PubMed Health⌕ Search

Biomedical subjects

S Echwald

Publications and source records attributed to S Echwald.

7 recordsLinked to original sources
PubMed2006

Possible role of adiponectin and insulin sensitivity in mediating the favorable effects of lower body fat mass on blood lipids.

AIMS: The objective of this study was to investigate the role of insulin sensitivity and serum adiponectin concentration as determinants, in middle-aged men, of the relationship between lower body fat and blood lipids after truncal fat has been accounted for. METHODS: Men (443) aged 39-65 yr, body mass index 18-43 kg/m(2), participated in the study. The following variables were measured: regional body fat distribution as assessed by dual-energy x-ray absorptiometry, maximal oxygen uptake, physical activity, fasting levels of serum adiponectin, triglycerides, and high-density lipoprotein- and total cholesterol. Plasma glucose and serum insulin were measured in the fasting state and after an oral glucose load. RESULTS: Lower body fat mass was inversely associated with serum triglycerides and total cholesterol and positively with serum high-density lipoprotein-cholesterol after adjustment for age, lean tissue mass, truncal fat mass, weight history, maximal oxygen uptake, and the level of physical activity (P < 0.0005). Serum adiponectin level and Matsudas insulin sensitivity index were positively intercorrelated, and both were positively correlated to lower body fat mass. When including adiponectin and insulin sensitivity in the analyses, the relationships between lower body fat mass and serum lipids were partly explained. CONCLUSION: For a given level of truncal fat mass, a large lower body fat mass is associated with an advantageous blood lipid profile, which may be partially mediated by the relationships to both insulin sensitivity and serum adiponectin level.

Absorptiometry, Photon↗
PubMed2005

Lower-body fat mass as an independent marker of insulin sensitivity--the role of adiponectin.

AIMS: To study the association between lower-body fat and estimates of whole-body insulin sensitivity in middle-aged men with and without a history of juvenile onset obesity, and to determine the possible mediating role of fasting serum adiponectin level as an insulin-sensitizing peptide. METHODS: A total of 401 men aged 39-65 y, body mass index 18-54 kg/m2, participated in the study. The following variables were measured on the study participants: regional body fat distribution as assessed by dual energy X-ray absorptiometry, abdominal sagittal diameter, maximal oxygen uptake (VO2max), physical activity, fasting and post-glucose load levels of plasma glucose, serum insulin, and blood non-esterified fatty acid plus fasting levels of serum adiponectin and HbA1c. RESULTS: Lower-body fat mass was positively associated with insulin sensitivity as estimated by Matsudas index also after adjusting for age, lean tissue mass, trunkal fat mass, weight changes since draft board examination, VO2max and the level of physical activity. In a subgroup of men selected for a large lower-body fat mass, fasting serum insulin concentration was 24% lower (P<0.01) and fasting serum adiponectin 33% higher (P<0.005) compared to a subgroup of men with a small lower-body fat mass but with similar trunkal fat mass. CONCLUSION: Lower-body fat mass is positively associated with an estimate of insulin sensitivity independently of trunkal fat mass in both lean and obese middle-aged men and this effect could partly be statistically explained by variations in serum adiponectin levels.

Absorptiometry, Photon↗
PubMed2005

Long-term influences of body-weight changes, independent of the attained weight, on risk of impaired glucose tolerance and Type 2 diabetes.

AIM: To investigate if weight gain during adulthood has effects on the risk of developing impaired glucose tolerance (IGT) or Type 2 diabetes beyond effect of attained weight. RESEARCH DESIGN AND METHODS: Data were obtained from a longitudinal study of two cohorts: one of juvenile-onset obese (n = 248) and one of randomly selected control (n = 320) men, weighed at average ages of 20, 33, 44 and 51 years, respectively. RESULTS: For any given BMI, the risk of IGT was higher the greater the weight gain since age 20 (odds ratio of 1.10 per unit kg/m2 of BMI gain, confidence interval 1.03-1.17, P = 0.004), and weight gain during both the early and later ages contributed to the increased risk. Obese men, maintaining weight since age 20, had lower risk of IGT than non-obese men who became similarly obese by age 51. The risk of Type 2 diabetes increased by weight gain in early adult life, but not by more recent weight gain in the later periods, probably because of the development of Type 2 diabetes leading to weight loss. CONCLUSIONS: Independent of attained level of body weight in middle-aged men, weight gain is associated with increased risk of IGT, and is greater in those not overweight in childhood.

