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      The Importance of Metabolic Factors in Endometrial Cancer: Evaluating the Utility of the Triglyceride-to-Glycemia Index and Triglyceride-to-High-Density Lipoprotein Ratio As Biomarkers

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          Abstract

          Introduction

          Endometrial cancer (EC) is the most common gynecological malignancy in developed countries worldwide. Its incidence is rising, making it a significant public health concern. The relationship between lipids, hyperglycemia, and anthropometric risk factors in the development of EC has gained increasing attention in recent years. Understanding the role of dyslipidemia as a part of metabolic syndrome is crucial for developing effective prevention and treatment strategies for EC. We investigate the association between dyslipidemia, hyperglycemia, and EC. This study aims to elucidate the potential contribution of altered lipid profiles and chronic hyperglycemia to endometrial carcinogenesis. By analyzing patients with benign and malignant endometrial pathologies, we seek to identify novel biomarkers and unravel the underlying mechanisms by which these metabolic factors influence the risk of developing EC.

          Material and methods

          Our retrospective unicentric study included 390 patients (192 diagnosed with EC and 198 with endometrial hyperplasia), in which we compared the clinical and biochemical characteristics, with a particular focus on lipid profiles and glycemic indices sampled 24-48 hours before surgery. The data obtained from the medical records were analyzed using statistical methods to compare selected metabolic factors between EC and endometrial hyperplasia.

          Results

          Our analysis revealed statistically significant differences in metabolic health and lipid profiles between patients diagnosed with EC and those with endometrial hyperplasia. The EC group exhibits trends towards higher levels of triglycerides (TG) and glycated hemoglobin, alongside a higher BMI. Notably, high-density lipoprotein cholesterol levels were lower in the EC group.

          Conclusion

          Although the triglycerides-to-fasting blood glucose index and the triglycerides-to-high-density lipoprotein cholesterol ratio did not demonstrate sufficient discriminatory power for predicting myometrial invasion depth in this study, further exploration of cost-effective emerging biomarkers warrants investigation in future studies.

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          Most cited references29

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          Diabetes mellitus and risk of endometrial cancer: a meta-analysis.

          E. Friberg, N Orsini, C Mantzoros … (2007)
          Diabetes has been associated with a statistically significantly increased risk of endometrial cancer in most, but not all studies. To provide a quantitative assessment of the association between diabetes and risk of endometrial cancer, we conducted a meta-analysis of case-control studies and cohort studies. We identified studies by a literature search of PubMed and Embase through to January 2007 and by searching the reference lists of relevant articles. Summary relative risks (RRs) with 95% CIs were calculated using random-effects model. The analysis of diabetes (largely type 2) and endometrial cancer is based on 16 studies (three cohort and 13 case-control studies), including 96,003 participants and 7,596 cases of endometrial cancer. Twelve of the studies showed a statistically significantly increased risk and four a non-significant increased risk of endometrial cancer. In our meta-analysis we found that diabetes was statistically significantly associated with an increased risk of endometrial cancer (summary RR 2.10, 95% CI 1.75-2.53). The risk estimates were somewhat stronger among case-control (RR 2.22, 95% CI 1.80-2.74) than among cohort studies (RR 1.62, 95% CI 1.21-2.16), stronger among studies adjusting only for age (RR 2.74, 95% CI 1.87-4.00) compared with multivariate adjustment (RR 1.92, 95% CI 1.58-2.33) and slightly lower in studies performed in the USA than in those performed Europe. The analysis of type 1 diabetes and endometrial cancer was based on three studies and found a statistically significant positive association (summary RR 3.15, 95%CI 1.07-9.29). Results from the meta-analysis support a relationship between diabetes and increased risk of endometrial cancer.
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            Surrogate markers of insulin resistance: A review.

