Diene Conjugates

Abstract

To the Editor:—Associate Professor Arshag Mooradian (J Am Geriatr Soc 1991;39:571–574) found significantly increased levels of diene conjugates (DC) in a group of elderly diabetics with complications in comparison with a control group of non-diabetic subjects. He concludes that this elevation is either due to increased free radical activity or secondary to greater availability of lipid substrate. Professor Mooradian further speculates that increased lipid peroxidation (which may be only one mechanism for producing DC) could have a pathogenetic role in diabetes-related complications. I do not dispute his findings but must take serious issue with the interpretation and significance of these data. Peroxidation is a major and often inevitable sequel of free radical attack on polyunsaturated lipids and may cause damage,1 but lipid peroxidation may also be the result, not the cause, of tissue damage.2 It must also be pointed out that peroxidation measured in the bulk plasma may bear no relationship to peroxidation occurring at the site(s) of tissue damage.3 We must also appreciate the difficulties of extrapolating in vitro findings to an in vivo situation. Although Jennings et al4 have previously demonstrated increased DC in a younger group of diabetic subjects, others have actually demonstrated reduced DC in diabetic subjects.5 In a study of elderly diabetics (with or without complications) which we published earlier this year,6 we found that elderly diabetics have significantly reduced concentrations of the antioxidant, vitamin C, when compared with an age-matched control group. In addition, we measured three other markers of free radical activity (FRA) not only at baseline but during supplementation of the diet with vitamin C for 6 weeks. Part of these data were presented at this year's Annual Meeting of the American Geriatrics Society in Chicago. We found no significant difference between the diabetic groups and age-matched controls in thiobarbituric acid reactivity, red cell glutathione concentrations, and diene conjugates. Furthermore, vitamin C supplementation for 6 weeks did not change the levels of any of these “markers” in the diabetic groups during the study. Differences in the study populations will account for some of these discrepancies and obvious contradictory findings to Professor Mooradian's work. Another more plausible explanation is the limitations of the currently available methods for quantification of lipid peroxidation and free radical activity. Most of these methods must be recognized as being indirect, subject to a variety of contaminants and influences, and poorly reproducible.7 Also, the findings of another study8 did not support the idea that the isomer, PL-9, 11-LA', which appears to be the main diene conjugate in human sera, tissue fluids, and tissues, reflects free radical activity at all. This leads to the conclusion that measurement of DC by UV-absorbance on extracted lipids cannot be used as an assay upon human samples.7 We have previously stated9 that measurement of several “markers” of free radical activity is more likely to increase the sensitivity for detecting lipid peroxidation and hence the effects of free radical activity. In this regard, the paper by Professor Mooradian, which only measures one “questionable” marker of FRA, should be interpreted with great caution. Investigators in the fields of basic science and free radical pathology are now increasingly turning to more specific and sophisticated measures of FRA such as electron spin resonance. Overall, the question of whether free radical activity is increased and pathogenetic in diabetes remains unresolved. Our enlightening in this area will only take place if other investigators with similar interests begin to employ more direct and specific methods in their studies. This is a stimulating prospect. The above letter was referred to Dr. Mooradian, but no reply was received.