Diabetes mellitus and endometrial carcinoma: Risk factors and etiological links

Wang, Ya; Zeng, Xinling; Tan, Jie; Xu, Yi; Yi, Cunjian

doi:10.1097/md.0000000000030299

Cited by 11 publications

(6 citation statements)

References 72 publications

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“…26 Elevated blood glucose levels and insulin resistance, commonly observed in individuals with diabetes, may contribute to the development and poor survival outcomes of EC, which may also affect the outcomes of conservative treatment for endometrial hyperplasia and early EC. 27,28 However, hypertension was not an independent risk factor for EC in our study, possibly due to the small sample size and selection bias.…”

Section: Discussioncontrasting

confidence: 57%

Triage method for endometrial biopsy in postmenopausal women: a multicenter retrospective cohort study

Shen,

Li,

Wang

et al. 2023

Menopause

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Objective To identify the optimal triage procedure for endometrial biopsies in postmenopausal women. Methods The clinical information of 470 postmenopausal women with endometrial biopsy results and postmenopausal bleeding (PMB) and/or transvaginal ultrasonography (TVU) abnormalities were collected at the gynecology departments of four general hospitals from March 2021 to March 2022. In the validation cohort, 112 women with TVU abnormalities who underwent endometrial biopsy at Xiangya hospital between May 2022 and May 2023 were enrolled. The endpoint was the final diagnosis based on hysteroscopy reports and biopsy pathology results. The sensitivity, specificity, positive predictive value, and negative predictive value were compared among the three triage methods. A nomogram prediction model was developed and validated. Results Referring women with TVU abnormalities for endometrial biopsy identified 100% malignant/premalignant lesions despite low specificity (19.7%). Among women with measurable endometrial thickness (ET), we suggest that the ET cutoff value for biopsy referral should be ≥4 mm. The PMB (odds ratio [OR], 3.241; 95% confidence interval [CI], 1.073-9.789), diabetes (OR, 10.915; 95% CI, 3.389-35.156), and endometrial thickness (OR, 1.277; 95% CI, 1.156-1.409) were independent predictive factors for endometrial (pre)malignancy. A nomogram prediction model was constructed (area under curve [AUC] = 0.802, 95% CI: 0.715 to 0.889). The ideal cutoff point was 22.5, with a sensitivity of 100.0% and a specificity of 15.7%. The external validation achieved an AUC of 0.798 (95% CI, 0.685-0.911). Conclusions It was possible to refer all postmenopausal women with TVU abnormity (ET ≥ 4 mm or other abnormal findings) for endometrial biopsy. Among women with TVU abnormalities, a nomogram was constructed, and a score greater than 22.5 suggested the need for referral for endometrial biopsy, while a score less than 22.5 suggested that regular follow-up was required, further improving the triage procedure.

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Section: Discussioncontrasting

confidence: 57%

Triage method for endometrial biopsy in postmenopausal women: a multicenter retrospective cohort study

Shen,

Li,

Wang

et al. 2023

Menopause

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“…Moreover, obesity (especially the visceral phenotype) is frequently complicated by insulin-resistance and type 2 diabetes, known as potential contributors to EC onset. 7 This makes obesity a significant risk factor for women's health, as it increases the likelihood of developing EC in addition to other types of cancer. EC development related to hyperstrogenism is a multistep process, starting from precancerous lesions (atypical hyperplasia) and progressing to invasive tumors.…”

Section: Introductionmentioning

confidence: 99%

“…Obesity and hyperestrogenism related to adipose tissue promote a pro‐inflammatory state that pushes endometrial proliferation, with accumulation of somatic genetic alterations, predisposing to the malignant transformation. Moreover, obesity (especially the visceral phenotype) is frequently complicated by insulin‐resistance and type 2 diabetes, known as potential contributors to EC onset 7 . This makes obesity a significant risk factor for women's health, as it increases the likelihood of developing EC in addition to other types of cancer.…”

Section: Introductionmentioning

confidence: 99%

miRNA levels are associated with body mass index in endometrial cancer and may have implications for therapy

