Identification of variables influencing resistin serum levels in patients with type 1 and type 2 diabetes mellitus.

BACKGROUND: Resistin, a peptide hormone, has been discussed controversially as a missing link between obesity and insulin resistance. In contrast to resistin mRNA expression in adipose tissue, data on human serum levels in obesity and diabetes mellitus is scarce. The physiological range of serum resistin levels, reference values or adjusted percentiles have not yet been determined, making the interpretation of serum resistin concentrations quite difficult. METHODS: Resistin serum concentrations were measured systematically by ELISA in 216 healthy controls, 555 patients with type 2 diabetes and 114 patients with type 1 diabetes. Mean values, median, and range were determined, and BMI-, gender-, and disease-adapted percentiles were calculated for all subgroups. RESULTS: Age and gender did not have any influence on resistin levels. BMI and resistin levels were positively correlated in healthy controls (p = 0.02), albeit with a weak correlation coefficient. This correlation was absent in patients with type 1 and type 2 diabetes. In both genders, healthy controls had significantly higher resistin levels than patients with type 1 and type 2 diabetes (7.9 +/- 0.2 ng/ml vs. 5.7 +/- 0.2 ng/ml and 5.5 +/- 0.1 ng/ml, respectively; p < 0.0001). There was no correlation between resistin levels and occurrence of diabetic retinopathy or nephropathy. CONCLUSIONS: Serum resistin levels can be measured by ELISA over a broad range from 0.6 ng/ml up to 27.7 ng/ml, suggesting that percentiles might be helpful in the interpretation of an individuals resistin value. While age and gender do not influence resistin levels, BMI and occurrence of diabetes have to be considered.     

The APOE4 allele is associated with a decreased risk of retinopathy in type 2 diabetics

Background

Common polymorphisms within the apolipoprotein E (APOE) gene are suggested to be associated with the development of type 2 diabetes mellitus (T2DM), but the potential association with T2DM complications (nephropathy, neuropathy and retinopathy) remains unclear. We perform the case–control study to analyse the association between the APOE polymorphism and risk of T2DM and to analysed the potential relationship between the APOE and T2DM complications.

Methods and results

APOE variants (rs429358 and rs7412) were genotyped by TaqMan assay in T2DM patients (N?=?1274; N?=?829 with complications including retinopathy, neuropathy and nephropathy status) and with PCR–RFLP in healthy nondiabetic controls (N?=?2055). The comparison of subjects with genotypes associated with low plasma cholesterol (APOE2/E2 and APOE2/E3 carriers vs. others) did not show an association with T2DM (OR [95% CI]?=?0.88 [0.71–1.08). The differences remained insignificant after adjusting for diabetes duration, sex and BMI. Carriers of at least one APOE4 allele (rs429358) are protected against T2DM related retinopathy (OR [95% CI]?=?0.65 [0.42–0.99]. Protection against retinopathy is driven mostly by females (OR [95% CI]?=?0.50 [0.25–0.99]); and remains significant (P?=?0.044) after adjustment for diabetes duration and BMI.

Conclusion

Common APOE polymorphism was not associated with T2DM in the Czech population. Yet, APOE4 allele revealed an association with retinopathy. In particular, female T2DM patients with at least one APOE4 allele exhibit lower prevalence of retinopathy in our study subjects.

     

Association between serum free IGF-I and IGFBP-3 levels in type-I diabetes patients affected with associated autoimmune diseases or diabetic complications

