Association between serum uric acid levels and cardiovascular events in hospitalized patients with type 2 diabetes.

AIMS: This study aimed to determine the association between serum uric acid (UA) levels and cardiovascular events in hospitalized patients with type 2 diabetes mellitus (T2DM). METHODS: A retrospective cohort study was conducted in 2227 hospitalized patients with T2DM. Cox proportional hazards regression was used to assess the association between serum UA and cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, heart failure, unstable angina, and arrhythmias requiring hospitalization. RESULTS: Among 1314 men, 143 (10.9%) experienced cardiovascular events. Serum UA level was not associated with the risk of cardiovascular events (hazard ratio [HR] per 100 µmol/L increase in serum UA: 1.12, 95% confidence interval [CI]: 0.90-1.40). Among 913 women, 96 (10.5%) experienced cardiovascular events. For every 100 µmol/L increase in serum UA level, the risk of experiencing a cardiovascular event increased by 27% (HR: 1.27, 95% CI: 1.02-1.57). CONCLUSIONS: In hospitalized patients with T2DM, baseline serum UA levels were positively associated with cardiovascular events in women, but not in men. Serum UA levels may be a significant independent risk factor for cardiovascular events in women with T2DM.

Predictors of Renal Function Decline in Chinese Patients with Type 2 Diabetes Mellitus and in a Subgroup of Normoalbuminuria: A Retrospective Cohort Study.

BACKGROUND: Risk factors related to renal function decline in type 2 diabetes mellitus (T2DM) remain uncertain. This study aimed to investigate risk factors in relation to renal function decline in patients with T2DM and in a subgroup of patients with normoalbuminuria. METHODS: This study was a retrospective cohort study, which included 451 patients with T2DM aged 63 ± 14 years admitted to a tertiary hospital in Beijing, China, between April and December 2010 and followed up for 6-60 months. Endpoint was renal function decline, defined as estimated glomerular filtration rate less than 60 mL/min 1.73 m2 or at least twofold increase of serum creatinine. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) for candidate risk factors of renal function decline. RESULTS: After a median follow-up of 3.3 years, 94 (20.8%) patients developed renal function decline. Increased age (HR, 1.045; 95% CI, 1.020-1.070), albuminuria (HR, 1.956; 95%CI, 1.271-3.011), mild renal dysfunction (HR, 4.521; 95%CI, 2.734-7.476), hyperfiltration (HR, 3.897; 95%CI, 1.572-9.663), and increased hemoglobin A1c (HR, 1.128; 95%CI, 1.020-1.249) were identified as major risk factors. Among a subgroup of 344 patients with normoalbuminuria at baseline, 53 (15.4%) patients developed renal function decline. Increased age (HR, 1.089; 95%CI, 1.050-1.129), mild renal dysfunction (HR, 4.667; 95%CI, 2.391-9.107), hyperfiltration (HR, 5.677; 95%CI, 1.544-20.872), smoking (HR, 2.886; 95%CI, 1.370-6.082), higher pulse pressure (HR, 1.022; 95%CI, 1.004-1.040), and increased fasting glucose (HR, 1.104; 95%CI, 1.020-1.194) were major risk factors. CONCLUSIONS: Risk factors of diabetic renal impairment in T2DM should be screened and evaluated at an early stage of diabetes. Albuminuria, mild renal dysfunction, hyperfiltration, increased blood glucose, increased pulse pressure, and smoking were all predictors for diabetic renal impairment and interventions that focus on these risk factors may reduce further decline in renal function.

Relationship Between Serum Zinc Level and Microvascular Complications in Patients with Type 2 Diabetes.

