CRP＋1444C/T多态性与2型糖尿病的关系

目的探讨C反应蛋白（CRP）＋1444C/T基因多态性与2型糖尿病（T2DM）的相关性。方法采用PCR-RFLP法对156例T2DM患者（T2DM组）和149例健康体检者（NC组）行＋1444C/T基因型检测,同时测定血清CRP水平。结果T2DM组血清CRP水平显著高于对照组;两组均未检测到TT基因型,两组CRP＋1444C/T的基因型和等位基因频率分布比较均无统计学差异,对照组CT基因型者CRP水平显著高于CC基因型者。结论CRP＋1444C/T基因多态性与T2DM无相关性,血清CRP水平升高与T2DM有关。     

Urinary albumin excretion rate is independently related to autonomic neuropathy in type 2 diabetes mellitus

OBJECTIVE: To evaluate if urinary albumin excretion rate (UAER) is independently related to subclinical autonomic neuropathy in type 2 diabetes. DESIGN: A controlled cross-sectional study. SETTING: Primary health care centre. SUBJECTS: Consecutive recently diagnosed (< 1 year) type 2 diabetic patients (group A, n = 150) and patients with long-standing (median 11 years) type 2 diabetes (group B, n = 146) chosen at random. A nondiabetic control group (group C, n = 150) matched for age and gender to group A. MAIN OUTCOME MEASURES: Neuropathy by cardiovascular reflex tests and UAER by nephelometry. METHODS: Univariate statistics in group A + B (t-test chi 2- or McNemars test) with Valsalva and breathing ratios as categorical grouping variables and the independent variables gender, smoking, systolic and diastolic blood pressure, fasting serum cholesterol, HDL cholesterol, triglycerides, haemoglobin A1c, glucagon stimulated C-peptide, fasting and postload 1 and 2 h blood glucose and serum insulin, UAER, coronary heart disease and congestive heart failure. Logistic regression analyses in group A + B with Valsalva and breathing ratios as dependent categorical variables and age, systolic blood pressure, congestive heart failure, coronary heart disease, fasting blood glucose, serum triglycerides and UAER as independent variables. RESULTS: Compared to nondiabetic subjects the diabetic patients of both groups were at increased risk of neuropathy as judged by the Valsalva ratio (P < 0.01). In known diabetic patients with a UAER > or = 30 mg 24-1 h neuropathy was more common than amongst their normoalbuminuric counterparts (Valsalva test P = 0.007, breathing test P = 0.02). In logistic regression analysis UAER independently explained abnormal Valsalva (P = 0.015) and breathing tests (P = 0.04) in the group A + B. CONCLUSIONS: UAER is independently related to subclinical autonomic neuropathy in type 2 diabetes.     

2型糖尿病病人冠状动脉病变与血清C-反应蛋白水平

目的探讨2型糖尿病合并冠心病患者冠状动脉病变与血清C-反应蛋白(C-reactive protein, CRP)的相关性。方法 2型糖尿病患者,经冠状动脉造影分为合并冠心病组和冠状动脉正常组,检测其 CRP水平,并对CRP和冠状动脉病变作相关分析。结果合并冠心病组CRP水平明显高于冠状动脉正常组,合并冠心病患者CRP水平随病变支数增加而增加。结论 2型糖尿病合并冠心病患者,随着冠状动脉粥样硬化病变程度加重,血清CRP水平明显升高。监测2型糖尿病患者血清CRP水平,对预测其冠状动脉粥样硬化病变的严重程度有一定意义。     

High-sensitivity C-reactive protein in subjects with type 2 diabetes mellitus and/or high blood pressure

Type 2 diabetes mellitus (DM2) and high blood pressure (HBP) may contribute to the development of cardiovascular disease, and inflammation may be an important factor in these diseases. In the present study, plasma levels of high-sensitivity C-reactive protein (hs-CRP) were measured in subjects with DM2 and/or HBP and compared to those of normal subjects. Eighty-nine subjects were analyzed for hs-CRP, including 13 normotensive patients with DM2, 17 patients with HBP, 34 hypertensive patients with DM2 (DM2+HBP) and 25 normal subjects. The plasma hs-CRP levels were significantly lower in the controls than in the HBP+DM2 group (p < 0.05). DM2 associated with HBP was also correlated with increased plasma hs-CRP levels (n = 89, r = 0.25, p = 0.0162). Only hypertensive patients with DM2 had higher levels of hs-CRP, a circulating inflammatory marker, than normal subjects. This finding suggests that patients with two associated diseases have a more active inflammatory state.     