BACKGROUND: Patients with type 1 diabetes (T1DM) present lower serum free IGF and IGFBP-3 values than healthy people. T1DM patients often present with associated autoimmune diseases such as thyroiditis or coeliac disease, and over time they frequently develop proliferative retinopathy, neuropathy or nephropathy in different combinations. OBJECTIVE: The aim of this study was to evaluate the effect of two associated autoimmune diseases or three diabetic complications on the serum free IGF-I or IGFBP-3 levels in T1DM patients, who also have a family history of T1DM. Design. 246 T1DM patients were enrolled, and then subdivided into groups according to diabetic complications or associated autoimmune diseases. Demographic and clinical data were recorded. Serum free IGF-I and IGFBP-3 levels were determined by IRMA. RESULTS: IGF-I and IGFBP-3 generally present correlated serum values as confirmed in this study. Those patients with autoimmune thyroiditis and coeliac disease presented with significantly lower serum values of IGFBP-3, whereas free IGF-I was significantly lower in patients with the different diabetic complications. Retinopathy presented a slightly significant reduction in serum free IGF-I, while neuropathy and nephropathy showed a more pronounced fall. The number of complications was related to progressively decreasing free IGF-I levels. T1DM family history was associated with lower serum free IGF-I concentrations. These findings were confirmed after correction for age, glycosylated haemoglobin levels, insulin treatment protocol, body mass index, serum creatinine and sex. CONCLUSION: Despite a direct correlation between serum free IGF-I and IGFBP-3, the correlation between the two molecules in patients with associated autoimmune diseases was lost, possibly due to different mechanisms of metabolic regulation.     

Statins research unfinished saga: desirability versus feasibility

Aims

Resistin is an adipocyte-derived factor implicated in obesity-associated type 2 diabetes (T2DM). This study examines the association between human serum resistin, T2DM and coronary heart disease.

Methods

One hundred and fourteen Saudi Arabian patients (male: female ratio 46:68; age 51.4 (mean ± SD)11.7 years; median and range: 45.59 (11.7) years and BMI: 27.1 (mean ± SD) 8.1 Kgm² median and range: 30.3 (6.3) were studied. Serum resistin and C-reactive protein (CRP), a marker of inflammation CRP levels, were measured in all subjects. (35 patients had type 2 diabetes mellitus (T2DM); 22 patients had coronary heart disease (CHD).

Results

Serum resistin levels were 1.2-fold higher in type 2 diabetes and 1.3-fold higher in CHD than in controls (p = 0.01). In addition, CRP was significantly increased in both T2DM and CHD patients (p = 0.007 and p = 0.002 respectively). The use of regression analysis also determined that serum resistin correlated with CRP levels (p = 0.04, R² 0.045).

Conclusion

The findings from this study further implicate resistin as a circulating protein associated with T2DM and CHD. In addition this study also demonstrates an association between resistin and CRP, a marker of inflammation in type 2 diabetic patients.     

Serum resistin and polymorphisms of androgen receptor GAGn and GGNn and aromatase TTTAn

There is evidence that androgens are regulators of insulin resistance (IR), and may be involved in the regulation of resistin, a cytokine that has been related with IR. Earlier studies found that androgen receptor length polymorphisms CAGn and GGNn and the aromatase polymorphism TTTAn may influence receptor or enzyme activity and serum concentrations of androgens. This study was designed to determine whether polymorphism length was related to serum resistin concentration and to other variables related with IR. In 1,580 persons chosen randomly from the general population of the Canary Islands (Spain), we measured polymorphism length, waist circumference, waist/hip ratio, BMI, and serum glucose concentration. In smaller subgroups, we also measured C-peptide (n = 677), resistin (n = 583), and leptin concentration (n = 754) and estimated IR (homeostasis model assessment-IR (HOMA2-IR)). In men, polymorphism length correlated with resistin concentration (CAGn, r = 0.13, P = 0.031; TTTAn, r = 0.15, P = 0.005; GGNn, r = -0.15, P = 0.026), and the correlations were confirmed in multivariate regression models. The length of CAGn and TTTAn correlated inversely with C-peptide (r = -0.13, P = 0.016 and r = -0.21, P < 0.001, respectively) and with estimated IR (r = -0.12, P = 0.032 and r = -0.19, P = 0.001, respectively). In men, length of the CAGn, GGNn, and TTTAn was associated with serum resistin concentration. These results support the hypothesis that androgens may be involved in the regulation of resistin. Resistin may be a link between IR and androgens.     

