Metformin reduces systemic methylglyoxal levels in type 2 diabetes
| Autor: | Paul J. Beisswenger, Benjamin S. Szwergold, Scott K. Howell, Allison D. Touchette, Sundeep Lal |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Male medicine.medical_specialty medicine.drug_class Endocrinology Diabetes and Metabolism medicine.medical_treatment Type 2 diabetes Deoxyglucose chemistry.chemical_compound Glycation Internal medicine Diabetes mellitus Internal Medicine medicine Humans Hypoglycemic Agents Insulin Lactic Acid Aged Glycemic Dose-Response Relationship Drug Biguanide Osmolar Concentration Methylglyoxal Middle Aged Pyruvaldehyde medicine.disease Metformin Sulfonylurea Compounds Treatment Outcome Endocrinology Diabetes Mellitus Type 2 chemistry Female medicine.drug |
| Zdroj: | Diabetes. 48:198-202 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diabetes.48.1.198 |
| Popis: | 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 compound metformin and of hyperglycemia on MG and its detoxification products in type 2 diabetes. MG and DL were measured by high-performance liquid chromatography in plasma from 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 HbA1c. MG was 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 (< or = 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 micromol/l, P = 0.03 and 0.06, respectively). MG correlated with rising HbA1c levels (R = 0.4, P = 0.03, slope = 13.2) in the nonmetformin 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. |
| Databáze: | OpenAIRE |
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