Effects of GCK,GCKR, G6PC2 and MTNR1B Variants on Glucose Metabolism and Insulin Secretion

Background

Single nucleotide polymorphisms (SNPs) from GCK, GCKR, G6PC2 and MTNR1B were found to modulate the fasting glucose levels. The current study aimed to replicate this association in the Chinese population and further analyze their effects on biphasic insulin secretion.

Methods/Principal Findings

SNPs from GCK, GCKR, G6PC2 and MTNR1B were genotyped in the Shanghai Chinese, including 3,410 type 2 diabetes patients and 3,412 controls. The controls were extensively phenotyped for the traits related to glucose metabolism and insulin secretion. We replicated the association between GCK rs1799884, G6PC2 rs16856187 and MTNR1B rs10830963 and fasting glucose in our samples (p = 0.0003∼2.0×10⁻⁸). GCK rs1799884 and G6PC2 rs16856187 showed association to HOMA-β, insulinogenic index and both first- and second-phases insulin secretion (p = 0.0030∼0.0396). MTNR1B rs10830963 was associated to HOMA-β, insulinogenic index and first-phase insulin secretion (p = 0.0102∼0.0426), but not second-phase insulin secretion (p = 0.9933). Combined effect analyses showed individuals carrying more risk allele for high fasting glucose tended to have a higher glucose levels at both fasting and 2 h during OGTTs (p = 1.7×10⁻¹³ and 0.0009, respectively), as well as lower HOMA-β, insulinogenic index and both first- and second-phases insulin secretion (p = 0.0321∼1.1×10⁻⁷).

Conclusions/Significance

We showed that SNPs from GCK, G6PC2 and MTNR1B modulated the fasting glucose levels in the normoglycaemic population while SNPs from G6PC2 and GCKR was associated with type 2 diabetes. Moreover, we found GCK and G6PC2 genetic variants were associated to both first- and second-phases insulin secretion while MTNR1B genetic variant was associated with first-phase insulin secretion, but not second-phase insulin secretion.     

Common Polymorphisms in MTNR1B,G6PC2 and GCK Are Associated with Increased Fasting Plasma Glucose and Impaired Beta-Cell Function in Chinese Subjects

Background

Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts.

Methodology/Principal Findings

Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6×10⁻⁵) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P = 0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P = 2.9×10⁻⁹) and reduced HOMA-B (P = 1.1×10⁻³). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG.

Conclusions/Significance

Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals.     

Effect of Chromium-Enriched Yeast on Fasting Plasma Glucose, Glycated Haemoglobin and Serum Lipid Levels in Patients with Type 2 Diabetes Mellitus Treated with Insulin

Chromium is required for a normal insulin function, and low levels have been linked with insulin resistance. The aim of this study was to follow the effect of chromium supplementation on fasting plasma glucose (FPG), glycated haemoglobin (HbA_1c) and serum lipids in patients with type 2 diabetes mellitus (DM2) on insulin therapy. Eleven randomly selected patients with DM2 on insulin therapy were supplemented with a daily dose of 100 μg chromium yeast for the first supplementation period of 2 weeks. In the second supplementation period, the chromium dose was doubled and continued for the next 6 weeks. The third phase was a 6-week washout period. After each period, the levels of FPG and HbA_1c were compared with the corresponding values at the end of the previous period. Serum triglycerides, total HDL and LDL cholesterol values after supplementation were compared with the baseline values. FPG decreased significantly after the first period of chromium supplementation (p?<?0.001), and a tendency to a further reduction was observed after the second supplementation period. Similarly, HbA_1c decreased significantly in both periods (p?<?0.02 and p?<?0.002, respectively). Eight weeks after withdrawal of chromium supplementation, both FPG and HbA_1c levels returned to their pre-intervention values. The serum lipid concentrations were not significantly influenced by chromium supplementation. Chromium supplementation could be beneficial in patients with DM2 treated with insulin, most likely due to lowered insulin resistance leading to improved glucose tolerance. This finding needs to be confirmed in a larger study.     

Short-Term Stability in Refractive Status Despite Large Fluctuations in Glucose Levels in Diabetes Mellitus Type 1 and 2

Purpose

This work investigates how short-term changes in blood glucose concentration affect the refractive components of the diabetic eye in patients with long-term Type 1 and Type 2 diabetes.