Calpain 10 SNP-44 gene polymorphism affects susceptibility to type 2 diabetes mellitus and diabetic-related conditions

The association of the gene encoding calpain 10 with type 2 diabetes mellitus (T2DM) has been reported. In this study we aimed to evaluate the association of SNP-19,-44, and -63 polymorphisms of calpain 10 with type 2 diabetes and diabetic-related conditions, such as diabetic retinopathy, nephropathy, and neuropathy in a Turkish population. The study group included 202 patients (133 female and 69 male) with T2DM, while the control group included 80 nondiabetic people (44 female and 36 male). Genotyping was done by the polymerase chain reaction and restriction fragment length polymorphism method. Calpain 10 SNP-44 TC genotype was found to be significantly frequent in type 2 diabetic patients with respect to the control group (p < 0.01). Body mass index (BMI) was found to be significantly high in TC genotype with type 2 diabetic patients (p < 0.05). SNP-44 T allele frequency was found to be lower in type 2 diabetic patients compared with the controls (p < 0.01). We conclude that the calpain 10 SNP-44 gene polymorphism may be accepted as a risk factor in the development of T2DM and elevated BMI in type 2 diabetic patients in a Turkish population.     

Serum CXCL16 as a Novel Marker of Renal Injury in Type 2 Diabetes Mellitus

Background

Soluble C-X-C chemokine ligand 16 (CXCL16), a scavenger receptor for oxidized low density lipoprotein, has been shown to promote atherogenic effects in vivo and to predict long-term mortality in acute coronary syndrome. The aim of this study was to explore the association of circulating CXCL16 levels with diabetic subjects with and without renal disease.

Methodology/Principal Findings

One hundred twenty Chinese subjects, which included patients with type 2 diabetes mellitus (T2DM), diabetic nephropathy (DN), and CKD, as well as healthy controls, were enrolled in this study. Serum CXCL16 levels were examined by immunoassay and other clinical biochemical parameters were tested based on standard methods. Our results indicated that, HDL and LDL cholesterol levels are significantly different in DN but not in T2D patients in comparison with healthy subjects. On the other hand, Serum CXCL16 levels were significantly increased in DN subjects compared with age and gender matched healthy and T2DM subjects (p<0.05 respectively). However, no significant changes in serum CXCL16 levels were found between T2DM and healthy subjects. Furthermore, serum CXCL16 concentration negatively correlated with estimated glomerular filtrate rate, creatinine clearance rate and blood albumin, and positively with 24 h proteinuria, blood urea nitrogen (BUN), creatinine, and uric acid after adjusting for age, gender and BMI in subjects with DN. Multiple stepwise regression analyses indicated that serum CXCL16 levels were independently associated with serum 24 h proteinuria, and BUN (p<0.05 respectively).

Conclusion

Serum CXCL16 may be an indicator of renal injury in subjects with T2DM. Understanding the exact mechanism of elevated CXCL16 in subjects with DN requires further study.     

Chemotactic cytokine receptor 5 gene polymorphism: relevance to microvascular complications in type 2 diabetes

We investigated the involvement of chemotactic cytokine receptor 5 (CCR5) gene polymorphism in microvascular complications of T2DM. All subjects were genotyped with the 59029 SNP in the CCR5 gene. The genotype/allele frequencies did not differ between T2DM patients and controls. Genotype distribution was compared in patients with and without complications (nephropathy, retinopathy and neuropathy). The frequency of A allele was significantly higher in patients with complications (OR for A allele 3.07, 95% CI 2.49-3.77). The A allele carriage was associated with diabetic nephropathy (OR 6.17, 95% CI 3.28-11.6). An association was observed between 59029 polymorphism and age at T2DM onset. The A allele was more frequent in early onset than in late onset patients. For AA homozygotes OR was 2.38 (1.19-4.76) and 2.26 (1.12-4.58) in complicated and uncomplicated subgroups, respectively. These results suggest that CCR5 gene polymorphism is associated with diabetic nephropathy in T2DM.     

