Acute and chronic hyperglycemia blunts microvascular reactivity in postmenopausal women with type 2 diabetes

Abstract

Type 2 diabetes (T2D) is strongly associated with increased risk of cardiovascular diseases via endothelial dysfunction. Hyperglycemia causes microvascular endothelial dysfunction and reduces muscle perfusion. Near-infrared spectroscopy (NIRS) measures microvascular reactivity in skeletal muscle during vascular occlusion/reperfusion. However, the impact of acute and chronic hyperglycemia on macrovascular endothelial function (brachial flow-mediated dilation, FMD) and microvascular reactivity (NIRS-derived tissue oxygen saturation index, TOI) has not been examined in postmenopausal women with and without T2D. We hypothesized that T2D women would have decreased FMD and TOI responsiveness in the fasted condition and greater vascular impairments during acute hyperglycemia compared to controls.Ten T2D (61 ± 5 years) and 10 normoglycemic postmenopausal women (CON, 62 ± 7 years) participated in the study. Hemoglobin A1C (HbA1C) and blood glucose were measured by finger prick at baseline (fasted condition). Brachial artery FMD was evaluated using ultrasound. Forearm muscle TOI magnitude and slope during arterial occlusion and reperfusion periods were measured using NIRS. An oral glucose tolerance test (OGTT) was performed to induce acute hyperglycemia. Blood glucose, FMD, and TOI were measure at baseline and 1 hour (1-h) after OGTT. Abdominal fat was assessed by waist circumference and visceral adipose tissue (VAT) obtained by a whole-body dual-energy X-ray absorptiometry scan.Fasting HbA1C and glucose, waist circumference, and VAT were higher in T2D compared to CON (all p < 0.05). The increase in blood glucose at 1-h was higher in T2D (Δ143 ± 15 mg/dl) compared to CON (Δ49 ± 5 mg/dl) (p < 0.01). FMD at baseline and the decreases in FMD at 1-h were similar in T2D (Δ-2.2 ± 0.2%) and CON groups (Δ-1.9 ± 0.4%) (all p < 0.01). At baseline, T2D showed blunted TOI occlusion magnitude (T2D: -16 ± 1 vs. CON: -21 ± 2%), TOI occlusion slope (T2D: -0.05 ± 0.01 vs. CON: -0.07 ± 0.01), TOI reperfusion magnitude (T2D: 21 ± 2 vs. CON: 32 ± 3%), and TOI reperfusion slope (T2D: 0.79 ± 0.10 vs. CON: 1.19 ± 0.14) compared to CON (all p < 0.05). At 1-h, T2D exhibited lower TOI occlusion magnitude (T2D: -17 ± 2 vs. CON: -24 ± 3%), TOI occlusion slope (T2D: -0.06 ± 0.01 vs. CON: -0.08 ± 0.01), TOI reperfusion magnitude (T2D: 23 ± 2 vs. CON: 33 ± 4%), and TOI reperfusion slope (T2D: 0.90 ± 0.19 vs. CON: 1.14 ± 0.15) compared to CON (all p < 0.05). HbA1C, a measure of chronic hyperglycemia, was positively correlated with VAT (r = 0.514, p = 0.02) and TOI occlusion slope (r = 0.460, p = 0.04) and negatively correlated with TOI reperfusion magnitude (r = -0.506, p = 0.02) and slope at baseline (r = -0.493, p = 0.03). In conclusion, women with T2D exhibited blunted microvascular reactivity despite similar FMD compared with normoglycemic women in the fasted condition. Acute hyperglycemia further blunted microvascular function, but not macrovascular endothelial function, in women with T2D. Blunted microvascular reactivity was associated with chronic hyperglycemia and elevated VAT in postmenopausal women. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.