Study Of Metabolic Disorders And Risk Factors Related To Uric Acid In Type 2 Diabetes Mellitus.

BackgroundThe prevalence of hyperuricemia has been increasing in recent years, not only in advanced countries but also in developing countries, along with the development of their economies. Hyperuricemia, a highly prevalent condition in the adult population, is associated with obesity and insulin resistance, and also associated with metabolic syndrome components.Metabolic syndrome and insulin resistance are well-established key risk factors for diabetes.and High serum uric acid levels are frequently observed among individuals with type 2 diabetes.while a modest positive association between plasma uric acid concentration and the incidence of type 2 diabetes in Chinese individuals had been confirmed, so it was necessary to explore risk factors related to hyperuricemia in type 2 diabetes mellitus and to clarify the role of hyperuricemia (HUA) in metabolic disorders of type 2 diabetes mellitus, and take it seriously to control high serum uric acid (SUA) levels in T2DM.The metabolic syndrome is a cluster of cardiovascular risk factors that is characterized by obesity, central obesity, insulin resistance, atherogenic dyslipidemia, and hypertension. Increasing evidence suggests that uric acid may play a role in the metabolic syndrome. The strongest evidence of a role for uric acid in the development of the metabolic syndrome has been from studies in animal models showing that decreasing uric acid levels can prevent or reverse features of the metabolic syndrome. Two mechanisms have been suggested to explain how hyperuricemia might induce the metabolic syndrome. The first mechanism is related to the fact that glucose uptake in skeletal muscle depends in part on increases in blood flow mediated by the insulin-stimulated release of nitric oxide from endothelial cells. Features of the metabolic syndrome develop in mice lacking endothelial nitric oxide synthase.The observations that hyperuricemia can induce endothelial dysfunction in rats and that treatment with allopurinol can improve endothelial function in patients with hyperuricemia would support this mechanism. The second mechanism concerns the inflammatory and oxidative changes uric acid induces in adipocytes, a process that is key in causing the metabolic syndrome in obese mice.In addition, xanthine oxidoreductase (the enzyme that generates uric acid from xanthine) is expressed in adipocytes and is critical to the process of adipogenesis; indeed, xanthine oxidoreductase knockout mice have only half the adipocyte mass of their control littermates.Historically, the elevated level of uric acid observed in the metabolic syndrome has been attributed to hyperinsulinemia, since insulin reduces renal excretion of uric acid.Hyperuricemia, however, often precedes the development of hyperinsulinemia,obesity,and diabetes, uric acid level predicts the development of metabolic syndrome per se, and one study that was demonstrated even in subjects who were free of all features of metabolic syndrome at baseline. An elevated uric acid level also predicts the development of hyperinsulinemia, obesity, fatty liver diseases, and diabetes in most but not all studies.Furthermore, in many studies uric acid remained an independent predictor of diabetes after controlling for baseline body mass index.And link between serum levels of UA and dyslipidemia has established,the combined effects of hyperuricemia and hypertension,insulin resistance,obesity, hyperlipoidemia may lead to complications of cardiovascular diseases, diabetic nephropathy,etc. in fact, diabetic subjects who continue to be hyperuricemic appear to be at increased risk for developing diabetic complications,especially renal disease.These studies suggest that uric acid cannot simply be viewed as a secondary phenomenon.while the Common Soil Hypothesis iucluded Metabolic syndrome, type 2 diabetes,and atherosclerotic vascular disease had been put forward at an earlier time that uric acid presents one of the candidates that may be involved in these three cardiometabolic disorders. So it was importantly essential to find out the link between uric acid and complications in type 2 diabetes.The positive association between uric acid concentration and diabetes may be explained by at least 3 potential mechanisms. First, metabolic syndrome, as a precursor of diabetes, induces high oxidative stress,which is worsened by the accompanying hyperuricemia. Uric acid usually has an antioxidative effect;however, uric acid becomes a strong oxidant in the environment of metabolic syndrome.Inflammation and oxidative stress induced by metabolic syndrome and hyperuricemia may predispose individuals to a higher risk for diabetes. Second, uric acid stimulates vascular smooth muscle proliferation and induces endothelial dysfunction. Uric acid has been shown to decrease endothelial nitric oxide production and to lead to endothelial dysfunction and insulin resistance. Consequently, uric acid induces vascular inflammation and artery damage, which in turn leads to an increased risk of diabetes and atherosclerosis. A recent study showed that hyperuricemia was associated with the severity of carotid plaque. And metabolic syndrome can explain most of the association between uric acid and carotid plaque, because adjusting for metabolic syndrome substantially attenuated the association. In addition, the data show a positive association between uric acid concentration and the HOMA insulin-resistance index, and adjustment for the HOMA index further attenuated the association between uric acid concentration and diabetes. These data suggest that insulin resistance, which is closely related to metabolic syndrome and inflammation, may also mediate the association between uric acid and diabetes risk.Third, uric acid is associated with increased renal glomerular pressure and increased renal sodium