Advertisement

Abnormal Carbohydrate and Lipoprotein Metabolism in Uremia

Possible Relationship to Atherogenesis
  • Gerald M. Reaven

Abstract

There is a good deal of evidence which indicates that abnormalities of carbohydrate and lipid metabolism occur frequently in patients with chronic renal failure (CRF). Given the increased incidence of atherosclerotic heart disease (ASHD) in patients with diabetes and/or hyperlipoproteinemia, it seems reasonable to wonder if the accelerated atherogenesis described in patients with CRF is related to the coexistence of abnormal carbohydrate and lipid metabolism in these patients. In this chapter I will attempt to approach this question by defining the effects of the uremic syndrome on carbohydrate and lipid metabolism and then suggesting possible mechanisms by which these changes could lead to atherosclerosis.

Keywords

Chronic Renal Failure Glucose Intolerance Lipoprotein Abnormality Plasma Insulin Response Hepatic Triglyceride Lipase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Reaven GM, Weisinger JR, Swenson RS: Insulin and glucose metabolism in renal insufficiency. Kidney Int 6:563–569, 1974.Google Scholar
  2. 2.
    Mondon CE, Dolkas CB, Reaven GM: Effect of acute uremia on insulin removal by the isolated perfused rat liver and muscle. Metabolism 27:133–142, 1978.PubMedCrossRefGoogle Scholar
  3. 3.
    Rabkin R, Unterhalter SA, Duckworth WC: Effect of prolonged uremia on insulin metabolism by isolated liver and muscle. Kidney Int 16:433–439, 1979.PubMedCrossRefGoogle Scholar
  4. 4.
    Swenson RS, Peterson DT, Eshleman M, Reaven GM: Effect of acute uremia on various aspects of carbohydrate metabolism in dogs. Kidney Int 4:267–272, 1973.PubMedCrossRefGoogle Scholar
  5. 5.
    Mondon CE, Dolkas CB, Reaven GM: The site of insulin resistance in acute uremia. Diabetes 25:571–576, 1978.CrossRefGoogle Scholar
  6. 6.
    DeFronzo RA: Pathogenesis of glucose intolerance in uremia. Metabolism 27:1866–1880, 1978.PubMedCrossRefGoogle Scholar
  7. 7.
    Sherwin RS, Bastle C, Finkelstein FO, Fisher M, Black H, Hendler R, Felig P: Influence of uremia and hemodialysis on the turnover and metabolic effects of glucagon. J Clin Invest 57:722–731, 1976.PubMedCrossRefGoogle Scholar
  8. 8.
    Soman J, Felig P: Glucagon and insulin binding to liver membranes in a partially nephrectomized uremic rat model. J Clin Invest 60:224–232, 1977.PubMedCrossRefGoogle Scholar
  9. 9.
    Mondon CE, Reaven GM: Evaluation of enhanced glucagon sensitivity as the cause of glucose intolerance in acutely uremic rats. Am J Clin Nutr 33:1456–1460, 1980.PubMedGoogle Scholar
  10. 10.
    Sanfelippo ML, Swenson RS, Reaven GM: Reduction of plasma triglycerides by diet in subjects with chronic renal failure. Kidney Int 11:54–61, 1977.PubMedCrossRefGoogle Scholar
  11. 11.
    Sanfelippo ML, Swenson RS, Reaven GM: Response of plasma triglycerides to dietary changes in patients on hemodialysis. Kidney Int 14:180–186, 1978.PubMedCrossRefGoogle Scholar
  12. 12.
    Reaven GM, Swenson RS, Sanfelippo ML: An inquiry into the mechanism of hypertriglyceridemia in patients with chronic renal failure. Am J Clin Nutr 33:1476–1484, 1980.PubMedGoogle Scholar
  13. 13.
    Bagdade JE, Porte D Jr, Bierman EL: Hypertriglyceridemia. A metabolic consequence of chronic renal failure. N Engl J Med 279:181–185, 1968.PubMedCrossRefGoogle Scholar
  14. 14.
    Bagdade JD: Uremic lipemia. Arch Intern Med 126:875–881, 1970.PubMedCrossRefGoogle Scholar
  15. 15.
    Boyer JL, Scheig RL: Inhibition of postheparin lipolytic activity in uremia and its relationship to hypertriglyceridemia. Proc Soc Exp Biol Med 134:603–605, 1970.PubMedGoogle Scholar
  16. 16.
    Fielding CJ: Further characterisation of lipoprotein lipase and hepatic post-heparin lipase from rat plasma. Biochim Biophys Acta 280:569–578, 1972.PubMedGoogle Scholar
  17. 17.
