Betatrophin Concentrations Research Articles

STUDY THE RELATIONS BETWEEN ANGIOPOIETIN-LIKE PROTEIN 4 (ANGPTL4) AND LIPOPROTEIN LIPASE AS PREDICTORS FOR ISCHEMIC HEART DISEASE IN PATIENTS WITH T2DM

Betatrophin production and blood lipid profile have been proven in previous research to have a correlation, both in the laboratory and in clinical settings. Investigations on the connection and contact behavior of lipoprotein lipase, betatrophin, and angiogenin- likeprotein3 (ANGPTL3) continue to vary from one another (LPL). This study aimed to evaluating the relationship between betatrophin, ANGPTL4, and LPL in addition to the severity of IHD in individuals with diabetes. There were sixty people with diabetes in the case group (30 with IHD and 30 without IHD). The control group included thirty people in total. While the serum concentration of ANGPTL4 was assessed using a double antibody sandwich ELISA, the serum concentrations of betatrophin, LPL, and ANGPTL4 were assessed using the enzyme-linked immunosorbent assay (ELISA). The levels of total cholesterol, fasting blood glucose, and triglycerides in each group were determined using an automated biochemical analyzer. The clinical baseline data for each patient group was incorporated into the analysis within the same time frame. Consequently, compared to diabetic patients without IHD and those in the control group, individuals with IHD had significantly higher levels of betatrophin, ANGPTL4 and LPL (p 0.05). With diabetic patients with IHD, the Gensini rating significantly and favorably correlated with TC, TG, LDL-C, betatrophin, LPL, and BMI (r = 0.201, 0.501, 0.045, 0.562, 0.611, and 0.431 and P = 0.041, 0.008, 0.038, 0.009, 0.002, and 0.039 respectively) In all groups of gensini score with (P<0.05), there is a statistically significant difference found in the levels of betatrophin, ANGPTL4, and LPL. In patients with diabetes, the degree of IHD was associated with the betatrophin, ANGPTL4, and LPL parameters.

Gender-Dependent Associations between Serum Betatrophin Levels and Lipoprotein Subfractions in Diabetic and Nondiabetic Obese Patients.

Betatrophin, also known as angiopoietin-like protein 8 (ANGPTL8), mainly plays a role in lipid metabolism. To date, associations between betatrophin and lipoprotein subfractions are poorly investigated. For this study, 50 obese patients with type 2 diabetes (T2D) and 70 nondiabetic obese (NDO) subjects matched in gender, age, and body mass index (BMI) as well as 49 gender- and age-matched healthy, normal-weight controls were enrolled. Serum betatrophin levels were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint gel electrophoresis. Betatrophin concentrations were found to be significantly higher in the T2D and NDO groups compared to the controls in all subjects and in females, but not in males. We found significant positive correlations between triglyceride, very low density lipoprotein (VLDL), large LDL (low density lipoprotein), small LDL, high density lipoprotein (HDL) -6-10 subfractions, and betatrophin, while negative correlations were detected between betatrophin and IDL, mean LDL size, and HDL-1-5. Proportion of small HDL was the best predictor of betatrophin in all subjects. Small LDL and large HDL subfractions were found to be the best predictors in females, while in males, VLDL was found to be the best predictor of betatrophin. Our results underline the significance of serum betatrophin measurement in the cardiovascular risk assessment of obese patients with and without T2D, but gender differences might be taken into consideration.

Alterations in serum concentrations of visfatin and betatrophin in dogs with hypothyroidism.

