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Nikolić VN, Stefanović M, Mitić D, Sunarić S, Stojiljkovic V, Trajković H, Ignjatović A, Stokanović D. Metformin dosage and galectin-3 levels: insights from PCOS patients preparing for IVF. Front Pharmacol 2025; 15:1505022. [PMID: 39958874 PMCID: PMC11825798 DOI: 10.3389/fphar.2024.1505022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 12/20/2024] [Indexed: 02/18/2025] Open
Abstract
This study explores the impact of metformin dosage and hyperprolactinemia on galectin-3 levels in women with Polycystic Ovary Syndrome (PCOS), providing novel insights into their roles in the metabolic and hormonal management of the condition. A cohort of 53 women, diagnosed using the Rotterdam criteria and undergoing in vitro fertilization (IVF) preparation, was analyzed to determine how these factors influence galectin-3, a biomarker in PCOS. Using high-performance liquid chromatography to measure metformin concentrations and ELISA for galectin-3, our results revealed that both metformin dosage and hyperprolactinemia significantly statistically associated with galectin-3 levels, while body mass index (BMI) showed no significant association. These findings challenge prior assumptions and suggest that galectin-3 may be regulated via pathways independent of metformin pharmacokinetics. Notably, the correlation between galectin-3 levels and metformin concentration was either absent or weak after adjusting for the daily dose, indicating that treatment duration and dosage, rather than absolute drug levels, may more critically influence galectin-3. This study offers deeper insights into the role of personalized metformin dosing in managing PCOS, enhancing the understanding of metabolic and hormonal regulation in this condition, and laying the groundwork for future targeted therapies.
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Affiliation(s)
- Valentina N. Nikolić
- Department of Pharmacology with Toxicology, University of Nis Faculty of Medicine, Niš, Serbia
| | - Milan Stefanović
- Department of Gynaecology and Obstetrics, University of Nis Faculty of Medicine, Niš, Serbia
- Gynaecology and Obstetrics Clinic, University Clinical Centre Niš, Niš, Serbia
| | - Dejan Mitić
- Department of Gynaecology and Obstetrics, University of Nis Faculty of Medicine, Niš, Serbia
- Gynaecology and Obstetrics Clinic, University Clinical Centre Niš, Niš, Serbia
| | - Slavica Sunarić
- Department of Chemistry, University of Niš Faculty of Medicine, Niš, Serbia
| | - Vladana Stojiljkovic
- Department of Biochemistry, Medical Faculty University of Niš, University Clinical Center Niš, Niš, Serbia
| | - Hristina Trajković
- Department of Pharmacology with Toxicology, University of Nis Faculty of Medicine, Niš, Serbia
| | - Aleksandra Ignjatović
- Department of Medical Statistics and Informatics, University of Nis Faculty of Medicine, Niš, Serbia
| | - Dragana Stokanović
- Department of Pharmacology with Toxicology, University of Nis Faculty of Medicine, Niš, Serbia
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Xia J, Wang Y, Qi BR. In vitro and in vivo effects of Galectin-3 inhibitor TD139 on inflammation and ERK/JNK/p38 pathway in gestational diabetes mellitus. Kaohsiung J Med Sci 2024; 40:916-925. [PMID: 39230472 DOI: 10.1002/kjm2.12890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 08/11/2024] [Accepted: 08/12/2024] [Indexed: 09/05/2024] Open
Abstract
This study aims to investigate the effects of the Galectin-3 (Gal-3) inhibitor TD139 on inflammation and the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 pathway in gestational diabetes mellitus (GDM). Human placental tissues were treated with TD139 and TNF-α, assessing Gal-3, ERK/JNK/p38 activation, and inflammatory cytokines. GDM was induced in mice via subcutaneous injections of streptozotocin (STZ). After confirming GDM, mice were treated with 15 mg/kg TD139 on GD 10.5 12.5, 14.5, 16.5, and 18.5. Serum inflammatory cytokines were measured on GD 20.5, and post-delivery placental tissues were analyzed. Data were analyzed using one-way or two-way repeated measures ANOVA with post hoc tests. TD139 suppressed TNF-α-induced increases in Gal-3, IL-1β, IL-6, MCP-1, and ERK/JNK/p38 activation in placental tissues. In STZ-induced GDM mice, TD139 reduced glucose levels, weight loss, and food and water intake. TD139 significantly lowered TNF-α, IL-1β, IL-6, and MCP-1 in serum and placental tissues and inhibited the ERK/JNK/p38 pathway. TD139 improved pup numbers in GDM mice compared to untreated ones. TD139 reduces inflammation and inhibits the ERK/JNK/p38 pathway in TNF-α stimulated placental tissues and STZ-induced GDM mice, suggesting its therapeutic potential for managing GDM-related placental inflammation and improving pregnancy outcomes. The study used TNF-α to mimic GDM in placental tissues and an STZ-induced GDM mouse model, which may not fully represent human GDM complexity. Future research should explore alternative models, and broader signaling pathways, and thoroughly evaluate TD139's safety in pregnancy.
