Advertisement

Diabetologia

, Volume 30, Issue 4, pp 214–221 | Cite as

Ketone bodies increase glomerular filtration rate in normal man and in patients with Type 1 (insulin-dependent) diabetes mellitus

  • R. Trevisan
  • R. Nosadini
  • P. Fioretto
  • A. Avogaro
  • E. Duner
  • E. Jori
  • A. Valerio
  • A. Doria
  • G. Crepaldi
Originals

Summary

The purpose of this study was to investigate whether the administration of acetoacetic and hydrochloric acids in a group of control and Type 1 (insulin-dependent) diabetic patients influenced renal haemodynamics. Renal plasma flow increased from 657±88 to 762±81 ml·min−1. 1.73 m−2 in diabetic patients (p<0.01) and from 590±71 to 691±135 in control subjects (p<0.01). Glomerular filtration rate increased from 135±9 to 180±8 ml·min−1·1.73 m−2 in diabetic patients (p< 0.001) and from 117±8 to 145±7 in control subjects (p<0.01). Similar effects on renal haemodynamics, even if less pronounced, were observed with low dose acetoacetic but not with hydrochloric acid infusion. Total protein, β2-microglobulin but not albumin excretion rates were increased by acetoacetic acid. We conclude that an acute increase in blood concentration of ketone bodies within the range found in diabetic patients with poor metabolic control (1) increases renal plasma flow and glomerular filtration rate both in control subjects and diabetic patients and (2) causes a tubular proteinuria.

