aShandong Provincial Key Laboratory of Metabolic Diseases, Qingdao Key Laboratory of Common Diseases Gout Laboratory, the Affiliated Hospital of Medical College, Qingdao University, China bDivision of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua cDepartment of Kinesiology, Health and Leisure Studies, National University of Kaohsiung, Kaohsiung, Taiwan.
Purpose of review:
To explore the causal relationship between metabolic syndrome, type 2 diabetes and hyperuricemia.
The prevalence of hyperuricemia in male adults with metabolic syndrome was increased and a large difference in prevalence of metabolic syndrome also existed in those with hyperuricemia compared with normouricemia. Even in those with normouricemia, higher serum uric acid levels were associated with metabolic syndrome. Serum uric acid was an independent risk factor for incident diabetes, and evidence showed that the patients with both gout and type 2 diabetes exhibited a mutual inter-dependent effect on higher incidences. Furthermore, obese patients often demonstrated insulin resistance and adipose tissue macrophage with low-grade inflammation, which is suggested to be the major contributor. Although alcohol intake is considered a risk for developing hyperuricemia, moderate alcohol intake showed a lower risk for developing type 2 diabetes and insulin resistance. Hyperinsulinemia reduces renal excretion of uric acid on the proximal tubular of the kidney leading to hyperuricemia, which has deleterious effects on endothelial function and on nitric oxide bioavailability, thus causing hyperinsulinemia.
We found evidence to suggest that insulin resistance plays a potentially key role in the causal relationship between metabolic syndrome, type 2 diabetes and hyperuricemia. Furthermore, it is likely that hyperuricemia and insulin resistance share a bidirectional causal effect.
"Hyperuricemia is the precursor of gout, which is the principal cause of inflammatory arthritis among adult men and older women . Hyperuricemia is furthermore recognized as an independent risk factor for metabolic and cardiorenovascular conditions including metabolic syndrome, type 2 diabetes (T2DM) and insulin resistance [4-7]. In addition, epidemiological evidence suggests that hyperuricemia may play a role in epidemics of hypertension and coronary heart disease [8,9]; however, recent evidence suggests no causal association between uric acid and ischemic heart disease and blood pressure . "
[Show abstract][Hide abstract] ABSTRACT: Background
The prevalence of hyperuricemia has doubled worldwide during the last few decades. The substantial increase in sweetened beverage (SB) consumption has also coincided with the secular trend of hyperuricemia. Recent studies do show that the consumption of SB can induce hyperuricemia. However, the association between SB and hyperuricemia remains unclear. The aim of this study was to evaluate the association between SB consumption and levels of uric acid in Mexican adults.
We performed a cross-sectional analysis of data from selected adults participating in the baseline assessment of the Health Workers Cohort Study. A total of 6,705 participants of both sexes between ages 18 and 70 years were included. SB intake was estimated using a validated semi-quantitative food frequency questionnaire. Biochemical and anthropometric information was collected using standard procedures. Hyperuricemia was defined as uric acid levels ≥ 7.0 mg/dL in men and ≥ 5.8 mg/dL in women. The association of interest was assessed by multiple logistic regression models.
The odds ratios (OR) for hyperuricemia in men who consume 0.5-1 SB/day was 1.59 (95% CI; 1.05-2.40) and 2.29 (95% CI; 1.55-3.38) for those who consume ≥3 SB/day when compared to men who consume less than half a SB/day. In women, the OR for hyperuricemia for those who consume >1.0- < 3.0 SB/day was 1.33 (95% CI; 1.04-1.70) and 1.35 (95% CI; 1.04-1.75) for those who consume ≥3 SB/day when compared to women who consume less than half a SB/day, independent of other covariables. Men and women with high SB consumption and a body mass index (BMI) ≥ 25 Kg/m2 had greater risk for hyperuricemia than men and women with low SB consumption and normal BMI < 25 Kg/m2.
Our findings suggest that the consumption of SB is associated with an increased risk of hyperuricemia in Mexican adults. However, longitudinal research is needed to confirm the association between SB intake and hyperuricemia.
