in response to chronic overfeeding, as well as negative energy balance, changes in the components of energy expenditure exhibit significant identical twin pair resemblance. Nutrient partitioning is emerging as a major determinant of the individual differences in metabolic rate responses to overfeeding or negative energy balance conditions. Taken as a whole, these observations consistently support the hypothesis that heredity plays a significant role in the various components of energy expenditure in humans.
Several major developments have occurred since the last edition of Handbook of Obesity: Clinical Applications, including new clinical trials, discoveries related to drug use, and greater understanding of the benefits of weight loss in obese patients. Now in its fourth edition, this volume continues to offer unparalleled depth and breadth of coverag
