High levels of circulating interleukin-10 in diabetic nephropathy patients

AIMS: The aim of our study was to analyse the level of circulating interleukin-10 (IL-10) and relate it to the grade of albuminuria in patients with diabetic nephropathy (DN) due to type 1 diabetes mellitus (DM). Since IL-10 has met the criteria for an anti-inflammatory and an immunosuppressive cytokine, its activity may be important for clinical outcome of DN. METHODS: The IL-10 level was measured by ELISA in serum samples from thirty patients with DN due to type 1 DM, and compared with thirty patients with type 1 DM without DN and a control group of thirty, healthy, age- and sex-matched people. RESULTS: We observed a greatly elevated concentration of circulating IL-10 in 30/30 DM patients with DN (mean 140 pg/mL +/- 102), compared to DM patients without DN in whom IL-10 was detectable in only 11/30 patients (0.79 pg/mL +/- 1.24), and the group of healthy people in whom IL-10 was detectable in only 3/30 donors (0.92 pg/mL +/- 0.17). IL-10 appeared to be the strongest independent predictor of albuminuria, followed by HbA1c, diastolic blood pressure and DN duration. There was a positive correlation between the values of IL-10 and albuminuria in DM patients with DN. The patients in the fourth quartile of albuminuria had a distinctly higher concentration of IL-10 than those in the lower quartiles. CONCLUSIONS: The increased concentration of IL-10 in the serum samples from DM patients with DN seems to depend on the severity of the nephropathy. The excessive IL-10 production may indirectly contribute towards DN progression. On the other hand, it may explain the relatively long course of diabetic nephropathy.     

Butyrylcholinesterase K variant and the APOE-ε4 allele work in synergy to increase the risk of coronary artery disease especially in diabetic patients

We have previously shown that butyrylcholinesterase-K (BCHE-K, G1615A/Ala539Thr) variant increases the risk of coronary artery disease (CAD). In addition, we have found that the presence of APOE-ε4 allele augments the risk of CAD in patients with type II diabetes mellitus (T2DM/CAD). Here we explored the concomitant presences of two alleles of the BCHE-K and APOE-ε4 in increasing the risk of CAD or diabetes in T2DM patients with or without CAD and CAD patients without T2DM. This case–control study comprised 631 subjects undergoing their first coronary angiography. They were matched and randomly assigned into four groups: type II diabetic patients with no sign of CAD (T2DM), type II diabetic patients with CAD/ND (T2DM/CAD), CAD patients with no sign of diabetes (CAD/ND), and healthy individuals (NCAD/ND). BCHE-K variant and APOE genotypes were detected by PCR-RFLP and serum lipid level was measured enzymatically. We found that BCHE-K and APOE-ε4 allele act synergistically to increase the risk of CAD in both T2DM, non-diabetic and total CAD (TCAD = T2DM/CAD + CAD/ND) individuals. The level of synergy 1.5 and 1.2 fold are higher in CAD patients (OR = 4.5; P = 0.011) with T2DM than the non-diabetic CAD patients (OR = 3.07; P = 0.024) and TCAD patients (OR = 3.74; P = 0.018), respectively. The CAD subjects with and without T2DM and TCAD patients carrying both APOE-ε4 allele and BCHE-K had significantly lower plasma HDL-C (P values = 0.008, 0.047, and 0.036, respectively) and higher plasma LDL-C (P values = 0.025, 0.048, and 0.04, respectively), than that of the control carriers both APOE-ε4 and BCHE-K. We have found that BCHE-K and APOE-ε4 allele not only act synergistically to increase the risk of CAD, particularly in T2DM subjects in population from western Iran, who have high levels of LDL-C and low levels of HDL-C, suggesting that a specific therapeutic intervention should be considered for these particular groups of patients.     