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Affiliation(s)
- Ji Xia
- Department of Obstetrics, Hainan Branch, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Sanya, China
| | - Yan Wang
- Department of Obstetrics, Hainan Branch, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Sanya, China
| | - Bang-Ruo Qi
- Department of Obstetrics, Hainan Branch, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Sanya, China
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Bahreiny SS, Bastani MN, Aghaei M, Dabbagh MR, Mahdizade AH. Circulating Galectin-3 levels in women with polycystic ovary syndrome: A meta-analysis. Taiwan J Obstet Gynecol 2024; 63:37-45. [PMID: 38216266 DOI: 10.1016/j.tjog.2023.10.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/27/2023] [Indexed: 01/14/2024] Open
Abstract
Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine disorder characterized by multifactorial and intricate pathogenesis. The discovery of novel markers has been a significant step toward understanding the mechanisms of PCOS. Galectin-3 has emerged as a novel factor in metabolic disorders. This meta-analysis examines the association between circulating Galectin-3 and PCOS. A systematic review and meta-analysis were performed to identify relevant articles in the electronic databases PubMed, Web of Science, Scopus, Cochrane, EMBASE, and Google Scholar. The search covered the period from January 2000 to March 2023 and followed a predefined search strategy. Eight articles were included in the analysis with a total of 594 participants (322 patients with PCOS and 272 controls). Pooled standardized mean difference (SMD) and 95 % confidence interval [CI] were used to evaluate the association between Galectin-3 levels and PCOS. The results indicated a significant association between PCOS and galectin-3 levels (SMD = 0.58; 95 % CI: 0.15-1.01; p = 0.007). In addition, subgroup analysis showed a significant difference in serum Galectin-3 levels in women with PCOS and a higher homeostatic model assessment for insulin resistance ratio (SMD = 0.89; 95 % CI: 0.45-1.33; p < 0.001). The researchers also performed meta-regression and subgroup analyses to specify sources of heterogeneity. The results of our meta-analysis suggest an association between increased levels of galectin-3 and PCOS. Galectin-3 plays a significant role in the progression of PCOS and could be used as a novel diagnostic biomarker. Nevertheless, it is essential to perform further studies to confirm and support our conclusions.
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Affiliation(s)
- Seyed Sobhan Bahreiny
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Medical Basic Sciences Research Institute, Physiology Research Center, Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Mohammad-Navid Bastani
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mojtaba Aghaei
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad Reza Dabbagh
- Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Amir Hossein Mahdizade
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Salehi R, Asare-Werehene M, Wyse BA, Abedini A, Pan B, Gutsol A, Jahangiri S, Szaraz P, Burns KD, Vanderhyden B, Li J, Burger D, Librach CL, Tsang BK. Granulosa cell-derived miR-379-5p regulates macrophage polarization in polycystic ovarian syndrome. Front Immunol 2023; 14:1104550. [PMID: 37033997 PMCID: PMC10081157 DOI: 10.3389/fimmu.2023.1104550] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 03/13/2023] [Indexed: 04/11/2023] Open
Abstract
Polycystic ovarian syndrome (PCOS) is associated with hyperandrogenemia and ovarian antral follicle growth arrest. We have previously demonstrated that androgen-induced exosomal release of miR-379-5p (miR379) from preantral follicle granulosa cells increases the proliferation of target cells via phosphoinositide-dependent kinase 1 (PDK1) upregulation. Androgen also increases inflammatory M1 macrophage abundance, but reduces anti-inflammatory M2 polarization in rat antral and preovulatory follicles. However, the role of small extracellular vesicles (sEVs; also known as exosomes) secretion in determining the cellular content and function of miRNAs in exosome-receiving cells is largely unknown. Our objectives were to determine: 1) the regulatory role of granulosa cells (GC)-derived exosomal miR379 on macrophage polarization and ovarian inflammation; 2) whether miR379-induced M1 polarization regulates GC proliferation; and 3) if this regulated process is follicular stage-specific. Compared with non-PCOS subjects, PCOS subjects had a higher M1/M2 ratio, supporting the concept that PCOS is an inflammatory condition. Ovarian overexpression of miR379 increased the number of M1 macrophages and the M1/M2 ratio in preantral follicles specifically. Transfection of macrophages with a miR379 mimic reduced the cellular content of PDK1 and induced M0→M1 polarization; whereas its inhibitor polarized M0→M2. Conditioned media from macrophages transfected with miR379 mimic and follicular fluid from PCOS subjects had higher galectin-3 content, a pro-inflammatory cytokine which specifically suppresses human antral follicle GC proliferation. These results indicate that miR379 inhibits M2 macrophage polarization, a condition which suppresses GC proliferation in a follicle stage-dependent manner, as exhibited in PCOS.