    Krauss RM, Levy RI, Fredrickson DS: Selective measurement of two lipase activities in postheparin plasma from normal subjects and patients with hyperlipoproteinemia. J Clin Invest 54:1107–1124, 1974.PubMedCrossRefGoogle Scholar
  18. 18.
    Mordasini R, Frey F, Flury W, Klose G, Greten H: Selective deficiency of hepatic triglyceride lipase in uremic patients. N Engl J Med 297:1362–1366, 1977.PubMedCrossRefGoogle Scholar
  19. 19.
    Bolzano K, Krempler F, Sandhofer F: Hepatic and extrahepatic triglyceride lipase activity in uraemic patients on chronic haemodialysis. Eur J Clin Invest 8:289–293, 1978.PubMedCrossRefGoogle Scholar
  20. 20.
    Crawford GA, Savdie E, Stewart JH: Heparin-released plasma lipases in chronic renal failure and after renal transplantation. Clin Sci 57:155–165, 1979.PubMedGoogle Scholar
  21. 21.
    Bagdade, JD, Albers JJ: Plasma high-density lipoprotein concentrations in chronic-hemo-dialysis and renal-transplant patients. N Engl J Med 296:1436–1439, 1977.PubMedCrossRefGoogle Scholar
  22. 22.
    Brunzell DD, Albers JJ, Haas LB, Goldberg AP, Agadoa L, Sherrard DJ: Prevalence of serum lipid abnormalities in chronic hemodialysis. Metabolism 26:903–910, 1977.PubMedCrossRefGoogle Scholar
  23. 23.
    Rapoport J, Aviram M, Chaimovitz C, Brook JG: Defective high-density lipoprotein composition in patients on chronic hemodialysis. N Engl J Med 299:1326–1329, 1978.PubMedCrossRefGoogle Scholar
  24. 24.
    Nikkilä EA: Metabolic regulation of plasma high density lipoprotein concentrations. Eur J Clin Invest 8:111–113, 1978.PubMedCrossRefGoogle Scholar
  25. 25.
    Reaven GM, Calciano A, Cody R, Lucas C, Miller R: Carbohydrate intolerance and hyperlipemia in patients with myocardial infarction without known diabetes mellitus. J Clin Endocrinol Metab 23:1013–1023, 1963.PubMedCrossRefGoogle Scholar
  26. 26.
    Heinle RA, Levy RI, Frederickson DS, Gorlin R: Lipid and carbohydrate abnormalities in patients with angiographically documented coronary artery disease. Am J Cardiol 24:178–186, 1969.PubMedCrossRefGoogle Scholar
  27. 27.
    Falsetti HL, Schnatz JD, Greene DG, Bunnell IL: Serum lipids and glucose tolerance in angiographically proved coronary artery disease. Chest 58:111–115, 1970.PubMedCrossRefGoogle Scholar
  28. 28.
    Kingsbury KJ: The relation between glucose tolerance and atherosclerotic vascular disease. Lancet 2:1374–1379, 1966.PubMedCrossRefGoogle Scholar
  29. 29.
    Sloan JM, Mackay JS, Sheridan B: Glucose tolerance and insulin response in atherosclerosis. Br Med J 4:586–588, 1970.PubMedCrossRefGoogle Scholar
  30. 30.
    Keen H, Jarrett RJ: Macroangiopathy—its prevalence in asymptomatic diabetes. Adv Metab Disord 2:(suppl)3–9, 1973.PubMedGoogle Scholar
  31. 31.
    Ostrander LD, Francis T, Hayner NS, Kjelsberg MO, Epstein FH: The relationship of cardiovascular disease to hyperglycemia. Ann Intern Med 62:1188–1198, 1965.PubMedGoogle Scholar
  32. 32.
    Epstein FH, Ostrander LD, Johnson BJ, Payne MW, Hayner NS, Keller JB, Francis T: Epidemiological studies of cardiovascular disease in a total community—Tecumseh, Michigan. Ann Intern Med 62:1170–1187, 1965.PubMedGoogle Scholar
  33. 33.
    Gordon T, Kannel, WB: Predisposition to atherosclerosis in the head, heart, and legs. JAMA 221:661–666, 1972.PubMedCrossRefGoogle Scholar
  34. 34.
    Garcia MJ, McNamara PM, Gordon T, Kannel WB: Morbidity and mortality in diabetics in the Framingham population. Sixteen year follow-up study. Diabetes 23:105–111, 1974.PubMedGoogle Scholar
  35. 35.
    Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR: Diabetes, blood lipids, and the role of obesity in coronary heart disease risk for women. The Framingham Study. Ann Intern Med 87:393–397, 1977.PubMedGoogle Scholar
  36. 36.
    Stout RW: Diabetes and atherosclerosis—the role of insulin. Diabetologia 16:141–150, 1979.PubMedCrossRefGoogle Scholar