BACKGROUND: Previous studies suggested that zinc level was related to a certain diabetic microvascular complication. However, the relationship between zinc level and all the microvascular complications in type 2 diabetic patients remains unknown. The purpose of this study was to analyze the relationship between zinc level and each diabetic microvascular complication and identify the features related to low serum zinc level. METHODS: We included the hospitalized patients with type 2 diabetes (T2D) at our department from May 30, 2013 to March 31, 2014. We initially compared the serum zinc levels between patients with specific microvascular complications and those without. We then analyzed the association between zinc level and each microvascular complication. Furthermore, we identified the unique features of patients with high and low serum zinc levels and analyzed the risk factors related to low zinc level. RESULTS: The 412 patients included 271 with microvascular complications and 141 without any microvascular complications. Serum zinc level was significantly lower in patients with diabetic retinopathy (P < 0.001), diabetic nephropathy (DN, P < 0.001), or diabetic peripheral neuropathy (P = 0.002) compared with patients without that specific complication. Lower zinc level was an independent risk factor for DN (odds ratio = 0.869, 95% confidence interval = 0.765-0.987, P < 0.05). The subjects with lower serum zinc level had manifested a longer duration of diabetes, higher level of hemoglobin A1c, higher prevalence of hypertension and microvascular complications, and lower fasting and 2-h C-peptide levels. CONCLUSIONS: Lower serum zinc level in T2D patients was related to higher prevalence of diabetic microvascular complications, and represented as an independent risk factor for DN. Patients with lower zinc level were more likely to have a longer duration of diabetes, poorer glucose control, and worse ß-cell function.

Twenty-year trends in major cardiovascular risk factors in hospitalized patients with acute myocardial infarction in Beijing.

BACKGROUND: Hypertension, diabetes mellitus, hypercholesterolaemia and current smoking are the strongest modifiable cardiovascular risk factors for acute myocardial infarction (AMI). We examined their changing trends over the last 20 years. METHODS: The clinical data of 3498 patients hospitalized in Peking University People's Hospital with AMI from 1991 to 2010 were used. Information was collected regarding to patients' demographic data, cardiovascular risk factors (hypertension, diabetes mellitus, hypercholesterolemia and current smoking). To assess trends over time in the prevalence of risk factors, we categorized patients into four groups (1991 to 1995, 1996 to 2000, 2001 to 2005 and 2006 to 2010). RESULTS: Highly significant increases were observed in the prevalence of hypertension from 40.8% to 55.6% for males and from 58.0% to 69.0% for females; and diabetes mellitus from 12.9% to 30.8% for males and from 23.0% to 42.3% for females. Similarly, the prevalence of hypercholesterolaemia decreased from 53.1% to 30.7% for males and from 57.0% to 44.0% for females. The prevalence of current smoking decreased in females from 29.0% to 11.1%, but remained unchanged in males. In addition, the proportion of patients with more than three modifiable risk factors increased from 19.0% to 27.1% and the age at onset of AMI extended to younger as well as older individuals. CONCLUSIONS: The prevalence of hypertension and diabetes mellitus are still increasing in patients with AMI in Beijing and although the prevalence of hypercholesterolaemia and current smoking decreased, high clustering of risk factors were commonly present. These adverse trends show a compelling need for more effective management of cardiovascular risk factors.

Effects of Chinese medicine Tongxinluo on hyperglycemia and beta-cell damage in streptozotocin-induced diabetic rats.

BACKGROUND: Oxidative stress has been implicated in the onset and progression of diabetes. Tongxinluo is a traditional Chinese medicine with potent antioxidant properties. The aim of this study was to test the hypothesis that pretreatment with Tongxinluo has similar effects as melatonin on preventing hyperglycemia and beta-cell damage in a rat model of streptozotocin (STZ)-induced diabetes. METHODS: Forty male Sprague Dawley rats were randomly assigned to four groups (n = 10 each): normal control (NC) group; STZ group (70 mg/kg, i.p.); Tongxinluo (1.0 g×kg(-1)×d(-1)) pretreated (TXL + STZ) group and melatonin (200 µg×kg(-1)×d(-1)) pretreated (MLT + STZ) group. Tongxinluo and melatonin were administered by gavage beginning 8 days before STZ injection and continuing until the end of the study (15 days after STZ administration). Blood glucose levels and body weights, malondialdehyde (MDA), and reduced glutathione (GSH) levels were measured, and immunofluorescence studies were performed in all of the groups. RESULTS: Pretreatment with Tongxinluo, as with melatonin, attenuated severe hyperglycemia and weight loss induced by STZ. In pancreatic homogenates, MDA levels were significantly lower and GSH levels were significantly higher in Tongxinluo pretreated group and in melatonin pretreated group than those in STZ group. Values of insulin staining were significantly improved in Tongxinluo pretreated group and in melatonin pretreated group as compared with those in STZ group. CONCLUSIONS: Tongxinluo, as melatonin, prevented hyperglycemia and beta-cell destruction induced by STZ in rats through reducing oxidative stress in pancreatic tissues. Tongxinluo may provide an alternative therapy for the prevention and treatment of diabetes.

