Association of Apolipoprotein E Polymorphisms and Risks of Ischemic Stroke in Chinese Patients with Type 2 Diabetes Mellitus.

BACKGROUND: The apolipoprotein E (APOE) gene polymorphisms have been intensively studied in patients with type 2 diabetes mellitus (T2DM) and ischemic stroke (IS) in recent years. However, it is unclear whether APOE gene polymorphisms are correlated with increased risk for developing IS in T2DM patients. Thus, this study was designed to examine the association between APOE gene polymorphisms and risks of IS in Chinese patients with T2DM. METHODS: This case-control study enrolled 243 subjects with T2DM as controls, and 210 subjects with T2DM complicated with IS as case patients. The genotypes were determined using real-time PCR while HbA1c and lipid levels were detected using commercially available kits. RESULTS: The systolic blood pressure (SBP), diastolic blood pressure (DBP), and the proportion of patients with a history of hypertension were higher in the case patients than that in the controls. We confirmed that the ε2/ε3 genotype, as well as SBP and history of hypertension, was the independent risk factor for developing IS in T2DM patients. CONCLUSIONS: We conclude that the ε2/ε3 genotype might contribute to the increased risk for developing IS in Chinese patients with T2DM.

A rare missense variant in the milk fat globule-EGF factor 8 (MFGE8) increases T2DM susceptibility and cardiovascular disease risk with population-specific effects.

AIMS: The milk fat globule-epidermal growth factor 8 (MFGE8), also called lactadherin, is an integrin ligand and a known mediator of inflammation and atherosclerosis in T2DM in studies using animal models. However, its role in the pathophysiology of human T2DM, obesity, and cardiovascular disease has been poorly explored. Aim of this study  was to investigate the role of a missense variant (rs371227978 C/T: Arg148His) in the MFGE8 gene identified through exome sequencing for its association with T2DM and cardiometabolic traits. METHODS: Exome-wide sequencing was performed using DNA samples from 68 Sikh individuals from multi-generation pedigrees affected with diabetes on Illumina's GAIIx using "SureSelect Human All Exon" panels. We further replicated this variant by de novo genotyping in a total of 4242 individuals of the Asian Indian Diabetic Heart Study/Sikh Diabetes Study using custom TaqMan genotyping assay. We also measured circulating concentrations of Mfge8 using frozen serum aliquots by enzyme-linked immunosorbent assay. RESULTS: Overall, only 1.78% of 4242 individuals were carriers of this variant with MAF being 0.009. Except for the significant correlation of this variant with T2DM and triglycerides, no other quantitative risk phenotype was significant. The minor per allele-associated increased risk for T2DM showed odds ratio of 1.95 (95% CI 1.18-3.23; p = 0.008) in unadjusted model and was 1.73 (95% CI 1.02-2.93; p = 0.043) after adjusting for the age, gender, and BMI. However, there was a strong correlation between serum Mfge8 concentrations with T2DM, (r2 = 0.38; p = 0.001), fasting glucose (r2= 0.36; p = 0.002), and triglycerides (r2 = 0.33; p = 0.005). Our data revealed a significant dose-related increase in MFGE8 genotypes for affecting serum Mfge8 (p = 2.1 × 10-3) and triglyceride concentrations (p = 3.2 × 10-3). For a per risk allele-associated increase of 4.74 ng/ml ± SD of 1.62 ng/ml of the Mfge8 concentration was found to increase T2DM risk to 1.7 fold (95% CI from 1 to 3 fold). CONCLUSIONS: Here, we report for the first time a novel population-specific rare variant in the MFGE8 gene linked with the increased Mfge8 concentrations and the risk for developing T2DM and cardiovascular risk factors in a population of Punjabi Sikhs from India. In view of a strong evidence from animal studies supporting the role of Mfge8 in obesity, insulin resistance, and the development of atherosclerosis in T2DM, our findings are important and timely. If validated in a large independent dataset, early screening of Mfge8 in blood levels may especially benefit those patients with genetically elevated Mfge8 levels to preventing or reducing the risk of T2DM and cardiovascular disease.

Association of Urine Haptoglobin With Risk of All-Cause and Cause-Specific Mortality in Individuals With Type 2 Diabetes: A Transethnic Collaborative Work.

