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      Relationship between advanced lung cancer inflammation index and long-term all-cause, cardiovascular, and cancer mortality among type 2 diabetes mellitus patients: NHANES, 1999–2018

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          Abstract

          Background

          Type 2 diabetes mellitus (T2DM) was a major global health threat. As a chronic low-grade inflammatory disease, the prognosis of diabetes was associated with inflammation. The advanced lung cancer inflammation index (ALI) served as a comprehensive index to assess inflammation. This study aimed to estimate the association between ALI and all-cause, cardiovascular disease (CVD), and cancer mortality in T2DM patients.

          Methods

          We extracted cohort data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2018 for analysis. The weighted Kaplan-Meier analysis and multivariate-adjusted Cox analysis were utilized to evaluate the relationship between ALI and all-cause, CVD, and cancer mortality in T2DM patients. Restricted cubic spline (RCS) analysis was employed to assess their non-linear relationship. Stratified analysis and interaction analysis were conducted to enhance the robustness of the results.

          Results

          The study incorporated a total of 3,888 patients. An increase in ALI was associated with a reduced risk of all-cause and CVD mortality in T2DM patients, but not related to cancer mortality. There were J-shaped and L-shaped non-linear relationships between ALI and all-cause, CVD mortality in T2DM patients, respectively. The inflection points were 90.20 and 93.06, respectively. For values below the inflection point, every 10U increase in ALI, both all-cause and CVD mortality risk decreased by 9%. Beyond the inflection point, all-cause mortality rose by 3%, while CVD mortality remained unaffected. Gender-stratified RCS analysis indicated a linear negative relationship between CVD mortality and ALI in female T2DM patients, whereas the trend in males aligned with the overall population.

          Conclusion

          Our research initially identified a significant correlation between increased ALI levels with decreased all-cause and CVD mortality in T2DM patients. There were J-shaped and L-shaped non-linear relationships between ALI and all-cause, CVD mortality in T2DM patients, respectively. For female patients, there was a linear negative relation between CVD mortality and ALI, whereas the trend in males aligned with the overall population. These findings suggested that maintaining ALI (for example, control body weight and keep albumin in the normal range) within a certain range in the clinical settings was crucial for improving all-cause and CVD mortality in T2DM patients.

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          Most cited references53

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          Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis.

          Estimates of the relative mortality risks associated with normal weight, overweight, and obesity may help to inform decision making in the clinical setting. To perform a systematic review of reported hazard ratios (HRs) of all-cause mortality for overweight and obesity relative to normal weight in the general population. PubMed and EMBASE electronic databases were searched through September 30, 2012, without language restrictions. Articles that reported HRs for all-cause mortality using standard body mass index (BMI) categories from prospective studies of general populations of adults were selected by consensus among multiple reviewers. Studies were excluded that used nonstandard categories or that were limited to adolescents or to those with specific medical conditions or to those undergoing specific procedures. PubMed searches yielded 7034 articles, of which 141 (2.0%) were eligible. An EMBASE search yielded 2 additional articles. After eliminating overlap, 97 studies were retained for analysis, providing a combined sample size of more than 2.88 million individuals and more than 270,000 deaths. Data were extracted by 1 reviewer and then reviewed by 3 independent reviewers. We selected the most complex model available for the full sample and used a variety of sensitivity analyses to address issues of possible overadjustment (adjusted for factors in causal pathway) or underadjustment (not adjusted for at least age, sex, and smoking). Random-effects summary all-cause mortality HRs for overweight (BMI of 25-<30), obesity (BMI of ≥30), grade 1 obesity (BMI of 30-<35), and grades 2 and 3 obesity (BMI of ≥35) were calculated relative to normal weight (BMI of 18.5-<25). The summary HRs were 0.94 (95% CI, 0.91-0.96) for overweight, 1.18 (95% CI, 1.12-1.25) for obesity (all grades combined), 0.95 (95% CI, 0.88-1.01) for grade 1 obesity, and 1.29 (95% CI, 1.18-1.41) for grades 2 and 3 obesity. These findings persisted when limited to studies with measured weight and height that were considered to be adequately adjusted. The HRs tended to be higher when weight and height were self-reported rather than measured. Relative to normal weight, both obesity (all grades) and grades 2 and 3 obesity were associated with significantly higher all-cause mortality. Grade 1 obesity overall was not associated with higher mortality, and overweight was associated with significantly lower all-cause mortality. The use of predefined standard BMI groupings can facilitate between-study comparisons.
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            Inflammation, metaflammation and immunometabolic disorders

            Proper regulation and management of energy, substrate diversity and quantity, as well as macromolecular synthesis and breakdown processes, are fundamental to cellular and organismal survival and are paramount to health. Cellular and multicellular organization are defended by the immune response, a robust and critical system
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              Inflammation in obesity, diabetes, and related disorders.

              Obesity leads to chronic, systemic inflammation and can lead to insulin resistance (IR), β-cell dysfunction, and ultimately type 2 diabetes (T2D). This chronic inflammatory state contributes to long-term complications of diabetes, including non-alcoholic fatty liver disease (NAFLD), retinopathy, cardiovascular disease, and nephropathy, and may underlie the association of type 2 diabetes with other conditions such as Alzheimer's disease, polycystic ovarian syndrome, gout, and rheumatoid arthritis. Here, we review the current understanding of the mechanisms underlying inflammation in obesity, T2D, and related disorders. We discuss how chronic tissue inflammation results in IR, impaired insulin secretion, glucose intolerance, and T2D and review the effect of inflammation on diabetic complications and on the relationship between T2D and other pathologies. In this context, we discuss current therapeutic options for the treatment of metabolic disease, advances in the clinic and the potential of immune-modulatory approaches.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2553745Role: Role: Role: Role:
                Role: Role: Role: Role:
                Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2516275Role: Role: Role: Role: Role:
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                28 November 2023
                2023
                : 14
                : 1298345
                Affiliations
                [1] 1Department of Physical Examination Center, Xiamen Humanity Hospital of Fujian Medical University , Xiamen, Fujian, China
                [2] 2Fuzhou International Travel Health Care Center , Fuzhou, China
                [3] 3Department of Gastroenterology, Xiamen Humanity Hospital of Fujian Medical University , Xiamen, Fujian, China
                [4] 4Department of Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University , Fuzhou, Fujian, China
                Author notes

                Edited by: David Wagner, University of Colorado Anschutz Medical Campus, United States

                Reviewed by: Ruben Fernandes, Fernando Pessoa University, Portugal; Cosmin Mihai Vesa, University of Oradea, Romania

                *Correspondence: Xuewen Wang, wxuew518@ 123456163.com ; Ruiqi Wang, 564809336@ 123456qq.com

                †These authors have contributed equally to this work and share first authorship

                Article
                10.3389/fendo.2023.1298345
                10726345
                38111710
                772ac73a-8d97-4fe2-9a3f-788607bf3733
                Copyright © 2023 Chen, Guan, Wang and Wang

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 September 2023
                : 07 November 2023
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 55, Pages: 13, Words: 7074
                Funding
                The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
                Categories
                Endocrinology
                Original Research
                Custom metadata
                Clinical Diabetes

                Endocrinology & Diabetes
                type 2 diabetes mellitus,advanced lung cancer inflammation index,national health and nutrition examination survey,all-cause mortality,cvd mortality,cancer mortality

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