Hypothyroidism in dogs is associated with obesity and altered lipid and carbohydrate metabolism. The adipokines, visfatin, and betatrophin, affect glucose tolerance. Betatrophin is involved in lipid regulation. Visfatin and betatrophin serum concentrations are altered in hypothyroid dogs. Dogs with naturally occurring hypothyroidism (n = 25) and healthy dogs (n = 25). Insulin, visfatin, and betatrophin serum concentrations were measured in all dogs and 19 of the hypothyroid dogs after 30 days of thyroxine treatment. Body condition score (BCS) was determined (1-9 scale). Visfatin concentrations were lower in hypothyroid compared with healthy dogs (mean, 95% confidence interval [CI]; 2.0 ng/mL, 1.2-3.3 vs 5.1 ng/mL, 3.3-7.8; P = .004) and increased post-treatment (3.1 ng/mL, 1.9-4.9 vs 2.6 ng/mL, 1.6-4.1; P = .05). Betatrophin concentrations were lower in lean to normal (body condition score [BCS], 3-5) hypothyroid dogs compared to lean to normal healthy dogs (52 pg/mL, 9-307 vs 597 pg/mL, 216-1648; P = .03), but were not different between overweight (BCS, 6-9) hypothyroid and healthy dogs (341 pg/L, 168-695 vs 178 pg/mL, 77-415; P = .26), and decreased post-treatment in overweight dogs (206 pg/mL, 87-488 vs 268 pg/mL, 112-640; P = .004). Visfatin concentrations were higher in overweight compared with lean to normal dogs (4.7 ng/mL, 3.3-6.6 vs 2.2 ng/mL, 1.2-4.2; P = .04). Betatrophin concentrations were positively correlated with BCS (r = .47, P = .02) and insulin concentrations (r = .48, P = .03) in hypothyroid dogs and negatively correlated with BCS (r = -.47, P = .02) and thyroid stimulating hormone concentrations (r = -.56, P = .01) in healthy dogs. Hypothyroidism in dogs is associated with alterations in visfatin and betatrophin concentrations that partially resolve with thyroxine treatment.

Cardiorespiratory and metabolic fitness indicators in novice volleyball trainees: effect of 1-week antioxidant supplementation with N-acetyl-cysteine/zinc/vitamin C.

ObjectivesThis study aimed to determine the effect of 7-day dietary supplementation of N-acetylcysteine (NAC)/zinc/vitamin C on the time-to-exhaustion (TTE), the cardiorespiratory fitness (CRF) index, and metabolic indicators.MethodsThis study enrolled volleyball student trainees (n = 18 men) who took NAC/zinc/vitamin C (750 mg/5 mg/100 mg) for 7 days at Jouf University, Saudi Arabia. The CRF index and TTE were determined. Serum concentrations of metabolic regulators (insulin, betatrophin, and hepatocyte growth factor), biomarkers of cellular damage/hypoxia, and indicators of lipid and glycemic control were measured.ResultsSupplementation improved the TTE and CRF index, and lowered cytochrome c, C-reactive protein, hypoxia-inducible factor-1α (HIF-1α), total cholesterol, insulin, and glycated hemoglobin values. Before and after supplementation, the CRF index was negatively correlated with body mass index and positively correlated with the TTE. Before supplementation, the CRF index was positively correlated with betatrophin concentrations, and hepatocyte growth factor concentrations were positively correlated with betatrophin concentrations and negatively correlated with the homeostasis model assessment of insulin resistance index. After supplementation, the CRF index was negatively correlated with HIF-1α concentrations and metabolites. Additionally, the TTE was negatively correlated with HIF-1α, cytochrome c, and triacylglycerol concentrations.ConclusionSupplementation of NAC/zinc/vitamin C improves metabolic and CRF performance.

Decreased serum betatrophin may correlate with the improvement of obstructive sleep apnea after Roux-en-Y Gastric Bypass surgery