OBJECTIVE: Haptoglobin is an acute-phase reactant with pleiotropic functions. We aimed to study whether urine haptoglobin may predict risk of mortality in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: We employed a transethnic approach with a cohort of Asian origin (Singapore) (N = 2,061) and a cohort of European origin (France) (N = 1,438) included in the study. We used survival analyses to study the association of urine haptoglobin with risk of all-cause and cause-specific mortality. RESULTS: A total of 365 and 525 deaths were registered in the Singapore cohort (median follow-up 7.5 years [interquartile range 3.5-12.8]) and French SURDIAGENE cohort (median follow-up 6.8 years [interquartile range 4.3-10.5], respectively. Singapore participants with urine haptoglobin in quartiles 2 to 4 had higher risk for all-cause mortality compared with quartile 1 (unadjusted hazard ratio [HR] 1.47 [95% CI 1.02-2.11], 2.28 [1.62-3.21], and 4.64 [3.39-6.35], respectively). The association remained significant in quartile 4 after multiple adjustments (1.68 [1.15-2.45]). Similarly, participants in the French cohort with haptoglobin in quartile 4 had significantly higher hazards for all-cause mortality compared with quartile 1 (unadjusted HR 2.67 [2.09-3.42] and adjusted HR 1.49 [1.14-1.96]). In both cohorts, participants in quartile 4 had a higher risk of mortality attributable to cardiovascular disease and infection but not malignant tumor. CONCLUSIONS: Urine haptoglobin predicts risk of mortality independent of traditional risk factors, suggesting that it may potentially be a novel biomarker for risk of mortality in patients with type 2 diabetes.

Ellisras Longitudinal Study 2017: elevated serum levels of carboxymethyl-lysine, an advanced glycation end-product, are associated with higher odds of developing endothelial dysfunction in black South African patients with type 2 diabetes mellitus (ELS 29).

This case-control study investigated the association between major types of serum advanced glycation end-products (AGEs) and selected serum/plasma markers of endothelial dysfunction in black patients with type 2 diabetes mellitus at Dr George Mukhari Academic Hospital. Serum AGEs were measured using either enzyme-linked immunosorbent assay (ELISA) or spectrofluoremetry. Serum markers of endothelial dysfunction were measured using either ELISA or calometry. The correlation and associations between major types of serum AGEs and markers of endothelial dysfunction were investigated using the Spearman correlation coefficient and bivariate logistic regression analysis, respectively. Although both serum total immunogenic AGEs and serum carboxymethyl-lysine (CML) were moderately and negatively associated with endothelial dysfunction, only serum CML was significantly associated with a higher odds for the development of endothelial dysfunction (low nitric oxide levels) in our diabetic subjects. It can therefore be concluded from this study that high serum levels of CML may predispose to endothelial dysfunction in black South Africans with type 2 diabetes.

miR-3188 (rs7247237-C>T) Single-Nucleotide Polymorphism Is Associated With the Incidence of Vascular Complications in Chinese Patients With Type 2 Diabetes.

miR-3188, one of the earliest discovered microRNAs, is involved in regulating the mTOR-p-PI3K/AKT pathway, thus affecting the progression of diabetic complications. In this study, we observed that the miR-3188 (rs7247237-C>T) polymorphism not only affected the production of nitric oxide (NO) production in endothelial cells, but also significantly associated with the incidence of vascular complications in Chinese patients with type 2 diabetes. Mechanistic analyses indicate that miR-3188 (rs7247237-T) polymorphism inhibited its own expression and upregulated the expression of gstm1 and trib3, which impairs NO production in human endothelial cells through inactivating AKT/eNOS signal transduction pathway. In addition, our clinical retrospective study indicated that, compared with patients with the CC genotype (n = 351), patients with rs7247237 TT + CT genotypes (n = 580) exhibited an increased risk of major vascular events during intensive glucose control treatment (hazard ratio = 1.560; 95% CI: 1.055-2.307, P = 0.025). Simultaneously, the risk of major vascular events was marginally decreased in patients with the CC genotype during intensive glucose control treatment compared with standard treatment (hazard ratio = 0.666; 95% CI: 0.433-1.016, P = 0.053). Our findings indicate that the miR-3188 (rs7247237-C>T) polymorphism is associated with the incidence of vascular complications in Chinese patients with type 2 diabetes, likely due to its remarkable effect on miR-3188 expression.

Association of C2, a derivative of the radial artery pressure waveform, with new onset of type 2 diabetes mellitus: the MESA study.

