Prevalence of diabetes related vascular complications in subjects with normal glucose tolerance,prediabetes, newly detected diabetes and known diabetes

AimsVarying prevalence of individual diabetes related vascular complications in prediabetes has been reported. However, very few studies have looked at both macrovascular and microvascular complications in prediabetes.MethodsStudy subjects without any history of diabetes underwent oral glucose tolerance test (OGTT) and were classified as either normal glucose tolerance (NGT), prediabetes (PD), newly detected diabetes mellitus (NDDM) on the basis of American Diabetes Association (ADA) criteria. Age and sex matched known diabetes mellitus (KDM) patients were also recruited. All the participants were subsequently screened for both macrovascular (CAD, CVA,PVD) and microvascular (retinopathy, nephropathy and neuropathy)complications of diabetes.ResultsPrevalence of vascular complications among prediabetes subjects was 11.1% as compared to 1.4% among NGT subjects, 13.9% among NDDM subjects and 23.8% among KDM subjects. There was no significant between complication rates in prediabetes and NDDM group (p = 0.060). The prevalence of macrovascular and microvascular complications among prediabetes subjects was 4.2% and 6.9% while the same in NDDM was 4.2% and 9.7%.ConclusionsThe proportion of subjects with prediabetes and vascular complications was about half of those with known diabetes and almost similar to those with newly detected diabetes mellitus.     

慢性阻塞性肺疾病患者sRAGE与AGEs水平变化及意义

目的探讨慢性阻塞性肺疾病患者血浆sRAGE与AGEs水平变化及意义。方法选取我院80例慢阻肺急性加重期患者与80例慢阻肺稳定期患者,分别测量其血浆sRAGE与AGEs浓度。结果慢阻肺急性加重期患者的血浆AGEs浓度明显高于慢阻肺稳定期患者(P0.01);而血浆sRAGE浓度明显低于稳定期患者(P0.01);Pearson相关分析结果显示,血浆AGEs浓度与FEV1%呈负相关,血浆sRAGE浓度与FEV1%呈正相关。结论血浆AGEs可能是慢阻肺的危险因素,血浆sRAGE则可能是慢阻肺的保护因素,两者对判断慢阻肺病情严重程度及预后具有一定的应用价值。     

Serum levels of soluble form of receptor for advanced glycation end products (sRAGE) are positively associated with circulating AGEs and soluble form of VCAM-1 in patients with type 2 diabetes

We have recently found that soluble form of receptor for advanced glycation end products (sRAGE) levels are positively associated with inflammatory biomarkers and the presence of coronary artery disease (CAD) in type 2 diabetic patients. Since advanced glycation end products (AGEs) up-regulate RAGE expression and endogenous sRAGE could be generated from the cleavage of cell surface RAGE, it is conceivable that sRAGE is positively associated with circulating AGEs levels in diabetes. In this study, we examined whether sRAGE were correlated to circulating levels of AGEs and soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) in patients with type 2 diabetes. Eighty-two Japanese type 2 diabetic patients underwent a complete history and physical examination, determination of blood chemistries, sRAGE, AGEs, sVCAM-1 and sICAM-1. Multiple regression analysis revealed that serum levels of AGEs and sVCAM-1 were independently correlated with sRAGE. This study demonstrated that serum levels of sRAGE were positively associated with circulating AGEs and sVCAM-1 levels in type 2 diabetic patients. Our present observations suggest sRAGE level may be elevated in response to circulating AGEs, thus being a novel marker of vascular injury in patients with type 2 diabetes.     

Increased serum ferritin levels are independently related to incidence of prediabetes in adult populations