Obesity is strongly correlated with obstructive sleep apnea (OSA), and bariatric surgery can effectively treat obesity and alleviate OSA. However, the contributing factors are still unclear. We aimed to explore the relationship between betatrophin and OSA in patients undergoing Roux-en-Y gastric bypass (RYGB) surgery. Our study consisted of thirty-seven individuals with OSA and type 2 diabetes (16 males, 21 females) undergoing RYGB surgery. The polysomnography test, anthropometric results, serum betatrophin, and abdominal magnetic resonance images were evaluated both before and 1 year after RYGB surgery. Factors that may correlate with the alleviation of OSA were investigated. In our study, RYGB surgery significantly decreased apnea hypopnea index (AHI) and serum betatrophin concentration (p < 0.001). The abdominal visceral fat area, subcutaneous fat area and HOMA-IR were also significantly decreased (p < 0.001). The preoperative AHI, postoperative AHI and the change in AHI were significantly correlated with the preoperative betatrophin, postoperative betatrophin and the change in betatrophin, respectively (p < 0.05). These correlations were still significant after adjustment for other risk factors. The change in betatrophin was also independently associated with the change in minimum oxygen saturation (p < 0.001). Our data might indicate that serum betatrophin was significantly independently correlated with the improvement of OSA after bariatric surgery.

The association of oxidative stress with serum irisin and betatrophin in pregnant women with gestational diabetes mellitus

Background. Irisin and betatrophin are polypeptide hormones implicated in glucose metabolism and insulin resistance (IR). Gestational diabetes mellitus (GDM) is accompanied by oxidative stress (OS) and the association between circulating irisin and betatrophin levels and GDM is controversial. The present study aimed to investigate the association of second-trimester irisin, betatrophin concentrations and their correlations between serum OS markers in GDM patients. Methods. The study included 45 GDM patients and 45-age matched pregnant women as controls. Serum fasting glucose, HOMA-IR, ischemia modified albumin (IMA), total oxidative stress (TOS), total antioxidant status (TAS), oxidative stress index (OSI), irisin and betatrophin were measured. Results. Serum irisin levels were decreased and TOS and OSI levels were found to be increased in the patient group. No significant difference was found with respect to serum betatrophin and IMA levels between study groups. A correlation analysis revealed no correlation between serum irisin and other assessed variables. Conclusions. Gestational diabetes mellitus is an OS condition in addition to being a metabolic disease. Although not correlated with OS, irisin but not betatrophin may be a useful biomarker to predict GDM.

Serum betatrophin and irisin levels in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) development is a complex process with well-known risk factors, however the role of betatrophin/angiopoietin-like protein 8 and irisin has been poorly investigated thus far. The aim of this study is to measure betatrophin and irisin serum levels in HCC, cirrhotic patients and controls, assess their relationship with cancer etiology and grade, metabolic abnormalities and liver dysfunction severity. Serum betatrophin and irisin concentrations were measured with commercially available ELISA kits in 69 cirrhotic patients with HCC, 24 patients with non-viral cirrhosis and 20 healthy volunteers. The severity of liver disfunction was assessed according to Child-Pugh (C-P) score, while HCC grade according to the Barcelona clinic liver cancer (BCLC) staging system. Serum betatrophin concentration was significantly higher (33.7 ± 13.4 versus 12.3 ± 2.0 ng/ml; P < 0.001), while serum irisin level significantly lower in HCC patients compared to controls (2.52 ± 1.14 versus 4.46 ± 1.34 μg/ml; P = 0.02). Betatrophin level was also significantly elevated among cirrhotic patients compared to healthy volunteers. More evident serum betatrophin increase was found in patients with viral disease (34.8 ± 12.9 versus 26.1 ± 13.8 ng/ml; P < 0.001). Serum irisin concentration was significantly decreased in more advanced HCC cases (stage A versus C according to BCLC: 3.4 ± 1.3 versus 1.89 ± 1.1 μg/ml; P = 0.02). Decline of serum irisin (A: 3.4 ± 1.2; B: 2.42 ± 0.8; C: 1.91 ± 1.19 μg/ml; P = 0.03) and up-regulation of serum betatrophin levels (A: 24.1 ± 13.8; B: 39.3 ± 11.4; C: 46.2 ± 9.4 ng/ml; P = 0.03) were observed in patients with more advanced cirrhosis according to C-P score. We concluded that betatrophin serum level increased in cirrhotic patients, compared to controls. Since there was no difference between cirrhotic patients with and without intercurrent HCC, we suppose it may have an influence on fibrosis development, however not hepatocarcinogensis. Irisin serum level decreased in HCC patients, especially with more advanced disease grade, and was inversely related to the severity of liver disfunction.

