Early Onset of Increased Transcapillary Albumin Escape in Awake Diabetic Rats

Alteration in transcapillary albumin escape rate (TERa,_alb) is an indicator of changes in macromolecular movement at the capillary filtering bed, which can change the balance of Starling forces for fluid movement from the vasculature to the interstitium and has an impact on volume homeostasis. TER_alb can be affected by morphological changes in the capillary membrane and/or alterations in the Starling forces driving larger solutes across the capillary membrane via convection. Previous studies have demonstrated an increased TER_alb in established insulin-dependent diabetes (IDDM); however, whether increased TER_alb is the result of morphological alterations in the microvasculature or contributes to microangiopathies could not be resolved. TER_alb was examined in awake Wistar rats with untreated IDDM induced by streptozocin infusion (65 mg/kg body wt i.v.) at 24 h and 7 and 15 days and compared with control and insulin-treated 7-day IDDM rats. Increased TER_alb occurred at the 24-h time point and remained elevated at 7 and 15 days of IDDM (P < 0.05). Blood volume remained unchanged; however, systemic protein concentration increased from 4.9 ± 0.1 g/dl in controls to 6.4 ± 0.4 g/dl in 15-day IDDM rats. Blood glucose was significantly increased, and glycosuria was evident at all three time points of IDDM. The observed increase in TER_alb within 24 h of IDDM is indicative of a functional change in the Starling forces in the capillaries, because specific morphological capillary damage is not evident at this time point in the model. The early onset of TER_alb in IDDM could indicate functional changes, such as capillary hypertension, and may contribute to future vascular complications in established IDDM.