Dietary determinants, inflammation, and type 2 diabetes: insights from observational studies

Background Incidence of type 2 diabetes has rapidly increased during the last decades. It is a chronic disease caused by impaired insulin action and insulin secretion. Potentially, the majority of the new cases are due to changes in lifestyle, including unfavourable changes in diet. Lifestyle interventions promoting a healthy diet and physical activity indeed showed that diet has a role in the development of type 2 diabetes. However, firm conclusions about the role of most dietary factors and their association with type 2 diabetes cannot be drawn yet. Evidence for an association between a dietary factor and type 2 diabetes is strengthened when a potential pathway is elucidated through which a dietary factor can be linked to type 2 diabetes. Chronic low-grade inflammation may be one of these pathways. Elevated concentrations of C-reactive protein (CRP) and pro-inflammatory cytokines, like TNF-α and IL-6, have been associated with a higher risk of type 2 diabetes, at least through a connection with overweight and abdominal obesity. Whether chronic low-grade inflammation is an intermediate in the association between dietary factors and risk of type 2 diabetes is not often studied so far. Objectives The first objective of this thesis was to study the role of selected dietary factors, i.e., fatty acids, fish, tea, meat, glycemic index (GI), and glycemic load (GL), on the development of type 2 diabetes in observational studies. The second objective was to study the extent to which chronic low-grade inflammation is a pathway through which diet can affect the processes leading to type 2 diabetes. Methods Data were used from several ongoing prospective cohort studies, i.e., CODAM study, Rotterdam study, EPIC-InterAct study, and Hoorn study. In these studies, information about diet was collected with food frequency questionnaires. As a reflection of dietary fatty acid composition, the association between serum fatty acids in cholesteryl esters and glucose metabolism status was studied cross-sectionally in the CODAM study (n= 471). The prospective associations between fish (i.e., total, lean, fatty), meat (i.e., unprocessed red meat, processed red meat, poultry), GI, and GL and risk of type 2 diabetes were studied in the Rotterdam study (n= ≈4,400; nincident cases= ≈460). The EPIC-InterAct case-cohort study was used to investigate the prospective association between intake of tea and risk of type 2 diabetes (nsubcohort= 16,154; nincident cases= 11,541; eight European countries). To investigate the second objective, the mediating role of CRP in the association between meat, GI, or GL and risk of type 2 diabetes was studied. Furthermore, the cross-sectional associations between a literature-based index that reflects the inflammatory potential of the diet, the Adapted Dietary Inflammatory Index (ADII), and markers of glucose metabolism were investigated in CODAM and Hoorn studies (n= 1,034). In the Rotterdam study, a dietary pattern that relates to CRP was constructed and related to risk of type 2 diabetes. Results Intake of lean fish (Relative Risk (RR)≥23 vs. 0 g/day= 1.30 [95%Confindence Interval (95%CI) 1.01, 1.68]) and intake of processed meat (RR>30 vs. 0 g/day= 1.73 [95%CI 1.16, 2.57]) were associated with a higher risk of type 2 diabetes. The intake of tea was associated with a lower risk of type 2 diabetes (RR≥4 vs. 0 cups/day= 0.84 [95%CI 0.81, 1.00]). No statistically significant associations were observed for the other dietary factors, i.e., proportions of saturated, mono-unsaturated, trans, and poly-unsaturated fatty acids in cholesteryl esters, intake of fatty fish, intake of red meat, intake of poultry, GI, and GL. Our findings showed that the mediating role of CRP in the association between intake of meat, GI, or GL and risk of type 2 diabetes was small. However, the total dietary inflammatory potential of the diet, as estimated by ADII and a pro-inflammatory dietary pattern, were associated with insulin resistance or risk of type 2 diabetes, respectively. Conclusion The findings in this thesis together with results from other studies indicate that high intake of tea and low intake of processed meat can help lower the risk of type 2 diabetes. The findings also suggest that some diets can affect the development of type 2 diabetes through harmful effects on chronic low-grade inflammation. Which combinations of dietary factors cause the pro-inflammatory properties of these diets remains to be determined.