INSIG2 gene rs7566605 polymorphism is associated with severe obesity in Japanese

The single nucleotide polymorphism (SNP) rs7566605 in the upstream region of the insulin-induced gene 2 (INSIG2) is associated with the obesity phenotype in many Caucasian populations. In Japanese, this association with the obesity phenotype is not clear. To investigate the relationship between rs7566605 and obesity in Japanese, we genotyped rs7566605 from severely obese subjects [n = 908, body mass index (BMI) >/= 30 kg/m(2)] and normal-weight control subjects (n = 1495, BMI < 25 kg/m(2)). A case-control association analysis revealed that rs7566605 was significantly associated with obesity in Japanese. The P value in the minor allele recessive mode was 0.00020, and the odds ratio (OR) adjusted for gender and age was 1.61 [95% confidential interval (CI) = 1.24-2.09]. Obesity-associated phenotypes, which included the level of BMI, plasma glucose, hemoglobin A1c, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and blood pressure, were not associated with the rs7566605 genotype. Thus, rs7566605 in the upstream region of the INSIG2 gene was found to be associated with obesity, i.e., severe obesity, in Japanese.     

Controversial association results for INSIG2 on body mass index may be explained by interactions with age and with MC4R

Among the single-nucleotide polymorphisms (SNPs) previously reported to be associated with body mass index (BMI) and obesity, we focus on a common risk variant rs7566605 upstream of the insulin-induced gene 2 (INSIG2) gene and a rare protective variant rs2229616 on the melanocortin-4 receptor (MC4R) gene. INSIG2 is involved in adipogenesis and MC4R effects hormonal appetite control in response to the amount of adipose tissue. The influence of rs2229616 (MC4R) on BMI and obesity has been confirmed repeatedly and insight into the underlying mechanism provided. However, a main effect of rs7566605 (INSIG2) is under debate because of inconsistent replications of association. Interaction of rs7566605 with age may offer an explanation. SNP–age and SNP–SNP interaction models were tested on independent individuals from three population-based longitudinal cohorts, restricting the analysis to an observed age of 25–74 years. KORA S3/F3, KORA S4/F4 (Augsburg, Germany, 1994–2005, 1999–2008), and Framingham-Offspring data (Framingham, USA, 1971–2001) were analysed, with a total sample size of N=6926 in the joint analysis. The effect of interaction between rs7566605 and age on BMI and obesity status is significant and consistent across studies. This new evidence for rs7566605 (INSIG2) complements previous research. In addition, the interaction effect of rs7566605 with the MC4R variant rs2229616 on BMI was observed. This effect size was three times larger than that in a previously reported single-locus main effect of rs2229616. This leads to the conclusion that SNP–age or SNP–SNP interactions can mask genetic effects for complex diseases if left unaccounted for.     

Potential association of INSIG2 rs7566605 polymorphism with body weight in a Chinese subpopulation

Herbert et al reported association with obesity of a common DNA variant rs7566605 at 10 kb upstream of the INSIG2 gene. We analyzed rs7566605 polymorphism in 3125 Chinese in a cross-sectional study. We found no significant association of rs7566605 polymorphism with body mass index (BMI) and waist circumference among all participants (P=0.52). However, if geographic location is considered, the C/C genotype of rs7566605 was marginally associated with increased levels of BMI and risk of obesity among individuals living in Shanghai (P=0.06), indicating that the C/C genotype may contribute to obesity in certain subpopulation among Chinese under certain environmental settings.     

A tagging SNP in INSIG2 is associated with obesity-related phenotypes among Samoans

Background  

A genome wide association study found significant association of a sequence variant, rs7566605, in the insulin-induced gene 2 (INSIG2) with obesity. However, the association remained inconclusive in follow-up studies. We tested for association of four tagging SNPs (tagSNPs) including this variant with body mass index (BMI) and abdominal circumference (ABDCIR) in the Samoans of the Western Pacific, a population with high levels of obesity.     