2 型糖尿病神经病变患者血清IL-6、8-iso-PGF2α 检测及意义

目的:探讨2型糖尿病神经病变(DPN)患者血清IL-6、8-iso-PGF2α水平的变化及意义。方法:选择2型糖尿病患者伴神经病变的患者55例,单纯2型糖尿病不伴有神经病变的患者25例,另选25例体检健康者作为对照组。采用ELISA法分别测定各组血清IL-6、8-iso-PGF2α水平。结果:血清IL-6、8-iso-PGF2α水平在糖尿病组和糖尿病神经病变组均较对照组显著升高,差异具有统计学意义(P<0.01)。DN组8-iso-PGF2α较DM组显著升高,差异具有统计学意义(P<0.05);但IL-6在两组间差异无统计学意义(P>0.05)。结论:IL-6在糖尿病神经病变发病中的作用不能肯定。8-iso-PGF2α可能通过氧化应激作用参与糖尿病神经病变的发生发展。     

Impaired myocardial deformation and ventricular vascular coupling in obese adolescents with dysglycemia

Patients with Diabetes mellitus (DM) are susceptible to coronary artery disease (CAD). However, the impact of DM on plaque progression in the non-stented segments of stent-implanted patients has been rarely reported. This study aimed to evaluate the impact of DM on the prevalence, characteristics and severity of coronary computed tomography angiography (CCTA) verified plaque progression in stented patients. A comparison between diabetic and non-diabetic patients was performed. A total of 98 patients who underwent clinically indicated serial CCTAs arranged within 1 month before and at least 6 months after percutaneous coronary intervention (PCI) were consecutively included. All the subjects were categorized into diabetic group (n = 36) and non-diabetic groups (n = 62). Coronary stenosis extent scores, segment involvement scores (SIS), segment stenosis scores (SSS) at baseline and follow-up CCTA were quantitatively assessed. The prevalence, characteristics and severity of plaque progression was evaluated blindly to the clinical data and compared between the groups. During the median 1.5 year follow up, a larger number of patients (72.2% vs 40.3%, P = 0.002), more non-stented vessels (55.7% vs 23.2%, P < 0.001) and non-stented segments (10.3% vs 4.4%, P < 0.001) showed plaque progression in DM group, compared to non-DM controls. More progressive lesions in DM patients were found to be non-calcified plaques (31.1% vs 12.8%, P = 0.014) or non-stenotic segments (6.6% vs 3.0%, p = 0.005) and were more widely distributed on left main artery (24.2% vs 5.2%, p = 0.007), the right coronary artery (50% vs 21.1%, P = 0.028) and the proximal left anterior artery (33.3% vs 5.1%, P = 0.009) compared to non-DM patients. In addition, DM patients possessed higher numbers of progressive segments per patient, ΔSIS and ΔSSS compared with non-DM individuals (P < 0.001, P = 0.029 and P < 0.001 respectively). A larger number of patients with at least two progressive lesions were found in the DM group (P = 0.006). Multivariate logistic regression analysis demonstrated that DM (OR: 4.81; 95% CI 1.64–14.07, P = 0.004) was independently associated with plaque progression. DM is closely associated with the prevalence and severity of CCTA verified CAD progression. These findings suggest that physicians should pay attention to non-stent segments and the management of non-stent segment plaque progression, particularly to DM patients.     

2型糖尿病合并冠心病患者血清IL-6、PCT、CatS、Gal-3与糖脂代谢、胰岛素抵抗和心功能的相关性分析

摘要 目的：探讨2型糖尿病（T2DM）合并冠心病患者血清白介素-6（IL-6）、降钙素原（PCT）、组织蛋白酶S（CatS）、半乳糖凝集素3（Gal-3）与糖脂代谢、胰岛素抵抗和心功能的相关性。方法：选择我院2019年2月～2021年2月收治的102例T2DM患者,将其根据是否伴有冠心病分成单纯T2DM组（n=62）和T2DM合并冠心病组（n=40）。另取同期健康体检人员50例作为对照组。比较三组血清IL-6、PCT、CatS、Gal-3水平。对比单纯T2DM组与T2DM合并冠心病组间糖脂代谢、胰岛素抵抗和心功能指标差异,并分析血清IL-6、PCT、CatS、Gal-3与上述指标的相关性。结果：单纯T2DM组、T2DM合并冠心病组的血清IL-6、PCT、CatS、Gal-3水平均高于对照组,且T2DM合并冠心病组上述各项指标水平均高于单纯T2DM组（P＜0.05）。T2DM合并冠心病组空腹血糖（FPG）、低密度脂蛋白胆固醇（LDL-C）水平以及胰岛素抵抗指数（HOMA-IR）均高于单纯T2DM组（P＜0.05）,而两组间餐后2 h血糖（2hPG）、糖化血红蛋白（HbA1c）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、空腹胰岛素（FINS）水平比较无统计学差异（P>0.05）。T2DM合并冠心病组左心室射血分数（LVEF）、左心室收缩末期容积（LVESV）及左心室舒张末期容积（LVEDV）均低于单纯T2DM组（P＜0.05）。Pearson相关性分析结果显示：T2DM合并冠心病患者的血清IL-6、PCT、CatS、Gal-3水平与LDL-C水平、HOMA-IR均呈正相关,而与LVEF、LVESV、LVEDV均呈负相关（P＜0.05）。结论：T2DM合并冠心病患者血清IL-6、PCT、CatS、Gal-3水平呈异常高表达,且和糖脂代谢、胰岛素抵抗和心功能密切相关,对患者病情具有一定辅助评估价值。     

