Gender Difference in the Association between Serum Uric Acid and Diabetes Mellitus

尿酸與糖尿病之相關性探討－臺灣北部某區域醫院成人健檢資料分析

10.3966/168232812013092303002

陳威志(Wei-Chih Chen)；陳昱竹(Yu-Chu Chen)；陳美如(Mei-Ju Chen)

diabetes mellitus ； gender difference ； uric acid

台灣家庭醫學雜誌

23卷3期（2013 / 09 / 01）

120 - 132

英文

目的：目前已知尿酸和胰島素阻抗及新陳代謝症候群有關，但針對尿酸和糖尿病的相關性及其在不同性別差異性進行探討的研究仍不多見。本研究透過分析統計全民健保成人預防保健資料，探討尿酸與糖尿病的相關性。方法：本研究使用2006至2011年北部某區域醫院所承作的健保成人健檢資料樣本共7,568人進行統計分析，依其過去病史、健康行為、身高、體重、血壓及實驗室檢查的數據，將受檢者血中尿酸濃度由低至高分成四組分析尿酸與糖尿病相關性，更進一步探討在不同性別中尿酸與糖尿病的關係。結果：經校正年齡、性別、吸菸、飲酒、BMI、高血壓、高血脂、GPT、肌酸酐、膽固醇和三酸甘油酯等多因子後，從資料統計中發現尿酸越高，糖尿病的風險有越低的趨勢。尿酸最高組和尿酸最低組糖尿病的風險比（OR）為0.53（p for trend ＜ 0.0001）。以性別進行分組發現，男性組在統計上呈現顯著關係（OR = 0.38, p for trend ＜ 0.0001）；進一步檢視不同性別中尿酸與不同程度血糖調節異常的相關性，發現在多因子校正分析後，男性組中新發現糖尿病（OR = 0.34, p for trend ＜ 0.0001）及已知糖尿病（OR = 0.43, p for trend ＜ 0.0001）和血中尿酸濃度呈顯著負相關，空腹血糖調節異常（impaired fasting glucose, IFG）則未見顯著趨勢；女性組別均未發現有統計上顯著的相關性。結論：尿酸較高的族群糖尿病的風險較低，其趨勢在男性更為顯著；尿酸與血糖相關異常的負相關性在男性且血糖異常程度較高的族群裡較為顯著，推測尿酸和血糖相關異常的關係可能有性別差異，且在較嚴重的血糖異常時血糖與尿酸之間的互動更為顯著。

Background and Objectives: The research assessed the association between serum uric acid (SUA) and diabetes mellitus by analyzing data from adult health screening under the National Health Insurance Plan. Methods: The study sample consisted of 7,568 persons undergoing health check-ups from 2006 to 2011 at a regional hospital in northern Taiwan. Logistic regression was used to assess the association between SUA levels and diabetes mellitus and gender differences in the relationship. Results: In multivariate logistic regression models, we found that higher SUA levels were inversely associated with diabetes mellitus. Compared with the lowest quartile, the highest quartile of SUA had an odds ratio of 0.53 (p trend ＜ 0.0001). In subgroup analysis by gender, the results were consistent among men (OR = 0.38, p for trend ＜ 0.0001). After multivariate adjustment, gender-specific analysis on the association between SUA and stages of impaired glucose regulation (IGR) found a significant inverse association in newly diagnosed diabetes mellitus (OR = 0.34, p for trend ＜ 0.0001) and known diabetes mellitus (OR = 0.43, p for trend ＜ 0.0001) groups but not in the group of impaired fasting glucose, in male subjects. Conclusion: Higher SUA levels were found to be inversely associated with diabetes mellitus, especially among men. There was stronger inverse association between SUA and IGR in men with more advanced stages of IGR. The findings suggested a gender difference in the relationship of SUA with IGR and the interaction between SUA and glucose regulation seemed to be more significant in advanced stages of IGR.

