The relationship between uric acid variability and cardiovascular risk factors in patients with diabetes

Aim: This study aimed to evaluate the relationship between uric acid variability and cardiovascular risk factors, primarily albuminuria and blood lipids, in patients with diabetes. Material and Method: Data from 174 patients with diabetes whose biochemical parameters were examined at least once a year were collected over the course of five years of regular follow-up. The five-year averages and standard deviations of each parameter for each person were calculated. The adjusted standard deviation for each parameter was considered as a measure of individual variability. The patients were divided into two groups according to the median of the mean uric acid and the median of the adjusted standard deviation of uric acid. Results: Between low and high uric acid variability groups, while there was no statistically significant difference for the mean values of following parameters, there was a difference in the variability of glucose (p=0.010), HbA1c (p=0.016), total cholesterol (p=0.008), and low-density lipoprotein-cholesterol (p=0.002). Moreover, there was difference in mean albuminuria (p= 0.019), albuminuria variability (p=0.040), mean triglyceride (p=0.011), triglyceride variability (p=0.018), and mean high-density lipoprotein-cholesterol cholesterol (p=0.008). Conclusion: Clinicians should pay attention to uric acid variability in addition to basal uric acid levels since it is associated with albuminuria, an atherogenic lipid profile, renal functions, and the variability of these parameters, independent of HbA1c and glucose levels.

Keywords:

Uric Acid, Diabetes Mellitus, Albuminuria Dyslipidemia, Cardiovascular Disease,

PDF

___

International Diabetes Federation. IDF Diabetes Atlas, Brussels, Belgium.: International Diabetes Federation; 2021. 10th edn.:[Available from: https://www.diabetesatlas.org.
Yoo TW, Sung KC, Shin HS, et al. Relationship between serum uric acid concentration and insulin resistance and metabolic syndrome. Circ J 2005; 69: 928-33.
Qin T, Zhou X, Wang J, et al. Hyperuricemia and the prognosis of hypertensive patients: a systematic review and meta‐analysis. J Clin Hypertens 2016; 18: 1268-78.
Juraschek SP, McAdams-Demarco M, Miller ER, et al. Temporal relationship between uric acid concentration and risk of diabetes in a community-based study population. Am J Epidemiol 2014; 179: 684-91.
Kuwabara M, Borghi C, Cicero AF, et al. Elevated serum uric acid increases risks for developing high LDL cholesterol and hypertriglyceridemia: A five-year cohort study in Japan. Int J Cardiol 2018; 261: 183-8.
Feig DI, Kang D-H, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med 2008; 359: 1811-21.
Akbas EM, Timuroglu A, Ozcicek A, et al. Association of uric acid, atherogenic index of plasma and albuminuria in diabetes mellitus. Int J Clin Exp Med 2014; 7: 5737-43.
Fang J, Alderman MH. Serum uric acid and cardiovascular mortality: the NHANES I epidemiologic follow-up study, 1971-1992. JAMA 2000; 283: 2404-10.
Konta T, Ichikawa K, Kawasaki R, et al. Association between serum uric acid levels and mortality: a nationwide community-based cohort study. Sci Rep 2020; 10: 1-7.
Cho SK, Chang Y, Kim I, Ryu S. U‐shaped association between serum uric acid level and risk of mortality: a cohort study. Arthritis Rheumatol 2018; 70: 1122-32.
Hu L, Hu G, Xu BP, et al. U-shaped association of serum uric acid with all-cause and cause-specific mortality in US adults: a cohort study. J Clin Endocrinol Metab 2020; 105: e597-e609.
Cheong E, Ryu S, Lee J-Y, et al. Association between serum uric acid and cardiovascular mortality and all-cause mortality: a cohort study. J Hypertens 2017; 35: S3-S9.
Culleton BF, Larson MG, Kannel WB, Levy D. Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study. Ann Intern Med 1999; 131: 7-13.
Wang M, Wang C, Zhao M, et al. Uric acid variability and all-cause mortality: a prospective cohort study in northern China. J Nutr Health Aging 2021; 25: 1235-40.
Grossman C, Grossman E, Goldbourt U. Uric acid variability at midlife as an independent predictor of coronary heart disease and all-cause mortality. PLoS One 2019; 14: e0220532.
Dong ZX, Tian M, Li H, et al. Association of serum uric acid concentration and its change with cardiovascular death and all-cause mortality. Dis Markers 2020; 2020: 7646384.
Lim SS, Yang Y-L, Chen S-C, et al. Association of variability in uric acid and future clinical outcomes of patient with coronary artery disease undergoing percutaneous coronary intervention. Atherosclerosis 2020; 297: 40-6.
Ceriello A, De Cosmo S, Rossi MC, et al. Variability in HbA1c, blood pressure, lipid parameters and serum uric acid, and risk of development of chronic kidney disease in type 2 diabetes. Diabetes, Obesity and Metabolism 2017; 19: 1570-8.
Kilpatrick ES, Rigby AS, Atkin SL. A1C variability and the risk of microvascular complications in type 1 diabetes: data from the Diabetes Control and Complications Trial. Diabetes Care 2008; 31: 2198-202.
Lachin JM, Genuth S, Nathan DM, Zinman B, Rutledge BN. Effect of glycemic exposure on the risk of microvascular complications in the diabetes control and complications trial--revisited. Diabetes 2008; 57: 995-1001.
Rothwell PM, Howard SC, Dolan E, et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet 2010; 375: 895-905.
Cavarretta E, Frati G, Sciarretta S. Visit-to-visit systolic blood pressure variability and cardiovascular outcomes: new data from a real-world Korean population. Am J Hypertens 2017; 30: 550-3.
Rothwell PM. Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension. Lancet 2010; 375: 938-48.
Frontoni S, Di Bartolo P, Avogaro A, Bosi E, Paolisso G, Ceriello A. Glucose variability: An emerging target for the treatment of diabetes mellitus. Diabetes Res Clin Pract 2013; 102: 86-95.
Okada H, Fukui M, Tanaka M, et al. Visit-to-visit blood pressure variability is a novel risk factor for the development and progression of diabetic nephropathy in patients with type 2 diabetes. Diabetes Care 2013; 36: 1908-12.
Hamm P, Shekelle RB, Stamler J. Large fluctuations in body weight during young adulthood and twenty-five-year risk of coronary death in men. Am J Epidemiol 1989; 129: 312-8.
Bangalore S, Fayyad R, Laskey R, DeMicco DA, Messerli FH, Waters DD. Body-weight fluctuations and outcomes in coronary disease. N Engl J Med 2017; 376: 1332-40.
Johnson RJ, Segal MS, Srinivas T, et al. Essential hypertension, progressive renal disease, and uric acid: a pathogenetic link? J Am Soc Nephrol 2005; 16: 1909-19.
Lytvyn Y, Perkins BA, Cherney DZ. Uric acid as a biomarker and a therapeutic target in diabetes. Can J Diabetes 2015; 39: 239-46.
Brovold H, Lund T, Svistounov D, et al. Crystallized but not soluble uric acid elicits pro-inflammatory response in short-term whole blood cultures from healthy men. Sci Rep 2019; 9: 10513.