Associations of galectin-3 expression and LGALS-3 (rs4652) gene variant with coronary artery disease risk in diabetics

BackgroundGalectin-3 protein encoded by lectin galactoside-binding soluble-3 (LGALS-3) gene is an important genetic factor in type 2 diabetes mellitus (T2DM) and its cardiovascular obstacles in various populations. We aimed to elicit the pro-inflammatory effect of galectin-3 as determined by interleukin-6 (IL-6) serum levels and to explore the relationship between galectin-3 (LGALS-3 rs4652) gene variant and its expression levels with coronary artery disease (CAD) risk among T2DM Egyptian patients.Methods112 lean subjects were compared to 100 T2DM without CAD and 84 T2DM with CAD. A tetra-primer amplification refractory mutation system polymerase chain reaction was used to test LGALS-3 (rs4652), and galectin3 expression was tested with a quantitative real-time polymerase chain reaction. Serum IL-6 was measured using an enzyme-linked immunosorbent assay.ResultsWe found that the prevalence of LGALS-3 (rs4652) AC genotype and galectin-3 gene expression levels in T2DM with CAD were significantly higher than the additional 2 groups and were correlated positively to IL-6 circulating levels. Also, the C allele carriers (AC+CC) had significantly higher relative Galectin-3 expression levels compared to the A allele carriers (AA).ConclusionsWe concluded that galectin-3 expression levels and LGALS-3 (rs4652) AC genotype were coronary artery disease risk factors in people with type two diabetes among an Egyptian sample.     

Bile acid metabolites in serum: intraindividual variation and associations with coronary heart disease, metabolic syndrome and diabetes mellitus

Bile acids (BAs) regulate glucose and lipid metabolism. In longitudinal and case-control-studies, we investigated the diurnal variation of serum concentrations of the 15 major BAs as well as the biosynthetic precursor 7α-hydroxy-4-cholesten-3-one (C4) and their associations, respectively, with coronary artery disease (CAD), diabetes mellitus type 2 (T2DM), and non-diabetic metabolic syndrome (MetS). In hourly taken blood samples of four healthy probands, the intraindividual 24 h variation of C4, conjugated and unconjugated BAs ranged from 42% to 72%, from 23% to 91%, and from 49% to 90%, respectively. Conjugated BA concentrations mainly increased following food intake. Serum levels of C4 and unconjugated BAs changed with daytime with maxima varying interindividually between 20h00 and 1h00 and between 3h00 and 8h00, respectively. Comparisons of data from 75 CAD patients with 75 CAD-free controls revealed no statistically significant association of CAD with BAs or C4. Comparisons of data from 50 controls free of T2DM or MetS, 50 MetS patients, and 50 T2DM patients revealed significantly increased fasting serum levels of C4 in patients with MetS and T2DM. Multiple regression analysis revealed body mass index (BMI) and plasma levels of triglycerides (TG) as independent determinants of C4 levels. Upon multivariate and principle component analyses the association of C4 with T2DM and/or MetS was not independent of or superior to the canonical MetS components. In conclusion, despite large intra- and interindividual variation, serum levels of C4 are significantly increased in patients with MetS and T2DM but confounded with BMI and TG.     