1. (2013).Diagnosis and classification of diabetes mellitus.Diabetes Care,36(Suppl 1),S67-74.
2. Wolfson WQ, Hunt HD, et al: The transport and excretion of uric acid in man; a sex difference in urate metabolism; with a note on clinical and laboratory findings in gouty women. J Clin Endocrinol Metab 1949; 9: 749-67
3. Anton, FM,Garcia Puig, J,Ramos, T,Gonzalez, P,Ordas, J(1986).Sex differences in uric acid metabolism in adults: evidence for a lack of influence of estradiol-17 beta (E2) on the renal handling of urate.Metabolism,35,343-8.
4. Bandaru, P,Shankar, A(2011).Association between serum uric acid levels and diabetes mellitus.Int J Endocrinol,2011,604715.
5. Chen, LK,Lin, MH,Lai, HY,Hwang, SJ,Chiou, ST(2008).Uric acid: a surrogate of insulin resistance in older women.Maturitas,59,55-61.
6. Chonchol, M,Shlipak, MG,Katz, R(2007).Relationship of uric acid with progression of kidney disease.Am J Kidney Dis,50,239-47.
7. Christensen, PJ,Steenstrup, OR(1958).Uric acid excretion with increasing plasma glucose concentration (pregnant and non-pregnant cases).Scand J Clin Lab Invest,10,182-5.
8. Daskalopoulou, SS,Tzovaras, V,Mikhailidis, DP,Elisaf, M(2005).Effect on serum uric acid levels of drugs prescribed for indications other than treating hyperuricaemia.Curr Pharm Des,11,4161-75.
9. Dehghan, A,van Hoek, M,Sijbrands, EJ,Hofman, A,Witteman, JC(2008).High serum uric acid as a novel risk factor for type 2 diabetes.Diabetes Care,31,361-2.
10. Döring, A,Gieger, C,Mehta, D(2008).SLC2A9 influences uric acid concentrations with pronounced sex-specific effects.Nat Genet,40(4),430-6.
11. Fang, J,Alderman, MH(2000).Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971-1992. National Health and Nutrition Examination Survey.JAMA,283,2404-10.
12. Feig, DI,Kang, DH,Johnson, RJ(2008).Uric acid and cardiovascular risk.N Engl J Med,359,1811-21.
13. Ford, ES,Li, C,Cook, S,Choi, HK(2007).Serum concentrations of uric acid and the metabolic syndrome among US children and adolescents.Circulation,115,2526-32.
14. Geer, EB,Shen, W(2009).Gender differences in insulin resistance, body composition, and energy balance.Gend Med,6(Suppl 1),60-75.
15. Goldbourt, U,Medalie, JH,Herman, JB,Neufeld, HN(1980).Serum uric acid: correlation with biochemical, anthropometric, clinical and behavioral parameters in 10,000 Israeli men.J Chronic Dis,33,435-43.
16. Golembiewska, E,Ciechanowski, K,Safranow, K,Kedzierska, K,Kabat-Koperska, J(2005).Renal handling of uric acid in patients with type 1 diabetes in relation to glycemic control.Arch Med Res,36,32-5.
17. Haj Mouhamed, D,Ezzaher, A,Neffati, F,Douki, W,Gaha, L,Najjar, MF(2011).Effect of cigarette smoking on plasma uric acid concentrations.Environ Health Prev Med,16,307-12.
18. Herman, JB,Keynan, A(1969).Hyperglycemia and uric acid.Isr J Med Sci,5,1048-52.
19. Herman, JB,Medalie, JH,Goldbourt, U(1976).Diabetes, prediabetes and uricaemia.Diabetologia,12,47-52.
20. Heyden, S,Borhani, NO,Tyroler, HA(1985).The relationship of weight change to changes in blood pressure, serum uric acid, cholesterol and glucose in the treatment of hypertension.J Chronic Dis,38,281-8.
21. Jeemon, P,Prabhakaran, D(2013).Does uric acid qualify as an independent risk factor for cardiovascular mortality?.Clin Sci (Lond),124,255-7.