Visceral adiposity and leptin are independently associated with C-reactive protein in Korean type 2 diabetic patients

The inflammatory marker, C-reactive protein (CRP) is associated with long-term cardiovascular events. The aim of the study was to investigate the factors contributing to serum CRP, assess the relationship between CRP level and the parameters of visceral obesity, and examine the association between leptin and CRP level in type 2 diabetic patients. 150 patients with type 2 diabetes were enrolled. These patients were recently diagnosed (≤3 years) with type 2 diabetes and were drug naive or taking sulfonylureas only. BMI, WC, and serum concentration of CRP, glycosylated hemoglobin (HbA1c), glucose, lipids, plasminogen activator-1 (PAI-1) and leptin were measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). We measured the carotid intima-media thickness (IMT). Fat mass assessed by dual-energy X-ray absorptionmetry and abdominal fat distribution was determined by CT scan. Serum concentration of CRP was significantly correlated with BMI (γ = 0.257, P < 0.01), WC (γ = 0.293, P < 0.01), fat mass (γ = 0.213, P < 0.01), total adipose tissue (γ = 0.263, P < 0.01), visceral adipose tissue (γ = 0.296, P < 0.01), insulin (γ = 0.189, P = 0.047), PAI-1 (γ = 0.206, P < 0.01), leptin (γ = 0.322, P < 0.01), mean IMT (γ = 0.132, P = 0.042), and HOMA-IR (γ = 0.172, P = 0.045). After adjustment for age and gender, multiple regression analysis showed that serum CRP was significantly associated with leptin (β = 0.326, P = 0.01) and visceral adipose tissue (β = 0.265, P = 0.035). In conclusion, serum CRP level is significantly associated with obesity, especially the visceral adipose tissue, and serum leptin is another important independent factor associated with CRP in Korean type 2 diabetic patients.     

2型糖尿病合并高血压患者血浆脂联素的变化

目的探讨2型糖尿病(T2DM)患者、DM合并高血压患者中血浆脂联素水平的变化。方法选取T2DM患者62例、T2DM合并高血压患者41例、健康对照者35名作为研究对象。测定受试者血浆脂联素水平、身高、体重等,比较脂联素水平的改变,以及与其他因素的相关性。结果T2DM患者血浆脂联素明显低于正常对照组(P<0.001),DM合并高血压者血浆脂联素又明显低于DM无高血压者(P<0.01)。在DM患者中,血浆脂联素与收缩压呈负相关(P<0.001)。结论T2DM患者血浆脂联素明显降低,T2DM合并高血压者血浆脂联素水平更低,脂联素在高血压发病过程中起一定作用。     

糖尿病大血管并发症与血清高分子质量脂联素水平的相关性

目的探讨2型糖尿病大血管并发症与血清高分子质量脂联素（HMM-ADPN,H-ADPN）水平之间的相关性。方法选取2010年12月至2012年12月接受治疗的106例2型糖尿病患者,分为单纯2型糖尿病组（A组,n=66）和2型糖尿病合并大血管病变组（B组,n=40）。测量所有受试者的身高、体质量、血压,同时分别测定高密度脂蛋白胆固醇（HDL．C）、低密度脂蛋白胆固醇（LDL-C）、三酰甘油（TG）、总胆固醇（TC）、糖化血红蛋白（HbAlc）、空腹血糖（FBG）、高敏C．反应蛋白（hs-CRP）、血清总脂联素（ADPN）、H．ADPN、空腹胰岛素（FINS）、颈动脉内膜中层厚度（CIMT）等。结果两组间血清H-ADPN水平差异有统计学意义（P〈0．05）,多因素logisticl回归分析显示,调整年龄、性别、体质量指数（BMI）及hs．CRP等因素后血清H．ADPN水平与HDL-C水平呈显著正相关（P〈0．05）,与收缩压及CIMT呈负相关（P〈0．05）.结论血清H．ADPN水平在糖尿病动脉粥样硬化过程中可能起重要作用,与2型糖尿病大血管并发症的发生和发展相关。     