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Affiliation(s)
- Reza Salehi
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, ON, Canada
- Department of Cellular and Molecular Medicine and Center for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON, Canada
- CReATe Fertility Centre, Toronto, ON, Canada
| | - Meshach Asare-Werehene
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, ON, Canada
- Department of Cellular and Molecular Medicine and Center for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON, Canada
| | | | - Atefeh Abedini
- Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Bo Pan
- Department of Animal BioScience, University of Guelph, Guelph, ON, Canada
| | - Alex Gutsol
- Division of Nephrology, Department of Medicine, Kidney Research Centre, University of Ottawa, Ottawa, ON, Canada
| | | | | | - Kevin D. Burns
- Division of Nephrology, Department of Medicine, Kidney Research Centre, University of Ottawa, Ottawa, ON, Canada
| | - Barbara Vanderhyden
- Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, ON, Canada
- Department of Cellular and Molecular Medicine and Center for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON, Canada
- Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Julang Li
- Department of Animal BioScience, University of Guelph, Guelph, ON, Canada
| | - Dylan Burger
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Department of Cellular and Molecular Medicine and Center for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON, Canada
- Division of Nephrology, Department of Medicine, Kidney Research Centre, University of Ottawa, Ottawa, ON, Canada
| | - Clifford L. Librach
- CReATe Fertility Centre, Toronto, ON, Canada
- Department of Obstetrics & Gynaecology, University of Toronto, Toronto, ON, Canada
- Department of Physiology, University of Toronto, Toronto, ON, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
| | - Benjamin K. Tsang
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, ON, Canada
- Department of Cellular and Molecular Medicine and Center for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON, Canada
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Review of Novel Potential Insulin Resistance Biomarkers in PCOS Patients—The Debate Is Still Open. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19042099. [PMID: 35206286 PMCID: PMC8871992 DOI: 10.3390/ijerph19042099] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/27/2022] [Accepted: 02/09/2022] [Indexed: 12/12/2022]
Abstract
Research on proteins and peptides that play roles in metabolic regulation, which may be considered potential insulin resistance markers in some medical conditions, such as diabetes mellitus, obesity and polycystic ovarian syndrome (PCOS), has recently gained in interest. PCOS is a common endocrine disorder associated with hyperandrogenemia and failure of ovulation, which is often accompanied by metabolic abnormalities, including obesity, dyslipidemia, hyperinsulinemia, and insulin resistance. In this review, we focus on less commonly known peptides/proteins and investigate their role as potential biomarkers for insulin resistance in females affected by PCOS. We summarize studies comparing the serum fasting concentration of particular agents in PCOS individuals and healthy controls. Based on our analysis, we propose that, in the majority of studies, the levels of nesfastin-1, myonectin, omentin, neudesin were decreased in PCOS patients, while the levels of the other considered agents (e.g., preptin, gremlin-1, neuregulin-4, xenopsin-related peptide, xenin-25, and galectin-3) were increased. However, there also exist studies presenting contrary results; in particular, most data existing for lipocalin-2 are inconsistent. Therefore, further research is required to confirm those hypotheses, as well as to elucidate the involvement of these factors in PCOS-related metabolic complications.
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Borovcanin MM, Vesic K, Jovanovic M, Mijailovic NR. Galectin-3 possible involvement in antipsychotic-induced metabolic changes of schizophrenia: A minireview. World J Diabetes 2021; 12:1731-1739. [PMID: 34754374 PMCID: PMC8554363 DOI: 10.4239/wjd.v12.i10.1731] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/24/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023] Open
Abstract
Recently, specific immunometabolic profiles have been postulated in patients with schizophrenia, even before full-blown disease and independent of antipsychotic treatment. Proteomic profiling studies offer a promising potential for elucidating the cellular and molecular pathways that may be involved in the onset and progression of schizophrenia symptoms, and co-occurrent metabolic changes. In view of all this, we were intrigued to explore galectin-3 (Gal-3) as a glycan, and in our previous study, we measured its elevated levels in remission of schizophrenia. The finding may be a consequence of antipsychotic treatment and may have an impact on the onset of inflammation, the development of obesity, and the presumed cognitive changes in schizophrenia. In the animal study, it was shown that downregulation of Gal-3 was beneficial in insulin regulation of obesity and cognitive preservation. Strategies involving plasma exchange are discussed in this review, particularly in the context of Gal-3 elimination.
