Impact of ENPP1 K121Q on Change of Insulin Resistance after Web-Based Intervention in Korean Men with Diabetes and Impaired Fasting Glucose

Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been studied in relation to type 2 diabetes mellitus (T2DM) and insulin resistance (IR). We hypothesized that the difference in genotype may be one of the factors that affect the outcome of intervention. We genotyped 448 men with fasting glucose≥5.6 mM/L, including 371 in subjects with K allele (KK) (69 control group [CG]; and 302 intervention group [IG]) and 77 in subjects with Q allele (KQ+QQ) (13 CG and 64 IG). The web-based intervention based on a lifestyle modification was delivered by e-mail once a month for 10 months. In the KK, IG demonstrated significantly decreased levels of fasting serum insulin (FSI) as compared to CG and homeostasis model of assessment of insulin resistance (HOMA-IR). In the KQ+QQ IG group, hemoglobin A1c (HbA1c), FSI and HOMA-IR were significantly decreased, and showed further reduction in the HOMA-IR than KQ+QQ CG. After analysis of covariance, K121Q did significantly influence the change of HbA1c in CG after appropriate adjustment. In a multivariate model, BMI change predicted HOMA-IR change (adjusted β=0.801; P=0.022) in KK IG subjects with T2DM. ENPP1 K121Q did not influence the change in IR. However, individuals with T2DM carrying the K121 variant are very responsive to the effect of BMI reduction on HOMA-IR.

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Genetic analysis of the ELOVL6 gene polymorphism associated with type 2 diabetes mellitus

Recent animal studies have indicated that overexpression of the elongation of long-chain fatty acids family member 6 (Elovl6) gene can cause insulin resistance and β-cell dysfunction. These are the major factors involved in the development of type 2 diabetes mellitus (T2DM). To identify the relationship between single nucleotide polymorphisms (SNP) of ELOVL6 and T2DM pathogenesis, we conducted a case-control study of 610 Han Chinese individuals (328 newly diagnosed T2DM and 282 healthy subjects). Insulin resistance and islet first-phase secretion function were evaluated by assessment of insulin resistance in a homeostasis model (HOMA-IR) and an arginine stimulation test. Three SNPs of the ELOVL6 gene were genotyped with polymerase chain reaction-restriction fragment length polymorphism, with DNA sequencing used to confirm the results. Only genotypes TT and CT of the ELOVL6 SNP rs12504538 were detected in the samples. Genotype CC was not observed. The T2DM group had a higher frequency of the C allele and the CT genotype than the control group. Subjects with the CT genotype had higher HOMA-IR values than those with the TT genotype. In addition, no statistical significance was observed between the genotype and allele frequencies of the control and T2DM groups for SNPs rs17041272 and rs6824447. The study indicated that the ELOVL6 gene polymorphism rs12504538 is associated with an increased risk of T2DM, because it causes an increase in insulin resistance.     

2型糖尿病合并非酒精性脂肪肝的危险因素研究

探讨2型糖尿病合并非酒精性脂肪肝的危险因素。方法 选择2017年1月~12月在我院住院的T2DM患者138例,根据是否合并NAFLD分为两组,合并NAFLD的86例患者设为观察组,52例单纯T2DM设为对照组。比较两组一般临床资料及生化指标,采用回归分析判定其中的独立相关的主要危险因素和（或）保护性因素。结果 两组患者BMI、收缩压、糖化血红蛋白、甘油三酯、高密度脂蛋白、低密度脂蛋白、尿酸、同型半胱氨酸、胰岛素抵抗指数等指标比较,差异有统计学意义（P≤0.05）;将上述有差异指标进行二元Logistic回归分析发现,BMI、TG、SUA、HbA1c、HOMA-IR与T2DM合并NAFLD呈正相关（OR＞1,P＜0.05）,HDL-C与T2DM合并NAFLD呈负相关（OR＜1,P≤0.05）。结论 T2DM合并NAFLD相当常见,BMI、HOMA-IR、HbA1c、TG、SUA是其危险因素,HDL-C 是其保护因素。胰岛素抵抗在并发NAFLD的T2DM者中更加明显。     

