Diabetologia

, Volume 39, Issue 9, pp 1074–1082 | Cite as

Effects of insulin and lipid emulsion on renal haemodynamics and renal sodium handling in IDDM patients

  • T. Pelikánová
  • I. Smrčková
  • J. KŘíŽová
  • J. StŘíbrná
  • V. Lánská
Originals

Summary

To evaluate the role of insulin and hypertriglyceridaemia in the regulation of renal haemodynamics and sodium handling in insulin-dependent diabetes mellitus (IDDM), 11 IDDM patients without microalbuminuria and 13 weight-, age-, protein intake- and sex-matched healthy control subjects were studied. Clearances of inulin (Cin), para-amino-hippuric acid (CPAH), sodium (CNa), and lithium (CLi) were measured in four 60-min clearance periods (periods I, II, III and IV) during isoinsulinaemia with lipid emulsion infusion (study 1), a hyperinsulinaemic isoglycaemic clamp with Intralipid infusion (study 2), and during time-controlled isoinsulinaemia (study 3). We found that Cin, CPAH and filtration fraction were comparable in IDDM and control subjects, whereas CNa was decreased in diabetic subjects (2.01±1.11 vs 3.03±1.32 ml/min; p<0.05) due to elevations of proximal tubular fractional and absolute reabsorptions of sodium (p<0.05). Insulin infusion did not affect Cin, increased CPAH (p<0.05) and, consequently, lowered the filtration fraction (p<0.01) in both groups. While acute hyperinsulinaemia resulted in increases in distal tubular fractional and absolute reabsorptions of sodium (p<0.01) contributing to a fall in CNa (p<0.01) in control subjects, in diabetic subjects the sodium-retaining effect of insulin was not significant. The lipid emulsion did not alter any of the estimated parameters. We conclude that IDDM without microalbuminuria is associated with a tendency to sodium retention which is not aggravated by insulin when compared to control subjects. Acutely induced hypertriglyceridaemia does not alter renal haemodynamics or renal sodium handling.

Keywords

Insulin-dependent diabetes mellitus insulin infusion lipid emulsion glomerular filtration rate renal sodium reabsorption 

