Betatrophin Levels Research Articles

Betatrophin association with serum triglyceride levels in obstructive sleep apnea patients

BACKGROUND:Obstructive sleep apnea (OSA) is a common sleep problem, in which patients are at increased risk for metabolic and cardiovascular problems, including metabolic syndrome, diabetes mellitus (DM), and dyslipidemia. Betatrophin is a novel protein that regulates fatty acid and triglyceride (TG) metabolism and is related to obesity and metabolic abnormalities, including metabolic syndrome, DM, and dyslipidemia. Although OSA and betatrophin share common abnormalities, their relationship has not been investigated.AIM:The aim of this study is to investigate the relationships among betatrophin, OSA, and the serum lipid profile.METHODS:Ninety consecutive patients with suspected OSA underwent polysomnography (PSG) to confirm OSA. Plasma betatrophin, leptin, adiponectin, and the full lipid profile were analyzed. The patients were categorized as OSA or control based on the apnea-hypopnea index (AHI).RESULTS:About 61% of patients had OSA, and 39% had normal PSG. The levels of betatrophin, leptin, and adiponectin were higher in patients with OSA (256.59 ± 29.35, 374.20 ± 37.93, and 17.86 ± 2.63 μg/mL, respectively) compared to the controls (141.86 ± 26.20, 205.53 ± 14.75, and 7.52 ± 1.02 μg/mL, respectively). Betatrophin levels were correlated with the AHI, leptin (r = 0.413, P = 0.002, r = 0.782, P = 0.000). TG levels were significantly higher, and high-density lipoprotein cholesterol (HDL-C) levels were lower, in OSA patients compared to controls (244 ± 20.33 vs. 138 ± 14.89, and 37.21 ± 1.26 vs. 43.78 ± 1.62, respectively). The TG level was correlated with betatrophin (r = 0.353, P = 0.013). Multiple regression analysis showed that the AHI, leptin, and arousals were independent predictors of betatrophin level (B = 1.70 P = 0.046 95%, B = 0.56 P < 0.005, and B = 1, 2, P = 0.003, respectively).CONCLUSIONS:Our results suggest a complex relationship between OSA, betatrophin, TG, and HDL, as well as other adipokines. Our results require further investigation to assess this complex association and re-evaluate previous related studies.

Study of Serum Betatrophin Level in The Patients of Type 2 Diabetes Mellitus

Background: Type 2 DM is due primarily to lifestyle and genetic factors. A number of lifestyle factors are known to be important to the development of type 2 DM. Betatrophin, also known as angiopoietin-like protein (ANGPTL8), is a circulating protein predominantly produced in the liver and adipose tissue. Betatrophin is induced as a result of insulin resistance. It is reported to modulate pancreatic β-cell mass and glucose homeostasis reflectable on lipid metabolism. Aim of the Study: Evaluation of the role of betatrophin in patients with type 2 diabetes mellitus. Patients and Methods: This clinical study was carried out at Clinical Pathology Department, Tanta University Hospital and included 80 subjects who were divided into two groups: Group 1:40 Patients diagnosed with type 2 diabetes mellitus. Group 2: 40 normal subjects with matched age and sex as a control group. Results: In type 2 diabetes mellitus patients group, serum betatrophin ranged from 25.83 to 860.65 ng/l with a median value of 54.815 ng/l while in control group, betatrophin ranged from 7.5-53.2 ng/l with a madian value of 11.250 ng/l. There was significant statistical difference in betatrophin between the two groups. (P < 0.001). Betatrophin was significantly higher in type 2 diabtes mellitus patients as compared to control group. Conclusion: Circulating betatrophine concentrations were significantly increased in patients with T2 DM and associated with glucose homeostasis and insulin sensitivity. Thus, the level of serum betatrophin has a potential role in detection and pathogenesis of T2DM.

Associations Between Plasma Betatrophin Levels and Coronary and Peripheral Artery Disease.