BACKGROUND: Although microvascular dysfunction is known to result from diabetes, it might also lead to diabetes. Lower values of C2, a derivative of the radial artery pressure waveform, indicate microvascular dysfunction and predict hypertension and cardiovascular disease (CVD). We studied the association of C2 with incident diabetes in subjects free of overt CVD. METHODS: Among multi-ethnic participants (n = 5214), aged 45-84 years with no diabetes, C2 was derived from the radial artery pressure waveform. Incident diabetes (N = 651) was diagnosed as new fasting glucose ≥ 126 mg/dL or antidiabetic medicine over ~ 10 years. The relative incidence density (RID) for incident diabetes per standard deviation (SD) of C2 was studied during ~ 10 years follow-up using four levels of adjustment. RESULTS: Mean C2 at baseline was 4.58 ± 2.85 mL/mmHg × 100. The RID for incident diabetes per SD of C2 was 0.90 (95% CI 0.82-0.99, P = 0.03). After adjustment for demographics plus body size, the corresponding RID was 0.81 (95% CI 0.73-0.89, P < 0.0001); body mass index (BMI) was the dominant covariate here. After adjustment for demographics plus cardiovascular risk factors, the RID was 0.98 (95% CI 0.89, 1.07, P = 0.63). After adjustment for all the parameters in the previous models, the RID was 0.87 (95% CI 0.78, 0.96, P = 0.006). CONCLUSIONS: In a multi-ethnic sample free of overt CVD and diabetes at baseline, C2 predicted incident diabetes after adjustment for demographics, BMI and CVD risk factors. Differences in arterial blood pressure wave morphology may indicate a long-term risk trajectory for diabetes, independently of body size and the classical risk factors.

Ethnicity-specific association of BMI levels at diagnosis of type 2 diabetes with cardiovascular disease and all-cause mortality risk.

AIM: To evaluate the risk of CVD and all-cause mortality at different BMI levels in conjunction with weight change prior to diagnosis of T2DM in a multi-ethnic population. METHODS: Longitudinal study of 51,455 patients with T2DM and without a history of comorbid diseases at diagnosis. Weight changes prior to diagnosis of T2DM were evaluated, and the risk of CVD and all-cause mortality at different BMI levels among three ethnic groups estimated using treatment effects model. RESULTS: White Europeans (WE), African-Caribbeans (AC), and South Asians (SA) were mean 52, 49, and 47 years with a mean BMI of 33.0, 32.0, and 30.0 kg/m2 at diagnosis, respectively. Among WE, normal weight patients developed CVD significantly earlier by 0.5 years (95% CI 0.1, 0.9 years; p = 0.018) compared to obese patients. Furthermore, those with normal body weight at diagnosis were significantly more likely to die earlier by 0.6 years (95% CI 0.03, 1.2 years; p = 0.037) among WE and by 2.5 years (95% CI 0.3, 4.6 years; p = 0.023) among SA compared to their respective obese patients. However, BMI at diagnosis was not associated with increased risk of CVD and death among AC. CONCLUSIONS: This study suggests a paradoxical association of BMI with cardiovascular and mortality risks in different ethnic groups, which may partially be driven by different cardiovascular and glycaemic risk profiles at diagnosis.

Association of the genetic variant rs2000999 with haptoglobin and diabetic macrovascular diseases in Chinese patients with type 2 diabetes.

AIMS: The common copy number variant (CNV) in the haptoglobin (Hp) gene may influence the susceptibility to diabetic macrovascular diseases. We aimed to investigate the relationship of the genetic variant rs2000999, located in the haptoglobin-related protein (HPR) gene, with serum Hp levels and diabetic macrovascular diseases in Chinese type 2 diabetes patients. METHODS: The Hp CNV and rs2000999 were genotyped in a group of 5457 Chinese patients with type 2 diabetes. Associations of rs2000999 with the common Hp CNV, susceptibility to diabetic macrovascular diseases and related metabolic traits were analysed. Furthermore, 886 patients were selected to detect serum Hp levels and to evaluate the correlation between rs2000999 and serum Hp levels. RESULTS: The genetic variant rs2000999 was not associated with diabetic macrovascular diseases (P = 0.6109), while subjects carrying the A allele had higher levels of low-density lipoprotein cholesterol (P = 0.0578) and a smaller inter-adventitial diameter of the common carotid artery (P = 0.0266). Additionally, rs2000999 exhibited strong association with serum Hp levels (P = 2.03 × 10-21). CONCLUSIONS: The genetic variant rs2000999 was not associated with diabetic macrovascular diseases but showed an association with metabolic traits and serum Hp levels in Chinese patients with type 2 diabetes.