Retinol binding protein 4 correlates with and is an early predictor of carotid atherosclerosis in type 2 diabetes mellitus patients

The association of retinol binding protein 4 (RBP4) with atherosclerosis of the carotid artery in type 2 diabetes mellitus (T2DM) remains undefined. We aimed to investigate the correlation of RBP4 expression with atherosclerosis of the carotid artery in T2DM. A total of 1,076 subjects were investigated for intima-media thickness of the bilateral common carotid arteries, and they were divided into three groups: in group I, patients had normal neck vascular ultrasound, in group II, intimal carotid artery media thickness was equal to or more than 1 mm, and in group III, carotid artery plaque was present. Height, weight, blood pressure (BP), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (apoA-1), apolipoprotein B (apoB) and lipoprotein (a) [Lp(a)] were determined by routine laboratory methods. RBP4 and high sensitivity C reactive protein (HsCRP) were measured by an enzyme-linked immuno-sorbent assay, and insulin concentration was measured by an electrochemiluminescence sandwich immunoassay. Duration of diabetes, waist and BP, FPG, HbA1c, TG, TC, LDL-C, APOB, Lp(a), HsCRP, RBP4 and homeostasis model assessment insulin resistance index (HOMA-IR) were significantly lower in group I than in the other two groups (P<0.01, P<0.01). Plasma levels of HbA1c, RBP4, LDL-C, TC, HOMA-IR, HsCRP and Lp(a), waist and BP were significantly increased in group III than in group II (P<0.01). Multivariate logistic regression analysis showed that there were seven factors associated with the occurrence of carotid artery atherosclerosis and its risks in descending order were: high LDL-C, high waist, high HsCRP, duration of diabetes, high HOMA-IR, HbA1c and high RBP4. Our finding supported that RBP4 was positively correlated with carotid atherosclerosis in patients with T2DM and could be used as an early predictor of cardiovascular disease.     

IRS2基因G1057D变异与中国汉族人肥胖型2型糖尿病的相关性

目的 研究IRS2基因G1057D突变与中国汉族人2型糖尿病（type 2 diabetes mellitus，T2DM）的相关性。方法 选取辽宁汉族人T2DM组218例，健康对照组221名，各分为肥胖和非肥胖两个亚组。应用聚合酶链反应-限制性片段长度多态性方法筛查IRS2 G1057D突变并探讨与T2DM的相关性。结果 （1）IRS2 G1057D总突变频率为29％。非肥胖DM组DD型频率显著低于非肥胖对照组，Logistic回归分析显示DD型OR值为0．265；而肥胖DM组DD型频率则显著高于肥胖对照组，Logistic回归分析显示DD型的OR值为3．991。（2）在非肥胖亚组：DM组DD型的WHR高于同组GG型（P〈0．01）；对照组DD型的FPG及2hCP低于同组GG型（P〈0．05，P〈0．01），HOMA-B高于同组GG型（P〈0．01）。在肥胖亚组：DM组DD型的WHR、HOMA-IR及2hPG、2hINS、2hCP均高于同组GG型，HOMA-B低于同组GG型；对照组DD型的WHR、2hINS、HOMA-IR及HOMA-B也分别高于及低于同组GG型（均P〈0．05）。结论 IRS2基因G1057D突变以肥胖为中介与他DM相关联。     

Association between plasma IL-6, the IL6 -174G>C gene variant and the metabolic syndrome in type 2 diabetes mellitus