Aim: Betatrophin, a recently identified circulating adipokine, affects lipid and glucose metabolism. However, association between plasma betatrophin levels and atherosclerotic diseases, such as coronary artery disease (CAD) and peripheral artery disease (PAD), has not been elucidated.Methods: We investigated plasma betatrophin levels in 457 patients undergoing elective coronary angiography who also had ankle-brachial index (ABI) test for PAD screening.Results: Of the 457 study patients, CAD was present in 241 patients (53%) (1-vessel [1-VD], n = 99; 2-vessel [2-VD], n = 71; 3-vessel disease [3-VD], n = 71). Compared to 216 patients without CAD, 241 with CAD had higher betatrophin levels (median 1120 vs. 909 pg/mL, p < 0.001). A stepwise increase in betatrophin levels was found depending on the number of > 50% stenotic coronary vessels: 909 in CAD(-), 962 in 1-VD, 1097 in 2-VD, and 1393 pg/ml in 3-VD (p < 0.001). Betatrophin levels correlated with the number of > 25% stenotic segments (r = 0.24, p < 0.001). PAD (ABI < 0.9) was found in 41 patients (9%). Plasma betatrophin levels were also significantly higher in 41 patients with PAD than in 416 without PAD (1354 vs. 981 pg/mL, p < 0.001). In the multivariate analysis, betatrophin levels were not a factor for CAD, but they were a significant factor for 3-VD and PAD independent of atherosclerotic risk factors. The odds ratios for 3-VD and PAD were 1.06 (95%CI = 1.01–1.11) and 1.07 (95%CI = 1.01–1.13) for a 100-pg/mL increase in betatrophin levels, respectively (p < 0.05).Conclusion: Plasma betatrophin levels were associated with the presence and severity of CAD and PAD, suggesting betatrophin has a role in atherosclerosis.

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.

Assessment of circulating betatrophin levels in intrahepatic cholestasis of pregnancy

Objective: To investigate maternal serum levels of betatrophin and their relationship with total bile acid (TBA) levels in patients with intrahepatic cholestasis of pregnancy (ICP). Materials and methods: Fifty-nine pregnant women with ICP (31 patients with severe and 28 patients with mild disease classifications) and 23 healthy women with uncomplicated pregnancies as the control group included the study. The maternal betatrophin, fasting blood glucose, fasting insulin (FI), and homeostatic model assessment of insulin resistance (HOMA-IR) levels of the groups were compared. Results: Serum betatrophin levels were significantly higher in the ICP groups than in the control group (p = .04 and p < .001, respectively). The FI levels and HOMA-IR values were significantly higher in the severe ICP group than in the control group (p = .006 and p = .001, respectively). While a significant positive correlation was found between betatrophin levels and fasting and postprandial TBA levels, there was no significant correlation among betatrophin and HOMA-IR or FI levels. Conclusions: Betatrophin levels were shown to correlate with TBA levels, it provides a model for future studies to understand the physiopathology of ICP, a complex metabolic disease. Changes in betatrophin levels may shed light on the pathogenesis of ICP.

The effect of GLP-1 agonist treatment on serum betatrophin levels and comparison with insulin treatment in type 2 diabetes mellitus patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

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.

Investigation of Blood Betatrophin Levels in Obese Children with Non-Alcoholic Fatty Liver Disease.

PurposeThe prevalence of obesity has significantly increased among children and adolescents worldwide and is becoming an important health care problem in parallel with the increased prevalence of obesity pediatric non-alcoholic fatty liver disease. Betatrophin is a newly define hormone that is commonly secreted by liver and plays role in glucose tolerance. This study aimed to investigate the relationship between serum betatrophin levels and non-alcoholic fatty liver disease in obese children.MethodsThe study included 40 obese children with a body mass index (BMI) above 95th centile, and 35 non-obese subjects with a BMI 3-85th centile, whose age and gender were similar to those of the patient group. For the evaluation of metabolic parameters fasting serum glucose, insulin, alanine aminotransferase, aspartate aminotransferase, lipid profile and serum betatrophin levels were measured. Total cholesterol: high-density lipoprotein cholesterol and low-density lipoprotein cholesterol: high-density lipoprotein cholesterol ratios were calculated as “atherogenic indices.”ResultsSerum betatrophin levels of the obese subjects were similar to that of non-obese subjects (p=0.90). Betatrophin levels were not correlated with the metabolic parameters.ConclusionIn the present study, levels of betatrophin are not different between obese and insulin resistant children and non-obese subjects, and they are not correlated with atherogenic indices. To elucidate the exact role of betatrophin in obesity, further studies are required to identify the betatrophin receptor and/or other possible cofactors.

