Hyperglycemia Is the Main Mediator of Prediabetes- and Type 2 Diabetes–Associated Impairment of Microvascular Function: The Maastricht Study

Prediabetes and type 2 diabetes (T2D) are associated with microvascular dysfunction (1), which may explain their increased risk of microvascular complications. However, mechanisms remain poorly understood. We investigated to what extent prediabetes- and T2D-associated microvascular dysfunction is potentially attributable to (composite indices of) hyperglycemia, insulin resistance, blood pressure, arterial stiffness, lipid profile, and/or low-grade inflammation.In the Maastricht Study (2), a T2D-enriched population-based cohort study ( n = 1,791, 49% women, aged 60 ± 8 years), we determined flicker light–induced retinal arteriolar %-dilation (1) using the Dynamic Vessel Analyzer, heat-induced skin %-hyperemia (1) using laser Doppler flowmetry, and diabetes status using the oral glucose tolerance test (normal glucose metabolism \[NGM\] \[ n = 1,040\], prediabetes [ n = 276], or T2D [ n = 475]) (Table 1). Mediating effects of composite indices on prediabetes- and T2D-associated microvascular dysfunction were estimated by linear regression.View this table:Table 1 General characteristics and retinal and skin measures for the retinal study population according to glucose metabolism statusAge- and sex-adjusted analyses showed lower retinal arteriolar %-dilation in prediabetes (B = −0.16 [95% CI –0.53; 0.21]), with further deterioration in T2D (B …