Roncero-Ramos, IreneGutierrez-Mariscal, Francisco MGomez-Delgado, FranciscoVillasanta-Gonzalez, AlejandroTorres-Peña, Jose DCruz-Ares, Silvia De LaRangel-Zuñiga, Oriol ALuque, Raul MOrdovas, Jose MDelgado-Lista, JavierPerez-Martinez, PabloCamargo, AntonioAlcalá-Diaz, Juan FLopez-Miranda, Jose2025-01-072025-01-072021-07-21https://hdl.handle.net/10668/24452In 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.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/ALT = alanine aminotransferaseAUC = area under curveAdipo-IR = Adipose tissue insulin resistance indexBMI = body mass indexCHD = coronary heart diseaseCORDIOPREV = CORonary Diet Intervention with Olive oil and cardiovascular PREVentionDBP = diastolic blood pressureDI = disposition indexFFA = free fatty acidsHDL-c = high-density lipoproteinHepatic-IR(fasting) = hepatic insulin resistance index derived from fasting valuesIGI = insulinogenic indexIR = insulin resistanceISI = insulin sensitivity indexLDL-c = low-density lipoproteinLF diet = low-fat dietMISI = muscular insulin sensitivity indexMUFA = monounsaturated fatty acidsMed diet = Mediterranean dietOGTT = oral glucose tolerance testPUFA = polyunsaturated fatty acidsSBP = systolic blood pressureT2DM = type 2 diabetes mellitusTG = triglyceridesAlanine TransaminaseDiabetes Mellitus, Type 2Diet, MediterraneanFatty AcidsFemaleGlucose Tolerance TestGlycated HemoglobinHumansHypoglycemic AgentsInsulin ResistanceInsulin-Secreting CellsLiverMaleMiddle Agedresearch article34298148open access10.1016/j.trsl.2021.07.0011878-1810http://www.translationalres.com/article/S1931524421001584/pdf