Adipose Insulin Resistance and Circulating Betatrophin Levels in Women with PCOS.

The role of IR and metabolic disorders has become a crucial topic of study in the pathogenesis of PCOS. Adipose tissue is an important target organ of insulin, and adipose IR plays an important role in the occurrence and development of PCOS. This study seeks to investigate the role of adipose IR in the development of PCOS and to examine its relationship with circulating betatrophin levels in women with PCOS. A cross-sectional analysis of a cohort of women with PCOS and healthy women was performed in this study. Serum betatrophin concentrations were measured by ELISA. Adipose IR was calculated using the product of fasting insulin and FFA concentrations, and the relationship between adipose IR, circulating betatrophin, and other parameters was analyzed. Adipose IR in women with PCOS was significantly higher than that in controls. We found that women with PCOS who have adipose IR (adipose IR ≥ 55) have a higher BMI and higher blood glucose, insulin, PRL, FFA, TG, HOMA-IR, AUCglucose, AUCinsulin, VAIfemale, and BAI levels than PCOS-afflicted women without adipose IR, while M-values, and SHBG and LH levels were lower. In women with PCOS, serum betatrophin levels were significantly increased compared with controls. Adipose IR negatively correlated with M values and positively with circulating betatrophin levels in the study population. After metformin treatment, circulating betatrophin levels and adipose IR in women with PCOS were significantly decreased compared with pretreatment. Adipose IR is associated with betatrophin levels in women with PCOS. The combination of adipose IR and circulating betatrophin measurements may be significant for screening patients with PCOS.

Anti proliferative and apoptotic effects on pancreatic cancer cell lines indicate new roles for ANGPTL8 (Betatrophin).

Despite considerable advances, the treatment of pancreatic cancer (PC) still requires much effort. Unusual regulation of the Wnt and apoptotic signaling pathways is widespread in cancer incidence. For instance, the WIF1 (Wnt inhibitory factor 1) gene is down-regulated in many cancers. The purpose of this study was to determine the effects of recombinant Betatrophin, a recently discovered hormone, on MiaPaca-II and Panc-1 pancreatic cell lines. Various concentrations of Betatrophin were added to MiaPaca-II and Panc-1 pancreatic cell lines during periods of 24 , 48, and 72 h. The MTT assay was applied to investigate cell proliferation after treatment. The rate of apoptotic cells was assessed using double-staining flow cytometry, and the expression levels of the WIF1 gene and Bcl2 protein was observed by real-time PCR and western blotting, respectively. The findings of this study suggest that Betatrophin has an anti-proliferative effect on both MiaPaca-II and Panc-1 cell lines, in line with the up-regulation of WIF1 as a tumor suppressor gene. Moreover, the induction of apoptosis by ANGPTL8 occurred by the down-regulation of Bcl2. Thus, Betatrophin can be proposed as a potential therapeutic drug for treating pancreatic cancer.

Serum concentrations of selected adipokines in virus-related liver cirrhosis and hepatocellular carcinoma.