AimTo comprehensively and exhaustively assess the relationship between serum ferritin levels and incidence of prediabetes in a prospective study.MethodsThis prospective cohort study (n = 7380) with a mean follow-up of 3.07 years (range: 1–7, 95% CI: 3.03–3.12) was conducted in Tianjin, China. Blood fasting glucose, oral glucose tolerance test, serum ferritin levels and other potentially confounding factors were measured at baseline and at each year of follow-up. Adjusted Cox proportional hazards regression models were used to assess the gender-specific relationship between baseline and mean serum ferritin quintiles and prediabetes.ResultsThe incidence of prediabetes was 85 per 1000 person-years among men and 44 per 1000 person-years among women during follow-up (from 2007 to 2014). After adjusting for potential confounders, hazard ratios (95% CI) for prediabetes across baseline ferritin quintiles were: for men, 1.00, 1.13 (0.90–1.40), 1.20 (0.97–1.48), 1.41 (1.14–1.73) and 1.73 (1.41–2.11); and for women, 1.00, 1.01 (0.74–1.38), 0.68 (0.48–0.96), 0.84 (0.61–1.15) and 1.07 (0.80–1.45), respectively. Similar results were also observed for mean ferritin levels.ConclusionBoth baseline and mean serum ferritin levels were significantly and linearly related to prediabetes in men, whereas U-shaped relationships were observed between baseline and mean serum ferritin and prediabetes in women. The relationship between prediabetes risk and mean serum ferritin levels may be more stable than one with baseline serum ferritin levels.     

Circulating advanced glycation end products (AGEs) and soluble form of receptor for AGEs (sRAGE) are independent determinants of serum monocyte chemoattractant protein-1 (MCP-1) levels in patients with type 2 diabetes

BACKGROUND: Atherosclerosis is an inflammatory disease. Monocyte chemoattractant protein-1 (MCP-1) is an essential chemokine responsible for the recruitment of monocytes to inflammatory lesions in the vasculature, an initial step of atherosclerosis. Since serum levels of MCP-1 are higher in patients with type 2 diabetes, inhibition of MCP-1 may be a novel therapeutic target for prevention of accelerated atherosclerosis in diabetes. However, little is known about the regulation and determinants of serum MCP-1 levels in patients with diabetes. In this study, we examined the determinants of serum MCP-1 levels in type 2 diabetic patients. METHODS: Eighty-six consecutive outpatients with type 2 diabetes (36 male and 50 female; mean age 68.4+/-9.6) underwent a complete history and physical examination, determination of blood chemistries, MCP-1, tumour necrosis factor-alpha, adiponectin, advanced glycation end products (AGEs), and soluble form of receptor for AGEs (sRAGE). We examined the association between MCP-1 levels and those in anthropometric, metabolic and inflammatory variables in these subjects. RESULTS: Univariate regression analysis showed that serum levels of MCP-1 were positively associated with AGEs (r=0.386, p<0.001) and sRAGE (r=0.315, p<0.001). After adjusting for age and sex, AGEs (p<0.001) and sRAGE (p<0.05) still remained significant. CONCLUSION: The results demonstrate for the first time that circulating levels of AGEs and sRAGE are independent determinants of serum MCP-1 levels in patients with type 2 diabetes. Our present observations suggest the AGEs-RAGE system may be mainly involved in the elevation of MCP-1 in type 2 diabetic patients.     

Elevated plasma fibrinogen levels in patients with essential hypertension are related to vascular complications.

AIM: We investigated whether or not fibrinogen is related to the cardiovascular risk profile and complications in hypertensive subjects. METHODS: Plasma fibrinogen and laboratory tests including factor VII, homocysteine and microalbuminuria were evaluated in 127 consecutive hypertensive subjects stratified according to cardiovascular risk. Parameters were age, gender, smoking, cholesterol, diabetes, target organ damage: left ventricular hypertrophy (LVH), carotid atherosclerotic complications and retinical vessels. RESULTS: Fibrinogen levels were significantly different between patients according to risk levels (low 290+/-73, n=20, high 342+/-94 mg/dl, n=39, very high risk 350+/-72, n=29, p=0.01), hypertension grade (II-III) and organ damage. Fibrinogen was significantly higher in patients with more severe carotid atherosclerotic lesions and vascular retinal lesions (grades II-III vs 0 and I). Also in patients, matched for age and sex, without and with carotid atherosclerotic lesions, fibrinogen was significantly higher in the latter group. No significant differences were found on the basis of IVS, creatinine and microalbuminuria. In hypertensive patients, fibrinogen directly correlated with age, by multiple linear regression. In hypertensive patients with diabetes, fibrinogen was significantly higher (466+/-176 mg/dL, n=14) than in those hypertensive without diabetes (333+/-87 mg/dL, n=113, p=0.001) and in all patients there was a a significant correlation (r=0.474, p<0.001) between blood glucose and fibrinogen. CONCLUSION: Hyperfibrinogenemia is a marker of vascular damage and could be an important factor contributing to the evolution of the complications.     