Linkage study of fibrinogen levels: the Strong Heart Family Study

Background

A common SNP upstream of the INSIG2 gene, rs7566605 (g.-10,1025G>C, Chr2:118,552,255, NT_022135.15), was reported to be associated with obesity (Body Mass Index, [BMI]) in a genome-wide association scan using the Framingham Heart Study but has not been reproduced in other cohorts. As BMI is a relatively insensitive measure of adiposity that is subject to many confounding variables, we sought to determine the relationship between the INSIG2 SNP and subcutaneous fat volumes measured by MRI in a young adult population.

Methods

We genotyped the INSIG2 SNP rs7566605 in college-aged population enrolled in a controlled resistance-training program, (the Functional Polymorphism Associated with Human Muscle Size and Strength, FAMuSS cohort, n = 752 volunteers 18–40 yrs). In this longitudinal study, we examined the effect of the INSIG2 polymorphism on subcutaneous fat and muscle volumes of the upper arm measured by magnetic resonance imaging (MRI) before and after 12 wks of resistance training. Gene/phenotype associations were tested using an analysis of covariance model with age and weight as covariates. Further, the % variation in each phenotype attributable to genotype was determined using hierarchical models and tested with a likelihood ratio test.

Results

Women with a copy of the C allele had higher levels of baseline subcutaneous fat (GG: n = 139; 243473 ± 5713 mm³ vs. GC/CC: n = 181; 268521 ± 5003 mm³; p = 0.0011); but men did not show any such association. Men homozygous for the G ancestral allele showed a loss of subcutaneous fat, while those with one or two copies of the C allele gained a greater percentage of subcutaneous fat with resistance training (GG: n = 103; 1.02% ± 1.74% vs. GC/CC: n = 93; 6.39% ± 1.82%; p = 0.035).

Conclusion

Our results show that the INSIG2 rs7566605 polymorphism underlies variation in subcutaneous adiposity in young adult women and suppresses the positive effects of resistance training on men. This supports and extends the original finding that there is an association between measures of obesity and INSIG2 rs7566605 and further implicates this polymorphism in fat regulation.     

The INSIG2 rs7566605 genetic variant does not play a major role in obesity in a sample of 24,722 individuals from four cohorts

Background  

In a genome-wide association study performed in the Framingham Offspring Cohort, individuals homozygous for the rs7566605 C allele located upstream of insulin-induced gene 2 (INSIG2) were reported to incur an increased risk of obesity. This finding was later replicated in four out of five populations examined. The goal of the study reported here was to assess the role of the INSIG2 single nucleotide polymorphism (SNP) in susceptibility to obesity in the prospective longitudinal Atherosclerosis Risk in Communities (ARIC) study (n = 14,566) and in three other cohorts: the Coronary Artery Risk Development in Young Adults (CARDIA) study (n = 3,888), the Genetic Epidemiology Network of Arteriopathy (GENOA) study (n = 4,766), and extremely obese and lean individuals ascertained at the University of Ottawa (n = 1,502). The combined study sample is comprised of 24,722 white, African-American, and Mexican-American participants.     

Genetic Variation and Insulin Resistance in Middle‐Aged Chinese Men

We investigated the effect of variants in the first three genes in the insulin signaling pathway and genes identified from genome wide association studies (GWAS) of T2D quantitative traits with IR (fasting insulin and the homeostasis model assessment of IR, HOMA‐IR) and evaluated gene–environment interactions with IR traits among 1879 nondiabetic middle‐aged men from a population‐based study conducted in Shanghai, China. One candidate gene, IGF1, was associated with fasting insulin and HOMA‐IR. We observed four BMI–gene interactions (P < 0.05) with HOMA‐IR (INRS rs7254060, INRS rs7254358, GLU4 rs2113050, and GLU4 rs7713127) and seven BMI–gene interactions with fasting insulin (INRS rs7254060, INRS rs7254358, INRS rs10417205, INRS rs1799817, GLU4 rs12054720 GLU4 rs2113050, and GLU4 rs7713127). There were four WHR–gene interactions with HOMA‐IR (INRS rs10417205, INRS rs12971499, INRS rs7254060, and INRS rs7254358), five WHR–gene interactions with fasting insulin (INRS rs10417205, INRS rs7254060, INRS rs7254358, GLU4 rs2113050, and GLU4 rs7713127), eight physical activity–gene interactions with HOMA‐IR (INRS rs10411676, INRS rs11671297, INRS rs2229431, INRS rs12461909, INRS rs6510950, INRS rs10420382, IRS2 rs913949, and IRS2 rs2241745) and five physical activity–gene interactions with fasting insulin (INRS rs2229431, INRS rs12461909, INRS rs10420382, IRS2 rs913949, and IRS2 rs2241745). Our results suggest that BMI, WHR and physical activity may modify IR‐associated variants.     