Abbreviations

IDDM

Insulin-dependent diabetes mellitus

GFR

glomerular filtration rate

RPF

renal plasma flow

Cin

clearance of inulin

CPAH

clearance of para-amino-hippuric acid

CNa

clearance of sodium

CLi

clearance of lithium

APRNa

absolute proximal tubular reabsorption of sodium

FPRNa

fractional proximal tubular reabsorption of sodium

ADRNa

absolute distal tubular reabsorption of sodium

FDRNa

fractional distal tubular reabsorption of sodium

FIRI

free plasma immunoreactive insulin

TG

serum triglycerides

NEFA

serum non-esterified fatty acids

MCR

metabolic clearance rate of glucose

FF

filtration fraction

ANOVA

analysis of variance

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Andersen AR, Christiansen JS, Andersen JK, Kreiner S, Deckert T (1983) Diabetic nephropathy in type 1 (insulin-dependent) diabetes: an epidemiological study. Diabetologia 25: 496–501Google Scholar
  2. 2.
    Krolewski AS, Warram JH, Christlieb AR, Busick EJ, Kahn CR (1985) The changing natural history of nephropathy in type 1 diabetes. Am J Med 78: 785–794Google Scholar
  3. 3.
    Mogensen CE (1971) Glomerular filtration rate and renal plasma flow in short-term and long-term juvenile diabetes mellitus. Scand J Clin Lab Invest 28: 91–100Google Scholar
  4. 4.
    Hostetter TH, Rennke HG, Brenner BM (1982) The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med 72: 375–380Google Scholar
  5. 5.
    Lervang HH, Jensen S, Brochner-Mortensen J, Ditzel J (1988) Early glomerular hyperfiltration and the development of late nephropathy in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 31: 723–729Google Scholar
  6. 6.
    Mogensen CE, Christensen CK (1984) Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311: 89–93Google Scholar
  7. 7.
    Ilstrup KM, Keane WF, Michels LD (1981) Intravascular and extravascular volumes in the diabetic rat. Life Sci 29: 717–724Google Scholar
  8. 8.
    Allen TJ, Cooper ME, O'Brien RC, Bach LA, Jackson B, Jerums G (1990) Glomerular filtration rate in streptozotocin-induced diabetic rats. Role of exchangeable sodium, vasoactive hormones, and insulin therapy. Diabetes 39: 1182–1190Google Scholar
  9. 9.
    Feldt-Rasmussen B, Mathiesen ER, Deckert T et al. (1987) Central role for sodium in the pathogenesis of blood pressure changes independent of angiotensin, aldosterone and catecholamines in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30: 610–617Google Scholar
  10. 10.
    O'Hare JP, Corrall RJ (1988) De natrio diabeticorum. Increased exchangeable sodium in diabetes. Diabet Med 5: 22–26Google Scholar
  11. 11.
    Skott P, Mathiesen ER, Hommel E, Gall M-A, Bruun NE, Parving H-H (1989) The increased proximal tubular reabsorption of sodium and water is maintained in long-term insulin-dependent diabetics with early nephropathy. Scand J Clin Lab Invest 49: 419–425Google Scholar
  12. 12.
    Brochner-Mortensen, J, Stockel M, Sorensen PJ, Nielsen AH, Ditzel J (1984) Proximal glomerulotubular balance in patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 27: 189–192Google Scholar
  13. 13.
    Hannedouche TP, Delgado AG, Gnionsahe DA, Boitard C, Lacour B, Grünfeld J-P (1990) Renal hemodynamics and segmental tubular reabsorption in early type 1 diabetes. Kidney Int 37: 1126–1133Google Scholar
  14. 14.
    Dieperink H, Eshoj O, Leyssac PP, Feldt-Rasmussen B (1993) Segmental tubular sodium reabsorption in type 1 diabetes. Diabet Med 10: 455–459Google Scholar
  15. 15.
    Körner A, Eklöf A-CH, Celsi G, Aperia A (1994) Increased renal metabolism in diabetes. Mechanism and functional implications. Diabetes 43: 629–633Google Scholar
  16. 16.
    Woods LL (1993) Mechanisms of renal hemodynamic regulation in response to protein feeding. Kidney Int 44: 659–675Google Scholar
  17. 17.
    Nosadini R, Trevisan R, Fioretto P et al. (1989) Kidney hemodynamics after ketone body and amino acid infusion in normal and IDDM subjects. Diabetes 38: 75–83Google Scholar
  18. 18.
    DeFronzo RA, Goldberg M, Agus Z (1976) The effects of glucose and insulin on renal electrolyte transport. J Clin Invest 58: 83–90Google Scholar
  19. 19.