Increased serum levels of interleukin-18 in patients with diabetic nephropathy

In the present study we measured interleukin-18 (IL-18) and tumour necrosis factor-alpha (TNF-alpha) levels by enzyme linked immunosorbent assay (ELISA) in sera from 65 diabetic [30 with type 1 insulin dependent diabetes mellitus (IDDM) and 35 with type 2 non-insulin dependent diabetes mellitus (NIDDM)] patients and 15 healthy volunteers, to investigate their associations with metabolic parameters and to elucidate their roles in the pathogenesis of diabetic complications especially diabetic nephropathy. Levels of IL-18 and TNF-alpha were significantly higher in both IDDM and NIDDM individuals as compared to the control group. Similarly, their levels in patients with diabetic nephropathy increased gradually according to the clinical stage of the disease, being highest in macroalbuminuric stage. Correlation analyses showed that the serum IL-18 and TNF-alpha concentration were positively correlated with each other and positively with fasting plasma glucose (FPG), 2h postprandial glucose, glycosylated hemoglobin (HbA1c), triglyceride, and urinary albumin levels and negative correlation between TNF-alpha and high density lipoprotein cholesterol (HDL-C) were also found in diabetic subjects. High serum levels of IL-18 and TNF-alpha suggested that they might play a role in the pathogenesis of DM and in the development of nephropathy in diabetic patients whether of type 1 or 2.     

The prevalence, type and severity of cardiovascular disease in diabetic and non-diabetic patients: a matched-paired retrospective analysis using coronary angiography as the diagnostic tool

People with diabetes mellitus have a 2-8-fold excess in cardiovascular mortality than people without diabetes. This study compared angiographically determined cardiovascular disease in 79 patients with diabetes mellitus and an equal number of matched controls without diabetes under the age of 55 years. Seventy-nine diabetic patients coming to coronary angiography during a 12-month period were reviewed retrospectively along with 79 control patients matched for age (+/- 3 years), sex, ethnic origin and risk factors (hyperlipidemia, body mass index and smoking history). The angiographic features of a consecutive series of 62 European and 17 Asian patients and their matched-paired controls were assessed. In all study subjects had undergone elective coronary angiography and ventriculography. Angiographic findings were graded to describe severity and extent of coronary atherosclerosis. Left ventricular systolic function was assessed by ejection fraction. The diabetic group had a significantly higher arterial systolic pressure than the non-diabetic group (p < 0.008) and they were clinically obese with a body mass index of >30. Detailed analysis of the angiograms showed that prevalence and severity of coronary artery disease in diabetic patients was greater. The mean 'severity score' was 11.66 for the diabetic group against 8.49 for the non-diabetic group (p < 0.037). Multivessel disease was more common in diabetic patients than in the controls, with three-vessel disease being the most common. Furthermore, 38 of 79 diabetic patients had three-vessel disease compared to 29 of 79 controls. Diabetic patients were also more likely to have more segments diseased in one vessel. Systolic function was reduced in the diabetic group, with a significantly lower (p < 0.05) mean ejection fraction. The present study supports the evidence that diabetic patients have more extensive coronary artery disease than non-diabetic patients and a poorer prognosis, and that the coronary arteries of the Asian patients were affected more adversely than those of the European group irrespective of the diabetic state.     

冠心病患者介入治疗前后血清IL-18、sCD40L 和hs-CRP 水平的 变化及其意义

目的:探讨冠心病患者血清白介素18(Interleukin-18,IL-18)、白细胞分化抗原40配体(CD40L)、及高敏C反应蛋白(hs-CRP)水平在经皮冠状动脉介入术治疗前后的变化和意义。方法:选择经冠状动脉造影确诊的冠心病患者85例,根据病变程度分为单支病变组(n=32)、双支病变组(n=28)和多支病变组(n=25),采用双抗体夹心ELISA法测定PCI术前术后血清IL-18、CD40L和hs-CRP水平。结果:血清IL-18水平测定结果:多支病变组高于双支病变组,双支病变组高于单支病变组;支架置入术后显著高于术前,差异均有统计学意义(P<0.01)。血清CD40L水平测定结果:多支病变组高于双支病变组和单支病变组,差异均有统计学意义(P<0.01),双支病变组与单支病变组间差异无统计学意义(P>0.05);支架置入术后较术前显著升高,差异有统计学意义(P<0.01)。血清hs-CRP水平测定结果:多支病变组高于双支病变组,双支病变组高于单支病变组;支架置入术后显著高于术前,差异均有统计学意义(P<0.01)。结论:冠心病患者血清IL-18、CD40L和hs-CRP与冠脉病变程度密切相关,介入治疗可使冠心病患者血清IL-18、CD40L和hs-CRP水平升高,监测血清中IL-18、CD40L和hs-CRP水平变化可了解治疗效果和炎症程度。     

