Glucagon resistance in individuals with obesity and hepatic steatosis can be measured using the GLUSENTIC test and index

Increased plasma levels of glucagon (hyperglucagone-mia) promote diabetes development but are also ob-served in patients with metabolic dysfunction–associated steatotic liver disease (MASLD). This may reflect hepatic glucagon resistance toward amino acid catabolism. A clinical test for measuring glucagon resistance has not been validated. We evaluated our glucagon sensitivity (GLUSENTIC) test, which consists of 2 study days: a glu-cagon injection and measurements of plasma amino acids and an infusion of mixed amino acids and subse-quent calculation of the GLUSENTIC index (primary out-come measure) from measurements of glucagon and amino acids. To distinguish glucagon-dependent from insulin-dependent actions on amino acid metabolism, we also studied patients with type 1 diabetes (T1D). The d-decline in total amino acids was 49% lower in MASLD fol-lowing exogenous glucagon (P = 0.01), and the calculated GLUSENTIC index was 34% lower in MASLD (P < 0.0001) but not T1D (P > 0.99). In contrast, glucagon-induced glucose increments were similar in control participants and participants with MASLD (P = 0.41). The GLUSENTIC test and index may be used to measure glucagon resistance in individuals with obesity and MASLD.