2型糖尿病患者血清高敏C反应蛋白水平与代谢综合征的相关性研究

目的通过对以不同的代谢综合征（MS）的组分出现的2型糖尿病（T2DM）患者的血清高敏C-反应蛋白（hsC-RP）水平的比较，探讨T2DM患者hsC-RP水平与MS的关系。方法共计调查了病例组（MS组）96例，T2DM对照组（T2DM组）104例，正常对照组80例。比较了以上三组及合并不同数量、不同种类MS组分的各组间hsC-RP水平，并进行各指标之间的相关分析。结果MS组患者hsC-RP水平明显高于正常对照组及T2DM组，且差异有统计学意义（P〈0．01），T2DM患者中hsC-RP水平与合并MS所含组分的数量呈正相关（P〈0．01），与合并MS所含组分的种类无关（P〉0．05）。吸烟、BMI、WHR、胰岛素抵抗、高TG血症、血糖、高血压与hsC-RP呈正相关。结论T2DM患者hsC-RP水平与MS有相关性，炎症反应可能在MS的发病机制中起重要作用。     

Elevated high sensitivity C-reactive protein is associated with type 2 diabetes mellitus: the Persian Gulf Healthy Heart Study

Previous studies have suggested that low-grade systemic inflammation is involved in the pathogenesis of type 2 diabetes mellitus. However, limited information is available about the relationship of diabetes mellitus and inflammation in Asia. We examined the association between high-sensitivity C-reactive protein (CRP) levels and diabetes in a general Iranian population. In an ancillary study to the Persian Gulf Healthy Heart Study, a cohort study of men and women aged > or = 25 years, a random sample of 1754 (49.2 percent males, 50.8 percent females) subjects were evaluated. High sensitivity C-reactive protein was measured by enzyme-linked immunosorbent assay. Elevated serum CRP was defined as more than 3.0 mg/l. The diabetes classification was based on the criteria of the American Diabetes Association. A total of 8.6 percent of the subjects (8.0 percent of males & 9.1 percent of females; p>0.05) had type 2 diabetes mellitus. Geometric mean of CRP was 1.94 mg/l (3.80 SD) in the studied population. The subjects with diabetes had a higher geometric mean of CRP levels than the subjects with no diabetes [3.67 (SD 3.71) versus 1.85 (3.83) respectively; p<0.0001)]. In multiple logistic regression analysis, diabetes showed a significant age-adjusted association with elevated CRP levels [Odds Ratio = 2.03, Confidence Interval (1.38-2.98); p<0.0001] after adjusting for sex, LDL-cholesterol, HDL-cholesterol blood pressure, smoking and body mass index. In conclusion, beyond traditional cardiovascular risk factors, elevated CRP is significantly correlated with diabetes in general population of the northern Persian Gulf. Further insight into the specific effects of proinflammatory cytokines and acute-phase proteins will be essential for the development of new preventive strategies for diabetes mellitus.     

Elevated plasma phospholipid transfer protein activity is a determinant of carotid intima-media thickness in type 2 diabetes mellitus

