The effect of metabolic regulation on microvascular permeability to small and large molecules in short-term juvenile diabetics

Abstract

The microvascular permeability to small and large molecules was studied during good and poor metabolic regulation in ten short duration juvenile diabetics. The following variables were measured; daily urinary albumin and β₂-microglobulin-excretion rates, whole body transcapillary escape rate of albumin (TER), glomerular filtration rate (GFR), capillary filtration coefficient (CFC), and capillary diffusion capacity (CDC). The urinary albumin and β₂-microglobulin concentration were measured by sensitive radioimmunoassays; TER was determined from the initial disappearance of intravenously injected ¹²⁵I-labelled human serum albumin; GFR was measured by single shot ⁵¹Cr-EDTA clearance; CFC was measured on the forearm by straingauge plethysmography and CDC for ⁵¹Cr-EDTA was determined in the hyperaemic anterior tibial muscle by the local clearance technique. All the above mentioned variables, except CDC, were significantly increased during poor metabolic regulation, indicating a functional microangiopathy. The mechanisms of these alterations appear to be increased filtration pressure in the microcirculation and/or increased porosity of the microvasculature. The findings of increased microvascular albumin passage are compatible with the hypothesis that the organic — histologically demonstrated — diabetic microangiopathy is a long-term effect of periods of increased extravasation of plasma proteins, with subsequent protein deposition in the microvascular wall, i. e. the concept of plasmatic vasculosis.