胰岛素泵治疗对不同病程2型糖尿病患者8-异前列腺素F2α的影响

8-异前列腺素F2α是细胞膜上脂化的花生四烯酸受自由基攻击后裂解而形成的前列腺素衍生物,其产生与机体氧化应激损伤关系极为密切,是评价氧化应激和脂质过氧化反应最有效的生物指标之一[1].其可以促进胰岛素抵抗及胰岛β细胞功能凋亡.2型糖尿病被证实与氧化应激及炎症密切相关,C-反应蛋白是反应炎症的重要因子.胰岛素泵强化治疗可在短期内获得理想的血糖控制,逆转高血糖的某些毒性作用,使胰岛β细胞功能得到恢复,胰岛素分泌增加,改善机体胰岛素抵抗[2].目前国内外对胰岛素泵干预对8-异前列腺素F2α及C反应蛋白的影响尚未见相关报道,本试验通过对不同病程的2型糖尿病患者胰岛素泵强化治疗,测定8-异前列腺素F2α及C反应蛋白的变化情况,探讨胰岛素泵在氧化应激及炎症中的作用.     

尿8-异-前列腺素F2α评估2型糖尿病合并不稳定型心绞痛患者罪犯血管斑块破裂的价值

目的 观察2型糖尿病(type 2 diabetes mellitus,T2DM)合并不稳定型心绞痛(unstable angina pectoris,UAP)罪犯血管斑块破裂患者尿8-异-前列腺素F2α(8-iso-prostaglandin F2α,8-iso-PGF2α)水平变化,探讨尿8-iso-PGF2α预测...     

血浆8-异前列腺素F2a和同型半胱氨酸在糖尿病患者中的变化

目的探讨糖尿病患者血浆同型半胱氨酸（Hcy）以及8-异前列腺素F2a（8-iso-PGF2a）变化情况及两者的相关性。方法 52例2型糖尿病患者根据24h尿蛋白排泄率检测结果分为单纯糖尿病组30例（DM组）、糖尿病肾病组22例（DN组）,健康体检者30例为对照组（NC组）。采用酶联免疫法测定血浆Hcy以及8-iso-PGF2a水平,Pearson′s分析进行相关性分析。结果 DN组8-iso-PGF2a、Hcy水平最高,与其他两组相比差异均有统计学意义（P〈0.05）。Pearson′s分析8-iso-PGF2a与超敏C反应蛋白（hs-CRP）、Hcy、三酰甘油（TG）、体质量指数（BMI）、纤维蛋白原（FIB）、血管内皮因子（vWF）、蛋白C（PC）、蛋白S（PS）呈正相关,与人抗凝血酶Ⅲ（ATⅢ）呈负相关。Hcy与hs-CRP、TG、vWF、FIB、PS呈正相关,而与ATⅢ呈负相关。结论 2型糖尿病患者氧化应激水平的上升与患者病情进展具有密切的关系,因此对2型糖尿病患者积极控制血糖的同时尽早对其进行抗凝及抗氧化治疗,这有利于预防微血管并发症的发生。     

初诊2型糖尿病患者前列环素与胰岛素抵抗的相关分析

目的分析初诊2型糖尿病(T2DM)患者血浆前列环素(PGI2)水平变化及其与胰岛素抵抗(IR)的相关性。方法选择初诊T2DM患者60例及健康对照组60例,测定体质量、身高、血脂、空腹血糖(FPG)、餐后2h血糖(2hPG)、空腹胰岛素(FINS)、餐后2h胰岛素(2hINS),计算胰岛素抵抗指数(HOMA-IR),测定血浆PGI2的稳定代谢产物6-酮-前列腺素F1α(6-keto-PGF1α)浓度,并作相关性分析。结果 T2DM组体质量指数(BMI)、三酰甘油(TG)、总胆固醇(TC)、FPG、2hPG、FINS、2hINS、HOMA-IR均高于健康对照组,差异有统计学意义(P0.05);T2DM组血浆6-keto-PGF1α水平较健康对照组明显下降(P0.01);血浆6-keto-PGF1α水平与HOMA-IR呈负相关(r=-0.82,P0.01)。结论 T2DM患者存在IR,血浆PGI2的代谢终末产物6-keto-PGF1α水平与IR密切相关。     

