Effects of Incretin-based Therapies on Weight-related Indicators among Patients with Type 2 Diabetes: A Network Meta-analysis / 生物医学与环境科学（英文）

Objective@#To evaluate the effects of incretin-based therapies on body weight as the primary outcome, as well as on body mass index (BMI) and waist circumference (WC) as secondary outcomes.@*Methods@#Databases including Medline, Embase, the Cochrane Library, and clinicaltrials.gov (www.clinicaltrials.gov) were searched for randomized controlled trials (RCTs). Standard pairwise meta-analysis and network meta-analysis (NMA) were both carried out. The risk of bias (ROB) tool recommended by the Cochrane handbook was used to assess the quality of studies. Subgroup analysis, sensitivity analysis, meta-regression, and quality evaluation based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were also performed.@*Results@#A total of 292 trials were included in this study. Compared with placebo, dipeptidyl-peptidase IV inhibitors (DPP-4Is) increased weight slightly by 0.31 kg [95% confidence interval ( ): 0.05, 0.58] and had negligible effects on BMI and WC. Compared with placebo, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lowered weight, BMI, and WC by -1.34 kg (95% : -1.60, -1.09), -1.10 kg/m (95% : -1.42, -0.78), and -1.28 cm (95% : -1.69, -0.86), respectively.@*Conclusion@#GLP-1 RAs were more effective than DPP-4Is in lowering the three indicators. Overall, the effects of GLP-1 RAs on weight, BMI, and WC were favorable.

Type 1 diabetes induced by immune checkpoint inhibitors / 中华医学杂志(英文版)

With the increasing use of immune checkpoint inhibitors (ICI) including anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) in cancers, ICI-induced type 1 diabetes has been reported throughout the world. In this review, we aim to summarize the characteristics of this disease and discuss the mechanism of it. As an immune-related adverse event, type 1 diabetes developed after the administration of anti-PD-1 or anti-PD-ligand 1 (PD-L1) in the combination with or without anti-CTLA-4. It usually presented with acute onset, and 62.1% of the reported cases had diabetic ketoacidosis. Only a third of them had positive autoantibodies associated with type 1 diabetes. Susceptible HLA genotypes might be associated. T-cell-stimulation by blocking of the interaction of PD-1 and PD-L1 in pancreatic β cells was the main mechanism involved in the pathology. Insulin was the only effective treatment of ICI-induced type 1 diabetes. In conclusions, ICI-induced type 1 diabetes is a potentially life-threating adverse event after the immunotherapy of cancers. Screening and early recognition is important. Further investigation of the mechanism may help to better understand the pathology of type 1 diabetes.

Comparison of Placebo Effect between Asian and Caucasian Type 2 Diabetic Patients: A Meta-Analysis / 中华医学杂志(英文版)

<p><b>Background</b>Placebo was defined as any therapy that is used for its nonspecific psychological and physiologic effect but has no specific pharmacologic impact on the condition being treated. Besides medication therapies, studies have found that the optimal dietary approach as well as physical activity and education are useful to control hyperglycemia in patients with type 2 diabetes (T2DM). The aim of this study was to evaluate the placebo effects of antidiabetic therapies in Asian and Caucasian T2DM patients and make a comparison between the two ethnicities.</p><p><b>Methods</b>A search using the MEDLINE database, EMBASE, and Cochrane Database was performed, from when recording began until December 2016. The main concepts searched in English were sulfonylurea (SU); alpha glucosidase inhibitors (AGI); metformin (MET); thiazolidinediones (TZD); dipeptidyl peptidase-4 inhibitors (DPP-4i); sodium-glucose cotransporter 2 inhibitors (SGLT2i); glucagon-like peptide-1 receptor agonist (GLP-1RA); type 2 diabetes (T2DM); placebo controlled; and randomized controlled trials. Using the Cochrane instrument, we evaluated the adequacy of randomization, allocation concealment procedures, and blinding.</p><p><b>Results</b>This study included 63 studies with a total of 7096 Asian patients involved and 262 studies with a total of 27,477 Caucasian patients involved. In Caucasian population, the use of placebo led to significant reductions of glycosylated hemoglobin (HbA1c), -0.683% (P = 0.008) in SU monotherapy treatment, -0.193% (P = 0.001) in DPP-4i treatment, and -0.230% (P < 0.001) in SGLT2i treatment, respectively. In Asian population, the use of placebo resulted in significant decreases of HbA1c, -0.162% (P = 0.012) in DPP-4i treatment and -0.269% (P = 0.028) in GLP-1RA add-on therapy, respectively. The placebo also significantly reduced body weight. In Caucasian population, placebo use resulted in 0.833 kg (P = 0.006) weight loss by SU treatment and 0.953 kg (P = 0.006) weight loss by GLP-1RA treatment. In Asian population, the placebo led to a weight change of 0.612 kg (P < 0.001) by GLP-1RA analog treatment. The changes of HbA1c and weight due to the placebo effect in other treatments were not significant in both Asian and Caucasian population. Comparisons of the placebo effect on HbA1c change and weight change in each treatment group indicated that no significant difference was found between Asian and Caucasian population.</p><p><b>Conclusions</b>The overall differences of the placebo effect on HbA1c changes as well as on body weight changes were not significant between Asian and Caucasian T2DM patients. The placebo effect on HbA1c changes and weight changes was not associated with baseline age, gender, baseline body mass index, baseline HbA1c, duration of diabetes, or study duration.</p>

