Alpha cell function interacts with diet to modulate prediabetes and type 2 diabetes

Authors: RONCERO-RAMOS, IRENE - UNIVERSIDAD DE CORDOBA; JIMENEZ-LUCENA, ROSA - UNIVERSIDAD DE CORDOBA; ALCALA-DIAZ, JUAN - UNIVERSIDAD DE CORDOBA; VALS-DELGADO, CRISTINA - UNIVERSIDAD DE CORDOBA; ARENAS-LARRIVA, ANTONIO - UNIVERSIDAD DE CORDOBA; RANGEL-ZUNIGA, ORIOL - UNIVERSIDAD DE CORDOBA; LEON-ACUNA, ANA - UNIVERSIDAD DE CORDOBA; MALAGON, MARIA - INSTITUTO DE SALUD CARLOS III; DELGADO-LISTA, JAVIER - UNIVERSIDAD DE CORDOBA; PEREZ-MARTINEZ, PABLO - UNIVERSIDAD DE CORDOBA; ORDOVAS, JOSE - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; CAMARGO, ANTONIO - UNIVERSIDAD DE CORDOBA; LOPEZ-MIRANDA, JOSE - UNIVERSIDAD DE CORDOBA

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/24/2018
Publication Date: 12/1/2018
Citation: Roncero-Ramos, I., Jimenez-Lucena, R., Alcala-Diaz, J.F., Vals-Delgado, C., Arenas-Larriva, A.P., Rangel-Zuniga, O.A., Leon-Acuna, A., Malagon, M.M., Delgado-Lista, J., Perez-Martinez, P., Ordovas, J.M., Camargo, A., Lopez-Miranda, J. 2018. Alpha cell function interacts with diet to modulate prediabetes and type 2 diabetes. Journal of Nutritional Biochemistry. 62:247-256. https://doi.org/10.1016/j.jnutbio.2018.08.012.
DOI: https://doi.org/10.1016/j.jnutbio.2018.08.012

Interpretive Summary: Pancreatic islets house three major cell types, each of which produces a different endocrine product: Alpha cells (A cells) secrete the hormone glucagon. Beta cells (B cells) produce insulin and are the most abundant of the islet cells. Delta cells (D cells) secrete the hormone somatostatin, which is also produced by several other endocrine cells in the body. Alpha- and beta-cells dysfunction is implicated in the development of Type 2 diabetes mellitus (T2DM). Our objective was to evaluate whether alpha- and beta-cell dysfunction may precede prediabetes (PreDM) and T2DM development. We included in the study 462 patients from the CORDIOPREV study without T2DM at baseline, of which 272 were PreDM. We measured glucose, insulin, glucagon and GLP-1 plasma levels in the oral glucose tolerance test (OGTT) performed at baseline and after 2 years of follow-up. Patients were randomized to consume two healthy diets, a Mediterranean diet (more than 35% fat) and a low-fat diet (less than 30% fat). Our results suggest that alpha-cell dysfunction precedes the T2DM development. This process seems to be independent of diet consumed, whereas foods might differentially modulate PreDM regression. Specifically, the consumption of the Mediterranean diet was associated with a decrease in the glucagon/insulin (G/I) ratio, suggesting an improvement in alpha cell functionality. By contrast, the consumption of a low-fat diet seems to induce PreDM regression by reducing insulin resistance as evidenced by the lower insulin levels in this group. These findings will help to tailor specific diets to patients on different stages of disease progression.

Technical Abstract: Alpha- and beta-cells dysfunction is implicated in the development of Type 2 diabetes mellitus (T2DM). We aimed to evaluate whether alpha- and beta-cell dysfunction may precede prediabetes (PreDM) and T2DM development. Furthermore, we explored the role of two healthy diets (Mediterranean and low-fat diets) modulating these processes. We included 462 patients from the CORDIOPREV study without T2DM at baseline, of which 272 were PreDM. During follow-up, 107 patients developed T2DM (T2DM-incident group), 30 developed PreDM (PreDM-incident group), 86 regressed to normoglycemia (PreDM-regression group) and 29 patients remained without PreDM or T2DM criteria (control group), according to the American Diabetes Association diagnosis criteria. We measured glucose, insulin, glucagon and GLP-1 plasma levels in the OGTT performed at baseline and after 2 years of follow-up. Patients were randomized to consume two healthy diets, a Mediterranean (more than 35%) and a low-fat (less than 30%). At baseline we already observed higher levels of glucagon and glucagon/insulin (G/I) ratio in the T2DM-incident group compared with PreDM-incident and control groups. T2DM Risk Assessment by COX analysis using G/I ratio at 30 min after an OGTT was able to assess the T2DM risk with an HR of 2.514. The two dietary models differentially influenced the PreDM regression. Specifically, the consumption of Mediterranean diet was associated with a decrease in G/I ratio (P=.034), whereas the low-fat diet reduced insulin levels (P=.002). Our results suggest that alpha-cell dysfunction precedes the T2DM development. This process seems to be independent of diet consumed. However the PreDM regression might be differentially modulated by diets.