22. Johnson, RJ,Kang, DH,Feig, D(2003).Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease?.Hypertension,41,1183-90.
23. Kodama, S,Saito, K,Yachi, Y(2009).Association between serum uric acid and development of type 2 diabetes.Diabetes Care,32,1737-42.
24. Meisinger, C,Doring, A,Stockl, D,Thorand, B,Kowall, B,Rathmann, W(2012).Uric acid is more strongly associated with impaired glucose regulation in women than in men from the general population: the KORA F4-Study.PLoS One,7,e37180.
25. Mellen, PB,Bleyer, AJ,Erlinger, TP(2006).Serum uric acid predicts incident hypertension in a biethnic cohort: the atherosclerosis risk in communities study.Hypertension,48,1037-42.
26. Modan, M,Halkin, H,Karasik, A,Lusky, A(1987).Elevated serum uric acid-a facet of hyperinsulinaemia.Diabetologia,30,713-8.
27. Nakanishi, N,Okamoto, M,Yoshida, H,Matsuo, Y,Suzuki, K,Tatara, K(2003).Serum uric acid and risk for development of hypertension and impaired fasting glucose or Type II diabetes in Japanese male office workers.Eur J Epidemiol,18,523-30.
28. Nan, H,Dong, Y,Gao, W,Tuomilehto, J,Qiao, Q(2007).Diabetes associated with a low serum uric acid level in a general Chinese population.Diabetes Res Clin Pract,76,68-74.
29. Nicholls, A,Snaith, ML,Scott, JT(1973).Effect of oestrogen therapy on plasma and urinary levels of uric acid.Br Med J,1,449-51.
30. Oda, E,Kawai, R,Sukumaran, V,Watanabe, K(2009).Uric acid is positively associated with metabolic syndrome but negatively associated with diabetes in Japanese men.Intern Med,48,1785-91.
31. Richette, P,Bardin, T(2010).Gout.Lancet,375,318-28.
32. Sánchez-Lozada, LG,Nakagawa, T,Kang, DH(2006).Hormonal and cytokine effects of uric acid.Curr Opin Nephrol Hypertens,15,30-3.
33. Sumino, H,Ichikawa, S,Kanda, T,Nakamura, T,Sakamaki, T(1999).Reduction of serum uric acid by hormone replacement therapy in postmenopausal women with hyperuricaemia.Lancet,354,650.
34. Taniguchi, Y,Hayashi, T,Tsumura, K,Endo, G,Fujii, S,Okada, K(2001).Serum uric acid and the risk for hypertension and Type 2 diabetes in Japanese men: The Osaka Health Survey.J Hypertens,19,1209-15.
35. Tuomilehto, J,Zimmet, P,Wolf, E,Taylor, R,Ram, P,King, H(1988).Plasma uric acid level and its association with diabetes mellitus and some biologic parameters in a biracial population of Fiji.Am J Epidemiol,127,321-36.
36. Vitart, V,Rudan, I,Hayward, C(2008).SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout.Nat Genet,40,437-42.
37. Whitehead, TP,Jungner, I,Robinson, D,Kolar, W,Pearl, A,Hale, A(1992).Serum urate, serum glucose and diabetes.Ann Clin Biochem,29(Pt 2),159-61.
38. Wu, TH,Chen, HH,Lee, TK(2000).Factors affecting the first recurrence of noncardioembolic ischemic stroke.Thromb Res,97,95-103.
39. Yano, K,Rhoads, G,Kagan, A(1977).Epidemiology of serum uric acid among 8000 Japanese-American men in Hawaii.J Chronic Dis,30,171-84.
40. Yoo, TW,Sung, KC,Shin, HS(2005).Relationship between serum uric acid concentration and insulin resistance and metabolic syndrome.Circ J,69,928-33.
41. Yuan, HJ,Yang, XG,Shi, XY,Tian, R,Zhao, ZG(2011).Association of serum uric acid with different levels of glucose and related factors.Chin Med J (Engl),124,1443-8.