Adult↗
PubMed2002

A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference.

METHODS: We analyzed data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R and K656N) of LEPR with body mass index (BMI; kg/m(2)) and waist circumference (WC). A total of 3263 related and unrelated subjects from diverse ethnic backgrounds including African-American, Caucasian, Danish, Finnish, French Canadian and Nigerian were studied. We tested effects of individual alleles, joint effects of alleles at multiple loci, epistatic effects among alleles at different loci, effect modification by age, sex, diabetes and ethnicity, and pleiotropic genotype effects on BMI and WC. RESULTS: We found that none of the effects were significant at the 0.05 level. Heterogeneity tests showed that the variations of the non-significant effects are within the range of sampling variation. CONCLUSIONS: We conclude that, although certain genotypic effects could be population-specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or WC in the overall population.

Alleles↗
PubMed2001

Pooling analysis of genetic data: the association of leptin receptor (LEPR) polymorphisms with variables related to human adiposity.

Analysis of raw pooled data from distinct studies of a single question generates a single statistical conclusion with greater power and precision than conventional metaanalysis based on within-study estimates. However, conducting analyses with pooled genetic data, in particular, is a daunting task that raises important statistical issues. In the process of analyzing data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R, and K656N) of LEPR with body mass index (BMI; kilograms divided by the square of the height in meters) and waist circumference (WC), we encountered the following methodological challenges: data on relatives, missing data, multivariate analysis, multiallele analysis at multiple loci, heterogeneity, and epistasis. We propose herein statistical methods and procedures to deal with such issues. With a total of 3263 related and unrelated subjects from diverse ethnic backgrounds such as African-American, Caucasian, Danish, Finnish, French-Canadian, and Nigerian, we tested effects of individual alleles; joint effects of alleles at multiple loci; epistatic effects among alleles at different loci; effect modification by age, sex, diabetes, and ethnicity; and pleiotropic genotype effects on BMI and WC. The statistical methodologies were applied, before and after multiple imputation of missing observations, to pooled data as well as to individual data sets for estimates from each study, the latter leading to a metaanalysis. The results from the metaanalysis and the pooling analysis showed that none of the effects were significant at the 0.05 level of significance. Heterogeneity tests showed that the variations of the nonsignificant effects are within the range of sampling variation. Although certain genotypic effects could be population specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or waist circumference in the general population.

Adipose Tissue↗
PubMed1993

Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus.

Since relative or absolute insulin deficiency and insulin insensitivity are involved in the aetiology of non-insulin-dependent diabetes mellitus (NIDDM), we examined whether patients with NIDDM exhibit genetic variability in the coding region of insulin receptor substrate-1 (IRS-1), a candidate gene that is ubiquitous in insulin-sensitive and insulin-like growth factor 1 (IGF1) sensitive tissues, including those that determine glucose production and clearance and those with regulatory effects on pancreatic beta-cell function. IRS-1 has a central role as an adaptor molecule that links the insulin-receptor and IGF1-receptor kinases with enzymes that regulate cellular metabolism and growth. Single-stranded conformation polymorphism analysis and direct nucleotide sequencing were applied to genomic DNA from 86 unrelated patients with NIDDM and 76 normoglycaemic controls. 10 of the patients with NIDDM and 3 of the controls were heterozygous at codon 972 for a polymorphism in which glycine was substituted with arginine. Moreover, at codon 513, 6 patients with NIDDM and 2 controls had a heterozygous polymorphism with a transition from alanine to proline. None of the polymorphism carriers had both aminoacid variants and the total allelic frequency of IRS-1 polymorphisms was about three times higher in patients with NIDDM than in controls (p = 0.02). Both aminoacid substitutions were located close to tyrosine phosphorylation motifs that are putative recognition sites for insulin and IGF1 signal transmission proteins. Analysis of the phenotypes showed that patients with NIDDM who had IRS-1 variants did not differ in their degree of insulin resistance compared with patients without known IRS-1 polymorphisms. However, carriers of the codon 972 variant had significantly lower plasma levels of fasting insulin and C-peptide. Our results suggest that aminoacid polymorphisms in IRS-1 may be involved in the aetiology of a subset of late-onset NIDDM.

Amino Acids↗