Telomere Maintenance Is Associated with Type 2 Diabetes Remission in Response to a Long-Term Dietary Intervention without Non-Weight Loss in Patients with Coronary Heart Disease: From the CORDIOPREV Randomized Controlled Trial

Author:

Ojeda-Rodriguez Ana1234,Alcala-Diaz Juan F.1234ORCID,Rangel-Zuñiga Oriol Alberto1234ORCID,Arenas-de Larriva Antonio P.1234,Gutierrez-Mariscal Francisco M.1234ORCID,Torres-Peña Jose D.1234,Mora-Ortiz Marina1234,Romero-Cabrera Juan L.1234,Luque Raul M.345ORCID,Ordovas Jose M.678,Perez-Martinez Pablo1234ORCID,Delgado-Lista Javier1234ORCID,Yubero-Serrano Elena M.1234ORCID,Lopez-Miranda Jose1234ORCID

Affiliation:

1. Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofia University Hospital, 14004 Cordoba, Spain

2. Department of Medical and Surgical Science, University of Cordoba, 14004 Cordoba, Spain

3. Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menendez Pidal, s/n, 14004 Cordoba, Spain

4. CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain

5. Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain

6. Nutrition and Genomics Laboratory, J.M. US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA

7. Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-Food), 28049 Madrid, Spain

8. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain

Abstract

In order to evaluate whether telomere maintenance is associated with type 2 diabetes remission, newly diagnosed type 2 diabetes patients without glucose-lowering treatment (183 out of 1002) from the CORDIOPREV study (NCT00924937) were randomized to consume a Mediterranean or low-fat diet. Patients were classified as Responders, those who reverted from type 2 diabetes during the 5 years of dietary intervention (n = 69), and Non-Responders, who did not achieve diabetes remission by the end of the follow-up period (n = 104). We found no differences in diabetes remission between the two diets, and we determined telomere length (TL) by measuring qPCR, telomerase activity using the TRAP assay, and direct redox balance based on the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSH) via colorimetric assay. Responders exhibited higher baseline TL in comparison with Non-Responders (p = 0.040), and a higher TL at baseline significantly predicted a higher probability of type 2 diabetes remission (OR 2.13; 95% CI, 1.03 to 4.41). After the dietary intervention, Non-Responders showed significant telomere shortening (−0.19, 95% CI −0.32 to 0.57; p = 0.005). Telomere shortening was significantly pronounced in type 2 diabetes patients with a worse profile of insulin resistance and/or beta-cell functionality: high hepatic insulin resistance fasting, a high disposition index (−0.35; 95% CI, −0.54 to −0.16; p < 0.001), and a low disposition index (−0.25; 95% CI, −0.47 to −0.01; p = 0.037). In addition, changes in TL were correlated to the GSH/GSSG ratio. Responders also showed increased telomerase activity compared with baseline (p = 0.048), from 0.16 (95% CI, 0.08 to 0.23) to 0.28 (95% CI, 0.15 to 0.40), with a more marked increase after the dietary intervention compared with Non-Responders (+0.07; 95% CI, −0.06–0.20; p = 0.049). To conclude, telomere maintenance may play a key role in the molecular mechanisms underlying type 2 diabetes remission in newly diagnosed patients. However, further larger-scale prospective studies are necessary to corroborate our findings.

Publisher

MDPI AG

Subject

Cell Biology,Clinical Biochemistry,Molecular Biology,Biochemistry,Physiology

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