Elevated plasma interleukin-6 (IL-6) is associated with coronary heart disease (CHD), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM). We and others have described an association between the human interleukin-6 -174G>C gene variant and body mass index (BMI). Within our previous sample of subjects with T2DM, we measured plasma IL-6 and grouped subjects by the WHO-defined metabolic syndrome, in order to study the association between the -174G>C gene variant, plasma IL-6 and the metabolic syndrome (and component parts). Genotype was obtained in 571 Caucasian subjects with plasma IL-6 measures. There was a significant association between genotype and plasma IL-6 (GG vs GC vs CC: 3.23+/-0.93 pg/ml vs 3.42+/-0.95 pg/ml vs 4.16+/-1.18 pg/ml, p=0.02; for GG/GC vs CC p=0.008). No interactions were observed between genotype and the individual components of the metabolic syndrome in determining plasma IL-6. Increased plasma IL-6 was also associated with the number of components (none vs 1 vs 2 vs > or =3: 2.67+/-0.71 pg/ml vs 2.97+/-0.94 pg/ml vs 4.07+/-1.13 pg/ml, p<0.0001). Within the sample, 76% of CC compared to 56% of GG subjects had the metabolic syndrome (p=0.007). Further analysis of association between the genotype and the components of the metabolic syndrome revealed no further associations than that with BMI previously described. The association of this gene variant with the metabolic syndrome is intimately linked with obesity per se. Further prospective work is required to explore the effect of this gene variant in relation to obesity, the metabolic syndrome and 'prediabetes'.     

Association of PD-L1 gene rs4143815 C>G polymorphism and human cancer susceptibility: A systematic review and meta-analysis

Programmed death ligand 1(PD-L1) mediated immune escape play important roles in the development of cancer. The gene polymorphism of PD-L1, in particular rs4143815 C?>?G, has been associated with the cancer risks, but with conflicting results. Therefore, this meta-analysis was aimed to assess the association between rs4143815 C?>?G and cancer susceptibility. A systematic literature search was performed to select the studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Eleven eligible studies containing 3711 cases and 3704 controls were enrolled in the meta-analysis. The results suggested that there is a strong association between rs4143815 C?>?G and the cancer risks (G vs. C: OR?=?1.386, 95% CI: 1.132–1.696, p?=?0.002; GG vs. CG?+?CC: OR?=?1.843 95% CI: 1.300–2.613, p?=?0.002; GG?+?CG vs. CC: OR?=?1.280, 95% CI: 1.040–1.576, p?=?0.020). Subgroup analysis based on cancer type suggested that PD-L1 rs4143815 C?>?G might increase the susceptibility to gastric cancer (G vs. C: OR?=?1.842, 95% CI: 1.403–2.418, p?<?0.001) and bladder cancer (G vs. C: OR?=?2.015, 95% CI: 1.556–2.608, p?<?0.001), and genotype GG carriers of PD-L1 rs4143815 C?>?G might have higher risks of HCC (GG vs. CG?+?CC: OR?=?2.226 95% CI: 1.562–3.172, p?<?0.001). PD-L1 rs4143815 C?>?G might confer an increased cancer risk, indicating this SNP may contribute to the pathogenesis of cancer and might be used as a potential biomarker to predict the susceptibility to cancer.     

不同浓度糖化血红蛋白及空腹血糖的2型糖尿病患者β-羟丁酸水平变化分析

目的:观察2型糖尿病(T2DM)患者不同糖化血红蛋白(HbA1c)及空腹血糖(FBG)水平时β-羟丁酸(β-HBA)血清水平的变化。方法:随机选择T2DM患者100例,男65例,女35例,年龄25～83岁,平均57±13岁。测定各患者血清β-HBA浓度,根据HbA1c水平将T2DM患者分为轻度组(HbA1c<7%)、中度组(7%≤HbA1c≤9%)、重度组(HbA1c>9%)。又根据FBG水平将T2DM患者分为轻度组(FBG<7mmol/L)、中度组(7mmol/L≤FBG≤mmol/L)、重度组(FBG>9mmol/L)。分析比较不同水平HbA1c和FBG组间β-HBA水平差异。结果:随着HbA1c水平的逐渐升高,β-HBA水平亦有逐渐升高的趋势,HbA1c重度组与轻度组和中度组比较差异有统计学意义(P<0.05)。不同FBG水平组间β-HBA没有统计学差异(P>0.05)。结论:在血浆HbA1c>9%的T2DM患者中,β-HBA显著升高,提示临床加强血糖控制,降低HbA1c,防止糖尿病酮症及酮症酸中毒。     

