Interaction Between Lactate and Uric Acid is Associated With a Higher Prevalence of Metabolic Syndrome: A Community-Based Study

Abstract

Background Increased blood lactate or uric acid (UA) levels are associated with an increased risk of metabolic syndrome (MS). The aim of this study was to investigate the effect of an interactive association between blood lactate and UA levels on MS.

Methods This community-based cross-sectional study included 2584 Chinese subjects aged ≥ 18 years. Participants were classified into 3 groups based on lactate or UA level tertiles or into 9 groups based on a combination of lactate and UA level tertiles.

Results The serum high-sensitivity C-reactive protein (hs-CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) levels and odds ratios (ORs) for MS increased across the blood lactate or UA level tertiles (all P for trend<0.05). Interactions between lactate and UA with hs-CRP level, HOMA-IR level, and ORs for MS (P<0.05 for all interactions) were also observed. The adjusted ORs for MS in participants in the third tertile of lactate and UA levels, in the third tertile of lactate levels and first tertile of UA levels, and in the first tertile of lactate levels and third tertile of UA levels were 6.02 (95% CI 2.87–12.64, P<0.001), 2.92 (95% CI 1.39–6.10, P=0.005), and 2.70 (95% CI 1.23–5.96, P=0.014), respectively, compared with those in the first tertiles of both lactate and UA levels.

Conclusion The interaction between lactate and UA is associated with a higher prevalence of MS in the Chinese population.

Key words

lactate - uric acid - inflammation - insulin resistance - metabolic syndrome - epidemiology

