Volume 07 · Issue 09 · 2015

Uric acid is a product of purine metabolism in the human body. For a long time, when it comes to uric acid, people are more likely to think of the damage to the kidneys and joints after its elevated levels. In recent years, more and more evidence shows that the threat of hyperuric acid to health is far more than that. It is usually associated with adult metabolic diseases such as obesity, hyperglycemia, hypertension and dyslipidemia. It is a related component of metabolic syndrome and another important "accomplice" of atherosclerotic cardiovascular disease. However, it is also believed that uric acid as an antioxidant has a protective effect on the cardiovascular system. Therefore, it is of great significance to re-examine the role of uric acid in atherosclerosis and deeply study the pathogenic mechanism of uric acid for the prevention and control of metabolic diseases.

Hyperuricemia is a disorder of purine metabolism. Generally, blood uric acid exceeding 420 μ mol/L (7 mg/dl) in men and 360 μ mol/L (6 mg/dl) in women is called hyperuricemia. In recent years, with the development of economy, the prevalence of hyperuricemia in China has increased rapidly. Population surveys in the early 1980s showed that the prevalence of hyperuricemia was 4% in men and 3% in women^[1]。 A population survey in Shandong in the late 1990s showed that the prevalence of hyperuricemia was 5.79% in men and 2.44% in women^[2]In the same period, the prevalence of hyperuricemia among people over 15 years old in Shanghai was 10.1% (14.2% men and 7.1% women)^[3]。 A survey in Nanjing in 2003 showed that the prevalence of hyperuricemia was as high as 13.3%, which was the same as that in Europe and America^[4]。 The prevalence of hyperuricemia in Shandong was 16.7% in 2009 and increased with age^[5]。 The prevalence of hyperuricemia in rural Jiangsu reached 12.2% in 2010^[6]In the same period, the prevalence of hyperuricemia in Heilongjiang and Inner Mongolia reached 13.7%, and the prevalence of hyperuricemia in males has reached 21.0%^[7]。

At present, hyperuricemia has become the second largest metabolic disease after diabetes, which not only involves joints and leads to joint deformities and fractures, but also leads to acute and chronic renal insufficiency, induces and aggravates diabetes, coronary heart disease, stroke and other cardiovascular and cerebrovascular diseases. The prevalence of hyperuricemia in diabetic patients is significantly higher than in the general population. In recent years, a large number of studies have shown that hyperuricemia affects many links of diabetes, including the occurrence and development of diabetes and its chronic complications. However, at present, clinicians have insufficient understanding of the harm of diabetes complicated with hyperuricemia, and lack of enough attention to the prevention and treatment of this disease, which leads to the difficulty of patients' condition to be well controlled for a long time. This article analyzes and summarizes the above problems, hoping to arouse the attention of the majority of clinical workers and provide theoretical basis for clinical practice.

sulfonylureas (SU) are the earliest oral hypoglycemic drugs put into clinical use, and their discovery can be traced back to 1940s. After 60 years of in-depth research, SU has developed to the third generation, its hypoglycemic mechanism has been further explored, its safety has been gradually improved, and its adverse reactions have been continuously reduced. Therefore, SU is still in an important position at present. This paper reviews the development history, Chinese evidence, function characteristics and guiding status of SU.

To investigate the association between hyperuricemia and urinary calculus in diabetic patients and non-diabetic healthy subjects.

Retrospectively analyzed the clinical data of diabetic patients and non-diabetic healthy subjects between January 2011 and September 2014, including body mass index, fasting plasma glucose, serum uric acid, serum creatinine, blood fat, estimated glomerular filtration rate(eGFR) and urinary ultrasound. A total of 2 186 non-diabetic healthy subjects and 4 045 diabetic patients were included in this study. The mean age of non-diabetic healthy subjects was (44±14) years; 762 males and 1 424 females. The mean age of diabetic patients was(59±13) years; 2 260 males and 1 785 females. The prevalences of urinary calculus in subjects with hyperuricemia and without in the two groups were compared with χ ² test; and the prevalences of urinary calculus in subjects with different levels of uric acid were calculated too. Besides, the influence of hyperuricemia, diabetes on the prevalence of urinary calculus were also analyzed.