The common genetic variant upstream of INSIG2 gene is not associated with obesity in Indian population

The high incidence of obesity has resulted in increased morbidity and mortality worldwide. Obesity, a common lifestyle disorder, is caused by multiple factors with heredity playing a strong causal role. Recently, a genetic variation upstream of insulin-induced gene 2 (INSIG2) (rs7566605) has been reported to be associated with obesity in four separate cohorts. Because the lifestyle and food preferences of a large proportion of Indian population differ from the rest of the world, we studied the impact of this polymorphism with body mass index (BMI). The study consisted of two cohorts--1577 healthy individuals from three major linguistic lineages in India and 610 coronary artery disease cases and controls. In the two cohorts studied, no significant association was observed between the polymorphism and BMI. However, frequency of homozygous variant genotype was higher in non-obese individuals as compared with obese individuals in both cohorts although the difference was marginally significant only in the case-control cohort under the assumption of a recessive model. Furthermore, regardless of age and sex, mean BMI did not vary with genotype under the assumptions of recessive model. Thus, in contrast to earlier reports, the variant upstream of INSIG2 is not a determinant of BMI in Indian population.     

Whole-exome sequencing of a pedigree segregating asthma

Background

Obesity has become a common human disorder associated with significant morbidity and mortality and adverse effects on quality of life. Sequence variants in two candidate genes, FTO and UCP-1, have been reported to be overrepresented in obese Caucasian population. The association of these genes polymorphisms with the obesity phenotype in a multiethnic group such as the Brazilian population has not been previously reported.

Methods

To assess the putative contribution of both FTO and UCP-1 to body mass index (BMI) and cardiovascular risk we genotyped SNPs rs9939609 (FTO) and rs6536991, rs22705565 and rs12502572 (UCP-1) from 126 morbidly obese subjects (BMI 42.9 ± 5.6 kg/m², mean ± SE) and 113 normal-weight ethnically matched controls (BMI 22.6 ± 3.5 kg/m², mean ± SE). Waist circumference, blood pressure, glucose and serum lipids were also measured. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphism (indels) for ethnic assignment and to estimate the proportion of European, African and Amerindian biogeographical ancestry in the Brazilian population.

Results

Cases did not differ from controls in the proportions of genomic ancestry. The FTO SNP rs9939609 and UCP-1 SNP rs6536991 were significantly associated with BMI (p= 0.04 and p<0.0001 respectively). An allele dose dependent tendency was observed for BMI for rs6536991 sample of controls. No other significant associations between any SNP and hypertension, hyperlipidemia and diabetes were noted after correction for BMI and no significant synergistic effect between FTO and UCP-1 SNPs with obesity were noted. There was not an association between rs9939609 (FTO) and rs6536991 (UCP-1) in with maximum weight loss after 1 year in 94 obese patients who underwent bariatric surgery.

Conclusion

Our data are consistent with FTO rs9939609 and UCP-1 rs6536991 common variants as contributors to obesity in the Brazilian population.

     

HSP70‐hom gene polymorphisms modify the association of diethylhexyl phthalates with insulin resistance