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>

Relationship Between Serum Zinc Level and Microvascular Complications in Patients with Type 2 Diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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 β-cell function.</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>

Replication of association study between type 2 diabetes mellitus and IGF2BP2 in Han Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The association between IGF2BP2 and type 2 diabetes mellitus (T2DM) has been repeatedly confirmed among different ethnic populations. However, in several genome-wide association studies (GWAS) from the Chinese Han population, the gene IGF2BP2 has not been replicated. The results of relevant studies for the association between IGF2BP2 and T2DM showed controversy in Chinese Han population. It is necessary to systematically evaluate the contribution of common variants in IGF2BP2 to T2DM in Chinese Han population.</p><p><b>METHODS</b>Two single-nucleotide polymorphisms (SNPs, rs4402960 and rs1470579) in IGF2BP2 were genotyped in Chinese Han population (3807 controls/4531 T2DM cases) by Illumina GoldenGate Indexing assay. The association between SNPs and T2DM was evaluated by multiple Logistic Regression analysis. A meta-analysis was used to estimate the effects of IGF2BP2 in 20854 Chinese Han individuals.</p><p><b>RESULTS</b>rs1470579 and rs4402960 were confirmed to have strong association with T2DM in the Chinese Han population (rs1470579 P = 1.80×10(-7), OR (95% CI) = 1.22 (1.14-1.32), rs4402960 P = 7.46×10(-9), OR (95% CI) = 1.26 (1.17-1.37), respectively). Moreover, 11 studies for rs4402960 were included in the meta-analysis and 7 studies for rs1470579. The meta-analysis also showed the association between T2DM and IGF2BP2 (rs1470579 OR of 1.15 (95% CI = 1.10-1.19), P < 0.0001 under an additive model and rs4402960 OR of 1.14 (95% CI = 1.10-1.18), P < 0.0001 under an additive model).</p><p><b>CONCLUSION</b>IGF2BP2 was strongly associated with the risk of T2DM in Chinese Han population.</p>

