Horm Metab Res 2001; 33(6): 370-378
DOI: 10.1055/s-2001-15415
Original Clinical

© Georg Thieme Verlag Stuttgart · New York

Glycemic Control Reverses Increases in Urinary Excretions of Immunoglobulin G and Ceruloplasmin in Type 2 Diabetic Patients with Normoalbuminuria

T. Narita 1 , H. Fujita 1 , J. Koshimura 1 , H. Meguro 1 , H. Kitazato 1 , T. Shimotomai 1 , E. Kagaya 2 , K. Suzuki 2 , M. Murata 3 , A. Usami 4 , S. Ito 1
  • 1 Division of Geriatric Medicine, Akita University Hospital, Akita, Japan
  • 2 First Department of Internal Medicine, Niigata University, Niigata, Japan
  • 3 Division of Internal Medicine, Akita Red Cross Hospital, Akita, Japan
  • 4 Division of Internal Medicine, Niigata Saiseikai Daini Hospital, Niigata, Japan
Further Information

Publication History

Publication Date:
31 December 2001 (online)

To examine whether urinary excretions of plasma proteins with molecular radii of 45 - 55 Å and different isoelectric points such as IgG (pl = 7.4) and ceruloplasmin (pl = 4.4) increase selectively in normoalbuminuric type 2 diabetic patients, urinary albumin excretion rate (AER), renal clearances of IgG, ceruloplasmin and α2-macroglobulin, and creatinine clearance (Ccr) were studied in timed overnight urine samples of 36 diabetic outpatients and 16 control subjects. Furthermore, to examine effect of glycemic control on these urinary protein excretions, the same analysis was performed before and after glycemic control in 17 diabetic inpatients admitted for glycemic control. Renal clearances of IgG and ceruloplasmin were significantly higher in diabetic outpatients than in the control group, whereas AER and renal clearance of α2-macroglobulin did not differ. Glycemic control caused significant decreases in renal clearances of IgG and ceruloplasmin, accompanied with tendency for Ccr to decrease (p = 0.055). The present results, together with our previous finding of selectively increased urinary excretions of 45 - 55 Å sized plasma proteins in parallel with enhanced glomerular filtration rate after acute protein loading, led us to conclude that enhanced intraglomerular hydraulic pressure may cause increases in clearances of IgG and ceruloplasmin, and that this change can be reversed by strict glycemic control in normoalbuminuric diabetic patients.

