Associations of GWAS-Supported Non-MHC Genes with Autoimmune Thyroiditis in Patients with Type 1 Diabetes.

PURPOSE: A genome-wide association study (GWAS) in Caucasian population identified five non-MHC genes (PHTF1, PTPN22, MAGI3, BCL2L15, and QRFPR) associated with risk of the co-occurrence of autoimmune thyroid diseases (AITD) and type 1 diabetes (T1D). The aim of this study is to replicate these associations with AITD in patients with T1D in Chinese Han population. PATIENTS AND METHODS: A case-control study was designed. Five single-nucleotide polymorphisms (SNPs) PHTF1 rs1111695, PTPN22 rs1217407, MAGI3 rs2153977, BCL2L15 rs2358994, and QRFPR rs7679475 were genotyped in 489 patients with T1D. Associations between genotypes and AITD risk were analyzed with logistic regression model. RESULTS: AITD occurred in 159 (32.5%) patients. When adjusting multiple factors by logistic regression, QRFPR rs7679475 was significantly associated with an increased risk of AITD in T1D patients in codominant model (G/G vs A/A, OR 2.93; 95% CI 1.44-5.96; P = 0.003), dominant model (G/A-G/G vs A/A, OR 1.81; 95% CI 1.17-2.79; P = 0.007) and recessive model (G/G vs A/A-G/A, OR 2.28; 95% CI 1.17-4.43; P = 0.015). Furthermore, we found a significant interaction between rs7679475 and female (P interaction = 0.005). In silico analysis indicated that rs7679475 is located in histone modification marked region and can change the binding of regulatory motifs. CONCLUSION: Our results suggested that QRFPR rs7679475 may influence the risk of AITD in patients with T1D in Chinese Han population, and this effect may be modulated by sex.

Educational attainment protects against type 2 diabetes independently of cognitive performance: a Mendelian randomization study.

AIMS: Observational studies have reported a negative association between educational attainment and type 2 diabetes (T2D), but the causality remains largely unknown. The aim of this study is to investigate the potential causal effect of educational attainment on T2D and whether such an effect is independent of cognitive performance. METHODS: We conducted two-sample Mendelian randomization (MR) analysis using genetic variants strongly associated with educational attainment and cognitive performance to estimate the causal associations with T2D, among 61,714 T2D cases and 593,952 controls. We also performed multivariable MR to explore the independent effects of educational attainment and cognitive performance on T2D risk. RESULTS: In univariable MR, we found evidence that genetically predicted higher educational attainment [odds ratio (OR) 0.53 per 1-standard deviation (SD) increase; 95% confidence interval (CI) 0.47-0.60] and cognitive performance (OR 0.79 per 1-SD increase; 95%CI 0.69-0.91) were related to decreased risk of T2D. Our further multivariable MR results suggested that more years of education led to a reduced likelihood of T2D independently of cognitive performance (OR 0.52; 95%CI 0.42-0.64). However, the protective effect of cognitive performance on T2D was attenuated once educational attainment was controlled for (OR 1.08; 95%CI 0.88-1.32). CONCLUSIONS: We provided evidence to suggest that educational attainment protects against T2D independently of cognitive performance, but does not support a negative causal association between cognitive performance and T2D independently of educational attainment. Education might represent a potential target for intervention to battle type 2 diabetes risk.

Chiglitazar monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomized, double-blind, phase 3 trial (CMAS).

Chiglitazar (Carfloglitazar) is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes. In this randomized phase 3 trial, we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen. Eligible patients were randomized (1:1:1) to receive chiglitazar 32 mg (n = 245), chiglitazar 48 mg (n = 246), or sitagliptin 100 mg (n = 248) once daily for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin A1C (HbA1c) from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin. Both chiglitazar and sitagliptin significantly reduced HbA1c at week 24 with values of -1.40%, -1.47%, and -1.39% for chiglitazar 32 mg, chiglitazar 48 mg, and sitagliptin 100 mg, respectively. Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg, with mean differences of -0.04% (95% confidential interval (CI) -0.22 to 0.15) and -0.08% (95% CI -0.27 to 0.10), respectively. Compared with sitagliptin, greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar. Overall adverse event rates were similar between the groups. A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported. The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions, thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.

Current status of metformin in addition to insulin therapy in adult patients with type 1 diabetes mellitus: An analysis from the Guangdong Type 1 Diabetes Mellitus Translational Medicine Study.