Methods

Blood glucose concentration, refractive error components (mean spherical equivalent MSE, J0, J45), central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (LT), axial length (AL) and ocular aberrations were monitored at two-hourly intervals over a 12-hour period in: 20 T1DM patients (mean age ± SD) 38±14 years, baseline HbA1c 8.6±1.9%; 21 T2DM patients (mean age ± SD) 56±11 years, HbA1c 7.5±1.8%; and in 20 control subjects (mean age ± SD) 49±23 years, HbA1c 5.5±0.5%. The refractive and biometric results were compared with the corresponding changes in blood glucose concentration.

Results

Blood glucose concentration at different times was found to vary significantly within (p<0.0005) and between groups (p<0.0005). However, the refractive error components and ocular aberrations were not found to alter significantly over the day in either the diabetic patients or the control subjects (p>0.05). Minor changes of marginal statistical or optical significance were observed in some biometric parameters. Similarly there were some marginally significant differences between the baseline biometric parameters of well-controlled and poorly-controlled diabetic subjects.

Conclusion

This work suggests that normal, short-term fluctuations (of up to about 6 mM/l on a timescale of a few hours) in the blood glucose levels of diabetics are not usually associated with acute changes in refractive error or ocular wavefront aberrations. It is therefore possible that factors other than refractive error fluctuations are sometimes responsible for the transient visual problems often reported by diabetic patients.     

C-Peptide Level in Fasting Plasma and Pooled Urine Predicts HbA1c after Hospitalization in Patients with Type 2 Diabetes Mellitus

In this study, we investigate how measures of insulin secretion and other clinical information affect long-term glycemic control in patients with type 2 diabetes mellitus. Between October 2012 and June 2014, we monitored 202 diabetes patients who were admitted to the hospital of Asahi Life Foundation for glycemic control, as well as for training and education in diabetes management. We measured glycated hemoglobin (HbA1c) six months after discharge to assess disease management. In univariate analysis, fasting plasma C-peptide immunoreactivity (F-CPR) and pooled urine CPR (U-CPR) were significantly associated with HbA1c, in contrast to ΔCPR and C-peptide index (CPI). This association was strongly independent of most other patient variables. In exploratory factor analysis, five underlying factors, namely insulin resistance, aging, sex differences, insulin secretion, and glycemic control, represented patient characteristics. In particular, insulin secretion and resistance strongly influenced F-CPR, while insulin secretion affected U-CPR. In conclusion, the data indicate that among patients with type 2 diabetes mellitus, F-CPR and U-CPR may predict improved glycemic control six months after hospitalization.     

Serum Trace Elements and Electrolytes Are Associated with Fasting Plasma Glucose and HbA<Subscript>1c</Subscript> in Postmenopausal Women with Type 2 Diabetes Mellitus

The primary aim of the research was to assess the level of trace elements and electrolytes in serum of postmenopausal diabetic women. Sixty-four postmenopausal women with type 2 diabetes mellitus (DM2) and 64 age- and body mass index-matched controls were examined. Serum trace elements were assessed using inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). Fasting plasma glucose (FPG) and glycated hemoglobin (HbA_1c) levels were evaluated using Randox kits. The obtained data demonstrate that DM2 patients were characterized by 42 and 34 % higher FPG and HbA_1c levels, respectively (p < 0.001). The level of Cu and Se in diabetic postmenopausal women was increased by 10 and 15 % in comparison to the respective control values (p = 0.002 and <0.001). Serum Mn, Zn, and Ni concentrations were lower than the control ones by 32 % (p = 0.003), 8 % (p = 0.003), and 23 % (p = 0.046), respectively. FPG and HbA_1c levels directly correlated with serum Se (p < 0.001) and Cu (p = 0.014 and p = 0.028) concentrations and inversely related to Zn (p < 0.001) and Tl (p = 0.023 and p = 0.029) levels. Multiple regression analysis demonstrated a significant association between serum Zn and Se and FPG and HbA_1c levels. It is proposed that Zn and Se play an important role in DM2 pathogenesis. Further studies are required to assess the intimate mechanisms of the observed differences.     