Aim of the studyHepatotropic viruses cause metabolic disturbances such as insulin resistance and hepatosteatosis. Moreover, metabolic factors, such as insulin resistance, obesity, and type 2 diabetes mellitus, increase the risk for hepatocellular carcinoma (HCC) in patients with virus-related liver cirrhosis. Cytokines secreted by the adipose tissue (adipokines) may be implicated in these metabolic disturbances, but there is little evidence regarding the role of adipokines in virus-related cirrhosis and HCC. Thus, we studied whether serum concentrations of selected adipokines were altered in patients with virus-related liver cirrhosis, including patients with HCC.Material and methodsWe included 43 patients with liver cirrhosis due to chronic hepatitis B or chronic hepatitis C. Of these patients, 36 had HCC and 7 did not have any malignant lesions. In addition to routine clinical and laboratory variables, we analyzed serum concentrations of betatrophin, insulin, vaspin, visfatin, and irisin.ResultsCompared with healthy controls, patients with HCC had significantly increased vaspin concentrations and significantly reduced irisin concentrations. Compared with controls, patients with virus-related cirrhosis, with or without HCC, had significantly increased concentrations of insulin and betatrophin. The serum visfatin concentration was non-significantly higher in patients with virus-related cirrhosis than in controls. None of the studied adipokines was a significant predictor of HCC. Serum concentrations of the studied adipokines were not related to cirrhosis severity or HCC stage.ConclusionsMetabolic parameters, including serum adipokine concentrations, are altered in patients with virus-related liver cirrhosis. Adipokines might be related to the HCC risk in these patients.

The Relationship between Circulating ANGPTL8/Betatrophin Concentrations and Adult Obesity: A Meta-Analysis.

In this study, we evaluated the relationship between circulating betatrophin levels and obesity. Obesity is a common public health problem that is increasing globally. Betatrophin, a newly identified protein, is predominantly expressed in white and brown fat tissues and in the liver. Growing evidence suggests that betatrophin plays a pivotal role in metabolism, including the synthesis and degradation of lipids in cells, and adipocyte differentiation. Previous studies have assessed the association between circulating betatrophin levels and obesity; however, this relationship remains unclear. Therefore, our study is aimed at examining the impact of betatrophin on obesity using a meta-analysis of the current evidence. We performed a meta-analysis to quantify the relationship between betatrophin levels and obesity. A literature search was conducted through the EMBASE, Web of Science, and MEDLINE databases. Retrieved studies were screened, without any language restrictions to identify relevant literature published up to December 2018. Observational studies, in which the association between circulating concentrations of betatrophin and obesity was evaluated, were considered suitable for the systematic review. Of the 65 manuscripts retrieved, 9 datasets from 6 studies, involving 681 participants, detected an association between circulating betatrophin and obesity. Circulating betatrophin levels of obese subjects were higher than those of nonobese subjects (random − effects weighted mean difference (WMD) = 0.250 μg/mL, 95% CI: 0.048–0.451, I2 = 94.8%, p = 0.015), yet with significant between-study heterogeneity. This heterogeneity appeared to be modified by glycemic status but not by age, the ELISA kits used, sample source, or body mass index. The high circulating betatrophin concentration may directly increase the risk of obesity in adults. Betatrophin may serve as a therapeutic target for obesity in adults.

Wyższe stężenie betatrofiny u pacjentów z noworozpoznaną cukrzycą

Introduction. Betatrophin is primarily produced in the liver and regulates the metabolism of triglycerides. Its elevated concentration might be associated with an increased risk of type 2 diabetes. The aim of the study was to evaluate the impact of betatrophin on beta cell function and to compare the concentration of betatrophin in patients newly diagnosed with type 1 diabetes mellitus (T1DM including LADA), type 2 diabetes mellitus (T2DM) and a control group (CG) of healthy volunteers. Patients and methods. The study included 210 patients with newly diagnosed diabetes (70 with T1DM, 140 with T2DM) and 70 CG. To evaluate the relationship between betatrophin and insulin secretion, a glucagon stimulation test was conducted. Results. Serum betatrophin concentrations were signi­ficantly elevated in T1DM and T2DM in comparison to the control group (3.47 [Q1 = 2.28, Q3 = 4.54] in T1DM vs. 1.81 [Q1 = 1.04, Q3 = 2.67] ng/ml in CG, p < 0.001; 3.12 [Q1 = 1.89, Q3 = 4.48] in T2DM vs. 1.81 [Q1 = 1.04, Q3 = 2.67] ng/ml in CG, p < 0.001). No statistically significant differences in betatrophin concentration were observed between the T1DM and T2DM groups. Significant correlations were established between betatrophin, triglyceride (TG) and high-density lipopro­tein (HDL) levels in all study participants, and C-peptide in the T1DM group. Conclusions. Betatrophin concentration was signi­ficantly elevated in patients with newly diagnosed T1DM and T2DM, compared to the control group and could be a biomarker of diabetes. Our study provided evidence which supports the impact of betatrophin on lipid metabolism. The positive correlation between betatrophin and C-peptide in the T1DM group suggests that betatrophin is associated with insulin secretion in T1DM.