References

  • 1 Parving H H, Osterby R, Anderson P, Whsueh W A. Diabetic nephropathy. In: Brenner BM (ed). The Kidney. 5th ed.  Philadelphia: ; Saunders, 1996: 1864-1892
  • 2 Nakamura Y, Myers B D. Charge selectivity of proteinuria in diabetic glomerulopathy.  Diabetes. 1988;  37 1202-1211
  • 3 Pietravalle P, Morano S, Cristina G, De Rossi M G, Mariani G, Cotroneo P, Ghirlanda G, Clementi A, Andreani D, Di Mario U. Charge selectivity of proteinuria in type I diabetes explored by Ig subclass clearance.  Diabetes. 1991;  40 1685-1690
  • 4 Deckert T, Kofoed-Enevoldsen A, Vidal P, Nørgaard K, Andreasen H B, Feldt-Rasmussen B. Size- and charge-selectivity of glomerular filtration in Type 1 (insulin-dependent) diabetic patients with and without albuminuria.  Diabetologia. 1993;  36 244-251
  • 5 Morano S, Pietravalle P, De Rossi M G, Mariani G, Cristina G, Medici F, Sensi M, Andreani D, Di Mario U. A charge selectivity impairment in protein permselectivity is present in type 2 diabetes.  Acta Diabetol. 1993;  30 138-142
  • 6 Fox J G, Quinn J D, Paterson K R, O’Reilly D StJ, Smith M P, Boulton-Jones J M. Glomerular charge selectivity in type 1 (insulin-dependent) diabetes mellitus.  Diabet Med. 1995;  12 387-391
  • 7 Torffvit O, Rippe B. Size and charge selectivity of glomerular filter in patients with insulin-dependent diabetes mellitus: Urinary immunoglobulins and glycosaminoglycans.  Nephron. 1999;  83 301-307
  • 8 Myers B D, Winetz J A, Chui F, Michaels A S. Mechanisms of proteinuria in diabetic nephropathy: A study of glomerular barrier function.  Kidney Int. 1982;  21 633-641
  • 9 Tomlanovich S, Been W M, Jones HW I II, Schwartz H C, Myers B D. Functional nature of the glomerular injury in progressive diabetic glomerulopathy.  Diabetes. 1987;  36 556-565
  • 10 Scandling J D, Myers B D. Glomerular size-selectivity and microalbuminuria in early diabetic glomerular disease.  Kidney Int. 1992;  41 840-846
  • 11 Gall M A, Rossing P, Kofoed-Enevoldsen A, Nielsen F S, Parving H H. Glomerular size- and charge-selectivity in Type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy.  Diabetologia. 1994;  37 195-201
  • 12 Myers B D, Nelson R G, Williams G W, Bennett P H, Hardy S A, Berg R L, Loon N, Knowler W C, Mitch W E. Glomerular function in Pima Indians with non-insulin-dependent diabetes mellitus of recent onset.  J Clin Invest. 1991;  88 524-530
  • 13 Hostetter T H, Rennke H G, Brenner B M. The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies.  Am J Med. 1982;  72 375-380
  • 14 Zatz R, Meyer T W, Rennke H G, Brenner B M. Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy.  Proc Natl Acad Sci USA. 1985;  82 5963-5967
  • 15 Anderson S, Brenner B M. Pathogenesis of diabetic nephropathy: Hemodynamic considerations.  Diabetes Metab Rev. 1988;  4 163-177
  • 16 Tencer J, Torflfrit O, Thysell H, Rippe B, Grubb A. Proteinuria selectivity index based upon α2-macroglobulin or IgM is superior to the IgG based index in differentiating glomerular diseases.  Kidney Int. 1998;  54 2098-2105
  • 17 Narita T, Koshimura J, Suzuki K, Murata M, Meguro H, Fujita H, Kitazato H, Ito S. Effects of short-term glycemic control, low protein diet and administration of enarapril on renal hemodynamics and protein permselectivity in Type 2 diabetic patients with microalbuminuria.  Tohoku J Exp Med. 1999;  189 117-133
  • 18 Anderson S, Vora J P. Current concepts of renal hemodynamics in diabetes.  J Diabetes Complications. 1995;  9 304-307
  • 19 Narita T, Kitazato H, Koshimura J, Suzuki K, Murata M, Ito S. Effects of protein meals on the urinary excretion of various plasma proteins in healthy subjects.  Nephron. 1999;  81 398-405
  • 20 Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus.  Diabetes Care. 1997;  20 1183-1195
  • 21 Bertolatus J A, Abuyousef M, Hunsicker L G. Glomerular sieving of high molecular weight proteins in proteinuric rats.  Kidney Int. 1987;  31 1257-1266
  • 22 Yamazaki M, Ito S, Usami A, Tani N, Hanyu O, Nakagawa O, Nakamura H, Shibata A. Urinary excretion rate of ceruloplasmin in non-insulin dependent diabetic patients with different stage of nephropathy.  Eur J Endocrinol. 1995;  132 681-687