Relationship of Hyperglycaemia, Hypoglycaemia, and Glucose Variability to Atherosclerotic Disease in Type 2 Diabetes.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is known to be associated with increased cardiovascular risk. The aim of this study was therefore to investigate the independent effects of hyperglycaemia, hypoglycaemia, and glucose variability on microvascular and macrovascular disease in T2DM. METHODS: Subjects with T2DM of <10 years duration and on stable antiglycaemic treatment underwent carotid intima-media thickness (CIMT), ankle-brachial index (ABI), albumin-creatinine ratio (ACR), and HbA1c measurement, as well as 72-hour continuous glucose monitoring. Macrovascular disease was defined as one or more of the following: history of ischaemic heart disease (IHD), cerebrovascular accident (CVA), ABI < 0.9, or abnormal CIMT. RESULTS: The study population comprised 121 subjects with T2DM (89 males : 32 females). The mean age was 62.6 years, and the mean DM duration was 3.7 years. Macrovascular disease was present in 71 patients (58.7%). In multivariate logistic regression analysis, body surface area (BSA) (OR 18.88 (95% CI 2.20-156.69), p = 0.006) and duration of blood glucose (BG) < 3.9 mmol/L (OR 1.12 (95% CI 1.014-1.228), p = 0.024) were independent predictors of macrovascular disease. BSA (OR 12.6 (95% CI 1.70-93.54), p = 0.013) and duration of BG < 3.9 mmol/L (OR 1.09 (95% CI 1.003-1.187), p = 0.041) were independent predictors of abnormal CIMT. Area under the curve for BG > 7.8 mmol/L (ß = 15.83, p = 0.005) was the sole independent predictor of albuminuria in generalised linear regression. CONCLUSIONS: This study demonstrates that hypoglycaemia is associated with the occurrence of atherosclerotic disease while hyperglycaemia is associated with microvascular disease in a Caucasian population with T2DM of recent duration.

The association between paraoxonase 1 activity and the susceptibilities of diabetes mellitus, diabetic macroangiopathy and diabetic microangiopathy.

We carried out this meta-analysis to explore the influence of paraoxonase 1 activity on the susceptibility of diabetes mellitus (DM), diabetic macroangiopathy and diabetic microangiopathy. Relevant studies were identified from PubMed, Web of Science and CNKI without language limitation, following the inclusion and exclusion criteria. Statistical analyses were implemented with the STATA 12.0 statistical software. Thirty-six case-control studies were included in the meta-analyses, in which 35 for the association between paraoxonase 1 activity and DM risk, 8 for diabetic macroangiopathy and 7 for diabetic microangiopathy. Paraoxonase 1 activity was significantly associated with the susceptibility of DM in pooled population (SMD = -1.37, 95% CI = -1.79 ∼ -0.96, P = .000), and Asians (SMD = -2.00, 95% CI = -2.56 ∼ -1.44, P = .000), but not in non-Asians (SMD = -0.44, 95% CI = -0.91 ∼ 0.03, P = .069). However, marked heterogeneity was existed (I2  = 98.10%, P = .000) and subgroup analyses failed to investigate the sources of heterogeneity. Then, meta-regression was performed and found that ethnicity could explain the observed between-study heterogeneity (P = .002). Meanwhile, significant associations were found between paraoxonase 1 activity and diabetic macroangiopathy (SMD = -1.06, 95% CI = -1.63 ∼ -0.48, P = .000) and diabetic microangiopathy (SMD = -0.72, 95% CI = -1.32 ∼ -0.13, P = .018). In conclusion, paraoxonase 1 activity plays important roles in the risk of DM, diabetic macroangiopathy and microangiopathy with ethnicity differences. Further studies with large sample and well design are needed to confirm these results.

High Diabetes Distress Among Ethnic Minorities Is Not Explained by Metabolic, Cardiovascular, or Lifestyle Factors: Findings From the Dutch Diabetes Pearl Cohort.