Partial remission and early stages of pediatric type 1 diabetes display immunoregulatory changes. A pilot study

Type 1 diabetes (T1D) is a chronic metabolic disease of unknown etiology that results from β-cell destruction. The onset of the disease, which arises after a long asymptomatic period of autoimmune attack, may be followed by a relapsing and remitting progression, a phenomenon that is most evident during the partial remission phase (PR). This stage lasts for a few months, shows minor requirements of exogenous insulin and could be explained by a recovery of immunological tolerance. This study aims to identify new biomarkers at early stages of pediatric T1D that reflect immunoregulatory changes. To that end, pediatric patients with T1D (n = 52) and age-related control subjects (n = 30) were recruited. Immune response-related molecules and lymphocyte subsets were determined starting at T1D onset and until the second year of progression. Results showed that circulating TGF-β levels decreased during PR, and that betatrophin concentration was increased in all the considered stages without differing among studied checkpoints. Moreover, an increase of regulatory T, B and NK subsets was found during T1D progression, probably reflecting an attempt to restore self-tolerance. By contrast, a reduction in monocyte levels was observed at the early stages of diabetes. The results reveal significant changes in immunological parameters during the different early stages of T1D in children, which could ultimately serve as potential biomarkers to characterize the progression of T1D.

Evaluation of the Circulating Betatrophin Concentration and its Possible Correlations Among Diabetic Patients with Dyslipidemia

Evaluation of the Circulating Betatrophin Concentration and its Possible Correlations Among Diabetic Patients with Dyslipidemia

Betatrophin for diagnosis and prognosis of mothers with gestational diabetes mellitus.

ObjectivesBetatrophin is a widely used diagnostic marker for type 2 diabetes mellitus (DM), but its clinical utility in diagnosing gestational DM (GDM) is unclear. We evaluated the relationship between betatrophin and the risk of GDM as well as the ability of betatrophin to predict postpartum type 2 DM (PDM).MethodsIn total, 386 patients were categorized into those with and without PDM. All underwent the oral glucose tolerance test while pregnant. Betatrophin was assessed to examine the diagnostic characteristics of GDM.ResultsThe betatrophin concentration was remarkably higher in patients with than without GDM. The patients were categorized into three groups; those with a betatrophin concentration of 300 to 600 pg/mL and >600 pg/mL had a higher risk of GDM after adjusting for body mass index, age, homeostatic model assessment–insulin resistance (HOMA-IR) concentration, and betatrophin concentration than those with a betatrophin concentration of <300 pg/mL. The HOMA-IR concentration tended to increase as the betatrophin concentration increased, and betatrophin was independently associated with GDM after adjusting for confounders. The betatrophin concentration was higher among pregnant patients with than without PDM.ConclusionsBetatrophin has high sensitivity but low specificity for diagnosing GDM and may be a promising predictor of PDM.

Serum betatrophin levels are reduced in patients with full-blown polycystic ovary syndrome

Betatrophin is defined as a new marker in glucose homeostasis and lipid metabolism. We aimed to investigate the role of serum betatrophin in full-blown polycystic ovary syndrome (PCOS) patients and 47-aged healthy women, 51 full-blown PCOS patients were included in this cross-sectional study. Betatrophin concentrations were significantly lower in PCOS group and displayed a positive correlation only with serum tryglyceride in control group (p < .05). A cutoff level (464.5 ng/L) was determined for betatrophin according to Receiver Operating Characteristic curve. Using this value, 64.7% of PCOS patients were classified as below the cutoff and in this group betatrophin was found to correlate negatively with fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (p = .038, p = .020, and p = .014, respectively), and positively with total testosterone (p = .041). In the rest of PCOS cases (35.3%) who had betatrophin higher than cutoff, positive correlation was found with low-density lipoprotein cholesterol (p = .009). In conclusion, betatrophin levels are reduced in full-blown PCOS patients who had worse metabolic phenotype.

