Population diversity of cardiovascular outcome trials and real-world patients with diabetes in a Chinese tertiary hospital / 中华医学杂志(英文版)

BACKGROUND@#Recent cardiovascular outcome trials (CVOTs) changed the therapeutic strategy of guidelines for type 2 diabetes. We compared the characteristics of patients from real-world hospital settings with those of participants in recent pragmatic randomized trials.@*METHODS@#This electronic medical record (EMR)-based retrospective observational study investigated the data of patients with diabetes from inpatient and outpatient settings in West China Hospital of Sichuan University from January 1, 2011, to June 30, 2019. We identified patients meeting the inclusion criteria of a pragmatic randomized trial (EMPA-REG OUTCOME) based on EMRs and compared their baseline characteristics with those of the trial participants. The cutoff for the clinical significance of each characteristic was set as its minimal clinically important difference based on expert consultation.@*RESULTS@#We included 48,257 inpatients and 36,857 outpatients with diabetes and found that 8389 (17.4%) inpatients and 2646 (7.2%) outpatients met the inclusion criteria for the EMPA-REG OUTCOME trial. Compared with the trial population, the real-world inpatients meeting the eligibility criteria of the EMPA-REG OUTCOME had similar age, blood pressure, and lipid profiles but comprised of fewer males, metformin users, anti-hypertensive drug users, and aspirin users, and had a lower body mass index. The group of outpatients meeting the eligibility criteria had fewer males, similar age, fewer metformin users, fewer insulin users, fewer anti-hypertensive drug users, and fewer aspirin users compared with the trial population.@*CONCLUSIONS@#The trial population in EMPA-REG OUTCOME represents only a small portion of patients with diabetes from the inpatient and outpatient departments of a Chinese tertiary medical center. Evidence localization in different clinical settings and validation are essential to enabling extrapolation of the results from CVOTs in patients with diabetes to Chinese clinical practice.

Efficacy and safety of avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone: a multicenter, randomized, controlled trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.</p><p><b>METHODS</b>This study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.</p><p><b>RESULTS</b>At week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups.</p><p><b>CONCLUSIONS</b>Compared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.</p><p><b>REGISTRATION NUMBER</b>ChiCTR-TRC-13003776.</p>

Effectiveness of different waist circumference cut-off values in predicting metabolic syndrome prevalence and risk factors in adults in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the effectiveness of waist circumference cut-off values in predicting the prevalence of metabolic syndrome (MetS) and risk factors in adults in China.</p><p><b>METHODS</b>A cross-sectional survey was condcuted in 14 provinces (autonomous region, municipality) in China. A total of 47,325 adults aged⋝20 years were selected by multistage stratified sampling, and questionnaire survey and physical and clinical examination were conducted among them. MetS was defined according to the International Diabetes Federation (IDF) criteria and modified IDF criteria.</p><p><b>RESULTS</b>The age-standardized prevalence of MetS was 24.2% (22.1% in men and 25.8% in women) and 19.5% (22.1% in men and 18.0% in women) according to the IDF criteria and modified IDF criteria respectively. The age-standardized prevalence of pre-MetS was 8.1% (8.6% in men and 7.8% in women) according to the modified IDF criteria. The prevalence of MetS was higher in urban residents than rural residents and in northern China residents than in southern China residents. The prevalence of central obesity was about 30% in both men and women according to the ethnicity-specific cut-off values of waist circumference for central obesity (90 cm for men and 85 cm for women). Multivariate regression analysis revealed no significant difference in risk factors between the two MetS definitions.</p><p><b>CONCLUSION</b>Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China. Conclusion Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China.</p>