  • 23 Ito S, Usami A, Yamazaki M, Shibata A. A radioimmunometric assay for urinary α2-macroglobulin.  Tohoku J Exp Med. 1995;  176 137-147
  • 24 Brodows R G, Nichols D, Shaker G, Kubasik N P. Evaluation of a new radioimmunoassay for urinary albumin.  Diabetes Care. 1986;  9 189-193
  • 25 Maroni B J, Steinman T I, Mitch W E. A method for estimating nitrogen intake of patients with chronic renal failure.  Kidney Int. 1985;  27 58-65
  • 26 Paul A A, Southgate D AT. McCance and Widdowson’s The Composition of Foods, 4th ed.  London:; HMSO Books, 1978: 7-8
  • 27 Isaksson B. Urinary nitrogen output as a validity test in dietary surveys.  Am J Clin Nutr. 1980;  33 4-5
  • 28 Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The sixth report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure.  Arch Intern Med. 1997;  157 2413-2446
  • 29 American Diabetes Association. Standards of medical care for patients with diabetes mellitus.  Diabetes Care. 1998;  21 S23-S31
  • 30 European Diabetes Policy Group. A desktop guideline to Type 2 diabetes mellitus.  Diabet Med. 1999;  16 716-730
  • 31 Chalmers J, MacMahon S, Mancia G, Whitworth J, Beilin L, Hansson L, Neal B, Rodgers A, Ni Mhurchu C, Clark T. 1999 WHO-International Society of Hypertension Guidelines for the management of hypertension. Guidelines Sub-Committee.  Clin Exp Hypertens. 1999;  21 1009-1060
  • 32 Ramsay L E, Williams B, Johnston G D, MacGregor G A, Poston L, Potter J F, Poulter N R, Russel G. Guidelines for management of hypertension: report of the third working party of the British Hypertension Society.  J Hum Hypertens. 1999;  13 569-592
  • 33 Deckert T, Feldt-Rasmussen B, Djurup R, Deckert M. Glomerular size and charge selectivity in insulin-dependent diabetes mellitus.  Kidney Int. 1988;  33 100-106
  • 34 Jerums G, Alien T J, Cooper M E. Triphasic changes in selectivity with increasing proteinuria in type 1 and type 2 diabetes.  Diabetic Med. 1989;  6 772-779
  • 35 Hoogenberg K, Sluiter W J, Navis G, Van Haeften T W, Smit A J, Reitsma W D, Dullaart R PF. Exogenous norepinephrine induces an enhanced microproteinuric response in microalbuminuric insulin-dependent diabetes mellitus.  J Am Soc Nephrol. 1998;  9 643-654
  • 36 Fujita H, Narita T, Ito S. Abnormality in urinary protein excretion in Japanese men with impaired glucose tolerance.  Diabetes Care. 1999;  22 823-826
  • 37 Deen W M, Bridges C R, Brenner B M, Myers B D. Heteroporous model of glomerular size selectivity: Application to normal and nephrotic humans.  Am J Physiol. 1985;  249 (Renal Fluid Electrolyte Physiol 18) F374-F389
  • 38 Myers B D. Pathophysiology of proteinuria in immune glomerular injury.  Am J Nephrol. 1990;  10 19-23
  • 39 Tencer J, Frick I M, Oqvist B, Aim P, Rippe B. Size selectivity of the glomerular barrier to high molecular weight proteins. The upper size limitation of the shunt pathways.  Kidney Int. 1998;  53 709-715
  • 40 Kaysen G A, Myers B D, Couser W G, Rabkin R, Felts J M. Biology of disease. Mechanisms and consequences of proteinuria.  Lab Invest. 1986;  54 479-498
  • 41 Ishibashi F. Glomerular clearance and tubular reabsorption of IgGl and IgG4 in microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM).  Diabetes Res Clin Prac. 1993;  22 45-51
  • 42 Morelli E, Loon N, Meyer T W, Peters W, Myers B D. Effects of converting-enzyme inhibition on barrier function in diabetic glomerulopathy.  Diabetes. 1990;  39 76-82
  • 43 Remuzzi A, Ruggenenti P, Mosconi L, Pata V, Viberti G C, Remuzzi G. Effect of low-dose enalapril on glomerular size-selectivity in human diabetic nephropathy.  J Nephrol. 1993;  6 36-43
  • 44 Rosenberg M E, Swanson J E, Thomas B L, Hostetter T H. Glomerular and hormonal response to dietary protein intake in human renal disease.  Am J Physiol. 1987;  253 (Renal Fluid Electrolyte Physiol 22) F1083-F1090

T. Narita,M.D. 

Division of Geriatric Medicine
Akita University Hospital

1-1-1 Hondo, Akita 010-8543
Japan


Phone: Phone:+ 81 (18) 884-6040

Fax: Fax:+ 81 (18) 884-6449

Email: E-mail:narita@med.akita-u.ac.jp

    >