血清γ-谷氨酰转肽酶水平与老年2型糖尿病患者并发急性冠脉综合征的相关性分析

目的:探讨血清γ-谷氨酰转肽酶(GGT)水平与老年2型糖尿病患者并发急性冠脉综合征的相关性。方法:选取2015年10月至2016年10月哈尔滨市第一医院收治的老年患者238例,根据病情分为单纯2型糖尿病组81例(DM组),单纯急性冠脉综合征组78例(ACS组),2型糖尿病患者合并急性冠脉综合征79例(DA组);选取同期来我院体检健康者83例作为对照组(NC组)。比较各组一般情况和血清学指标。结果:(1)DA组BMI大于NC组、DM组和ACS组,血清GGT、糖化血红蛋白(HbA1C)、低密度脂蛋白胆固醇(LDL-C)水平显著高于NC组、DM组和ACS组,血清总胆固醇(TC)、甘油三酯(TG)水平均高于NC组,高密度脂蛋白胆固醇(HDL-C)水平低于NC组(P0.05)。(2)血清GGT水平与TG、LDC-C水平呈正相关(p0.05)。结论:血清GGT水平升高是老年2型糖尿病患者并发急性冠脉综合征的独立危险因素,及时监测老年2型糖尿病患者GGT水平对预测急性冠脉综合征的发生具有重要意义。     

Impact of cardiovascular risk factors on coronary heart disease and mortality among middle aged diabetic men: a general population study.

OBJECTIVE--To investigate the effect of cardiovascular risk factors on coronary heart disease and all cause mortality in middle aged diabetic men. DESIGN--Prospective population study based on data collected from second screening (from 1974 to 1977) in the multifactor primary prevention trial and follow up until March 1983. SETTING--Gothenburg, Sweden. SUBJECTS--6897 Men aged 51 to 59, of whom 232 were self reported diabetics and 6665 were non-diabetic; none had a history of myocardial infarction. MAIN OUTCOME MEASURES--Incidences of coronary heart disease and mortality from all causes. RESULTS--Diabetic men with a serum cholesterol concentration greater than 7.3 mmol/l had a significantly higher incidence of coronary heart disease during follow up than those with a concentration less than or equal to 5.5 mmol/l (28.3% v 5.4%; p = 0.020); corresponding figures for non-diabetic men were 9.4% and 2.4% respectively. In multivariate logistic regression analyses serum cholesterol concentration and smoking habit were independent predictors of coronary heart disease (odds ratio serum cholesterol concentration 6.1 (95% confidence interval 2.1 to 17.6) current smoking 2.9 (1.1 to 7.5)) and of all cause mortality (3.2 (1.3 to 7.9), 3.0 (1.4 to 6.7) respectively) in diabetic men whereas systolic blood pressure, body mass index, family history, marital state, and alcohol abuse were not. Low occupational class was an independent predictor of mortality (2.4 (1.01 to 5.5)), but not of coronary heart disease, in diabetic men. CONCLUSIONS--Middle aged diabetic men with hypercholesterolaemia are at very high risk of developing coronary heart disease and of dying prematurely. Lowering serum cholesterol concentration in such subjects seems to be warranted.     