Liddle's syndrome caused by a novel mutation of the gamma-subunit of epithelial sodium channel gene SCNN1G in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen the mutation of the beta and gamma subunits of epithelial sodium channel gene SCNN1 in two families with Liddle's syndrome.</p><p><b>METHODS</b>Two patients clinically diagnosed as Liddle's syndrome and their family members were enrolled. Peripheral blood samples were collected and total genomic DNA was prepared. Polymerase chain reaction (PCR) was used to amplify the exon 13 of the SCNN1B and SCNN1G gene. PCR products were purified and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>A heterozygous nonsense mutation at codon 564 of the SCNN1B gene from CGA(Arg) to stop codon(TGA) was detector in the proband of family 1. More importantly, a novel heterozygous nonsense mutation of CAG(Gln) to stop codon TAG at codon 567 of the SCNN1G gene was detected in the proband and another two members of family 2.</p><p><b>CONCLUSION</b>Screening for specific mutations of the SCNN1 gene in relatives of patients with Liddle's syndrome can be used to identify the previously unrecognized cases within the family. A new nonsense mutation(Q567X) of the SCNN1G gene is likely the cause of Liddle's syndrome in family 2.</p>

PPARGC1A gene Thr394Thr G/A polymorphism and its association with type 2 diabetes mellitus and insulin resistance in a Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To examine the association of the Thr394Thr polymorphism of PPARGC1A gene with type 2 diabetes (T2DM), insulin resistance (IR) and other metabolic disorders in a Chinese population.</p><p><b>METHODS</b>Three hundred and seven subjects including 151 T2DM patients and 156 normal glucose tolerant controls (NC) were enrolled in this study. The Thr394Thr G/A polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Glucose, insulin, lipids levels were determined in all subjects. Body mass index (BMI), waist circumferences, index of homeostasis model assessment-insulin resistance (HOMA-IR) and blood pressure were also measured.</p><p><b>RESULTS</b>The diabetic subjects had higher levels of BMI, waist circumferences, blood systolic pressure, triglycerides and lower levels of high density lipoprotein-cholesterol (HDL-C) compared with those of control subjects (P<0.05). About 43.7% (66/151) of the T2DM subjects had the AG genotype, while 37.2% (58/156) in the NC group. The frequency of the A allele was 0.225 in T2DM, and 0.186 in the NC subjects. There were no significant differences either in genotype or allelic distribution of G/A polymorphism between the two groups. In the T2DM group, subjects with AA and GA genotypes had significantly higher levels of HOMA-IR, waist circumferences and lower levels of HDL-C (P<0.05) than those carrying GG genotype. HOMA-IR in subjects with AA and AG were significantly higher than those with GG genotype in both groups.</p><p><b>CONCLUSION</b>The A allele of the Thr394Thr (G-->A) polymorphism of the PPARGC1A gene was associated with insulin resistance, and may be related to central obesity and decreased HDL-C levels in Chinese population. The relationship between this polymorphism and T2DM needs further investigation.</p>

Mesenchymal stem cells transplantation mildly ameliorates experimental diabetic nephropathy in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diabetic nephropathy is a common complication of diabetes mellitus. This study aimed to explore whether mesenchymal stem cells (MSCs) transplantation could attenuate diabetic nephropathy in experimental diabetic rats.</p><p><b>METHODS</b>Sprague-Dawley rats received a single intraperitoneal injection of streptozotocin (STZ) (60 mg/kg). Diabetic rats were randomized to four groups: diabetes control group (DC), ciclosporin A group (CsA), MSC group, and MSC + CsA group (MSCA). Bone marrow mesenchymal stem cells were cultured, identified and labeled by 5-bromo-2'-deoxyuridine (BrdU) in vitro. Then they were transplanted to diabetic rats via introcardiac infusion. Ciclosporin A was administered daily at 5 mg/kg. At 1, 2, 4, 8 weeks after transplantation, random blood glucose, urine albumin/creatinine ratio (Alb/Cr), endogenous creatinine clearance rate and renal mass index were tested. Renal morphology and labeled cells were examined.</p><p><b>RESULTS</b>Cultured MSCs expressed mesenchymal cell phenotype, and could be multidifferentiated to osteogenic and adipogenic cells. Labeled MSCs could be detected in the kidney of nephropathic rats, mainly in renal interstitium, but they did not propagate after engrafting in kidney. Over the course of the experiment, MSCA group showed a significant decrease in blood glucose compared with MSC group, CsA group and DC group (P < 0.05, respectively). The Alb/Cr in MSCA group and MSC group were significantly lower than CsA group and DC group (P < 0.05). And the Alb/Cr in MSCA group showed a significant decrease compared with MSC group (0.74 vs 0.84, P < 0.05). There was a significant difference in renal mass index between the MSCA group and DC group (5.66 vs 6.37, P < 0.05). No significant difference was found in creatinine clearance rate among 4 groups (P > 0.05). Treatment with MSC + CsA significantly ameliorated the morphology of diabetic kidney.</p><p><b>CONCLUSION</b>MSC could mildly ameliorate diabetic nephropathy by decreasing blood glucose, Alb/Cr ratio and renal mass index.</p>