Recent studies suggest that diethylhexyl phthalates (DEHP) could contribute to the development of insulin resistance (IR) through oxidative stress, and that heat shock protein (HSP) could be related with the association between DEHP and IR. Therefore, we evaluated the effect modification of genetic polymorphisms of HSP70‐hom, an oxidative stress related gene, on the relation between exposure to DEHP and IR. We obtained repeated blood and urine samples from 414 elderly female participants and measured urinary levels of mono‐(2‐ethyl‐5‐hydroxyhexyl) phthalate (MEHHP) and mono‐(2‐ethyl‐5‐oxohexyl) phthalate (MEOHP) as metabolites of DEHP. We also measured serum levels of fasting glucose and insulin, derived the homeostatic model assessment (HOMA) index to assess IR, and genotyped two HSP70‐hom polymorphisms (rs2227956 and rs2075800). A mixed effect model and penalized regression spline were used to estimate the associations between DEHP exposure and IR by genetic polymorphisms. The molar sum of MEHHP and MEOHP (∑DEHP) were significantly associated with HOMA (β = 0.30, P = 0.022). When stratified by genotype at rs2227956, the relationship between ∑DEHP and HOMA was statistically significant in participants with TT (β = 0.32, P = 0.048) or TC (β = 0.60, P = 0.008), while at rs2075800 there was a marginal association for the GA genotype (β = 0.33, P = 0.097). When haplotypes were constituted across the two HSP70‐hom polymorphisms (rs2227956 and rs2075800), the association was apparent only in participants with the T‐A haplotype (β = 0.39, P = 0.029). Our study suggests that HSP70‐hom polymorphisms modify the association of DEHP with IR. Environ. Mol. Mutagen. 55:727–734, 2014. © 2014 Wiley Periodicals, Inc.     

Association analyses of the INSIG2 polymorphism in the obesity and cholesterol levels of Korean populations

Background  

While INSIG2 has been reported to be associated with BMI in many populations, conflicting results have prevented consensus over its role. In analyses of mice and cell cultures the gene has been found to be involved in the regulation of cholesterol synthesis; however, no relationship has been found with cholesterol metabolism in human epidemiological research. Therefore, this study attempts to assess the effect of rs7566605 near INSIG2 on both obesity- and cholesterol-related traits in Koreans.     

Monocyte chemoattractant protein‐1 gene polymorphism and its serum level have an impact on anthropometric and biochemical risk factors of metabolic syndrome in Indian population

Monocyte chemoattractant protein‐1 (MCP‐1), encoded by gene CCL‐2 (Chemokine C‐C motif 2), is the ligand of chemokine receptor CCR‐2. Concurrent clinical alteration in several metabolic aspects, including central obesity, dysglycemia, dyslipidemia and hypertension, is clinically characterized as metabolic syndrome (MetS). Role of MCP‐1 in each of these aspects has been established in vitro and in animal studies as well. We here report genetic association of ?2518 A>G MCP‐1 (rs 1024611) gene polymorphism and level of MCP‐1 with MetS in North Indian subjects. We analysed (n = 386, controls and n = 384, MetS subjects) for MCP‐1 gene polymorphism using PCR‐RFLP, its serum level using ELISA, anthropometric (body mass index, waist and hip circumferences, waist–hip ratio and blood pressure) and biochemical (serum lipids, plasma glucose and insulin levels) variables in a genetic association study. The body mass index, waist circumference, hip circumference, waist–hip ratio, blood pressure, serum lipids, insulin and fasting plasma glucose level were significantly high in MetS subjects. Regression analysis showed significant correlation of body mass index, waist and hip circumference, systolic/diastolic blood pressure, fasting glucose, total cholesterol, high‐density lipoprotein, low‐density lipoprotein fasting insulin and HOMA‐IR with MetS. MCP‐1 allele and genotype were significantly associated with MetS. Serum MCP‐1 level was high in overall cases. In conclusions, the MCP‐1 2518A>G (rs 1024611) polymorphism has significant impact on risk of MetS, and MCP‐1 level correlates with anthropometric and biochemical risk factors of MetS.     

INSIG-2 promoter polymorphism and obesity related phenotypes: association study in 1428 members of 248 families

Background  

Obesity is a major public health problem. Body mass index (BMI) is a highly heritable phenotype but robust associations of genetic polymorphisms to BMI or other obesity-related phenotypes have been difficult to establish. Recently a large genetic association study showed evidence for association of the single nucleotide polymorphism (SNP) rs7566605, which lies 10 Kb 5' to the first exon of the insulin-induced gene 2 (INSIG-2), with obesity in several cohorts. We tested this polymorphism for association with body mass related phenotypes in a large family study whose mean BMI was consistent with moderate overweight.     

