The effect of acute hyperglycemia on microvascular reactivityKralj, Lana (Avtor) Lenasi, Helena (Mentor) Battelino, Tadej (Komentor) acute hyperglycemiamicrocirculationskin microvascular reactivityendothelial functionnitric oxideautonomic nervous system reactivityheart rate variabilitylaser Doppler flowmetrywavelet analysisBackground & Aims: While the long-term harmful effects of chronic hyperglycemia are well understood, the microvascular impact of short-term, acutely elevated glucose levels remains less well defined. Available studies suggest that acute hyperglycemia may transiently impair microvascular endothelial function and affect the autonomic nervous system (ANS), but the findings are discrepant. Clarifying these effects is clinically relevant, as even transient impairments in endothelial or ANS function may represent early events in the development of cardiovascular complications. We aimed to investigate the effects of acute hyperglycemia induced by an oral glucose tolerance test (OGTT) on skin microvascular and ANS reactivity in young, healthy volunteers, and to elucidate underlying mechanisms. Hypotheses: (H1) Acute hyperglycemia significantly alters the skin microcirculation reactivity, most likely by: • decreasing the endothelium-dependent vasodilation and • altering the ANS reactivity (H2) The effect of acute hyperglycemia on skin microcirculation depends on the time after exposure to a glucose load. Methods: Skin microvascular reactivity was assessed in 28 young, healthy participants (16 females and 12 males) before and 45 and 120 minutes after OGTT or water loading. Glucose levels were assessed by sensor for noninvasive continuous glucose monitoring (FreeStyle Libre 2, Abbott Laboratories, Illinois, USA). Laser Doppler flowmetry (LDF) monitored basal perfusion and microvascular response to post-occlusive reactive hyperemia (PORH) and iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Wavelet analysis (WA) with implemented cone of influence correction was applied to assess endothelium nitric oxide-independent (endo NOi), nitric oxide-dependent (endo NOd), and myogenic spectral components. ANS reactivity was evaluated by time- (root mean square of successive RR interval differences (RMSSD), standard deviation of normal-to-normal RR intervals (SDNN)), and frequency-domain (low-frequency (LF), high-frequency (HF) power and their ratio (LF/HF)) heart rate variability (HRV) metrics. Results: OGTT induced time-dependent changes in specific microvascular and HRV parameters. Significant interactions between time and intervention (OGTT / water loading) were observed in the endo NOi (p = 0.014) and myogenic (p = 0.029; two-way repeated measures ANOVA) wavelet bands evaluated from the SNP response, indicating that glucose and water loading differently affected these components over time. On the other hand, no statistically significant differences between glucose and water loading were observed in the spectral components derived from basal perfusion or from the responses to ACh and PORH. Additionally, significant interactions in time-domain HRV parameters (RMSSD: p = 0.009, SDNN: p = 0.008; two-way repeated measures ANOVA) suggested that glucose loading alters the overall ANS balance. Conclusions: Our work provides novel insights into potential mechanisms underlying physiological responses to acute glucose loading. We confirmed both our hypotheses and demonstrated that OGTT-induced acute hyperglycemia triggers subtle microvascular changes in young healthy individuals. These changes are mainly reflected in a transient decrease of endothelium-dependent vasodilation, most likely involving NO-independent signaling pathways. Additionally, we observed effects on vascular smooth muscle responsiveness and ANS reactivity. The effects of acute hyperglycemia on skin microcirculation depended on the time after exposure to a glucose load, indicating dynamic adaptation to acute physiological stress. Our integrated approach, employing WA with implemented COI correction as a central analytical method, may offer a potentially applicable noninvasive tool for an early detection of microvascular and ANS dysfunction associated with acute hyperglycemia.20252025-11-26 07:15:08Doktorsko delo/naloga176257sl