Aim/hypothesis The plasma activity of phospholipid transfer protein (PLTP), which has putative pro- and anti-atherogenic roles in lipoprotein metabolism, is increased in type 2 diabetes mellitus. We analysed the relationship between carotid artery intima–media thickness (IMT), an established marker of atherosclerosis, and PLTP activity in diabetic patients and control subjects. Methods The IMT (mean of three segments in both carotid arteries by ultrasonography), clinical variables, plasma PLTP activity (phospholipid vesicle–HDL system), lipoproteins, C-reactive protein and insulin were measured in 87 non-smoking men and women, who had type 2 diabetes mellitus, no cardiovascular disease, and were not on insulin or lipid-lowering medication, and in 83 age-matched control subjects. Results In diabetic patients, carotid IMT (p=0.02), pulse pressure (p=0.003), plasma PLTP activity (p<0.001), triglycerides (p=0.01), C-reactive protein (p<0.01) and insulin (p<0.001) were higher, whereas HDL cholesterol was lower (p<0.001) than in control subjects. Multiple stepwise linear regression analysis demonstrated that in type 2 diabetic patients IMT was independently associated with age (p<0.001), sex (p=0.001), pulse pressure (p=0.003), plasma PLTP activity (p=0.03) and HDL cholesterol (p=0.03), but not with very low density lipoprotein+LDL cholesterol, triglycerides, C-reactive protein and insulin (all p>0.20). The relationship between plasma PLTP activity and IMT was not significant in control subjects. Conclusions/interpretation Plasma PLTP activity is a positive determinant of IMT in type 2 diabetes mellitus, suggesting that high PLTP activity is involved in accelerated atherosclerosis in this disease.     

Increased epicardial fat and plasma leptin in type 1 diabetes independently of obesity

Background and aimVisceral fat and related adipokines, such as leptin and adiponectin, have been recently suggested to play a role in type 1 diabetes. Nevertheless epicardial fat, the visceral fat of the heart, has been poorly explored in type 1 diabetes. In this study we sought to measure epicardial fat thickness, plasma leptin and adiponectin levels in type 1 diabetic subjects.Methods and results15 subjects with type 1 diabetes (age 52.8 ± 12, 10 females, 5 males, BMI 27.8 ± 5.2) and 15 non-diabetic controls underwent echocardiographic epicardial fat thickness measurement and blood tests for adipokines and Hemoglobin A1c (HbA1c). There were no differences in BMI, age, sex, blood pressure, inflammatory markers and adiponectin between subjects with diabetes and controls. Daily insulin requirement of subjects with type 1 diabetes was 0.54 ± 0.2 UI/kg and HbA1c was 7.6 ± 1.0 reflecting acceptable glycemic control. Patients with Type 1 diabetes showed significantly higher epicardial fat thickness (7.2 ± 2.1 vs 4.9 ± 2.5 mm p < 0.01) and plasma leptin levels (25.9 ± 19 vs 18 ± 12 ng/ml p < 0.01) than controls. Leptin resulted in the best independent correlate of epicardial fat thickness (R² = 0.48, p = 0.04, β = 2.45).ConclusionsOur study provides two major findings of novelty: 1) subjects with type 1 diabetes have higher epicardial fat and serum leptin levels than non-diabetic subjects, 2) epicardial fat thickness and serum leptin levels are the best independent correlates of each other in patients with type 1 diabetes independently of BMI, HbA1c, daily insulin requirement. The mechanisms that link epicardial fat to leptin levels in type 1 diabetes remain to be elucidated.     

High-sensitivity C-reactive protein is associated with hippocampus volume in nondementia patients with type 2 diabetes mellitus

The elevated level of high-sensitivity C-reactive protein (HSCRP) is associated with cognitive dysfunction, for which changes in the hippocampus plausibly play a pivotal role. We tested the hypothesis that an elevated level of HSCRP correlates with hippocampus volume and insulin resistance in nondementia patients with type 2 diabetes mellitus. Subjects included 45 nondementia patients with type 2 diabetes mellitus, who were divided into 2 groups: high-HSCRP group (age, 65 ± 6 years [mean ± SD]; n = 17) and normal-HSCRP group (65 ± 7 years, n = 28). Hippocampus volume has been quantitated with computer-assisted analysis using a magnetic resonance imaging voxel-based specific regional analysis system developed for the study of Alzheimer disease (VSRAD), which yields a z score as the end point for assessment of hippocampal volume. The z score was higher in the high-HSCRP group than in the normal-HSCRP group (P < .0001). The fasting plasma glucose (P < .05) and insulin concentrations (P < .0001) and the homeostasis model assessment (HOMA) index (P < .0001) were higher in the high-HSCRP group than in the normal-HSCRP group. Multiple regression analysis showed that HSCRP levels were independently predicted by z score and HOMA index. Our results indicate that the elevated level of HSCRP in Japanese nondementia patients with type 2 diabetes mellitus is characterized by increased hippocampus volume and insulin resistance, and that the z score and HOMA index are independent predictors of HSCRP.     

