Background: Acute mental stress elicits neuroendocrine and cardiovascular responses that influence glucose metabolism. Abnormal glucose tolerance (Abnl-GT), a classification which combines prediabetes and diabetes, is either due to insulin resistance (Abnl-GT-IR) or β-cell insufficiency (Abnl-GT-βCI). Abnl-GT-IR reflects a classic dyslipidemia, metabolic syndrome linked cardiometabolic risk profile, whereas Abnl-GT-βCI shows a more sympathetic nervous system (SNS)-cardiac-stress-linked, cardiometabolic risk profile. We hypothesized that Abnl-GT-IR will show a pattern of acute stress reactivity more tightly coupled to dyslipidemia-IR metabolic features, with greater acute neuroendocrine and cardiac stress marker reactivity in Abnl-GT-βCI, consistent with a stress-linked cardiometabolic phenotype. Objective: In Abnl-GT-IR versus Abnl-GT-β-CI we compared and associated the acute-stress reactivity of neuroendocrine and cardiac stress markers. Methods: We included 397 South African adults (45±12 years; 55% men; 68% Black; BMI 28±7 kg/m 2 ) from the SABPA study. Abnl-GT was defined by HbA1c≥5.7% or fasting glucose ≥100 mg/dL, or antidiabetic therapy. Insulin resistance was classified by HOMA-IR>2.79 with Abnl-GT-βCI defined as Abnl-GT without IR. An acute stress task was applied for 1-minute (Stroop Color-Word Conflict test). Hemodynamic changes were assessed via Finometer and pre-and-post stress blood samples drawn. Reactivity changes from baseline (%Δ) were calculated for all neuroendocrine (cortisol, adrenocorticotrophic hormone (ACTH), dehydroepiandrosterone (DHEA)) and cardiac stress (cardiac-troponin-T(cTnT), amino-terminal pro-Brain-natriuretic peptide (NT-proBNP) biomarkers. Associations were assessed by regression models adjusted for age, sex, ethnicity, hypertension status, alcohol use and smoking. Results: Abnl-GT was present in 38% (150/397) with Abnl-GT-IR occurring 55% (83/150) and Abnl-GT-βCI in 45% (67/150). Abnl-GT-IR had higher baseline concentrations of cortisol, ACTH, DHEA, cTnT, fasting glucose, and insulin, but lower NT-proBNP (all P< 0.05), compared to Abnl-GT-βCI. During stress testing, cortisol blunting occurred in both groups, but only Abnl-GT-IR showed reduced ACTH and DHEA reactivity. Abnl-GT-IR had greater NT-proBNP and insulin responses, whereas Abnl-GT-βCI had greater cTnT reactivity. In Abnl-GT-IR cortisol reactivity associated with insulin reactivity alone (P=0.041), whereas NT-proBNP associated with glucose and insulin reactivity (all P< 0.01). In Abnl-GT-βCI cortisol reactivity associated with DHEA, and glucose reactivity (all P< 0.05), yet inversely with cTnT reactivity (P< 0.001). Conclusions: Acute stress responses varied by Abnl-GT etiology. In Abnl-GT-IR, cardiac stress was linked to insulin reactivity. In contrast, Abnl-GT-βCI primarily engaged central neuroendocrine pathways driven by multi-stress-systems activity, highlighting the role of physiological stress in this etiology. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Wentzel et al. (Fri,) studied this question.