The prevalence of urinary calculus in hyperuricemia group(7.9%) was significantly higher than that in normal serum uric acid group(3.5%) in non-diabetic group (χ²=5.453, P< 0.05); and it was significantly higher in hyperuricemia group than that in the subjects with normal serum uric acid in diabetic patients (13.9% vs 10.5%, χ²=4.786, P<0.05). The prevalence of urinary calculus increased with serum uric acid (non-diabetic subjects: χ²=9.008, P<0.05; diabetic subjects: χ²=9.278, P<0.05). The prevalence of urinary calculus was significantly higher in the group with serum uric acid>420 μmol/L than the subjects with serum uric acid ≤300 μmol/L (non-diabetic subjects:OR=3.037, 95% confidence interval (CI): 1.386-6.655, P<0.01; diabetic subjects:OR=1.520, 95%CI: 1.120-2.063, P<0.01). The risk of urinary calculus increased significantly in patients with hyperuricemia, diabetes or both diseases compared with that in non-diabetic non-hyperuricemia subjects (hyperuricemia: 7.9% vs 3.5%,OR=2.405, 95% CI: 1.125-5.140, P<0.05; diabetes: 10.5% vs 3.5%,OR=3.292, 95%CI: 2.543-4.262, P<0.01; both hyperuricemia and diabetes: 13.9% vs 3.5%,OR=4.501, 95% CI: 3.170-6.390, P<0.01).

The prevalence of urinary calculus in hyperuricemia patients is higher than that in normal serum uric acid subjects among non-diabetic healthy subjects and diabetic patients, and higher prevalence of urinary calculus occurs in hyperuricemia patients complicated with diabetes.

To investigate the clinical risk factors of diabetes mellitus in patients with gout.

Total 7 326 patients (6 800 males and 526 females) from the gout clinic of Affiliated Hospital of Qingdao University between May 2009 and May 2015 were chosen as case group, while 8 370 people without gout (7 301 male and 1 069 female) were chosen as control group. The height, weight, waistline, hipline, blood pressure, fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), creatinine (Cr) and uric acid (UA) of both groups were monitored. Clinical and biochemical differences of the two groups were analyzed. The morbidity rate of diabetes in the two groups were also compared. According to different criterions, the subjects were divided into several subgroups. The t test, chi-square test and linear regression analysis were using when data were analyzed.

The morbidity rate of diabetes in case group was 15.5%, and it was higher than that in control group(9.9%, χ ²= 93.57, P<0.05). The incidence of diabetes was positively correlated with age, and was always higher in the case group than that of the control group with the same age scale (χ²=14.85, P<0.05). In case group, FPG was positively correlated with UA level(F=4.14, t=76.24, r>1,P<0.05), while UA level was negatively correlated with FPG (F=4.14, t=90.40, r<1,P<0.05). The morbidity of diabetes were all significantly higher in the gout patients when combined with hypertension, hyperlipidemia or obesity when compared with that in patients with simple gout (χ²=4.46,3.95, 4.42, all P<0.05), and the mean level of FPG and UA were all higher too (t=-3.38--2.00, all P<0.05). The multiple linear regression analysis indicated that the FPG in gout patients combined with diabetes was affected by age, body mass index, systolic blood pressure, TG and UA(standardized coefficient β=0.122, 0.038, 0.046, 0.184, 0.034, allP<0.05). When gout patients developed abnormal glucose metabolism, the body mass index, waist-hip ratio, systolic blood pressure, diastolic blood pressure, FPG and TG in those patients were all signficantly higher than those in gout patients with normal glucose tolerance(t=4.27-50.62, all P<0.05), except for Cr and UA (t=0.48, 0.38, both P>0.05).

Hypertension, hyperlipidemia, obesity, age and hyperuricemia are the risk factors for gout patients developing diabetes; when gout patients combined with diabetes, the patients' UA level reduces.

To evaluate the glucose metabolism status of 1 671 inpatients in the Department of Orthopaedics.

All adult inpatients in orthopaedic department were accessed consecutively from July, 2012 to January, 2014. Oral glucose tolerance test (OGTT) was performed in patients with random blood glucose ≥7.0 mmol/L or fasting plasma glucose(FPG) ≥5.0 mmol/L. Chi-square test and t test were used for between-group comparison of rate and mean, respectively.

A total of 1 671 patients were included in this study. The prevalence of diabetes mellitus (DM) and impaired glucose regulation(IGR) were 25.20% (416/1 671) and 8.32% (139/1 671), respectively. OGTT were performed in 328 patients including 133 newly-diagnosed DM (40.55%) and 139 IGR (42.37%). The total prevalence of abnormal glucose metabolism was 33.52%. When the patients were stratified by age, the diagnosis rate of DM increased in those over 50 and the difference was statistical significant between groups(χ²=33.784, P<0.001). And the detection rate of DM reached 58.73% in 60~70 years; Compared with euglycemic patients, the hospital stay of DM was much longer (t=2.294, P= 0.022). If with FPG test alone, 47.48% IGR and 60.90% DM would remain undiagnosed.

