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 beta2-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 beta2-microglobulin concentration were measured by sensitive radioimmunoassays; TER was detemined from the initial disappearance of intravenously injected 125I-labelled human serum albumin; GFR was measured on the forearm by straingauge plethysmography and CDS for 51Cr-EDTA clearance; CFC was measured on the forearm by straingauge plethysmography and CDC, for 51Cr-EDTA was determined in the jyperaemic anterio 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 - histologicallly 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 to plasmatic vasculosis.

The effect of short-term glucagon infusion on kidney function in normal man

“…growth hormone [9], hypoxia, due to increased oxygen affinity of the red cells [2], and hyperosmolality [13]. In a recent investigation, however, we found no evidence for the involvement of the above mentioned mechanisms [12].…”

“…GFR is elevated, RPF unchanged, FF increased and urinary fi2-microglobulin and albumin excretion enhanced [9,12]. Qualitatively, the same alterations were demonstrated during glucagon infusion, except for one crucial point, the unchanged urinary albumin excretion.…”

“…It is well documented that functional alterations occur in the microcirculation all over the body in poorly controlled juvenile diabetics [9,12]. The changes are particularly well documented in the kidneys, viz.…”

Diabetic nephropathy: Fault or destiny?

“…From the onset of insulin dependent diabetes increased renal function and size are seen in all cases [10], particularly during periods of poor metabolic control [11]. In addition an increase in the volume of the mesangial region and in basement membrane thickness in the glomeruli is found in all insulin dependent diabetics two-three years after the onset of diabetes [12].…”

“…It is possible that those patients, who during a period of poor metabolic control, are particularly prone to increase their GFR and urinary albumin excretion [11] will eventually develop diabetic nephropathy. If this is so, these patients should demonstrate traces of albumin in 24 h urine samples more frequently than patients who do not ultimately develop nephropathy.…”