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      Association of Circulating Carbohydrate Antigen 19-9 Level with Type 2 Diabetic Kidney Disease in Chinese Adults: A Cross-Sectional Study

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          Abstract

          Objective

          Very few and conflicting data are available regarding the correlation between circulating carbohydrate antigen 19-9 (CA19-9) levels and diabetic kidney disease (DKD) and its components including albuminuria and a low estimated glomerular filtration rate (eGFR). This study aimed to examine the association of circulating CA19-9 and DKD in Chinese patients with type 2 diabetes mellitus (T2DM).

          Methods

          A total of 402 hospitalized T2DM patients between September 2017 and December 2021 were included in this cross-sectional study. There were 224 and 178 subjects in non-DKD and DKD groups, respectively. Serum CA19-9 was measured by chemiluminescence method, and its potential relationship with DKD was evaluated by multivariate logistic regression and correlation analyses, and receiver operating characteristic (ROC) curve analysis.

          Results

          T2DM patients with DKD had significantly higher serum CA19-9 levels than those without, and serum CA19-9 levels were positively related to urinary albumin-to-creatinine ratio and negatively to eGFR ( P<0.01). Multivariate regression analysis revealed that serum CA 19-9 was an independent factor of DKD [odds ratio (OR), 1.018; 95% confidence interval (CI), 1.002–1.035; P<0.05]. Moreover, an increased progressively risk of DKD with an increase in serum CA19-9 quartiles was observed ( P for trend <0.001), and T2DM patients in the highest serum CA19-9 quartile were associated with an increased likelihood of DKD when compared to those in the lowest quartile (OR: 2.936, 95% CI 1.129–7.633, P<0.05). Last, the analysis of ROC curves suggested that serum CA 19-9 at a cut of 25.09 U/mL resulted in the highest Youden index with sensitivity 43.8% and 75.4% specificity to predict the presence of DKD.

          Conclusion

          These results showed that high circulating CA19-9 was related to DKD and may serve as a useful biomarker of DKD in hospitalized Chinese T2DM patients.

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          Most cited references46

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          A new equation to estimate glomerular filtration rate.

          Andrew Levey, Lesley Stevens, Christopher H Schmid … (2009)
          Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.
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            Diagnostic and prognostic value of CEA, CA19–9, AFP and CA125 for early gastric cancer

            Fan Feng, Yangzi Tian, Guanghui Xu … (2017)
            Background The diagnostic and prognostic significance of carcinoembryonic antigen (CEA), carbohydrate associated antigen 19–9 (CA19–9), alpha-fetoprotein (AFP) and cancer antigen 125 (CA125) in early gastric cancer have not been investigated yet. Thus, the present study aimed to explore the diagnostic and prognostic significance of the four tumor markers for early gastric cancer. Methods From September 2008 to March 2015, 587 early gastric cancer patients were given radical gastrectomy in our center. The clinicopathological characteristics were recorded. The association between levels of CEA and CA19–9 and clinicopathological characteristics and prognosis of patients were analyzed. Results There were 444 men (75.6%) and 143 women (24.4%). The median age was 57 years (ranged 21–85). The 1-, 3- and 5-year overall survival rate was 99.1%, 96.8% and 93.1%, respectively. The positive rate of CEA, CA19–9, AFP and CA125 was 4.3%, 4.8%, 1.5% and 1.9%, respectively. The positive rate of all markers combined was 10.4%. The associations between the clinicopathological features and levels of CEA and CA19–9 were analyzed. No significant association was found between CEA level and clinicopathological features. However, elevated CA19–9 level was correlated with female gender and presence of lymph node metastasis. Age > 60 years old, presence of lymph node metastasis and elevation of CEA level were independent risk factors for poor prognosis of early gastric cancer. Conclusions The positive rates of CEA, CA19–9, APF and CA125 were relatively low for early gastric cancer. Elevation of CA19–9 level was associated with female gender and presence of lymph node metastasis. Elevation of CEA level was an independent risk factor for the poor prognosis of early gastric cancer.
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              Direct effect of cholesterol on insulin secretion: a novel mechanism for pancreatic beta-cell dysfunction.

              S Gunawardana, Mark W Head, David W Piston … (2007)
              Type 2 diabetes is often accompanied by abnormal blood lipid and lipoprotein levels, but most studies on the link between hyperlipidemia and diabetes have focused on free fatty acids (FFAs). In this study, we examined the relationship between cholesterol and insulin secretion from pancreatic beta-cells that is independent of the effects of FFAs. Several methods were used to modulate cholesterol levels in intact islets and cultured beta-cells, including a recently developed mouse model that exhibits elevated cholesterol but normal FFA levels. Acute and metabolic alteration of cholesterol was done using pharmacological reagents. We found a direct link between elevated serum cholesterol and reduced insulin secretion, with normal secretion restored by cholesterol depletion. We further demonstrate that excess cholesterol inhibits secretion by downregulation of metabolism through increased neuronal nitric oxide synthase dimerization. This direct effect of cholesterol on beta-cell metabolism opens a novel set of mechanisms that may contribute to beta-cell dysfunction and the onset of diabetes in obese patients.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Diabetes Metab Syndr Obes
                Journal ID (iso-abbrev): Diabetes Metab Syndr Obes
                Journal ID (publisher-id): dmso
                Title: Diabetes, Metabolic Syndrome and Obesity
                Publisher: Dove
                ISSN (Electronic): 1178-7007
                Publication date (Electronic): 31 January 2024
                Publication date Collection: 2024
                Volume: 17
                Pages: 467-477
                Affiliations
                [1 ]Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University , Luzhou, People’s Republic of China
                [2 ]Metabolic Vascular Disease Key Laboratory of Sichuan Province , Luzhou, People’s Republic of China
                [3 ]Sichuan Clinical Research Center for Diabetes and Metabolism , Luzhou, People’s Republic of China
                [4 ]Sichuan Clinical Research Center for Nephropathy , Luzhou, People’s Republic of China
                [5 ]Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou , Luzhou, People’s Republic of China
                [6 ]Clinical medical College, Southwest Medical University , Luzhou, People’s Republic of China
                Author notes
                Correspondence: Pijun Yan, Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University , Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86-830-3165361, Email peter2007110361@126.com
                Author information
                http://orcid.org/0000-0001-6692-2401
                http://orcid.org/0000-0001-7765-1416
                Article
                Publisher ID: 434972
                DOI: 10.2147/DMSO.S434972
                PMC ID: 10838495
                PubMed ID: 38312210
                SO-VID: 67707f90-5b7e-434a-8400-a88c62a3f4a6
                Copyright © © 2024 Yan et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 18 September 2023
                Date accepted : 16 January 2024
                Page count
                Figures: 1, Tables: 4, References: 46, Pages: 11
                Funding
                Funded by: the key Research and Development Program of Science and Technology Department of Sichuan Province;
                This work was supported by grants from the key Research and Development Program of Science and Technology Department of Sichuan Province (2022YFS0612).
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: carbohydrate antigen 19-9,urinary albumin-to-creatinine ratio,diabetic kidney disease,estimated glomerular filtration rate,chinese population
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: carbohydrate antigen 19-9, urinary albumin-to-creatinine ratio, diabetic kidney disease, estimated glomerular filtration rate, chinese population

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