Atorvastatin lowers C-reactive protein and improves endothelium-dependent vasodilation in type 2 diabetes mellitus

Endothelial dysfunction is frequently found in diabetic subjects. This study was performed to investigate whether atorvastatin therapy was able to reverse endothelial dysfunction in type 2 diabetes and, if so, whether the effect was due to its antiinflammatory action. Eighty patients (baseline low density lipoprotein, 4.37 +/- 0.71 mmol/liter) were randomized to atorvastatin (10 mg daily for 3 months, followed by 20 mg daily for 3 months) or placebo in a double blind study. Endothelial function was assessed by high resolution vascular ultrasound, and high sensitivity C-reactive protein (CRP) was assessed by immunoturbidimetric assay. Diabetic patients had higher CRP (P < 0.01) than matched nondiabetic controls, and both endothelium-dependent and independent vasodilation were impaired (P < 0.01). Atorvastatin (10 and 20 mg) lowered plasma cholesterol by 32.9% and 38.0%, triglyceride by 15.4% and 23.1%, and low density lipoprotein by 43.4% and 50.1%, respectively. At 6 months, plasma CRP decreased in the atorvastatin group compared with baseline (P < 0.05). Endothelium-dependent vasodilation improved in the atorvastatin group compared with the placebo group (P < 0.05). The percent change in endothelium-dependent vasodilation at 6 months correlated with the percent change in CRP (r = -0.44; P < 0.05), but not with changes in plasma lipids. In conclusion, treatment with atorvastatin in type 2 diabetes led to a significant improvement in endothelium-dependent vasodilation, which might be partly related to its anti-inflammatory effect.     

Strong decrease of high sensitivity C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus

OBJECTIVE: Statins are known to reduce CRP concentrations, but whether high doses are more effective is not known. METHODS: In a prospective double-blind multicenter study in 186 DM2 patients without manifest coronary artery disease and with dyslipidemia, the effect of a 30-week treatment with 10 and 80 mg atorvastatin or placebo on the reduction of hs-CRP levels was measured. RESULTS: Median CRP levels increased with 6.6% in the placebo group and were reduced by 15 and 47%, respectively, with atorvastatin 10 and 80 mg (P<0.001; significantly different from 10 mg atorvastatin and from placebo (P<0.001). Variation in IL-6 and plasma lipids associated for 21 and 8%, respectively, with variation in CRP levels (P<0.001 and P=0.01). Of patients with a baseline CRP level above an arbitrary threshold of 3.0 mg/l, 56% in the 80 mg atorvastatin group reached a level of less than 3.0 mg/l, versus 23% randomized to 10 mg atorvastatin (P<0.01) and 17% in the placebo group (P<0.005). CONCLUSIONS: In DM2 patients high dose atorvastatin induced a strong reduction in CRP levels. The decrease in CRP was mainly independent of effects on lipid lowering and changes in IL-6 levels. The pleiotropic effect of high-dose atorvastatin on inflammation could add to its cardioprotective effect in high-risk patients.     

罗格列酮对2型糖尿病患者C反应蛋白的影响

目的观察罗格列酮（RSG）治疗2型糖尿病（T2DM）前后血清高敏C反应蛋白（hsC-RP）的变化。方法采用随机、双盲、安慰剂平行对照法将120例已合用磺脲类和双胍类药物的T2DM患者随机分为安慰剂组和RSG组,治疗12周。结果安慰剂组的HbA1c明显下降（P〈0.05）,其他指标均无显著变化;RSG组与基线比较FPG、2hPG、HbA1c、胰岛素抵抗指数、hsC-RP均明显下降（P均〈0.01）。结论RSG治疗T2DM,除能改善胰岛素抵抗,降低血糖,还有明显的抗炎症作用,使hsC-RP下降。     