BACKGROUND: Limited data on the efficacy of the additional metformin therapy in patients with type 1 diabetes mellitus (T1DM) under real-life conditions have been available so far. METHODS: Patients aged ≥18 years with a duration of T1DM for at least 1 year were included in this multicenter observational study. Patients with insulin combined with metformin therapy (MET group) were compared with those with insulin therapy only (INS group). RESULTS: A total of 76 patients in the MET group were compared with 655 patients in the INS group. At baseline, patients with dyslipidemia were more prevalent in the MET group (17.6% vs 9.0%; P = .006), and they also had a higher body mass index (BMI) (21.7 ± 3.2 kg/m2 vs 20.4 ± 2.6 kg/m2 ; P < .001) than those in the INS group. But glycosylated hemoglobin (HbA1c) and daily insulin dose were not significantly different between the two groups. After 1-year follow-up, HbA1c decreased in both groups, while the daily insulin dose decreased in the MET group, but did not change in the INS group (-0.02 IU/kg [-0.16, 0.09] vs 0 IU/kg [-0.09, 0.09]; P = .029). The additional metformin therapy led to no change of BMI and weight in the MET group, while the body weight increased from 53.7 ± 8.6 kg to 55.0 ± 7.9 kg in the INS group (P < .001). CONCLUSIONS: Metformin is initiated more in T1DM patients with dyslipidemia or higher BMI in current practice in China. The addition of metformin is effective in maintaining weight and reducing the insulin dosage without improving glycemic control in patients with T1DM.

Demographic and clinical characteristics of patients with type 1 diabetes mellitus: A multicenter registry study in Guangdong, China.

BACKGROUND: A lack of demographic and clinical data hinders efforts of health care providers in China to support patients with type 1 diabetes mellitus (T1D). Therefore, the aim of the present retrospective study was to provide an overview of the demographic and clinical characteristics of Chinese patients with T1D. METHODS: Hospital medical records of patients with T1D (diagnosed between January 2000 and December 2011) in 105 secondary and tertiary hospitals across Guangdong province were reviewed. Data were collected on patient age at diagnosis, presentations at onset, physical examination, and diabetes management. RESULTS: In all, 3173 patients diagnosed with T1D between January 2000 and December 2011 were included in the study (46.2% female). The median age at diagnosis was 27.5 years (interquartile range [IQR] 18.0-38.0) years and the median body mass index (BMI) at onset was 19.6 kg/m2 (IQR 17.4-21.8 kg/m2 ). Among adult patients, 0.9% were obese, 6.6% were overweight, 62.3% were normal weight, and 30.3 % were underweight. The prevalence of diabetic ketoacidosis (DKA) at onset was 50.1%. The proportion of patients with retinopathy, nephropathy, and neuropathy was 8.1%, 20.7 %, and 11.1%, respectively. CONCLUSION: The adult-onset form of T1D is not rare in China. The registry participants were characterized by older age at onset, lower BMI, and a higher prevalence of DKA at onset compared with those in regions with a high incidence of T1D, such as northern Europe. These findings contribute to a better understanding of the heterogeneity of T1D in different populations and so will help healthcare providers to develop management models that are more suitable for these patients.

Glycaemic control and its associated factors in Chinese adults with type 1 diabetes mellitus.

BACKGROUND: Glycaemic control is a great challenge in the management of type 1 diabetes mellitus (T1DM). There is limited data concerning glycaemic control among adults with T1DM. We used data from the Guangdong T1DM Translational Medicine Study to evaluate glycaemic control and its associated factors in Chinese adults with T1DM. METHODS: This cross-sectional analysis included 827 participants who were 18 years of age or older and had been living with T1DM for at least 1 year. Participants with HbA1c levels <7% were compared against those with HbA1c levels ≥ 7%. A multivariate logistic regression model was used to examine factors associated with glycaemic control. RESULTS: Among the 827 participants, the mean age was 34.2 ± 12.1 years and the median (interquartile range) duration of diabetes was 6.1 (3.4, 10.4) years. The median HbA1c level was 8.5% (7.5%, 10.2%). Only one-fifth of participants had HbA1c levels <7%. Insufficient glycaemic control (HbA1c ≥ 7%) was strongly associated with infrequent self-monitoring of blood glucose (OR = 1.21, 95% CI 1.14 ~ 1.29, p = 0.000), high insulin dose (OR = 1.27, 95% CI 1.07 ~ 1.52, p = 0.006), smoking (OR = 3.11, 95% CI 1.44 ~ 6.72, p = 0.004), low-frequency clinical visits (OR = 2.74, 95% CI 1.47 ~ 5.10, p = 0.001), the presence of diabetic autoantibodies (OR = 1.63, 95% CI 1.07 ~ 2.48, p = 0.022) and low fasting C-peptide (FCP) levels (OR = 1.21, 95% CI 1.01 ~ 1.46, p = 0.049) after adjustment for age at disease onset, education level, household income and diet control. CONCLUSIONS: Most adult patients with T1DM did not achieve the HbA1c target. Identifying determinants for glycaemic control provides us valuable information to improve glycaemic control in these patients. Copyright © 2015 John Wiley & Sons, Ltd.