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Affiliation(s)
- Milica M Borovcanin
- Department of Psychiatry, University of Kragujevac, Faculty of Medical Sciences, Kragujevac 34000, Sumadija, Serbia
| | - Katarina Vesic
- Department of Neurology, University of Kragujevac, Faculty of Medical Sciences, Kragujevac 34000, Sumadija, Serbia
| | - Milena Jovanovic
- PhD Studies, University of Kragujevac, Faculty of Medical Sciences, Kragujevac 34000, Sumadija, Serbia
- Clinic for Nephrology and Dialysis, University Clinical Center Kragujevac, Kragujevac 34000, Sumadija, Serbia
| | - Natasa R Mijailovic
- Department of Pharmacy, University of Kragujevac, Faculty of Medical Sciences, Kragujevac 34000, Sumadija, Serbia
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Faust K, Freitag N, Barrientos G, Hartel C, Blois SM. Galectin-Levels Are Elevated in Infants Born Preterm Due to Amniotic Infection and Rapidly Decline in the Neonatal Period. Front Immunol 2021; 11:599104. [PMID: 33717050 PMCID: PMC7949913 DOI: 10.3389/fimmu.2020.599104] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 12/23/2020] [Indexed: 11/13/2022] Open
Abstract
Galectin (gal)-1, -3, and -9 are members of a family of glycan binding proteins that mediate complex interactions between decidual, inflammatory and trophoblast cells modulating several processes during gestation, control of the maternal immune system, and parturition. Their immunomodulatory role in preterm birth and postnatal expression in preterm infants is unknown. We performed a single center prospective study of 170 preterm infants with a gestational age below 35 weeks. Peripheral venous blood samples were collected during the neonatal period and galectin-1, -3, and -9 were determined by ELISA. We noted a strong decline of circulating gal-1 and -3 levels but not gal-9 from birth to day 7 of life. There was an inverse correlation of gal-1 and -3 levels at birth with gestational age. Gal-1 levels were remarkably increased in infants born to amniotic infection syndrome (AIS), which was also observed for gal-9 levels. Infants who developed early-onset sepsis had higher levels of gal-3 at day 1 as compared to unaffected infants. Our observational data imply that galectin-1, -3, and -9 levels are elevated in preterm infants born in an inflammatory milieu such as AIS or EOS. Future studies need to address whether galectins mediate inflammation-induced preterm birth and could therefore be a target for clinical trials.
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Affiliation(s)
- Kirstin Faust
- Department of Pediatrics, University of Luebeck, University Hospital of Schleswig-Holstein, Lübeck, Germany.,German Center for Infection Research, Lübeck, Germany
| | - Nancy Freitag
- Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Charité-Universitätsmedizin Berlin, Berlin, Germany.,Charité-Universitätsmedizin Berlin, Division of General Internal and Psychosomatic Medicine, Berlin, Germany
| | - Gabriela Barrientos
- Laboratorio de Medicina Experimental, Hospital Alemán-Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
| | - Christoph Hartel
- German Center for Infection Research, Lübeck, Germany.,Department of Paediatrics, University of Würzburg, Würzburg, Germany
| | - Sandra M Blois
- Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Charité-Universitätsmedizin Berlin, Berlin, Germany
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8
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Zhang Z, Kang X, Guo Y, Zhang J, Xie J, Shao S, Xiang Y, Chen G, Yu X. Association of circulating galectin-3 with gestational diabetes mellitus, progesterone, and insulin resistance. J Diabetes 2021; 13:54-62. [PMID: 32671973 DOI: 10.1111/1753-0407.13088] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 06/05/2020] [Accepted: 07/11/2020] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND/OBJECTIVE Because galectin-3 has been proposed to regulate obesity and insulin resistance in mice, we hypothesized that circulating galectin-3 levels are associated with presence of gestational diabetes mellitus (GDM), progesterone, and insulin resistance. METHODS Circulating galectin-3 levels were measured using an enzyme-linked immunosorbent assay (ELISA) in women with GDM (n = 137) and their controls (n = 81). Associations of galectin-3 and progesterone with GDM and insulin resistance were evaluated using regression models. RESULTS Circulating galectin-3 levels were increased in the individuals with GDM (P < .001) and associated significantly with progesterone (r = 0.42, P < .001), gestational age at sampling (r = 0.23, P < .001), current body mass index (BMI; r = 0.17, P = .02), estrogen (r = 0.15, P < .03), fasting glucose (r = 0.41, P < .001), fasting insulin (r = 0.39, P < .001), and homeostasis model assessment of insulin resistance (HOMA-IR; r = 0.44, P < .001). After adjustment for potential confounders, including current BMI, subjects in the highest tertile of galectin-3 levels were more likely to have GDM (odds ratio 4.71, 95% confidence interval 2.01-11.06) as compared with the lowest tertile. The association between circulating galectin-3 levels and GDM remained significant after adjusting for progesterone, but significantly attenuated after adjustment with HOMA-IR. Furthermore, the multiple linear regression analyses after adjustment for confounders showed an independent association between galectin-3 levels and HOMA-IR (β = .41, P < .001), suggesting that association of circulating gelactin-3 levels with GDM might be mediated via insulin resistance. Progesterone demonstrated the expected associations with galectin-3, GDM, and HOMA-IR. CONCLUSIONS Circulating galectin-3 levels are associated with GDM possibly through increased insulin resistance. The association of galectin-3 with progesterone highlights a potential role of progesterone in its interaction with galectin-3.