    Skott P, Hother-Nielsen O, Bruun NE et al. (1989) Effects of insulin on kidney function and sodium excretion in healthy subjects. Diabetologia 32: 694–699Google Scholar
  20. 20.
    Friedberg CE, van Buren M, Bijlsma JA, Koomans HA (1991) Insulin increases sodium reabsorption in diluting segment in humans: evidence for indirect mediation through hypokalemia. Kidney Int 40: 251–256Google Scholar
  21. 21.
    Friedberg CE, Koomans HA, Bijlsma JA, Rabelink TJ, Dorhout Mees EJ (1991) Sodium retention by insulin may depend on fall in plasma potassium. Metabolism 40: 201–204Google Scholar
  22. 22.
    Stenvinkel P, Bolinder J, Alvestrand A (1992) Effects of insulin on renal haemodynamics and the proximal and distal tubular sodium handling in healthy subjects. Diabetologia 35: 1042–1048Google Scholar
  23. 23.
    Norgaard K, Jensen T, Skott P et al. (1991) Effects of insulin on renal haemodynamics and sodium handling in normal subjects. Scand J Clin Lab Invest 51: 367–376Google Scholar
  24. 24.
    Kageyama S, Yamamoto J, Isogai Y, Fujita T (1994) Effect of insulin on sodium reabsorption in hypertensive patients. Am J Hypertens 7: 409–415Google Scholar
  25. 25.
    Endre T, Mattiasson I, Berglund G, Hulthen UL (1994) Insulin and renal sodium retention in hypertension-prone men. Hypertension 23: 313–319Google Scholar
  26. 26.
    Skott P, Vaag A, Bruun NE et al. (1991) Effect of insulin on renal sodium handling in hyperinsulinaemic type 2 (non-insulin-dependent) diabetic patients with peripheral insulin resistance. Diabetologia 34: 275–281Google Scholar
  27. 27.
    Moorhead JF, Chan MK, El-Nahas M, Varghese Z (1982) Lipid nephrotoxicity and chronic progressive glomerular and tubulo-interstitial disease. Lancet II:1309–1311Google Scholar
  28. 28.
    Mulec H, Johnson S-AA, Bjorck S (1990) Relation between serum cholesterol and diabetic nephropathy. Lancet 335: 1537–1538Google Scholar
  29. 29.
    Kasiske BL, O'Donnell MP, Cowardin W, Keane WF (1990) Lipids and the kidney. Hypertension 15: 443–450Google Scholar
  30. 30.
    French SW, Yamanaka W, Ostward R (1967) Dietary induced glomerulosclerosis in the guinea pig. Arch Pathol 83: 204–210Google Scholar
  31. 31.
    Wellmann K, Volk BW (1970) Renal changes in experimental hypercholesterolaemia in normal and in subdiabetic rabbits. Lab Invest 22: 144–155Google Scholar
  32. 32.
    Diamond JR, Karnovsky MJ (1987) Exacerbation of chronic aminonucleotide nephrosis by dietary cholesterol supplementation. Kidney Int 32: 671–677Google Scholar
  33. 33.
    Kasiske BL, O'Donnell MP, Garvis WJ, Keane WF (1988) Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectomy model of chronic renal failure. Circulation Res 62: 267–274Google Scholar
  34. 34.
    Iverius PH (1972) The interactions between human plasma lipoproteins and connective tissue glycosaminoglycans. J Biol Chem 247: 2607–2613Google Scholar
  35. 35.
    Stenvinkel P, Ottosson-Seeberger A, Alvestrand A (1995) Renal hemodynamies and sodium handling in moderate renal insufficiency: The role of insulin resistance and dyslipidemia. J Am Soc Nephrol 5: 1751–1760Google Scholar
  36. 36.
    Stenvinkel P, Thörne A, Nordenström J, Alvestrand A (1996) Effects of acute hypertriglyceridaemia on renal haemodynamics and electrolytes. J Am Soc Nephrol 6: 444 (Abstract)Google Scholar
  37. 37.
    DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: A method for quantifying insulin secretion and resistance. Am J Physiol 237:E214-E227Google Scholar
  38. 38.
    Schwartz Sorensen S, Kjaer T, Amdisen A, Bjerregaard Pedersen E (1987) Effect of intravenous sodium loading on renal tubular handling of sodium and water in unilaterally nephrectomized humans. Scand J Clin Invest 47: 461–468Google Scholar
  39. 39.
    White RP, Samson EF (1954) Determination of inulin in plasma and urine by use of anthron. J Lab Clin Med 43: 475–478Google Scholar
  40. 40.
    Smith HM, Finkelstein N, Aliminosa L, Crowford B, Groher M (1945) The renal clearances of substituted hippuric acid derivates and other aromatic acids in dog and man. J Clin Invest 24: 338–341Google Scholar
  41. 41.
