Case Control Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jan 15, 2021; 12(1): 47-55
Published online Jan 15, 2021. doi: 10.4239/wjd.v12.i1.47
Relationship between serum Dickkopf-1 and albuminuria in patients with type 2 diabetes
Ning-Ning Hou, Cheng-Xia Kan, Na Huang, Yong-Ping Liu, En-Wen Mao, Yu-Ting Ma, Fang Han, Hong-Xi Sun, Xiao-Dong Sun
Ning-Ning Hou, Cheng-Xia Kan, Na Huang, Yong-Ping Liu, En-Wen Mao, Yu-Ting Ma, Hong-Xi Sun, Xiao-Dong Sun, Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province, China
Fang Han, Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province, China
Author contributions: Huang N and Kan CX performed the majority of experiments and wrote the manuscript; Hou NN and Sun XD designed the study and revised the manuscript; Liu YP, Mao EW, Ma YT, Sun HX, and Han F provided analytical tools.
Supported by National Natural Science Foundation of China, No. 81870593; Natural Science Foundation of Shandong Province of China, No. ZR2018MH008; Shandong Province Higher Educational Science and Technology Program for Youth Innovation, No. 2020KJL004; Municipal Science and Technology Development Program of Weifang, No. 2018YX025.
Institutional review board statement: The study was approved by the Medical Ethics Committee of the Affiliated Hospital of Weifang Medical University.
Informed consent statement: Informed consent was obtained from all individuals.
Conflict-of-interest statement: No conflict of interest is reported.
Data sharing statement: The datasets analyzed during the present study are available from the corresponding authors on reasonable request.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Xiao-Dong Sun, MD, PhD, Associate Professor, Doctor, Research Fellow, Department of Endocrinology, Affiliated Hospital of Weifang Medical University, No. 2428 Yuhe Road, Weifang 261031, Shandong Province, China.
Received: July 16, 2020
Peer-review started: July 16, 2020
First decision: September 17, 2020
Revised: September 28, 2020
Accepted: November 10, 2020
Article in press: November 10, 2020
Published online: January 15, 2021
Research background

Diabetic kidney disease (DKD) is a microvascular complication of diabetes with complex pathogenesis. Wingless signaling-mediated renal fibrosis is associated with DKD. Dickkopf-1, a negative regulator of Wingless, has been proven to be participating in renal fibrosis, glucose metabolism, and inflammation. However, whether serum Dickkopf-1 levels are associated with diabetic kidney disease remains unclear.

Research motivation

Are there any correlations between serum Dickkopf-1 levels and glucose levels or albuminuria in type 2 diabetic individuals? Answering this question will provide significant insight into understanding the roles of Dickkopf-1 in DKD.

Research objectives

In this study, we assessed the relationship between serum Dickkopf-1 levels and albuminuria in individuals with type 2 diabetes. This will be helpful for the exploration of the mechanism of Dickkopf-1 in DKD.

Research methods

Seventy-three type 2 diabetes and 24 healthy individuals were enrolled in this case-control study. Diabetic individuals were separated into normal albuminuria, microalbuminuria, and macroalbuminuria groups based on their urinary albumin/creatinine ratios (UACR). Clinical characteristics and metabolic indices were recorded. Serum Dickkopf-1 levels were determined by enzyme-linked immunosorbent assay.

Research results

No significant difference in serum Dickkopf-1 levels was found between healthy individuals and the normal albuminuria group. However, the levels in the microalbuminuria group were significantly lower than those in the normal albuminuria group, and those in the macroalbuminuria group were the lowest. Bivariate analysis revealed that serum Dickkopf-1 levels were positively correlated with hemoglobin A1c levels and estimated glomerular filtration rate, but negatively correlated with diabetes duration, systolic blood pressure, serum creatinine level, and UACR. Multiple and logistic regression showed that serum Dickkopf-1 levels were independently associated with UACR.

Research conclusions

We have identified that serum Dickkopf-1 levels are negatively associated with UACR. Lower serum Dickkopf-1 levels could be a critical risk factor for albuminuria in diabetes.

Research perspectives

Dickkopf-1, as an endogenous inhibitor of the Wnt pathway, mediates various effects on the microvascular complications of diabetes, including DKD. The value of the study allows scientists to better understand the mechanisms of DKD for treatment in the future.