Glyoxalase System in Clinical Diabetes Mellitus and Correlation with Diabetic Complications

<jats:p>1. The metabolism of methylglyoxal by the glyoxalase system may be linked to the development of diabetic complications. The glyoxalase system was characterized in blood samples from patients with insulin-dependent diabetes mellitus (n = 43), patients with non-insulin-dependent diabetes mellitus (n = 107) and 21 normal healthy control subjects.</jats:p> <jats:p>2. The concentrations of glyoxalase metabolites, methylglyoxal, S-D-lactoylglutathione and D-lactate, were increased in diabetic patients, relative to normal control subjects: methylglyoxal [median, range (n) pmol/g], insulin-dependent patients, 470.7, 85.6-1044.3 (42), P &lt; 0.001, non-insulin-dependent patients, 286.8, 54.7-2370 (105), P &lt; 0.001, control subjects, 79.8, 25.3-892.9 (21); S-D-lactoylglutathione [mean ± SD (n) pmol/106 erythrocytes], combined diabetic patients, 3.37 ± 0.85 (24), control subjects 4.76 ± 1.95 (8) P &lt; 0.05; D-lactate [mean ± SD or median, range (n) nmol/g], insulin dependent patients, median 18.3, 5.7-57.4 (42), P &lt; 0.001, non-insulin-dependent patients, 20.0 ± 8.9, 2.6-48.4 (105), P &lt; 0.001, control subjects 9.7 ± 4.3, 1.8-19.7 (21). The reduced glutathione concentrations in blood samples from the insulin-dependent and non-insulin-dependent diabetic patient groups were not different from the control group values (P&gt;0.05).</jats:p> <jats:p>3. The activities of glyoxalase enzymes in erythrocytes were increased: glyoxalase I activity [mean ± SD (n) m-units/106 erythrocytes] was increased in diabetic patients, relative to normal control subjects: insulin-dependent patients, 4.35 ± 1.54 (41), P &lt; 0.001; non-insulin-dependent patients, 4.61 ± 1.79 (101), P &lt; 0.001; control subjects, 3.21 ± 1.81 (21); glyoxalase II activity [mean ± SD (n) m-units/106 erythrocytes] was increased in the non-insulin-dependent diabetic patient group, relative to normal control subjects [non-insulin-dependent diabetic patients, 2.10 ± 0.46 (102); subject controls, 1.83 ± 0.27 (21); P &lt; 0.05].</jats:p> <jats:p>4. In insulin-dependent diabetic patients, the concentration of methylglyoxal correlated positively with the duration of diabetes, and the concentration of D-lactate correlated positively with haemoglobin A1c and negatively with the reduced glutathione concentration. D-Lactate concentration correlated positively with blood glucose concentration in patients with non-insulin-dependent diabetes mellitus.</jats:p> <jats:p>5. There was a positive logistic correlation of duration of disease with retinopathy, nephropathy, neuropathy, or any combination thereof. Retinopathy also gave a positive logistic correlation with haemoglobin A1c concentrations and a negative logistic correlation with D-lactate concentration.</jats:p> <jats:p>6. When paired for duration of diabetes, patients with retinopathy, neuropathy or nephropathy, or any combination thereof, had significantly higher age, level of haemoglobin A1c and glyoxalase I activity than patients with uncomplicated diabetes (P &lt; 0.05).</jats:p> <jats:p>7. We conclude that the glyoxalase system is modified in erythrocytes in both insulin-dependent and non-insulin-dependent diabetic patients and that this modification is related to the development of diabetic complications.</jats:p>