Assessment of gender-related differences in vitamin D levels and cardiovascular risk factors in Saudi patients with type 2 diabetes mellitus

Diabetes is a major risk factor for cardiovascular disease (CVD) including stroke, coronary heart disease, and peripheral artery disease. It remains a leading cause of mortality throughout the world, affecting both women and men. This investigation was aimed to study gender based differences in cardiovascular risk factors of adult population with type-2 diabetes mellitus (T2DM) and to check the correlation between serum HbA1C, lipid profile and serum vitamin D levels, in T2DM patients of Riyadh, Saudi Arabia. This hospital-based cross-sectional study involving subjects was divided into two gender based groups; normal male (800), diabetic male (800) and normal female (800) and T2DM females (800). Blood samples were analyzed for fasting glucose (FBG), HbA1c, total cholesterol (TC), triglycerides (Tg), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and serum levels of 25(OH)-vitamin D in all groups. All the glycemic control parameters and lipid profile parameters were found to be significantly different in diabetic vs non-diabetic group (p < 0.001) in both genders. The results also show that vitamin D concentration decreased significantly (p < 0.001) in diabetic patients than the healthy individuals in both the genders. Vitamin-D and HbA1C were negatively correlated in both males and females in T2DM patients and significant at P < 0.05. Our study reveals that dyslipidemia remains one of the major risk factors of CVD in T2DM. In addition to dyslipidemia, decreased levels of vitamin-D associated with increased HbA1C alarms the early diagnosis of Type 2 Diabetes.     

Microvascular abnormalities in capillaroscopy correlate with higher serum IL-18 and sE-selectin levels in patients with type 1 diabetes complicated by microangiopathy

Microvascular abnormalities are one of the most important causes of persistent diabetic complications. The aim of this study was to compare microvascular changes examined by nailfold capillaroscopy with serum concentrations of soluble E-selectin (sE-selectin) and IL-18 in type 1 diabetic patients with and without microangiopathy. Serum levels of sE-selectin and IL-18 were determined by an enzyme-linked immunosorbent assay in 106 patients with type 1 diabetes and in 40 healthy controls. All diabetic patients were evaluated by extensive clinical, laboratory and capillaroscopic studies. Morphological changes were observed by nailfold capillaroscopy in 86 out of 106 (81%) diabetic patients. Severe capillaroscopic changes were seen in 32 out of 54 (59%) patients with microangiopathy, but in only seven out of 52 (13%) patients without microangiopathy. Higher serum levels of sE-selectin (p < 0.001) and IL-18 (p < 0.05) were demonstrated in diabetic patients compared to controls. Significant differences of sE-selectin (p , 0.001) and IL-18 (p < 0.01) serum concentrations were observed between diabetic patients with microangiopathy and controls. Moreover, comparison between patients with and without microangiopathic complications showed a significantly higher capillaroscopic score and sE-selectin serum concentration in the group with microangiopathy (p < 0.001). Furthermore, diabetic patients with severe microvascular changes in capillaroscopy showed significantly higher IL-18 (p < 0.001) and sE-selectin (p < 0.05) serum levels than subgroups without changes or with mild abnormalities. Our findings suggest that abnormalities in nailfold capillaroscopy may reflect the extent of microvascular involvement and are associated with higher sE-selectin and IL-18 serum levels, as well as with microangiopathic complications in diabetic patients.     

Role of Serum Vaspin in Progression of Type 2 Diabetes: A 2-Year Cohort Study

Vaspin is a novel adipocytokine that has potential insulin-sensitizing effects. The aim of this study is to explore the role of vaspin in the progression of type 2 diabetes mellitus (T2DM) in humans through a longitudinal process. This was a 2-year follow-up study that included 132 patients with T2DM and 170 non-diabetic subjects. The serum vaspin and adiponectin levels were determined with ELISA. Anthropometric measurements, circulating glucose, hemoglobin A1c, insulin level, liver function, kidney function, and lipid profile were measured for each participant. The new onset of T2DM was counted in non-diabetic subjects and the glycemic control was analyzed in T2DM patients at follow-up. At enrollment, the serum vaspin and adiponectin levels were lower in T2DM patients compared with non-diabetic subjects. Significant positive correlation between serum vaspin and HDL-C levels (r = 0.23, P = 0.006) was observed in non-diabetic controls. The serum vaspin concentration was also significantly correlated with body mass index (BMI) (r = 0.19, P = 0.028), waist-hip ratio (WHR) (r = 0.17, P = 0.035) and homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.14, P = 0.029) in T2DM patients. In cohort analyses, it was found that lower serum vaspin [odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.10–0.87, P = 0.015] and adiponectin (OR = 0.35, 95% CI: 0.20–0.72, P = 0.015) levels at baseline were risk factors for new onset of T2DM at follow-up. The percentage of insulin treatment in T2DM patients was higher in the sub-group with lower serum vaspin level than that in the sub-group with higher vaspin level at follow-up (55.3% vs. 44.7%, P = 0.020). Our study indicates that low serum concentration of vaspin is a risk factor for the progression of T2DM.     

