Different Measures of Hyperglycemia Are Negatively Associated With Skin Microvascular Flowmotion: The Maastricht Study

Objective: Diabetes can lead to microvascular complications such as diabetic neuropathy, nephropathy, and retinopathy. Hyperglycemia may initiate microvascular function impairment early in the course of diabetes, even prior to its clinical establishment during the pre-diabetes stage. Microvascular vasomotion, that is, the rhythmic arteriolar constriction and dilation, is an important function that regulates oxygen and nutrient delivery within the tissue and regulates peripheral resistance. Using laser Doppler flowmetry (LDF), vasomotion in skin microcirculation can be measured as flowmotion. Changes in flowmotion have been shown in individuals with obesity, and type 1 or type 2 diabetes mellitus. However, no data are available on associations between hyperglycemia and flowmotion in the general population. Our aim was to study whether measures of hyperglycemia were associated with different components of skin microvascular flowmotion (SMF) in a population-based cohort (The Maastricht Study). Methods: Data from 7293 participants of The Maastricht Study were used. SMF was measured using LDF. Endothelial, neurogenic and myogenic component SMF power were used as dependent variables. We investigated the associations of glucose metabolism status (normal glucose metabolism, prediabetes, and type 2 diabetes mellitus), measures of hyperglycemia (fasting plasma glucose [FPG], 2-h post-load glucose [2 h-PG], HbA1c, advanced glycation end-products [AGEs] assessed as skin autofluorescence [SAF]), and indices of glucose variability (incremental glucose peak [IGP] and continuous glucose monitoring [CGM] -assessed as standard deviation [SD]) with each component of SMF power. We used linear regression analyses with adjustments for confounders, and trend analyses. Results: We observed consistent negative associations between HbA1c levels and all three (endothelial, neurogenic, and myogenic) skin microvascular flowmotion (SMF) powers in the additionally adjusted model. Similarly, in the conservative model, we found that multiple hyperglycemia metrics such as GMS trend, PreD, T2DM, FPG, 2 h-PG, and HbA1c were consistently negatively associated with all three SMF powers. Conclusions: We showed that skin microvascular flowmotion is reduced in individuals with (pre)diabetes. In addition, different measures of hyperglycemia are negatively associated with skin microvascular flowmotion.