2型糖尿病患者肠道菌群及细胞因子的变化分析

目的探讨2型糖尿病患者肠道菌群及细胞因子的变化。方法选择在兰溪市中医院就诊的2型糖尿病患者共100例,根据糖化血红蛋白水平分为观察组A 38例与观察组B 62例,其中观察组A患者糖化血红蛋白≥7.0%、观察组B患者糖化血红蛋白7.0%,同时选择50例正常人为对照组。收集3组患者新鲜粪便,检测双歧杆菌、乳酸杆菌、肠球菌、酵母菌、拟杆菌及肠杆菌等肠道菌群的含量,同时检测3组患者的白介素-2(IL-2),比较3组患者肠道菌群及细胞因子的差异。结果观察组A与观察组B患者的肠杆菌、酵母菌数量均明显多于对照组(t=3.63、2.13,2.45、2.01,P0.05或P0.01),观察组A患者的肠杆菌、酵母菌数量多于观察组B患者(t=2.42、2.33,P0.05);观察组A与观察组B患者的双歧杆菌、乳酸杆菌、拟杆菌数量均明显少于对照组(t=3.48、2.36、2.28,2.15、2.04、1.99,P0.05或P0.01),观察组A患者的双歧杆菌、乳酸杆菌、拟杆菌数量少于观察组B(t=2.22、2.18、2.09,P0.05);3组肠球菌数量比较差异无统计学意义(P0.05);观察组A与观察组B患者的血清IL-2水平明显低于对照组(t=3.88、2.36,P0.05或P0.01),观察组A患者的血清IL-2水平低于观察组B患者(t=2.31,P0.05)。结论 2型糖尿病患者肠道内肠杆菌、酵母菌增多,而双歧杆菌、乳酸杆菌、拟杆菌减少,IL-2水平降低,其变化的幅度与血糖升高水平相关,因此在2型糖尿病患者的治疗中应关注肠道菌群失调及免疫功能下降情况,及早干预治疗。     

Heparanase levels are elevated in the urine and plasma of type 2 diabetes patients and associate with blood glucose levels

Heparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains of heparan sulfate proteoglycans. Utilizing an ELISA method capable of detection and quantification of heparanase, we examined heparanase levels in the plasma and urine of a cohort of 29 patients diagnosed with type 2 diabetes mellitus (T2DM), 14 T2DM patients who underwent kidney transplantation, and 47 healthy volunteers. We provide evidence that heparanase levels in the urine of T2DM patients are markedly elevated compared to healthy controls (1162 ± 181 vs. 156 ± 29.6 pg/ml for T2DM and healthy controls, respectively), increase that is statistically highly significant (P<0.0001). Notably, heparanase levels were appreciably decreased in the urine of T2DM patients who underwent kidney transplantation, albeit remained still higher than healthy individuals (P<0.0001). Increased heparanase levels were also found in the plasma of T2DM patients. Importantly, urine heparanase was associated with elevated blood glucose levels, implying that glucose mediates heparanase upregulation and secretion into the urine and blood. Utilizing an in vitro system, we show that insulin stimulates heparanase secretion by kidney 293 cells, and even higher secretion is observed when insulin is added to cells maintained under high glucose conditions. These results provide evidence for a significant involvement of heparanase in diabetic complications.     

老年2型糖尿病患者肠道双歧杆菌生长与血糖相关性

目的 探讨老年2型糖尿病患者肠道双歧杆菌生长与血糖的相关性,从肠道菌群角度为2型糖尿病的防治与研究提供新的途径。方法 根据纳入和排除标准,抽取2015年4月‒10月福建某三甲医院糖尿病健康教育俱乐部的2型糖尿病患者90例,收集其粪便和血液标本,检测患者肠道双歧杆菌以及血糖状况,采用Spearman等级相关法分析两者之间的相关性。结果 老年2型糖尿病患者肠道长双歧杆菌、短双歧杆菌、青春双歧杆菌、婴儿双歧杆菌和双歧杆菌总菌的定量结果分别是（0.0001±0.0006）、（4.405±8.475）、（4.752±2.779）、（0.003±0.005）和（8.069±8.206）logN/g。空腹血糖和早餐餐后血糖分别为（8.638±1.913）、（9.763±1.910）mmol/L。相关分析显示：青春双歧杆菌和婴儿双歧杆菌与早餐后2 h血糖呈现负相关（r=-0.213、-0.217,P<0.05）,但相关性不显著;双歧杆菌总菌与空腹血糖和早餐后2 h血糖有负相关关系（r=-0.302、-0.559,P<0.01）。结论 老年2型糖尿病患者肠道内双歧杆菌数量减少,血糖与肠道双歧杆菌的数量呈负相关,尤其是早餐后2 h血糖,其相关机制有待进一步研究。     