^* Contributed equally

• References

• 1 Zhang GM, Zhu Y, Ye DW. Metabolic syndrome and renal cell carcinoma. World J Surg Oncol 2014; 12: 236
• 2 Kaur J. A comprehensive review on metabolic syndrome. Cardiol Res Pract 2014; 2014: 943162
• 3 Crawford SO, Hoogeveen HC, Brancati FL. et al. Association of blood lactate with type 2 diabetes: The atherosclerosis risk in communities carotid MRI study. Int J Epidemiol 2010; 39: 1647-1655
• 4 Juraschek SP, Shantha GPS, Chu AY. et al. Lactate and risk of incident diabetes in a case-cohort of the atherosclerosis risk in communities (ARIC) study. PLoS One 2013; 8: e55113
• 5 Billiet L, Doaty S, Katz JD. et al. Review of hyperuricemia as new marker for metabolic syndrome. ISRN Rheumatol 2014; 2014: 852954
• 6 Ye J. Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int J Obes (Lond) 2009; 33: 54-66
• 7 Tsushima Y, Nishizawa H, Tochino Y. et al. Uric acid secretion from adipose tissue and its increase in obesity. J Biol Chem 2013; 288: 27138-27149
• 8 Samuvel DJ, Sundararaj KP, Nareika A. et al. Lactate boosts TLR4 signaling and NF-kappaB pathway-mediated gene transcription in macrophages via monocarpboxylate transporters and MD-2 up-regulation. J Immunol 2009; 182: 2476-2484
• 9 Miao H, Chen L, Hao L. et al. Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes. Sci Rep 2015; 5: 13092
• 10 Emanuela F, Grazia M, Marco de R. et al. Inflammation as a link between obesity and metabolic syndrome. J Nutr Metab 2012; 2012: 476380
• 11 Kippen I, Klinenberg JR, Weinberger A. et al. Factors affecting urate solubility in vitro. Ann Rheum Dis 1974; 33: 313-317
• 12 Ye W, Zheng Y, Zhang S. et al. Oxamate improves glycemic control and insulin sensitivity via inhibition of tissue lactate production in db/db mice. PLoS One 2016; 11: e0150303
• 13 Baldwin W, McRae S, Marek G. et al. Hyperuricemia as a mediator of the proinflammatory endocrine imbalance in the adipose tissue in a murine model of the metabolic syndrome. Diabetes 2011; 60: 1258-1269
• 14 Granchi C, Bertini S, Macchia M. et al. Inhibitors of lactate dehydrogenase isoforms and their therapeutic potentials. Curr Med Chem 2010; 17: 672-697
• 15 Takir M, Kostek O, Ozkok A. et al. Lowering uric acid with allopurinol improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia. J Investig Med 2015; 63: 924-929
• 16 Liu P, Wang H, Zhang F. et al. The Effects of allopurinol on the carotid intima-media thickness in patients with type 2 diabetes and asymptomatic hyperuricemia: A three-year randomized parallel-controlled study. Intern Med 2015; 54: 2129-2137
• 17 Mongraw-Chaffin ML, Matsushita K, Brancati FL. et al. Diabetes medication use and blood lactate level among participants with type 2 diabetes: the atherosclerosis risk in communities carotid MRI study. PLoS One 2012; 7: e51237
• 18 Matsushita K, Williams EK, Mongraw-Chaffin ML. et al. The association of plasma lactate with incident cardiovascular outcomes: The ARIC study. Am J Epidemiol 2013; 178: 401-409
• 19 Muraki I, Tanigawa T, Yamagishi K. et al. Nocturnal intermittent hypoxia and C reactive protein among middle-aged community residents: A cross-sectional survey. Thorax 2010; 65: 523-527
• 20 Lee JM, Okumura MJ, Davis MM. et al. Prevalence and determinants of insulin resistance among U.S. adolescents: A population-based study. Diabetes Care 2006; 29: 2427-2432
• 21 Chen YD, Varasteh BB, Reaven GM. Plasma lactate concentration in obesity and type 2 diabetes. Diabetes Metab 1993; 19: 348-354
• 22 Ohlson LO, Larsson B, Björntorp P. et al. Risk factors for type 2 (non-insulin-dependent) diabetes mellitus. Thirteen and one-half years of follow-up of the participants in a study of Swedish men born in 1913. Diabetologia 1988; 31: 798-805
• 23 Lee HK, Cho YM, Kwak SH. et al. Mitochondrial dysfunction and metabolic syndrome-looking for environmental factors. Biochim Biophys Acta 2010; 1800: 282-289
• 24 Gonzalez-Franquesa A, Patti ME. Insulin resistance and mitochondrial dysfunction. Adv Exp Med Biol 2017; 982: 465-520
• 25 Marín-García J. The Role of mitochondria in the metabolic syndrome and insulin resistance. In: Marín-García J. (ed) Mitochondria and their role in cardiovascular disease. New York: Springer; 2012: 401-412
• 26 Hashimoto T, Hussien R, Oommen S. et al. Lactate sensitive transcription factor network in L6 cells: Activation of MCT1 and mitochondrial biogenesis. FASEB J 2007; 21: 2602-2612
• 27 Boutens L, Hooiveld GJ, Dhingra S. et al. Unique metabolic activation of adipose tissue macrophages in obesity promotes inflammatory responses. Diabetologia 2018; 61: 942-953
• 28 Roberts CK, Hevener AL, Barnard RJ. Metabolic syndrome and insulin resistance: Underlying causes and modification by exercise training. Compr Physiol 2013; 3: 1-58
• 29 Ishizaka N, Ishizaka Y, Toda E. et al. Association between serum uric acid, metabolic syndrome, and carotid atherosclerosis in Japanese individuals. Arterioscler Thromb Vasc Biol 2005; 25: 1038-1044
• 30 Lee JM, Kim HC, Cho HM. et al. Association between serum uric acid level and metabolic syndrome. J Prev Med Public Health 2012; 45: 181-187
• 31 Nejatinamini S, Ataie-Jafari A, Qorbani M. et al. Association between serum uric acid level and metabolic syndrome components. J Diabetes Metab Disord 2015; 14: 70
• 32 Ford ES, Li C, Cook S. et al. Serum concentrations of uric acid and the metabolic syndrome among US children and adolescents. Circulation 2007; 115: 2526-2532
• 33 Sun HL, Pei D, Lue KH. et al. Uric acid levels can predict metabolic syndrome and hypertension in adolescents: A 10-year longitudinal study. PLoS One 2015; 10: e0143786
• 34 Lyngdoh T, Marques-Vidal P, Paccaud F. et al. Elevated serum uric acid is associated with high circulating inflammatory cytokines in the population-based colaus study. PLoS One 2011; 6: e19901
• 35 Netea MG, Kullberg BJ, Blok WL. et al. The role of hyperuricemia in the increased cytokine production after lipopolysaccharide challenge in neutropenic mice. Blood 1997; 89: 577-582
• 36 di Giovine FS, Malawista SE, Thornton E. et al. Urate crystals stimulate production of tumor necrosis factor alpha from human blood monocytes and synovial cells. Cytokine mRNA and protein kinetics, and cellular distribution. J Clin Invest 1991; 87: 1375-1381
• 37 Jin M, Yang F, Yang I. et al. Uric acid, hyperuricemia and vascular diseases. Front Biosci (Landmark Ed) 2012; 17: 656-669
• 38 Ghaemi-Oskouie F, Shi Y. The role of uric acid as an endogenous danger signal in immunity and inflammation. Curr Rheumatol Rep 2011; 13: 160-166
• 39 Denoble AE, Huffman KM, Stabler TV. et al. Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proc Natl Acad Sci U S A 2011; 108: 2088-2093
• 40 Nestel P, Lyu R, Low LP. et al. Metabolic syndrome: Recent prevalence in East and Southeast Asian populations. Asia Pac J Clin Nutr 2007; 16: 362-367
• 41 Xi B, He D, Hu Y. et al. Prevalence of metabolic syndrome and its influencing factors among the Chinese adults: The China Health and Nutrition Survey in 2009. Prev Med 2013; 57: 867-871