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Affiliation(s)
- Zeqing Zhang
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xuehui Kang
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yaming Guo
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jianhua Zhang
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Junhui Xie
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shiying Shao
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ying Xiang
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China
- Key Laboratory of Organ Transplantation, Ministry of Public Health, Wuhan, China
| | - Gang Chen
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China
- Key Laboratory of Organ Transplantation, Ministry of Public Health, Wuhan, China
| | - Xuefeng Yu
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Alves MT, de Souza IDP, Ferreira CN, Cândido AL, Bizzi MF, Oliveira FR, Reis FM, Gomes KB. Galectin-3 is a potential biomarker to insulin resistance and obesity in women with polycystic ovary syndrome. Gynecol Endocrinol 2020; 36:760-763. [PMID: 32157924 DOI: 10.1080/09513590.2020.1739267] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder that affects women in reproductive age. This study aimed to evaluate Gal-3 levels and its role on metabolic parameters in women with PCOS. Gal-3 was measured in 44 PCOS and 25 women recruited as control group for the case-control study. Gal-3 levels were similar between PCOS and control groups (p > 0.05), but showed a positive correlation with glucose levels in the oral glucose tolerance test (OGTT) (r = 0.403, p = 0.037), body mass index (BMI) (r = 0.469, p = 0.027), insulin levels (r = 0.453, p = 0.030) and HOMA-IR (r = 0.738, p = 0.037) in PCOS group. The data suggest that Gal-3 plays a role in the pathophysiology of the insulin resistance and obesity in PCOS group.
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Affiliation(s)
- Michelle T Alves
- Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Cláudia N Ferreira
- Colégio Técnico, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Ana Lúcia Cândido
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Mariana F Bizzi
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Flávia R Oliveira
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Maternidade Odete Valadares - Fundação Hospitalar do Estado de Minas Gerais, Belo Horizonte, Brazil
| | - Fernando M Reis
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Karina B Gomes
- Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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10
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Investigation of galectin-3, lipocalin 2, retinol binding protein (RBP), small dense low-density lipoprotein (sdLDL) in patients with hirsutism. Postepy Dermatol Alergol 2019; 36:177-183. [PMID: 31320851 PMCID: PMC6627252 DOI: 10.5114/ada.2019.84593] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Accepted: 01/12/2018] [Indexed: 12/02/2022] Open
Abstract
Introduction Hirsutism is defined as excessive terminal hair in androgen-dependent areas in women. Adipose tissue is no longer regarded as a storage site for triglycerides or as a source of free fatty acids but is currently emerging as a key constituent of energy metabolism secreting numerous enzymes, cytokines, growth factors, and hormones. Aim To evaluate serum levels of galectin-3 (Gal3), lipocalin-2 (LCN2), retinol binding protein (RBP), and small dense low-density lipoprotein (sdLDL) in patients with hirsutism and patients co-presenting with polycystic ovary syndrome (PCOS) and hirsutism. Material and methods The study included 90 patients that were divided into three groups: (I) patients with idiopathic hirsutism (IH) (n = 30), (II) PCOS patients with hirsutism (H-PCOS) (n = 30), and (III) the control group (n = 30). Informed consent was obtained from each participant. Idiopathic hirsutism was scored using the modified Ferriman-Gallwey (mFG) scoring system and the diagnosis of PCOS was established based on the modified Rotterdam criteria. Human Gal3, LCN2, RBP, and sdLDL levels were analysed using a commercially available double-antigen sandwich enzyme-linked immunosorbent assay. Results No significant difference was found between the three groups with regard to serum Gal3, LCN2, RBP, and sdLDL levels (p > 0.05). Median values were higher in the H-PCOS group than in the other two groups: body weight (median: 76.5 kg) (p < 0.001), waist circumference (median: 82.5 cm) (p = 0.001). Conclusions No significant correlation was found between the adipokines that play a role in the aetiology of numerous diseases and some mediators of the lipid metabolism and hirsutism.
