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Beisswenger PJ, Howell SK, Touchette AD, Lal S, Szwergold BS
Metformin reduces systemic methylglyoxal levels in type 2 diabetes
Diabetes (1999) 48:198-202.
Abstract
Methylglyoxal (MG) is a reactive alpha-dicarbonyl that is thought to contribute to diabetic complications either as a direct toxin or as a precursor for advanced glycation end products, It is produced primarily from triose phosphates and is detoxified to D-lactate (DL) by the glyoxalase pathway. Because guanidino compounds can block dicarbonyl groups, we have investigated the effects of the diamino biguanide comyound ntetformin and of hyperglycemia on MG and its detoxification products in type 2 diabetes. MG and DI; were measured by high- performance Liquid chromatography in plasma front 57 subjects with type 2 diabetes, Of these subjects 27 were treated with diet, sulfonylureas, or insulin (nonmetformin), and 30 were treated with metformin; 28 normal control subjects were also studied, Glycemic control was determined by HbA(1c). MG mas significantly elevated in diabetic subjects versus the normal control subjects (189.3 +/- 38.7 vs. 123.0 +/- 37 nmol/l, P = 0.0001), MG levels were significantly reduced by high-dosage (1,500-2,500 mg/day) metformin (158.4 +/- 44.2 nmol/l) compared with nonmetformin (189.3 +/- 38.7 nmol/l, P = 0.03) or low- dosage (less than or equal to 1,000 mg/day) metformin (210.98 +/- 51.0 nmol/l, P = 0.001), even though the groups had similar glycemic control. Conversely, DL levels were significantly elevated in both the low- and high-dosage metformin groups relative to the nonmetformin group (13.8 +/- 7.7 and 13.4 +/- 4.6 vs. 10.4 +/- 3.9 mu mol/l, P = 0.03 and 0.06, respectively), MG correlated with rising HbA(1c) levels (R = 0.4, P = 0.03, slope = 13.2) in the non-metformin subjects but showed no increase with worsening glycemic control in the high- dosage metformin group (R = 0.0004, P = 0.99, slope = 0.02). In conclusion, MG is elevated in diabetes and relates to glycemic control, Metformin reduces MG in a dose-dependent fashion and minimizes the effect of worsening glycemic control on MG levels, To the extent that elevated MG levels lead to their development, metformin treatment may protect against diabetic complications by mechanisms independent of its antihyperglycemic effect.
Note
Publication Date: 1999-01-01.
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