Type 2 Diabetes Mellitus is associated with functional capillary rarefaction – The Maastricht Study

Alfons J.H.M. Houben, Miranda T. Schram, Dennis M.J. Muris, Ronald M.A. Henry, Carla J.H. van der Kallen, Simone J.S. Sep, Annemarie Koster, Pieter C. Dagnelie, Coen D.A. Stehouwer

Background:
Longterm hyperglycemia is thought to play a pivotal role in diabetic microangiopathy. But in type 2 diabetes (T2DM) the effects of hyperglycemia should be delineated from the effects of the metabolic syndrome on the microcirculation, as the various components of this syndrome are also associated with microcirculatory abnormalities. We therefore investigated whether chronic hyperglycemia  and T2DM status are independently associated with structural and functional capillary density in an observational population-based cohort study.

Methods:
Using intravital microscopy we measured skin capillary density before and after ischemia (recruitment) and during venous congestion in 641 participants of the Maastricht Study; 418 had normal glucose metabolism (NGM) and 223 had T2DM as assessed with an oral glucose tolerance test. We used multiple linear regression analysis to investigate the associations of T2DM and HbA1c with skin capillary density values. Associations were adjusted for age, sex, waist circumference, total-to-HDL cholesterol ratio, triglycerides, systolic blood pressure, diastolic blood pressure, smoking, prior CVD, and anti-hypertensive and lipid lowering medication.

Results:
Participants with T2DM had significantly higher baseline capillary densities (β 6.26 [95%CI: 2.27; 10.25] capillaries/mm2; P < 0.001) and a significantly lower capillary recruitment (β -14.06 [-20.55; -7.57] %; P < 0.001), after adjustment for potential confounders. T2DM was not associated with capillary density during venous congestion. In addition, HbA1c was significantly associated with a lower capillary recruitment (β -3.25 [-6.46; -0.05] %; P = 0.04), after adjustment for confounders. HbA1c was not associated with baseline capillary density and density during venous congestion.

Conclusion:
T2DM is associated with increased baseline skin capillary densities and with decreased functional capillary densities. In addition, longterm hyperglycemia (HbA1c) is associated with decreased number of functional capillaries that can be recruited.