The Association between HbA1c,Fasting Glucose, 1-Hour Glucose and 2-Hour Glucose during an Oral Glucose Tolerance Test and Cardiovascular Disease in Individuals with Elevated Risk for Diabetes

Objective

To determine the association between HbA1c, fasting plasma glucose (FPG), 1-hour (1 hPG) and 2-hour (2 hPG) glucose after an oral glucose tolerance test (OGTT) and cardiovascular disease in individuals with elevated risk for diabetes.

Design

We studied the relationship between baseline, updated mean and updated (last) value of HbA1c, FPG, 1 hPG and 2 hPG after an oral 75 g glucose tolerance test (OGTT) and acute CVD events in 504 individuals with impaired glucose tolerance (IGT) at baseline enrolled in the Finnish Diabetes Prevention Study.

Setting

Follow-up of clinical trial.

Participants

504 individuals with IGT were followed with yearly evaluations with OGTT, FPG and HbA1c.

Main Outcome Measure

Relative risk of CVD.

Results

Over a median follow-up of 9.0 years 34 (6.7%) participants had a CVD event, which increased to 52 (10.3%) over a median follow-up of 13.0 years when including events that occurred among participants following a diagnosis of diabetes. Updated mean HbA1c, 1 hPG and 2 hPG, HR per 1 unit SD of 1.57 (95% CI 1.16 to 2.11), p = 0.0032, 1.51 (1.03 to 2.23), p = 0.036 and 1.60 (1.10 to 2.34), p = 0.014, respectively, but not FPG (p = 0.11), were related to CVD. In analyses of the last value prior to the CVD event the same three glycaemic measurements were associated with the CVD events, with HRs per 1 unit SD of 1.45 (1.06 to 1.98), p = 0.020, 1.55 (1.04 to 2.29), p = 0.030 and 2.19 (1.51 to 3.18), p<0.0001, respectively but only 2 hPG remained significant in pairwise comparisons. Including the follow-up period after diabetes onset updated 2 hPG (p = 0.003) but not updated mean HbA1c (p = 0.08) was related to CVD.

Conclusions and Relevance

Current 2 hPG level in people with IGT is associated with increased risk of CVD. This supports its use in screening for prediabetes and monitoring glycaemic levels of people with prediabetes.     

Plasma Adiponectin Levels in High Risk African‐Americans with Normal Glucose Tolerance,Impaired Glucose Tolerance,and Type 2 Diabetes**

Objective: We studied plasma adiponectin, insulin sensitivity, and insulin secretion before and after oral glucose challenge in normal glucose tolerant, impaired glucose tolerant, and type 2 diabetic first degree relatives of African‐American patients with type 2 diabetes. Research Methods and Procedures: We studied 19 subjects with normal glucose tolerance (NGT), 8 with impaired glucose tolerance (IGT), and 14 with type 2 diabetes. Serum glucose, insulin, C‐peptide, and plasma adiponectin levels were measured before and 2 hours after oral glucose tolerance test. Homeostasis model assessment‐insulin resistance index (HOMA‐IR) and HOMA‐β cell function were calculated in each subject using HOMA. We empirically defined insulin sensitivity as HOMA‐IR < 2.68 and insulin resistance as HOMA‐IR > 2.68. Results: Subjects with IGT and type 2 diabetes were more insulin resistant (as assessed by HOMA‐IR) when compared with NGT subjects. Mean plasma fasting adiponectin levels were significantly lower in the type 2 diabetes group when compared with NGT and IGT groups. Plasma adiponectin levels were 2‐fold greater (11.09 ± 4.98 vs. 6.42 ± 3.3811 μg/mL) in insulin‐sensitive (HOMA‐IR, 1.74 ± 0.65) than in insulin‐resistant (HOMA‐IR, 5.12 ± 2.14) NGT subjects. Mean plasma adiponectin levels were significantly lower in the glucose tolerant, insulin‐resistant subjects than in the insulin sensitive NGT subjects and were comparable with those of the patients with newly diagnosed type 2 diabetes. We found significant inverse relationships of adiponectin with HOMA‐IR (r = ?0.502, p = 0.046) and with HOMA‐β cell function (r = ?0.498, p = 0.042) but not with the percentage body fat (r = ?0.368, p = 0.063), serum glucose, BMI, age, and glycosylated hemoglobin A1C (%A1C). Discussion: In summary, we found that plasma adiponectin levels were significantly lower in insulin‐resistant, non‐diabetic first degree relatives of African‐American patients with type 2 diabetes and in those with newly diagnosed type 2 diabetes. We conclude that a decreased plasma adiponectin and insulin resistance coexist in a genetically prone subset of first degree African‐American relatives before development of IGT and type 2 diabetes.     

