Association between plasma homocysteine and progression of early nephropathy in type 2 diabetic patients

Abstract

There is now growing evidence supporting the association between renal insufficiency and accumulation of plasma homocysteine (Hcy). However, the role of Hcy in the development of diabetic nephropathy (DN) in type 2 diabetic patients is not clearly elucidated. To this end, we performed a prospective observational study in 208 patients and 49 controls. We show that baseline level of Hcy is significantly enhanced in patients with DN and is associated with the severity of the disease. Focusing on patients at early DN stage (n = 157), after four-year follow-up, we find that increase in plasma Hcy level correlates with greater renal failure characterized by faster decline in estimated glomerular filtration rate (eGFR). Using a multivariate linear regression model, we show that plasma Hcy remains significantly associated with eGFR decline after controlling for other progression promoters. Our results support that plasma Hcy is an independent risk factor as well as an early predictor for DN progression in type 2 diabetic patients.

Keywords: Homocysteine; diabetic nephropathy; glomerular filtration rate.

Figure 1

Plasma homocysteine levels in control and type 2 diabetic patients. Box plot graph indicates the quartiles of the values measured in each group. Normo: normoalbuminuria; Micro: microalbuminuria; Macro: macroalbuminuria. *P<0.001 vs. Micro. †P<0.001 vs. Normo (Bonferroni’s test).

Figure 2

Correlation between baseline homocysteine abundance and annual decline in eGFR. Data from 157 diabetic patients included in the four years’ follow-up were graphed in the scatterplot. The linear regression line and the confidence intervals are also shown.