OBJECTIVE: To determine the effect of acute psychotic stress on glucose homeostasis in nondiabetic subjects. RESEARCH DESIGN AND METHODS: Beta-cell function and insulin sensitivity were determined by the homeostasis model assessment in 39 nondiabetic patients with acute psychotic stress reaction admitted to a psychiatric ward. The clinical global impression (CGI) score was used to evaluate the level of psychological stress. Patients were assessed on admission, after 2 weeks, before discharge, and 6 months after discharge. RESULTS: The mean CGI score decreased significantly with time: 5.3 +/- 0.8 and 1.6 +/- 0.7 on admission and predischarge, respectively (P < 0.001). This was associated with a significant reciprocal increase of mean beta-cell function from 96.8 +/- 33.2 to 134.4 +/- 60% at admission and postdischarge, respectively (P < 0.003), and a decrease of mean insulin sensitivity from 101.7 +/- 36 to 77.1 +/- 34.8% (P < 0.001). In contrast, mean glucose and HbA(1c) levels did not change significantly. Subgroup analysis demonstrated that patients with the highest stress score on admission (> or =6) had significantly higher glucose (P = 0.01) and insulin levels (P = 0.04) than patients with lower score (<6). Furthermore, insulin sensitivity and CGI score on admission were inversely correlated (r = -0.38, P < 0.02). In these patients, no correlation was found between beta-cell function or insulin sensitivity and BMI. CONCLUSIONS: These data indicate that beta-cell function and insulin sensitivity are inversely correlated with acute psychotic stress.