Summary
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.
Article PDF
Similar content being viewed by others
References
Beard JT (1983) Serum uric acid and coronary heart disease. Am Heart J 106: 397–400
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 287–324
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: 173–178
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: 401–410
Yano K, Rhoads GG, Kagan A (1977) Epidemiology of serum uric acid among 8000 Japanese-American men in Hawaii. J Chron Dis 30: 171–184
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: 11–18
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: 557–569
Reunanen A, Takkunen H, Knekt P, Aromaa A (1982) Hyperuricemia as a risk factor for cardiovascular mortality. Acta Med Scan [Suppl] 668: 49–59
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: 959–977
Herman JB, Goldbourt U (1982) Uric acid and diabetes: Observations in a population study. Lancet II: 240–243
Reaven GM, Chen YDI, Donner CC, Fraze E (1985) How insulin resistant are patients with insulin dependent diabetes mellitus? Clin Endocrinol Metab 61: 32–36
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 15–30
DeFronzo RA, Ferrannini E (1982) The pathogenesis of non-insulin-dependent diabetes: an update. Medicine 61: 125–140
Bergman RN, Finegood DT, Ader M (1985) Assessment of insulin sensitivity in vivo. Endocr Rev 6: 45–86
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: 809–817
Singer P, Godicke W, Voigt S, Hajdu I, Weiss M (1985) Post prandial hyperinsulinemia in patients with mild essential hypertension. Hypertension 7: 182–186
Lucas CP, Estigarribia JA, Darga LL, Reaven GM (1985) Insulin and blood pressure in obesity. Hypertension 7: 702–706
Christlieb AR, Krolewski AS, Warram JH, Soeldner JS (1985) Is insulin the link between hypertension and obesity? Hypertension 7 [Suppl II]: II-54–II-57
Fournier AM, Gadia MT, Kubrusly BB, Skyler JS, Sosenko JM (1986) Blood pressure, insulin and glycemia in non-diabetic subjects. Am J Med 80: 861–864
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: 599–602
Reaven GM, Greenfield MS (1981) Diabetic hypertriglyceridemia: Evidence for three clinical syndromes. Diabetes 30 [Suppl 2]: 66–75
Wyngaarden JB, Kelley WN (1976) Gout and hyperuricemia. Grune & Stratton, New York, pp 21–37
Fox IH, John D, DeBruyne S, Dwosh I, Marliss EB (1985) Hyperuricemia and hypertriglyceridemia: Metabolic basis for the association. Metabolism 34: 741–746
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 46–59
National Diabetes Data Group (1979) Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28: 1039–1057
Harris MI, Hadden WC, Knowler EC, Bennett PH (1985) International criteria for the diagnosis of diabetes and impaired glucose tolerance. Diabetes Care 8: 562–567
Breckenridge A (1966) Hypertension and hyperuricemia. Lancet I: 15–18
Fessel WJ (1980) High uric acid as an indicator of cardiovascular disease: independence from obesity. Am J Med 68: 401–404
Gotfredsen A, McNair P, Christiansen C, Transbol I (1982) Renal hypouricaemia in insulin treated diabetes mellitus. Clin Chim Acta 120: 355–361
Bengtsson C, Tibblin E (1974) Serum uric acid levels in women. Acta Med Scand 196: 93–102
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: 1293–1295
Flamenbaum W (1983) Metabolic consequences of antihypertensive therapy. Ann Int Med 98: 875–880
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: 817–821
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)
DeFronzo RA (1981) The effect of insulin on renal sodium metabolism. A review with clinical implications. Diabetologia 21: 165–171
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 266–269
Breslau NA, Pak CYC (1983) Lack of effect of salt intake on urinary uric acid excretion. J Urol 129: 531–532
Barsotti G, Mezzomo N, Cristofano C, Giovannetti S (1983) Serum uric acid in mild essential hypertension. Clin Nephrol 20: 145–148
Fox IH (1981) Metabolic basis for disorders of purine nucleotide degradation. Metab Clin Exp 30: 616–634
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 1043–1114
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: 1382–1389
Stout RW (1987) Insulin and atheroma — an update. Lancet I: 1077–1079
Orchard TJ, Becker DJ, Bates M, Kuller LH, Drash AL (1983) Plasma insulin and lipoprotein concentrations: an atherogenic association? Am J Epidemiol 118: 326–337
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: 677–685
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: 38–52
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: 205–210
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: 371–377
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: 462–471
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: 599–602
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)
Bray GA (1979) Obesity. Disease a month 26: 1–85
Fuller JH, Shipley MJ, Rose G (1980) Coronary-heart-disease risk and impaired glucose tolerance. The Whitehall Study. Lancet 1: 1373–1376
Kannel WB, Sorlie P (1975) Hypertension in Framingham. In: Paul O (ed) Epidemiology and control of hypertension. Grune & Stratton, Orlando, pp 553–590
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 A
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Modan, M., Halkin, H., Karasik, A. et al. Elevated serum uric acid — a facet of hyperinsulinaemia. Diabetologia 30, 713–718 (1987). https://doi.org/10.1007/BF00296994
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00296994