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.

Serum Betatrophin Concentrations and the Risk of Incident Diabetes: A Nested Case-Control Study from Chungju Metabolic Disease Cohort.

BackgroundBetatrophin is a newly identified hormone derived from the liver and adipose tissue, which has been suggested to regulate glucose and lipid metabolism. Circulating levels of betatrophin are altered in various metabolic diseases, although the results are inconsistent. We aimed to examine whether betatrophin is a useful biomarker in predicting the development of diabetes.MethodsA nested case-control study was performed using a prospective Chungju Metabolic disease Cohort Study. During a 4-year follow-up period, we analyzed 167 individuals who converted to diabetes and 167 non-converters, who were matched by age, sex, and body mass index. Serum betatrophin levels were measured by an ELISA (enzyme-linked immunosorbent assay).ResultsBaseline serum betatrophin levels were significantly higher in the converter group compared to the non-converter group (1,315±598 pg/mL vs. 1,072±446 pg/mL, P<0.001). After adjusting for age, sex, body mass index, fasting plasma glucose, systolic blood pressure, total cholesterol, and family history of diabetes, the risk of developing diabetes showed a stepwise increase across the betatrophin quartile groups. Subjects in the highest baseline quartile of betatrophin levels had more than a threefold higher risk of incident diabetes than the subjects in the lowest quartile (relative risk, 3.275; 95% confidence interval, 1.574 to 6.814; P=0.010). However, no significant relationships were observed between serum betatrophin levels and indices of insulin resistance or β-cell function.ConclusionCirculating levels of betatrophin could be a potential biomarker for predicting new-onset diabetes. Further studies are needed to understand the underlying mechanism of this association.

Circulating betatrophin is associated with insulin resistance in humans: cross-sectional and interventional studies in vivo and in vitro.

Betatrophin has a closely relationship with metabolism. However, its effect on metabolism disorder remains unclear. This study was comprised of a series of cross-sectional and interventional studies in vivo and vitro. PCOS women with IR and healthy women were recruited from the general population and outpatients. Plasma betatrophin levels were measured with ELISA. Insulin sensitivity was assessed with EHC. Gene expressions at mRNA and protein levels were determined with RT-PCR and Western blotting. Influences of insulin, metformin, rosiglitazone and over- or knockdown-expression of betatrophin were analyzed ex vivo. Our results indicated that IR women had higher betatrophin levels compared with the controls. Circulating betatrophin was positively correlated with BMI, WHR, Fat%, triglyceride, total cholesterol, LDL-C, AUCglucose and AUCinsulin, luteinizing Hormone, FAI and HOMA-IR but negatively with M-value. Metformin treatment in PCOS women with IR led to a reduction of betatrophin levels. Insulin stimulation in hepatocytes increased betatrophin expression. Metformin or rosiglitazone led to a reduction of betatrophin expression in insulin-stimulated hepatocytes. In hepatocytes/macrophages co-culture systems, betatrophin expression was significantly increased, whereas this increase was eliminated by rosiglitazone. In hepatocytes, overexpression and knockdown of betatrophin decreased or increased insulin-stimulated insulin receptor, protein kinase B and insulin receptor substrate-1 phosphorylation respectively. Serum from metformin-treated women with IR decreased betatrophin expression and reinforced insulin signals. Thus, the present study provides the in vivo and in vitro evidence, suggesting that there is a cell cross-talking between hepatocytes with macrophages for the regulating betatrophin and it may be a useful marker for IR and metabolic disorders.

The Correlation Between Circulating Betatrophin and Insulin Resistance in General Population: A Meta-Analysis.

