Reduced incretin effect precedes diabetes development following duodenopancreatectomy in individuals without diabetes

The incretin effect (IE) is a key factor regulating β cell functional response and affecting the dynamics of\r\ninsulin secretion (1). The main actors in the IE are the incretin hormones GIP and GLP-1, which are secreted by\r\nspecialized enteroendocrine cells in response to glucose, amino acids, and lipids. It is well known that the IE is greatly\r\nreduced in type 2 diabetes (T2D), albeit with considerable variability (2). However, longitudinal studies investigating the\r\nlong-term consequences of the impaired IE in individuals without diabetes or those who are prediabetic are still lacking.\r\nTo identify possible latent impairments in the IE that could begin in the nondiabetic state, we conducted a study using\r\nacute surgical removal of β cell mass as a surrogate model of the β cell loss occurring during the natural history of T2D.\r\n35 individuals without diabetes scheduled for pancreatoduodenectomy underwent an in-depth metabolic evaluation before\r\nand after surgery (Supplemental Methods and Supplemental Figure 2; supplemental material available online with this\r\narticle; https://doi.org/10.1172/jci.insight.175133DS1). Based on postsurgical OGTT-derived glucose tolerance, we\r\nclassified the individuals as having normal glucose tolerance (post-NGT) (n = 10), impaired glucose tolerance (post-IGT)\r\n(n = 15), or diabetes mellitus (post-DM) after surgery (n = 10). Baseline characteristics of study participants are shown in\r\nSupplemental Table 1. Before surgery, study participants had similar […]