Correlation between Serum Resistin Level and Adiposity in Obese Individuals

Objective: Resistin is associated with insulin resistance in mice and may play a similar role in humans. The aim of our study was to examine the relationship of serum resistin level to body composition, insulin resistance, and related obesity phenotypes in humans. Research Methods and Procedures: Sixty‐four young (age 32 ± 10 years), obese (BMI 32.9 ± 5.6), nondiabetic subjects taking no medication, and 15 lean (BMI 21.1 ± 1.3) volunteers were studied cross‐sectionally. Thirty‐five of the subjects were also reevaluated after 1.5 years on a weight reduction program entailing dieting and exercise; changes of serum resistin were compared with changes of BMI, body composition, fat distribution, and several indices of insulin sensitivity derived from plasma glucose and serum insulin levels measured during 75‐g oral glucose tolerance test. Results: In a cross‐sectional analysis, serum resistin was significantly higher in obese subjects than in lean volunteers (24.58 ± 12.93 ng/mL; n = 64 vs. 12.83 ± 8.30 ng/mL; n = 15; p < 0.01), and there was a correlation between resistin level and BMI, when the two groups were combined (ρ = 0.35, p < 0.01). Although cross‐sectional analysis in obese subjects revealed no correlation between serum resistin and parameters related to adiposity or insulin resistance, longitudinal analysis revealed change in serum resistin to be positively correlated with changes in BMI, body fat, fat mass, visceral fat area, and mean glucose and insulin (ρ = 0.39, 0.40, 0.44, 0.50, 0.40, and 0.50; p = 0.02, 0.03, 0.02, <0.01, 0.02, and <0.01, respectively). Discussion: Resistin appears to be related to human adiposity and to be a possible candidate factor in human insulin resistance.     

The manganese superoxide dismutase Val16Ala polymorphism is associated with decreased risk of diabetic nephropathy in Chinese patients with type 2 diabetes

The aim of the present study was to evaluate the relationship of the manganese superoxide dismutase (MnSOD) Val16Ala (V16A) polymorphism with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in Chinese patients, a case-control study was performed. This case-control study included 172 non-diabetic (non-DM) subjects and 257 T2DM patients with or without DN. Among T2DM patients, 154 had DN [albumin excretion rate (AER) >or= 30 mg/24 h] and 103 did not (AER < 30 mg/24 h), but the latter with known diabetes duration >or=10 years. The DN patients were further divided into groups with microalbuminuria (DN-1; n = 92; 300 > AER >or= 30 mg/24 h) and overt albuminuria nephropathy (DN-2; n = 62; AER >or= 300 mg/24 h). PCR-restriction fragment length polymorphism (RFLP) was used to detect genotypes of the V16A polymorphism for all subjects. The genotypic distributions of the V16A polymorphism in non-DM and T2DM subjects were in Hardy-Weinberg equilibrium and Ala allelic frequencies did not differ (11.9% vs. 9.1%; P > 0.05). The AA+VA genotypic frequencies of DN patients were significantly lower than those of non-DN patients (11.6% vs. 24.3%; P = 0.008). Multiple logistic regression analysis revealed that except for HbA1C, triglyceride, and BMI, which were high risk factors for the development of DN, the AA+VA genotype of the MnSOD-V16A polymorphism was an independent protective factor from the development of DN (odds ratio = 0.42; 95% CI = 0.18-0.95; P = 0.037) in T2DM patients. Our results suggested that the MnSOD-V16A polymorphism is associated with decreased risk of diabetic nephropathy in Chinese patients with type 2 diabetes.     