Many inconsistent findings are reported on the correlation between circulating betatrophin and insulin resistance in the different population. The aim of this analysis was to explore the correlation between the level of betatrophin and insulin resistance in the general population. The databases of PubMed, EMBASE, and the Cochrane Library (inception to October 26, 2016) were searched without language restrictions for publications that reported studies on associations between betatrophin and insulin resistance in adults. Subgroup analyses were performed to investigate potential sources of heterogeneity. The pooled effect size was calculated using a random-effects model. Twenty-five studies were included in this meta-analysis. Meta-analysis showed that betatrophin was positively and significantly correlated with insulin resistance (r=0.16, 95% CI: 0.08-0.25). When all participants were divided into DM, GDM, and Non-DM groups, this association was also significant in T2DM, GDM, and Non-DM participants (T2DM: r=0.09, 95% CI: 0.01-0.17; I 2=45.1%; GDM: r=0.39, 95% CI: 0.24-0.55; I 2=0.0%; non-DM: r=0.15, 95% CI: 0.04-0.26; I 2=89.3%), and it was obvious that heterogeneity existed in Non-DM group (I 2=89.3%, p<0.001). Subgroup analysis revealed that gender, serum sample and ELISA kits for full-length betatrophin had significant influence on the association between betatrophin and insulin resistance. In conclusion, the level of circulating betatrophin is positively associated with insulin resistance in the general population, especially in T2DM and GDM patients. Gender, serum sample, and ELISA kits for full-length betatrophin may affect this association. More large-scale studies are needed to determine whether improving insulin resistance concomitantly declines betatrophin levels in different diseases.

Insulin upregulates betatrophin expression via PI3K/Akt pathway

Betatrophin is regarded as a liver-produced hormone induced by insulin resistance (IR). However, it remains largely unknown how IR regulates betatrophin expression. To study whether IR could regulate betatrophin expression and the corresponding molecular mechanisms, betatrophin levels were examined in 6 in vitro IR models which were established using human hepatocytes L02 with different agents, including tumor necrosis factor-α, interleukin-1β, dexamethasone, palmitate, high glucose and insulin and betatrophin levels were elevated only in the insulin group. These results suggest that it is insulin, not IR that promotes betatrophin expression. In the meantime, PI3K/Akt pathway was activated by insulin and suppressed by above agents that caused IR. Insulin-upregulated betatrophin expression was suppressed by PI3K/Akt inhibitors and IR, suggesting that insulin upregulates and IR decreases betatrophin production through PI3K/Akt pathway. Consistently, the treatment of insulin in mice dose-dependently upregulated betatrophin levels, and the administration of metformin in IR mice also stimulated betatrophin production since published study showed metformin improved PI3K/Akt pathway and IR. In humans, compared with those without insulin treatment, serum betatrophin levels were increased in type 2 diabetic patients with insulin treatment. In conclusion, insulin stimulates betatrophin secretion through PI3K/Akt pathway and IR may play an opposite role.

Assessment of serum betatrophin concentrations in patients with chronic hepatitis C-related liver cirrhosis

Objective The aim of this study was to evaluate serum betatrophin concentrations in patients with chronic hepatitis C-related liver cirrhosis and to explore its potential relations with liver cirrhosis progression and insulin resistance (IR). Background Hepatitis C virus infection is a serious clinical condition that usually progresses to liver cirrhosis. Betatrophin is a newly discovered hormone that has been considered as important regulator of pancreatic β-cell proliferation. Patients and methods We analyzed 70 patients who were diagnosed with chronic hepatitis C-related liver cirrhosis. Patients were assorted into three groups according to Child–Pugh score. In addition, a control group was included and consisted of 20 healthy volunteers. Serum betatrophin and IR were evaluated for all patients and controls. Results Patients with cirrhosis showed significantly higher circulating betatrophin levels in comparison with healthy controls ( P r = 0.66; P P r = 0.96; P Conclusion Serum betatrophin was significantly increased in patients with chronic hepatitis C-related liver cirrhosis and its level positively associated with liver cirrhosis severity and IR.

Plasma Betatrophin Levels of Subjects Classified with Normal, Impaired, and Diabetic Glucose Tolerance, and Subjects with Impaired Fasting Glucose.