胰升血糖素样肽-1及其受体与 2 型糖尿病的治疗

胰岛素对治疗 2 型糖尿病有一定效果,但长期使用会引起低血糖反应;双胍类药物降糖疗效显著,但会引起消化道不良反应 . 因此,寻找一种安全有效的药物是 2 型糖尿病治疗的当务之急 . 胰升血糖素样肽-1 作为一种胰岛素分泌促进剂和胰岛素增敏剂越来越受人们的关注,将它用于治疗糖尿病不会产生低血糖,对 1 型和 2 型糖尿病都有疗效 . 讨论胰升血糖素样肽-1及其受体的最新研究状况 .     

Association between the Melatonin Receptor 1B Gene Polymorphism on the Risk of Type 2 Diabetes,Impaired Glucose Regulation: A Meta-Analysis

Background

Melatonin receptor 1B (MTNR1B) belongs to the seven-transmembrane G protein-coupled receptor superfamily involved in insulin secretion, which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) since it was first identified as a loci associated with fasting plasma glucose level through genome wide association approach. The relationship between MTNR1B and T2D has been reported in various ethnic groups. The aim of this study was to consolidate and summarize published data on the potential of MTNR1B polymorphisms in T2D risk prediction.

Methods

PubMed, EMBASE, ISI web of science and the CNKI databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Heterogeneity and publication bias were also tested.

Results

A total of 23 studies involving 172,963 subjects for two common polymorphisms (rs10830963, rs1387153) on MTNR1B were included. An overall random effects per-allele OR of 1.05 (95% CI: 1.02–1.08; P<10⁻⁴) and 1.04 (95% CI: 0.98–1.10; P = 0.20) were found for the two variants respectively. Similar results were also observed using dominant or recessive genetic model. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. Significant results were found in Caucasians when stratified by ethnicity; while no significant associations were observed in East Asians and South Asians. Besides, we found that the rs10830963 polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility.

Conclusions

This meta-analysis demonstrated that the rs10830963 polymorphism is a risk factor for developing impaired glucose regulation and T2D.     

Effect of Hemodialysis on Plasma Glucose Profile and Plasma Level of Liraglutide in Patients with Type 2 Diabetes Mellitus and End-Stage Renal Disease: A Pilot Study

The effect of hemodialysis on the plasma glucose profile and liraglutide level after liraglutide injection was investigated in patients with diabetes and end-stage renal disease (ESRD). Either 0.6 mg or 0.9 mg liraglutide was subcutaneously administered daily to 10 Japanese type 2 diabetic patients with ESRD. Hemodialysis was conducted on days 1 and 3. Plasma liraglutide and glucose concentrations were measured by enzyme-linked immunosorbent assay and a continuous glucose monitoring system, respectively. The safety profile of liraglutide was also assessed. Hemodialysis had no effect on the pharmacokinetic parameters of liraglutide in patients with diabetes and ESRD; the maximum plasma concentration (C_max), t_max, area under the concentration-time curve (AUC), and CL/f were unaltered. Similarly, hemodialysis did not affect the mean or minimum glucose levels, AUC, or duration of hyperglycemia (>180 mg/dL) and hypoglycemia (<70 mg/dL) following liraglutide administration. However, significant increases in mean amplitude of glycemic excursions (MAGE) and standard deviation (SD) as markers of glucose fluctuation, and the maximum glucose level were observed during hemodialysis. No adverse events, including hypoglycemia, were observed after liraglutide injection, either off-hemodialysis (day 2) or on-hemodialysis (day 3). Liraglutide was well tolerated in patients with type 2 diabetes and ESRD undergoing hemodialysis. The present results suggested that hemodialysis did not affect the pharmacokinetic profile of liraglutide or most glycemic indices, with the exception of MAGE, SD, and the maximum glucose level. These results suggested that it may be possible to use liraglutide during hemodialysis for diabetes with ESRD, without dose adjustment. Trial Registration UMIN Clinical Trials Registry (UMIN-CTR) UMIN000010159     

