Simin Zhang

Silent myocardial ischemia detected by single photon emission computed tomography (SPECT) and risk of cardiac events among asymptomatic patients with type 2 diabetes: A meta-analysis of prospective studies

OBJECTIVE To assess the value of detecting silent myocardial ischemia (SMI) by single photon emission computed tomography (SPECT) in predicting risk of cardiac events among patients with type 2 diabetes mellitus (T2DM) who do not have overt cardiac symptoms. MATERIALS AND METHODS Electronic databases (PubMed, Cochrane Library, EMBASE, and others) and original article references were systematically searched through February 1, 2013. A fixed-effects model was applied to pooled data to estimate relative risks (RR) and 95% confidence intervals (CI). RESULTS Ten prospective studies with follow-up ranging from 1 to 6 years were identified. Among the total of 1360 asymptomatic patients with T2DM screened by SPECT, the cumulative prevalence rate of SMI was 26.1%. Patients with SMI were at increased risk of experiencing endpoints relative to patients without SMI: RR (95% CI) for cardiac death, 4.60 (1.78-11.84); non-fatal cardiac events, 3.48 (2.30-5.28); total cardiac events, 3.48 (2.59-4.68); and all-cause mortality, 2.20 (1.14-4.25). The risk of cardiac death and non-fatal cardiac events increased with increasing severity of SPECT-detected abnormalities. CONCLUSIONS SMI detected by SPECT is associated with increased risk of cardiac death, all-cause mortality, and non-fatal cardiac events in T2DM patients without overt cardiac symptoms. Advanced intervention procedures including intensive drug management should be implemented to reduce the risk of cardiac events for SMI-positive T2DM patients.

Association of serum ferritin levels with metabolic syndrome and insulin resistance in a Chinese population

AIMS Increased iron is associated with type 2 diabetes, dyslipidemia, and high blood pressure. Therefore, serum ferritin may be a suitable biomarker to detect metabolic syndrome (MetS). We investigated the relationship between serum ferritin, and the prevalence of MetS and insulin resistance (IR). METHODS This cross-sectional study assessed 2,786 Chinese participants, aged 25-75 years. MetS was defined using the 2006 International Diabetes Federation guidelines. IR was assessed with homeostasis model assessment estimated IR (HOMA-IR). Regression analysis was used to estimate the association between serum ferritin and the prevalence of MetS and IR. RESULTS MetS prevalence within each serum ferritin quartile (Q1-4) was 31.7%, 37.1%, 43.6%, and 55.4%, respectively in men (P<0.001), and 30.1%, 34.8%, 48.2%, and 66.9%, respectively in women (P<0.001). Increased serum ferritin correlated with the number of MetS components (P<0.001). The odds ratio for MetS in the ferritin Q4 group was 1.95 (1.39-2.73) for men and 1.66(1.12-2.47) for women, compared with Q1. Serum ferritin correlated positively with HOMA-IR in men (regression coefficient: 0.058, P=0.009) and women (regression coefficient: 0.082, P=0.001). CONCLUSION MetS prevalence increased with elevated serum ferritin levels, and serum ferritin levels were independently associated with MetS and IR.

Age at diagnosis and C-peptide level are associated with diabetic retinopathy in Chinese.

