Glomerular Morphology by Light Microscopy in Non-Insulin-Dependent Diabetes Mellitus: Lack of Glomerular Hypertrophy

Schmitz, A.; Gundersen, Hans Jørgen G.; Østerby, Ruth

doi:10.2337/diab.37.1.38

Cited by 67 publications

(24 citation statements)

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“…Patients with IDDM have been reported to develop glomerular hyperfiltration that is not reverse with insulin therapy alone [SandahlChristiansen et al, 1981]. Interestingly, in patients suffering from non-insulin dependent diabetes (NIDDM), where plasma C-peptide levels are normal or above normal, no significant glomerular hyperfiltration is observed [Friedman et al, 1981;Schmitz et al, 1988]. Infusion of C-peptide into IDDM patients to produce physiological levels of this hormone has been shown to produce a significant reduction in glomerular filtration rate and an elevation in renal plasma flow [Johansson et al, 1992].…”

Section: Role Of Insulin and C-peptide Synergismmentioning

confidence: 99%

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: Role of insulin and C‐peptide

Joshua

Zhang

Falcone

et al. 2005

J of Cellular Biochemistry

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Complications associated with insulin-dependent diabetes mellitus (type-1diabetes) primarily represent vascular dysfunction that has its origin in the endothelium. While many of the vascular changes are more accountable in the late stages of type-1diabetes, changes that occur in the early or initial functional stages of this disease may precipitate these later complications. The early stages of type-1diabetes are characterized by a diminished production of both insulin and C-peptide with a significant hyperglycemia. During the last decade numerous speculations and theories have been developed to try to explain the mechanisms responsible for the selective changes in vascular reactivity and/or tone and the vascular permeability changes that characterize the development of type-1diabetes. Much of this research has suggested that hyperglycemia and/or the lack of insulin may mediate the observed functional changes in both endothelial cells and vascular smooth muscle. Recent studies suggest several possible mechanisms that might be involved in the observed decreases in vascular nitric oxide (NO) availability with the development of type-1 diabetes. In addition more recent studies have indicated a direct role for both endogenous insulin and C-peptide in the amelioration of the observed endothelial dysfunction. These results suggest a synergistic action between insulin and C-peptide that facilitates increase NO availability and may suggest new clinical treatment modalities for type-1 diabetes mellitus.

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Section: Role Of Insulin and C-peptide Synergismmentioning

confidence: 99%

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: Role of insulin and C‐peptide

Joshua

Zhang

Falcone

et al. 2005

J of Cellular Biochemistry

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“…Type I as well as type II diabetic patients were included in this study because both groups are affected by diabetic nephropathy (5,(22)(23)(24). Since the two groups did not differ significantly with regard to the quantities measured in general, no distinction was made between them in the following discussion.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Matrix Proteins as Early Markers in Diabetic Nephropathy

Jäckle-Meyer

Szukics²,

Neubauer³

et al. 1995

CCLM

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Summary: Basement membrane thickening and mesangial expansion characterize the renal involvement in diabetes mellitus and precede any symptoms of renal dysfunction, e. g., albuminuria and changes in glomerular filtration rate. Since the morphological changes can only be diagnosed by biopsy, this study was designed to investigate whether the urinary excretion of renal extracellular matrix proteins might reflect the morphological alterations.To specify the extent of renal involvement in diabetes, the patients, type I as well as type II diabetics, were classified according to their urinary albumin excretion: normal albumin excretion below 30 μg/min, microalbuminuria from 30 to 300 μg/min, and overt albuminuria above 200 μg/min. Laminin, collagen IV, and fibronectin, all intrinsic components of the renal extracellular matrix, were determined in serum and urine by radioimmunoassay or enzymelinked-immunosorbent-assay, respectively. The results are given as median values (x). Additionally, the urinary fragment pattern of fibronectin was analysed qualitatively by immunoblotting.Laminin concentrations in serum and in urine did not change in diabetics. Collagen IV decreased in serum of patients with increased albumin excretion (controls: χ = 255 μg/l, normoalbuminuric patients: χ = 56 μg/l J microalbuminuric patients: χ = 52 μg/l, and patients with overt albuminuria: χ = 70 μg/l; α < 0.01) and increased in urine (controls, normoalbuminuric and microalbuminuric patients: not detectable, patients with overt albuminuria: χ = 5 ng/12 h; α < 0.001). Fibronectin was elevated in serum (controls: χ = 355 mg/1; normoalbuminuric patients: χ = 640 mg/1, microalbuminuric patients: χ = 710 mg/1, and patients with overt albuminuria: χ = 630 mg/1; α < 0.0001) and in urine, even in patients with normal albumin excretion (controls: χ = 16.8 μg/12 h, normoalbuminuric patients: x= 121 μg/12h, microalbuminuric patients: x = 108μg/12h, patients with overt albuminuria: χ = 186 \ig/l2 h; α < 0.01). The urinary fragment pattern of fibronectin, consisting of two main bands of a relative molecular mass of M r 75000 and 45000, was not altered in controls and diabetics. Type I and type II diabetic patients did not show significant differences in any quantities tested.It was shown in this study that the determination of laminin and collagen IV in serum and urine gave no information exceeding the routinely used quantities of kidney function. But the renal fibronectin excretion was elevated before any functional changes occurred. It was concluded that this might be indicative of the early mesangial expansion in diabetes mellitus. The determination of urinary fibronectin could therefore probably serve as a more sensitive marker for renal involvement in diabetes mellitus than microalbuminuria or changes in glomerular filtration rate.

