No abstract

The present knowledge of the state of the microvasculature in diabetic subjects early during the course of the disease and prior to any clinical signs of retinopathy and nephropathy is reviewed. Functional changes in the peripheral vascular bed have been demonstrated by various methods in the retina, the skin and the conjunctiva. The common features of these functional changes appear to be a loss of normal vascular tone and increased permeability. There is also evidence of a functional disorder of the glomerular capillaries in young diabetics early during their disease, as indicated by increased glomerular filtration rates. Based on the presence of a functional microangiopathy, a dynamic concept of the development of clinical microangiopathy is presented. It is suggested that the functional changes may occur very early and might in some instances come before the degenerative vascular changes. Thus they might participate in the mechanism of the development of the long-term diabetic syndrome.

Functional changes in the microvascular system appear to precede the morphological changes in the conjunctiva and retina of young subjects with diabetes mellitus. Similar functional changes might occur in the renal microvascular system and hemodynamics and possibly lead to a disturbance in the glomerular filtration rate. A preliminary study of the glomerular filtration rate (GFR) using the radioactive vitamin B12 method in young, insulin-treated patients with short duration of diabetes is reported. The average GFR in eighteen diabetic subjects was 137.8 ml. per min. per 1.73m2 with a standard deviation of 24.3 ml. in contrast to the average GFR in twelve control subjects which was 102.9 ml. with a standard deviation of 15.1 ml. This difference in GFR is highly significant. The reasons for the increased GFR in diabetics with short duration of their disease are discussed.

We performed a follow-up study of the glomerular function in a series of 29 Type 1 (insulin-dependent) diabetic patients who had been studied 18 years previously. Initial median duration of diabetes was 2 years (range 0-9) and at follow-up 21 (17-27) years. At follow-up, 8 diabetic patients exhibited increased urinary albumin excretion rate 515 (32-3234) micrograms/min with glomerular filtration rates significantly lower than 21 diabetic patients with normal urinary albumin excretion (85 vs 126 ml/min/1.73 m2; p less than 0.01). The patients with increased urinary albumin excretion rate also had higher arterial blood pressure (145/90 vs 120/80) mm Hg; p less than 0.02) and increased frequency of proliferative retinopathy (7 out of 8 vs 2 out of 21; p = 0.0001) as compared to the group with normal urinary albumin excretion. However, we found no association of increased urinary albumin excretion rate (incipient or overt nephropathy) to early glomerular hyperfiltration as median initial glomerular filtration rate was 142 ml/min/1.73 m2 in the diabetic patients with increased urinary albumin excretion and 147 ml/min/1.73 m2 in the patients with normal excretion rate (p greater than 0.05).