Effects of pioglitazone and metformin on plasma adiponectin in newly detected type 2 diabetes mellitus

OBJECTIVE: This prospective study evaluates the effect of insulin sensitizers, pioglitazone (PGZ) and metformin (MET) on plasma adiponectin and leptin levels in subjects newly diagnosed with type 2 diabetes mellitus (T2DM). DESIGN: Double blind, randomized, active control, dose escalation study of 12 weeks treatment duration. PATIENTS: Thirty apparently healthy, treatment-naive T2DM patients diagnosed within the past 6 months. MEASUREMENTS: Plasma adiponectin and leptin levels were estimated by enzyme-linked immunosorbent assay (ELISA), and insulin resistance by the homeostasis model of assessment (HOMA-IR). RESULTS: Baseline plasma levels of adiponectin were lower in diabetic (n = 30) subjects than matched controls (n = 10, 6.6 +/- 1.1 vs 10.4 +/- 4.2 microg/ml, P = 0.021). The 12-week treatment with PGZ significantly increased adiponectin concentrations (6.6 +/- 1.1-17.9 +/- 7.4 microg/ml, P < 0.001) with no alteration in the MET treated group (6.8 +/- 1.5-6.7 +/- 2.8 microg/ml, P = 0.9). A significant decrease in plasma leptin levels was observed in the MET treated group (32.0 +/- 28.9-21.4 +/- 23.3 ng/ml, P = 0.024) but not in the PGZ treated group (23.9 +/- 24.1-22.4 +/- 25.4 ng/ml, P = 0.69). The alterations in plasma adiponectin and leptin levels were not associated with any change in body mass index (BMI). PGZ therapy improved insulin sensitivity to a greater degree (P = 0.007 and P = 0.001 for fasting plasma insulin (FPI) and HOMA-IR, respectively) than MET (P = 0.75 and P = 0.02 for FPI and HOMA-IR, respectively) but this improvement was not significantly different from that of MET at the end of 12 weeks (P = 0.146 and P = 0.09 for FPI and HOMA-IR, respectively). However, improvement in insulin sensitivity with PGZ was not commensurate with the increase in adiponectin. Better control of postbreakfast plasma glucose (PBPG) as well as decrease in serum triglycerides (TGs) were also seen with PGZ (PBPG, P < 0.001; TGs, P = 0.013). The rest of the parameters were comparable. Adverse reactions reported were minor and did not result in treatment discontinuation. CONCLUSIONS: Pioglitazone therapy appears to be better in achieving glycaemic control and increasing plasma adiponectin and insulin sensitivity in newly detected type 2 diabetics.     

Dynamics of serum C-reactive protein (CRP) level and cosmophysical activity

BACKGROUND: C-reactive protein (CRP), an acute phase reactant, plays an important part in the investigation of the role of inflammation in pathology. Many cardiovascular events show significant associations with various cosmophysical parameters. The aim of this study was to investigate the relationship between the level of CRP and the levels of solar, geomagnetic (GMA), and cosmic ray activity. METHODS: The results of 25,399 serum CRP tests carried out over a 3-year period were compared with the monthly and daily levels of solar, geomagnetic, and cosmic ray activity during the same period. The cosmophysical data were obtained from the National Oceanic Atmospheric Administration (NOAA) in the U.S. and from the Russian Academy of Science. RESULTS: On a monthly basis, CRP levels showed no correlation with GMA (n=36, r=0.258, p=0.13), but there was a significant inverse relationship with neutron activity (r=-0.35, p=0.03). For the daily comparisons, CRP levels were significantly correlated with GMA (n=1057, r=0.97, p=0.02), and there was a significant inverse relationship with neutron activity (r=-0.97, p=0.025). Daily neutron activity was higher on days with CRP levels of 0-1.0 mg/dl (n=289) and above1.0-1.5 mg/dl (n=1213) than on days with higher CRP values (>1.5; n=23,897; p<0.0001). CONCLUSION: The level of serum CRP, in addition to its association with inflammation, is related to the daily level of GMA and inversely to the level of neutron activity.