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“…As the disease progresses, loss of filtration area and glomerular damage are reflected in a falling creatinine clearance, a rising serum creatinine, and a steady decline in renal function (6,9,10). Microalbuminuria is believed to represent leaky nephrons without overt reduction in the single nephron glomerular filtration rate, whereas a rise in serum creatinine indicates the transition from leaky to occluded glomeruli in which filtration is reduced (9).…”

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Increased Collagen IV Excretion in Diabetes

Cohen

Lautenslager²,

Shearman³

2001

Diabetes Care

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OBJECTIVE -Increased albumin excretion in diabetes is believed to be derived from hemodynamic and/or permeability abnormalities, whereas mesangial matrix expansion gives rise to the reduction in glomerular filtration surface and decline in renal function in diabetic nephropathy. We postulated that the overproduction of extracellular matrix proteins underlying glomerulosclerosis in diabetes might be associated with the excretion of increased amounts of type IV collagen in the urine.RESEARCH DESIGN AND METHODS -To explore this hypothesis, we measured the urinary excretion of (human) collagen IV by immunoassay in 65 patients with type 1 or type 2 diabetes and various degrees of albuminuria and examined its relationship to filtration function assessed by the reciprocal of the serum creatinine (RSC).RESULTS -Collagen IV excretion showed a significant (P Ͻ 0.001) inverse correlation (r ϭ Ϫ0.62) with the RSC, and this correlation pertained regardless of whether albumin excretion was in the low (Յ100 g/mg creatinine; r ϭ Ϫ0.73) or high (Ͼ100 g/mg; r ϭ Ϫ0.53) range. In contrast, albumin excretion showed insignificant correlation with either collagen IV excretion (r ϭ 0.12) or with the RSC (r ϭ Ϫ0.20). Urinary collagen IV was significantly higher (P Ͻ 0.05) in patients with an RSC value Յ100 (28.3 Ϯ 2.4 ng/mg creatinine) than in patients with an RSC value Ͼ100 (16.0 Ϯ 0.8 ng/mg creatinine).CONCLUSIONS -Because not all patients with microalbuminuria progress to declining renal function and some patients who develop nephropathy do not manifest albuminuria, the findings in this cross-sectional analysis suggest that measurement of urine collagen IV may be a useful noninvasive indicator to detect diabetic renal disease entering a phase of compromised renal function. Diabetes Care 24:914 -918, 2001I n its earliest phases, the development of diabetic nephropathy in human patients is marked by increased urinary excretion of albumin (1). In type 1 diabetes, microalbuminuria usually does not become manifest until several years after the onset of the disease, and its appearance may antedate overt nephropathy by many years (1,2). In type 2 diabetes, microalbuminuria may be present at the time of diagnosis, and the interval to appearance of overt nephropathy may be more contracted (3). As albumin excretion becomes more pronounced, glomerular structural changes are observed, most notably as an accumulation of extracellular matrix in the glomerular mesangium and a thickening of the peripheral glomerular basement membrane (4 -8).As the disease progresses, loss of filtration area and glomerular damage are reflected in a falling creatinine clearance, a rising serum creatinine, and a steady decline in renal function (6,9,10). Microalbuminuria is believed to represent leaky nephrons without overt reduction in the single nephron glomerular filtration rate, whereas a rise in serum creatinine indicates the transition from leaky to occluded glomeruli in which filtration is reduced (9). In type 1 diabetes, the magnitude of the mesangial expansion...

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Glomerular Morphology by Light Microscopy in Non-Insulin-Dependent Diabetes Mellitus: Lack of Glomerular Hypertrophy

Cited by 67 publications

References 0 publications

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: Role of insulin and C‐peptide

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: Role of insulin and C‐peptide

Extracellular Matrix Proteins as Early Markers in Diabetic Nephropathy

Increased Collagen IV Excretion in Diabetes

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