Cardiometabolic and metabolic profiles in irritable bowel syndrome associated with type 2 diabetes

Irritable bowel syndrome (IBS), a common disorder of gut-brain interaction, has been increasingly associated with metabolic dysfunction and cardiometabolic risk. This study aimed to comprehensively assess cardiometabolic risk factors in individuals with IBS and to characterize their metabolic profiles in comparison with those of healthy and diabetic cohorts. First, in a retrospective database analysis, cardiometabolic risk factors of patients with IBS (<i>n</i> = 582,377) were compared with healthy controls (HCs) (<i>n</i> = 1,492,376). Following propensity score matching (<i>n</i> = 492,468), cardiometabolic parameters were analyzed during a follow-up period of 1-24 mo postindex. Second, a total of 234 individuals underwent comprehensive metabolic phenotyping using state-of-the-art nuclear magnetic resonance spectroscopy, comparing blood profiles of patients diagnosed with type 2 diabetes (T2D), IBS, and HC. We observed an increased cardiometabolic risk profile in patients with IBS compared with HC, characterized by higher mean body mass index, higher triglyceride levels, lower high-density lipoprotein cholesterol, and higher hemoglobin A1c levels. Odds ratios (ORs) were significantly increased in IBS, particularly for chronic hyperglycemia (OR = 16.32; <i>P</i> < 0.001). Results were confirmed by deep metabolic phenotyping, revealing a metabolic tendency in patients with IBS toward profiles characteristic of T2D by alterations in amino acid (glycine, histidine, and phenylalanine), glucose (glucose, lactate, and pyruvate), and lipid metabolism (parameters related to very low-density lipoproteins). Our findings confirm that IBS is linked to a distinct cardiometabolic risk profile and reveal metabolic associations relevant to T2D.<b>NEW & NOTEWORTHY</b> We identified a distinct cardiometabolic risk profile in patients with IBS, characterized by elevated BMI, triglycerides, HbA1c, and reduced HDL-C levels. Metabolic phenotyping reveals a pattern in patients with IBS comparable with T2D profiles, including altered amino acid, glucose, and lipid metabolism.