Aim: Diabetic kidney disease (DKD) develops in approximately 40% of patients who are diabetic and is the leading cause of end stage renal disease worldwide. Our previous study indicated that abdominal obesity is an important risk factor of DKD, consistent with several observational studies. However, the causal correlation between the abdominal obesity and DKD remains unclear.
Scientific rational: To identify the causal correlation between the abdominal obesity and DKD, we intend to use the approach of Mendelian randomization, which has traditionally been used to determine whether a candidate risk factor is causally related to a clinical outcome using the genotype as an instrument. In a Mendelian randomization study, genetic variants is used as to divide a population into genotypic subgroups, in an analogous way as how participants are divided into arms in a randomized controlled trial. By dividing participants into subgroups with different genetically exposures to the risk factor, we can evaluate the causal effect of the risk factor on disease risk. A recent large-scale Genome wide association study (GWAS) identified 48 SNPs associated with abdominal obesity, and combining these 48 SNPs into a weighted polygenic risk score, we can determine whether a genetic predisposition to abdominal obesity is associated with DKD.
Project duration: The duration of this project will be three years, from 2020 to 2023.
Public health impact: We expected to identify the causal association between abdominal obesity and the development of DKD. If further research validates our findings, two recommendations on the risk assessment and intervention of DKD might be considered by clinical practice: (1) Clinical screening of abdominal obesity by simple anthropometric measures to identify diabetic patients who might be more susceptible to diabetic nephropathy; (2) Interventions aiming to reduce abdominal adipose tissue may become an important adjunct to glycemic and blood pressure control for reducing the risk of DKD.