Metabolomics Shows an Association of Betatrophin with Bile Acids, Suggesting an Involvement of Betatrophin in Bile Acid–Mediated Metabolic Control

Betatrophin, also known as ANGPTL8, is secreted by liver and adipose tissue and plays an important role in glucose and lipid metabolism, but the mechanisms behind this remain unclear. Betatrophin is highly activated by active triiodothyronine (T3), a key player in metabolic control, which in turn is activated by bile acids (BA) via the BA-G-protein-coupled receptor TGR5-cAMP-deiodinase (D2), mediating the conversion of prohormone thyroxine to T3. We here measured betatrophin by ELISA and also applied GWAS and targeted metabolomic profiling in 233 serum samples of coronary angiographied patients. We found a correlation between betatrophin and BMI (r=0.142, p&amp;lt;0.001), fasting glucose (r=0.133, p=0.002), insulin (r=0.221, p&amp;lt;0.001), triglycerides (r=0.233, p&amp;lt;0.001), HDL (-0.122, p=0.004), and oxLDL (r=0.247, p&amp;lt;0.001). GWAs also found a genome wide-association between betatrophin and genomic variants in sterol transporter genes ABCG5/G8 and ABCA1. In the metabolomic assay we identified BA as the top metabolites to be associated with betatrophin concentration in serum (CDCA, r=0.234, p&amp;lt;0.001; GDCA, r=0.247, p&amp;lt;0.001; GCA, r=0.269, p&amp;lt;0.001; GCDCA, r=0.268, p&amp;lt;0.001; GLCA, r=0.211, p=0.002; TDCA, r=0.184, p=0.006). In conclusion, this study for the first time describes the association between betatrophin and BA. As (i) T3 is activated by BA via the BA-TGR5-cAMP-D2 signalling pathway and (ii) T3 is a strong activator of betatrophin, the link between betatrophin concentration and BA suggests that, at least in part, the impact of BA on energy homeostasis and metabolic control may be mediated via betatrophin. Moreover, TGR5 receptors have also been identified on pancreatic islet α- and β-cells and are stimulating insulin secretion in β-cells and able to restore β-cell mass and function under hyperglycemic conditions. Altogether, this may elucidate the impact of betatrophin on lipid and glucose metabolism. Disclosure A. Leiherer: None. A. Muendlein: None. K. Geiger: None. C.H. Saely: None. E. Brandtner: None. J. Ebner: None. B. Larcher: None. A. Mader: None. P. Fraunberger: None. H. Drexel: None.

Serum betatrophin/angiopoietin-like protein 8 (ANGPTL8) levels in pregnancies affected by hyperemesis gravidarum