Effect of Probiotic Soy Milk on Serum Levels of Adiponectin,Inflammatory Mediators,Lipid Profile,and Fasting Blood Glucose Among Patients with Type II Diabetes Mellitus

Probiotic therapies are going to be an effective alternative therapeutic strategy in the treatment and management of diabetes. The mechanism behind the essential effects of probiotic therapies in diabetic patients was not fully understood. The objective of this study was to evaluate the effects of probiotic soy milk containing Lactobacillus planetarum A7 on inflammation, lipid profile, fasting blood glucose, and serum adiponectin among patients with type 2 diabetes mellitus. Forty patients with type 2 diabetes, at the age of 35–68 years old, were assigned to two groups in this randomized, double-blind, controlled clinical trial. The patients in the intervention group consumed 200 ml/day of probiotic soy milk containing L. planetarum A7 and those in control group consumed 200 ml/day of pure soy milk for 8 weeks. Serum TNF-α, C reactive protein, adiponectin, lipid profile, and fasting blood glucose were determined before and after intervention. In intervention group, serum adiponectin in pre- and post-treatment did not show any significant changes (2.52 ± 0.74 vs 2.84 ± 0.61, P = 0.658), as well as changes in serum TNF-α and C reactive protein (172.44 ± 5.7 vs 172.83 ± 7.6, P = 0.278, 4.2 ± 1.4 vs 4.5 ± 1.9, P = 0.765, respectively). Low-density cholesterol and high-density cholesterol changed significantly (P = 0.023, P = 0.017, respectively), but fasting blood glucose did not show any significant changes. The results of this study showed that consumption of probiotic soy milk and soy milk has no effect on serum adiponectin and inflammation, but it can change lipid profile among type 2 diabetic patients.     

Asthma,Type 1 and Type 2 Diabetes Mellitus,and Inflammatory Bowel Disease amongst South Asian Immigrants to Canada and Their Children: A Population-Based Cohort Study

BACKGROUND

There is a high and rising rate of immune-mediated diseases in the Western world. Immigrants from South Asia have been reported to be at higher risk upon arrival to the West. We determined the risk of immune-mediated diseases in South Asian and other immigrants to Ontario, Canada, and their Ontario-born children.

METHODS

Population-based cohorts of patients with asthma, type 1 diabetes (T1DM), type 2 diabetes (T2DM), and inflammatory bowel disease (IBD) were derived from health administrative data. We determined the standardized incidence, and the adjusted risk of these diseases in immigrants from South Asia, immigrants from other regions, compared with non-immigrant residents of Ontario. The risk of these diseases in the Ontario-born children of immigrants were compared to the children of non-immigrants.

RESULTS

Compared to non-immigrants, adults from South Asia had higher risk of asthma (IRR 1.56, 95%CI 1.51-1.61) and T2DM (IRR 2.59, 95%CI 2.53-2.65). Adults from South Asia had lower incidence of IBD than non-immigrants (IRR 0.32, 95%CI 0.22-0.49), as did immigrants from other regions (IRR 0.29, 95%CI 0.20-0.42). Compared to non-immigrant children, the incidence of asthma (IRR 0.66, 95%CI 0.62-0.71) and IBD (IRR 0.47, 95%CI 0.33-0.67) was low amongst immigrant children from South Asia. However, the risk in Ontario-born children of South Asian immigrants relative to the children of non-immigrants was higher for asthma (IRR 1.75, 95%CI 1.69-1.81) and less attenuated for IBD (IRR 0.90, 95%CI 0.65-1.22).

CONCLUSION

Early-life environmental exposures may trigger a genetic predisposition to the development of asthma and IBD in South Asian immigrants and their Canada-born children.     