Resistin,Adiponectin, Ghrelin,Leptin, and Proinflammatory Cytokines: Relationships in Obesity

Objective: To evaluate interactions among leptin, adiponectin, resistin, ghrelin, and proinflammatory cytokines [tumor necrosis factor receptors (TNFRs), interleukin‐6 (IL‐6)] in nonmorbid and morbid obesity. Research Methods and Procedures: We measured these hormones by immunoenzyme or radiometric assays in 117 nonmorbid and 57 morbidly obese patients, and in a subgroup of 34 morbidly obese patients before and 6 months after gastric bypass surgery. Insulin resistance by homeostasis model assessment, lipid profile, and anthropometrical measurements were also performed in all patients. Results: Average plasma lipids in morbidly obese patients were elevated. IL‐6, leptin, adiponectin, and resistin were increased and ghrelin was decreased in morbidly obese compared with nonmorbidly obese subjects. After adjusting for age, gender, and BMI in nonmorbidly obese, adiponectin was positively associated with HDLc and gender and negatively with weight (β = ?0.38, p < 0.001). Leptin and resistin correlated positively with soluble tumor necrosis factor receptor (sTNFR) 1 (β = 0.24, p = 0.01 and β = 0.28, p = 0.007). In the morbidly obese patients, resistin and ghrelin were positively associated with sTNFR2 (β = 0.39, p = 0.008 and β = 0.39, p = 0.01). In the surgically treated morbidly obese group, body weight decreased significantly and was best predicted by resistin concentrations before surgery (β = 0.45, p = 0.024). Plasma lipids, insulin resistance, leptin, sTNFR1, and IL‐6 decreased and adiponectin and ghrelin increased significantly. Insulin resistance improved after weight loss and correlated with high adiponectin levels. Discussion: TNFα receptors were involved in the regulatory endocrine system of body adiposity independently of leptin and resistin axis in nonmorbidly obese patients. Our results suggest coordinated roles of adiponectin, resistin, and ghrelin in the modulation of the obesity proinflammatory environment and that resistin levels before surgery treatment are predictive of the extent of weight loss after bypass surgery.     

Hyperthyroidism is associated with higher plasma endothelin-1 concentrations

The objective of this study was to determine the change of plasma endothelin (ET)-1 concentrations and insulin resistance index after therapy for hyperthyroidism. We studied 20 patients with hyperthyroidism (15 women and 5 men; age, 34.0 +/- 2.8 years), and 31 patients with euthyroid goiters as controls (27 women, 4 men; age, 37.0 +/- 2.4 years). All hyperthyroid patients were treated with antithyroid drugs. The patients received evaluations before and after normalization of thyroid function. The evaluations included body mass index (BMI), body fat, and measurement of circulating concentrations of thyroid hormones, glucose, insulin, and ET-1. Hyperthyroid subjects had higher plasma ET-1 concentrations than the control group (P < 0.001). No significant differences in serum glucose and insulin concentrations or insulin resistance index estimated by the R value of the homeostasis model assessment (HOMA-R) were noted between the groups. Plasma ET-1 concentrations decreased after correction of hyperthyroidism compared with pretreatment (P = 0.006). Serum glucose concentrations decreased after correction of hyperthyroidism (P = 0.005). Moreover, both body weight-adjusted insulin concentrations and the HOMA-R index were also decreased after correction of hyperthyroidism compared with pretreatment (P = 0.026 and P = 0.019, respectively). Pearson's correlation revealed that plasma ET-1 levels positively correlated with serum triiodothyronine (T3) and free thyroxine (FT4) levels. Serum insulin levels and the HOMA-R index positively correlated with BMI and body fat. The HOMA-R index also positively correlated with serum T3 and FT4 levels. Neither insulin levels nor the HOMA-R index correlated with ET-1 levels. Hyperthyroidism is associated with higher plasma ET-1 concentrations. In addition, correction of hyperthyroidism is also associated with a decrease of plasma ET-1 levels as well as the insulin resistance index calculated by HOMA-R.     

