With respect to GIP secretion, most studies quantifying GIP secretion reported that the GIP levels are normal or even higher in T2D subjects compared with healthy controls. However, reductions in the GLP-1 levels were found in patients suffering from a long disease duration and poor compensation. A recent meta-analysis revealed a negative influence of HbA1c levels on plasma GLP-1 responses. Other gastrointestinal peptides play a role in the regulation of energy intake, appetite and overall energy homeostasis in humans. They are AICAR secreted by different cells in the intestine and from the pancreas, and their release is modulated by food ingestion. PYY is co-secreted predominantly from the endocrine L cells in the ileum together with GLP-1. PYY plays an important regulatory role in GIT function. PP is secreted from endocrine cells in the pancreas. Both PYY and PP, when infused intravenously, reduce appetite and energy intake in healthy humans. They are secreted in response to all three macronutrients, with fat being the most potent stimulus. In healthy Actinomycin D humans, it was shown that the presence of fat in the small intestine induced stimulation of PYY and PP in a manner dependent on fat digestion and the presence of free fatty acids. This finding is in accordance with our results; in healthy subjects, we detected significantly greater secretion of PYY and PP after ingestion of the M-meal compared with the V-meal. The course of PYY secretion consisted of two phases. The initial rise in the PYY level is likely due to a link to the proximal small intestine, and the continuous rise reflects the direct contact of lipids with the distal small intestine. This result was not detected in our diabetic group of patients; their postprandial response with respect to both peptides was significantly higher after the V-meal. Similarly, a previous study suggested that both insulin resistance and abnormal glucose metabolism impaired the PYY response to fat intake. To the best of our knowledge, this is the first report of the different secretory responses of PP after both isocaloric meals in T2D patients compared with healthy controls.