Efficacy and safety of insulin treatment in type 2 diabetes using a new index called glucose safety control index / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To recommend an index named glucose safety control index (GSCI) to evaluate the efficacy and safety for insulin regimens.</p><p><b>DATA SOURCES</b>We searched databases for primary studies published in English. The main search concepts were type 2 diabetes, insulin treatment, premixed insulin, premixed insulin analogs, basal inuslin, basal inuslin analogs, bolus insulin, bolus insulin analogs, safety and efficacy.</p><p><b>STUDY SELECTION</b>Studies were eligible for inclusion if they met all of the following criteria: (1) type 2 diabetic patients aged >18 years were included; (2) random control studies with at least 12 weeks of follow-up; (3) different insulin regimens were evaluated.</p><p><b>RESULTS</b>When long-acting basal insulin therapy compared with neutral protamine Hagedorn (NPH) insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 100%, the proportion of GSCIΔA1c ratio more than 1 was 94.44%. When premixed insulin therapy compared with oral hypoglycemic agents plus basal insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 45.5%, the proportion of GSCIΔA1c ratio more than 1 was 38.9%. When premixed insulin therapy compared with oral hypoglycemic agents, the proportion of GSCI%A1c ratio less than 1 was 100%, the proportion of GSCIΔA1c ratio more than 1 was 50%. When premixed insulin therapy compared with basal-bolus insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 37.5%, the proportion of GSCIΔA1c ratio more than 1 was 50%.</p><p><b>CONCLUSION</b>According to the GSCI ratio, long-acting basal insulin therapy tended to be superior to NPH therapy, oral hypoglycemic agents plus basal insulin therapy tended to be superior to premixed insulin therapy, noninsulin antidiabetic agents and premixed insulin therapy was comparable, and basal-bolus insulin therapy tended to be superior to premixed insulin therapy in type 2 diabetes.</p>

Management status of type 2 diabetes mellitus in tertiary hospitals in Beijing: gap between guideline and reality / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diabetes has become one of the most common chronic diseases and the third leading cause of death in China. Many programs have been initiated at national and local levels to address the illness. However, the effect of these programs in daily outpatient clinics is still unclear. The objective of this study was to investigate the management status of type 2 diabetes mellitus (T2DM) and factors associated with it in diabetes clinics of tertiary hospitals in Beijing.</p><p><b>METHODS</b>A cross-sectional survey was conducted in six tertiary hospitals in Beijing. Control criteria were defined based on 2007 China guideline for type 2 diabetes (CGT2D).</p><p><b>RESULTS</b>A sample of 1151 patients, age (60.8 ± 9.2) years, and with a median disease duration of 7.3 years was included. The hemoglobin A1c (HbA1c) mean level was (7.15 ± 1.50)%, the percentage of patients achieving the targets for HbA1c was 37.8%, blood pressure 65.6%, triglyceride (TG) 48.8%, high-density lipoprotein (HDL) 59.2%, low-density lipoprotein (LDL) 34.0%, and total cholesterol (TC) 42.0%. The factors independently associated with glycemic control were diabetes duration (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.919 - 0.982, P < 0.01), body mass index (BMI) (OR = 0.914, 95%CI: 0.854 - 0.979, P = 0.01) and smoking (OR = 0.391, 95%CI: 0.197 - 0.778, P < 0.01). The factors independently associated with blood pressure control were BMI (OR = 0.915, 95%CI: 0.872 - 0.960, P < 0.01) and male gender (OR = 0.624, 95%CI: 0.457 - 0.852, P < 0.01). The factor independently associated with LDL control was education level (OR = 1.429, 95%CI: 1.078 - 1.896, P = 0.013).</p><p><b>CONCLUSIONS</b>The management status of T2DM patients in tertiary hospitals in Beijing has improved remarkably. However, there is still room for further improvement to reach the guideline target. Long diabetes duration, high BMI, smoking, male gender and low education level were independently associated with poor metabolic control.</p>

