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December 4, 1991, Vol 266, No. 21 >
ARTICLE | December 4, 1991

Relationship Between Resistance to Insulin-Mediated Glucose Uptake, Urinary Uric Acid Clearance, and Plasma Uric Acid Concentration FREE

Francesco Facchini, MD; Y.-D. Ida Chen, PhD; Clarie B. Hollenbeck, PhD; Gerald M. Reaven, MD
[+] Author Affiliations

Reprint requests to Geriatric Research, Education, and Clinical Center (182-B), Veterans Affairs Medical Center, 3801 Miranda Ave, Palo Alto, CA 94304 (Dr Reaven).


JAMA. 1991;266(21):3008-3011. doi:10.1001/jama.1991.03470210076036
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References

Objective.  —To define the relationship, if any, between insulin-mediated glucose disposal and serum uric acid.

Design.  —Cross-sectional study of healthy volunteers.

Setting.—  General Clinical Research Center, Stanford (Calif) University Medical Center.

Participants.  —Thirty-six presumably healthy individuals, nondiabetic, without a history of gout.

Measurements.  —Obesity (overall and regional), plasma glucose and insulin responses to a 75-g oral glucose load, fasting uric acid concentrations, plasma triglyceride and high-density lipoprotein—cholesterol concentrations, systolic and diastolic blood pressure, insulin-mediated glucose disposal, and urinary uric acid clearance.

Results.  —Magnitude of insulin resistance and serum uric acid concentration were significantly related (r =.69; P<.001), and the relationship persisted when differences in age, sex, overall obesity, and abdominal obesity were taken into account (r =.57; P<.001). Insulin resistance was also inversely related to urinary uric acid clearance (r = -.49; P<.002), and, in addition, urinary uric acid clearance was inversely related to serum uric acid concentration (r = -.61; P<.001).

Conclusions.  —Urinary uric acid clearance appears to decrease in proportion to increases in insulin resistance in normal volunteers, leading to an increase in serum uric acid concentration. Thus, it appears that modulation of serum uric concentration by insulin resistance is exerted at the level of the kidney.(JAMA. 1991;266:3008-3011)

REFERENCES

1 +
Reaven G.  Role of insulin resistance in human disease: Banting lecture. Diabetes . 1988;;37:1595-1607.
2 +
Gertler MM, Garn SM, Levine SA.  Serum uric acid in relation to age and physique in health and coronary heart disease. Ann Intern Med . 1951;;34:1421-1431.
3 +
Myers AR, Epstein FH, Dodge HJ, Mikkelsen WM.  The relationship of serum uric acid to risk factors in coronary heart disease. Am J Med . 1968;;45:520-528.
4 +
Klein R, Klein BE, Coroni JC, Maready J, Cassell JC, Tyroler HA.  Serum uric acid: its relationship to coronary heart disease risk factors and cardiovascular disease, Evans County, Georgia. Arch Intern Med . 1973;;132:401-410.
5 +
Kagan A, Gordton T, Rhoads GG, Shiffmann JC.  Some factors related to coronary heart disease incidence in Honolulu Japanese men: the Honolulu Heart Study. Int J Epidemiol . 1975;;4:271-279.
6 +
Coronary Drug Project Research Group.  Serum uric acid: its association with other risk factors and with mortality in coronary heart disease. J Chronic Dis . 1976;;29:557-569.
7 +
Takkunen H, Reunanen A.  Hyperuricemia and other cardiovascular risk factors. Adv Exp Med Biol . 1977;;76B:238-244.
8 +
Persky VW, Dyer AR, Idris-Soven E, et al.  Uric acid: a risk factor for coronary heart disease? Circulation . 1979;;59:969-977.
9 +
Brand FEN, McGee DL, Kannel WB, Stokes J III, Castelli WP.  Hyperuricemia as a risk factor of coronary heart disease: the Framingham Study. Am J Epidemiol . 1985;;121:11-18.
10 +
Wyngaarden JB, Kelley WN. Gout and Hyperuricemia . New York, NY: Grune & Stratton; 1976;.
11 +
Wyngaarden JB, Kelley WN.  Gout.  In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Gold-stein JL, Brown MS, eds. Metabolic Basis of Inherited Disease . 5th ed. New York, NY: McGraw-Hill International Book Co; 1983;:1043-1144.
12 +
Golay A, Chen N, Chen Y-DI, Hollenbeck C, Reaven GM.  Effect of central obesity on regulation of carbohydrate metabolism in obese patients with varying degrees of glucose tolerance. J Clin Endocrinol Metab . 1990;;71:1299-1304.
13 +
Trivedi RC, Rebar L, Berta E, Stong L.  New enzymatic method for serum uric acid at 500 nm. Clin Chem . 1978;;24:1908-1911.
14 +
Kadish AH, Little RL, Sternberg JC.  A new and rapid method for determination of glucose by measurement of rate of oxygen consumption. Clin Chem . 1971;;14:116-131.
15 +
Hales CN, Randle PJ.  Immunoassay of insulin with insulin antibody precipitate. Biochem J . 1963;;88:137-146.
16 +
Kaplan AL, Pesce AJ.  Methods of creatinine analysis.  In: Kaplan AL, Pesce AJ, eds. Clinical Chemistry . Philadelphia, Pa: CV Mosby Co; 1989;:1016-1018.
17 +
Greenfield MS, Doberne L, Kraemer FB, Tobey TA, Reaven GM.  Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp. Diabetes . 1981;;30:387-392.
18 +
Modan M, Halkin H, Karasik A, Lusky A.  Elevated serum uric acid: a facet of hyperinsulinaemia. Diabaetologia . 1987;;30:713-718.
19 +
Hollenbeck CB, Chen N, Chen Y-DI, Reaven GM.  Relationship between the serum insulin response to oral glucose and insulin-stimulated glucose utilization in normal subjects. Diabetes . 1984;;33:460-463.
20 +
Defronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ.  The effect of insulin in renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest . 1975;;55:845-855.
21 +
Holmes EW, Kelley WN, Wyngaarden JB.  The kidney and uric acid excretion in man. Kidney Int . 1972;;2:115-118.

