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

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 CORDIOPREV 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 ADA recommendation for levels of HbA1c, fasting plasma glucose and 2h plasma glucose after OGTT, 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 five-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 five years of follow-up. BACKGROUND: Our current knowledge regarding the etiology of type 2 diabetes points to hepatic insulin resistance and beta cell functionality as two major abnormalities underlying the disease. Previous studies have associated type 2 diabetes remission with weight loss, together with a decrease in liver fat content and a higher beta cell recovery. TRANSLATIONAL SIGNIFICANCE: Patients with lower hepatic insulin resistance and better beta cell functionality had a higher probability of remission without significant weight loss or pharmacological treatment. These results suggest that clinicians could identify patients with specific phenotypes in early-diagnosed type 2 diabetes that could be the key to achieve higher remission rates without weight loss or pharmacological treatment.