A pilot study on a combined non-invasive screening test for metabolic dysfunction-associated steatotic liver disease...

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 ¹³C-methionine breath test (BT). We aimed to evaluate combining these tests for an efficient, non-invasive screening tool.

On three study days, 26 subjects (11 [43.3%] female, 61± 16 years) subjects underwent either an OGTT, a ¹³C-methionine BT or both tests combined. Diagnostic outcomes of the individual and combined tests were compared using cumulative ¹³C percentage dose recovered (cPDR), plasma glucose concentrations and Homeostatic Model Assessment (HOMA)-indexes for insulin resistance and beta-cell function.

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 ¹³C-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.

Combining a ¹³C-methionine BT with an OGTT significantly impacts ¹³C-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.