重型颅脑损伤患者血浆8-异前列腺素F2α浓度的检测及临床价值

目的分析血浆8-异前列腺素F2α(8-iso-PGF2α)水平与重型颅脑损伤(STBI)患者外伤严重程度及6个月死亡的关系。方法选取120例STBI患者(外伤组)及120例健康体检者(对照组)作回顾性研究。用酶联免疫吸附试验检测两组血浆8-iso-PGF2α浓度,采用多元线性回归分析法分析其与外伤严重程度的关系。采用受试者工作特征曲线分析血浆8-iso-PGF2α浓度对外伤后6个月死亡的预测价值。结果外伤组血浆8-iso-PGF2α水平高于对照组(t=17.682,P0.001)。血浆8-isoPGF2α水平与STBI患者格拉斯哥昏迷评分呈负相关(t=-5.780,P0.001),且是外伤后6个月死亡的独立危险因素(OR=1.007,95%CI=1.004~1.010,P0.001)。血浆8-iso-PGF2α水平可预测外伤后6个月死亡(灵敏度:0.82,特异度:0.64,曲线下面积=0.826,95%CI=0.747~0.889)。结论 STBI患者血浆8-iso-PGF2α水平升高,且与其外伤严重度及长期预后密切相关。     

血清单核细胞趋化蛋白-1、8-异前列腺素F2a与2型糖尿病增殖期视网膜病变的关系

目的 糖尿病增殖期视网膜病变(PDR)是导致失明的主要危险因素之一,目前发病机制尚未完全明确.通过研究血清单核细胞趋化蛋白-1(MCP-1)、8-异前列腺素F2a(8-iso-PGF2a)与2型糖尿病PDR的关系,探讨炎症反应和氧化应激在2型糖尿病PDR中的作用机制及临床意义.方法 选择2012年6月至12月血压正常的非增殖期和增殖期的2型糖尿病视网膜病变病人106例,其中非增殖期病人50例(NPDR组)和增殖期病人56例(PDR组).测定血清MCP-1、8-iso-PGF2a、空腹血糖(FBG)、24小时尿微量白蛋白(24hUMA)和糖化血红蛋白(HbA1c),比较它们之间的差异,分析PDR发生的相关危险因素.结果 PDR病人血清中的MCP-1、8-iso-PGF2a和24hUMA明显高于NPDR病人(P均＜0.01),血清MCP-1、24hUMA分别与血8-iso-PGF2a呈正相关(r=0.915,0.865,P＜0.01).血清8-iso-PGF2a是24hUMA和血清MCP-1的独立影响因素(β=0.865,0.915;P =0.000).糖尿病视网膜病变家族史、24hUMA、血清MCP-1、8-iso-PGF2a是PDR病变的独立危险因素(OR=1.21,1.63,1.86,1.57).结论 氧化应激和炎症反应可能共同参与糖尿病PDR的发展,血清MCP-1和8-iso-PGF2a有可能作为预测糖尿病视网膜病变进展的标志物,但尚需大样本的临床研究进一步证实.     

