Is there a dose-response relation of dietary glycemic load to risk of type 2 diabetes? Meta-analysis of prospective cohort studies

Background: Although much is known about the association between dietary glycemic load (GL) and type 2 diabetes (T2D), prospective cohort studies have not consistently shown a positive dose-response relation. Objective: We performed a comprehensive examination of evidence on the dose response that links GL to T2D and sources of heterogeneity among all prospective cohort studies on healthy adults available in the literature. Design: We conducted a systematic review of all prospective cohort studies and meta-analyses to quantify the GL-T2D relation both without and with adjustment for covariates. Results: Among 24 prospective cohort studies identified by August 2012, the GL ranged from similar to 60 to similar to 280 g per daily intake of 2000 kcal (8.4 MJ). In a fully adjusted meta-analysis model, the GL was positively associated with RR of T2D of 1.45 (95% CI: 1.31, 1.61) for a 100-g increment in GL (P < 0.001; n = 24 studies; 7.5 million person-years of follow-up). Sex (P = 0.03), dietary instrument validity (P < 0.001), and ethnicity (European American compared with other; P = 0.04) together explained 97% of the heterogeneity among studies. After adjustment for heterogeneities, we used both funnel and trim-and-fill analyses to identify a negligible publication bias. Multiple influence, cumulative, and forecast analyses indicated that the GL-T2D relation tended to have reached stability and to have been underestimated. The relation was apparent at all doses of GL investigated, although it was statistically significant only at >95 g GL/2000 kcal. Conclusion: After we accounted for several sources of heterogeneity, findings from prospective cohort studies that related the GL to T2D appear robust and consistently indicate strong and significantly lower T2D risk in persons who consume lower-GL diets. This review was registered at http://www.crd.york.ac.uk/PROSPERO as CRD42011001810. Am J Clin Nutr 2013;97:584-96.