OBJECTIVE: Diabetes distress among patients from ethnic minorities is still poorly understood. We investigated the association between ethnicity and diabetes distress among ethnic minority groups of people with type 2 diabetes in the Netherlands, focusing on the possible effects of glycemic control, lifestyle factors, cardiovascular risk factors, and diabetes complications. RESEARCH DESIGN AND METHODS: Cross-sectional data from the Dutch Diabetes Pearl cohort included people with type 2 diabetes from primary, secondary, and tertiary diabetes care programs. We used the 20-item Problem Areas in Diabetes Survey (PAID) scale to assess diabetes distress; a score ≥40 is considered to represent high distress. Ethnicity was estimated on the basis of country of birth. Sociodemographic and lifestyle data were self-reported; cardiovascular and metabolic data were retrieved from medical charts. Logistic regression analysis determined the association between ethnicity and diabetes distress, with Caucasians as the reference group. RESULTS: Diabetes distress scores and ethnicity were available for 4,191 people with type 2 diabetes: 3,684 were Caucasian, 83 were Asian, 51 were Moroccan, 92 were African, 134 were Latin American, 46 were Turkish, and 101 were Hindustani-Surinamese. Overall, participants in minority groups had worse health outcomes than those of Caucasian descent, and diabetes distress was more prevalent (ranging from 9.6 to 31.7%, compared with 5.8% among Caucasians), even after adjusting for age, sex, education level, alcohol use, smoking, BMI, lipid profile, HbA1c, medication use, and the presence of diabetes complications. CONCLUSIONS: Among people with type 2 diabetes in the Netherlands, ethnicity is independently associated with high diabetes distress. Further research is warranted to explain the higher prevalence of diabetes distress in minority groups and to develop effective interventions.

Haemoglobin A1c variability as an independent correlate of atherosclerosis and cardiovascular disease in Chinese type 2 diabetes.

OBJECTIVE: To examine the association between haemoglobin A1c variability and macrovascular complication in type 2 diabetes. METHODS: We retrospectively enrolled 5278 diabetes patients with no history of cardiovascular disease and atherosclerosis by ultrasound at their first visit to the hospital from 1999 to 2010. Patients had a median of 4 haemoglobin A1c (range = 3-9) measurements during follow-up. Average haemoglobin A1c and haemoglobin A1c variability were calculated as intra-individual mean, standard deviation, coefficient of variation and adjusted standard deviation. Cardiovascular disease events and ultrasound results were re-evaluated from the medical history at the end of the study. RESULTS: A total of 972 patients had macrovascular complication. Compared to those without atherosclerosis/cardiovascular disease (n = 4306), haemoglobin A1c intra-individual mean and haemoglobin A1c variability levels were significantly higher in patients with macrovascular complication ( p < 0.001). Multivariable logistic regression analysis showed that haemoglobin A1c variability was associated with macrovascular complication. Moreover, 488 patients with only atherosclerosis had significantly higher haemoglobin A1c intra-individual mean and haemoglobin A1c variability values than those without atherosclerosis/cardiovascular disease ( p < 0.001), but in 484 patients with cardiovascular disease incidents, only higher haemoglobin A1c intra-individual mean level was found ( p = 0.004). CONCLUSIONS: In Chinese type 2 diabetes, haemoglobin A1c variability was associated with macrovascular complication. Long-term stabilization of glucose is important in diabetes management, especially in the early stage of atherosclerosis.

Racial/ethnic disparities among Asian Americans in inpatient acute myocardial infarction mortality in the United States.

BACKGROUND: Acute myocardial infarction (AMI) is a common high-risk disease with inpatient mortality of 5% nationally. But little is known about this outcome among Asian Americans (Asians), a fast growing racial/ethnic minority in the country. The objectives of the study are to obtain near-national estimates of differences in AMI inpatient mortality between minorities (including Asians) and non-Hispanic Whites and identify comorbidities and sociodemographic characteristics associated with these differences. METHOD: This is a retrospective analysis of 2010-2011 state inpatient discharge data from 10 states with the largest share of Asian population. We identified hospitalization with a primary diagnosis of AMI using the ICD-9 code and used self-reported race/ethnicity to identify White, Black, Hispanic, and Asian. We performed descriptive analysis of sociodemographic characteristics, medical comorbidities, type of AMI, and receipt of cardiac procedures. Next, we examined overall inpatient AMI mortality rate based on patients' race/ethnicity. We also examined the types of AMI and a receipt of invasive cardiac procedures by race/ethnicity. Lastly, we used sequential multivariate logistic regression models to study inpatient mortality for each minority group compared to Whites, adjusting for covariates. RESULTS: Over 70% of the national Asian population resides in the 10 states. There were 496,472 hospitalizations with a primary diagnosis of AMI; 75% of all cases were Whites, 10% were Blacks, 12% were Hispanics, and 3% were Asians. Asians had a higher prevalence of cardiac comorbidities, including hypertension, diabetes, and kidney failure compared to Whites (p-value< 0.01). There were 158,623 STEMI (ST-elevation AMI), and the proportion of hospitalizations for STEMI was the highest for Asians (35.2% for Asians, 32.7% for Whites, 25.3% for Blacks, and 32.1% for Hispanics). Asians had the highest rates of inpatient AMI mortality: 7.2% for Asians, 6.3% for Whites, 5.4% for Blacks, and 5.9% for Hispanics (ANOVA p-value < 0.01). In adjusted analyses, Asians (OR = 1.11 [95% CI: 1.04-1.19]) and Hispanics (OR = 1.14 [1.09-1.19]) had a higher likelihood of inpatient mortality compared to Whites. CONCLUSIONS: Asians had a higher risk-adjusted likelihood of inpatient AMI mortality compared to Whites. Further research is needed to identify the underlying reasons for this finding to improve AMI disparities for Asians.