Serum ferritin levels are associated with vascular damage in patients with nonalcoholic fatty liver disease

Background and aims

Increased ferritin and body iron stores are frequently observed in nonalcoholic fatty liver disease (NAFLD), associated with heightened susceptibility to vascular damage. Conflicting data have been reported on the role of iron in atherosclerosis, with recent data suggesting that excess iron induces vascular damage by increasing levels of the hormone hepcidin, which would determine iron trapping into macrophages, oxidative stress, and promotion of transformation into foam cells. Aim of this study was to investigate the relationship between iron status and cardiovascular damage in NAFLD.

Methods and results

Vascular damage was evaluated by common carotid arteries intima-media thickness (CC-IMT) measurement and plaque detection by ecocolor-doppler ultrasonography in 506 patients with clinical and ultrasonographic diagnosis of NAFLD, hemochromatosis gene (HFE) mutations by restriction analysis in 342 patients. Serum hepcidin-25 was measured by time-of-flight mass spectrometry in 143 patients. At multivariate analysis CC-IMT was associated with systolic blood pressure, glucose, LDL cholesterol, abdominal circumference, age, and ferritin (p = 0.048). Carotid plaques were independently associated with age, ferritin, glucose, and hypertension. Ferritin reflected iron stores and metabolic syndrome components, but not inflammation or liver damage. Hyperferritinemia was associated with increased vascular damage only in patients with HFE genotypes associated with hepcidin upregulation by iron stores (p < 0.0001), and serum hepcidin-25 was independently associated with carotid plaques (p = 0.05).

Conclusion

Ferritin levels, reflecting iron stores, are independent predictors of vascular damage in NAFLD. The mechanism may involve upregulation of hepcidin by increased iron stores in patients not carrying HFE mutations, and iron compartmentalization into macrophages.     

Genes for systemic vascular complications are differentially expressed in the livers of Type 2 diabetic patients

Aims/hypothesis Type 2 diabetes is characterised by excessive hepatic glucose production and frequently leads to systemic vascular complications. We therefore analysed the relationship between the gene expression profile in the liver and the pathophysiology of Type 2 diabetes.Methods Liver biopsy samples were obtained from twelve patients with Type 2 diabetes and from nine non-diabetic patients. To assay gene expression globally in the livers of both groups, we made complementary DNA (cDNA) microarrays consisting of 1080 human cDNAs. Relative expression ratios of individual genes were obtained by comparing cyanine 5-labelled cDNA from the patients with cyanine 3-labelled cDNA from reference RNA from the liver of a non-diabetic patient.Results On assessing the similarities of differentially expressed genes, the gene expression profiles of the twelve diabetic patients formed a separate cluster from those of the non-diabetic patients. Of the 1080 genes assayed, 105 (9.7%) were up-regulated and 134 (12%) were down-regulated in the diabetic livers (p<0.005). The genes up-regulated in the diabetic patients included those encoding angiogenic factors such as vascular endothelial growth factor, endothelin and platelet-derived growth factor. They also included TGF superfamily genes such as TGFA and TGFB1 as well as bone morphogenetic proteins. Among the down-regulated genes in the diabetic patients were molecules defending against stress, e.g. flavin-containing monooxygenase and superoxide dismutase.Conclusions/interpretation These findings suggest that livers of patients with Type 2 diabetes have gene expression profiles indicative of an increased risk of systemic vascular complications.Electronic Supplementary Material Supplementary material is available in the online version of this article at Abbreviations aRNA antisense RNA - BMP bone morphogenetic protein - cDNA complementary DNA - Cy cyanine - FMO flavin-containing monooxygenase - NASH non-alcoholic steatohepatitis - PDGF platelet-derived growth factor - SSC standard saline citrate - SOD superoxide dismutase - VCAM vascular cell adhesion molecule - VEGF vascular endothelial growth factor     

Serum levels of soluble vascular cell adhesion molecule are related to hyperdynamic circulation in patients with liver cirrhosis

