Omega-3 Fatty Acids in Diabetes Mellitus: Gift from the Sea?

The potential role of omega-3 fatty acids in the prevention of atherosclerotic disease in the nondiabetic population currently engenders interest, enthusiasm, and controversy. Some apparently beneficial effects of omega-3 fatty acids on platelet function, eicosanoid formation, plasma triglyceride levels, and blood pressure have been described in patients with diabetes mellitus. However, enthusiasm for the use of omega-3 fatty acids in diabetes has been dampened by reports of potentially deleterious effects of these agents, including increased plasma glucose, glycosylated hemoglobin, plasma total cholesterol and LDL cholesterol, and serum apolipoprotein B levels. These adverse effects have been achieved with large, perhaps excessive, doses of omega-3 fatty acids, in the range of 4–10 g/day. The magnitude of these adverse effects has been small (typically 10–36%). It cannot be assumed that the effects of omega-3 fatty acids are the same in patients with diabetes mellitus as in nondiabetic subjects or patients with primary hyperlipidemia. First, the biosynthesis and composition of fatty acids is abnormal in diabetic animals and possibly in diabetic patients. Second, many potential mechanisms implicated in the pathogenesis of atherosclerosis are present in diabetic but not necessarily in nondiabetic subjects. Third, the mechanisms of many of the risk factors in diabetic patients differ from the mechanisms of these abnormalities in nondiabetic subjects, reflecting the effects of insulin deficiency, hyperglycemia, and their sequelae. Finally, because diabetes is a heterogeneous group of diseases, the effects of omega-3 fatty acids must be addressed separately for patients with insulindependent diabetes mellitus, non-insulin-dependent diabetes mellitus, and possibly other forms of diabetes. Thus, it is not possible to assess thepotential risks and benefits of dietary fish and fish oils in diabetic patients. Studies are needed to determine the regulation of fatty acid synthesis and the fatty acid composition of phospholipids in diabetic patients under defined conditions of metabolic control and diet and to determine the effects of dietary fish and fish oils in appropriate quantities on the fatty acid composition of phospholipids, the mechanisms involved in the pathogenesis of vascular disease in diabetes, and the incidence of microvascular and atherosclerotic complications.