ObjectiveThe association between serum betatrophin levels and hyperemesis gravidarum (HEG) remains unknown. The aim of this study was to determine and understand the alterations in serum betatrophin levels in pregnancies complicated by HEG compared with unaffected normal pregnancies. Study designA cohort study was carried out to evaluate serum betatrophin levels in patients with HEG. Serum betatrophin concentrations were measured with other metabolic markers for lipids and glucose metabolism in 40 singleton pregnancies affected by HEG and 40 gestational age– and body mass index–matched controls. ResultsThe serum betatrophin concentrations were significantly higher in pregnant women with HEG than in the controls (1000 [600–1100] vs. 900 [500–1000] pg/ml, p = 0.003). The serum total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels were significantly higher in patients with HEG than in the healthy counterparts at the first trimester of pregnancy (158.5 ± 29.4 vs. 143.8 ± 29.7 mg/dl and 47.3 ± 14.2 vs. 40.1 ± 8.6 mg/dl, p = 0.031 and p = 0.007, respectively). Receiver operating characteristic (ROC) analyses demonstrated that the area under the curve (AUC) indicative of the betatrophin value for discriminating HEG patients was 0.690 (95% CI: 0.574–0.806, p = 0.003). The optimal cutoff value was 976 pg/ml with a sensitivity of 50% (95% CI: 33.80–66.20%) and a specificity of 82.5% (95% CI: 67.22–92.66%). We also found a positive correlation between betatrophin levels and HDL-C (r = 0.311; p = 0.005). Logistic regression analyses demonstrated that increased levels of betatrophin and HDL-C were risk factors for HEG with odds ratios (95% confidence interval) of 4.884 (1.589–15.009) and 5.346 (1.044–27.366), respectively. ConclusionWe conclude that serum betatrophin concentrations were increased in pregnancies affected by HEG. Furthermore, HDL-C levels seem to be associated with alterations in serum betatrophin levels.

Association of serum betatrophin with fibroblast growth factor-21 in women with polycystic ovary syndrome.

Betatrophin and fibroblast growth factor-21 (FGF-21), which are recently discovered members of hepatokine/adipokine family, have been proposed to be associated with some metabolic disorders in which insulin resistance plays a major role. We aimed to investigate serum betatrophin and FGF-21 concentrations in women with polycystic ovary syndrome (PCOS). In this cross-sectional study, we recruited 31 women with PCOS and 34 women as healthy controls. Serum betatrophin level and its relationship with serum FGF-21 level as well as metabolic parameters were examined. Serum betatrophin level was significantly higher in women with PCOS‏ than the control group [1.10 (0.20-4.20) vs 0.70 (0.20-3.50)ng/ml, p=0.004], whereas FGF-21 did not differ between the groups [74.80 (7.80-435.90) vs 119.30 (10.50-443.40)pg/ml, p=0.13]. Serum betatrophin correlated positively with LH levels (r=0.26, p=0.03). After controlling BMI, there was a significant positive correlation between betatrophin and FGF-21 (r=0.25, p=0.04). Multivariate regression analysis revealed that FGF-21 and presence of PCOS were the significant predictors of betatrophin concentrations (R2=0.22, F=2.56, p=0.03). Our results indicate that betatrophin levels are increased and associated with LH and FGF-21 levels, but not with insulin resistance, in women with PCOS.

Association of Serum Betatrophin with Fibroblast Growth Factor-21 in Women with Polycystic Ovary Syndrome

Betatrophin and fibroblast growth factor-21 (FGF-21), which are recently discovered members of hepatokine/adipokine family, have been proposed to be associated with some metabolic disorders in which insulin resistance plays a major role. We aimed to investigate serum betatrophin and FGF-21 concentrations in women with polycystic ovary syndrome (PCOS). In this cross-sectional study, we recruited 31 women with PCOS and 34 women as healthy controls. Serum betatrophin level and its relationship with serum FGF-21 level as well as metabolic parameters were examined. Serum betatrophin level was significantly higher in women with PCOS‏ than the control group [1.10 (0.20–4.20) vs 0.70 (0.20–3.50) ng/ml, p = 0.004], whereas FGF-21 did not differ between the groups [74.80 (7.80–435.90) vs 119.30 (10.50–443.40) pg/ml, p = 0.13]. Serum betatrophin correlated positively with LH levels (r = 0.26, p = 0.03). After controlling BMI, there was a significant positive correlation between betatrophin and FGF-21 (r = 0.25, p = 0.04). Multivariate regression analysis revealed that FGF-21 and presence of PCOS were the significant predictors of betatrophin concentrations (R2 = 0.22, F = 2.56, p = 0.03). Our results indicate that betatrophin levels are increased and associated with LH and FGF-21 levels, but not with insulin resistance, in women with PCOS.