There is increasing evidence that plasma markers of low-grade inflammation modulate the risk of developing type 2 diabetes: for each 1 log mg/L increment in C-reactive protein (CRP) levels, there is a 26% increased risk (1), and for each 1 log μg/mL increment in adiponectin levels, there is a 28% decreased risk (2). However, the Mediterranean diet is able to reduce the incidence of future diabetes by 19–23% (3). Using the data of a randomized trial (MEditerranean DIet and Type 2 diAbetes [MEDITA]) (4), we investigated 1) whether the Mediterranean diet has a durable effect on circulating levels of CRP and adiponectin in subjects with newly diagnosed type 2 diabetes and 2) whether the changes in these inflammatory markers influenced the development of diet failure.
In a two-arm, single-center trial, 215 men and women with newly diagnosed type 2 diabetes were randomized to a Mediterranean diet (n = 108) or a low-fat diet (n = 107), with a total follow-up of 8.1 years. Body weight, HOMA index, CRP, and adiponectin were assessed at baseline visit; at year 1, year 2, and year 4; and at the end of the trial (EOT), defined as the time at which participants left the study for having reached the primary end point (HbA1c >7% [53 mmol/mol]). We used an HbA1c level of >7% (53 mmol/mol) to define dietary failure.
The two treatment groups were well matched for demographic and clinical characteristics. At baseline, CRP and adiponectin levels did not differ between the two groups. At year 1, CRP fell by 37% and adiponectin rose by 43% in the Mediterranean diet group, while remaining unchanged in the low-fat diet group. Changes in CRP and HOMA values were numerically higher and total adiponectin levels were lower in each of the patients in the Mediterranean diet group that developed diet failure than their counterparts without failure. Among those who had not developed diet failure in the Mediterranean diet group, there was a significant reduction in CRP and HOMA at year 2 and 4, whereas there were no changes in CRP in participants who had developed failure (Fig. 1). There were no significant changes in adiponectin levels among participants either with or without diet failure in the low-fat diet group; among those who had not developed diet failure in the Mediterranean diet group, there was a significant increase in adiponectin at year 2 and 4, whereas there were no changes in adiponectin in participants who had developed failure (Fig. 1).
To our knowledge, this study is the first dietary intervention trial to demonstrate a sustained effect of the Mediterranean diet in ameliorating the inflammatory milieu in newly diagnosed type 2 diabetes. The study also showed that ongoing inflammatory activity is associated with diet failure in newly diagnosed type 2 diabetes and demonstrated the effects of a Mediterranean diet in ameliorating this process.
Whether changing the inflammatory milieu of type 2 diabetes with the Mediterranean diet would result in improved cardiovascular risk has yet to be proven. However, the PREvención con DIeta MEDiterránea (PREDIMED) study (5) clearly showed that a Mediterranean diet supplemented with extra virgin olive oil or nuts reduced the incidence of major cardiovascular events in subjects at high cardiovascular risk, including those (about 50%) with type 2 diabetes.
Funding. This study was supported in part by the Second University of Naples and the Associazione Salute con Stile.
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
Author Contributions. M.I.M. and K.E. researched the data and wrote the manuscript. G.B. researched the data, contributed to the discussion, and reviewed and edited the manuscript. M.P., L.S., and D.G. contributed to the discussion and reviewed and edited the manuscript. D.G. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Clinical trial reg. no. NCT00725257, clinicaltrials.gov.