The aim of this study was to investigate the determinants of serum total homocysteine level (tHcy) in patients with type 2 diabetes mellitus (DM) according to sex.

A total of 1,276 Japanese, diabetics ( n = 280) with a control group of non-diabetics ( n = 996), were enrolled into the study from 2003 to 2005. This cross-sectional study was conducted for all the subjects, using personal data regarding clinical characteristics and lifestyle. Multiple regression analysis was performed to analyze the association of tHcy with selected factors.

In diabetic subjects, estimated glomerular filtration rate (eGFR) and serum creatinine levels (Cre), even those within the normal range, were strongly associated with tHcy after adjustment in both sexes; the standardized partial regression coefficient of eGFR for tHcy was −0.251, ( p = 0.001) in diabetic men and −0.523, ( p HbA1c was also associated with tHcy in diabetic men only, though not as significantly. Age and presence of hypertension were significantly associated with tHcy in women.

This study suggests that there are some differences in the factors associated with tHcy between diabetics and non-diabetics, and between the sexes. There is, therefore, circumstantial evidence that elevated tHcy should be evaluated clinically. Because tHcy was strongly associated with eGFR and Cre, even within the normal ranges, tHcy may have important implications regarding the microangiopathy of the kidney and atherosclerosis.