Objective To find the associations between diabetic retinopathy and age at diagnosis, C-peptide level and thyroid-stimulating hormone (TSH) level in Chinese type 2 diabetes mellitus. Methods 3100 hospitalized type 2 diabetic patients in Peking University Peoples Hospital were included in this retrospective study. Their medical history and the laboratory data were collected. All the patients received examination of diabetic retinopathy (DR) by professional ophthalmologist. Results Comparisons among patients with NDR, NPDR and PDR showed that with the progression of diabetic retinopathy, patients turned to have older age but younger age at diagnosis of diabetes, and have higher SBP, longer duration of diabetes, higher mean HbA1c but lower fasting and 2 hours postprandial C-peptide level. Moreover, with the progression of diabetic retinopathy, patients turned to have higher prevalence of primary hypertension, higher prevalence of peripheral vascular sclerosis, higher proportion with insulin treatment. TSH level was comparable among the three groups of patients. Association analysis showed that after adjusting for age, sex, duration of diabetes, body mass index, HbA1c, blood pressure and albuminurea creatinine ratio and insulin treatment, age at diagnosis (OR 0.888, 95%CI 0.870–0.907, p = 0.00) and postprandial C-peptide (OR 0.920, 95%CI 0.859–0.937, p = 0.00) are the independent associated factors of DR in Chinese type 2 diabetes. Conclusions According to the results, postprandial C-peptide level and age at diabetes may be two independent associated factors with DR in Chinese type 2 diabetes. The lower level of postprandial C-peptide, the younger age at diagnosis, may indicate the higher prevalence of DR.

Comparisons of weight changes between sodium-glucose cotransporter 2 inhibitors treatment and glucagon-like peptide-1 analogs treatment in type 2 diabetes patients: A meta-analysis

To evaluate the efficacy of weight changes from baseline of the sodium‐glucose cotransporter 2 (SGLT2) inhibitors treatment and glucagon‐like peptide‐1 (GLP‐1) analogs treatment after comparisons with a placebo in type 2 diabetes patients, and the associated factors.

Serum leptin level is associated with glycaemic control in newly diagnosed type 2 diabetes patients: A 1-year cohort study

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since mardi 21 juin 2016

The Association Between the Dosage of SGLT2 Inhibitor and Weight Reduction in Type 2 Diabetes Patients: A Meta-Analysis

Sodium glucose cotransporter 2 (SGLT2) inhibitors may induce urinary glucose excretion via the inhibition of renal glucose reabsorption, improve glycemic control, and lower body weight. The aim of this meta‐analysis was to evaluate weight changes in patients who received different dosages of SGLT2 inhibitors.

Combined Influence of Genetic Variants and Gene-gene Interaction on Sulfonylurea Efficacy in Type 2 Diabetic Patients.

UNLABELLED Several genes have been shown to influence the response to sulfonylureas in previous studies. However, their interactions and combined genetic influence on sulfonylurea efficacy remain mostly unexplored. So the aim of this study was to examine the interactions of these published susceptibility alleles and access the potential utility of combining information for drug response prediction. METHODS We genotyped 5 variants of these genes in a total of 747 diabetic patients enrolled in a trial of glibenclamide (CYP2C9, KCNJ11, TCF7L2, KCNQ1 and CDKN2A/2B gene). All the patients were followed for 48 weeks. Treatment failure was fasting blood glucose level≥7.0 mmol/L. A Cox regression model was used to evaluate the relationship between genetic variants and treatment failure over a period of 48 weeks. The receiver operating characteristic (ROC) curve, the area under the curve (AUC) and the multifactor dimensionality reduction method (MDR) analyses were used to assess the gene-gene interaction and also the predictive power of the combined variants. RESULTS The relationship beween risk alleles and FBG reduction at the end of the first month was not significant (Low Risk Group 10.8% (1.2-20.7%), Middle Risk Group 10.7% (1.3-21.1%), High Risk Group 8.51% (- 0.1-18.4%), P=0.212). After adjusting for sex, age, BMI, total dose of glibenclamide and baseline HbA1c, Cox regression showed a borderline significant association between the number of risk alleles and glibenclamide treatment failure (HR=1.125, 95%CI 1.016-1.246, P=0.023). There was potential gene-gene interaction between KCNJ11 and CDKN2A/2B gene using MDR method. The area under the ROC curve was 0.547, and the testing balanced accuracy of the best genetic model in MDR analysis was 0.5643. CONCLUSION Our study demonstrated that the combined genetic variants were borderline significantly associated with the efficacy of glibenclamide, and there are gene-gene interaction between KCNJ11 and CDKN2A/2B. More evidence was needed for increasing the predictive value of genetic variants on glibenclamide efficacy.