This study was aimed to investigate whether betatrophin shows glucose intolerance or not. To access the plasma betatrophin levels after basal and glucose load, groups were classified as normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT) according to WHO 2012 criteria. An oral glucose tolerance test was performed on age-matched subjects (n=220) with a body mass index (BMI)<27 kg/m2. Subjects were categorized as normoglycemic (n=55), IFG (n=50), IGT (n=60), and DM (n=55) according to the WHO criteria. Baseline betatrophin levels in DGT are significantly higher than in NGT (p<0.005), IFG (p<0.004), and IGT (p<0.001). Male subjects have significantly higher betatrophin levels than female subjects (p<0.01). In DGT, betatrophin of male subjects was found to be significantly higher than the betatrophin of male subjects in NGT (p<0.04), IFG (p<0.01), and IGT (p<0.01). Significant relationship between betatrophin and both ages and HbA1c in all groups were observed. When ages were accepted as an independent factor, significant correlation between betatrophin and ages were found. Betatrophin is increased and associated with age and HbA1c in DGT. Males had higher betatrophin levels compared with females in DGT group. As no obvious betatrophin deficiency to substitute in IFG and IGT individuals were observed, betatrophin levels appeared to be related to the pathogenesis of the diabetic stages rather than prediabetic stages.

Assessment of circulating betatrophin concentrations in lean glucose-tolerant women with polycystic ovary syndrome

The aims of the current study were to investigate the betatrophin levels in lean glucose-tolerant women with polycystic ovary syndrome (PCOS), and to explore the relationships between these levels and antropometric, hormonal and metabolic parameters. The study population consisted of 50 lean (body mass index [BMI] < 25 kg/m2) women diagnosed with PCOS using the Rotterdam criteria, and 60 age- and BMI-matched healthy controls without any features of clinical or biochemical hyperandrogenism. Before recruitment, glucose tolerance was evaluated in all of the subjects using the 2-h 75 g oral glucose-tolerance test, and only those exhibiting normal glucose tolerance were enrolled. Serum betatrophin levels were significantly higher in women with PCOS (median 322.3; range 44.7–1989.3 ng/L) compared to the controls (median 199.9; range 6.2–1912.9 ng/L; p = .005). In the control group, no significant correlation was evident between betatrophin levels and clinical or biochemical parameters. In the PCOS group, betatrophin levels were positively correlated with prolactin levels (r = .286, p = .046) and negatively correlated with BMI (r = −.283, p = .049), waist/hip ratio (r = −.324, p = .023), and low-density lipoprotein cholesterol levels (r = −.385, p = .006).Impact statementWhat is already known on this subject: Several studies have suggested that primary alteration in beta-cell function is a pathophysiological feature of PCOS, and insulin resistance is the most significant predictor of beta-cell dysfunction independent of obesity.Betatrophin is a circulating protein that is primarily expressed in the liver in humans. Early experimental investigations demonstrated that overexpression of betatrophin significantly promoted pancreatic beta-cell proliferation, insulin production and improved glucose tolerance. Few studies have investigated the association between PCOS and betatrophin. However, in contrast to our study, the authors included overweight/obese patients and glucose tolerance was not evaluated before recruitment.What the results of this study add: Our results showed that serum betatrophin levels were significantly higher in lean glucose-tolerant PCOS women than in age- and BMI-matched healthy controls.What are the implications of these findings for clinical practice and/or further research: Elevated betatrophin levels in PCOS women, in the absence of obesity and glucose intolerance, may reflect a compensatory mechanism in order to counteract metabolic syndrome-related risk factors.

Renal function is independently associated with circulating betatrophin.