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Cao MY, Wang J, Gao XL, Hu YB. Serum galectin-3 concentrations in patients with ankylosing spondylitis. J Clin Lab Anal 2019; 33:e22914. [PMID: 31106498 PMCID: PMC6642303 DOI: 10.1002/jcla.22914] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Revised: 04/15/2019] [Accepted: 04/23/2019] [Indexed: 12/18/2022] Open
Abstract
Objective The aim of our study was to assess potential correlations between serum galectin‐3 concentrations and Ankylosing Spondylitis Disease Activity (ASDAS) index in patients with ankylosing spondylitis (AS). Methods A total of 112 patients with AS were included, and 130 healthy subjects were considered as controls. We collected the detailed medical history, and ASDAS index was used to assess the disease severity in patients with AS. Results The serum galectin concentrations were higher in AS patients compared to the health groups (14.1 ± 9.6 vs 9.2 ± 3.7, P < 0.001). The correlation analysis showed that serum galectin concentrations were significantly positively correlated with C‐reactive protein and erythrocyte sedimentation rate (r = 0.369, P < 0.001; r = 0.240, P = 0.011). In addition, the positively correlation of serum galectin‐3 with global pain index (r = 0.238, P = 0.011) was observed in AS patients. A significant positively correlation between serum galectin and ASDAS index in AS patients was found (r = 0.367; P < 0.001). In multiple linear regression analysis, the results indicated that increased serum galectin still was correlated with ASDAS index (r = 0.322, P < 0.001) in patients with AS. Conclusions Serum galectin concentrations were found to be correlated with ASDAS index in patients with AS.
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Affiliation(s)
- Ming-Yu Cao
- Department of Joint Surgery, Sixth Affiliated Hospital of Xinjiang Medical University, Ürümqi, China
| | - Jiang Wang
- Department of Traumatic Orthopaedics, Sixth Affiliated Hospital of Xinjiang Medical University, Ürümqi, China
| | - Xiao-Liang Gao
- Department of Spine Surgery, Sixth Affiliated Hospital of Xinjiang Medical University, Ürümqi, China
| | - Ya-Bin Hu
- Department of Spine Surgery, The Second Hospital of Nanjing, Nanjing, China
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12
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Anik Ilhan G, Kanlioglu C, Arslan G, Yildizhan B, Pekin T. Galectin-3 as a novel biomarker in women with PCOS. Arch Gynecol Obstet 2018; 298:821-825. [DOI: 10.1007/s00404-018-4862-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Accepted: 07/28/2018] [Indexed: 12/18/2022]
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Pang J, Nguyen VT, Rhodes DH, Sullivan ME, Braunschweig C, Fantuzzi G. Relationship of galectin-3 with obesity, IL-6, and CRP in women. J Endocrinol Invest 2016; 39:1435-1443. [PMID: 27444618 DOI: 10.1007/s40618-016-0515-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Accepted: 07/12/2016] [Indexed: 01/07/2023]
Abstract
PURPOSE To evaluate the association of galectin-3 (Gal3) with obesity and inflammatory status in a cohort of metabolically healthy, predominantly African-American women with varying cardiovascular disease (CVD) risk as determined by CRP levels. METHODS We assessed the association between BMI and serum levels of Gal3, IL-6, CRP, and adiponectin in metabolically healthy women (N = 97) to determine the overall association between Gal3, obesity, and inflammation in groups at different CVD risk. RESULTS Obese women had significantly higher serum Gal3 compared to non-obese participants (P = 0.0016), although Gal3 levels were comparable among different classes of obesity. BMI (R 2 = 0.1406, P = 0.0013), IL-6 (R 2 = 0.0689, P = 0.035), and CRP (R 2 = 0.0468, P = 0.0419), but not adiponectin, positively predicted the variance of Gal3 levels in the total study population. However, the predicting effect of BMI (R 2 = 0.2923, P = 0.0125) and inflammation (R 2 = 0.3138, P = 0.038) on Gal3 was only present in women at low/moderate risk of CVD (CRP ≤ 3 µg/mL). CONCLUSIONS Gal3 is positively correlated with obesity and inflammation in women, while the presence of elevated CVD risk may disturb the strength of Gal3 as a biomarker of inflammation.
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Affiliation(s)
- J Pang
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, 1919 W Taylor Street, Chicago, IL, 60612, USA
| | - V T Nguyen
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, 1919 W Taylor Street, Chicago, IL, 60612, USA
| | - D H Rhodes
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, 1919 W Taylor Street, Chicago, IL, 60612, USA
| | - M E Sullivan
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, 1919 W Taylor Street, Chicago, IL, 60612, USA
| | - C Braunschweig
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, 1919 W Taylor Street, Chicago, IL, 60612, USA
| | - G Fantuzzi
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, 1919 W Taylor Street, Chicago, IL, 60612, USA.