Effect of race on the glycaemic response to sitagliptin: Insights from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).

AIM: Pooled efficacy studies suggest that glycaemic responses to dipeptidyl-peptidase 4 inhibitors in type 2 diabetes are greatest in Asians, who may also respond better to alpha-glucosidase inhibitors. We assessed the glycaemic impact of sitagliptin by race in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), and whether this was enhanced in Asians with concomitant acarbose therapy. MATERIALS AND METHODS: TECOS enrolled 14 671 patients with type 2 diabetes, cardiovascular disease and HbA1c of 48-64 mmol/mol (6.5%-8.0%), and randomized them, double-blind, to sitagliptin or placebo. There were 3265 patients (22.3%) from Asian countries. Background glucose-lowering therapies were unaltered for the first 4 months post randomization unless clinically essential, facilitating comparison of sitagliptin-associated effects in self-identified East Asian, Other (South) Asian, White Caucasian, Hispanic, Black and Indigenous groups. RESULTS: Median baseline HbA1c by race was 54 to 57 mmol/mol (7.1%-7.4%). Mean 4-month reduction in placebo-adjusted HbA1c was greatest in East Asians (-6.6 mmol/mol [-0.60%] vs ≤6.0 mmol/mol [≤0.55%] in other groups), with significantly greater reduction vs the 2 largest groups (White Caucasians, Other Asians; P < .0001) after adjustment for covariates. After the first 4 months, East and Other Asians were more likely to initiate additional oral therapy (metformin and/or sulfonylureas) than insulin vs White Caucasians (P < .0001). Acarbose use increased in the Asian patients, but no glycaemic interaction with allocated study medication was observed (adjusted P = .12). CONCLUSIONS: The greatest initial reduction in HbA1c with sitagliptin in the TECOS population was in East Asians. No enhanced glycaemic effect was seen when sitagliptin was given with acarbose.

Mendelian randomization analysis to assess a causal effect of haptoglobin on macroangiopathy in Chinese type 2 diabetes patients.

BACKGROUND: Haptoglobin (Hp) functions as an antioxidant by binding with haemoglobin. We investigated whether serum Hp has a causal effect on macroangiopathy via Mendelian randomization (MR) analysis with common variants of the Hp gene in Chinese patients with type 2 diabetes. METHODS: A total of 5687 type 2 diabetes patients were recruited and genotyped for the Hp gene. Clinical features and vascular imaging tests were applied to diagnose macroangiopathy. The association between common Hp genotypes and macroangiopathy was analyzed in the whole population. Serum Hp levels were measured by enzyme-linked immunosorbent assay in a subset of 935 patients. We individually analyzed the correlations among Hp levels, Hp genotypes and macroangiopathy. Further, 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative marker of DNA damage, was examined to evaluate the levels of oxidative stress. RESULTS: Common Hp genotypes were correlated with macroangiopathy (OR = 1.140 [95% CI 1.005-1.293], P = 0.0410 for the Hp 1 allele). Serum Hp levels were associated with both common Hp genotypes (P = 3.55 × 10-31) and macroangiopathy (OR = 2.123 [95% CI 1.098-4.102], P = 0.0252) in the subset of 935 patients. In the MR analysis, the directional trends of the observed and predicted relationships between common Hp genotypes and macroangiopathy were the same (OR 1.357 and 1.130, respectively). Furthermore, common Hp genotypes and Hp levels were associated with serum 8-OHdG levels (P = 0.0001 and 0.0084, respectively). CONCLUSIONS: Our study provides evidence for a causal relationship between serum Hp levels and macroangiopathy in Chinese type 2 diabetes patients by MR analysis.

Dapagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in people with type 2 diabetes (CVD-REAL Nordic) when compared with dipeptidyl peptidase-4 inhibitor therapy: A multinational observational study.

AIMS: To compare the sodium-glucose-cotransporter-2 (SGLT-2) inhibitor dapagliflozin with dipeptidyl peptidase-4 (DPP-4) inhibitors with regard to risk associations with major adverse cardiovascular (CV) events (MACE; non-fatal myocardial infarction, non-fatal stroke or cardiovascular mortality), hospitalization for heart failure (HHF), atrial fibrillation and severe hypoglycaemia in patients with type 2 diabetes (T2D) in a real-world setting. METHODS: All patients with T2D prescribed glucose-lowering drugs (GLDs) during 2012 to 2015 were identified in nationwide registries in Denmark, Norway and Sweden. Patients were divided into two groups: new users of dapagliflozin and new users of DPP-4 inhibitors, matched 1:3 by propensity score, calculated by patient characteristics, comorbidities and drug treatment. Cox survival models were used to estimate hazard ratio (HR) per country separately, and a weighted average was calculated. RESULTS: After matching, a total of 40 908 patients with T2D were identified as new users of dapagliflozin (n = 10 227) or a DPP-4 inhibitor (n = 30 681). The groups were well balanced at baseline; their mean age was 61 years and 23% had CV disease. The mean follow-up time was 0.95 years, with a total of 38 760 patient-years. Dapagliflozin was associated with a lower risk of MACE, HHF and all-cause mortality compared with DPP-4 inhibitors: HRs 0.79 (95% confidence interval [CI] 0.67-0.94), 0.62 (95% CI 0.50-0.77), and 0.59 (95% CI 0.49-0.72), respectively. Numerically lower, but non-significant HRs were observed for myocardial infarction (0.91 [95% CI 0.72-1.16]), stroke (0.79 [95% CI 0.61-1.03]) and CV mortality (0.76 [95% CI 0.53-1.08]) Neutral associations with atrial fibrillation and severe hypoglycaemia were observed. CONCLUSIONS: Dapagliflozin was associated with lower risks of CV events and all-cause mortality compared with DPP-4 inhibitors in a real-world clinical setting and a broad T2D population.

Development of a cardiovascular diseases risk prediction model and tools for Chinese patients with type 2 diabetes mellitus: A population-based retrospective cohort study.

AIMS: Evidence-based cardiovascular diseases (CVD) risk prediction models and tools specific for Chinese patients with type 2 diabetes mellitus (T2DM) are currently unavailable. This study aimed to develop and validate a CVD risk prediction model for Chinese T2DM patients. METHODS: A retrospective cohort study was conducted with 137 935 Chinese patients aged 18 to 79 years with T2DM and without prior history of CVD, who had received public primary care services between January 1, 2010 and December 31, 2010. Using the derivation cohort over a median follow-up of 5 years, the interaction effect between predictors and age were derived using Cox proportional hazards regression with a forward stepwise approach. Harrell's C statistic and calibration plot were used on the validation cohort to assess the discrimination and calibration of the models. The web calculator and chart were developed based on the developed models. RESULTS: For both genders, predictors for higher risk of CVD were older age, smoking, longer diabetes duration, usage of anti-hypertensive drug and insulin, higher body mass index, haemoglobin A1c (HbA1c), systolic and diastolic blood pressure, a total cholesterol to high-density lipoprotein-cholesterol (TC/HDL-C) ratio and urine albumin to creatinine ratio, and lower estimated glomerular filtration rate. Interaction factors with age demonstrated a greater weighting of TC/HDL-C ratio in both younger females and males, and smoking status and HbA1c in younger males. CONCLUSION: The developed models, translated into a web calculator and color-coded chart, served as evidence-based visual aids that facilitate clinicians to estimate quickly the 5-year CVD risk for Chinese T2DM patients and to guide intervention.

Ethnicity influences cardiovascular outcomes and complications in patients with type 2 diabetes.

