cysteinylglycine and Diabetes-Mellitus--Type-2

Metformin treatment increases circulating homocysteine levels. We studied whether administration of folate reduces serum total homocysteine levels in patients on long-term metformin treatment.. A prospective, randomized, double-blind, placebo-controlled study lasting for 12 weeks and taking place in a university hospital setting.. Thirty patients treated with a metformin dose of at least 1000 mg day-1 for a minimum of 1 year were included. At baseline serum total homocysteine levels were within the reference range. One patient who withdrew and one who died were excluded from the statistical evaluation. Twenty-six of the remaining patients suffered from NIDDM, the other two from hyperlipidaemia.. Patients were randomized into two groups at week 0. The folate group received 0.25 mg day-1 of folate in addition to 60 mg day-1 of Fe2+, while the placebo group received only 60 mg day-1 of Fe2+.. Fasting homocysteine, cysteine, cysteinylglycine, vitamin B12 and folate were measured at week 0, 4 and 12. Changes from week 0 to week 4 and from week 0 to week 12 were calculated.. Folate administration reduced serum levels of total homocysteine in the folate group as compared with the placebo group by 13.9% (P < 0.01) and 21.7% (P < 0.001) at week 4 and 12, respectively. In the folate group versus the placebo group serum levels of vitamin B12 increased by 9.9% (P = 0.010) and 9.6% (P = 0.043) while folate levels increased by 96.9 and 89.9% at week 4 and 12, respectively.. The present study indicates that the homocysteine-increasing effect of metformin can be counteracted by folate administration.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptides; Double-Blind Method; Female; Folic Acid; Hematinics; Homocysteine; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vitamin B 12

Non-insulin dependent (Type 2) diabetes mellitus (NIDDM) is a risk factor for cardiovascular diseases (CVD). Oxidative stress mechanisms are often reported to be implied in type 2 diabetes mellitus. In order to determine their clinical relevance, we investigated several plasma indicators in the Turkish patients with NIDDM: (i) homocysteine (Hcy) and cysteine (Cys) which contribute to increase the risk of atherosclerosis during NIDDM, (ii) glutathione (GSH) and cysteinylglycine (CysGly) resulting from GSH degradation catalyzed by gamma-glutamylcysteine transferase (GGT), (iii) malonaldehyde (MDA) as a marker for lipid peroxidation, and (iv) total antioxidant status (TAS). Our main results were evaluated based on sex and diabetic status. In female patients, plasma concentrations of MDA and Hcy were significantly higher than in controls, while GSH levels were significantly lower. In males, a difference between control and diabetic groups was noticed only for Hcy, levels being also higher in patients. In the diabetic group, increase in serum glucose concentration was significantly correlated with increased GGT activity. In both controls and diabetic patients, GGT activity was correlated with a raised Cys concentration and a decreased GSH level. In both controls and diabetic patients, there were significant positive correlations between Cys and Hcy and between GSH and Hcy. We concluded that GSH and MDA levels are clinical indicators for an oxidative process linked to type 2 diabetes mellitus, especially in women.

Topics: Adult; Aged; Antioxidants; Blood Glucose; Case-Control Studies; Catalysis; Chromatography, High Pressure Liquid; Cysteine; Diabetes Mellitus, Type 2; Dipeptides; Female; gamma-Glutamyltransferase; Glutathione; Homocysteine; Humans; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Sex Factors; Smoking; Sulfhydryl Compounds; Turkey