Advertisement

Serum Uric Acid concentration is associated with insulin resistance and impaired insulin secretion in adults at risk for Type 2 Diabetes

Published:November 17, 2020DOI:https://doi.org/10.1016/j.pcd.2020.10.006

      Highlights

      • Serum uric acid (SUA) concentration is associated with increased insulin resistance.
      • SUA concentration is associated with impaired insulin secretion.
      • SUA concentration is not associated with beta-cell dysfunction in primary prevention for type 2 diabetes.
      • SUA could be a good biochemical marker for insulin resistance in primary prevention.

      Abstract

      Aims

      Insulin resistance (IR) predisposes to type 2 diabetes mellitus (T2DM). Although previous studies have associated serum uric acid concentration with IR in T2DM, its association with impaired insulin secretion and beta-cell dysfunction in subjects at risk for developing T2DM remains uncertain. Thus, we aimed to analyze the association of serum uric acid concentration with IR using surrogate insulin resistance/secretion and beta-cell function indices in subjects at risk for developing T2DM.

      Methods

      This is a cross-sectional study that included 354 subjects who underwent an oral glucose tolerance test who had at least two risk factors for T2DM without any chronic disease.

      Results

      Participants were 51 ± 8 years old, 72.2% were women, had a mean body mass index of 29.9 ± 6.5 kg/m2 and mean serum uric acid concentration of 5.7 ± 1.3 mg/dL. HOMA-IR, first-phase insulin secretion (S1PhOGTT), second-phase insulin secretion (S2PhOGTT), Matsuda and disposition indices were significantly correlated with serum uric acid concentrations (r = 0.239, r = 0.225, r = 0.201, r = −0.287, r = −0.208; respectively). After multiple linear regression analysis, serum uric acid concentration was independently associated with HOMA-IR (β = 0.283), HOMA-B (β = 0.185), S1PhOGTT (β = 0.203), S2PhOGTT (β = 0.186), and Matsuda Index (β = −0.322). A serum uric acid concentration of 5.5 mg/dL had the best sensitivity/sensibility to identify subjects with IR (HOMA-IR ≥2.5).

