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      Increased serum fetuin-B concentration is associated with HOMA-β and indices of liver steatosis in women with polycystic ovary syndrome: a pilot study

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          Abstract

          Objective

          PCOS women are characterized by insulin resistance and have higher tendency to the development of hepatic steatosis. Fetuin-B has been introduced as a hepatokine/adipokine, which is increased in hepatic steatosis and may be connected with glucose metabolism disturbances. The aim of the study was to evaluate the relationships between serum fetuin-B concentration and indices of insulin resistance, insulin secretion and markers of liver steatosis in PCOS women in comparison to the control group.

          Patients and methods

          The study group included 108 women – 57 women with PCOS and 51 women matched for age and BMI as a control group. Serum concentration of fetuin-B was estimated. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment β cell function (HOMA-β) were calculated. Fatty liver index (FLI), lipid accumulation product (LAP) and visceral adiposity index (VAI) were used as markers of liver steatosis.

          Results

          We found higher serum concentration of fetuin-B and FLI in PCOS women in comparison to the control group (all P < 0.05). We observed a positive relationship between serum fetuin-B concentration and HOMA-β ( r = 0.43, P = 0.01), HOMA-IR ( r = 0.31, P = 0.01), FLI ( r = 0.29, P = 0.02), VAI ( r = 0.29, P = 0.02) and LAP ( r = 0.32, P = 0.01) in PCOS women. We also noticed a relationship between HOMA-IR and FLI ( r = 0.42, P = 0.01), VAI ( r = 0.38, P = 0.004) and LAP ( r = 0.41, P = 0.001) in this group. Multiple regression analysis revealed that HOMA-β (β = 0.39, P = 0.002) and LAP (β = 0.27, P = 0.02) were independently connected with serum fetuin-B levels in women with PCOS.

          Conclusions

          Serum fetuin-B levels are higher in women with PCOS and are independently connected with HOMA-β and hepatic steatosis.

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          Most cited references24

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          Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study.

          Ultrasound is used to screen for hepatic steatosis, the most common liver disease in the United States. However, few studies have prospectively evaluated the accuracy of ultrasound to diagnose hepatic steatosis. Therefore, a double blinded prospective study was performed in consecutive patients undergoing liver biopsy to evaluate the accuracy of ultrasound to diagnose hepatic steatosis. Real time ultrasound was performed just prior to the biopsy by a single investigator masked to the clinical diagnosis. The liver biopsy was reviewed by a pathologist masked to the clinical indication or sonographic findings. Of 73 consecutive patients studied, macrovesicular steatosis of any severity on biopsy was found in 46 (63%) and micro vesicular fat found in 51 (69.9%). The overall impression of the sonographer for the presence of macrovesicular hepatic steatosis of any degree had a sensitivity of 60.9% and a specificity of 100%. The sensitivity increased to 100% and the specificity to 90% when there was > or =20% of fat. The zonular distribution of the fat did not alter the diagnostic accuracy of ultrasound. Ultrasound had a poor yield in the diagnosis of microvesicular fat with an overall sensitivity of 43% and a specificity of 73%. The combination of increased echogenicity and portal vein blurring on ultrasound had the greatest sensitivity in the diagnosis of hepatic steatosis. Real time ultrasound using a combination of sonographic findings has a high specificity but underestimates the prevalence of hepatic steatosis when there is<20% fat.
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            A simple index of lipid overaccumulation is a good marker of liver steatosis

            Background Liver steatosis is often found in association with common cardiometabolic disorders, conditions that may all occur in a shared context of abdominal obesity and dyslipidemia. An algorithm for identifying liver steatosis is the fatty liver index (FLI). The lipid accumulation product (LAP) is an index formulated in a representative sample of the US population to identify cardiometabolic disorders. Because FLI and LAP share two components, namely waist circumference and fasting triglycerides, we evaluated the ability of LAP to identify liver steatosis in the same study population from the Northern Italian town where FLI was initially developed. Methods We studied 588 individuals (59% males) aged 21 to 79 years. Liver steatosis was detected by ultrasonography and coded ordinally as none, intermediate and severe. 44% of the individuals had liver steatosis. Using proportional-odds ordinal logistic regression, we evaluated the ability of log-transformed LAP (lnLAP) to identify liver steatosis. We considered the benefits to our model of including terms for sex, age, suspected liver disease and ethanol intake. We calculated the 3-level probability of liver steatosis according to lnLAP and sex, providing tables and nomograms for risk assessment. Results An ordinal proportional-odds model consisting of lnLAP and sex offered a reasonably accurate identification of liver steatosis. The odds of more severe vs. less severe steatosis increased for increasing values of lnLAP (odds ratio [OR] = 4.28, 95%CI 3.28 to 5.58 for each log-unit increment) and was more likely among males (OR = 1.88, 95%CI 1.31 to 2.69). Conclusion In a study sample of adults from Northern Italy, the simple calculation of LAP was a reasonably accurate approach to recognizing individuals with ultrasonographic liver steatosis. LAP may help primary care physicians to select subjects for liver ultrasonography and intensified lifestyle counseling, and researchers to select patients for epidemiologic studies. A more thorough assessment of LAP's potential for identifying liver steatosis will require its cross-evaluation in external populations.
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              Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A.

              Fetuins are serum proteins with diverse functions including the regulation of osteogenesis and inhibition of unwanted mineralization. Besides the alpha2-Heremans and Schmid glycoprotein/fetuin-A, the recently identified fetuin-B is a second member of the fetuin family [Olivier, Soury, Risler, Smih, Schneider, Lochner, Jouzeau, Fey and Salier (1999) Genomics 57, 352-364; Olivier, Soury, Ruminy, Husson, Parmentier, Daveau and Salier (2000) Biochem. J. 350, 589-597], which belongs to the cystatin superfamily. We compared the expressions of fetuin-B and fetuin-A at the RNA level and established that both genes are most highly expressed in liver tissue. Like fetuin-A, fetuin-B mRNA is also highly expressed in tongue and placenta tissues. We demonstrated for the first time that fetuin-B is also expressed at the protein level in sera and several organs of mouse, rat and human. We isolated contiguous genomic clones containing both fetuin-B and fetuin-A genes, indicating that these genes are closely linked at the genome level. The close proximity of both these genes may explain our observation that fetuin-B expression was decreased in fetuin-A-deficient mice. Unlike fetuin-A, the amount of fetuin-B protein in human serum varied with gender and was higher in females than in males. Functional analysis revealed that fetuin-B, similarly to fetuin-A, is an inhibitor of basic calcium phosphate precipitation, albeit less active when compared with fetuin-A. Therefore fetuin-B may have a function that is partly overlapping, if not identical, with the function of fetuin-A.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                August 2019
                15 July 2019
                : 8
                : 8
                : 1159-1167
                Affiliations
                [1 ]Department of Endocrinology , Diabetology and Internal Medicine, Medical University of Białystok, Białystok, Poland
                [2 ]Department of Internal Medicine and Metabolic Diseases , Medical University of Białystok, Białystok, Poland
                [3 ]Department of Reproduction and Gynecological Endocrinology , Medical University of Białystok, Białystok, Poland
                Author notes
                Correspondence should be addressed to A Adamska: ak001@ 123456wp.pl
                Article
                EC-19-0243
                10.1530/EC-19-0243
                6686951
                31307012
                bdb82fc2-a2b3-45e8-bd15-b6346592e8a9
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 21 June 2019
                : 15 July 2019
                Categories
                Research

                fetuin-b,pcos,homa-β,liver steatosis
                fetuin-b, pcos, homa-β, liver steatosis

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