AIM: To determine whether cardiovascular outcomes in type 2 diabetes (T2D) differ according to ethnicity, and whether ethnicity influences the effect of gender on these outcomes in Caucasians, East-Southeast-Asians, Middle-Easterners, South-Asians and Pacific-Islanders. METHODS: We compared demographics, HbA1c, lipid profile, renal function markers, and prevalence of macrovascular and microvascular complications between ethnic groups. Cross-sectional data was prospectively collected from 204 consecutive patients at Westmead Hospital's T2D clinic from April-October 2015. Univariate analysis was performed using chi-squared test for categorical data, and Mann-Whitney-U or Kruskal-Wallis test for continuous data. RESULTS: Compared to Caucasians, South-Asians were diagnosed younger, were currently younger, had lower body-mass-index (BMI) and better renal function but higher rates of non-ST-elevation myocardial infarction (STEMI, 21.7% versus 3.5%, p<0.05). East-Southeast-Asians had lower BMI but more nephropathy than Caucasians (59% versus 39%, p<0.05). East-Southeast-Asian males had fewer CVD than Caucasians, but this protection was absent in East-Southeast-Asian females. Middle-Easterners had more non-STEMI than Caucasians (5.3% vs 3.5%, p<0.05). Middle-Eastern females were not at lower CVD risk than males. Caucasians had most PVD (20% versus 6%, p<0.05). CONCLUSIONS: Ethnicity influences rates of diabetes-related complications. Female CVD protection is altered in some groups. Ethnicity should be considered in assessing CVD and complications risk.

The fasting serum triglyceride levels of elderly population with different progression stages of diabetes mellitus in China.

AIMS: This cross-sectional study aimed to investigate triglyceride level among Chinese elderly population with different diabetic progressions and related factors of triglyceride. METHODS: Study participants (≥65years) were recruited from a nationwide cross-sectional surveillance and were divided into four subgroups according to diabetic progression. Their information was obtained via questionnaire and physical examination. Their lipids in fasting serum samples were analyzed. RESULTS: The serum triglyceride levels (mmol/L, mean±SD) were 1.3±0.8 (subgroup of no prediabetes and no DM), 1.5±1.0 (subgroup of prediabetes), 1.6±1.1 (subgroup of newly diagnosed DM) and 1.7±1.1 (subgroup of previously diagnosed DM), respectively. Only one female participant had a higher triglyceride than upper limit for prevention of acute pancreatitis (11.0mmol/L). However, 23.1% of participants and 34.8% of DM participants had higher triglyceride than upper limit for prevention of cardiovascular diseases (1.7mmol/L). Triglyceride level was positively correlated with diabetic progression (rs=0.17, p<0.01). Age, gender, waist-to-height ratio (rather than BMI), systolic pressure, serum total cholesterol and HDL-C levels were statistically correlated with triglyceride level for total participants (R2=0.39, p<0.01). CONCLUSIONS: Aggravation of serum triglyceride level was related to diabetic progression in Chinese elderly population. Triglyceride control was unsatisfactory in Chinese elderly population, especially in elderly population with DM.

Relationships between blood pressure and blood glucose among offspring of parents with type 2 diabetes: Prediction of incident dysglycemia in a biracial cohort.

AIMS: We assessed blood pressure (BP) and blood glucose (BG) values in healthy subjects, and examined baseline BP as a predictor of incident prediabetes during follow-up. METHODS: Participants in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study underwent screening assessments (anthropometry, BP, OGTT) and were stratified into normal BP (NBP), prehypertension, or hypertension, and normal glucose regulation (NGR), prediabetes (IFG/IGT), or type 2 diabetes (T2D) status. NGR subjects who met all inclusion criteria were enrolled in a 5-yr prospective study, with the primary outcome of incident prediabetes. RESULTS: We screened 602 adults (341 black, 261 white) and enrolled 343 (193 black, 150 white) for prospective follow-up. Systolic and diastolic BP correlated significantly with fasting and nonfasting BG (P=0.003-<0.0001). Compared to NGR group, more prediabetic subjects had prehypertension (42.5% vs. 36.2%) and fewer had NBP (35.9% vs. 48.6%) (P=0.009). During ~5years of follow-up, 26.3% of NBP and 35.7% of prehypertensive subjects developed prediabetes (P=0.02). Kaplan-Meier analysis showed higher probability of incident prediabetes among participants with prehypertension compared to NBP during ~5years of follow-up (P=0.0012). CONCLUSIONS: In our biracial cohort, BP and BG values were significantly correlated, and BP status predicted incident prediabetes among initially normoglycemic individuals. These findings suggest co-evolution of factors involved in the dysregulation of BP and BG.