, Volume 30, Issue 9, pp 713–718 | Cite as

Elevated serum uric acid — a facet of hyperinsulinaemia

  • M. Modan
  • H. Halkin
  • A. Karasik
  • A. Lusky


In a representative sample of the adult Jewish population in Israel (n=1016) excluding known diabetic patients and individuals on antihypertensive medications, serum uric acid showed a positive association with plasma insulin response (sum of 1- and 2-hour post glucose load levels) in both males (r=0.316, p<0.001) and females (r=0.236, p<0.001). This association remained statistically significant in both sexes (p<0.001) after accounting by multiple regression analysis for age and major correlates of serum uric acid, i.e. body mass index, glucose response (sum of 1- and 2-hour post load levels), systolic blood pressure and total plasma triglycerides. The net portion of the variance of serum uric acid attributable to insulin response was 12% in males and 8% in females, the total variance accountable by all these variables being 17% and 19% respectively. We conclude that elevated serum uric acid is a feature of hyperinsulinaemia/insulin resistance.

Key words

Serum uric acid hyperinsulinaemia Type 2 (non-insulin-dependent) diabetes impaired glucose tolerance hypertension obesity plasma triglycerides 


  1. 1.
    Beard JT (1983) Serum uric acid and coronary heart disease. Am Heart J 106: 397–400Google Scholar
  2. 2.
    Emerson BT (1978) Abnormal urate excretion associated with renal and systemic disorders, drugs and toxins. In: Kelley WN, Weiner IM (eds) Uric acid (Handbook of Experimental Pharmacology, vol 51) Springer, Berlin Heidelberg New York, pp 287–324Google Scholar
  3. 3.
    Okada M, Ueda K, Omae T, Takeshita M, Hirota Y (1982) The relationship of serum uric acid to hypertension and ischemic heart disease in Hisayama population, Japan. J Chron Dis 35: 173–178Google Scholar
  4. 4.
    Klein R, Klein BE, Cornoni JC, Mareadi J, Cassel JC, Tyroler A (1973) Serum uric acid: its relationship to coronary heart disease risk factors and cardiovascular disease. Arch Intern Med 132: 401–410Google Scholar
  5. 5.
    Yano K, Rhoads GG, Kagan A (1977) Epidemiology of serum uric acid among 8000 Japanese-American men in Hawaii. J Chron Dis 30: 171–184Google Scholar
  6. 6.
    Brand FN, McGee DL, Kannel WB, Stokes J 3rd, Castelli WP (1985) Hyperuricemia as a risk factor of coronary heart disease: The Framingham Study. Am J Epidemiol 121: 11–18Google Scholar
  7. 7.
    The Coronary Drug Project Research Group (1976) Serum uric acid: its association with other risk factors and with mortality in coronary heart disease. J Chron Dis 29: 557–569Google Scholar
  8. 8.
    Reunanen A, Takkunen H, Knekt P, Aromaa A (1982) Hyperuricemia as a risk factor for cardiovascular mortality. Acta Med Scan [Suppl] 668: 49–59Google Scholar
  9. 9.
    Persky VW, Dyer AR, Idris-Soven E, Stamler J, Shekelle RB, Schoenberger JA, Berkson DM, Lindberg HA (1979) Uric acid: A risk factor for coronary heart disease? Circulation 59: 959–977Google Scholar
  10. 10.
    Herman JB, Goldbourt U (1982) Uric acid and diabetes: Observations in a population study. Lancet II: 240–243Google Scholar
  11. 11.
    Reaven GM, Chen YDI, Donner CC, Fraze E (1985) How insulin resistant are patients with insulin dependent diabetes mellitus? Clin Endocrinol Metab 61: 32–36Google Scholar
  12. 12.
    Olefsky JM, Kolterman OG, Scarlett JA (1982) Insulin action and resistance in obesity and non-insulin dependent type II diabetes mellitus. Am J Physiol 243: E 15–30Google Scholar
  13. 13.
    DeFronzo RA, Ferrannini E (1982) The pathogenesis of non-insulin-dependent diabetes: an update. Medicine 61: 125–140Google Scholar
  14. 14.
    Bergman RN, Finegood DT, Ader M (1985) Assessment of insulin sensitivity in vivo. Endocr Rev 6: 45–86Google Scholar
  15. 15.
    Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Chetrit A, Fuchs Z (1985) Hyperinsulinemia — a link between hypertension, obesity and glucose intolerance. J Clin Invest 75: 809–817Google Scholar
  16. 16.
    Singer P, Godicke W, Voigt S, Hajdu I, Weiss M (1985) Post prandial hyperinsulinemia in patients with mild essential hypertension. Hypertension 7: 182–186Google Scholar
  17. 17.
    Lucas CP, Estigarribia JA, Darga LL, Reaven GM (1985) Insulin and blood pressure in obesity. Hypertension 7: 702–706Google Scholar
  18. 18.
    Christlieb AR, Krolewski AS, Warram JH, Soeldner JS (1985) Is insulin the link between hypertension and obesity? Hypertension 7 [Suppl II]: II-54–II-57Google Scholar
  19. 19.
    Fournier AM, Gadia MT, Kubrusly BB, Skyler JS, Sosenko JM (1986) Blood pressure, insulin and glycemia in non-diabetic subjects. Am J Med 80: 861–864Google Scholar
  20. 20.
    Abrams ME, Jarrett RJ, Keen H, Boyns DR, Crossley JN (1969) Oral glucose tolerance and related factors in a normal population sample. II. Interrelationship of glycerides, cholesterol and other factors with the glucose and insulin response. Br Med J 1: 599–602Google Scholar
  21. 21.
    Reaven GM, Greenfield MS (1981) Diabetic hypertriglyceridemia: Evidence for three clinical syndromes. Diabetes 30 [Suppl 2]: 66–75Google Scholar
  22. 22.
    Wyngaarden JB, Kelley WN (1976) Gout and hyperuricemia. Grune & Stratton, New York, pp 21–37Google Scholar
  23. 23.
    Fox IH, John D, DeBruyne S, Dwosh I, Marliss EB (1985) Hyperuricemia and hypertriglyceridemia: Metabolic basis for the association. Metabolism 34: 741–746Google Scholar
  24. 24.
    Modan M, Lubin F, Lusky A, Chetrit A, Fuchs Z, Halkin H (1987) Interrelationships of obesity, habitual diet, physical activity and glucose intolerance in the four main Israeli Jewish ethnic groups: The Israel GOH Study. In: Berry EM, Blondheim SH, Eliahou EH, Shafrir E (eds) Recent advances in obesity, research V. John Libbey, London, pp 46–59Google Scholar
  25. 25.
    National Diabetes Data Group (1979) Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28: 1039–1057Google Scholar
  26. 26.
    Harris MI, Hadden WC, Knowler EC, Bennett PH (1985) International criteria for the diagnosis of diabetes and impaired glucose tolerance. Diabetes Care 8: 562–567Google Scholar
  27. 27.
    Breckenridge A (1966) Hypertension and hyperuricemia. Lancet I: 15–18Google Scholar
  28. 28.
    Fessel WJ (1980) High uric acid as an indicator of cardiovascular disease: independence from obesity. Am J Med 68: 401–404Google Scholar
  29. 29.
    Gotfredsen A, McNair P, Christiansen C, Transbol I (1982) Renal hypouricaemia in insulin treated diabetes mellitus. Clin Chim Acta 120: 355–361Google Scholar
  30. 30.
    Bengtsson C, Tibblin E (1974) Serum uric acid levels in women. Acta Med Scand 196: 93–102Google Scholar
  31. 31.
    Murphy MB, Kohner E, Lewis PJ, Schumer D, Dollery CT (1982) Glucose intolerance in hypertensive patients treated with diuretics: a fourteen year old follow up. Lancet II: 1293–1295Google Scholar
  32. 32.
    Flamenbaum W (1983) Metabolic consequences of antihypertensive therapy. Ann Int Med 98: 875–880Google Scholar
  33. 33.
    Messerli FH, Fröhlich ED, Dreslinski GR, Suarez DH, Aristimuno GG (1980) Serum uric acid in essential hypertension: an indicator of renal vascular involvement. Ann Int Med 93: 817–821Google Scholar
  34. 34.
    Machoff C, Froech T, Thomas C, Asplin C, Pohl S (1986) Ketoacids are increased in obese patients with type II diabetes. Clin Res 34: 549 A (Abstract)Google Scholar
  35. 35.
    DeFronzo RA (1981) The effect of insulin on renal sodium metabolism. A review with clinical implications. Diabetologia 21: 165–171Google Scholar
  36. 36.
    Steele TH (1978) Urate excretion in man, normal and gouty. In: Kelley WN, Weiner IM (eds) Uric acid (Handbook of Experimental Pharmacology, vol 51) Springer, Berlin Heidelberg New York, pp 266–269Google Scholar