Prevalence and risk factors of peripheral arterial disease in diabetic patients over 50 years old in China / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the prevalence of peripheral arterial disease (PAD) in China type 2 diabetic patients and to demonstrate the relationships between putative risk factors and PAD.</p><p><b>METHODS</b>In total 1,397 type 2 diabetic patients aged 50 years and older were enrolled and determined ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) in 15 Class III Grade A hospitals in 7 major cities of China.</p><p><b>RESULTS</b>Mean patient age was 63.7 +/- 8.2 years and mean duration of diabetes mellitus was 9.39 +/- 7.4 years. Two hundreds and seventy-two (19.47%) patients were diagnosed as PAD by ABI < 0.9, 122 (18.37%) in male and 150 (20.46%) in female. PAD patients had a significantly longer duration of diabetes mellitus, higher hemoglobin A1c, and a significantly lower mean body mass index than non-PAD ones. Aging, smoking, and systolic blood pressure were found to be positively related with the prevalence of PAD. In terms of lipid profiles, no variable was found to relate with PAD. Notably, baPWV showed as the same significant guiding index for PAD, almost matched with ABI.</p><p><b>CONCLUSIONS</b>PAD is a common complication in China type 2 diabetic patients. Therefore, PAD screening and treatment should be emphasized for diabetic patients with high risk factors.</p>

Molecular scanning of candidate mtDNA gene fragment in diabetic pedigrees / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore novel pathogenic mutation in the mitochondrial DNA gene in diabetic pedigree.</p><p><b>METHODS</b>Twenty-eight suspected mitochondrial DNA diabetic families were recruited. The gene fragment was produced by PCR, and mutation was detected by direct sequencing.</p><p><b>RESULTS</b>In one pedigree, the proband and her mother were found carrying the most common nt3243 A --> G mutation and another 16S rRNA 3205C --> T mutation. But only 3205C --> T was found in her affected brother. All the two patients were deaf and developed diabetes in early age, characterized by impaired beta cell function and low body mass index (BMI). The proband had relatively higher lactic acid concentration than normal individuals. A novel ND1 gene 3434 A --> G(TAT --> TGT) mutation was explored in another proband with deafness and her affected family members.</p><p><b>CONCLUSION</b>16SrRNA 3205C --> T mutation was found in a mitochondrial diabetes mellitus pedigree, implying its potential pathogenic role in diabetes. Another novel ND1 3434 A --> G mutation was found in another diabetic pedigree. Because this mutation causes amino acid change (Tyr --> Cys) and is co-segregated with diabetes, it may be diabetogenic.</p>

Progress in molecular-genetic researches on congenital adrenal hyperplasia—11?-hydroxylase deficiency / 中华内分泌代谢杂志

11?-hydroxylase deficiency is one of the main causes of congenital adrenal hyperplasia (CAH),which is caused by the mutation of CYP11B1 gene that encodes the enzyme.Researches have shown that mutations of CYP11B1 gene would result in decreased activity or inactivation of the enzyme in classical 11?- hydroxylase deficiency,and their relationship between genotype and phenotype of 11?-hydroxylase deficiency is not clear.