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  • 1
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; dextran clearance ; IgG4 ; IgG ; IgG/IgG4 selectivity index ; diabetic nephropathy ; tubular function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Albuminuria is the first clinical event in the development of diabetic nephropathy. We assessed glomerular charge- and size selectivity in 51 patients with Type 1 (insulin-dependent) diabetes mellitus of juvenile onset and 11 healthy individuals. Patients were allocated to five groups. The urinary albumin excretion rate was normal in group D1; 30–100 mg/24 h in group D2; 101–300 mg/24 h in group D3 and greater than 300 mg/24 h in groups D4 and D5. Group D5 had elevated serum creatinine (above 110 μmol/l). Glomerular filtration rate and renal plasma flow were determined by constant infusion techniques and tubular protein reabsorption by excretion of β2-microglobulin. Charge selectivity was estimated from the IgG/IgG4 selectivity index. Size selectivity was measured by dextran clearance. Dextran was measured by refractive index detection after fractionation (2 Å fractions in the range 26–64 Å) by size exclusion chromatography. IgG/IgG4 selectivity index was significantly decreased in patients with albuminuria (p〈0.001). The drop in IgG/IgG4 selectivity index was found in patients with minimal albuminuria (D2) and was not accompanied by any changes in tubular function or glomerular haemodynamics. Size selectivity was significantly altered only in patients with the most advanced nephropathy (D5) as reflected by an increase in the clearance of 62 Å dextran (p〈0.04). We conclude that loss of glomerular charge selectivity precedes or accompanies the formation of new glomerular macromolecular pathways in the development of diabetic nephropathy.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Acta diabetologica 31 (1994), S. 19-25 
    ISSN: 1432-5233
    Keywords: Sodium retention ; Insulin treatment ; Recent onset type 1 diabetes ; Hyperinsulinaemia ; Improved glycaemic control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hypothesis that total body exchangeable sodium (ENa) is elevated in type 1 (insulin-dependent) diabetic patients with short-duration diabetes and no signs of microangiopathy was tested. Also tested was whether peripheral hyperinsulinaemia, in terms of the amounts of insulin injected subcutaneously, contributes to the increased ENa. Three studies were performed. Study 1 was a cross-sectional study comprising 28 type 1 diabetic men (aged 18–35 years) with short-duration diabetes (〈5 years) and no signs of diabetic complications, and 22 control subjects. Study 2 was a prospective study of 17 newly diagnosed diabetic patients (age 20–35 years, median 27 years) who were studied on two occasions on different insulin doses. Study 3 was a 12-month prospective intervention study of 21 type 1 diabetic patients with incipient nephropathy, who had been randomized either to recieve continuous subcutaneous insulin infusion for improvement of glycaemic control or to remain on conventional insulin treatment. In study 1, ENa was higher in short-duration type 1 diabetic men than in controls (3003±325 vs 2849±207 mEq/1.73 m2,P〈0.05) and was correlated significantly with the insulin dose (r=0.38,P〈0.05). In study 2, of the newly diagnosed diabetic patients, 11 received a reduced insulin dose and 6 an increased dose as compared with the initial study. ENa was reduced in all patients receiving less insulin (P〈0.001) and remained unchanged in patients receiving more insulin. In study 3, ENa was unchanged in patients treated for 12 months with insulin pumps, in spite of a reduction in HbA1c from 9.3±1.7 to 7.2±0.8%,P〈0.01. In conclusion sodium volume expansion in IDDM is an early abnormality not affected by improving glycaemic control, but associated with, and thus possibly causally related to, the daily injected insulin dose.
    Type of Medium: Electronic Resource
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