The prevention of type 2 diabetes : should we recommend vegetable oils instead of fatty fish ? 1 , 2

More than 50 y ago Scott and Griffith (1) reported on the very low prevalence of diabetes in Alaskan Eskimos in Metabolism; they observed only one patient with diabetes. Since that time, it has been suggested that omega-3 polyunsaturated fatty acids (FAs) could play a role in the etiology of type 2 diabetes and insulin resistance. Landmark animal studies by Storlien et al (2) showed, for example, that replacing part of omega-6 FAs with omega-3 FAs improved insulin sensitivity in liver and muscle, supporting this hypothesis. Thereafter, several epidemiologic cohort studies showed a lower incidence of diabetes in participants who consumed (more) fish compared with non–fish eaters. For example, we observed this finding in a small cohort of Dutch elderly men and women and in men from Finland and the Netherlands (3, 4). More recently an inverse association between the intake of omega-3 FAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the incidence of diabetes was reported in the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk study (5). However, our investigation of the Rotterdam study showed no significant association, and even pointed at a weak positive association between fish consumption and diabetes risk (6), which was similar to the positive association between long-chain FAs and diabetes as reported for the Harvard cohorts (7). This issue of the Journal includes 2 interesting articles that may shed some more light on these rather conflicting observations. The first one is a cohort study from Asia on omega-3 FAs and diabetes, which is, to my knowledge, the first such study from this region (8). The article shows that total omega-3 FA intake is inversely associated with diabetes incidence in the Singapore Chinese Health Study, an association which is entirely due to intake of a-linolenic acid (ALA), not to intake of EPA/DHA. Also, no association with various types of fish was observed. It is always relevant to investigate diet-disease relations in other cultures. The mean marine-omega-3 FA intake in the Singapore study amounted to ’300 mg/d, which was generally higher than in previously reported cohorts. Perhaps there are not enough lowomega-3 consumers in this Asian cohort to make the association with diabetes visible, but the overall range of intakes was quite large. Mean intake of nonmarine omega-3 FAs, originating primarily from grains, cooking oils, and legumes/soy, was relatively low at 510 mg/d. In the Netherlands and the United States, intake is generally higher at ’0.5% of energy or 1 g/d, primarily originating from margarines and vegetable oils. With . 2000 incident cases, the study was well powered. One could question the very low energy intake in the lowest quintiles of omega-3 FA intake, but this may be more usual in Asian situations. As in most large cohort studies a validated semiquantitative food-frequency questionnaire was used, in this case consisting of 165 items. Despite this, the use of a biomarker of FA intake may be useful to circumvent, for example, body mass index– related underor overreporting, which a problem that makes the nutritional epidemiology of type 2 diabetes a daunting task. Interestingly, the second article in this issue includes these biomarkers. Djoussé et al (9) studied the association between plasma omega-3 FAs and incident diabetes in the Cardiovascular Health Study (CHS). They measured plasma phospholipids in ’3100 elderly individuals, a cohort in which 204 incident cases occurred. Their results are interesting; they confirm recent observations that intake of fish or EPA/DHA is not associated with diabetes risk but in contrast show that plasma EPA/DHA is associated with a reduced incidence. The risk is especially reduced in the highest quartile of plasma EPA/DHA. For ALA, the results are slightly different. The reduced risk of diabetes in the highest quartile of plasma ALA is even stronger than that for EPA/DHA. And, in contrast to the results for EPA/ DHA, ALA intake is also associated with a reduced risk. The authors conclude that ALA is associated with a reduced risk, and that previous studies of fish and EPA/DHA intake may have shown a positive association with diabetes due to residual confounding or due to other ingredients in fish. This is indeed an interesting explanation for the contradictory findings using fish consumption as the exposure variable. We previous suggested (6) that nutrients such as selenium could be involved, because selenium was shown to increase diabetes risk in the SELECT (Selenium and Vitamin E Cancer Prevention Trial) Study. Alternatively, contaminants may also play a role. Regarding the plasma observations, we recently reviewed studies on plasma FA and glucose tolerance, including prospective studies on diabetes (10). The cohort studies showed no clear association of plasma EPA/DHA with diabetes, and 4 out of the 5 cohorts