The development of functional changes in the kidney in juvenile diabetes, prior to overt nephropathy, was studied by the use of two tests provoking the increase in urinary protein excretion, namely physical exercise and lysine injection. Urinary excretion of albumin, beta-2-microglobulin, and light chain excretion was measured. Thirty-seven young male diabetics and eleven control subjects were studied by the exercise test (450 kpm/min for 20 min followed by 600 kmp/min for 20 or 30 min). In normal subjects, no increase in albumin excretion was found. Similar results were obtained in patients having had diabetes for 1 year or less. In patients, however, with diabetes for 2 to 20 years and with normal baseline excretion, significant increases in albumin excretion were demonstrated, as evidence of abnormal glomerular permeability during exercise, where increased filtration pressure may occur. Thus, during exercise, changes are disclosed that are not demonstrable during baseline conditions. The changes in albumin excretion occurred independent of changes in heart rate and blood pressure. No increase in beta-2-microglobulin or light chain excretion was noted in any of the subjects indicating that tubular protein reabsorption was undisturbed during the exercise load. Patients with increased baseline values exhibited still higher increases in albumin excretion during exercise. Thirty-two young male diabetic patients and nine control subjects were studied by the lysine test. Lysine, 0.4 g/kg body wt, was injected i.v. A sharp rise in beta-2-microglobulin excretion after lysine by a factor of 1440 occurred in the normal subjects, whereas albumin excretion increased only by a factor of 30, a clear indication of inhibition of tubular protein reabsorption. No significant change in the response was noted in the diabetic patients with normal baseline albumin values, irrespective of duration of diabetes. Only patients with elevated baseline values responded with abnormally high albumin values after lysine, whereas the beta-2-microglobulin and light chain responses were normal, indicating increased glomerular permeability. It is concluded that the exercise test is the more sensitive test of the two because abnormalities, probably of glomerular origin, can be demonstrated early in the course of diabetes.