  37. 37.
    Breslau NA, Pak CYC (1983) Lack of effect of salt intake on urinary uric acid excretion. J Urol 129: 531–532Google Scholar
  38. 38.
    Barsotti G, Mezzomo N, Cristofano C, Giovannetti S (1983) Serum uric acid in mild essential hypertension. Clin Nephrol 20: 145–148Google Scholar
  39. 39.
    Fox IH (1981) Metabolic basis for disorders of purine nucleotide degradation. Metab Clin Exp 30: 616–634Google Scholar
  40. 40.
    Kelley WN (1983) Gout. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 1043–1114Google Scholar
  41. 41.
    Marangou AG, Weber KM, Boston RC, Aitken PM, Heggie JCP, Kirsner RLG, Best JD, Alford FP (1986) Metabolic consequences of prolonged hyperinsulinemia in humans: evidence for induction of insulin insensitivity. Diabetes 35: 1382–1389Google Scholar
  42. 42.
    Stout RW (1987) Insulin and atheroma — an update. Lancet I: 1077–1079Google Scholar
  43. 43.
    Orchard TJ, Becker DJ, Bates M, Kuller LH, Drash AL (1983) Plasma insulin and lipoprotein concentrations: an atherogenic association? Am J Epidemiol 118: 326–337Google Scholar
  44. 44.
    Garcia-Webb P, Bonser AM, Whiting D, Masarei JRL (1983) Insulin resistance — a risk factor for coronary heart disease? Scand J Clin Lab Invest 43: 677–685Google Scholar
  45. 45.
    Pyörälä K, Savolainen E, Kaukola S, Haapakoski J (1985) Plasma insulin as coronary heart disease risk factor: relationship to other risk factors and predictive value during 9 1/2 year follow-up of the Helsinki Policemen Study population. Acta Med Scand [Suppl] 701: 38–52Google Scholar
  46. 46.
    Ducimetiere P, Eschwege E, Papoz L, Richard JL, Claude JR, Rosselin G (1980) Relationship of plasma insulin level to the incidence of myocardial infarction and coronary heart disease. Diabetologia 19: 205–210Google Scholar
  47. 47.
    Cullen K, Stenhouse NS, Wearne KL, Welborn TA (1983) Multiple regression analysis of risk factors for cardiovascular disease and cancer mortality in Busselton, Western Australia — 13 year study. J Chron Dis 36: 371–377Google Scholar
  48. 48.
    Howard BV, Knowler WC, Vasquez B, Kennedy AL, Pettitt DJ, Bennett PH (1984) Plasma and lipoprotein cholesterol and triglyceride in the Pima Indian population. Arteriosclerosis 4: 462–471Google Scholar
  49. 49.
    Abrams ME, Jarrett RJ, Keen H, Boyns DR, Crossley JH (1969) Early glucose tolerance and related factors in a normal population sample. II. Interrelationship of glycerides, cholesterol and other factors with glucose and insulin response. Br Med J 1: 599–602Google Scholar
  50. 50.
    Modan M, Halkin H, Segal P, Lusky A (1985) Hyperinsulinemia — a link between glucose intolerance obesity hypertension and dyslipoproteinemia — The Israel GOH Study. Diabetes 34 [Suppl 1]: 64 (Abstract)Google Scholar
  51. 51.
    Bray GA (1979) Obesity. Disease a month 26: 1–85Google Scholar
  52. 52.
    Fuller JH, Shipley MJ, Rose G (1980) Coronary-heart-disease risk and impaired glucose tolerance. The Whitehall Study. Lancet 1: 1373–1376Google Scholar
  53. 53.
    Kannel WB, Sorlie P (1975) Hypertension in Framingham. In: Paul O (ed) Epidemiology and control of hypertension. Grune & Stratton, Orlando, pp 553–590Google Scholar
  54. 54.
    Grundy SM (1984) Recommendations for the treatment of hyperlipidemia in adults: a joint statement of the Nutrition Committee and the Council on Arteriosclerosis of the American Heart Association. Arteriosclerosis 4: 445 A-468 AGoogle Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • M. Modan
    • 1
    • 2
  • H. Halkin
    • 1
    • 2
  • A. Karasik
    • 1
    • 2
  • A. Lusky
    • 1
    • 2
  1. 1.Department of Clinical EpidemiologyChaim Sheba Medical CenterTel Hashomer
  2. 2.Department of MedicineTel Aviv University Sackler School of MedicineIsrael

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