MiRNA-146a的单核苷酸多态性rs2910164与2型糖尿病相关性的系统分析

目的 对miR-146a rs2910164 与T2DM相关性进行荟萃分析.方法 在Pubmed、EMBASE、以及CNKI、万方数据库进行文献检索,收集病例对照研究,对纳入的文献进行质量评价,并获取相关数据,使用Stata12进行meta分析.结果共检索文献499篇,最终有4篇符合入选标准,其中病例组共2069人,对照组1950人.结果显示rs2910164的基因位点及各遗传模型与T2DM均无明显相关性,但以种族进行分层分析,在各遗传模型中纯合子模型及隐性模型提示与白种人T2DM有关,增加T2DM的发病风险(OR=1.79 95% CI 1.07~3.00, PH=0.216;GG+GC/CC:OR=1.80 95% CI 1.09~2.97, PH=0.314).在敏感性分析中去除Wang等人的研究,此基因位点及纯合子模型与T2DM有关,也提示增加T2DM的发病风险(G/C:OR=1.32 95% CI 1.05~1.67, PH =0.104;GG/CC:OR=1.97 95% CI 1.49~2.61, PH=0.420).结论 miR-146a rs2910164可能增加T2DM的患病风险,但仍需纳入更多高质量、更多不同种族的文献研究,进行综合分析.     

A common functional variant in the interleukin-6 gene is associated with increased body mass index in subjects with type 2 diabetes mellitus

Circulating levels of interleukin-6 (IL-6) are raised in insulin resistant states such as obesity, impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM). Growing evidence suggests that IL-6 is not only produced by fat cells but is also capable of inducing insulin resistance in these cells. The expected result of this in vivo, would be to increase adipose mass and subsequently body mass index (BMI). The IL-6 -174G > C common functional gene variant has consistently been associated with increased plasma IL-6, insulin resistance, and increased cardiovascular risk. We looked at the association between genotype and BMI in 571 Caucasian subjects with T2DM. There was a significant linear association between genotype and BMI: Median (interquartile range) GG 28.8 kg/m2 (26.0-31.6) vs GC; 29.4 kg/m2 (26.3-32.5) vs CC; 30.4 kg/m2 (26.1-33.0), p=0.05. When the group was divided by the median BMI (29.1 kg/m2), 62% of -174CC subjects were in the higher group compared to 38% in the lower group (p=0.008). By contrast, in 2,652 non-diabetic Caucasian men with a median BMI of 26.1 kg/m2, there was no difference in genotype distribution (p=0.288). The frequency of the -174C allele was lower in type 2 diabetes compared to the non-diabetic men (-174C allele frequency: 0.35[0.33-0.38] vs 0.43[0.42-0.45], p <0.00001; -174CC homozygotes: 12.3 vs 18.3%, respectively). The -174C allele is associated with higher BMI in type 2 diabetes, but not amongst healthy subjects. The increased cardiovascular risk associated with the -174C allele may account for the lower frequency of this allele in those with type 2 diabetes.     

Impacts of CD152 polymorphisms on cervical cancer susceptibility

AimThe objective of this study was to discuss the effect of CD152 polymorphisms rs231775, rs3087243 and rs5742909 on the susceptibility to cervical cancer.MethodsThe databases of PubMed, EMBASE, Cochrane Library, ISI Web of Science, Google Scholar Web, CNKI and Wanfang were searched for eligible studies. Chi-square-based Q test examined heterogeneity between included studies, and when P_{heterogeneity} was less than 0.05, random-effect model was used to calculate odds ratios (ORs) with their 95 % confidence intervals (95 % CIs); or else, fixed-effect model was selected. Sensitivity analysis was implemented to determine the stability of final results through removing enrolled studies one at a time and then re-obtaining overall estimates. Publication bias among included studies was checked employing Begg’s funnel plot and Egger’s test.ResultsCD152 polymorphism rs231775 decreased cervical cancer risk in total analysis under the genetic models of GG vs. AA, GG vs. AA + AG and G vs. A (OR = 0.73, 95 % CI = 0.59–0.91; OR = 0.78, 95 % CI = 0.65–0.94; OR = 0.92, 95 % CI = 0.87–0.98), and so did the polymorphism rs3087243 in total analysis under the comparisons of AA vs. GG, AA + GA vs. GG, AA vs. GG + GA, A vs. G and GA vs. GG (OR = 0.51, 95 % CI = 0.42–0.60; OR = 0.71, 95 % CI = 0.62–0.82; OR = 0.57, 95 % CI = 0.50–0.66; OR = 0.70, 95 % CI = 0.64–0.77; OR = 0.83, 95 % CI = 0.72–0.97). Besides, the polymorphism rs5742909 elevated the disease onset in total analysis under the contrasts of TT vs. CC, TT + CT vs. CC, TT vs. CC + CT, T vs. C and CT vs. CC (OR = 2.66, 95 % CI = 1.75–4.04; OR = 1.54, 95 % CI = 1.24–1.91; OR = 2.13, 95 % CI = 1.12–4.03; OR = 1.44, 95 % CI = 1.17–1.78; OR = 1.49, 95 % CI = 1.22–1.83).ConclusionCD152 polymorphisms rs231775 and rs3087243 significantly decrease the risk of cervical cancer, while rs5742909 may increase the disease risk.     

