Beta cell functionality and hepatic insulin resistance are major contributors to type 2 diabetes remission and starting pharmacological therapy: from CORDIOPREV randomized controlled trial

Authors: RONCERO-RAMOS, IRENE - University Of Cordova (UCO), Spain; GUTIERREZ-MARISCAL, FRANCISCO - University Of Cordova (UCO), Spain; GOMEZ-DELGADO, FRANCISCO - University Of Cordova (UCO), Spain; VILLASANTA-GONZALEZ, ALEJANDRO - University Of Cordova (UCO), Spain; TORRES-PENA, JOSE - University Of Cordova (UCO), Spain; DE LA CRUZ-ARES, SILVIA - University Of Cordova (UCO), Spain; RANGEL-ZUNIGA, ORIOL - University Of Cordova (UCO), Spain; LUQUE, RAUL - Instituto De Salud Carlos Iii; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DELGADO-LISTA, JAVIER - University Of Cordova (UCO), Spain; PEREZ-MARTINEZ, PABLO - University Of Cordova (UCO), Spain; CAMARGO, ANTONIO - University Of Cordova (UCO), Spain; ALCALA-DIAZ, JUAN - University Of Cordova (UCO), Spain; LOPEZ-MIRANDA, JOSE - University Of Cordova (UCO), Spain

Submitted to: Translational Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/14/2021
Publication Date: 7/20/2021
Citation: Roncero-Ramos, I., Gutierrez-Mariscal, F.M., Gomez-Delgado, F., Villasanta-Gonzalez, A., Torres-Pena, J.D., De La Cruz-Ares, S., Rangel-Zuniga, O.A., Luque, R.M., Ordovas, J.M., Delgado-Lista, J., Perez-Martinez, P., Camargo, A., Alcala-Diaz, J.F., Lopez-Miranda, J. 2021. Beta cell functionality and hepatic insulin resistance are major contributors to type 2 diabetes remission and starting pharmacological therapy: from CORDIOPREV randomized controlled trial. Translational Research. https://doi.org/10.1016/j.trsl.2021.07.001.
DOI: https://doi.org/10.1016/j.trsl.2021.07.001

Interpretive Summary: The prevalence of type 2 diabetes mellitus (T2DM) is steadily increasing worldwide with the resulting greater socioeconomic burden on health services, the economy and society. Therefore, the prevention of type 2 diabetes should be a high priority in the general population and, even more, in cardiovascular patients. Moreover, in recent years it has been discovered that remission of T2DM may be possible. In this regard, HNRCA scientists in Boston, in collaboration with Spanish research examined liver and pancreatic mechanisms that could be involved in this remission in a population of cardiovascular disease patients undergoing a long-term dietary intervention study. The results demonstrate that newly-diagnosed T2DM patients with better pancreas functionality and liver handling of insulin had a higher probability of T2DM remission in a dietary intervention without pharmacological treatment or weight loss, whereas among patients not achieving remission, those with worse pancreas functionality and liver handling of insulin had the highest risk of starting glucose-lowering treatment after 5 years of follow-up. Therefore, it is essential that proper dietary treatment is implemented as soon as T2DM is diagnosed in an individual.

Technical Abstract: In order to assess whether previous hepatic IR (Hepatic-IRfasting) and beta-cell functionality could modulate type 2 diabetes remission and the need for starting glucose-lowering treatment, newly-diagnosed type 2 diabetes participants who had never received glucose-lowering treatment (190 out of 1002) from the CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (a prospective, randomized and controlled clinical trial), were randomized to consume a Mediterranean or a low-fat diet. Type 2 diabetes remission was defined according to the American Diabetes Association recommendation for levels of HbA1c, fasting plasma glucose and 2h plasma glucose after oral glucose tolerance test, and having maintained them for at least 2 consecutive years. Patients were classified according to the median of Hepatic-IRfasting and beta-cell functionality, measured as the disposition index (DI) at baseline. Cox proportional hazards regression determined the potential for Hepatic-IRfasting and DI indexes as predictors of diabetes remission and the probability of starting pharmacological treatment after a 5-year follow-up. Low-Hepatic-IRfasting or high-DI patients had a higher probability of diabetes remission than high-Hepatic-IRfasting or low-DI subjects (HR:1.79; 95% CI 1.06-3.05; and HR:2.66; 95% CI 1.60-4.43, respectively) after a dietary intervention with no pharmacological treatment and no weight loss. The combination of low-Hepatic-IRfasting and high-DI presented the highest probability of remission (HR:4.63; 95% CI 2.00-10.70). Among patients maintaining diabetes, those with high- Hepatic-IRfasting and low-DI showed the highest risk of starting glucose-lowering therapy (HR:3.24;95% CI 1.50-7.02). Newly-diagnosed type 2 diabetes patients with better beta-cell functionality and lower Hepatic-IRfasting had a higher probability of type 2 diabetes remission in a dietary intervention without pharmacological treatment or weight loss, whereas among patients not achieving remission, those with worse beta-cell functionality and higher Hepatic-IRfasting index had the highest risk of starting glucose-lowering treatment after 5 years of follow-up.