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1 +
Reaven G.  Role of insulin resistance in human disease: Banting lecture. Diabetes . 1988;;37:1595-1607.
2 +
Gertler MM, Garn SM, Levine SA.  Serum uric acid in relation to age and physique in health and coronary heart disease. Ann Intern Med . 1951;;34:1421-1431.
3 +
Myers AR, Epstein FH, Dodge HJ, Mikkelsen WM.  The relationship of serum uric acid to risk factors in coronary heart disease. Am J Med . 1968;;45:520-528.
4 +
Klein R, Klein BE, Coroni JC, Maready J, Cassell JC, Tyroler HA.  Serum uric acid: its relationship to coronary heart disease risk factors and cardiovascular disease, Evans County, Georgia. Arch Intern Med . 1973;;132:401-410.
5 +
Kagan A, Gordton T, Rhoads GG, Shiffmann JC.  Some factors related to coronary heart disease incidence in Honolulu Japanese men: the Honolulu Heart Study. Int J Epidemiol . 1975;;4:271-279.
6 +
Coronary Drug Project Research Group.  Serum uric acid: its association with other risk factors and with mortality in coronary heart disease. J Chronic Dis . 1976;;29:557-569.
7 +
Takkunen H, Reunanen A.  Hyperuricemia and other cardiovascular risk factors. Adv Exp Med Biol . 1977;;76B:238-244.
8 +
Persky VW, Dyer AR, Idris-Soven E, et al.  Uric acid: a risk factor for coronary heart disease? Circulation . 1979;;59:969-977.
9 +
Brand FEN, McGee DL, Kannel WB, Stokes J III, Castelli WP.  Hyperuricemia as a risk factor of coronary heart disease: the Framingham Study. Am J Epidemiol . 1985;;121:11-18.
10 +
Wyngaarden JB, Kelley WN. Gout and Hyperuricemia . New York, NY: Grune & Stratton; 1976;.
11 +
Wyngaarden JB, Kelley WN.  Gout.  In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Gold-stein JL, Brown MS, eds. Metabolic Basis of Inherited Disease . 5th ed. New York, NY: McGraw-Hill International Book Co; 1983;:1043-1144.
12 +
Golay A, Chen N, Chen Y-DI, Hollenbeck C, Reaven GM.  Effect of central obesity on regulation of carbohydrate metabolism in obese patients with varying degrees of glucose tolerance. J Clin Endocrinol Metab . 1990;;71:1299-1304.
13 +
Trivedi RC, Rebar L, Berta E, Stong L.  New enzymatic method for serum uric acid at 500 nm. Clin Chem . 1978;;24:1908-1911.
14 +
Kadish AH, Little RL, Sternberg JC.  A new and rapid method for determination of glucose by measurement of rate of oxygen consumption. Clin Chem . 1971;;14:116-131.
15 +
Hales CN, Randle PJ.  Immunoassay of insulin with insulin antibody precipitate. Biochem J . 1963;;88:137-146.
16 +
Kaplan AL, Pesce AJ.  Methods of creatinine analysis.  In: Kaplan AL, Pesce AJ, eds. Clinical Chemistry . Philadelphia, Pa: CV Mosby Co; 1989;:1016-1018.
17 +
Greenfield MS, Doberne L, Kraemer FB, Tobey TA, Reaven GM.  Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp. Diabetes . 1981;;30:387-392.
18 +
Modan M, Halkin H, Karasik A, Lusky A.  Elevated serum uric acid: a facet of hyperinsulinaemia. Diabaetologia . 1987;;30:713-718.
19 +
Hollenbeck CB, Chen N, Chen Y-DI, Reaven GM.  Relationship between the serum insulin response to oral glucose and insulin-stimulated glucose utilization in normal subjects. Diabetes . 1984;;33:460-463.
20 +
Defronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ.  The effect of insulin in renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest . 1975;;55:845-855.
21 +
Holmes EW, Kelley WN, Wyngaarden JB.  The kidney and uric acid excretion in man. Kidney Int . 1972;;2:115-118.

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