Ravegnini,

Gorini,

Coada

et al. 2024

Cancer Science

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Endometrial cancer (EC) is the most prevalent gynecological cancer in high‐income countries. Its incidence is skyrocketing due to the increase in risk factors such as obesity, which represents a true pandemic. This study aimed to evaluate microRNA (miRNA) expression in obesity‐related EC to identify potential associations between this specific cancer type and obesity. miRNA levels were analyzed in 84 EC patients stratified based on body mass index (BMI; ≥30 or <30) and nine noncancer women with obesity. The data were further tested in The Cancer Genome Atlas (TCGA) cohort, including 384 EC patients, 235 with BMI ≥30 and 149 with BMI <30. Prediction of miRNA targets and analysis of their expression were also performed to identify the potential epigenetic networks involved in obesity modulation. In the EC cohort, BMI ≥30 was significantly associated with 11 deregulated miRNAs. The topmost deregulated miRNAs were first analyzed in 84 EC samples by single miRNA assay and then tested in the TCGA dataset. This independent validation provided further confirmation about the significant difference of three miRNAs (miR‐199a‐5p, miR‐449a, miR‐449b‐5p) in normal‐weight EC patients versus EC patients with obesity, resulting significantly higher expressed in the latter. Moreover, the three miRNAs were significantly correlated with grade, histological type, and overall survival. Analysis of their target genes revealed that these miRNAs may regulate obesity‐related pathways. In conclusion, we identified specific miRNAs associated with BMI that are potentially involved in modulating obesity‐related pathways and that may provide novel implications for the clinical management of obese EC patients.

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“…As a result, metabolic alterations detected in cancer and diabetes could contribute to finding more beneficial treatment options. 32 Moreover, the changes in LCAT activity and concomitant lipid profile in EC or EC and concurrent type 2 diabetes, as well as ox-LDL in patients with EC and concurrent type 2 diabetes, have not been fully studied. 28 Studying these factors may be beneficial to discover new elements contributing to the pathogenesis of EC and diabetes.…”

Section: Introductionmentioning

confidence: 99%

“…Considering the increased risk of EC in diabetes, 31 several underlying mechanisms, such as high‐glucose environment, signaling pathway activation, and chronic inflammation, are hypothesized. As a result, metabolic alterations detected in cancer and diabetes could contribute to finding more beneficial treatment options 32 . Moreover, the changes in LCAT activity and concomitant lipid profile in EC or EC and concurrent type 2 diabetes, as well as ox‐LDL in patients with EC and concurrent type 2 diabetes, have not been fully studied 28 .…”

Section: Introductionmentioning

confidence: 99%

Lipid profile, ox‐LDL, and LCAT activity in patients with endometrial carcinoma and type 2 diabetes: The effect of concurrent disease based on a case–control study

Qahremani,

Rabizadeh,

Mirmiranpoor

et al. 2023

Health Science Reports

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Background and AimThe role of lecithin: cholesterol acyltransferase (LCAT) and oxidized low‐density lipoprotein (ox‐LDL) in endometrial cancer (EC) or EC with concurrent type 2 diabetes is still unclear. This study investigated the LCAT activity, ox‐LDL, and lipid profile in EC patients with or without type 2 diabetes and compared them with healthy individuals and patients with type 2 diabetes alone.MethodsIn this cross‐sectional, case–control study, 93 female participants were recruited. The participants were divided into four groups, including EC with type 2 diabetes (n = 19), EC without type 2 diabetes (n = 17), type 2 diabetes (n = 31), and healthy controls (n = 26). Sociodemographic information, the LCAT activity, triglyceride (TG), total cholesterol, high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), and ox‐LDL levels were collected. One‐way analysis of variance and analysis of covariance, Student's t‐test, Mann–Whitney U‐test, and χ2‐test were used to compare demographic features and laboratory results among studied groups. Regression analyses were also performed to evaluate the interaction effect between EC and type 2 diabetes on serum LCAT activity.ResultsThe LCAT activity was significantly lower, and ox‐LDL levels were significantly higher in all patient groups compared to the healthy controls (p < 0.001). EC patients had significantly lower LCAT activity and higher ox‐LDL levels than type 2 diabetes and healthy groups (p < 0.05). Higher levels of TG and lower levels of HDL‐C were observed in all patient groups compared to the healthy group (all p < 0.001). Patients with EC and concomitant type 2 diabetes had significantly lower serum LDL‐C levels than healthy and type 2 diabetes groups (p < 0.05).ConclusionsThe combination of EC and type 2 diabetes had a subadditive effect on LCAT activity and ox‐LDL level. The lowest LCAT activity and the highest ox‐LDL levels were observed in patients with EC and concurrent type 2 diabetes.

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Diabetes mellitus and endometrial carcinoma: Risk factors and etiological links

Cited by 11 publications

References 72 publications

Triage method for endometrial biopsy in postmenopausal women: a multicenter retrospective cohort study

Triage method for endometrial biopsy in postmenopausal women: a multicenter retrospective cohort study

miRNA levels are associated with body mass index in endometrial cancer and may have implications for therapy

Lipid profile, ox‐LDL, and LCAT activity in patients with endometrial carcinoma and type 2 diabetes: The effect of concurrent disease based on a case–control study

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