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14
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Karakose M, Demircan K, Tutal E, Demirci T, Arslan MS, Sahin M, Celik HT, Kazanci F, Karakaya J, Cakal E, Delibasi T. Clinical significance of ADAMTS1, ADAMTS5, ADAMTS9 aggrecanases and IL-17A, IL-23, IL-33 cytokines in polycystic ovary syndrome. J Endocrinol Invest 2016; 39:1269-1275. [PMID: 27146815 DOI: 10.1007/s40618-016-0472-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Accepted: 04/17/2016] [Indexed: 12/18/2022]
Abstract
PURPOSE Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) are involved in inflammation and fertility. The aim of this investigation was to evaluate the serum levels of ADAMTS1, ADAMTS5, ADAMTS9, IL-17, IL-23, IL-33 and to find out the relationship between these inflammatory cytokines and ADAMTSs in PCOS patients. METHODS A case-control study was performed in a training and research hospital. Eighty patients with PCOS and seventy-eight healthy female volunteers were recruited in the present study. Serum ADAMTS and IL levels were determined by a human enzyme-linked immunoassay (ELISA) in all subjects. RESULTS The IL-17A, IL-23 and IL-33 levels were significantly higher in the PCOS patients compared to the controls (p < 0.05). We could not find significant difference between the groups in terms of ADAMTS1, ADAMTS5 and ADAMTS9 levels. IL-17A had positive correlations with LDL cholesterol and IL-33 and negative correlations with ADAMTS1, ADAMTS5, and ADAMTS9. IL-33 had positive correlation with LDL cholesterol and IL-17A. In ROC curve analysis, PCOS can be predicted by the use of IL-17A, IL-23 and IL-33 which at a cut-off value of 8.37 pg/mL (44 % sensitivity, 83 % specificity), 26.75 pg/mL (36 % sensitivity, 64 % specificity) and 14.28 pg/mL (83 % sensitivity, 39 % specificity), respectively. CONCLUSIONS The results of the study might suggest that ADAMTS and IL molecules have a role in the pathogenesis of the PCOS. Further efforts are needed to establish causality for ADAMTS-IL axis.
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Affiliation(s)
- M Karakose
- Department of Endocrinology and Metabolism, Diskapi Yildirim Beyazit Training and Research Hospital, Irfan Bastug Caddesi, 06110, Ankara, Turkey.
| | - K Demircan
- Department of Medical Biology, Turgut Ozal University School of Medicine, Gimat, Ankara, Turkey
| | - E Tutal
- Department of Endocrinology and Metabolism, Diskapi Yildirim Beyazit Training and Research Hospital, Irfan Bastug Caddesi, 06110, Ankara, Turkey
| | - T Demirci
- Department of Endocrinology and Metabolism, Diskapi Yildirim Beyazit Training and Research Hospital, Irfan Bastug Caddesi, 06110, Ankara, Turkey
| | - M S Arslan
- Department of Endocrinology and Metabolism, Diskapi Yildirim Beyazit Training and Research Hospital, Irfan Bastug Caddesi, 06110, Ankara, Turkey
| | - M Sahin
- Department of Endocrinology and Metabolism, Ankara University, School of Medicine, Ankara, Turkey
| | - H T Celik
- Department of Biochemistry, Turgut Ozal University School of Medicine, Gimat, Ankara, Turkey
| | - F Kazanci
- Department of Biochemistry, Turgut Ozal University School of Medicine, Gimat, Ankara, Turkey
| | - J Karakaya
- Department of Biostatistics, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, Turkey
| | - E Cakal
- Department of Endocrinology and Metabolism, Diskapi Yildirim Beyazit Training and Research Hospital, Irfan Bastug Caddesi, 06110, Ankara, Turkey
| | - T Delibasi
- Department of Endocrinology and Metabolism, Diskapi Yildirim Beyazit Training and Research Hospital, Irfan Bastug Caddesi, 06110, Ankara, Turkey
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Harazono Y, Kho DH, Balan V, Nakajima K, Hogan V, Raz A. Extracellular galectin-3 programs multidrug resistance through Na+/K+-ATPase and P-glycoprotein signaling. Oncotarget 2016; 6:19592-604. [PMID: 26158764 PMCID: PMC4637307 DOI: 10.18632/oncotarget.4285] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Accepted: 06/05/2015] [Indexed: 01/21/2023] Open
Abstract
Galectin-3 (Gal-3, LGALS3) is a pleotropic versatile, 29-35 kDa chimeric gene product, and involved in diverse physiological and pathological processes, including cell growth, homeostasis, apoptosis, pre-mRNA splicing, cell-cell and cell-matrix adhesion, cellular polarity, motility, adhesion, activation, differentiation, transformation, signaling, regulation of innate/adaptive immunity, and angiogenesis. In multiple diseases, it was found that the level of circulating Gal-3 is markedly elevated, suggesting that Gal-3-dependent function is mediated by specific interaction with yet an unknown ubiquitous cell-surface protein. Recently, we showed that Gal-3 attenuated drug-induced apoptosis, which is one of the mechanisms underlying multidrug resistance (MDR). Here, we document that MDR could be mediated by Gal-3 interaction with the house-keeping gene product e.g., Na+/K+-ATPase, and P-glycoprotein (P-gp). Gal-3 interacts with Na+/K+-ATPase and induces the phosphorylation of P-gp. We also find that Gal-3 binds P-gp and enhances its ATPase activity. Furthermore Gal-3 antagonist suppresses this interaction and results in a decrease of the phosphorylation and the ATPase activity of P-gp, leading to an increased sensitivity to doxorubicin-mediated cell death. Taken together, these findings may explain the reported roles of Gal-3 in diverse diseases and suggest that a combined therapy of inhibitors of Na+/K+-ATPase and Gal-3, and a disease specific drug(s) might be superior to a single therapeutic modality.