Abnormal glucose metabolism occurrs in about 1/3 orthopaedic inpatients with higher incidence observed in aged patients. Hospital stay is longer for diabetic patients. OGTT may improve screening rate of abnormal glucose metabolism.

To examine the association of newly identified obesity-related genes' SNPs with obesity in Chinese children.

A total of 201 Chinese children with obesity were selected as research subjects from January to September 2010. One hundred eighty three healthy adult blood donors were selected as normal controls. Mass spectrometry techniques were used to study the distributions of the alleles and genetype of newly identified obesity susceptibility loci in patients and controls. And the relationship between newly identified obesity-related loci gene polymorphism and obesity in Chinese children were studied.

The distributions of three gene polymorphisms (rs7138803 of FAIM2 gene, A frequency of alleles in the obesity group was obviously higher than that of normal control group (35.5% to 26.5%), two groups compare difference was statistically significant (χ²=6.94, P=0.0084); rs10838738 of MTCH2 gene, G frequency of alleles in the obesity group was obviously higher than that of normal control group (35.3% to 27.7% ), two groups compare difference was statistically significant (χ²=5.04, P=0.0248); and rs7647305 of ETV5 gene, C frequency of alleles in the obesity group was obviously higher than that of normal control group (94.3% to 90.5%)two groups compare difference was statistically significant (χ²=3.93, P=0.0475)) in obesity patients and healthy controls have significant differences. And the distributions of genetypes (rs7138803 of FAIM2 gene) in obesity patients and healthy controls have significant differences.

The gene polymorphisms of rs7138803 of FAIM2 gene, rs10838738 of MTCH2 gene and rs7647305 of ETV5 gene confer significant susceptibility to obesity in Chinese children.

To investigate the correlation between serum leptin (LEP)/adiponectin (APN) (L/A) ratio and metabolic syndrome (MS) in children and adolescents.

Total of 3 520 children and adolescents between 6 and 18 years of age were selected from the subjects that had been recruited for 2004 survey conducted by Beijing Children and Adolescent MS (BCAMS) study. Adjusted criteria issued by International Diabetes Federation (IDF) in 2007 were used to establish a diagnosis of MS. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum leptin and adiponectin levels. Areas under the receiver operating characteristi c curve (ROC) were also examined to determine the diagnostic value of L/A in the diagnosis of MS in children.Multiple comparisons were made between groups using analysis of variance (ANOVA) and the chi-square test. Pearson correlation analysis was performed to determine the correlation between L/A values and various components of MS.

(1) As the L/A value increased, body mass index (BMI), blood pressure (BP), central obesity (CO%) and insulin resistance (IR%) increased progressively, as did, MS detection rate (MS%) increased (χ² =male: 108.63 ;female: 94.30) (all P< 0.01). (2) L/A ratio area under curve (AUC) of ROC (AUC=0.803) in boys was higher than leption (AUC= 0.771) and adiponectin (AUC=0.703, allP<0.05).L/A ratio AUC of ROC (AUC=0.838) in girls was higher than leptin (AUC=0.817,P=0.0785). L/A ratio and leptin AUC of ROC are higher than adiponectin (AUC= 0.717, all P<0.05).

L/A is a better marker for the diagnosis of MS in Children better than leptin and adiponectin alone. L/A could be used as an indicator for MS in children and adolescents, and played an auxiliary role in the diagnosis of obesity-related MS in children.

To explore the relationship between anxiety and the quality of life in patients with type 2 diabetes mellitus (T2DM) to perform specific community prevention, and to provide reference to improve the quality of life in patients T2DM.

Total of 776 participants who lived in 32 villages / communities of Xuzhou were enrolled with the multi-stage cluster random sampling method, and were investigated with a self-designed questionnaire, the Pittsburgh sleep quality index (PSQI), self rating Anxiety Scale (SAS), self rating Depression Scale (SDS) and the amount of specific quality of life in patients with diabetes mellitus (DSQL). The patients were divided into mild, moderate and severe anxiety groups. One-way analysis were used to analyze differences among several groups, Multiple linear regression and Pearson χ ² were used to analyze the association between anxiety and quality of life.

