Long-chain polyunsaturated fatty acids and diabetes mellitus

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Dear Sir:

The recent report in the Journal by Salmerón et al (1) suggests that replacing 2% of energy from trans fatty acids isoenergetically with polyunsaturated fatty acids (PUFAs) would lead to a 40% lower risk of type 2 diabetes. These authors also suggested that intakes of total fat and monounsaturated fatty acids are not associated with the risk of type 2 diabetes, but that intake of trans fatty acids is positively associated with the risk in women. This work is supported by evidence indicating that increased intakes of long-chain PUFAs (LCPUFAs) reduce insulin resistance and, thus, decrease the risk of type 2 diabetes. Ginsberg et al (2) showed that the number of insulin receptors decreases when Ehrlich cells, which show all the binding characteristics of mammalian insulin receptor, were enriched in monounsaturated fatty acids and increases when enriched in PUFAs. In male Wistar rats, fish oil intake not only results in a significant decrease in plasma total and LDL cholesterol but also in normoglycemia, dose-dependent hypoinsulinemia, a dose-dependent increase in glucose utilization and clearance in vivo, and an increase in insulin sensitivity (3). Breast-fed infants have a significantly higher percentage of docosahexaenoic acid (DHA) and LCPUFAs in muscle phospholipids and lower plasma glucose concentrations than do formula-fed infants (4). Children who have either never or not recently been breast-fed show a significantly inverse correlation between fasting plasma glucose and the percentage of both DHA and total LCPUFAs (4). Thus, higher LCPUFA concentrations in the skeletal muscle membrane are associated with lower fasting plasma glucose concentrations. These results are interesting because it is known that low concentrations of DHA and other LCPUFAs in skeletal muscle membrane phospholipids are associated with insulin resistance and obesity in adults. Furthermore, a high-fat, low-carbohydrate intake was shown to reduce the ability of insulin to inhibit endogenous glucose production (5), whereas substitution of dietary saturated for monounsaturated fat was shown to impair insulin sensitivity in healthy men and women (6). On the other hand, insulin sensitivity was shown to be correlated positively with the percentages of arachidonic acid (AA), the total percentage of 20–22-carbon PUFAs, and the ratio of the percentage of AA to the percentage of dihomo--linolenic acid in the muscle phospholipid fraction (7). This suggests that the fatty acid composition of muscles and dietary fatty acids modulate the action of insulin. There is also evidence to suggest that LCPUFAs play a role in type 1 diabetes.

We observed that prior treatment of Wistar rats with oils rich in eicosapentaenoic acid (EPA), DHA, AA, and -linolenic acid (GLA) prevents the development of alloxan-induced diabetes mellitus (8). Additionally, prior oral administration of 99–99.9% pure GLA, AA, EPA, and DHA completely prevents the occurrence of alloxan-induced diabetes mellitus in experimental animals (9). These findings suggest that LCPUFAs protect ß cells from the cytotoxic actions of alloxan. In vitro studies showed that alloxan-induced apoptosis of ß cells can be prevented by GLA, AA, EPA, and DHA (9). Earlier studies with LCPUFAs concentrated on the effects of these fatty acids to prevent or arrest the complications of diabetes mellitus. Conversely, we showed that LCPUFAs actually protect ß cells from the cytotoxic effects of alloxan. This finding, coupled with the observation that cod liver oil (a rich source of EPA and DHA) consumed during pregnancy is associated with a reduced risk of type 1 diabetes in the offspring, indicates that LCPUFAs protect against type 1 diabetes (10). Tumor necrosis factor (TNF-) plays a significant role in insulin resistance and is involved in pancreatic ß cell damage; therefore, TNF- participates in the pathogenesis of both type 1 and type 2 diabetes (reviewed in 8, 9, 11). LCPUFAs inhibit the production of TNF- both in vitro and in vivo (reviewed in 11), which may explain the beneficial effect of LCPUFAs in both type 1 and type 2 diabetes. The results of Salmerón et al (1) lend further support for the role of LCPUFAs in the pathogenesis of diabetes. In view of these findings, it would be prudent to study whether supplementation with LCPUFAs can protect high-risk individuals from diabetes.

REFERENCES

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