Improvement of Glycemic Control after Re-Emphasis of Lifestyle Modification in Type 2 Diabetic Patients Reluctant to Additional Medication

Purpose

The aim of this study is to observe glycemic changes after emphasizing the importance of lifestyle modification in patients with mild or moderately uncontrolled type 2 diabetes.

Materials and Methods

We examined 51 type 2 diabetic patients with 7.0-9.0% hemoglobin A1c (HbA1c) who preferred to change their lifestyle rather than followed the recommendation of medication change. At the enrollment, the study subjects completed questionnaires about diet and exercise. After 3 months, HbA1c levels were determined and questionnaires on the change of lifestyle were accomplished. We divided the study subjects into 3 groups: improved (more than 0.3% decrease of HbA1c), aggravated (more than 0.3% increase of HbA1c) and not changed (-0.3% ResultsAmong the total 51 subjects, 18 patients (35.3%) showed the decreased levels of HbA1c after 3 months with mean change of -0.74±0.27%, and HbA1c values of 11 patients (21.5%) were less than 7%. In addition, the HbA1c level was significantly reduced in patients who reportedly followed the lifestyle modification such as diet and exercise for 3 months, compared with the one obtained from patients who refused this lifestyle change (p=0.002).

Conclusion

In this study, 35.3% of the patients with mild or moderately uncontrolled type 2 diabetes showed the significant improvement of HbA1c levels after 3 months by simply regulating their daily diet and exercise without change of medication. This suggests that the lifestyle modification is significantly associated with the improvement of glucose control.     

Association between BDNF Polymorphism and Depressive Symptoms in Patients Newly Diagnosed with Type 2 Diabetes Mellitus

PurposeLittle is known about the relationship between brain-derived neurotrophic factor (BDNF) gene polymorphisms and psychiatric symptoms in diabetes patients. We investigated the effects of BDNF Val/66/Met polymorphism, glucose status, psychological susceptibility, and resilience on anxiety and depression symptoms in patients newly diagnosed with type 2 diabetes mellitus (T2DM).Materials and MethodsWe examined biochemical factors and BDNF polymorphism in 89 patients who were newly diagnosed with T2DM. Psychiatric symptoms were investigated with the Hospital Anxiety and Depression Scale (HADS), and the Connor-Davidson Resilience Scale (CD-RISC) and Impact of Event Scale (IES) were used to assess psychological resilience and susceptibility to psychological distress, respectively. Logistic regression analyses were conducted to investigate factors associated with psychiatric symptoms.ResultsWe determined that 62 patients (70%) were Met-carriers. No significant differences were found between the Val/Val homozygous and Met-carrier groups regarding age, sex, body mass index, and clinical factors related to glycemic control and lipid profiles. HADS-anxiety and HADS-depression scores and IES factor scores were higher in the Met-carrier than the Val/Val homozygous group. Hemoglobin A1c (HbA1c) level was significantly inversely correlated with the severity of depressive symptoms. Resilience factors showed significant inverse correlations, and IES factors showed positive correlations with depressive symptom severity. In the logistic regression analysis model, depressive symptoms were significantly associated with HbA1c and BDNF polymorphism, whereas only the hyperarousal factor of the IES scale was associated with anxiety.ConclusionDepressive symptoms are associated with the presence of the Met-carriers and lower HbA1c in patients newly diagnosed with T2DM.     