Of the 776 enrolled diabetes mellitus patients, the prevalent rate of anxiety was 58.89% (457/776), the percentage of none, mild, moderate and severe anxiety were 41.11%(319/776), 49.61%(385/776), 7.99%(62/776), 1.29% (10/776)respectively. The scores of qualities of life in patients with type 2 diabetes with none, mild, moderate and severe anxiety were (40 ± 9), (47 ± 11), (52 ± 15) and (65 ± 13). There were significant differences between different groups (F=43.589, P<0.05). The correlation analysis between anxiety and total DSQL scale and components of DSQL showed that except for the social relationship dimension of DSQL(r=0.046, P>0.05), there were positive correlation between anxiety and total DSQL scale and the other dimensions of DSQL. The correlation between anxiety and total score of DSQL, physiological function dimension, psychological dimension and treatment dimension were 0.395, 0.454, 0.341, 0.150 (P<0.05, all above).The results showed that the correlation between anxiety and physical dimensions of DSQL was the strongest. After adjust for age, sex, culture degree, marriage, family income, course of disease, complication, blood glucose control, sleep quality, depression and so on, the regression coefficient of anxiety and quality of life was 0.239, ranked at the first factor in numerous oners.

Compared with other potential risk factors, the anxiety is the highest negatively related to the quality of life of patients with type 2 diabetes mellitus.

To investigate the role of exendin-4 treatment on fat metabolism of brown adipose tissue in C57BL/6J mice induced with high-fat diet.

Thirty six-week-old C57BL/6J mice were randomly divided into 3 groups(10 mice in each group): control group, high-fat diet (HFD) group, and HFD group treated with exendin-4. After 16 weeks, the body weight, body fat composition, free fatty acids, leptin, triglycerides level of each group were measured. The mRNA and protein expression of glucose transporter type 4 (GLUT-4), peroxisome proliferative activated receptor γ2(PPAR-γ2), perilipin and uncoupling protein 1(UCP-1) in the scapular brown adipose tissue were detected with real-time quantitative polymerase chain reaction(PCR) and Western blotting methods. One-way ANOVA was used when data were compared among multiple groups and t analysis was applied for comparison between two groups.

Compared with those in control group, the body weight, body fat composition, free fatty acids, leptin and triglyceride levels increased significantly in the HFD group (t=7.34, 6.11, 8.33, 10.51, 4.19, all P<0.05); the mRNA and protein expression of GLUT-4, PPAR-γ2, perilipin and UCP-1 in the scapular brown adipose tissue in HFD group decreased significantly when compared with those in control group (t=7.15-34.79, all P< 0.05). Compared with those in the HFD group, the body weight, body fat composition, free fatty acids, leptin and triglyceride levels decreased significantly in the exendin-4-treating group(t=5.63, 4.04, 8.85, 6.06, 3.07, all P<0.05), while the mRNA and protein expression of GLUT-4, PPAR-γ2, perilipin and UCP-1 increased significantly in the scapular brown adipose tissue in the exendin-4-treating group(t=5.38-21.69, all P<0.05).

GLP-1 receptor agonist may reduce body weight via regulating lipid metabolism in brown fat.

To investigate the therapeutic effect of resveratrol on diabetic cataract in SD rats.

Forty-five SD rats(weighted (300±5) g) were randomly divided by using random number table into normal control group, diabetic model group and resveratrol group, 15 in each group. Diabetic cataract was induced by streptozotocin(STZ) in diabetic model group and resveratrol group. No treatment was given to the rats in normal control group, diabetic model group. The 400 mg/kg resveratrol was administrated by gavage in resveratrol group. At the end of 4, 8 and 12 weeks after the treatment of resveratrol, eyeballs were harvested and cataract formation in all rats was recorded, meanwhile the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and the level of malondialdehyde(MDA) in lenses were measured respectively. And the apoptosis of lens epithelial cells was detected and statisticed using terminal deoxynucleotidy transferase mediated x-dutpnik end labeling(TUNEL) method. Data were compared between groups by using t test.

At the end of 4, 8 and 12 weeks, lens of normal control group were transparent, lens opacity in resveratrol group was higher than those in control group, but was lower than those in diabetic model group. At the end of 4, 8 and 12 weeks, the grey value of lens in resveratrol group was 27.5±2.2, 34.4±1.8, 46.4±5.1 respectively, and were all significantly lower than those in diabetic model group(t=24.063, 53.411, 54.027, all P<0.05), but were all markablly higher than those in control group(t=-8.902, -31.567, -44.013, all P<0.05). At the above-mentioned time points, the activity of SOD and GSH-Px were botn significantly higher than those in diabetic model group(t=-145.738--18.193, all P<0.05), but lower than those in control group(t=11.388-95.746, all P<0.05); the activity of MDA was lower than those in diabetic model group(t=33.027, 29.623, 40.976, all P<0.05), but higher than those in control group (t=-14.920, -22.851, -39.992, all P<0.05). At the end of 4, 8 and 12 weeks, the apoptosis rate of lens epithelial cells in resveratrol group were 0.66±0.17, 17.89±0.24, 28.21±0.38, respectively, which were higher than those in control group(t=-25.958, -77.897, -80.725, all P<0.05), but obviously lower in diabetic group(t=101.729, 45.940, 167.104, all P<0.05).