First evidence of genetic association between the MIF-173G/C single-nucleotide polymorphisms and polycystic ovary syndrome

Citation Li C, Qiao B, Zhan Y, Qi W, Chen Z‐J. First evidence of genetic association between the MIF‐173G/C single‐nucleotide polymorphisms and polycystic ovary syndrome. Am J Reprod Immunol 2011; 66: 416–422 Problem The purpose of this study was to investigate whether polymorphism of MIF gene is associated with PCOS. Method of study The MIF‐173G/C single‐nucleotide polymorphism (SNP) was detected in 529 PCOS patients and 585 healthy female controls of Chinese Han ancestry. The association of the gene variants with clinical and metabolic parameters and hormone levels was investigated. Results The frequencies of genotypes and allelotypes of the MIF‐173G/C SNP did significantly differ between women with PCOS and healthy controls (P = 0.017 and P = 0.003, respectively). They did significantly differ between obese PCOS patients and obese controls (P = 0.029 and P = 0.039, respectively). The MIF‐173 CC and CG genotypes were associated with higher body mass index (BMI) and waist‐to‐hip ratio (WHR) in both PCOS patients (P < 0.001, P = 0.001) and normal controls (P < 0.001, P = 0.002). The PCOS patients with CC and CG genotypes had higher fasting plasma glucose levels (P < 0.001), higher fasting insulin levels (P < 0.001), and higher HOMA‐IR (P < 0.001) compared with patients with the GG genotype. Conclusion The MIF‐173G/C polymorphism is associated with PCOS in Chinese Han women and may contribute to the phenotypic expression of PCOS.     

Prevalence of diabetes and pre‐diabetes in a cohort of Italian young adults with Williams syndrome

Williams syndrome (WS) is a rare, multisystemic genomic disorder showing a high prevalence of impaired glucose metabolism in adulthood. The reason for this association is unknown, though hemizygosity for genes mapping to the WS chromosome region has been implicated. Twenty‐two Italian young adults with WS (13 females, 9 males) were studied. A 75 g oral glucose tolerance test (OGTT) was performed and β‐cell function was estimated with Homeostasis Model Assessment (HOMA)‐B%, Insulinogenic Index, and corrected insulin response whereas insulin sensitivity was assessed with HOMA‐Insulin Resistance Index, Quantitative Insulin Check Index, and composite Insulin Sensitivity Index. One patient had known diabetes mellitus (DM), whereas impaired glucose tolerance (IGT) was diagnosed in 12 patients and DM in one (63.6% prevalence of impaired glucose metabolism). IGT patients were more insulin resistant than those with normal glucose tolerance (NGT), whereas β‐cell function was unchanged or increased. Islet autoimmunity was absent. Logistic regression showed that impaired glucose metabolism was not associated with age, body mass index (BMI), or family history of DM. β‐cell function, insulin sensitivity, and post‐load insulin levels did not differ between WS patients with NGT and healthy controls comparable for gender, age, and BMI, though WS–NGT patients had higher post‐load glucose values. These data confirm the high prevalence of impaired glucose metabolism in WS young adults, thus suggesting the need for screening these patients with OGTT. IGT is associated with reduced insulin sensitivity, but not with impaired β‐cell function, islet autoimmunity, and traditional risk factors for type 2 DM. © 2013 Wiley Periodicals, Inc.     

