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Associations of betatrophin levels with irisin in Chinese women with normal glucose tolerance.

ABSTRACT: Betatrophin may increase islet β cell proliferation in insulin resistance and irisin may improve glucose tolerance in mice. To examine the relationship between betatrophin and irisin, we investigated it in middle-aged Chinese subjects with normal glucose tolerance (NGT) and type 2 diabetes mellitus (T2DM).A total of 460 permanent residents of Fengxian District, aged 40-60 years and without T2DM, were enrolled. Anthropometric parameters, oral glucose tolerance test (OGTT) results, glycosylated haemoglobin levels, blood lipid levels, insulin sensitivity (homeostasis model assessment of insulin resistance, HOMA-IR), β cell function (homeostasis model assessment-β, HOMA-β), estimated glomerular filtration rate (eGFR) and body fat composition were determined. Matched for age, gender and body mass index (BMI, 18-28 kg/m2), newly diagnosed T2DM (n = 50, male/female = 23/27) and NGT (n = 50, male/female = 21/29) subjects were selected based on the results of an OGTT. Serum betatrophin and irisin levels were determined by enzyme linked immune sorbent assay (ELISA).Males had higher levels of betatrophin compared with females in both the NGT and T2DM groups. Compared with NGT subjects, the level of betatrophin in the T2DM group was higher, and males in the T2DM group had higher betatrophin levels than males in the NGT group, but there was no significant difference in betatrophin levels in females between the T2DM and NGT groups. Spearman's correlation analysis revealed that serum betatrophin levels in females with NGT were positively correlated with irisin and negatively correlated with FINS (fasting insulin) levels ( p < 0.05), but no correlation was found between betatrophin and irisin levels in males with NGT or in males or females with T2DM. In females with T2DM, circulating betatrophin levels were positively correlated with weight, BMI and hip circumference (p < 0.05) but negatively correlated with FPG (fasting plasma glucose) and HOMA-IR (p < 0.05).Gender differences in the relationship between betatrophin and irisin indicate that there might be cytokine-mediated crosstalk among the liver, adipose tissue and skeletal muscle.

SUBMITTER: Xie X

PROVIDER: S-EPMC4391688 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:Are PCOS risk variants identified in women of Han Chinese ethnicity also associated with risk of PCOS or the phenotypic features of PCOS in European women?One variant, rs2268361-T, in the intron of FSHR was associated with PCOS and lower FSH levels, while another variant rs705702-G near the RAB5B and SUOX genes was associated with insulin and glucose levels after oral glucose testing in women with PCOS of European ethnicity.Three of the eleven variants associated with PCOS in the Han Chinese genome-wide association studies were also associated with PCOS in at least one European population when corrected for multiple testing (DENND1A, THADA and YAP1). However, additional replication is needed to establish the importance of these variants in European women and to determine the relationship to PCOS phenotypic traits.The study was a case-control examination in a discovery cohort of women with PCOS (n = 485) and controls (n = 407) from Boston (Boston 1). Replication was performed in women from Greece (cases n = 884 and controls n = 311) and an additional cohort from Boston (Boston electronic medical record (EMR); n = 350 cases and n = 1258 controls).Women had PCOS defined by the National Institutes of Health criteria in Boston 1 and Greece (n = 783), with additional subjects fulfilling the Rotterdam criteria (hyperandrogenism, polycystic ovary morphology and regular menses) in Greece (n = 101). Controls in Boston and Greece had regular menstrual cycles and no hyperandrogenism. The second cohort from Boston was defined using the EMR and natural language processing. Allele frequencies for variants associated with PCOS in Han Chinese women were examined in PCOS cases and controls, along with the relationship to quantitative traits.A variant rs2268361-T in an intron of FSHR was associated with PCOS (0.84 [0.76-0.93], OR [95% CI]; P = 0.002). The rs2268361-T was associated with lower FSH levels (-0.15 ± 0.05; P = 0.0029). A variant rs705702-G near RAB5B and SUOX was associated with insulin (-0.16 ± 0.05, P = 0.0029) and glucose levels (-0.20 ± 0.05, P = 0.0002) 120 min after an oral glucose test.The study was large and contained replication cohorts, but was limited by a small number of controls in the Greek cohort and a small number of cases in the second Boston cohort. The second Boston group was identified using electronic medical record review, but was validated for the cardinal features of PCOS.This study demonstrates a cross-ethnic PCOS risk locus in FSHR in women of European ancestry with PCOS. The variant may influence FSH receptor responsiveness as suggested by the associated change in FSH levels. The relationship between a variant near RAB5B and SUOX and glucose stimulated insulin and glucose levels suggests an influence of one of these genes on glucose tolerance, but the absence of a relationship with PCOS points to potential differences in the international PCOS patient populations.The project was supported by Award Number R01HD065029 from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development, Award Number 1 UL1 RR025758, Harvard Clinical and Translational Science Center, from the National Center for Research Resources, award 1-10-CT-57 from the American Diabetes Association and the Partners Healthcare Center for Personalized Genetics Project Grant. C.K.W. is a consultant for Takeda Pharmaceuticals.NCT00166569.

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Associations of betatrophin levels with irisin in Chinese women with normal glucose tolerance.

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