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  • Author: Wei Ye x
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Yunyi Ding Department of Nephrology, Hangzhou TCM Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Siyao Lv Department of Gastroenterology, Hangzhou TCM Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Ruijie Xie Division of Clinical Epidemiology and Aging Research, University of Heidelberg, Heidelberg, Germany

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Wei Ye Department of Gastroenterology, Hangzhou TCM Hospital, Hangzhou, China

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Yichen Luo School of Mechanical Engineering, Zhejiang University, Hangzhou, China

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Yayu Li Department of Nephrology, Hangzhou TCM Hospital, Hangzhou, China

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Objective

The aim of this study was to investigate the relationship between weight-adjusted-waist index (WWI) and diabetic kidney disease in individuals afflicted with type 2 diabetes.

Methods

Comprehensive data were ascertained from the National Health and Nutrition Examination Survey in 2013–March 2020. Weighted univariate, multivariate logistic regression models, subgroup analyses and tests for interaction were performed. Additionally, we employed smooth curve fitting to assess linear correlations and the threshold effects were calculated by applying a binary linear regression model. Breakpoints are identified by a model with maximum likelihood ratio and a two-step recursive approach. Receiver operating characteristic curve (ROC) along with the area under the curve (AUC) value predict the capability of WWI and body mass index for diabetic kidney disease.

Results

A total of 10,661 individuals diagnosed with type 2 diabetes were included, and the overall prevalence of diabetic kidney disease was 20.74%. WWI exhibited a positive correlation with the likelihood of diabetic kidney disease in type 2 diabetes patients (OR: 1.17, 95% CI: 1.03–1.33). The results of subgroup analysis showed significant interaction for gender (P < 0.05). Among female patients, U-shaped correlations were observed with a breakpoint at 11.48. Additionally, weight-adjusted waist index (AUC = 0.664) proved to be a more effective predictor of diabetic kidney disease compared to body mass index (AUC = 0.555).

Conclusion

In patients with type 2 diabetes, increased weight-adjusted-waist index is implicated with an increased risk of diabetic kidney disease. WWI can be used as a new anthropometric index to predict diabetic kidney disease, and its predictive ability is stronger than body mass index.

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Xi Zhang Department of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
Graduate School, Wannan Medical College, Wuhu, Anhui, People’s Republic of China

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Xiurong Shen Department of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
Graduate School, Wannan Medical College, Wuhu, Anhui, People’s Republic of China

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Wan Zhou Department of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
Institute of Endocrine and Metabolic Diseases, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China

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Mengyun Xu Department of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
Institute of Endocrine and Metabolic Diseases, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China

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Yan Xing Department of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
Institute of Endocrine and Metabolic Diseases, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China

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Jianping Weng Department of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
Institute of Endocrine and Metabolic Diseases, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China

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Shandong Ye Department of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
Institute of Endocrine and Metabolic Diseases, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China

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Suowen Xu Department of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
Institute of Endocrine and Metabolic Diseases, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China

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Zhi Zhang Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China

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Wei Wang Department of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
Institute of Endocrine and Metabolic Diseases, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China

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A variety of studies have demonstrated the role of lipocalin 2 (LCN2) in both diabetes and neurological disorders. Nevertheless, the relationship between LCN2 and diabetic peripheral neuropathy (DPN) needs to be elucidated in humans. Therefore, this study aimed to investigate the association of LCN2 with DPN in type 2 diabetes (T2D). A total of 207 participants with T2D and 40 participants with normal glucose tolerance (NGT) were included in this study. All participants were classified into DPN group and non-DPN (NDPN) group based on the Toronto Clinical Neuropathy Scoring (TCNS). Demographic and biochemical parameters were measured. Serum LCN2 levels were determined using an ELISA technique. Serum LCN2 levels in NGT group were lower than those in either DPN group (P = 0.000) or NDPN group (P = 0.043), while serum LCN2 levels in DPN group were higher than NDPN group (P = 0.001). Moreover, serum LCN2 levels positively correlated to TCNS scores, which reflects neuropathy severity (r = 0.438, P = 0.000). Multivariate stepwise regression analysis showed that BMI, triglycerides, and diastolic pressure were independently associated with serum LCN2 in DPN. Additionally, logistic regression analysis demonstrated that LCN2 (odds ratio (OR) = 1.009) and diabetes duration (OR = 1.058) were independently associated with the occurrence of DPN in T2D. Our report reveals the association of serum LCN2 with DPN in T2D. LCN2 might be used to evaluate DPN severity and serve a role in the pathogenesis of DPN.

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Xue-Lian Zhang Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Xinyi Zhao Department of Physiology, School of Medicine, Jinan University, Guangzhou, China

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Yong Wu Department of Physiology, School of Medicine, Jinan University, Guangzhou, China
Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China

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Wen-qing Huang Department of Transfusion Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China

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Jun-jiang Chen Department of Physiology, School of Medicine, Jinan University, Guangzhou, China
Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China

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Peijie Hu Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China

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Wei Liu Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Yi-Wen Chen Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Jin Hao Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Rong-Rong Xie Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Hsiao Chang Chan Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China

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Ye Chun Ruan Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China

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Hui Chen Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

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Jinghui Guo Department of Physiology, School of Medicine, Jinan University, Guangzhou, China

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Objective

The beneficial effect of angiotensin(1–7) (Ang(1–7)), via the activation of its receptor, MAS-1, has been noted in diabetes treatment; however, how Ang(1–7) or MAS-1 affects insulin secretion remains elusive and whether the endogenous level of Ang(1–7) or MAS-1 is altered in diabetic individuals remains unexplored. We recently identified an important role of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl channel, in the regulation of insulin secretion. Here, we tested the possible involvement of CFTR in mediating Ang(1–7)’s effect on insulin secretion and measured the level of Ang(1–7), MAS-1 as well as CFTR in the blood of individuals with or without type 2 diabetes.

Methods

Ang(1–7)/MAS-1/CFTR pathway was determined by specific inhibitors, gene manipulation, Western blotting as well as insulin ELISA in a pancreatic β-cell line, RINm5F. Human blood samples were collected from 333 individuals with (n  = 197) and without (n  = 136) type 2 diabetes. Ang(1–7), MAS-1 and CFTR levels in the human blood were determined by ELISA.

Results

In RINm5F cells, Ang(1–7) induced intracellular cAMP increase, cAMP-response element binding protein (CREB) activation, enhanced CFTR expression and potentiated glucose-stimulated insulin secretion, which were abolished by a selective CFTR inhibitor, RNAi-knockdown of CFTR, or inhibition of MAS-1. In human subjects, the blood levels of MAS-1 and CFTR, but not Ang(1–7), were significantly higher in individuals with type 2 diabetes as compared to those in non-diabetic healthy subjects. In addition, blood levels of MAS-1 and CFTR were in significant positive correlation in type-2 diabetic but not non-diabetic subjects.

Conclusion

These results suggested that MAS-1 and CFTR as key players in mediating Ang(1–7)-promoted insulin secretion in pancreatic β-cells; MAS-1 and CFTR are positively correlated and both upregulated in type 2 diabetes.

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