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Editorial |
Georgetown University Medical Center Washington, DC
At the annual meeting of the American College of Nutrition held in San Francisco in 1996, a symposium was held concerning the role of disturbed glucose/insulin homeostasis in the pathogenesis of various chronic diseases and the nutritional means to prevent or lessen insulin resistance and its consequences. The symposium proved quite successful due, in part, to the recognized importance of the material reviewed. So-called insulin resistance is common; and hyperglycemia and/or hyperinsulinemia, frequent signs of this resistance, are associated with many chronic disorders [1,2]. Accordingly, a decision was made to invite authors to prepare review papers on the subjects of the symposium. In the October 1997 issue of the Journal of the American College of Nutrition, the first two papers appeared: "The Effects of Glucose/Insulin Perturbations on Aging and Chronic Disorders of Aging: The Evidence" by H.G. Preuss [3] and "Nutritional Factors Influencing the Glucose/Insulin System" by R.A. Anderson [4]. Now two more papers will follow in this issue of the journal: "The Glucose/Insulin System: Regulation of and Responsiveness to Vitamin C" by J.J. Cunningham and "Zinc, Insulin and Diabetes" by A.B. Chausmer.
Parallels exist between the original two papers in the symposium and the present ones, i.e., all discuss use of natural substances to overcome insulin resistance. The paper written earlier by Anderson focuses on the role chromium plays in preventing insulin resistance and the deleterious outcomes associated with this state. The two papers in this issue deal with use of vitamin C and zinc to prevent or lessen the degree of insulin resistance. Why is it important to overcome or, at least, lessen the degree of insulin resistance? Poor response of tissues to circulating insulin, when it becomes severe enough to increase glucose and insulin levels above the accepted range, is designated as Type II diabetes [5–7]. Since Type II diabetes is not infrequently associated with various maladies, more subtle forms of elevated circulating glucose concentrations and insulin resistance might also lead to similar maladies, albeit more gradually over a longer time frame [8]. Reaven further expanded on the correlation between insulin resistance and human disease [2]. He described Syndrome X, which he believed to be due to insulin resistance with hyperinsulinemia. Composing this syndrome are glucose intolerance, circulating lipid disturbances, obesity, and hypertension. In addition, the states of insulin resistance and hyperinsulinemia have also been proposed to play a role in tumor formation and aging [9–11]. Accordingly, the ability to prevent insulin resistance and subsequent elevations of circulating glucose appears to be quite important in the quest to produce a longer and healthier lifespan.
In reviewing all papers on this subject in this written symposium, another interesting association becomes apparent—the interplay in actions between substances that increase insulin sensitivity and antioxidants. In earlier studies on chromium, an element recognized to enhance insulin sensitivity [12], it was noted that chromium had antioxidant properties [13]. In contrast, we see in the present two papers by Cunningham and Chausmer that products characteristically classified as antioxidants can enhance insulin sensitivity. Although zinc itself is not an antioxidant, it is a necessary component of an endogenous antioxidant system, superoxide dismutase, and is referred to by many as an antioxidant. Further correlations are that diabetes is associated with more lipid peroxidation via increased free radical formation [14], and many disease states associated with free radicals are the same as those found with insulin resistance [15]. Therefore, one could argue whether the predominate pathological mechanism behind aging, cardiovascular perturbations, cancer, and some eye disorders is due to the destructive influences of free radicals or insulin resistance with its hyperglycemia and hyperinsulinemia. In all likelihood, both are involved and take a significant toll.
The association of insulin resistance with enhanced free radical formation reminds me of some previous research on a circulating renal growth factor [16]. It soon became apparent that many growth factors were vasoconstrictive [17]; while, on the other hand, many vasoconstrictors were being reported to be growth factors. The latter was evident in the actions of Angiotensin II [18]. Whether a substance was characterized initially as a growth or a vasoconstrictive factor depended on the focus of the research initially carried out on it. The same may hold true for the current substances. As indicated above, chromium is well recognized for its ability to augment insulin sensitivity but has antioxidant properties, whereas vitamin C and zinc are more in the antioxidant camp, but as we see in the following two paper in the glucose/insulin symposium have beneficial effects in diabetes. The relationship between these two effects may prove to be very important.
Future studies should consider using combinations of insulin sensitizers and antioxidants to treat or to be adjuncts to treating such conditions as diabetes, hypertension, cardiovascular diseases, some cancers, aging, etc. Recently, we reported the ability of a combination of proanthocyanidins extracted from grapeseed (ActiVinTM), zinc, and chromium to prevent the development of hypertension in aging rats [19]. The combination appeared to function better than any one of the agents alone. It would be of considerable interest to test similar combinations in clinical studies examining the therapeutics of conditions associated with insulin resistance and/or enhanced free radical production.
Received January 1, 1998. REFERENCES
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