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Affiliation(s)
- Yosuke Harazono
- Departments of Oncology and Pathology, School of Medicine, Wayne State University, and Karmanos Cancer Institute, Detroit, MI 48201, USA.,Department of Maxillofacial Surgery, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
| | - Dhong Hyo Kho
- Departments of Oncology and Pathology, School of Medicine, Wayne State University, and Karmanos Cancer Institute, Detroit, MI 48201, USA
| | | | - Kosei Nakajima
- Departments of Oncology and Pathology, School of Medicine, Wayne State University, and Karmanos Cancer Institute, Detroit, MI 48201, USA
| | - Victor Hogan
- Departments of Oncology and Pathology, School of Medicine, Wayne State University, and Karmanos Cancer Institute, Detroit, MI 48201, USA
| | - Avraham Raz
- Departments of Oncology and Pathology, School of Medicine, Wayne State University, and Karmanos Cancer Institute, Detroit, MI 48201, USA
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Cai G, Ma X, Chen B, Huang Y, Liu S, Yang H, Zou W. Galectin-3 induces ovarian cancer cell survival and chemoresistance via TLR4 signaling activation. Tumour Biol 2016; 37:11883-11891. [DOI: 10.1007/s13277-016-5038-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 03/28/2016] [Indexed: 02/07/2023] Open
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Yilmaz H, Cakmak M, Inan O, Darcin T, Akcay A. Increased levels of galectin-3 were associated with prediabetes and diabetes: new risk factor? J Endocrinol Invest 2015; 38:527-33. [PMID: 25501605 DOI: 10.1007/s40618-014-0222-2] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Accepted: 11/23/2014] [Indexed: 12/20/2022]
Abstract
PURPOSE Galectin-3 (Gal-3) is a marker of cardiac fibrosis and predicts incident heart failure. Gal-3-deficient mice are resistant to multiple low-dose streptozotocin-induced diabetes. Recent experimental studies suggested an important role for Gal-3 in the regulation of adiposity, metaflammation and type 2 diabetes. This study aimed to examine the relationship between Gal-3 and newly diagnosed prediabetes and diabetes. METHODS Gal-3 concentrations were measured in 118 participants and 56 age- and sex-matched healthy controls. All subjects underwent a 75-g oral glucose tolerance test and were stratified into normal, prediabetic, and diabetes mellitus subgroups. DM was defined as a plasma glucose level ≥126 mg/dL in the fasting state or ≥200 mg/dL in the second hour after glucose loading. Impaired fasting glucose was defined as an FPG level of 100-125 mg/dL, and impaired glucose tolerance was defined as a 2-h plasma glucose level of 140-199 mg/dL. RESULTS Sixty-one patients had prediabetes (Group 1), 57 had diabetes (Group 2), and 56 had neither diabetes nor prediabetes (Group 3). Gal-3 levels correlated with FPG (r = 0.787, P < 0.01), 2hPG (r = 0.833, P < 0.01), CRP (r = 0.501, P < 0.01), and HOMA-IR (r = 0.518, P < 0.01). Gal-3 levels were higher in Group 2 than in Groups 1 and 3 [1,053.9 (358.1) and 744.1 (119.3) vs. 481.7 (175.4) pg/mL; P < 0.001]. Gal-3 is an independent predictor of diabetes in multivariate logistic analysis. In ROC analysis, a Gal-3 cutoff value of 803.55 pg/mL diagnoses diabetes with a sensitivity of 80.7 % and a specificity of 85.5 % (AUC = 0.912). CONCLUSIONS Gal-3 is a promising biomarker for detecting prediabetes and diabetes.
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Affiliation(s)
- H Yilmaz
- Department of Internal Medicine, School of Medicine, Turgut Ozal University, Alparslan Türkes Cad. No: 57, 06510, Emek, Ankara, Turkey.
| | - M Cakmak
- Department of Internal Medicine, Turgut Ozal University, School of Medicine, Ankara, Turkey
| | - O Inan
- Yenimahalle State Hospital, Ankara, Turkey
| | - T Darcin
- Agrı State Hospital, Agrı, Turkey
| | - A Akcay
- Department of Internal Medicine, School of Medicine, Turgut Ozal University, Alparslan Türkes Cad. No: 57, 06510, Emek, Ankara, Turkey
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