Clinical Studies with Acarbose for the Control of Hyperglycemia which is the Major Pathogenetic Factor of the Complications of Diabetes Mellitus

Abstract

The pathogenesis of the long-term complications of diabetes mellitus is still not resolved. It is still not unanimously accepted that hyperglycemia is the underlying cause of the complications of diabetes mellitus (DM). Three possible direct major pathogenetice factors contribute to the development of these complications: 1. The hyper-perfusion hypothesis of Brenner et al. which claims that the hyperglycemia of DM is accompanied by capillary hyper-perfusion which expresses itself as glomerular hyperfiltration in the kidneys in the form of higher GFR and RPF [1] and as hyperperfusion in the retinae in fluorescence angiography [2]. The retinal hyperperfusion occurs early in the diabetic long before any retinal lesion has developed [3]. Newly diagnosed IDDM in man is consistently accompanied by glomerular hyperfiltration [2–4]. Similar hyperfiltration was described in the early stages of experimental diabetes in animals [4, 5]. Thus hemodynamic changes which begin as hyperperfusion and are associated with increased intracapillary hydraulic pressure are thought to be the direct cause of diabetic microangiopathy [5–7]. Diabetic patients with higher GFRs were found to be the ones most likely to develop diabetic nephropathy [8] when compared to those patients with normal GFR. Decreasing the raised glomerular capillary pressure by Enalapril [9] or a low protein diet attenuate the early elevation of glomerular capillary pressure and flow and the subsequent glomerular structural damage [5]. These hemodynamic changes in the capillaries occur early in clinical as well as in experimental diabetes [4, 10], and are associated with a marked elevation in the HbA1c [9]. Once again this indicates the importance of the hyperglycemia as a major underlying cause of this train of events.