      Conclusions

      Serum uric acid concentration is significantly associated with IR and impaired insulin secretion, but not with beta-cell dysfunction, in subjects at risk for developing T2DM.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Primary Care Diabetes
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Di Pino A.
        • DeFronzo R.A.
        Insulin resistance and atherosclerosis: implications for insulin sensitizing agents.
        Endocr. Rev. 2019; 40: 1447-1467https://doi.org/10.1210/er.2018-00141
        • GBD 2015 Mortality and Causes of Death Collaborators
        Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015.
        Lancet. 2016; 388: 1459-1544https://doi.org/10.1016/S0140-6736(16)31012-1
        • Murray C.J.L.
        • Vos T.
        • Lozano R.
        • et al.
        Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010.
        Lancet. 2012; 380: 2197-2223https://doi.org/10.1016/S0140-6736(12)61689-4
        • Chatterjee S.
        • Khunti K.
        • Davies M.J.
        Type 2 diabetes.
        Lancet. 2017; 389: 2239-2251https://doi.org/10.1016/S0140-6736(17)30058-2
        • Yazıcı D.
        • Sezer H.
        Insulin resistance, obesity and lipotoxicity.
        Adv. Exp. Med. Biol. 2017; 960: 277-304https://doi.org/10.1007/978-3-319-48382-5_12
        • Watt M.J.
        • Miotto P.M.
        • De Nardo W.
        • Montgomery M.K.
        The liver as an endocrine organ—linking NAFLD and insulin resistance.
        Endocr. Rev. 2019; 40: 1367-1393https://doi.org/10.1210/er.2019-00034
        • Petersen M.C.
        • Shulman G.I.
        Mechanisms of insulin action and insulin resistance.
        Physiol. Rev. 2018; 98: 2133-2223https://doi.org/10.1152/physrev.00063.2017
        • Lillioja S.
        • Mott D.M.
        • Spraul M.
        • et al.
        Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians.
        N. Engl. J. Med. 1993; 329: 1988-1992https://doi.org/10.1056/NEJM199312303292703
        • Isomaa B.
        • Almgren P.
        • Tuomi T.
        • et al.
        Cardiovascular morbidity and mortality associated with the metabolic syndrome.
        Diabetes Care. 2001; 24: 683-689https://doi.org/10.2337/diacare.24.4.683
        • DeFronzo R.A.
        • Tobin J.D.
        • Andres R.
        Glucose clamp technique: a method for quantifying insulin secretion and resistance.
        Am. J. Physiol. 1979; 237: E214-E223https://doi.org/10.1152/ajpendo.1979.237.3.E214
        • Lorenzo C.
        • Williams K.
        • Haffner S.M.
        Insulin secretion based on the late oral glucose tolerance test period and incident diabetes: the San Antonio Heart Study: Insulin secretion, OGTT and incident diabetes.
        Diabet. Med. 2012; 29: e151-e158https://doi.org/10.1111/j.1464-5491.2012.03660.x
        • Gómez-Sámano M.A.
        • Cuevas-Ramos D.
        • Grajales-Gómez M.
        • et al.
        Reduced first-phase insulin secretion increases postprandial lipidemia in subjects with impaired glucose tolerance.
        BMJ Open Diab. Res. Care. 2017; 5: e000344https://doi.org/10.1136/bmjdrc-2016-000344
        • Stumvoll M.
        • Mitrakou A.
        • Pimenta W.
        • et al.
        Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity.
        Diabetes Care. 2000; 23: 295-301https://doi.org/10.2337/diacare.23.3.295
        • Virdis A.
        • Masi S.
        • Casiglia E.
        • et al.
        Identification of the uric acid thresholds predicting an increased total and cardiovascular mortality over 20 years.
        Hypertension. 2020; 75: 302-308https://doi.org/10.1161/HYPERTENSIONAHA.119.13643
        • Qiu Q.
        • Gong Y.
        • Liu X.
        • et al.
        Serum uric acid and impaired glucose tolerance: The Cardiometabolic Risk in Chinese (CRC) study.
        Cell Biochem. Biophys. 2015; 73: 155-162https://doi.org/10.1007/s12013-015-0597-5
        • Johnson R.J.
        • Perez-Pozo S.E.
        • Sautin Y.Y.
        • et al.
        Hypothesis: could excessive fructose intake and uric acid cause type 2 diabetes?.
        Endocr. Rev. 2009; 30: 96-116https://doi.org/10.1210/er.2008-0033
        • Sluijs I.
        • Beulens J.W.J.
        • van der D.L.A.
        • et al.
        Plasma uric acid is associated with increased risk of type 2 diabetes independent of diet and metabolic risk factors.
        J. Nutr. 2013; 143: 80-85https://doi.org/10.3945/jn.112.167221
        • Culleton B.F.
        • Larson M.G.
        • Kannel W.B.
        • Levy D.
        Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study.
        Ann. Intern. Med. 1999; 131: 7-13https://doi.org/10.7326/0003-4819-131-1-199907060-00003