Effects of Chinese medicine Tongxinluo on hyperglycemia and beta-cell damage in streptozotocin-induced diabetic rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Determinants for inadequate glycaemic control in Chinese patients with mild-to-moderate type 2 diabetes on oral antidiabetic drugs alone / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Prevalence of inadequate glycaemic control among patients with type 2 diabetes mellitus (T2DM) remains high. We assessed glycaemic control in the real-life practice among people with T2DM in metropolises in China who were treated with oral antidiabetic drugs (OAD) alone and to determine factors associated with inadequate glycaemic control in this population.</p><p><b>METHODS</b>An observational, cross-sectional multicentre study was conducted in 16 metropolitan medical centers. People with T2DM who had been followed-up before the index visit which occurred from January to September 2007 were included in the study. All subjects were ≥ 30 years of age at the time of T2DM diagnosis and had received monotherapy or combination therapy of OAD for at least 6 months. Demographic and clinical data were collected from medical records. The main study outcome was the inadequate glucose control rate, which was calculated by the proportion of patients with haemoglobin A(1C) (HbA(1C)) ≥ 6.5% detected on the index visit.</p><p><b>RESULTS</b>In this cohort of 455 patients with T2DM whose mean age was 60.6 years and mean disease duration was 6.1 years, 45.5% had inadequate glycaemic control. The mean (SD) HbA(1C) was 6.7% (1.3). Multivariate Logistic regression showed that physical inactivity, disease duration > 10 years, body mass index (BMI) ≥ 24 kg/m(2), low homeostasis model assessment of β-cell function (HOMA-β) index, less frequency of medical visit and hypertriglyceridaemia were independent determinants of inadequate glycaemic control. Higher incidence of self-reported hypoglycemia experience (47.1% vs. 34.8%, P = 0.008) and more fear of hypoglycemia quantified by Worry subscale of the Hypoglycaemia Fear Survey (HFS) II were happened in subjects with good glycemic control.</p><p><b>CONCLUSION</b>Approximately one half of these outpatients with T2DM from the metropolitan medical centers in China had inadequate glycaemic control treated with OAD alone, which raises the need for more effective educational and therapeutic approaches on management of hypertriglycemia, enhancing physical exercise and weight control, and at the same time, lowering the hypoglycemic risk and diminishing the hypoglycemic fear of patients.</p>

Meta-analysis of the association of Pro12Ala polymorphism of peroxisome proliferator activated receptor gamma gene with type 2 diabetes in Chinese Han population / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the association of Pro12Ala polymorphism of peroxisome proliferator activated receptor gamma (PPARgamma) gene with type 2 diabetes (T2DM) in Chinese Han population.</p><p><b>METHODS</b>The present investigation was carried out using the keywords "PPARgamma", "pparg", "Pro12Ala", "type 2 diabetes", and "Chinese. The odds ratios (OR) for Ala12 used as the metric of choice were calculated in the dominant and additive model separately. The Meta-analysis was conducted by software STATA 11.0.</p><p><b>RESULTS</b>(1) We identified 22 studies, of which 17 studies involving 3927 type 2 diabetes cases and 3364 controls fell into the inclusion criteria. The analysis indicated no significant inter-study heterogeneity and publication bias. (2) The frequencies of the minor allele Ala12 in type 2 diabetes and control groups were 4.8% and 4.6% respectively. (3) The combined overall OR of dominant and additive model calculated by fix-effects meta-analysis for type 2 diabetes and the Pro12Ala polymorphism, were 0.95 (95% CI: 0.80, 1.12) and 0.93 (95% CI: 0.79, 1.09) respectively.</p><p><b>CONCLUSION</b>In this meta-analysis, the Pro12Ala gene variant (rs1801282) is not found to be associated with the susceptibility for type 2 diabetes in Chinese Han population.</p>

Contribution of the Akt2 gene to type 2 diabetes in the Chinese Han population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

High-normal serum uric acid is associated with albuminuria and impaired glomerular filtration rate in Chinese type 2 diabetic patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recently, some studies had shown that elevated serum uric acid (SUA) itself may increase the risk for development of renal disease in patients with diabetes. This study aimed to explore whether SUA was a predictor of microalbuminuria and impaired renal function in type 2 diabetes in Chinese patients.</p><p><b>METHODS</b>This cross-sectional study included 2108 type 2 diabetic patients. Kidney function was estimated using the simplified modification of diet in renal disease (MDRD) equation to obtain estimated glomerular filtration rate. The urine samples were obtained for measuring the albumin-to-creatinine ratio (ACR).</p><p><b>RESULTS</b>According to the ACR level, these patients were divided into two groups, normal ACR (NA) and non-normal ACR (non-NA). Both SUA and creatinine were significantly higher in the non-NA group than those in the NA group ((318.89 ± 107.52) vs. (283.44 ± 88.64) µmol/L, and (95.08 ± 53.24) vs. (79.63 ± 18.20) µmol/L, respectively). Logistic regression analysis showed that diabetic duration, systolic blood pressure, creatinine and SUA were the independent predictors of albuminuria. Furthermore, to identify the factors associated with renal function, these patients were divided into two groups according to the MDRD level (MDRD < 90 or MDRD ≥ 90). Both SUA and creatinine were significantly higher in the lower MDRD group than those in the higher MDRD group ((301.90 ± 96.46) vs. (264.07 ± 84.74) µmol/L, and (89.10 ± 31.00) vs. (66.37 ± 11.15) µmol/L, respectively). Logistic regression analysis showed that only age and SUA were the independent predictors of MDRD.</p><p><b>CONCLUSION</b>High-normal SUA was associated with albuminuria and impaired glomerular filtration rate in Chinese type 2 diabetic patients.</p>