Resveratrol could increase the antioxidase activity, and inhibit the apoptosis of lens epithelial cells in diabetic cataract rats, thus delays the generation and development of catarac.

Nonalcoholic fatty liver disease (NAFLD) is a clinical syndrome characterized by diffuse steatosis and lipid accumulation of hepatocytes, excluding alcohol and other definite liver damage factors. Depending on whether the diseased tissue is accompanied by inflammatory reaction and fibrosis, NAFLD can be classified into simple fatty liver disease (NAFL), steatohepatitis (NASH) and cirrhosis. In recent years, with the improvement of people's living standards and lifestyle changes, NAFLD has become a common disease that seriously threatens people's health. In western countries, the prevalence of NAFLD in the general population is 20% ~30%^[1,2]。 The pathogenesis of NAFLD is still unclear, and many factors are involved in its occurrence and development, including genetics, metabolism and diet. NAFLD is considered to be a manifestation of insulin resistance in the liver, so it is closely related to metabolic syndrome (MS), obesity, type 2 diabetes (T2DM), dyslipidemia, hypertension, and an independent risk factor for cardiovascular disease. Recently, more and more studies suggest that blood uric acid (SUA) may play an important role in the occurrence and development of NAFLD. The correlation between hyperuricemia (HUA) and NAFLD has become a hot research topic in recent years. This article will review it in order to better clarify the role of HUA in the development of NAFLD.

With the widespread application of insulin, the reports of acute painful neuropathy in diabetes after insulin therapy are gradually increasing, and a few patients, especially those with type 1 diabetes, can develop acute neuropathy at the initial stage of intensive insulin therapy^[1]The reason may be related to axonal degenerative lesions of small myelinated A δ fibers and unmyelinated C fibers^[2]。 This kind of diabetic neuropathy characterized by damage of superficial sensory nerve has attracted the attention of scholars at home and abroad, but it has not been deeply studied, and its pathogenesis is not very clear. Combined with literature review and clinical practice, the progress of acute painful neuropathy in insulin-related diabetes mellitus is briefly introduced below.

growth hormone (GH) replacement therapy is the only proven therapeutic measure for patients with growth hormone deficiency^[1,2], GH replacement therapy has a significant growth-promoting effect. As early as 1958, a successful case of replacement therapy with growth hormone for children with growth hormone deficiency (GHD) was reported abroad for the first time^[3]。 In the 1980s, "inclusion body technology" made it technically possible to obtain recombinant human growth hormone (rhGH). DNA recombination technology enabled mass production of rhGH, which overcame the yield limitation of pituitary extract and solved some application safety problems^[4]。 Up to now, rhGH has been in clinical application for more than 20 years, and its effectiveness has been affirmed, but its safety has been widely concerned. On the one hand, GH antagonizes the effect of insulin on glucose metabolism by reducing peripheral blood glucose uptake, promoting glycogenolysis and gluconeogenesis; On the other hand, GH can also promote lipid decomposition, thus promoting lipid oxidation and inhibiting glucose decomposition^[5]。 Because of the antagonistic effect of growth hormone on insulin and the effect of raising blood sugar, its influence on the incidence of diabetes has been paid more and more attention. This article will discuss the influence of growth hormone on the glucose metabolism and the incidence of diabetes in children and adolescents in existing studies, in order to arouse doctors' attention to the changes of glucose metabolism in patients receiving GH replacement therapy.

At present, my country has become the country with the largest number of diabetic patients in the world. The prevalence of adult diabetes in China is 11.6%, while the prevalence of prediabetes is estimated to reach 50.1%. Only a quarter of patients receive treatment, of which only 39.7% have good blood sugar control^[1]。 Glycosylated glycemic protein (HbA_1c) Long-term elevated levels increase the risk of microvascular and macrovascular complications in patients^[2]。 There are many reasons for poor blood glucose control in diabetic patients, among which patients' medication compliance is a very important influencing factor. Good medication compliance can help improve patients' blood glucose levels, Rhee, etc.^[3]A retrospective analysis of 1 560 patients with type 2 diabetes showed that for every 25% increase in medication adherence, their HbA_1cLevel decreased by 0.34% (P=0.000 9）。 Egede et al.^[4]A 12-year follow-up of 11 272 patients showed a 48% reduction in the likelihood of poor glycemic control for every 1% increase in medication adherence (odds ratio 0.52, 95%CI：0.4~0.6）。