Contribution of the Akt2 gene to type 2 diabetes in the Chinese Han population.

BACKGROUND: The Akt2 protein kinase is thought to be a key mediator of the insulin signal transduction process. Akt2 is suggested to play a role in glucose metabolism and the development or maintenance of proper adipose tissue and islet mass. In order to determine whether the Akt2 gene plays a role in the pathogenesis of type 2 diabetes characterized by insulin resistance, and to further identify if variations in this gene have a relationship with type 2 diabetes, we sequenced the entire coding region and splice junctions of Akt2 and made a further case-control study to explore the association between single-nucleotide polymorphisms (SNPs) in this gene and type 2 diabetes in the Chinese Han population. METHODS: We selected 23 probands with a type 2 diabetic pedigree whose family members' average onset age was within 25 to 45 years old. The body mass index of all the participants was lower than 28 kg/m(2) and all of them were insulin-resistant (the fasting insulin level > 100 pmol/L or 16 µIU/ml). The entire coding region and splice junctions of Akt2 were directly sequenced in these 23 probands. SNPs with a frequency of minor allele over 20 percent were selected to be further studied in a case-control study. We chose 743 non-diabetic subjects as the control group and 742 type 2 diabetic patients as the case group. All these subjects were genotyped. A Snapshot Technology Platform (Applied Biosystems) was used for genotyping. RESULTS: The Akt2 genes from all 23 subjects were successfully sequenced. We did not identify any mutation in the type 2 diabetic pedigree. Two SNPs were identified, 13010323T > C and 13007939G > T. 13010323T > C was in intron 9, which was the location of rs2304188 reported in Genbank. Its minor allele frequency was 13.04%. 13007939G > T was in the 3'-untranslated region (UTR) of exon 14, which was the location of rs2304186 reported in Genbank. Its minor allele frequency was 34.78%. The allele frequency of rs2304188 and rs2304186 were consistent with the frequency reported in Genbank. In the case-control study with 742 patients and 743 controls, there was no significant difference between the two groups for the allele frequency of rs2304186 (odd ratio: 0.96, 95% confidence interval: 0.82 - 1.12, P = 0.597). CONCLUSIONS: The Akt2 gene is not a major cause of diabetes in a non-obese Chinese Han population characterized by insulin resistance. There is no significant relationship between rs2304186 and type 2 diabetes in the Chinese Han population.

Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population.

BACKGROUND: KCNJ11, ABCC8, PPARG, and HNF4A have been found to be associated with type 2 diabetes in populations with different genetic backgrounds. The aim of this study was to test, in a Chinese Han population from Beijing, whether the genetic variants in these four genes were associated with genetic predisposition to type 2 diabetes. METHODS: We studied the association of four representative SNPs in KCNJ11, ABCC8, PPARG, and HNF4A by genotyping them using ABI SNaPshot Multiplex System in 400 unrelated type 2 diabetic patients and 400 unrelated normoglycaemic subjects. RESULTS: rs5219 (E23K) in KCNJ11 was associated with genetic susceptibility to type 2 diabetes (OR = 1.400 with 95% CI 1.117 1.755, P = 0.004 under an additive model, OR = 1.652 with 95% CI 1.086 2.513, P = 0.019 under a recessive model, and OR = 1.521 with 95% CI 1.089 2.123, P = 0.014 under a dominant model) after adjusting for sex and body mass index (BMI). We did not find evidence of association for ABCC8 rs1799854, PPARG rs1801282 (Pro12Ala) and HNF4A rs2144908. Genotype-phenotype correlation analysis revealed that rs1799854 in ABCC8 was associated with 2-hour postprandial insulin secretion (P = 0.005) after adjusting for sex, age and BMI. Although no interactions between the four variants on the risk of type 2 diabetes were detected, the multiplicative interaction between PPARG Pro12Ala and HNF4A rs2144908 was found to be associated with 2-hour postprandial insulin (P = 0.004 under an additive model for rs2144908; and P = 0.001 under a dominant model for rs2144908) after adjusting for age, sex and BMI, assuming a dominant model for PPARG Pro12Ala. CONCLUSIONS: Our study replicated the association of rs5219 in KCNJ11 with type 2 diabetes in Chinese Han population in Beijing. And we also observed that ABCC8 as well as the interaction between PPARG and HNF4A may contribute to post-challenge insulin secretion.

[Cross-sectional study of the pathophysiologic and clinical features in the first-degree relatives of type 2 diabetic patients].