IL-12 serum levels in patients with type 2 diabetes treated with sulphonylureas

Interleukin-12 (IL-12) has been identified as a pro-inflammatory cytokine which is thought to contribute to the development of atherosclerosis. However, to date, the various associations between factors related to the course of type 2 diabetes, like metabolic compensation, beta cell secretory dysfunction, insulin resistance and IL-12 serum levels, remain unclear. Our study involved 41 patients with type 2 diabetes, 19 patients with coronary artery disease (CAD), and 19 healthy controls. We measured serum levels of fasting glucose, HbA₁c, 1,5-anhydro-d-glucitol, and lipids. In addition, serum levels of C-peptide, insulin, proinsulin and IL-12 were assayed. HOMA_IR score was calculated. The serum concentrations of IL-12 were higher in diabetics than in either patients with CAD or healthy controls, and were correlated with BMI, C-peptide, insulin, HOMA_IR, proinsulin and HDL serum levels. Multiple regression analysis revealed that the IL-12 serum level in type 2 diabetics primarily is dependent upon fasting proinsulin concentration. Our results demonstrate that elevated IL-12 serum levels in type 2 diabetics treated with sulphonylureas are induced especially by peripheral insulin resistance and beta cells dysfunction, as expressed by fasting serum proinsulin levels. This finding gives us hope that treatment to decrease peripheral insulin resistance and to avoid excessive proinsulin secretion might be successful in the prevention of IL-12-induced atherosclerosis.     

Soluble LDL-immune complexes in type 2 diabetes and vascular disease.

BACKGROUND AND AIMS: The oxidative modification of LDL has been shown to affect its clearance and to exert cytotoxic and immunogenic effects. The objective of our study was to analyse markers of LDL oxidation-soluble LDL containing immune complexes (LDL-ICs) in type 2 diabetes with micro- and macrovascular disease. PATIENTS AND METHODS: The study included 69 diabetic patients with coronary artery disease (DM + CAD), 78 non-diabetics with CAD, 47 controls, and 27 diabetics with nephropathy and 36 free from complications. OxLDL antibodies and advanced glycated end-products were measured by ELISA, and LDL-IC apo B content after PEG precipitation. RESULTS: Determination of a broad range of oxLDL antibody activity in all study groups showed no significant differences. In contrast, the content of apo B, a component of the antigen moiety of oxLDL-ICs, was higher in CAD and diabetes (+ CAD) than in LDL-ICs isolated from controls (p < 0.001). LDL-ICs did not differ between patients with CAD + DM and CAD patients free from diabetes. LDL-IC levels in diabetic patients with or without microangiopathy were significantly higher than in healthy volunteers (PEG-apo B 0.278 +/- 0.107 vs. 0.165 +/- 105 g/l, p < 0.002; PEG-IgG 151.7 +/- 76 vs. 115.4 +/- 62 g/l, p < 0.05). However, there was no significant difference in the level of circulating LDL-ICs between the subgroup of diabetic patients with nephropathy/retinopathy and patients free of microvascular disease (Ab-oxLDL 27.7 +/- 10.4 vs. 27.1 +/- 9.3 AU, NS; PEG-apo B 0.324 +/- 0.111 vs. 0.287 +/- 0.124 g/l, NS; PEG-IgG 1.68 +/- 0.68 vs. 1.42 +/- 0.80 g/l, NS). There was a statistically significant positive correlation between AGE content and LDL-ICs (r = 0.35, p < 0.009). A significant but inverse correlation was recorded between triglyceride concentration and level of LDL-ICs in DM + CAD (r = - 0.32, p < 0.016) and CAD patients (r = - 0.35, p < 0.002). A highly significant negative correlation between triglycerides and circulating LDL-ICs (r = - 0.54, p < 0.039) was observed in patients with early nephropathy, but not in those with physiological proteinuria. It is known that at a high triglyceride level in type 2 diabetes, the majority of LDL are small and dense, thus being more susceptible to oxidative modification. This could be a possible mechanism explaining why more LDL-ICs, with a level inversely correlating with triglyceride concentration, are generated in diabetes. CONCLUSION: The increased level of circulating LDL-ICs is a risk factor for the general population, including those with diabetes. Our results suggested the contribution of LDL-ICs to the development of atherosclerosis to probably be more significant than the direct contribution of oxLDLAb itself.     