Genome-wide association scans identified CTNNBL1 as a novel gene for obesity

Obesity is a major public health problem with strong genetic determination; however, the genetic factors underlying obesity are largely unknown. In this study, we performed a genome-wide association scan for obesity by examining approximately 500 000 single-nucleotide polymorphisms (SNPs) in a sample of 1000 unrelated US Caucasians. We identified a novel gene, CTNNBL1, which has multiple SNPs associated with body mass index (BMI) and fat mass. The most significant SNP, rs6013029, achieved experiment-wise P-values of 2.69 x 10(-7) for BMI and of 4.99 x 10(-8) for fat mass, respectively. The SNP rs6013029 minor allele T confers an average increase in BMI and fat mass of 2.67 kg/m(2) and 5.96 kg, respectively, compared with the alternative allele G. We further genotyped the five most significant CTNNBL1 SNPs in a French case-control sample comprising 896 class III obese adults (BMI > or = 40 kg/m(2)) and 2916 lean adults (BMI < 25 kg/m(2)). All five SNPs showed consistent associations with obesity (8.83 x 10(-3) < P < 6.96 x 10(-4)). Those subjects who were homozygous for the rs6013029 T allele had 1.42-fold increased odds of obesity compared with those without the T allele. The protein structure of CTNNBL1 is homologous to beta-catenin, a family of proteins containing armadillo repeats, suggesting similar biological functions. beta-Catenin is involved in the Wnt/beta-catenin-signaling pathway which appears to contribute to maintaining the undifferentiated state of pre-adipocytes by inhibiting adipogenic gene expression. Our study hence suggests a novel mechanism for the development of obesity, where CTNNBL1 may play an important role. Our study also provided supportive evidence for previously identified associations between obesity and INSIG2 and PFKP, but not FTO.     

Association of the human adiponectin gene and insulin resistance

Adiponectin is an adipocyte-secreted protein that modulates insulin sensitivity and whose low circulating concentration is associated with insulin resistance. In the present study, we analysed the association between two single-nucleotide polymorphisms (SNPs) in the adiponectin gene and insulin resistance in 253 nondiabetic subjects. In addition, we investigated whether this association is modulated by body mass index (BMI) levels. The SNPs +45T>G and +276G>T in the human adiponectin gene were detected in real-time PCR with LightCycler. No association was found with the +45T>G SNP. The +276G>T SNP was associated with higher BMI (P<0.01), plasma insulin (P<0.02) and HOMA(IR) (P<0.02). To analyse the possible interaction between BMI and the adiponectin gene on insulin resistance, the study group was divided into two subgroups, according to the BMI below or above the median of 26.2 kg/m(2). In both subgroups, subjects carrying the +276G>T SNP had higher HOMA(IR); however, the difference was highly significant among leaner (P<0.001), but not among heavier individuals, indicating that BMI status and the adiponectin gene interact in modulating insulin resistance. Among individuals with BMI <26.2 kg/m(2), the relative risk of insulin resistance was 9.7 (CI: 1.32-87.7, P<0.035). In a subgroup of 67 subjects, carriers of the +276G>T SNP had significantly (P<0.05) lower mean serum adiponectin levels (25.7 ng/ml) compared to noncarriers (37.0 ng/ml), suggesting a possible influence of the +276G>T SNP on adiponectin levels. In summary, we observed an association between the +276G>T SNP in the adiponectin gene and insulin resistance. In particular, among leaner individuals, the adiponectin gene appears to determine an increased risk to develop insulin resistance.     

初诊DM2患者脂联素、炎性因子与胰岛素抵抗的相关分析

目的：分析初诊2型糖尿病（DM2）患者脂联素、IL-6、TNF-α水平变化及其与胰岛素抵抗（IR）、肥胖的相关性。方法：选择初诊DM292例,分为肥胖组（体重指数BMI≥25kg/m^2）42例、非肥胖组（BMI〈25kg/m^2）50例、正常对照组40例,测定血清脂联素、IL-6、TNF-α、体重、身高、血脂、空腹血糖（fPG）、餐后2h血糖（2hPG）、空腹胰岛素（fINS）、餐后2h胰岛素（2hINS）、计算胰岛素抵抗指数（HOMA-IR）,做相关性分析。结果：肥胖组脂联素低于非肥胖组（P〈0.05）及正常对照组（P〈0.01）,非肥胖组又低于正常对照组（P〈0.05）。而肥胖组IL-6、TNF-α高于非肥胖组（P〈0.05）及正常对照组（P〈0.01）,非肥胖组又高于正常对照组（P〈0.05）。脂联素与BMI、HOMA-IR呈负相关,IL-6、TNF-α与BMI、HOMA-IR呈正相关。结论：脂联素、IL-6、TNF-α与IR密切相关,参与了糖脂代谢紊乱。     