Association between serum uric acid and different states of glucose metabolism and glomerular filtration rate / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recently, it has been suggested that the serum uric acid (SUA) level decreased in diabetic patients. The aim of this study was to explore the association between SUA level and different state of glucose metabolism and glomerular filtration rate (GFR) reflected by the simplified Modification of Diet in Renal Disease (MDRD) equation and to test the hypothesis that high MDRD is one of the determinants of SUA level.</p><p><b>METHODS</b>This cross-sectional study included 2373 subjects in Beijing who underwent a 75 g oral glucose tolerance test (OGTT) for screening of diabetes. According to the states of glucose metabolism, they were divided into normal glucose tolerance, impaired glucose regulation and diabetes.</p><p><b>RESULTS</b>Multiple stepwise linear regression analysis showed that adjusted by gender, SUA was positively correlated with body mass index (BMI), waist/hippo ratio, systolic blood pressure (SBP) and triglyceride, meanwhile negatively correlated with age, hemoglobin A1c, fasting insulin and MDRD. There was an increasing trend in SUA concentration and a decreasing trend in MDRD when the levels of fasting plasma glucose (FPG) increased from low to high up to the FPG level of 8.0 mmol/L; thereafter, the SUA concentration started to decrease with further increases in FPG levels, and the MDRD started to increase with further increases in FPG levels.</p><p><b>CONCLUSION</b>This study confirmed the previous finding that SUA decreased in diabetes and provided the supporting evidence that the increased MDRD might contribute to the fall of SUA.</p>

HLA-DQ, DR allele polymorphism of type 1 diabetes in the Chinese population: a meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Type 1 diabetes (T1D) is a multifactorial disease. This article aims to evaluate the relationship between allele polymorphism of HLA-DQ, DR and T1D in the Chinese population.</p><p><b>METHODS</b>The odds ratios (ORs) of HLA-DQ, DR allele distributions in patients with T1D were analyzed against healthy controls. All the relevant studies in Pubmed and CNKI were identified, and poor qualified studies were excluded. The meta-analysis software REVMAN 4.2 was applied for investigating heterogeneity among individual studies and for summarizing all the studies. The publication bias were also evaluated.</p><p><b>RESULTS</b>DQA1*0301, DQA1*0501, DQB1*0201, DQB1*0302 were the susceptible alleles (all P < 0.05) in the Chinese population, their merger ORs 2.40, 3.15, 3.66, and 2.67 respectively. DQA1*0103, DQA1*0201, DQA1*0401, DQB1*0301, DQB1*0402, DQB1*0501, DQB1*0503, DQB1*0601 and DQB1*0602 were the protective alleles (P < 0.05), their merger ORs were 0.11, 0.45, 0.30, 0.38, 0.23, 0.37, 0.25, 0.48, and 0.30 respectively. In serum level, DR3, DR4, DR9 alleles were the susceptible alleles (all P < 0.05) and their merger ORs were 5.58, 1.53, 1.66, 29.78, and 6.65 respectively. HLA-DR2, DR5, and DR7 alleles were the protective alleles (all P < 0.05) and their merger ORs were 0.39, 0.51, and 0.50. In genetic type level, DRB1*04, DRB1*0301, DRB1*0901 were the susceptible alleles (all P < 0.05) and their merger ORs were 2.19, 6.43, 1.31, 3.83, and 8.08. DRB1*07, DRB1*08, DRB1*12, DRB1*13, DRB1*14, DRB1*16, DRB1*0406 alleles were the protective alleles (all P < 0.05) and their merger ORs were 0.44, 0.27, 0.45, 0.13, 0.19, 0.40, and 0.27 respectively.</p><p><b>CONCLUSIONS</b>In the Chinese population, some HLA-DQ, DR alleles are relevant to T1D which are not totally the same as non-Chinese populations.</p>

Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Multicenter clinical study on the efficacy and safety of inhalable insulin aerosol in the treatment of type 2 diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A new inhalable insulin aerosol (Inh-Ins) was developed in China. The aim of this multicenter clinical study was to evaluate the efficacy and safety of this new Inh-Ins as a treatment of type 2 diabetes. Regular porcine insulin (RI) was used as a control.</p><p><b>METHODS</b>This study is a prospective, randomized, open-label, parallel-group multicenter clinical trial in which 253 qualified patients with type 2 diabetes received the insulin Glargine daily at bedtime plus either a pre-meal Inh-Ins or a pre-meal subcutaneous RI for 12 weeks. HbA1c, fasting plasma glucose (FPG), the 1-hour-postprandial blood glucose (1hPBG) and the 2-hour-postprandial blood glucose (2hPBG) were measured. Events were monitored for adverse effects.</p><p><b>RESULTS</b>After 12 weeks, the HbA1c decreased significantly from baseline in both treatment groups, with no significant difference between the two regimens. In the Inh-Ins group, FPG, both 1hPBG and 2hPBG significantly declined from baseline after the 8th- and 12th-weeks of treatment. The reduced values of FPG or 1hPBG between the two groups showed a more significant hypoglycemic effect with the Inh-Ins than the RI. After 12 weeks, the pulmonary carbon monoxide diffusing capacity (DLco) was significantly lower in Inh-Ins group than in the RI. The main side effects of Inh-Ins were coughing, excessive sputum, and hypoglycemia.</p><p><b>CONCLUSIONS</b>Inh-Ins was effective in decreasing HbA1c like the RI. It was better in lowering the FPG and the 1hPBG than the RI. Its main side effects were coughing, excessive sputum, and hypoglycemia. Also, Inh-Ins slightly impaired DLco.</p>

The investigation of the periodontal status of type 2 diabetes mellitus families / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the periodontal status of the family members of type 2 diabetes mellitus.</p><p><b>METHODS</b>A total of 167 subjects in 43 families of type 2 diabetes were enrolled in this study (71 male, 96 female; mean age: 49.2). Periodontal index including probing depth (PD), plaque index (PLI), bleeding index (BI), attachment loss (AL) and the numbers of tooth loss were recorded.</p><p><b>RESULTS</b>Ninety-seven diabetic patients all have periodontitis, 50 mild, 24 moderate and 23 severe periodontitis. Of 48 non-diabetic patients, there are 5 gingivitis, 30 mild, 11 moderate and 2 severe periodontitis. There is statistically significant difference in the incidence of gingivitis mild moderate and severe periodontitis between diabetic and non-diabetic patients (chi(2) = 17.96, P < 0.05). The periodontal index PD, AL and numbers of tooth loss in diabetes family members were significantly higher than those of non-diabetes family members (P < 0.05). The clinical parameters were not different between well-controlled family member and non-diabetes family member.</p><p><b>CONCLUSIONS</b>Periodontal destruction of diabetes members was more severe than that of non-diabetes members. Diabetes mellitus may be a risk factor for periodontitis.</p>

Status quo and prospects for genetic studies on type 2 diabetes / 中国医学科学院学报

Type 2 diabetes is the main type of diabetes in diabetic population. Along with the rapid changes of life style and increased life expectancy, the prevalence of type 2 diabetes increases rapidly worldwide. However, strong evidences have shown that genetic factors play important roles in the pathogenesis of type 2 diabetes, except for some rare subtypes of type 2 diabetes. The genetic patterns of the common forms of type 2 diabetes do not follow the role of classic Mendelian inheritance. Therefore, the type 2 diabetes is regarded as a complex disease caused by interaction between gene and environment. However, little progress has been made during past two decades in the genetic epidemiology of type 2 diabetes. This article reviews the current status of genetic epidemiology of type 2 diabetes and proposes strategies for future researches.