2型糖尿病患者的血脂和血尿酸水平的临床分析

目的 为了研究2型糖尿病（DM2）患者测定血脂和血尿酸的临床意义。方法采用生化法测定了98例DM2的血脂和血尿酸水平,其中包括TC、TG、HDL-C、LDL-C和SUA,并与64名正常对照组进行了对比和相关性分析。结果 98例DM2患者的血脂水平分析：TC、TG、LDL-C和SUA水平较之64名正常对照组明显增高（P均＜0.01）,HDL-C水平明显降低（P＜0.05）。血脂TC、TG和LDL-C与SUA呈正相关,r分别为0.612、0.584和0.503（P＜0.05）,HDL-C与SUA呈负相关,r为-0.561（P＜0.05）。结论 DM2患者的血脂紊乱和SUA的增高是造成动脉粥样硬化（AS）的危险因素,故应控制饮食和积极治疗以减缓AS的发生.     

2型糖尿病人群DNA氧化损伤情况分析

目的 了解2型糖尿病人群DNA氧化损伤的情况.方法 采用酶联免疫吸附法(ELISA)检测,健康人群和2型糖尿病人群尿样DNA中8-羟基脱氧鸟苷(8-OHdG)的含量.结果 尿样DNA中的8-OHdG水平显示,长于半年病程2型糖尿病病例和2型糖尿病伴肾病病例分别为22.37±5.62 ng/mgGr和23.80±7.58 ng/mgGr,明显高于健康人的15.74±6.10 ng/mgGr (P<0.05).结论 长于半年病程2型糖尿病病例和2型糖尿病伴肾病病例的DNA氧化损伤水平均高于健康人群.对于预防和监测2型糖尿病病人,测定尿样中8-OHdG含量是一个简单、准确的方法.     

辛伐他汀对高脂血症患者早期氧化应激及循环中维生素E的影响——附30例报告

目的：研究辛伐他汀对高脂血症患者早期氧化应激的抑制作用,评估辛伐他汀抑制氧化应激是否独立于降低胆固醇,及氧化应激改变时维生素E的变化。方法：对30例高脂血症患者（高脂血症组）和20名健康受试者（对照组）,进行治疗前分别测量其血清总胆固醇、尿8-异前列腺素F2ａ和血浆维生素E含量并进行比较。干预治疗时,将30例高脂血症患者随机分为随机饮食组（饮食组）或饮食加服辛伐他汀10 mg/d组（治疗组）各15例,分别在基线、第3日、第30日时测量上述指标并进行比较。结果：与对照组相比,高脂血症组的血清总胆固醇、尿8-异前列腺素F2ａ含量较高,维生素E含量较低（P〈0.05～0.01）。与饮食组比较,治疗组治疗第3日尿8-异前列腺素F2ａ开始减少（P〈0.05）,第30日时,尿8-异前列腺素F2ａ明显减少,而维生素E增多,血清总胆固醇降低（均为P〈0.05）。结论：高脂血症患者应用辛伐他汀,在早期即可降低尿8-异前列腺素F2ａ,减轻氧化应激,且这种作用不依赖于血脂的降低,随着应用时间的延长,亦能降低总胆固醇,增加循环中抗氧化维生素E水平。     

脑出血患者血浆8-表氧前列腺素F2α的检测及临床意义

目的揭示血浆8-表氧前列腺素F2α(8-iso-PGF2α)浓度与脑出血预后的关系。方法选取86例高血压性基底节出血患者为脑出血组,另选86例体检者为对照组。采用酶联免疫吸附法(ELISA)法检测血浆8-isoPGF2α浓度,记录患者入院时格拉斯哥昏迷评分、血肿量、脑室积血及脑出血后3个月预后等资料。比较脑出血组和对照组血浆8-iso-PGF2α浓度的变化,分析脑出血患者3个月内死亡和预后不良的危险因素,评价血浆8-isoPGF2α浓度对脑出血患者3个月内死亡及预后不良的预测价值。结果脑出血组血浆8-iso-PGF2α浓度为(576.69±229.98)pg/ml较对照组的(67.67±21.54)pg/ml明显升高,差异有统计学意义(t=22.37,P<0.05);脑出血后3个月内死亡16例(18.61%)、预后不良29例(33.72%);入院时血浆8-iso-PGF2α浓度是脑出血后3个月内死亡(OR=1.28,95%CI为1.08~2.67,P<0.05)和预后不良(OR=1.31,95%CI为1.10~2.99,P<0.05)的独立危险因素。结论脑出血患者血浆8-iso-PGF2α浓度明显升高,与脑出血后3个月内死亡和预后不良有关。     

Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia

Oxidative stress, through the production of reactive oxygen species (ROS), has been proposed as the root cause underlying the development of insulin resistance, beta-cell dysfunction, impaired glucose tolerance and type 2 diabetes mellitus (T2DM). It has also been implicated in the progression of long-term diabetes complications, including microvascular and macrovascular dysfunction. Excess nourishment and a sedentary lifestyle leads to glucose and fatty acid overload, resulting in production of ROS. Additionally, reaction of glucose with plasma proteins forms advanced glycation end products, triggering production of ROS. These ROS initiate a chain reaction leading to reduced nitric oxide availability, increased markers of inflammation and chemical modification of lipoproteins, all of which may increase the risk of atherogenesis. With the postulation that hyperglycaemia and fluctuations in blood glucose lead to generation of ROS, it follows that aggressive treatment of fasting and postprandial hyperglycaemia is important for prevention of micro and macrovascular complications in T2DM.     

Oxidative stress parameters in type I,type II and insulin-treated type 2 diabetes mellitus; insulin treatment efficiency

BACKGROUND: Our aim was to evaluate oxidative stress parameters on three groups of diabetic patients, insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM), and insulin-treated type 2 diabetes mellitus (ITDM2), with similar HbA1c value and to determine if insulin's impact on these parameters was the same for IDDM and ITDM2. METHODS: This study has been conducted on 18 IDDM, 55 NIDDM, 27 ITDM2, compared to 12 healthy subjects. Plasmatic concentrations of thiobarbituric acid reactive substances (TBARS), fatty acids, total antioxidant status (TAS), alpha-tocopherol, and erythrocyte reduced glutathione (GSH) were measured as well as enzymatic activities of superoxide dismutase (SOD), and glutathione peroxidase/reductase. RESULTS: Diabetic patients have significant increase of SOD activity, of TBARS concentration (concomitant with low levels of unsaturated fatty acids) and significant decrease of GSH and alpha-tocopherol. NIDDM have significantly lower levels of GSH and higher levels of TBARS compared to IDDM. ITDM2 values are intermediate between IDDM and NIDDM but are far from reaching those of IDDM. CONCLUSION: Diabetic patients undergo an important oxidative stress that is nearly corrected for IDDM, but only partially improved for ITDM2, although length of insulin treatment and HbA1c values are similar, suggesting metabolic differences between the two types of diabetes.     

Educating patients with type 2 diabetes

The patient is the self-manager of type 2 diabetes. The role of the health care professional is to provide the knowledge, skills, and behavior change support to empower the patient to do so. Recent governmental, financial, and clinical factors influence how health care professionals perform this role. Such factors coupled with a growing body of research evidence are shaping the way diabetes self-management education is provided.     