The performance of a diabetic retinopathy risk score for screening for diabetic retinopathy in Chinese overweight/obese patients with type 2 diabetes mellitus.

INTRODUCTION: Diabetic retinopathy (DR) is a common chronic microvascular diabetic complication. The presence of DR may indicate microcirculatory dysfunction in other organ systems besides visual morbidity. The objective of this study was to develop a simple diabetic retinopathy risk score to identify DR in Chinese overweight/obese patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: A multicentre hospital-based cross-sectional study was carried out in Guangdong Province between August 2011 and March 2012. The evaluated 2699 patients included 1263 males and 1436 females, with an average age of 59.4 ± 13.0 years. RESULTS: The diabetic retinopathy risk score was conducted by age, duration of DM, history of antihypertensive drug treatment, and waist circumference. The area under the receiver operating characteristics curve for DR was 0.700 (95% CI 0.671-0.729). Comparing Youden's index of different values, the optimal cut-off point was 20 to predict DR. The odds ratio for one unit increase in the diabetic retinopathy risk score associated with the risk of DR was 1.104 (95% CI 1.089-1.120). CONCLUSIONS: Our data suggest that the diabetic retinopathy risk score could be a reliable primary screening tool for the presence of DR in Chinese overweight/obese patients with T2DM.

Cardiometabolic risk profiles associated with chronic complications in overweight and obese type 2 diabetes patients in South China.

BACKGROUND: Type 2 diabetes is often accompanied by altered cardiometabolic risk profiles, including abdominal obesity, hypertension, and dyslipidaemia. The association of altered cardiometabolic risk profiles with chronic complications of diabetes is not well investigated. METHODS: We recruited 2954 type 2 diabetes patients with a body mass index ≥25 kg/m2 who visited the diabetes clinics of 62 hospitals in 21 cities in Guangdong province of China from August 2011 to March 2012. Demographic characteristics, personal and family medical histories, and data on chronic complications of diabetes were collected. Clinical examinations and laboratory assessment were conducted. RESULTS: Abdominal obesity was found in 91.6% of the study population, elevated blood pressure in 78.3%; elevated serum triacylglycerols in 57.8%, and reduced serum HDL-C in 55.9%. Among the cardiometabolic risk factors, elevated blood pressure was significantly associated with almost all the chronic complications of diabetes. After adjusting for age, gender, duration of diabetes, and HbA1c, elevated blood pressure was significantly associated with diabetic retinopathy (OR 1.63, 95% CI: 1.22-2.19), diabetic nephropathy (OR 3.16, 95% CI: 2.25-4.46), cardiovascular disease (OR 2.71, 95% CI: 1.70-4.32), and stroke (OR 1.90, 95% CI: 1.15-3.12). Abdominal adiposity was significantly associated with diabetic nephropathy (OR 1.39, 95% CI: 1.11-1.74). Elevated triacylglycerols was significantly associated with diabetic retinopathy (OR 1.29, 95% CI: 1.05-1.58) and diabetic nephropathy (OR 1.30, 95% CI: 1.05-1.58). Reduced HDL-C was significantly associated with stroke (OR 1.41, 95% CI: 1.05-1.88). CONCLUSIONS: Altered cardiometabolic risk profiles, and elevated blood pressure in particular, were significantly associated with chronic complications in overweight and obese patients with type 2 diabetes. Future studies on the prevention of chronic complications of diabetes might make lowering blood pressure a primary target.

[Prevalence and risk factors for dyslipidemia in diabetics with overweight or obesity].

