HYPERURICEMIA CORRECTION IN MEN WITH METABOLIC SYNDROME: ACARBOSE POTENTIAL

The study was aimed at the investigation of “test” (6 days) and longer-term (8 weeks) acarbose treatment effects on plasma uric acid (UA) concentration in patients with metabolic syndrome (MS). Material and methods. In total, 33 men with MS and carbohydrate metabolism disturbances were administered 6-day “test” acarbose therapy. At baseline and 7 days later, saccharose tolerance test was performed, with the measurement of venous plasma levels of fasting UA, fasting fructose, glucose (fasting, 60 and 120 minutes after saccharose load), and insulin (fasting and 120 minutes after the load). 4 weeks later, 20 patients were administered 8-week acarbose therapy, with standard gradual dose increase. At baseline and after the treatment, venous plasma concentrations of UA and fructose were measured. Results. Hyperfructosemia was observed in 100% of the patients, with mean plasma fructose concentration of 0,82±0,97 mmol/l. Hyperuricemia was observed in 51,5% (n=17), with mean plasma UA concentration of 413,2±86,5 mmol/l. Six-week acarbose therapy resulted in a significant decrease of UA levels (p=0,0015) and fructose levels (p=0,049), as well as in postprandial levels of glucose (p=0,03) and insulin (p=0,013). Eight-week acarbose therapy was associated with mean decrease of plasma UA concentration by 5,8% (p=0,04), but no significant changes in fasting plasma levels of fructose (p>0,05).

Hyperuricemia, fructose, metabolic syndrome, impaired glucose tolerance, diabetes mellitus, acarbose

1. Bos M. J., Koudstaal P. J., Hofman A. et al. Uric acid is a risk factor for myocardial infarction and stroke. The Rotterdam study//Stroke 2006; 37 (6): 1503–1507.

2. Kim S. Y, Guevara J. P., Kim K.M. et al. Hyperuricemia and risk of stroke: a systematic review and meta-analysis. Arthritis Rheum. 2009; 61 (7): 885–892.

3. Krishnan E. Hyperuricemia and incident heart failure. Circ. Heart Fail. 2009; 2 (6): 556–562.

4. Chen J. H., Chuang S. Y., Chen H. J. et al. Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study. Arthritis Rheum. 2009; 61 (2): 225–232.

5. 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 (1): 7–13.

6. Fang J., Alderman M. H. Serum uric acid and cardiovascular mortality. The NHANES (Epidemiologic Follow–up Study, 1971–1992). JAMA 2000; 283 (18): 2404–2410.

7. Anker S. D., Doehner W., Rauchhaus M. et al. Uric acid and survival in chronic heart failure: validation and application in metabolic, functional, and hemodynamic staging. Circulation 2003; 107 (15): 1991–1997.

8. Emmerson B. Hyperlipidaemia in hyperuricaemia and gout. Ann. Rheum. Dis. 1998; 57 (9): 509–510.

9. Wannamethee G. S. Serum Uric Acid Is Not an Independent Risk Factor for Coronary Heart Disease. Curr. Hypertens. Rep. 2001; 3 (3): 190–196.

10. Lee J., Sparrow D., Vokonas P. S. et al. Uric acid and coronary heart disease risk: evidence for a role of uric acid in the obesityinsulin resistance syndrome. Am. J. Epidemiol. 1995; 142 (3): 288–294.

11. Kerkalainen P., Sarlund H., Laakso M. Long-term association of cardiovascular risk factors with impaired insulin secretion and insulin resistance. Metabolism 2000; 49 (10): 1247–1254.

12. Krishnan E., Kwoh C. K., Schumacher H. R., Kuller L. Hyperuricemia and incidence of hypertension among men without metabolic syndrome. Hypertension 2007; 49 (2): 298–303.

13. Mellen P. B., Bleyer A. J., Erlinger T. P. et al. Serum uric acid predicts incident hypertension in a biethnic cohort. The Atherosclerosis Risk in Communities Study. Hypertension 2006; 48 (6): 1037–1042.

14. Shelmadine B., Bowden R. G., Wilson R. L. et al. The effects of lowering uric acid levels using allopurinol on markers of metabolic syndrome in end-stage renal disease patients: a pilot study. Anadolu Kardiyol Derg. 2009; 9 (5): 385–389.

15. Dawson J., Walters M. Uric acid and xanthine oxidase: future therapeutic targets in the prevention of cardiovascular disease? Br. J. Clin. Pharmacol. 2006; 62 (6): 633–644.

16. Dawson J., Quinn T., Walters M. Uric acid reduction: a new paradigm in the management of cardiovascular risk? Curr. Med. Chem. 2007; 14 (17): 1879–1886.

17. Zimmet P., Magliano D., Matsuzawa Y. et al. The metabolic syndrome: a global public health problem and a new definition. J. Atheroscler. Thromb. 2005; 12 (6): 295–300.

18. Хмелевский Ю. В., Усатенко О. К. Основные биохимические константы человека в норме и при патологии. Киев: Здоров’я; 1987.

19. Nakagawa T., Hu H., Zharikov S. et al. A causal role for uric acid in fructose-induced metabolic syndrome. Am. J. Physiol. Renal. Physiol. 2006; 290: F625–F631.

20. 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 (1): 96–116.

21. Nakagawa T., Tuttle K. R., Short R. A., Johnson R. J. Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome. Nat. Clin. Pract. Nephrol. 2005; 1 (2): 80–86.

22. Perez-Pozo S. E., Schold J., Nakagawa T. et al. Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. Int. J. Obes. (Lond.) 2010; 34 (3): 454–461.

23. Johnson R. J., Segal M. S., Sautin Y. et al. Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am. J. Clin. Nutr. 2007; 86 (4): 899–906.

24. Gaby A. R. Adverse Effects of Dietary Fructose. Altern. Med. Rev. 2005; 10 (4): 294–306.