Oxidative stress in families of type 1 diabetic patients

OBJECTIVE: The link between hyperglycemia and the complications of diabetes is unknown. It is still discussed whether oxidative stress precedes or merely reflects diabetic complications. To search for a familial predisposition to oxidative stress, we investigated indexes of glucose and lipid metabolism, markers of plasma and cell lipid oxidation, a marker of oxidant-induced protein damage, and the effects of oxygen radicals on erythrocytes (or red blood cells [RBCs]) of patients with type 1 diabetes and their relatives. RESEARCH DESIGN AND METHODS: We recruited 30 type 1 diabetic subjects (10 without diabetic complications, 10 with retinopathy, and 10 with nephropathy), 36 nondiabetic siblings, 37 nondiabetic parents of type 1 diabetic subjects, and 3 control groups of healthy subjects without a family history of diabetes. Levels of blood creatinine, glucose, HbA(1c), cholesterol, triglycerides, lipoprotein(a) (Lp[a]), fibrinogen, malondialdehyde (MDA), and advanced oxidation protein products were determined. The RBC response to oxidative stress (3-h incubation at 37 degrees C with or without a radical generating system) was evaluated by measuring RBC glutathione (GSH), RBC-MDA, and hemolysis. RESULTS: Diabetic patients had higher levels of blood glucose (P < 0.001), HbA(1c) (P < 0.001), Lp(a) (P < 0.01), and fibrinogen (P < 0.05) than control subjects. Siblings of diabetic patients had higher Lp(a) levels (P < 0.001). Parents had higher levels of plasma glucose (P < 0.05) and Lp(a) (P < 0.01). Plasma and RBC-MDA were significantly elevated in diabetic subjects and relatives compared with control subjects. Basal RBC-GSH was lower in diabetic subjects (P < 0.01). In diabetic subjects, incubations of cells caused a decrease in RBC-GSH of a lesser degree than that in control subjects, but they caused a significant increase in hemolysis. Among relatives, hemolysis was increased both at baseline and after incubation. Plasma MDA levels were associated with blood glucose, creatinine, and fibrinogen levels (multiple r = 0.5, P < 0.001), and basal RBC-MDA levels were associated with plasma Lp(a), fibrinogen, and plasma MDA levels (r = 0.6, P < 0.001). Basal RBC-GSH content correlated with serum glucose and RBC-MDA production (r = 0.3, P < 0.01). CONCLUSIONS: Our study is the first to present evidence that markers of lipoprotein metabolism (Lp[a]), oxidative stress (plasma and RBC-MDA), and cellular fragility (hemolysis) are abnormal in nondiabetic relatives of type 1 diabetic subjects, thereby supporting the view that familial elements of diabetes even precede the onset of diabetes. It seems reasonable that the same biological markers considered major predictors of cardiovascular disease can also trace familial susceptibility to type 1 diabetes, just as they have been associated with the development of type 2 diabetes.     

Orthostatic hypertension in patients with type 2 diabetes

OBJECTIVE: The prevalence and clinical importance of orthostatic hypertension (OHT) in diabetic patients has not been elucidated, in contrast to orthostatic hypotension, which is occasionally found in diabetic patients with autonomic neuropathy. RESEARCH DESIGN AND METHODS: The prevalence and severity of orthostatic hypertension was investigated in 277 Japanese male patients with type 2 diabetes, including 90 hypertensive patients and 128 nondiabetic age-matched male subjects. Patients treated with antihypertensive drugs were excluded from the study. OHT was defined as an increase in diastolic blood pressure (DBP) from <90 to >or=90 mmHg and/or an increase in systolic blood pressure (SBP) from <140 to >or=140 mmHg after standing from supine position. Clinical profiles and several serum biochemical parameters were determined in addition to chest X-rays and electrocardiograms. RESULTS: The prevalence of OHT in normotensive and hypertensive diabetic patients was significantly higher than in control subjects (12.8 vs. 1.8%, P < 0.01, for normotensive patients; 12.6 vs. 11.1%, not significant, for hypertensive patients). Orthostasis induced a mean increase of 6.8 +/- 11.4 mmHg in SBP and 9.1 +/- 5.2 mmHg in DBP in diabetic patients with OHT compared with those without OHT (-1.0 +/- 9.0 and 3.8 +/- 6.6 mmHg, respectively). Vibration sensation in the lower limb was reduced in diabetic patients with OHT, but the percent coefficient of variation of RR interval, cardio-to-thoracic ratio on chest X-ray, and serum triglyceride levels were higher in these patients compared with normotensive diabetic patients without OHT. CONCLUSIONS: Orthostatic hypertension is a novel complication in normotensive diabetic patients and may associate with early stage neuropathy and development of sustained hypertension.