    Novak M (1965) Colorimetric ultramicromethod for the determination of free fatty acids. J Lipid Res 6: 431–433Google Scholar
  42. 42.
    Skott P, Waag A, Hother-Nielsen O et al. (1991) Effects of hyperglycaemia on kidney function, atrial natriuretic factor and plasma renin in patients with insulin-dependent diabetes mellitus. Scand J Lab Invest 51: 715–727Google Scholar
  43. 43.
    Tuttle KR, Bruton JL, Perusek MC, Lancaster JL, Kopp DT, DeFronzo RA (1991) Effect of strict glycemic control on renal hemodynamic response to amino acids and renal enlargement in insulin-dependent diabetes mellitus. N Engl J Med 324: 1626–1632Google Scholar
  44. 44.
    Christiansen JS, Gammelgaard J, Frandsen M, Parving H-H (1981) Increased kidney size, glomerular filtration rate, and renal plasma flow in short-term insulin dependent diabetics. Diabetologia 20: 451–456Google Scholar
  45. 45.
    Skott P, Hommel E, Bruun NE, Arnold-Larsen S, Parving HH (1988) Effects of acetazolamide on kidney function in type 1 (insulin-dependent) diabetic patients with diabetic nephropathy. Diabetologia 31: 806–810Google Scholar
  46. 46.
    Shirley DG, Singer DR, Sagnella GA et al. (1991) Effect of single test dose of lithium carbonate on sodium and potassium excretion in man. Clin Sci 81: 59–63Google Scholar
  47. 47.
    Olsen NV, Olsen MH, Fogh-Andersen N et al. (1993) Lithium clearance method and the renal response to low-dose dopamine in man: a randomized, controlled study. Clin Sci 84: 237–242Google Scholar
  48. 48.
    Schultz SG, Curran PF (1970) Coupled transport of sodium and organic solutes. Physiol Rev 50: 637–718Google Scholar
  49. 49.
    Stenvinkel P, Alvestrand A (1994) Insulin causes renal vasodilatation independently of renal prostaglandins in healthy humans. Nephrol Dial Transplant 9: 1728–733Google Scholar
  50. 50.
    Baron AD, Laakso M, Brechtel G, Edelman SV (1991) Mechanism of insulin resistance in insulin-dependent diabetes mellitus: a major role for reduced skeletal muscle blood flow. J Clin Endocrinol Metab 73: 637–643Google Scholar
  51. 51.
    Hall JE, Brands MW, Mizelle HL, Gaillard CA, Hildebrandt DA (1991) Chronic intrarenal hyperinsulinaemia does not cause hypertension. Am J Physiol 260:F663-F669Google Scholar
  52. 52.
    Trevisan R, Fioretto P, Semplicini A et al. (1990) Role of insulin and atrial natriuretic peptide in sodium retention in insulin-treated IDDM patients during isotonic volume expansion. Diabetes 39: 289–298Google Scholar
  53. 53.
    Baum M (1987) Insulin stimulates volume absorption in the rabbit proximal convolute tubule. J Clin Invest 79: 1104–1109Google Scholar
  54. 54.
    Fine LG, Badie-Dezfooly B, Lowe AG, Hamzeh A, Wells J, Salehmoghaddam S (1985) Stimulation of Na+-H+ anti-port is an early event in hypertrophy of renal proximal tubular cells. Proc Natl Acad Sci USA 82: 1736–1740Google Scholar
  55. 55.
    Gesek FA, Schoolwerth AC (1991) Insulin increases NA+/H+ exchange activity in proximal tubules from normotensive and hypertensive rats. Am J Physiol 260:F695-F703Google Scholar
  56. 56.
    Rabkin R, Ryan MP, Duckworth WC (1984) The renal metabolism of insulin. Diabetologia 27: 351–357Google Scholar
  57. 57.
    Moore RD (1973) Effect of insulin upon sodium pump in frog skeletal muscle. J Physiol 232: 23–45Google Scholar
  58. 58.
    Madsen KM, Tisher CC (1986) Structural-functional relationships along the distal nephron. Am J Physiol 250:F1-F15Google Scholar
  59. 59.
    Prager R, Wallace P, Olefsky JM (1987) In vivo kinetics of insulin action on peripheral glucose disposal and hepatic glucose output in normal and obese subjects. J Clin Invest 78: 472–481Google Scholar
  60. 60.
    Ferrannini E, Garrett EJ, Bevilacqua S, DeFronzo RA (1983) Effect of fatty acid on glucose production and utilization in man. J Clin Invest 72: 1737–1747Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • T. Pelikánová
    • 1
    • 2
  • I. Smrčková
    • 2
  • J. KŘíŽová
    • 2
  • J. StŘíbrná
    • 2
  • V. Lánská
    • 2
  1. 1.Department of DiabetesPostgraduate Medical SchoolPragueCzech Republic
  2. 2.Institute for Clinical and Experimental MedicinePragueCzech Republic

Personalised recommendations