  37. 37.
    Peters N, Hales CN: Plasma insulin concentrations after myocardial infarction. Lancet 1:1144–1145, 1965.PubMedCrossRefGoogle Scholar
  38. 38.
    Nikkilä EA, Miettinen TA, Vesenne MR, Pelkonen R: Plasma insulin in coronary heart disease. Lancet 2:508–511, 1965.PubMedCrossRefGoogle Scholar
  39. 39.
    Tzagournis M, Chiles R, Ryan JM, Skillman TG: Interrelationships of hyperinsulinism and hypertriglyceridemia in young patients in coronary heart disease. Circulation 38:1156–1163, 1968.PubMedGoogle Scholar
  40. 40.
    Malherbe C, deGasparo M, Berthet P, deHertogh R, Hoet JJ: The pattern of plasma insulin response to glucose in patients with a previous myocardial infarction—the respective effects of age and disease. Eur J Clin Invest 1:265–270, 1970.Google Scholar
  41. 41.
    Gertler MM, Leetma HE, Saluste E, Rosenberger JL, Guthrie RG: Ischemic heart disease. Insulin, carbohydrate and lipid interrelationships. Circulation 46:103–111, 1972.PubMedGoogle Scholar
  42. 42.
    Sorge F, Schwartkopff W, Neuhaus GU: Insulin response to oral glucose in patients with a previous myocardial infarction and in patients with peripheral vascular disease. Diabetes 25:586–594, 1976.PubMedCrossRefGoogle Scholar
  43. 43.
    Eschwege E, Ducimetiere P, Rosselin GE, Claude JR, Richard JL: 0–2 hr OGTT plasma glucose and insulin levels as coronary heart disease risk factors in middle-aged active men. Abstracts, 10th Congress of the IDF, 1979, p 59.Google Scholar
  44. 44.
    Albrink MJ, Man EB: Serum triglycerides in coronary heart disease. Arch Intern Med 103:4–8, 1959.CrossRefGoogle Scholar
  45. 45.
    Ostrander LD, Neff BJ, Block WD, Francis T, Epstein FH: Hyperglycemia and hypertriglyceridemia among persons with coronary heart disease. Ann Intern Med 67:34–41, 1967.PubMedGoogle Scholar
  46. 46.
    Santen RJ, Willis PW, Fajans SS: Atherosclerosis in diabetes mellitus. Arch Intern Med 130:833–843, 1972.PubMedCrossRefGoogle Scholar
  47. 47.
    Kännel WB, Castelli WP, Gordon T, McNamara PM: Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. Ann Intern Med 74:1–12, 1971.PubMedGoogle Scholar
  48. 48.
    Carlson LA, Böttiger LE, Ischaemic heart-disease in relation to fasting values of plasma triglycerides and cholesterol. Stockholm prospective study. Lancet 1:865–868, 1972.PubMedCrossRefGoogle Scholar
  49. 49.
    Castelli WP, Doyle JT, Gordon T, Harnes CG, Hjortland MC, Hulley SB, Kagan A, Zukel WJ: HDL-cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study. Circulation 55:767–772, 1977.PubMedGoogle Scholar
  50. 50.
    Logan RL, Thomson M, Riemersma RA, Oliver MF, Olsson AG, Rossner S, Callmer E, Walldius G, Kaijser L, Carlson LA, Lockerbie L, Lutz W: Risk factors for ischaemic heart-disease in normal men aged 40. Edinburgh-Stockholm study. Lancet 1:951–954, 1978.Google Scholar
  51. 51.
    Brunzell JD, Sherrard DJ: Atherosclerotic risk factors in a chronic dialysis population. Abstract, American Society of Nephrology, 12th Annual Meeting, 1979, p 118A.Google Scholar
  52. 52.
    Miller GJ, Miller NE: Plasma high density lipoprotein concentration and development of ischaemic heart-disease. Lancet 1:16–19, 1975.PubMedCrossRefGoogle Scholar
  53. 53.
    Rhoads GG, Gulbrandsen CL, Kagan A: Serum lipoproteins and coronary heart disease in a population study of Hawaiian Japanese men. N Engl J Med 294:293–298, 1976.PubMedCrossRefGoogle Scholar
  54. 54.
    Barr DP, Russ EM, Eder HA: Protein-lipid relationships in human plasma. II. In atherosclerosis and related conditions. Am J Med 11:480–493, 1951.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1985

Authors and Affiliations

  • Gerald M. Reaven
    • 1
    • 2
  1. 1.Department of MedicineStanford University School of MedicineUSA
  2. 2.Geriatric Research, Education and Clinical CenterVeterans Administration Medical CenterPalo AltoUSA

Personalised recommendations