Background: In patients with liver cirrhosis, serum levels of soluble vascular cell adhesion molecule‐1 (sVCAM‐1) have been associated with increasing fibrosis and are related to angiogenesis. Aim: To assess the possible correlation between sVCAM‐1 and splanchnic and systemic haemodynamic and clinical staging of cirrhotic patients. Methods: We assessed, using immunoassays, the serum levels of sVCAM‐1, in the peripheral and hepatic vein, in all consecutive patients with liver cirrhosis, who underwent a haemodynamic study as part of its routine clinical work‐up. Results: We studied 86 patients [61 M/25 F; age 51.1 (8.3) years] with alcoholic (31) or viral (HBV:6, HCV:49) cirrhosis, 10 of them with hepatocellular carcinoma (Milan criteria). The mean follow‐up was 391(187) days; 29 patients died or underwent transplantion during follow‐up. A strong correlation in serum levels of sVCAM‐1 was observed between the peripheral and the hepatic vein (r=0.8; P=0.0001). There was no correlation between levels of sVCAM‐1 and hepatic venous pressure gradient. At univariate analysis, sVCAM‐1 was inversely related with mean arterial pressure (r=?0.292; P=0.007), systemic vascular resistance (SVR) (r=?0.37; P=0.005) and serum sodium levels (r=?0.326; P=0.002). In multivariate linear regression only SVR remained as an independent variable associated to sVCAM‐1. A correlation of sVCAM‐1 with Child–Pugh scores, model for end‐stage liver disease (MELD) and the clinical stage proposed in the Baveno IV consensus conference was also observed. Finally, patients who died or underwent transplantion during follow‐up had significantly greater values of sVCAM‐1 at baseline than those who did not [3505(1329) vs. 2488(1208) P=0.001]. Conclusion: This study supports a potential role of sVCAM‐1 as a marker of hyperdynamic circulation, closely related to the different stage of liver cirrhosis.     

男性糖尿病患者外周血内皮祖细胞与血管病变关系的研究

目的探讨男性糖尿病（DM）患者血管病变与外周血内皮祖细胞（EPCs）数量及功能的关系。方法对15名健康者（NC组）、20例DM未合并血管病变者（DM组）、18例DM合并血管病变者（DVP组）及10例非糖尿病冠心病者（NDCHD组）采集空腹静脉血,分离并培养EPCs。应用流式细胞技术、M1vr法、Boyden小室法、黏附法对EPCs进行鉴定、计数,以及细胞增殖、迁移及黏附功能测定。结果（1）EPCs与HbA1c呈负相关（r=0.54,p=0．02）。（2）EPCs数量和增殖功能在NDCHD组〈DVP组〈DM组〈NC组（P〈0.05）。（3）EPCs迁移功能NDCHD组与DVP组间无差异,且两组均低于DM组,DM组又低于NC组（P〈0．05）;黏附功能四组间无差异。结论男性DM患者尤其是合并血管病变者,存在EPCs数量减少以及增殖、迁移功能下降,其与血管病变的发生发展相关。     

The assessment of neuropathic pain in patients with prediabetes

AimsNeuropathic pain is associated with several clinical conditions, including anxiety, depression, sleep disorders, and decreased quality of life; however, less evaluated in prediabetes. This study aims to assess neuropathic pain through validated diagnostic tools in prediabetes.MethodsOne hundred and seventy-two patients with prediabetes and 170 controls were included in this cross-sectional study. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale and Douleur Neuropathique 4 Questions (DN4) were used to evaluate neuropathic pain. The Visual Analog Scale (VAS) was used to estimate pain intensity.ResultsTwenty-three (13.4%) and 12 (7%) patients with prediabetes were diagnosed with neuropathic pain using DN4 and LANSS questionnaires, respectively. Neuropathic pain rates of the patients were higher than controls with two pain scales (p < 0.001). VAS scores were higher in prediabetes group than in controls (p = 0.021). LANSS, DN4, and VAS scores were positively correlated with HbA1c level (r = 0.184, p = 0.016; r = 0.180, p = 0.018; r = 0.188, p = 0.014, respectively). LANNS and DN4 scores were higher in female patients than in males (p < 0.001).ConclusionsNeuropathic pain was increased in prediabetes by DN4 and LANNS questionnaires. An appropriate diagnosis of neuropathic pain in prediabetes may prevent patients from different pain-related clinical conditions.     