Insulin resistance and obesity-related factors in Prader-Willi syndrome: comparison with obese subjects

Prader-Willi syndrome (PWS), the most common genetic cause of marked obesity in humans, is usually due to a de novo paternally derived chromosome 15q11-q13 deletion or maternal disomy 15 [(uniparental disomy (UPD)]. Obesity is due to energy imbalance, but few studies have examined fat patterning and obesity-related factors in subjects with PWS (deletions and UPD) compared with subjects with simple obesity. We examined for differences in fatness patterning and lipid, leptin, and glucose and insulin levels in subjects with simple obesity and PWS and adjusted for gender, age, and body mass index (BMI). Fasting peripheral blood samples and cross-sectional magnetic resonance image scans at the level of the umbilicus were obtained in 55 subjects ranging in age from 10.4 to 49 years: 20 PWS deletion, 17 PWS UPD, and 18 obese controls. Subcutaneous fat area (SFA) and intra-abdominal visceral fat area (VFA) were calculated. No significant difference was seen between the PWS deletion subjects or PWS UPD subjects for fatness measurements or leptin levels. Twenty-three of 37 PWS subjects met the criteria for obesity (BMI > 95th percentile). No significant differences were observed for SFA and VFA between the PWS subjects judged to be obese and control subjects with simple obesity. There was an overall trend for decreased VFA in the PWS subjects but not significantly different. VFA was significantly positively correlated with both fasting insulin and total cholesterol in PWS deletion subjects but not in PWS UPD subjects or obese controls. Fasting insulin level was significantly lower in the obese PWS subjects compared with subjects with simple obesity, and insulin sensitivity (QUICKI) was significantly higher in PWS subjects with obesity. Homeostasis model assessment (HOMA) and QUICKI values were correlated and in opposite directions with triglycerides in the obese PWS subjects but not in the obese controls. Subjects in each group were stratified according to published criteria on the basis of their level of visceral fat (e.g. > or = 130 cm(2)) to assess the influence of VFA on metabolic abnormalities. In the obese PWS subjects, the fasting triglyceride, glucose, and insulin levels, and HOMA value were significantly elevated, while the QUICKI value was significantly lower in those with VFA > or = 130 cm(2). Such significant differences were not seen in the obese control group. Our results indicate that VFA may be regulated differently in PWS subjects compared to individuals with simple obesity. Insulin resistance is lower in PWS subjects and insulin sensitivity is higher compared with obese controls. PWS subjects with increased VFA may be at a higher risk of obesity-related complications compared to PWS subjects without increased VFA.     

100 obese patients after laparoscopic adjustable gastric banding - the influence on BMI, gherlin and insulin concentration, parameters of lipid balance and co-morbidities

PurposeObesity is a widespread health issue caused by chronic impaired balance between energy supply and its expenditure. It leads to gathering of excessive fat tissue and numerous co-morbidities.The aim of this study is to present the influence of laparoscopic adjustable gastric banding (LAGB) on plasma ghrelin, insulin, glucose, triglycerides, total, HDL- and LDL-cholesterol concentration as well as on alanine and aspartate aminotransferase in obese patients and influence on co-morbidities such as type 2 diabetes mellitus, dislipidemy, hypertension and sleep apnea.Materials and methods100 obese patients underwent LAGB: 34 men – average age 39.18±12.17 years old and 66 women – average age 37.0±12.6 years old. During 6 months follow-up, particular measurements have been conducted in different time points. Evaluation of body mass loss (%EWL, %EBL) and the homeostatic model assessment insulin resistance (HOMA IR) was conducted. In the same time ghrelin, insulin, glucose, triglycerides, total cholesterol, HDL- and LDL-cholesterol concentration was determined after 7 days, 1, 3 and 6 months after the surgery.ResultsSignificant decrease in BMI and HOMA IR was observed as well as in insulin and glucose concentration. Increase in ghrelin concentration in comparison to preoperative values was also stated.ConclusionsLAGB leads to significant body mass loss, improvement in patients’ general health state and to normalization of metabolic parameters. Improvement or total resolution of type 2 diabetes (T2DM), hypertension and sleep apnea was also noticed.