HbA1c和FPG水平与2型糖尿病患者视网膜病变的相关性分析

目的：探讨糖化血红蛋（HbA1c）、空腹血糖（FPG）与2型糖尿病患者视网膜病变（DR）的相关性。方法：对我院2010年1月-2012年12月住院或门诊的336例2型糖尿病（T2DM）患者进行眼底检查或眼底血管荧光素造影检测,按有无视网膜病变分为视网膜病变（DR）组和无视网膜病变（NDR）组,并对HbA1c、FBG水平进行检测。结果：DR组较NDR组HbA1c水平高,差异有统计学意义（P〈0．05）,HbA1c水平和DR分期呈正相关（I=0．526,P〈0．001）,而DR组和NDR组FPG水平差异无无统计学意义（P〉0．05）。结论：可将HbA1c作为2型糖尿病患者视网膜病变发生和发展的监测指标之一。     

2型糖尿病患者心脏代谢指数与白蛋白尿的关系研究

摘要 目的：探讨2型糖尿病（T2DM）患者心脏代谢指数（CMI）与白蛋白尿的关系。方法：选取2012年2月~2020年7月期间在江苏大学附属医院内分泌代谢科就诊且被诊断为T2DM的患者555例,收集患者的临床资料。根据CMI不同数值将患者分为低CMI（L-CMI）组（n=185）、中CMI（M-CMI）组（n=185）和高CMI（H-CMI）组（n=185）,按照尿白蛋白/肌酐比值（UACR）将研究对象分为正常白蛋白尿组（n=294）、微量白蛋白尿组（n=209）和大量白蛋白尿组（n=52）,然后对CMI与T2DM患者发生异常白蛋白尿的关系进行分析,通过受试者工作特征（ROC）曲线评估CMI对T2DM患者发生异常白蛋白尿的预测价值。结果：不同UACR组的收缩压（SBP）、舒张压（DBP）、体质量指数（BMI）、CMI、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、糖化血红蛋白（HbA1c）、空腹血糖（FPG）、空腹胰岛素（FINS）、空腹C肽（FC-P）、稳态模型评估胰岛素抵抗指数（HOMA-IR）、尿素氮（BUN）、血尿酸（SUA）、血肌酐（Scr）及肾小球滤过率（eGFR）比较均有统计学差异（P＜0.05）。L-CMI组、M-CMI组、H-CMI组异常白蛋白尿发生比例分别为21.08%、42.70%、77.30%,异常白蛋白尿发生比例呈显著递增趋势（P＜0.05）。Spearman秩相关分析结果显示,T2DM患者UACR与FINS、BUN、 CMI、Scr、SUA、SBP、DBP、BMI、TG、TC、HbA1c、FPG、FC-P、HOMA-IR呈正相关（P<0.05）,与eGFR、HDL-C呈负相关（P<0.05）。多元线性回归分析显示,CMI对UACR的影响强度最大（P＜0.05）。Logistic回归分析结果显示,年龄、SBP、CMI、TC、LDL-C及HbA1c是T2DM患者发生异常白蛋白尿的独立危险因素（P＜0.05）。CMI预测异常白蛋白尿发生的曲线下面积为0.801,预测异常白蛋白尿的敏感性、特异性分别为68.60%、76.90%。结论：T2DM患者异常白蛋白尿发生风险与CMI密切相关,提示CMI有望成为临床上糖尿病肾病（DKD）的预测指标。     

MTHFR gene variant is not associated with diabetic nephropathy in Japanese.

Genetic predisposition has been implicated in diabetic nephropathy. The C677T variant of the MTHFR gene has been suggested to play a role in the development of not only vascular diseases but also diabetic microangiopathies. By using polymerase chain reaction-restriction length polymorphism (PCR-RFLP) method using Hinf I, we investigated whether this variant is associated with diabetic nephropathy in Japanese. By analysing 274 unrelated Japanese patients with type II DM with or without nephropathy, there was no significant difference in the genotype distribution of this variant. The distribution of the three genotypes were not different among patients with micro- or macroalbuminuria and those without nephropathy. Although previous reports suggest a role of this variant with diabetic microangiopathies, our observations suggest that this variant is does not play an important role in the pathogenesis of diabetic nephropathy in Japanese.     

Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance

The adipokine resistin has been implicated in obesity and insulin resistance. Liver cirrhosis is associated with decreased body fat mass and insulin resistance. We determined plasma resistin levels in 57 patients with cirrhosis, 13 after liver transplantation, and 30 controls and correlated these with hemodynamic as well as hepatic and systemic metabolic parameters. Patients with cirrhosis had, dependent on the clinical stage, an overall 86% increase in resistin levels (P < 0.001) with hepatic venous resistin being higher than arterial levels (P < 0.001). Circulating resistin was significantly correlated with plasma TNF-alpha levels (r = 0.62, P < 0.001). No correlation was observed between resistin and hepatic hemodynamics, body fat mass, systemic energy metabolism, and the degree of insulin resistance. However, plasma resistin in cirrhosis was negatively associated with hepatic glucose production (r = -0.47, P < 0.01) and positively with circulating free fatty acids (FFA; r = 0.40, P < 0.01) and ketone bodies (r = 0.48, P < 0.001) as well as hepatic ketone body production (r = 0.40, P < 0.01). After liver transplantation, plasma resistin levels remained unchanged, whereas insulin resistance was significantly improved (P < 0.01). These data provide novel insights into the role of resistin in the pathophysiological background of a catabolic disease in humans and also indicate that resistin inhibition may not represent a suitable therapeutic strategy for the treatment of insulin resistance and diabetes in patients with liver cirrhosis.     

血清CTRP5、CTRP12、CTRP13与老年2型糖尿病患者糖脂代谢和颈动脉粥样硬化的关系

摘要 目的：探讨血清补体1q/肿瘤坏死因子相关蛋白（CTRP）5、CTRP12、CTRP13与老年2型糖尿病（T2DM）患者糖脂代谢和颈动脉粥样硬化（CAS）的关系。方法：选取2021年1月～2023年1月徐州医科大学附属医院收治的198例老年T2DM患者纳入T2DM组,另选取同期100名体检健康老年人纳入对照组,根据是否CAS将老年T2DM患者分为CAS组131例和非CAS组67例。检测血清CTRP5、CTRP12、CTRP13和糖脂代谢指标[空腹血糖（FPG）、餐后2h血糖（2hBG）、糖化血红蛋白（HbA1c）、稳态模型评估-胰岛素抵抗指数（HOMA-IR）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）]。采用Pearson相关性分析老年T2DM患者血清CTRP5、CTRP12、CTRP13与糖脂代谢指标水平的相关性,采用多因素Logistic回归模型和受试者工作特征（ROC）曲线分析老年T2DM患者CAS的影响因素及血清CTRP5、CTRP12、CTRP13水平对其的诊断价值。结果：与对照组比较,T2DM组血清CTRP5、FPG、2hBG、HbA1c、HOMA-IR、TC、TG、LDL-C水平升高,CTRP12、CTRP13、HDL-C水平降低（P＜0.05）。Pearson相关性分析显示,老年T2DM患者血清CTRP5与FPG、2hBG、HbA1c、HOMA-IR、TC、TG、LDL-C水平呈正相关,与HDL-C水平呈负相关（P＜0.05）;血清CTRP12、CTRP13与FPG、2hBG、HbA1c、HOMA-IR、TC、TG、LDL-C水平呈负相关,与HDL-C水平呈正相关（P＜0.05）。多因素Logistic回归模型分析显示,HbA1c、HOMA-IR、LDL-C、CTRP5升高为老年T2DM患者CAS的独立危险因素,CTRP12、CTRP13升高为独立保护因素（P＜0.05）。ROC曲线分析显示,血清CTRP5、CTRP12、CTRP13水平联合诊断老年T2DM患者CAS的曲线下面积（AUC）为0.915,大于血清CTRP5、CTRP12、CTRP13水平单独诊断的0.790、0.785、0.789。结论：老年T2DM患者血清CTRP5水平升高,CTRP12、CTRP13水平降低,与糖脂代谢紊乱和CAS密切相关,血清CTRP5、CTRP12、CTRP13水平联合对老年T2DM患者CAS具有较高的诊断价值。     