OBJECTIVE: To explore the pathophysiologic and clinical features and investigate the roles of insulin resistance and insulin secretion in the pathogenesis of type 2 diabetes mellitus. METHODS: A total of 888 first-degree relatives without glucose intolerance history underwent an oral glucose test (OGTT) and their level of HbA1c, insulin concentration and lipid levels were determined. The homeostasis model assessment was used to estimate insulin resistance (HOMA(IR)) and beta-cell function (HOMA-beta). The ratio of incremental glucose (DeltaG30) and insulin (DeltaI30) response was used to evaluate the early insulin secretion. DeltaI30/DeltaG30/HOMAIR was used to evaluate the glucose disposition index (DI). RESULTS: In the subjects, 167 were diagnosed with diabetes, 180 with impaired glucose tolerance or/and impaired fasting glucose (impared glucose regulation), 457 with normal glucose tolerance and normal HbA1c, and 84 with normal glucose tolerance and high HbA1c. From normal glucose tolerance through impared glucose regulation to diabetes mellitus, the HOMA(IR), body mass index (BMI), waist/hip ratio (WHR) and serum triglyceride (TG) progressively increased, HOMA-beta cell, DeltaI30/DeltaG30, DI and high density liproprotein (HDL) progressively decreased. Subjects with normal glucose tolerance were divided into three tertile subgroups (1/3, 2/3 and 3/3 groups) with different area under the curve of OGTT glucose, after being adjusted by sex, age, BMI, the 3/3 group was found having higher HOMA(IR), and lower HOMA-beta, DeltaI30/DeltaG30/, and DI than the 1/3 group. CONCLUSION: Both insulin resistance and impaired beta cell function are important pathophysiologic changes contributing to the onset and development of type 2 diabetes. These changes and lipid profile have occurred before a patient is diagnosed with abnormal glucose tolerance.

[Insulin sensitivity and beta function in the first-degree relatives of type 2 diabetic patients].

OBJECTIVE: To investigate the roles of insulin resistance and beta-cell function in the pathogenesis of type 2 diabetes mellitus. METHODS: 614 first-degree relatives without glucose intolerance history underwent an oral glucose test (OGTT) and their levels of HbA1c were determined. According to the single OGTT results and WHO criteria, 118 (19.2%) of the 614 subjects were newly diagnosed with diabetes, 121 (19.7%) with impaired glucose tolerance (IGT) or/and impaired fasting glucose (IFG), 375 with normal glucose tolerance (NGT), of which 316 (51.5%) subjects were with HbA1c in normal level range (4% approximately 6%) and the others with high HbA1c level (9.6%). Homeostasis model assessment of insulin resistance (Homa(IR)) was used to estimate insulin resistance, Homa-beta cell was used to evaluate basal insulin secretion, incremental glucose (DeltaG30) and insulin (DeltaI30) response was calculated as the difference between the values 30 min after glucose intake to evaluate the early insulin secretion, DeltaI30/DeltaG30/HOMA(IR) was used to evaluate the disposition index (DI). RESULTS: Decreasing glucose tolerance was associated with insulin resistance, beta cell function and DI. From normal glucose tolerance condition through IFG /IGT to diabetic, the Homa IR progressively increased (NGT 0.76 +/- 0.6, IFG/IGT 1.0 +/- 0.6, DM 1.5 +/- 0.6, P < 0.001), Homa-beta cell (NGT 5.3 +/- 0.7, IFG/IGT 5.1 +/- 0.7, DM 4.1 +/- 0.9), I30/DeltaG30 (NGT 2.8 +/- 0.9, IFG/IGT 2.2 +/- 1.0, DM 1.3 +/- 1.0) and DI (NGT 2.0 +/- 0.9, IFG/IGT 1.1 +/- 0.9, DM -0.2 +/- 1.2), progressively decreased (P < 0.001). Normal subjects were divided into three tertile groups with different area under the curve of OGTT glucose. After adjusted by sex, age, BMI and WHR, the upper terile group was found having high Homa IR and lower Homa-beta, DeltaI30/DeltaG30/, I than lower tertile group. CONCLUSION: Abnormal glucose tolerance is common in first-degree relatives of non-insulin-dependent Diabetes Mellitus patients, both insulin resistance and impaired beta cell function are associated with impaired glucose metabolism, which have existed before diagnosis of IFG, IGT and diabetes.