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Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus.
1. L R Solomon
2. K Cohen
+ Author Affiliations
Abstract
The effects of vitamin B6 on erythrocyte metabolism, erythrocyte hemoglobin O2 affinity (P50), and nonenzymatic glycosylation were studied in 15 Caucasian men with type II (non-insulin-dependent) diabetes mellitus. A control group of 13 healthy Caucasian men was also evaluated. Before treatment, diabetic subjects had low mean cell hemoglobin concentration values and increases in both erythrocyte 2,3-diphosphoglycerate (2,3-DPG) levels and erythrocyte hexokinase activities. Although all three of these changes are associated with a decrease in hemoglobin O2 (Hb-O2) affinity, P50 values were normal in diabetic subjects. Moreover, P50 values normalized to pH 7.4 (P50(7.4] were inversely related to the level of glycosylated hemoglobin (HbA1c). Both erythrocyte 2,3-DPG and erythrocyte ATP were also inversely related to HbA1c. Vitamin B6 nutriture, as determined by erythrocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, was normal in all diabetic subjects before vitamin B6 therapy. Nonetheless, HbA1c levels decreased after 6 wk of treatment with 150 mg/day pyridoxine and increased again during placebo administration. These changes were not explained by changes in fasting blood glucose. Pyridoxine therapy also decreased P50(7.4) values and increased erythrocyte AST and ALT activities but had no effect on 2,3-DPG, ATP, or the activities of hexokinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. These observations suggest that 1) nonenzymatic glycosylation may play a role in regulating both erythrocyte metabolism and Hb-O2 affinity in diabetic subjects, and 2) vitamin B6 therapy may modify nonenzymatic glycosylation of hemoglobin in this population.
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Vitamin B12. A neuropathy caused by vitamin B12 deficiency is characterized by numbness of the feet, pins-and-needles sensations, or a burning feeling (Davidson S 1954; Sancetta SM et al 1951). Supplementation that restores normal B12 levels is a part of successful treatment of diabetic neuropathy (Bhatt HR et al 1983). In a review of clinical trials conducted between 1954 and 2004, vitamin B12, as well as combination therapy of vitamin B12 and methylcobalamin, was shown to reduce pain (Sun Y et al 2005).
The most common forms of supplemental B12 are cyanocobalamin or hydroxycobalamin. The natural form of B12 found in food is methylcobalamin (or a similar form, adenosylcobalamin). The structure of B12 is very complex, with numerous methyl groups attached. Methyl groups (CH3) are used in beneficial methylation reactions, such as those that reduce homocysteine. Methylcobalamin appears to be the most effective form of vitamin B12 to protect the nerves.
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