BMC Public Health 05/2014; 14(1):445. DOI:10.1186/1471-2458-14-445 · 2.26 Impact Factor
"On the other hand, high uric acid levels might predict the development of metabolic syndrome consequentially leading to diabetes   and can also increase severity of the already developed disease by leading to a higher incidence of certain diabetic complications . The mechanism by which these metabolic states are interconnected seems yet to be clarified, although there is evidence that hyperuricemia, metabolic syndrome, and type II diabetes share the same causal origin in which insulin resistance would play a key role . Anyhow, development of novel therapeutic agents targeting both diabetes "
[Show abstract][Hide abstract] ABSTRACT: The leaves of Morus alba L. have a long history in Traditional Chinese Medicine and also became valued by the ethnopharmacology of many other cultures. The worldwide known antidiabetic use of the drug has been suggested to arise from a complex combination effect of various constituents. Moreover, the drug is also a potential antihyperuricemic agent. Considering that type 2 diabetes and hyperuricemia are vice-versa in each other's important risk factors, the use of mulberry originated phytotherapeutics might provide an excellent option for the prevention and/or treatment of both conditions. Here we report a series of relevant in vitro and in vivo studies on the bioactivity of an extract of mulberry leaves and its fractions obtained by a stepwise gradient on silica gel. In vivo antihyperglycemic and antihyperuricemic activity, plasma antioxidant status, as well as in vitro glucose consumption by adipocytes in the presence or absence of insulin, xanthine oxidase inhibition, free radical scavenging activity, and inhibition of lipid peroxidation were tested. Known bioactive constituents of M. alba (chlorogenic acid, rutin, isoquercitrin, and loliolide) were identified and quantified from the HPLC-DAD fingerprint chromatograms. Iminosugar contents were investigated by MS/MS, 1-deoxynojirimycin was quantified, and amounts of 2-O-alpha-D-galactopyranosyl-1-deoxynojirimicin and fagomine were additionally estimated.
Evidence-based Complementary and Alternative Medicine 12/2013; 2013(3):948627. DOI:10.1155/2013/948627 · 1.88 Impact Factor
"In the report of the US National Health and Nutrition Examination Survey, among patients with gout, 74% had hypertension and 26% had diabetes . Hypertension, DM, and hyperuricemia are mutually related; therefore, regular monitoring of serum uric acid levels is desirable in hypertensive patients with DM . "
[Show abstract][Hide abstract] ABSTRACT: Angiotensin II type 1 receptor blockers (ARB) are a frequently used class of antihypertensive drug. The ARB losartan is known to decrease the serum uric acid (SUA) level. However, there are very few clinical data comparing the effects of other ARBs on SUA level under the conditions of clinical practice. This study evaluated and compared the long-term effects of monotherapy with five ARBs on SUA level in Japanese hypertensive patients with type 2 diabetes mellitus (DM).
We identified hypertensive patients with type 2 DM who had been treated with monotherapy with losartan (n = 214), valsartan (n = 266), telmisartan (n = 185), candesartan (n = 458), or olmesartan (n = 192), in whom laboratory data of SUA between November 1, 2004 and July 31, 2011 were available, from the Nihon University School of Medicine's Clinical Data Warehouse (NUSM's CDW). We used a propensity-score weighting method and a multivariate regression model to adjust for differences in the background among ARB users, and compared the SUA level. The mean exposure of losartan was 264.7 days, valsartan 245.3 days, telmisartan 235.9 days, candesartan 248.9 days, and olmesartan 234.5 days.
In losartan users, mean SUA level was significantly decreased from baseline, while it was conversely increased in users of other ARBs; valsartan, telmisartan, candesartan, and olmesartan. The mean reduction of SUA level from baseline was significantly greater in losartan users compared with that in other ARB users. Comparison of ARBs other than losartan showed no significant difference in mean change in SUA level from baseline.
Our study showed that losartan had the most beneficial effect on SUA level among five ARBs, and that there was no significant difference in the unfavorable effects on SUA level among four ARBs other than losartan, at least during one year. These findings provide evidence of an effect of ARBs on SUA level, and support the benefit of the use of losartan in hypertensive patients with type 2 DM.
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