NAD(P)H oxidase-stimulating activity of serum from type 2 diabetic patients with retinopathy mediates enhanced endothelial expression of E-selectin

Endothelial expression of E-selectin is enhanced in diabetic patients with retinopathy, however, the underlying mechanisms are unclear. Therefore, this study was aimed to determine if endothelial expression of E-selectin is stimulated with serum from type 2 diabetic patients with retinopathy, and whether this process is related to NAD(P)H oxidase-derived oxidative stress. Serum was obtained from type 2 diabetic patients with (T2DR) or without (T2DM) retinopathy, and age-matched non-diabetic healthy person (Control). Serum was added to in vitro-grown human coronary artery endothelial cells (HCAEC), after which E-selectin expression, reactive oxygen species (ROS) production, and NAD(P)H oxidase activity were measured. Serum from T2DR induced a significantly higher expression of E-selectin than serum from T2DM and control in association with an enhanced production of ROS in HCAEC. T2DR serum enhanced E-selectin expression in a ROS-dependent manner since this process was significantly attenuated not only by tiron (1 mM), a superoxide scavenger, but also by DPI (10 micromol/L) and apocynin (100 micromol/L), inhibitors of NAD(P)H oxidase. Furthermore, the activity of NADH oxidase was markedly increased by T2DR serum, and this was accompanied by the enhanced membrane translocation of p47phox, a cytosolic subunit of NAD(P)H oxidase. These findings suggest that serum from T2DR induced up-regulation of E-selectin expression in HCAEC, and this process might be dependent on activation of endothelial NADH oxidase via an enhanced membrane translocation of p47phox.     

Downregulation of mapk/mak/mrk overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus

BackgroundType 1 diabetes mellitus (T1DM) is one of the most common endocrine diseases in children. T-cell autoreactivity toward b-cells is controlled by significant changes in metabolism of T cells. Mammalian target of rapamycin (mTOR) is an important intracellular regulator of metabolism and cell growth. MAPK/MAK/MRK overlapping kinase 1 (MOK1) is one of the less known regulators of mTOR. We sought to investigate if MOK1 and mTOR mRNA levels in peripheral blood mononuclear cells (PBMCs) of T1DM pediatric patients are different compared to healthy subjects.MethodsThis study included 172 adolescents with T1DM and 36 healthy adolescent volunteers designated for control group (CG). MOK1 and mTOR mRNA levels were determined in PBMCs by qPCR.ResultsT1DM patients have significant downregulation of MOK1 mRNA levels in PBMCs compared CG (P=0.018), while there was no significant difference in mTOR mRNA levels (P=0.891). Furthermore, in T1DM patients, MOK1 significantly correlated with age, triglycerides and mTOR, while mTOR correlated significantly with BMI and systolic blood pressure. Overweight T1DM subjects had significantly lower MOK1 (P=0.034) and mTOR (P=0.017) mRNA levels, together with significantly higher levels of systolic blood pressure (P<0.001), total cholesterol (P=0.001), LDL-cholesterol (P=0.001) and CRP (P<0.001). Multi - variate analysis showed that MOK1 was independently negatively associated with T1DM when adjusted for sex, age, HDL-C and CRP (OR=0.417 (95%CI: 0.175-0.997), p=0.049).ConclusionsOur study demonstrated for the first time that T1DM is associated with MOK1 downregulation. In addition, downregulation of both mTOR and MOK1 gene expressions was associated with cardiovascular risk factors in overweight T1DM patients.