2型糖尿病患者APPL1、AFABP与胰岛素抵抗指数的相关性研究

目的:分析2型糖尿病(T2DM)患者磷酸酪氨酸衔接蛋白(APPL1)、脂肪细胞型脂肪酸结合蛋白(AFABP)与稳态模型评估胰岛素抵抗指数(HOMA-IR)的相关性。方法:选择2015年6月~2016年5月至我院就诊T2DM患者100例作为患病组,选取同期在我院健康体检者100例作为健康组,对研究对象进行指标如空腹血糖(FPG)、空腹血清胰岛素(FINS)、糖化血红蛋白(Hb A1c)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、APPL1、AFABP等检测,并根据公式计算HOMA-IR、及体重指数(BMI),分析APPL1、AFABP与各指标相关性。结果:患病组与健康组TC、HDL、LDL水平无明显差异(P0.05),患病组BMI、FPG、FINS、Hb A1c、TG、HOMA-IR、APPL1、AFABP与健康组比较明显较高(P0.05);APPL1与BMI、FINS、Hb A1c、HOMA-IR呈负相关性(P0.05),与FPG呈正相关性;AFABP与BMI、FPG、FINS、Hb A1c、HOMA-IR呈正相关性(P0.05)。结论:T2DM患者APPL1、AFABP较高,APPL1、AFABP与HOMA-IR呈直线相关性,表明APPL1、AFABP与T2DM患者胰岛素抵抗密切相关,该研究为APPL1、AFABP可以作为T2DM治疗的新靶点提供了理论依据。     

UCP-866G/A和ADIPQ+45T/G基因多态性的交互作用与2型糖尿病 合并冠心病发病风险的关系

目的：探讨UCP2-866G/A 和ADIPOQ+45T/G 基因多态性的交互作用与2型糖尿病合并冠心病发病风险的关系。方法：随机 选取2014 年10 月至2015 年5 月在佳木斯大学附属第一医院就诊的130 例单纯2 型糖尿病患者和128 例2 型糖尿病合并冠心 病患者进行病例对照研究。分别采用聚合酶链反应- 限制性片段长度多态性（PCR-RFLP）方法和聚合酶链反应- 高分辨率溶解曲 线（PCR-HRM）方法检测UCP2-866G/A 和ADIPOQ+45T/G 的基因多态性,并用非条件Logistic 回归分析两基因间的交互作用。 结果：在两组间分别进行UCP2-866G/A 和ADIPOQ+45T/G 基因多态性的单独关联分析,两变异位点的基因型和等位基因的频率 在两组间的分布及遗传模型关联分析均无统计学差异（P>0.05）。两变异位点联合分析发现,UCP2-866 G/A 的GG、GA 分别和 ADIPOQ+45T/G 的TG 在2 型糖尿病合并冠心病中存在正向交互作用（P=0.000,ORI=ORAB/(ORA× ORB)=30.533/(0.549× 0.116) >1;P=0.007,ORI= ORAB/(ORA× ORB)=13.914/(0.525× 0.116)>1。结论：该研究显示： UCP-866G/A 和ADIPOQ+ 45T/G 单一基因的 多态性与2 型糖尿病合并冠心病患病风险无关,而两者之间的交互作用可能增加2 型糖尿病合并冠心病的发病风险。     

Plasma 6-keto-PGF1 alpha, thromboxane B2 and PGE2 during diabetic ketoacidosis

In 10 patients admitted to hospital with diabetic ketoacidosis plasma prostanoids 6-keto-PGF alpha, thromboxane B2 and PGE2 were studied before treatment and following recovery. During ketoacidosis the median plasma 6-keto-PGF1 alpha and PGE2 were significantly increased compared to those of a normal reference group: 5.2 pg/ml and 3.9 pg/ml versus 1.7 pg/ml and 0.4 pg/ml (p less than 0.01 and p less than 0.05). In response to therapy both prostanoids decreased significantly towards a normal level, 6-keto-PGF1 alpha: 0.5 pg/ml p less than 0.01 and PGE2: 0.08 p less than 0.05 respectively. The changes in plasma 6-keto-PGF1 alpha were negatively correlated to changes in pH, rho: -0.7788 p = 0.0135, whereas the changes in PGE2 were positively correlated to serum creatinine at admittance, rho: 0.6976, p = 0.0368 and to the amount of intravenous fluid and insulin used during treatment, rho: 0.7500 p = 0.0126 and rho: 0.8424, p = 0.0023 respectively. Plasma thromboxane B2 concentrations were not elevated and did not change after treatment of the ketoacidosis.     