            Bhawna Singh, Alpana Saxena (2010)
            Insulin resistance is a hallmark of obesity, diabetes, and cardiovascular diseases, and leads to many of the abnormalities associated with metabolic syndrome. Our understanding of insulin resistance has improved tremendously over the years, but certain aspects of its estimation still remain elusive to researchers and clinicians. The quantitative assessment of insulin sensitivity is not routinely used during biochemical investigations for diagnostic purposes, but the emerging importance of insulin resistance has led to its wider application research studies. Evaluation of a number of clinical states where insulin sensitivity is compromised calls for assessment of insulin resistance. Insulin resistance is increasingly being assessed in various disease conditions where it aids in examining their pathogenesis, etiology and consequences. The hyperinsulinemic euglycemic glucose clamp is the gold standard method for the determination of insulin sensitivity, but is impractical as it is labor- and time-intensive. A number of surrogate indices have therefore been employed to simplify and improve the determination of insulin resistance. The object of this review is to highlight various aspects and methodologies for current and upcoming measures of insulin sensitivity/resistance. In-depth knowledge of these markers will help in better understanding and exploitation of the condition.
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              Cholesterol and breast cancer risk: a systematic review and meta-analysis of prospective studies.

              Mathilde Touvier, Philippine Fassier, Mathilde His … (2015)
              The objective of the present study was to conduct the first systematic review and meta-analysis of prospective studies investigating the associations between total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels and the risk of breast cancer. Relevant studies were identified in PubMed (up to January 2014). Inclusion criteria were original peer-reviewed publications with a prospective design. Random-effects models were used to estimate summary hazard ratios (HR) and 95% CI. Distinction was made between studies that did or did not exclude cancer cases diagnosed during the first years of follow-up, thereby eliminating potential preclinical bias. Overall, the summary HR for the association between TC and breast cancer risk was 0.97 (95% CI 0.94, 1.00; dose-response per 1 mmol/l increment, thirteen studies), and that between HDL-C and breast cancer risk was 0.86 (95% CI 0.69, 1.09; dose-response per 1 mmol/l increment, six studies), with high heterogeneity (I2= 67 and 47%, respectively). For studies that eliminated preclinical bias, an inverse association was observed between the risk of breast cancer and TC (dose-response HR 0.94 (95% CI 0.89, 0.99), seven studies, I2= 78%; highest v. lowest HR 0.82 (95% CI 0.66, 1.02), nine studies, I2= 81%) and HDL-C (dose-response HR 0.81 (95% CI 0.65, 1.02), five studies, I2= 30 %; highest v. lowest HR 0.82 (95% CI 0.69, 0.98), five studies, I2= 0%). There was no association observed between LDL-C and the risk of breast cancer (four studies). The present meta-analysis confirms the evidence of a modest but statistically significant inverse association between TC and more specifically HDL-C and the risk of breast cancer, supported by mechanistic plausibility from experimental studies. Further large prospective studies that adequately control for preclinical bias are needed to confirm the results on the role of cholesterol level and its fractions in the aetiology of breast cancer.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cureus
                Journal ID (iso-abbrev): Cureus
                Journal ID (issn): 2168-8184
                Title: Cureus
                Publisher: Cureus (Palo Alto (CA) )
                ISSN (Electronic): 2168-8184
                Publication date (Electronic, pub): 10 June 2024
                Publication date (Electronic, collection): June 2024
                Volume: 16
                Issue: 6
                Electronic Location Identifier: e62099
                Affiliations
                [1 ] Obstetrics and Gynaecology, Elias Emergency University Hospital, Bucharest, ROU
                [2 ] Obstetrics and Gynaecology, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
                Author notes
                Article
                DOI: 10.7759/cureus.62099
                PMC ID: 11236432
                PubMed ID: 38989325
                SO-VID: 9f8fa6e5-5885-487f-b4cd-d2b45f17125e
                Copyright © Copyright © 2024, Marin et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date accepted : 10 June 2024
                Categories
                Subject: Endocrinology/Diabetes/Metabolism
                Subject: Epidemiology/Public Health
                Subject: Obstetrics/Gynecology

                Keywords: triglycerides-to-high density lipoprotein cholesterol ratio,triglycerides-fasting blood glucose index,lipid profile,endometrial hyperplasia,endometrial cancer
                Data availability:
                Keywords: triglycerides-to-high density lipoprotein cholesterol ratio, triglycerides-fasting blood glucose index, lipid profile, endometrial hyperplasia, endometrial cancer

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