老年2型糖尿病患者血清促甲状腺激素水平及其与冠脉病变程度的相关性分析

目的:探讨老年2型糖尿病(T2DM)患者血清促甲状腺激素(TSH)水平及其与患者冠脉病变程度的相关性。方法:回顾性分析2015年6月～2017年6月我院收治的88例老年T2DM患者(T2DM组)、50例健康体检者(对照组)的临床资料,根据血清TSH水平将T2DM组分为四个亚组,A组(0.45～1.49 m IU/L,n=18)、B组(1.50～2.49 m IU/L,n=23)、C组(2.50～3.49 m IU/L,n=22)、D组(≥4.5 m IU/L,n=25)。比较T2DM组与对照组TSH水平的差异,并根据计算机断层血管造影(CTA)结果计算Gensini评分,分析Gensini评分与血清TSH水平的相关性。结果:T2DM组血清TSH水平显著高于对照组,且随着血清TSH水平的升高,T2DM患者的年龄、TC、TG、LDL-C明显增加,而HDL-C、T3明显降低(P0.05)。C组病变支数显著多于A组,重度病变的比例明显升高,而D组病变支数、病变程度与A组、B组、C组比较差异均有统计学意义(P0.05)。血清TSH水平与Gensini评分呈显著正相关(r=0.577,P0.05)。结论:老年T2DM患者血清TSH水平显著升高,且与患者冠脉病变严重程度呈显著正相关,血清TSH水平有助于评估老年T2DM患者冠脉病变的严重程度。     

The prevalence,type and severity of cardiovascular disease in diabetic and non-diabetic patients: A matched-paired retrospective analysis using coronary angiography as the diagnostic tool

People with diabetes mellitus have a 2–8-fold excess in cardiovascular mortality than people without diabetes. This study compared angiographically determined cardiovascular disease in 79 patients with diabetes mellitus and an equal number of matched controls without diabetes under the age of 55 years. Seventy-nine diabetic patients coming to coronary angiography during a 12-month period were reviewed retrospectively along with 79 control patients matched for age (±3 years), sex, ethnic origin and risk factors (hyperlipidemia, body mass index and smoking history). The angiographic features of a consecutive series of 62 European and 17 Asian patients and their matched-paired controls were assessed. In all study subjects had undergone elective coronary angiography and ventriculography. Angiographic findings were graded to describe severity and extent of coronary atherosclerosis. Left ventricular systolic function was assessed by ejection fraction. The diabetic group had a significantly higher arterial systolic pressure than the non-diabetic group (p < 0.008) and they were clinically obese with a body mass index of >30. Detailed analysis of the angiograms showed that prevalence and severity of coronary artery disease in diabetic patients was greater. The mean severity score was 11.66 for the diabetic group against 8.49 for the non-diabetic group (p < 0.037). Multivessel disease was more common in diabetic patients than in the controls, with three-vessel disease being the most common. Furthermore, 38 of 79 diabetic patients had three-vessel disease compared to 29 of 79 controls. Diabetic patients were also more likely to have more segments diseased in one vessel. Systolic function was reduced in the diabetic group, with a significantly lower (p < 0.05) mean ejection fraction. The present study supports the evidence that diabetic patients have more extensive coronary artery disease than non-diabetic patients and a poorer prognosis, and that the coronary arteries of the Asian patients were affected more adversely than those of the European group irrespective of the diabetic state. (Mol Cell Biochem 261: 263–269, 2004)