Table 2.

Mechanism and clinical value of Klotho in complications of diabetes.

Complication	Mechanism	Pathway	Source of evidence	Clinical value
Diabetic nephropathy	Inhibit podocyte apoptosis, stabilize glomerular filtration barrier, and reduce renal fibrosis	Nrf2、TRPC6、Wnt/β-catenin、TGF-β/Smad	Multi center meta-analysis	Serum and urine levels can predict early kidney injury (21, 52, 70)
Diabetes retinopathy	Reduce oxidative stress damage, inhibit abnormal neovascularization, and protect retinal nerve cells	PI3K/Akt-Nrf2/HO-1、VEGF-A	Queue study+in vitro experiment	Predicting lesion progression (57, 71, 72)
Diabetes cardiomyopathy	Inhibit myocarditis, reduce myocardial fibrosis, and improve mitochondrial function	NLRP3 inflammasome、Nrf2、Wnt/β-catenin	Animal experiments+small sample clinical trials	Negative correlation with cardiac function indicators, which can serve as potential predictive indicators (62, 63)
Diabetes cardiovascular disease	Anti vascular calcification, improving endothelial function, inhibiting atherosclerosis	FGFRs、NF-κB	Queue research+mechanism verification	Can serve as potential predictive indicators for myocardial infarction and stroke (73–75)
Neuropathy in diabetes	Reduce oxidative stress in nerve cells and inhibit the release of inflammatory factors	Nrf2、NF-κB	A small number of animal experiments	Potential predictive indicators but insufficient evidence at present (16, 26, 34, 35)
Metabolic syndrome	Improving insulin resistance and regulating glucose and lipid metabolism balance	FGF21/β-Klotho、IGF-1	cross-sectional study	Expression level is negatively correlated with disease risk (49, 82, 83)