Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy

Abstract

SummaryWe investigated in a randomized, prospective study the influence of improved blood glucose control during 2-3 years in young insulin-dependent diabetic (IDDM) patients with microalbuminuria, which is indicative of early nephropathy. Patients were randomized either to intensive treatment by continuous subcutaneous insulin infusion (CSII) (n = 9) or CT (n = 9). Kidney biopsies were taken at baseline and after 26-34months. End points were structural changes in the glomeruli. Sensitive, quantitative, morphometric methods were used. The blood glucose control improved significantly (p ---0.01) during the study in the CSII-group as glycated haemoglobin (HbAlc) fell from 10.1% ([95 % CI] 8.9-11.3) to 8.6 % (7.9-9.2), but not in the . Mean HbAIr during the study period was significantly lower in the CSII-group than in the CTgroup, 8.7% (8.1-9.3) vs 9.9% (8.5-11.3), p =0.04. Basement membrane thickness (BMT) increased in both groups, most (CT vs CSII, p = 0.03) in the CTgroup: 140 nm (50-230) vs CSII: 56 nm (27-86). In the CT-group only an increase was seen in matrix/mesangial volume fraction (p = 0.006) and matrix star volume (p =0.04). Furthermore, a positive correlation between mean HbAlc during the study and change from baseline in BMT (r=0.70, p =0.001) and matrix/glomerular volume fraction (r --0.33,p = 0.09, NS) was demonstrated. Albumin excretion rate correlated significantly to BMT and most of the matrix parameters. The present study shows that during a period of only 2.5 years, a close relationship between the level of mean blood glucose and progression of glomerular morphological changes in early diabetic nephropathy can be demonstrated. [Diabetologia (1994) 37: 483-490] Key words Diabetic glomerulopathy, microalbuminuria, basement membrane thickness, mesangial expansion, mesangial matrix, stereology, hyperglycaemia.Even though hyperglycaemia is a prerequisite for the development of diabetic nephropathy, the impact of long-term hyperglycaemia on the progression of early diabetic nephropathy is not well understood. Abbreviations: IDDM, insulin-dependent diabetes mellitus; CSII, continuous subcutaneous insulin infusion; CT, conventional treatment (2, 3 or multiple injections daily); BMT, basement membrane thickness; AER, urinary albumin excretion rate; CI, confidence interval.Pirart [1] showed in a study comprising both IDDM and NIDDM patients, that the risk of development of serious complications including nephropathy, is associated with more severe hyperglycaemia. In cross-sectional [2--6] and long-term retrospective studies [7,8] an association between the level of glycated haemoglobin and microalbuminuria, which is an early sign of diabetic nephropathy [9,10], has been found. Improved blood glucose control obtained in prospective randomized studies has retarded the progression of AER [11] and the risk of developing clinical nephropathy [12,13]. However, it is not known if reducing mean blood glucose affects the progression of morphological changes at a very early stage of diabetic nephropathy. There...

Risk of nephropathy can be detected before the onset of microalbuminuria during the early years after diagnosis of type 1 diabetes.

“…Other studies of renal biopsies suggest that levels of urine albumin excretion below the cutoff for MA increase concomitantly with histological changes in renal morphology that are compatible with early diabetic renal injury (15,16). These data, together with our study, suggest that the rate of change of the ACR is a biochemical estimate of the rate of renal morphological changes related to diabetic nephropathy.…”

Long-term prevention of diabetic nephropathy: an audit

“…In previous studies not using RAAS-blocking treatment, an annual increase in UAER of 5-70% in type 1 diabetic patients with microalbuminuria has been reported [4,5,[7][8][9][10]. In contrast, we found an overall decrease in UAER after the introduction of RAAS-blocking treatment.…”

“…Subsequently, multiple trials have looked at progression rates from micro-to macroalbuminuria and reported progression rates ranging from 5.6 to 30%/year [5][6][7][8][9][10]. Intervention trials have demonstrated that ACEIs reduce the progression from micro-to macroalbuminuria and preserve GFR in type 1 diabetic patients [11][12][13][14][15].…”

“…In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary AER (UAER) of 6-14%/year and a risk of developing diabetic nephropathy (DN) of 3-30%/year have previously been reported [1][2][3][4][5][6][7][8][9][10]. Several clinical trials of short or medium duration have shown a beneficial effect of blocking the renin-angiotensin-aldosterone system (RAAS) with an ACE inhibitor (ACEI) on progression of albuminuria, the development of diabetic nephropathy and the decline in kidney function [6,7,[9][10][11][12][13][14][15].…”

Gliquidone decreases urinary protein by promoting tubular reabsorption in diabetic Goto-Kakizaki rats

“…AGEs can also increase extracellular matrix and mesangial cell proliferation (Ziyadeh 1993). The diabetic glomerular lesions include structural and functional changes in glomerular filtration membrane barriers, such as thickening of the glomerular basement membrane (GBM) and loss of podocytes (Bangstad et al 1994, Wolf et al 2005, resulting in increased protein excretion. In fact, tubular lesions have been found in diabetics even when the urinary albumin excretion rate is within a normal range.…”