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D-Lysine, the non-physiological isomer of L-lysine, can competitively reduce protein non-enzymatic glycation in vitro. To study the effect of D-lysine in vivo, 6-8-week old Sprague-Dawley rats with streptozotocin-induced diabetes mellitus were treated from diagnosis for 45 days with two daily subcutaneous injections of D-lysine (0.5 g.ml-1.day-1). Another group of diabetic rats was only injected with equal volumes of physiological saline (0.9% NaCl). Glycated haemoglobin was measured by ion exchange chromatography, and glycated serum and lens proteins by boronate affinity gel chromatography. Serum and urinary creatinine concentrations were evaluated by the alkaline-picrate reaction. Urinary lysine concentrations at mid- and end-study were evaluated by cation exchange chromatography. Blood glucose concentrations, serum creatinine levels and creatinine clearances, measured at the end of the study, were similar in both diabetic groups (&gt; 22.0 mmol/l, &lt; or = 106 mumol/l and approximately 0.02 ml/s, respectively). Urinary lysine concentration in D-lysine-treated diabetic animals was more than 50-fold higher than in placebo-treated diabetic rats. In D-lysine-treated vs placebo-treated diabetic animals, a statistically significant reduction was found in the levels of glycated haemoglobin (stable HbA1; mean +/- SD = 3.00 +/- 0.74% vs 4.02 +/- 0.46%, p &lt; 0.05; labile HbA1 = 3.92 +/- 0.89% vs 5.84 +/- 0.61%, p &lt; 0.005), glycated serum proteins (1.40 +/- 0.47% vs 2.52 +/- 1.15%, p &lt; 0.05) and glycated lens proteins (4.90 +/- 0.96% vs 5.98 +/- 0.65%, p &lt; 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

d-Lysine reduces the non-enzymatic glycation of proteins in experimental diabetes mellitus in rats