reabsorption, and these renal reactions are greatly enhanced by high insulin concentrations.Among diabetic patients, hyperuricemia has been associated with microalbuminuria. The combined effects of insulin resistance and hyperuricemia on renal functions may lead to increased glucose intolerance, hypertension, and diabetes risk.Therefore,uric acid,was closed related to individual component of metabolic syndrome, serum uric acid might be a strong and independent risk factor for diabetes,diabetic subjects who continue to be hyperuricemic appear to be at increased risk for developing diabetic complications, The study population was an important part of T2DM, aged 40-80 years (average 61.5±10.5 years) at a Scr level of 51-159μmol/L (0.6-1.8 mg/dl) consisted of T2DM subjects with the full required information that were included for the current data analysis to explore the incidence of hyperuricemia in T2DM and some kinds of risk factors related to elevated serum uric acid in T2DM in the southern China, while metabolic disorders and complications related to hyperuricemia in T2DM can also be considered.We hope that specific measures on uric acid control in T2DM could taken into account.Methods1.Design Retrospective study.2.Study population The study population consisted of subjects with T2DM who werereceiving care at the Zhujiang Hospital of Southern Medical University from August 2007 to June 2010, Definitions of T2DM according to WHO Consultation 1999:characteristic diabetic symptoms combination randomtime plasma glucose≥11.1mmol/l,or FPG≥7.0 mmol/1, or oral glucose tolerance test (OGTT) 2h PG≥11.1 mmol/1. one additional plasma/blood glucose test result with a value in the diabetic range is essential, either fasting, from a random (casual) sample, or from the oral glucose tolerance test (OGTT). characteristic diabetic symptoms meams thirst, polyuria, and elucidative weight loss, Randomtime means any time in a day regardless of last meal and food intake dose.Among them, There were 159 subjects aged 40-80 years (average 61.5±10.5 years) at a Scr level of 51-159μmol/L (0.6-1.8 mg/dl) and a duration disease of 0-28 years with the full required information that were included for the current data analysis.3.Exclusion criteria T2DM with acute complications or diseases may iuduce secondary hyperuricemia such as Leukemia, polycythemia, multiple myeloma,thyroid disease, diabetes insipidus, malignant tumor,etc. DM subjects who were excluded included those who were on thiazide diuretics(these drugs cause iatrogenic elevation in SUA), pregnant women, and those who were taking medications for hyperuricaemia,such as allopurinol, and other drugs known as to influence the metabolism of uric acid one month before observation; Subjects who were taking lipid-lowering agents before observation were also excluded。4.Grouping Normotensive uric acid level (NUA group) 119cases, hyperuricemia (HUA group) 40 cases.5. Definitions of hyperuricemia Hyperuricemia is defined as serum uric acid level≥7 mg/dl (420μmol/L) in men, and≥6.0 mg/dl (360μmol/L) in women before menopause, or≥7 mg/dl (420μmol/L) in women after menopause.6.0bserved indicators Uric acid (UA), cholesterol(TC,3.1-5.7 mmol/L), triglyceride (TG,0.4-1.7 mmol/L), high density lipoprotein (HDL,1.04-1.90 mmol/L), low density lipoprotein (LDL,2.00-3.37 mmol/L), serum creatinine (SCr), urea nitrogen (BUN),fasting plasma glucose(FPG),glycosylated hemoglobin (HbAlc%),Body Mass Index (BMI), urinary microglobulin(U-MA,0-30 mg/L, the lowest cutoff value was 11.2mg/L in our hospital). 7. Definitions of complications in T2DM. (1) Coronary heart disease (CHD):clear history of myocardial infarction,definite angina pectoris attack or electrocardiogram manifestations with ST-T changes, reference to the criteria of ACC/AHA;(2)Cerebral infarction (CI):confirmed by Cranial CT or MRI scan; (3) Carotid atherosclerosis (CA):carotid B ultrasonography found local eminence,thickening,or stick out to intracavity, carotid atery inner-middle membrane thickness (LMT)≥1.0 mm; (4) Diabetic nephropathy(DN):U-MA>30 mg/L; (5) Diabetic retinopathy(DR):more than stage 2 of diabetic retinopathy by ocular fundus examination; (6) Hypertension(HT):defined as systolic blood pressure(SBP)≥140 mmHg and/or diastolic blood pressure(DBP)≥90mmHg(1999 World Health Organization-international society of hypertension guidelines).8.Statistical AnalysisData were analyzed using SPSS version 12.0. Quantitative data are expressed as mean and standard deviation (mean±SD) comparisons between the quantitative data were done by t-tests and categorical variables were done by chi-square tests.Binary Logistic regression procedures were used to examine the risks of having hyperuricemia.Odds ratio (OR)of kinds of risk factors and 95% confidence interval(CI) will be calculated,P values of<0.05 were considered to be statistically significant.Result1.40 cases of T2DM had a incidence of HUA in 159 patients (25.2%).2.A single-variable analysis showed that male, body mass index (≥25 kg/m2), hypertension, serum creatinine (≥110μmol/L), blood urea nitrogen (≥7.0 mmol/L), microalbuminuria (≥11.2 mg/L), triglyceride (≥1.70 mmol/L), high-density lipoprotein (<1.04 mmol/L), low density lipoprotein (>3.37 mmol/L) were all risk factors related to HUA (P<0.05) in T2DM. 3. Binary logistic regression analysis indicated serum creatinine, body mass index and triglyceride were independent risk factors of HUA in T2DM.4.Main risk factors related to hyperuricemia had a high incidence rate in T2DM.5.Patients with HUA had a significantly higher incidence rate of coronary artery disease, carotid atherosclerosis, cerebral infarction, diabetic nephropathy and diabetic retinopathy than that with normal uric acid level (NUA) (P<0.05).ConclusionKinds of risk factors got a relationship with elevated serum uric acid in T2DM, while metabolic disorders and complications were related to hyperuricemia in T2DM.