GLP-1 受体激动剂联合门冬胰岛素30 对2 型糖尿病患者控糖效果及体重的影响

目的:探讨胰高血糖素样肽-1(GLP-1)受体激动剂联合门冬胰岛素30对2型糖尿病患者控糖效果及体重的影响。方法:选取116例2型糖尿病患者为研究对象,随机数字表法分成研究组(A组,n=58)和对照组(B组,n=58)两组。B组予以门冬胰岛素30治疗方案,A组则采用门冬胰岛素30联合利拉鲁肽治疗方案,均持续治疗24周后观察疗效。比对两组患者治疗前后控糖指标、脂质生化指标及体重指数(BMI)等变化情况,记录其甲级血糖控制率、血糖总控制率及低血糖发生率差异。结果:1治疗6个月后,两组患者除HDL-C水平较治疗前对比无统计学意义(P0.05)外,FBG、2 h PG、Hb A1c等控糖指标,TG、TC、LDL-C等脂质生化指标及BMI水平均较治疗前显著降低,其中A组降幅大于B组,差异具有统计学意义(P0.05);2A组甲级控制率及血糖总控制率分别为70.7%和100.0%,均显著高于B组的37.9%和93.1%(P0.05);3两组患者治疗期间均无严重不良反应及严重低血糖事件发生,其中A组轻微低血糖发生率为6.9%(4/58),显著低于B组的24.1%(14/58),差异具有统计学意义(P0.05)。结论:将门冬胰岛素30联合GLP-1受体激动剂方案应用于2型糖尿病患者的临床治疗中,疗效确切,血糖控制效果良好,能有效改善其血脂水平、抑制体重发展,于患者预后提升有利。     

Hepatic Insulin-Positive Cells and Major Transcription Factors (PDX1, MAFA,NGN3) in Rat Models of Type 1 and Type 2 Diabetes Mellitus

Journal of Evolutionary Biochemistry and Physiology - Due to a high occurrence of diabetes mellitus (DM) and its complications, insulin-positive cells detected in different organs are of great...     

Increased Plasma Manganese, Partially Reduced Ascorbate,1 and Absence of Mitochondrial Oxidative Stress in Type 2 Diabetes Mellitus: Implications for the Superoxide Uncoupling Protein 2 (Ucp-2) Pathway

Oxidative stress is an important component of diabetes and its complications. Manganese (Mn), the key component of the Mitochondrial antioxidant (MnSOD), plays a key role in the superoxide uncoupling protein 2 (UCP-2) pathway in inhibiting of glucose-stimulated insulin secretion (GSIS). The interactions of Mn with ascorbate and other components of this pathway have not been defined in type-2 diabetes. Fifty established type 2 diabetics (30 males, 20 females) and 30 non-diabetics (controls; 18 males, 12 females) matched for age and sex were investigated. Dietary intake, particularly of micronutrients as assessed by 24-h dietary recall was similar between diabetics and controls. Weight and height of all subjects were determined and body mass index (BMI) computed after clinical assessment. Fasting plasma glucose, manganese, ascorbic acid, creatinine and K⁺ levels were determined; K⁺ was to assess the K⁺ channels, whereas creatinine was to assess probability of oxidative stress nephropathy. Body mass index was greater in DM than in controls (p < 0.001). Fasting plasma glucose and Mn levels (p < 0.00 and p < 0.01, respectively) were higher in diabetes than in the controls. Manganese level was greater than twice the levels in controls. Ascorbic acid was not significantly different (p > 0.05), but was 50% lower than the level in non-diabetics. Potassium like Mn and glucose was significantly higher in diabetes mellitus (DM) than in controls (p < 0.001). Creatinine was not significantly different between diabetics and controls (p > 0.05). Correlations among all parameters were not significantly different. These findings suggest absence of significant oxidative stress in the mitochondria, probably excluding a role for UCP-2-superoxide pathway in the inhibition of glucose-stimulated insulin secretion (GSIS), calling for caution in the precocious conclusion that interruption of UCP-2 activity may provide a viable strategy to improve β-cell dysfunction in type 2 diabetes mellitus.