Key words

Type 1 diabetes glomerular filtration rate ketone bodies albumin excretion rate 

References

  1. 1.
    Stalder G, Schmid R (1959) Severe functional disorders of glomerular capillaries and renal haemodynamics in treated diabetes mellitus during childhood. Ann Paediat 193: 129–138Google Scholar
  2. 2.
    Ditzel J, Schwartz M (1967) Abnormally increased glomerular filtration rate in short-term insulin-treated diabetic subjects. Diabetes 16: 264–267Google Scholar
  3. 3.
    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
  4. 4.
    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
  5. 5.
    Viberti GC, Keen H (1984) Patterns of proteinuria in diabetes mellitus. Diabetes 133: 686–691Google Scholar
  6. 6.
    Wiseman J, Saunders AJ, Keen H, Viberti GC (1985) Effect of blood control on increased glomerular filtration rate and kidney size in insulin-dependent diabetes. N Engl J Med 312: 617–621Google Scholar
  7. 7.
    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
  8. 8.
    Christiansen JS (1984) On the pathogenesis of the increased glomerular filtration rate in short-term insulin-dependent diabetes. (Thesis) Laegeforeningens forlag, pp 1–44Google Scholar
  9. 9.
    Parving H-H, Christiansen JS, Noer I (1980) The effect of glucagon infusion on kidney function in short-term insulin-dependent juvenile diabetics. Diabetologia 20: 350–354Google Scholar
  10. 10.
    Christiansen JS, Gammelgaard J, Frandsen M (1982) Kidney function and size in type 1 (insulin-dependent) diabetic patients before and during growth hormone administration for one week. Diabetologia 22: 333–337Google Scholar
  11. 11.
    Nosadini R, Del Prato S, Tiengo A, Duner E, Toffolo G, Cobelli C, Faronato P, Moghetti P, Muggeo M (1982) Insulin sensitivity, binding and kinetics in pancreatogenic and type I diabetes. Diabetes 31: 346–355Google Scholar
  12. 12.
    Clements AH, Hough DL, D'Orazio PA (1982) Development of the biostator glucose clamping algorithm. Clin Chem 28: 1899–1908Google Scholar
  13. 13.
    Chantler C, Garnet ES, Parsons V, Veale N (1969) Glomerular filtration rate measurement in man by the single injection method using 51Cr-EDTA. Clin Sci 37: 169–180Google Scholar
  14. 14.
    Ram MD, Evans K, Chisholm GD (1967) Measurements of effective renal plasma-flow by the clearance of 125I hippuran. Lancet 1: 645–646Google Scholar
  15. 15.
    Nosadini R, Avogaro A, Trevisan R, Duner E, Marescotti C, Iori E, Cobelli C, Toffolo G (1985) Acetoacetate and 3-hydroxybutyrate kinetics in obese and insulin-dependent diabetic humans. Am J Physiol 248: R611-R620Google Scholar
  16. 16.
    Fery F, Balasse EO (1980) Differential effects of sodium acetoacetate and acetoacetic acid infusions on alanine and glutamine metabolism in man. J Clin Invest 66: 323–331Google Scholar
  17. 17.
    Keen H, Chlouverakis C (1963) An immunoassay method for urinary albumin at low concentrations. Lancet 2: 913–914Google Scholar
  18. 18.
    Evrin PE, Peterson PA, Wide L, Berggard I (1971) Radioimmunoassay for β 2-microglobulin in human biological fluids. Scand J Clin Lab Invest 28: 439–443Google Scholar
  19. 19.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254Google Scholar
  20. 20.
    Huggett ASG, Nixon DA (1957) Use of glucose-oxidase, peroxidase and O-dianisidine in determination of blood and urinary glucose. Lancet 2: 368–370Google Scholar
  21. 21.
    Lloyd B, Burrin J, Smithe P, Alberti K (1978) Simple automated enzymatic fluorimetric assay for blood glucose, lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate. Clin Chem 24: 1724–1729Google Scholar
  22. 22.
    Price C, Lloyd B, Alberti K (1977) A kinetic spectrophotometric assay for rapid determination of acetoacetate in blood. Clin Chem 23: 1893–1897Google Scholar
  23. 23.
    Nagakawa S, Hakayama H, Sasaky T, Yoshino K, Yu YY, Shinozaki K, Aoki S, Mashino K (1973) A simple method for the determination of serum free insulin levels in insulin-treated patients. Diabetes 22: 590–600Google Scholar
  24. 24.
    Faloona G, Unger RH (1974) Glucagon. In: Jaffe B, Behrman H (eds) Methods of hormone radioimmunoassay. Academic Press, New York, pp 317–330Google Scholar
  25. 25.
    Peake GT (1974) Growth hormone. In: Jaffe B, Behrman H (eds) Methods of hormone radioimmunoassay. Academic Press, New York, pp 103–121Google Scholar
  26. 26.
    Heding L (1975) Radioimmunological determination of human C peptide in serum. Diabetologia 11: 541–548Google Scholar
  27. 27.
    Schwartz HC, King C, Schwartz AL, Edmunds D, Schwartz R (1976) Effects of pregnancy on hemoglobin A1c in normal gestional diabetic women. Diabetes 25: 1118–1128Google Scholar
  28. 28.
    Sealey JE, Gerten-Banes J, Laragh W (1972) The renin system: variations in man measured by radioimmunoassay or bioassay. Kidney Int 1: 240–253Google Scholar
  29. 29.
    Snedecor GW, Cochran WG (1967) Statistical methods. Iowa State University Press, Ames, IowaGoogle Scholar
  30. 30.
    Mauer SM, Steffes MW, Azar S, Sandberg SK, Brown DM (1978) The effect of Goldblatt hypertension on the development of glomerular lesions of diabetes mellitus in the rat. Diabetes 27: 738–744Google Scholar
  31. 31.
    Nosadini R, Noy G, Nattrass M, Hadson A, Johnston D, Burrin J, Orskov H, Alberti KGMM (1982) The metabolic and hormonal response to acute normoglycaemia in type 1 (insulin-dependent) diabetes. Diabetologia 23: 220–228Google Scholar
  32. 32.
    Trevisan R, Nosadini R, Fioretto P, Iori E, Avogaro A, Duner E (1986) The effects of ketone body infusion on kidney function in normal and insulin-dependent diabetic subjects. Eur J Clin Invest 16: 48 (Abstract)Google Scholar
  33. 33.
    Chapman CB, Henschel A (1949) The effect of water diuresis on renal plasma flow. Science 109: 232–233Google Scholar
  34. 34.
    Brochner-Mortensen J (1973) The glomerular filtration rate during moderate hyperglycaemia in normal man. Acta Med Scand 194: 31–37Google Scholar
  35. 35.
    Crawford B, Ludemann H (1951) The renal response to intravenous injection of sodium chloride solutions in man. J Clin Invest 30: 1456–1462Google Scholar
  36. 36.
    DuBois D, DuBois F (1916) A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 17: 863–871Google Scholar
  37. 37.
    Mogensen CE (1972) Kidney function and glomerular permeability to macromolecules in early juvenile diabetes. (Thesis) Dan Med Bull [Suppl 3] 19: 1–40Google Scholar
  38. 38.
    Parving H-H, Viberti GC, Keen H, Christiansen JS, Lassen NA (1983) The haemodynamic origin of diabetic microangiopathy. Metabolism 32: 943–949Google Scholar
  39. 39.
    Ditzel J, Brochner-Mortesen J (1983) Tubular reabsorption rates as related to elevated glomerular filtration in diabetic children. Diabetes 32 [Suppl 2]: 28–33Google Scholar
  40. 40.
    Owen OE, Licht JH, Sapir DG (1981) Renal function and effects of partial rehydration during diabetic ketoacidosis. Diabetes 30: 510–518Google Scholar
  41. 41.
    Nagulesparan M, Flock EV, Kennedy A, Baird R, Bennet PH (1985) Increased proteinuria during fasting in obese non-insulin-dependent diabetics. Diabetic Nephrop 1: 150–155Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • R. Trevisan
    • 2
  • R. Nosadini
    • 1
  • P. Fioretto
    • 1
  • A. Avogaro
    • 2
  • E. Duner
    • 2
  • E. Jori
    • 1
  • A. Valerio
    • 1
  • A. Doria
    • 1
  • G. Crepaldi
    • 1
  1. 1.Patologia Medica I ePoliclinico UniversitarioPaduaItaly
  2. 2.Malattie del RicambioPoliclinico UniversitarioPaduaItaly

Personalised recommendations