OBJECTIVE: To explore the prevalence and risk factors for dyslipidemia in diabetics with overweight or obesity. METHODS: Diabetics with overweight or obesity were recruited from 62 tertiary and secondary hospitals in Guangdong Province between August 2011 and March 2012. Dyslipidemia was diagnosed as total cholesterol (TC) ≥ 5.7 mmol/L or triglycerides (TG) ≥ 1.7 mmol/L or low-density-lipoprotein cholesterol (LDL-C) ≥ 3.6 mmol/L or high-density-lipoprotein cholesterol (HDL-C) < 1.29 mmol/L in females or HDL-C < 1.03 mmol/L in males. Binary Logistic regression was used to assess the associations between dyslipidemia and associated risk factors. RESULTS: Dyslipidemia was detected in 3160/3593 (87.9%) diabetics with overweight or obesity. And the prevalence of hypertriglyceridemia, low blood HDL-C, hypercholesterolemia and high blood LDL-C was 52.5% (1888/3593) , 54.1% (1945/3593), 33.1% (1188/3593) and 27.4% (985/3593) respectively. Among those with dyslipidemia, patients with simple and mixed dyslipidemia accounted for 34.1% and 53.9% respectively. In binary Logistic regression analysis, the presence of dyslipidemia were associated with female gender (OR = 1.593, 95%CI 1.233-2.057), hemoglobinA1c(HbA1c) (OR = 1.120, 95%CI 1.054-1.191), body mass index (OR = 1.084, 95%CI 1.022-1.150), hypertension (OR = 1.331, 95%CI 1.033-1.714), history of diabetes (OR = 1.586, 95%CI 1.186-2.120) and hyperuricacidemia (OR = 2.270, 95%CI 1.642-3.138). CONCLUSIONS: The prevalence of dyslipidemia is quite high in diabetics with overweight or obesity. The controls of blood pressure, serum uric acid level, blood glucose and body weight may reduce the prevalence of dyslipidemia, prevent and delay the development of cardiovascular complications and reduce the mortality of diabetics with overweight or obesity.

Prevalence and determinants of hyperuricemia in type 2 diabetes mellitus patients with central obesity in Guangdong Province in China.

This study investigated the prevalence and determinants of hyperuricemia in Chinese type 2 diabetes mellitus (T2DM) patients with central obesity. A multicentric hospital-based cross-sectional study was carried out in Guangdong Province between August 2011 and March 2012. At each hospital, Chinese T2DM patients with central obesity who were aged over 20 years, whose serum uric acid levels were measured, and who had lived in Guangdong Province for >=1 year, were recruited. Hyperuricemia was defined as serum uric acid >420 µmol/L in men and >360 µmol/L in women. Binary logistic regression was used to assess associated risk factors for hyperu-ricemia. A total of 2,917 T2DM patients with central obesity took part. The overall prevalence of hyperuricemia was 32.6% (36.1% for women, 28.4% for men). Binary logistic regression analyses demonstrated that women (OR: 1.576; 95% confidence interval (CI): 1.231, 2.018), high BMI (OR: 1.228; 95% CI: 1.094, 1.379), waist cir-cumference (OR: 1.135; 95% CI: 1.009, 1.276), hypertension (OR: 1.603; 95% CI: 1.263, 2.035), high total cho-lesterol (OR: 1.133; 95% CI: 1.002, 1.281), triglycerides (OR: 1.134; 95% CI: 1.069, 1.203), low HDL-cholesterol (OR: 0.820; 95% CI: 0.677, 0.995) and low estimated glomerular filtration rate (OR: 0.840; 95% CI: 0.815, 0.866) were risk factors associated with hyperuricemia. Hyperuricemia is prevalent in Chinese T2DM patients with central obesity and is significantly positively associated with women, cardiovascular risk factors such as obesity, hypertension and dyslipidemia, and low eGFR.

[A cross-sectional survey of blood pressure control in overweight or obese type 2 diabetic patients in Guangdong province].

OBJECTIVE: To investigate the current situation and influential factors of blood pressure (BP) control in type 2 diabetic patients with overweight or obesity in Guangdong province. METHODS: From August 2011 to March 2012, type 2 diabetic patients with overweight or obesity were recruited from 60 hospitals in 20 cities of Guangdong province, and received standard questionnaires. The conditions of demographic data, clinical examinations, the most recent laboratory assessment, history of disease and drug therapy were recorded. RESULTS: A total of 4029 patients were collected with age of (58.9 ± 12.9) years, and body mass index (BMI) of (27.28 ± 2.76) kg/m². Among the participants, controlled BP was achieved in 23.8% patients. Multiple logistic regression analysis showed that older age, obesity, previous history of hypertension and inadequate glycemic control were the independent factors related to unsatisfactory blood pressure control rate. Among the patients with hypertension, 53.5% took 1 kind of antihypertensive drug, 32.5% took two, and 11.3% took three or more. CONCLUSIONS: Type 2 diabetic patients with overweight or obesity in Guangdong province have poor BP control. Thus, active lifestyle interventions and drug therapy as a comprehensive management way should be taken for the population so as to reduce their cardiovascular events.

