Glomerular structure in type-1 (insulin-dependent) diabetic patients with normo- and microalbuminuria

Walker, James; Close, C. F.; Jones, Susan Y.; Rafftery, Martin; Keen, H.; Viberti, Giancarlo; Østerby, Ruth

doi:10.1038/ki.1992.116

Cited by 94 publications

(81 citation statements)

References 14 publications

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“…The Diabetes Control and Complications Trial confirms these results in a large-scale study, even though the design of the study focused on retinopathy [28]. An association between the degree of AER and structural parameters has only been found when a "structural index", which included BMT and matrix volume fraction, was constructed [9,29]. In the present study the results were very consistent: at the end of the study, AER showed a positive correlation with all of the structural parameters.…”

Section: Discussionsupporting

confidence: 48%

“…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].…”

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confidence: 99%

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

Bangstad¹,

Østerby²,

Dahl‐Jørgensen³

et al. 1994

Diabetologia

150

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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...

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Section: Discussionsupporting

confidence: 48%

mentioning

confidence: 99%

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

Bangstad¹,

Østerby²,

Dahl‐Jørgensen³

et al. 1994

Diabetologia

150

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“…Despite being normotensive, our type 1 diabetic patients demonstrated the characteristic lesions of diabetic glomerulopathy, some to quite an extensive degree; other studies have also reported patients with normotension and classical glomerular lesions [30,31].Thus we believe that although this group may not be entirely typical, they are representative.…”

Section: Are the Differences Due To Blood Pressure?contrasting

confidence: 45%

Are glomerular volume differences between type 1 and type 2 diabetic patients pathologically significant?

2007

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The observation that patients with type 2 diabetes tend to have larger glomeruli than patients with type 1 diabetes was first made more than 10 years ago. It has also been noted that type 2 diabetic patients with nephropathy often have more heterogeneous renal function and structure than type 1 patients. However, whether these observations are linked or have any bearing on the progression of nephropathy in the two types of diabetes remains uncertain. Here we put forward several hypotheses as to why glomerular volume in type 1 differs from that in type 2 diabetes. We suggest that although type 1 and type 2 diabetic patients appear to progress through similar stages of diabetic nephropathy, the route they take may differ. Differences in the way in which the glomeruli respond to the diabetic milieu may enable some type 2 diabetic patients to preserve their filtration surface in the face of an expanding mesangium.

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“…Differing study outcomes could be related to differences in glycemic control, center differences such as those encountered in the present study, or the much larger number of subjects in this report. Nonetheless, it is clear from the present study and previously published work that significant diabetic lesions are often present in normoalbuminuric subjects within a few years after onset of type 1 diabetes (5,9,22,23,25,26). Although on average, as demonstrated here and previously, microalbuminuric type 1 diabetic Data are means Ϯ SD.…”

Section: Discussionmentioning

confidence: 49%

“…The increase in GBM width and the fact that most of the increase in Vv(Mes/ glom) is due to increased Vv(MM/glom) (6,(25)(26)(27) are consistent with the central role of accumulation in the pathogenesis of DN. Even after adjustment for BSA and age, GlomVol was not significantly increased in the diabetic subjects.…”

Section: Tablementioning

confidence: 53%

The Early Natural History of Nephropathy in Type 1 Diabetes

2002

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Renal structural abnormalities are known to precede the development of proteinuria, hypertension, and reduced renal function in patients with type 1 diabetes. The determinants of these early structural abnormalities are, however, largely unknown. The International Diabetic Nephropathy Study (IDNS) has recruited 243 children and adults (aged 10 -40 years) in Montreal, Minneapolis, and Paris to identify and quantify these determinants. All study subjects were normotensive and had normal-to-high glomerular filtration rates (GFRs) and urinary albumin excretion rates (AERs) <100 g/ min at study entry. Only 8

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Glomerular structure in type-1 (insulin-dependent) diabetic patients with normo- and microalbuminuria

Cited by 94 publications

References 14 publications

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

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

Are glomerular volume differences between type 1 and type 2 diabetic patients pathologically significant?

The Early Natural History of Nephropathy in Type 1 Diabetes

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