        • Taniguchi Y.
        • Hayashi T.
        • Tsumura K.
        • et al.
        Serum uric acid and the risk for hypertension and Type 2 diabetes in Japanese men: The Osaka Health Survey.
        J. Hypertens. 2001; 19: 1209-1215https://doi.org/10.1097/00004872-200107000-00005
        • American Diabetes Association 2
        Classification and diagnosis of diabetes: standards of medical care in diabetes—2019.
        Diabetes Care. 2019; 42: S13-S28https://doi.org/10.2337/dc19-S002
        • Ueda P.
        • Woodward M.
        • Lu Y.
        • et al.
        Laboratory-based and office-based risk scores and charts to predict 10-year risk of cardiovascular disease in 182 countries: a pooled analysis of prospective cohorts and health surveys.
        Lancet Diabetes Endocrinol. 2017; 5: 196-213https://doi.org/10.1016/S2213-8587(17)30015-3
        • Matthews D.R.
        • Hosker J.R.
        • Rudenski A.S.
        • et al.
        Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.
        Diabetologia. 1985; 28: 412-419https://doi.org/10.1007/BF00280883
        • Wallace T.M.
        • Levy J.C.
        • Matthews D.R.
        Use and abuse of HOMA modeling.
        Diabetes Care. 2004; 27: 1487-1495https://doi.org/10.2337/diacare.27.6.1487
        • Matsuda M.
        • DeFronzo R.A.
        Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp.
        Diabetes Care. 1999; 22: 1462-1470https://doi.org/10.2337/diacare.22.9.1462
        • Seltzer H.S.
        • Allen E.W.
        • Herron A.L.
        • Brennan M.T.
        Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus.
        J. Clin. Invest. 1967; 46: 323-335https://doi.org/10.1172/JCI105534
        • Utzschneider K.M.
        • Prigeon R.L.
        • Faulenbach M.V.
        • et al.
        Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels.
        Diabetes Care. 2009; 32: 335-341https://doi.org/10.2337/dc08-1478
        • Spatola L.
        • Ferraro P.M.
        • Gambaro G.
        • et al.
        Metabolic syndrome and uric acid nephrolithiasis: insulin resistance in focus.
        Metabolism. 2018; 83: 225-233https://doi.org/10.1016/j.metabol.2018.02.008
        • Larsen T.R.
        • Gerke O.
        • Diederichsen A.C.P.
        • et al.
        The association between uric acid levels and different clinical manifestations of coronary artery disease.
        Coron Artery Dis. 2018; 29: 194-203https://doi.org/10.1097/MCA.0000000000000593
        • Johnson R.J.
        • Nakagawa T.
        • Sanchez-Lozada L.G.
        • et al.
        Sugar, uric acid, and the etiology of diabetes and obesity.
        Diabetes. 2013; 62: 3307-3315https://doi.org/10.2337/db12-1814
        • Kawamoto R.
        • Ninomiya D.
        • Kasai Y.
        • et al.
        Interaction between gender and uric acid on hemoglobin A1c in community-dwelling persons.
        J. Endocrinol. Invest. 2018; 41: 421-429https://doi.org/10.1007/s40618-017-0760-5
        • King C.
        • Lanaspa M.A.
        • Jensen T.
        • Tolan D.R.
        • Sánchez-Lozada L.G.
        • Johnson R.J.
        Uric acid as a cause of the metabolic syndrome.
        Contrib. Nephrol. 2018; 192: 88-102https://doi.org/10.1159/000484283
        • Tang W.
        • Fu Q.
        • Zhang Q.
        • et al.
        The association between serum uric acid and residual β-cell function in type 2 diabetes.
        J. Diabetes Res. 2014; : 709691https://doi.org/10.1155/2014/709691
        • Fang J.
        • Alderman M.H.
        Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971–1992. National Health and Nutrition Examination Survey.
        JAMA. 2000; 283: 2404-2410https://doi.org/10.1001/jama.283.18.2404
        • Aziz K.M.A.
        Effect of serum uric acid in augmentation of insulin secretion and improvement of HbA1c in diabetic patients: proposed statistical regression models for uric acid, HbA1c and insulin.
        J. Res. Diabetes. 2014; 2014: 1-14https://doi.org/10.5171/2014.237887
        • Yoo T.W.
        • Sung K.C.
        • Shin H.S.
        • et al.
        Relationship between serum uric acid concentration and insulin resistance and metabolic syndrome.
        Circ. J. 2005; 69: 928-933https://doi.org/10.1253/circj.69.928
        • Lee J.
        • Sparrow D.
        • Vokonas P.S.
        • Landsberg L.
        • Weiss S.T.
        Uric acid and coronary heart disease risk: evidence for a role of uric acid in the obesity-insulin resistance syndrome. The Normative Aging Study.
        Am. J. Epidemiol. 1995; 142: 288-294https://doi.org/10.1093/oxfordjournals.aje.a117634