A pilot study on a combined non-invasive screening test for metabolic dysfunction-associated steatotic liver disease and type 2 diabetes

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Background Type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) are increasing globally, with mitochondrial dysfunction being a core component in their development. While a 75g oral glucose tolerance test (OGTT) can be used to diagnose T2D, hepatic metabolic and mitochondrial dysfunction can be assessed using a 13 C-methionine breath test (BT). We aimed to evaluate combining these tests for an efficient, non-invasive screening tool. Methods On three study days, 26 subjects (11 [43.3%] female, 61± 16 years) subjects underwent either an OGTT, a 13 C-methionine BT or both tests combined. Diagnostic outcomes of the individual and combined tests were compared using cumulative 13 C percentage dose recovered (cPDR), plasma glucose concentrations and Homeostatic Model Assessment (HOMA)-indexes for insulin resistance and beta-cell function. Results In the combined test, cPDR 90min was significantly lower (cPDR 90min 2.3± 0.2% vs. 5.7± 0.5%; p< 0.0001), accompanied by a rightward shift of the 13 C-increase towards later time points. When breath collection of the combined test was extended, cPDR 145min (5.7± 0.4%) was practically identical to cPDR 90min of the single test (p= 0.99). OGTT results, plasma glucose, and HOMA-indexes did not differ significantly between tests. Conclusions Combining a 13 C-methionine BT with an OGTT significantly impacts 13 C-methionine kinetics, but not OGTT results. A potential mechanism includes a glucose-induced delay of gastric emptying. Combined testing may be feasible when time-adjusted measurements are used, potentially allowing simultaneous screening for both T2D and MASLD-associated mitochondrial dysfunction in clinical practice.