Decreased Glycemic Difference Between Diabetes and Nondiabetes in the Elderly Leads to the Reduced Diagnostic Accuracy of Hemoglobin A1c for Diabetes Screening in an Aged Chinese Population

BACKGROUND This study investigated the impact of age on the accuracy of glycated hemoglobin (HbA1c) for diabetes screening and explored the possible cause(s). MATERIALS AND METHODS Data from 3,050 Chinese participants 25-75 years of age without known diabetes in a population-based cross-sectional survey were analyzed. Diabetes was diagnosed by the oral glucose tolerance test (OGTT). The performance of HbA1c for detecting OGTT-defined diabetes in tertile groups (divided by age) was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve (ROC). The effect of age on the difference in glucose levels between participants with and without diabetes and the impact of this difference on the performance of HbA1c were evaluated. RESULTS In young (25-41 years old), middle-aged (41-53 years old), and old (55-72 years old) participants, the ROC AUC (95% confidence interval) of HbA1c for detecting OGTT-defined diabetes was 0.958 (0.915, 1.000), 0.891 (0.852, 0.930), and 0.861 (0.821, 0.901), respectively (P = 0.005). The difference of fasting plasma glucose between participants with diabetes and those without diabetes decreased with increasing age: 3.01 (2.80, 3.22) mmol/L, 2.90 (2.71, 3.09) mmol/L, and 2.33 (2.16, 2.50) mmol/L in the three consecutive age groups, respectively. A similar pattern was found in 2-h postprandial plasma glucose. The impact of age on the diagnostic power of HbA1c diminished after data were rearranged to artificially increase the difference between participants without diabetes and those with diabetes. CONCLUSIONS The accuracy of HbA1c for detecting OGTT-defined diabetes declines with age. This is largely due to the decreased separation in glycemic levels between participants with diabetes and without diabetes in the elderly.

IL-1B rs1143623 and EEF1A1P11-RPL7P9 rs10783050 polymorphisms affect the glucose-lowing efficacy of metformin in Chinese overweight or obese Type 2 diabetes mellitus patients

AIM To investigate the potential genetic effect on metformin efficacy in overweight or obese Chinese Type 2 diabetes mellitus (T2DM) patients. PATIENTS & METHODS 768 SNPs in or close to 207 genes were genotyped in 84 patients treated with metformin + glibenclamide/Xiaoke Pill. Significant SNPs were then verified in 107 recent-onset overweight or obese T2DM patients treated with metformin alone. Genotyping was done by Illumina GoldenGate Assay. RESULTS In the discovery stage, 22 SNPs were nominally significant. IL1B rs1143623 (p = 0.011) and EEF1A1P11-RPL7P9 rs10783050 (p = 0.021) were still significantly associated with the relative change of HbA1c in the replication stage. CONCLUSION IL1B rs1143623 and EEF1A1P11-RPL7P9 rs10783050 polymorphisms may contribute to metformins glucose-lowing efficacy in overweight or obese Chinese T2DM patients.

Association of serine racemase gene variants with type 2 diabetes in the Chinese Han population

A genome‐wide association study in the Chinese Han population has identified several novel genetic variants of the serine racemase (SRR) gene in type 2 diabetes. Our purpose was to systematically evaluate the contribution of SRR variants in the Chinese Han population. rs391300 and rs4523957 in SRR were genotyped respectively in the two independent populations. A meta‐analysis was used to estimate the effects of SRR in 21,305 Chinese Han individuals. Associations between single‐nucleotide polymorphisms and diabetes‐related phenotypes were analyzed among 2,615 newly diagnosed type 2 diabetes patients and 5,029 controls. Neither rs391300 nor rs4523957 were associated with type 2 diabetes in populations. Furthermore, meta‐analysis did not confirm an association between type 2 diabetes and SRR. In the controls, rs391300‐A and rs4523957‐G were associated with higher 30‐min plasma glucose in an oral glucose tolerance test. The present study did not confirm that SRR was associated with type 2 diabetes.