[A cross-sectional survey on current status of type 2 diabetes mellitus with overweight or obesity in Guangdong province].

OBJECTIVE: To explore the glycemic control status and related risk factors of overweight or obesity patients with type 2 diabetes mellitus (T2DM) in Guangdong province. METHODS: The medical records of overweight or obesity patients with T2DM from 60 tertiary and secondary hospitals in Guangdong Province were collected by questionnaire and physical examination. And the clinical data were analyzed to explore the influencing factors of glycemic control. The HbA1c level was used to assess glycemic control. HbA1c < 7.0% indicated that glycemic control was up to standard. RESULTS: From August 2011 to March 2012, 5241 T2DM patients were recruited. The scope of current analysis was restricted to 4768 subjects with true data and deficiency no more than 5%. There were 2252 males and 2516 females. The age range was from 16 to 90 years, a median age 59.0 (50.0 - 69.0) years, onset age of diabetes 52.0 (44.0 - 60.0) years; a range of disease duration from 1 day to 42 years and a median of 5.0 (2.0 - 11.0) years. The median body mass index was 26.33(24.88 - 28.34) kg/m(2) and median waist circumference 93.0 (88.0 - 100.0) cm. Median HbA1c was 8.1% (6.9% - 10.1%) and only 26.2% patients reached the target level of HbA1c < 7.0%. Influencing factors of poor glycemic control were central obesity, high levels of resting heart rate, concurrent fatty liver and high intensity of treatment. And influencing factors of good glycemic control were regular exercises, smoking cessation, regular glycemic monitoring and good control of total cholesterol/triglyceride. CONCLUSION: A majority of Guangdong type 2 diabetics fail to achieve target values for glycemic control. There is an urgent need for comprehensive management for improving glycemic control.

Apelin-APJ induces ICAM-1, VCAM-1 and MCP-1 expression via NF-κB/JNK signal pathway in human umbilical vein endothelial cells.

Apelin receptor (APJ) deficiency has been reported to be preventive against atherosclerosis. However, the mechanism of this effect remains unknown. In this study, quantitative real-time RT-PCR, Western blotting and ELISA analyses revealed a significant increase in the expression of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) treated with apelin. Inhibitors of cellular signal transduction molecules were used to demonstrate involvement of nuclear factor kappa-B (NF-κB) and c-Jun N-terminal kinase (JNK) pathways in apelin-APJ-induced activation of adhesion molecules and chemokines. Inhibition of APJ expression by RNA interference abrogated apelin-induced expression of adhesion molecules and chemokines and apelin-stimulated cellular signal transduction in HUVECs. The apelin-APJ system in endothelial cells is involved in the expression of adhesion molecules and chemokines, which are important for the initiation of endothelial inflammation-related atherosclerosis. Therefore, apelin-APJ and the cell signaling pathways activated by this system in endothelial cells may represent targets for therapy of atherosclerosis.

[Cross-sectional study of current situation of glycemic control with type 1 diabetes in Guangdong Province].

OBJECTIVE: To investigate the glycemic control and the related factors of type 1 diabetic patients in Guangdong Province. METHODS: Medical records and blood samples of type 1 diabetic patients were collected in 89 tertiary and secondary hospitals from all of the 21 cities in Guangdong Province. The clinical data were analyzed to explore the correlates of glycemic control. HbA1c levels, measured in Guangdong Diabetes Center, were used to assess glycemic control. RESULTS: 851 patients were enrolled from August 6, 2010 to May 25, 2011. There were 408 males and 443 females. The median (interquartile range) age was 29.6 years (20.3 - 41.3 years). The onset age of diabetes was 25.3 years (15.7 - 35.5 years). The disease duration was 3.3 years (1.0 - 7.3 years). The BMI was 19.9 kg/m(2) (17.9 - 21.8 kg/m(2)). HbA1c levels were 8.6% (6.9% - 11.0%) and only 234 (27.50%) patients reached the age-specific target levels. Correlates with poorer glycemic control were 13 - 19 years old (vs 7 - 12 and ≥ 20 years old), lower household income, not on dietary intervention, never accepting diabetic education and shorter diabetic duration. CONCLUSION: The majority of Guangdong type 1 diabetic patients did not achieve target values for glycemic control, indicating an urgent need for comprehensive management to improve glycemic control.