Serum testosterone in Nigerian men with type 2 diabetes mellitus and its relationship with insulin sensitivity and glycemic control

BackgroundThere is increasing evidence that testosterone deficiency has key associations with insulin sensitivity and glycemic control. Its presence may therefore contribute to and/or exacerbate clinical disease in men with type 2 diabetes mellitus (T2DM). This study sought to determine the frequency of low free testosterone and explore its relationship with, insulin sensitivity and glycemic control among Nigerian men with T2DM.MethodsOne hundred and four men with type 2 DM and one hundred and one apparently healthy non-diabetic men matched for age, were recruited into the study Socio-demographic data, anthropometric measurements and blood samples were obtained for measurement of serum total testosterone (TT), sex hormone binding globulin (SHBG), fasting plasma insulin, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c) and fasting lipid profile in all the subjects. Insulin sensitivity (%IS) and free testosterone (CFT) were then calculated.ResultsThe median CFT for men with T2DM was significantly lower than that of non-diabetic controls (0.17 nmol/L vs 0.58 nmol/L respectively; P < 0.001). 52.9% of men with T2DM had low CFT, as compared with 21.4% amongst the non-diabetic controls; P < 0.001.Among men with T2DM, those with lower CFT had significantly lower median % S and higher mean HbA1c than those with normal CFT (37.0% versus 63.0%; P = 0.021 and 7.79 (2.03) % versus 7.02 (1.94) %; P = 0.038 respectively]. HbA1c had significant negative correlations with both CFT (correlation coefficient: ?0.239 (P < 0.05) and TT (correlation coefficient: 0.354; P < 0.01.There was no significant difference in serum lipids when T2DM men with low serum CFT were compared with T2DM men with normal serum CFT levels.ConclusionWe conclude that low serum testosterone is common among men with T2DM and has a significant association with glycemic control (HbA1c) and insulin sensitivity.     

Common Adiponectin Gene Variants Show Different Effects on Risk of Cardiovascular Disease and Type 2 Diabetes in European Subjects

Alterations in the secretion of adipokines may explain the link between obesity, type 2 diabetes (T2DM) and coronary artery disease (CAD). These conditions have been associated with variation in the adiponectin gene, although evidence for this relationship has been variable, with differences found even in similar samples. This study aims to clarify these inconsistencies by determining the impact of identified adiponectin gene ( ADIPOQ ) variants (−11391G>A,−1377C>G[promoter] and +45T>G[exon 2] and +276G>T[intron 2]) on the prospective risk of CAD and T2DM in healthy men, and on adverse metabolic markers, in myocardial infarct survivors and controls from different parts of Europe. The hazard ratio for cardiovascular disease varied across the −11391GG/GA/AA(p = 0.03) and −11371CC/CG/GG(p = 0.05) genotypes only. In contrast, only the +45T>G variant (3.80[1.76-8.24]) was associated with T2DM, while two haplotypes GCTT/GCGG (p < 0.05) and +276G>T(p = 0.01) increased risk in interaction with obesity. The variants were associated with a number of biomarkers in Southern but not Northern Europe (p = 0.01), despite no significant differences in allele or haplotype frequencies (p > 0.44). A risk haplotype could not be identified in either sample. Adiponectin gene variants are hence currently poor markers for the development of T2DM and CAD. Their influence on risk depends significantly on interactions that are not currently understood with either genetic variation elsewhere or the environment of the sample studied.     

CDKAL1基因rs7754860位点G<C多态性与2型糖尿病易感关系的Meta分析*◆

背景：遗传学研究显示2型糖尿病可能存在遗传易感性,但研究结论存在一定的差异。 目的：探讨CDKAL1(细胞周期素依赖激酶5调节亚单位相关蛋白1类似物1)基因rs7754860位点G相似文献