The relationship among homocysteine, creatinine clearance, and albuminuriain patients with type 2 diabetes

OBJECTIVE - Although it is accepted that elevated plasma homocysteine (tHcy ) levels occur in end-stage renal disease and type 2 diabetes, the changes with milder renal dysfunction (e.g., microalbuminuria) are less clearly est ablished. This study explores the relationship among tHcy, creatinine clear ance (Ccr), and albumin excretion rate (AER) in a population with type 2 di abetes. RESEARCH DESIGN AND METHODS - A total of 260 patients with type 2 diabetes were screened in our outpatient clinic during 10 months. Fasting blood samp les were collected, and AER was calculated from an overnight timed urine sa mple. Ccr was calculated using the Cockroft-Gault formula. RESULTS - A total of 198 subjects (76%) had normoalbuminuria (< 20 mug/min) , 50 subjects (19%) had microalbuminuria (20-200 mug/min), and 12 subjects (5%) had macroalbuminuria (greater than or equal to 200 mug/min). Those wit h microalbuminuria had higher levels of tHcy than those with normoalbuminur ia (13.2 +/- 7.8 vs. 11.3 +/- 4.6 mu mol/l, P < 0.05). Patients were then s ubdivided based on low Ccr (< 80 ml(.)min-1(.)1.73 m(-2)) and normal Ccr (g reater than or equal to 80(.)min(-1.)1.73-2). None of the patientswith macr oalburninuria had normal Ccr. In those with normoa levels were higher than in those with low Ccr than in those with normal Ccr (12.0 +/- 4.6 vs. 10.0 +/- 4.4 mu mol/l, P < 0.01). The same was found for those with microalbumin uria (low Ccr versus normal Ccr: 14.6 +/- 9.0 vs. 10.2 +/- 2.8 mu mol/l, P < 0.02). For normal Ccr, tHcy was similar irrespective of AER (normoalbumin uria versus microalbuminuria: 10.0 +/- 4.4 vs. 10.2 +/- 2.8 mu mol/l NS). F or low Ccr, tHcy was higher in those with microalbuminuria versus normoalbu minuria (14.6 +/- 9.0 vs. 12.0 +/- 4.6 mu mol/l, P = 0.01). Using multivari ate regression, Ccr, but neither AER nor the presence of albuminuria, was a n independent predictor of tHcy. CONCLUSIONS - These data strongly suggest that in patients with type 2 diab etes the relationship between plasma tHcy and AER is largely due to associa ted changes in renal function, as defined by Ccr.