甘露糖结合凝集素与糖尿病及其血管并发症

甘露糖结合凝集素(MBL)是一种由肝脏合成与分泌的凝集素.编码MBL的基因突变产生无功能的蛋白,致使血清中MBL的含量降低.MBL可激活补体,而补体激活及炎性反应是糖尿病血管并发症的重要发病机制.因此,探讨MBL与糖尿病的关系有可能进一步揭示糖尿病的病因,并为糖尿病血管并发症的治疗开辟一条新途径.     

Soluble endothelial protein C receptor and high sensitivity C reactive protein levels as markers of endothelial dysfunction in patients with type 1 and type 2 diabetes mellitus: Their role in the prediction of vascular complications

Background and objectiveEndothelial dysfunction in diabetes mellitus (DM) is an important factor in the pathogenesis of micro and macrovascular complications. We aimed to measure soluble endothelial protein C receptor (sEPCR) and high sensitivity C reactive protein (hsCRP) levels as markers of endothelial damage in both types of diabetes mellitus and to determine if they can be used as predictors of vascular complications.MethodsFifty patients with DM, 20 with type 1 and 30 with type 2 as well as 30 healthy subjects were included. All were subjected to measurement of sEPCR and hsCRP by enzyme linked immunosorbent assay.ResultssEPCR and hsCRP were significantly increased when compared to the control group in both types of DM. sEPCR was a significant predictor of macrovascular complications and thrombosis in type 1 p = 0.02, and p = 0.015, respectively. hsCRP was a significant predictor of macrovascular complications in type 2 p = 0.04.ConclusionPatients with type 1 and type 2 DM exhibit higher sEPCR and hsCRP levels compared to healthy controls which suggesting endothelial damage. sEPCR could be used as a predictor of macrovascular complications and thrombosis in type 1 DM, whereas, hsCRP might be used as a predictor of macrovascular complications in type 2 DM.     

Serum fucose levels in diabetic patients

Summary The total serum fucose level in diabetic patients is slightly increased in comparison with normal healthy subjects, mainly due to the presence of non protein-bound fucose. The serum fucose content after glucose loading does not show any difference between controls and potential diabetics (prediabetics). The determination of total serum fucose in patients with hyperglycemia may be complicated by the elevated blood glucose and it is necessary to use the method of internal standardization to avoid a possible error.This work was presented at the 6th Annual Meeting of the European Association for the Study of Diabetes, Warsaw, September 1970.     

老年糖尿病前期颈动脉内中膜厚度及血管内皮细胞功能的改变

目的探讨老年糖尿病前期颈动脉内中膜厚度(IMT)及血管内皮功能的变化并探讨其危险因素。方法研究对象均为≥60岁的老年人,包括26名正常人、单纯空腹血糖受损(IFG)26例、糖耐量受损(IGT)40例及空腹血糖受损(IFG)合并IGT患者30例,检测血糖、胰岛素、血脂等临床指标,并以彩色多普勒超声测量受试者的颈动脉IMT;检测各组的内皮素-1(ET-1)和一氧化氮(NO)的水平。结果①IFG、IGT、IFG+IGT三组的IMT值、ET-1和NO值均高于NGT组(均P<0.01),IFG+IGT组的NO高于IGT组(P<0.05)。②直线相关分析显示IMT与BMI、NO、TG正相关(P<0.01);NO与FINS、2 h PBG、HOMAIR、IMT、ET-1、TC、TG正相关(P<0.01);ET-1与NO、TG正相关(P<0.01),与FINS、HOMA-IR、HOMA-β正相关(P<0.05)。③多元回归分析显示IMT影响因子依次为收缩压、TG、BMI;ET-1的影响因子依次为NO、SBP、TG;NO的影响因子依次为SBP、HOMA-IR、PBG、TG。结论老年糖尿病前期患者的颈动脉内膜中层增厚,其血管内皮细胞功能已发生变化;与IMT相比,血管内皮细胞功能的变化与糖代谢紊乱有更好的相关性。