ObjectiveBetatrophin has been identified as a marker linking liver with beta cell function and lipid metabolism in murine models. Until now, the regulation of circulating betatrophin in humans is not entirely clear. We here analyzed the relation of betatrophin levels to phenotypes of the metabolic syndrome and speculated that renal function might influence circulating betatrophin levels and explain age-dependent changes of betatrophin.SubjectsWe analyzed blood samples from 535 individuals participating in the Metabolic Syndrome Berlin Potsdam study.ResultsIn a crude analysis we found a positive correlation between betatrophin levels and HbA1c (r = 0.24; p < 0.001), fasting glucose (r = 0.20; p < 0.001) and triglycerides (r = 0.12; p = 0.007). Furthermore betatrophin was positively correlated with age (r = 0.47; p <0.001), systolic blood pressure (r = 0.17; p < 0.001), intima media thickness (r = 0.26; p < 0.001) and negatively correlated with CKD-EPI eGFR (r = -0.33; p < 0.001) as an estimate of renal function. Notably, eGFR remained highly associated with betatrophin after adjustment for age, waist circumference, gender, HbA1c and lipid parameters in a multivariate linear regression model (β = -0.197, p< 0.001).ConclusionsOur data suggest that circulating levels of betatrophin depend on age, gender, waist circumference, total/HDL cholesterol ratio and renal function. Especially the association to eGFR highlights the importance for future studies to address renal function as possible influence on betatrophin regulation and consider eGFR as potential confounder when analyzing the role of betatrophin in humans.

Correlation of the levels of serum betatrophin, adiponectin, and interleukin-1β in newly diagnosed type 2 diabetes with different stages of urinary albumin

267 newly-diagnosed patients with type 2 diabetes were divided into normoalbuminuria group[group N-UAlb, urinary albumin to creatinine ratio (UACR) 300 mg/g, n=76). The control group(group NC)consisted of 114 healthy individuals. Serum betatrophin, adiponectin(APN), and interleukin-1β(IL-1β)levels were determined with ELISA methods and the parameters of body mass index(BMI), estimated glomerular filtration rate(eGFR), HbA1C,fasting plasma glucose(FPG), OGTT 2h plasma glucose(2hPG), fasting insulin(FINS), OGTT 2h postprandial insulin(2hPINS), fasting C-peptide(FCP), homeostasis model assessment insulin resistant index(HOMA-IR), and blood lipid were collected. Compared with group NC, the serum betatrophin levels in patients with type 2 diabetes were obviously increased. In patients with type 2 diabetes, betatrophin levels increased along with the increase of UACR and there were significant differences in betatrophin among the three groups(P<0.01). Betatrophin positively correlated with UACR, HbA1C,FPG, 2hPG, FINS, 2hPINS, HOMA-IR, TC, LDL-C, and TG(r were 0.785, 0.225, 0.136, 0.241, 0.386, 0.223, 0.411, 0.216, 0.193, and 0.298, all P<0.05), and betatrophin were also positively correlated with APN and IL-1β(r were 0.643 and 0.710, both P<0.01). Stepwise multiple regression analysis showed that UACR, HbA1C,FINS, and TG were independent relevant factors affecting betatrophin levels. (Chin J Endocrinol Metab, 2017, 33: 116-119) Key words: Diabetes mellitus, type 2; Betatrophin; Adiponectin; Interleukin-1β; Albuminuria

Increased circulating full-length betatrophin levels in drug-naïve metabolic syndrome

Betatrophin is a newly identified circulating adipokine playing a role in the regulation of glucose homeostasis and lipid metabolism. But its role in metabolic syndrome (MetS) remains unknown. Therefore, we aimed to compare the circulating betatrophin concentrations between patients with MetS and healthy controls. We recruited 47 patients with MetS and 47 age and sex matched healthy controls. Anthropometric and biochemical measurements were performed, and serum betatrophin levels were detected by ELISA. Full-length betatrophin levels in patients with MetS were significantly higher than those in controls (694.84 365.51 pg/ml versus 356.64 287.92 pg/ml; P <0.001). While no significant difference of total betatrophin levels was found between the two groups (1.20 0.79 ng/ml versus 1.31 1.08 ng/ml; P = 0.524). Full-length betatrophin level was positively correlated with fasting plasma glucose (FPG) (r = 0.357, P = 0.014) and 2-hour plasma glucose (2hPG) (r = 0.38, P <0.01). Binary logistic regression models indicated that subjects in the tertile of the highest full-length betatrophin level experienced higher odds of having MetS (OR, 8.6; 95% CI 2.8-26.8; P <0.001). Our study showed that full-length betatrophin concentrations were increased in drug-naïve MetS patients.