老年2型糖尿病合并慢性肾脏病患者肠道菌群变化

目的 探讨合并慢性肾脏病的老年2型糖尿病患者肠道菌群变化情况,为后续研究提供参考。 方法 选择2018年11月至2019年7月在我院内科确诊的老年2型糖尿病及并发慢性肾脏病患者作为糖尿病组(20例)及糖尿病肾病组(20例),选择本院健康老年体检者(30例)为对照组。测定各组对象血清甲状旁腺激素(PTH)、超敏C反应蛋白(hs CRP)、血肌酐(Scr)、血磷(P)、血钙(Ca2+)、碱性磷酸酶(ALP)、糖化血红蛋白(HbA1c)水平,同时分析各组对象肠道大肠埃希菌、双歧杆菌、乳杆菌、酵母菌、真杆菌的差异。 结果 糖尿病肾病组患者肠道大肠埃希菌数量高于糖尿病组和对照组,糖尿病组患者肠道大肠埃希菌数量高于对照组(均P2+水平高于糖尿病组和对照组,糖尿病组患者血清Scr、P、Ca2+水平高于对照组(均P2+、HbA1c、ALP、hs CRP水平呈正相关,双歧杆菌、真杆菌数量与Scr、P、Ca2+、HbA1c、ALP、hs CRP水平呈负相关(均P结论 糖尿病肾病患者肠道菌群失调,其特征为大肠埃希菌数量增多,双歧杆菌、真杆菌数量减少。大肠埃希菌数量升高,双歧杆菌和真杆菌数量降低均为糖尿病并发慢性肾脏病的危险因素。     

MiR-199a is overexpressed in plasma of type 2 diabetes patients which contributes to type 2 diabetes by targeting GLUT4

Decreased GLUT4 expression and impaired GLUT4 cell membrane translocation are involved in type 2 diabetes mellitus (T2DM) pathogenesis so the factors impacting GLUT4 expression may be associated with T2DM. In this study, we identified four miRNAs: miR-31, miR-93, miR-146a, and miR-199a which suppress GLUT4 expression in HEK293T cells. Subsequently, we determined expression of these four miRNAs in plasma samples of T2DM patients, T2DM susceptible individuals, and healthy controls and found miR-199a was overexpressed in patients’ plasma compared with healthy control. Because the miR-199a binding site in GLUT4 3′UTR is highly conserved among vertebrates, we detected the glucose uptake in rat L6 myoblast cells through gain- and loss-of-function of miR-199a. We found that miR-199a can repress glucose uptake in L6 cells, which was rescued by GLUT4 overexpression. These results indicate that T2DM patients may have a high level miR-199a that reduce GLUT4 expression and contribute to the insulin resistance. Hence, miR-199a may be a novel biomarker for risk estimation and classification in T2DM patients.     

强化降糖治疗对2型糖尿病患者生存质量及血糖的影响研究

目的:探讨强化降糖治疗对2型糖尿病(T2DM)患者生存质量及血糖的影响.方法:将120例T2DM患者随机分为观察组和对照组.对照组按照<中国糖尿病防治指南>给予标准降糖治疗,治疗组给予强化降糖治疗.两组患者在治疗前和随访3年后分别进行生存质量评价和血糖指标测查.结果:治疗后,治疗组生存质量各维度评分及总分与治疗前和对照组比较显著下降(P＜0.05),对照组治疗前后生存质量各维度评分及总分差异无统计学意义(P＞0.05);两组治疗后血糖水平均明显降低,与治疗前比较有显著性差异(P＜0.05),且治疗组与对照组比较显著降低(P＜0.05).结论:采用强化降糖治疗,可以达到血糖的理想控制,提高患者的生存质量.     

Cost-effectiveness of self-monitoring of blood glucose in patients with type 2 diabetes mellitus managed without insulin

Background

The benefits of self-monitoring blood glucose levels are unclear in patients with type 2 diabetes mellitus who do not use insulin, but there are considerable costs. We sought to determine the cost effectiveness of self-monitoring for patients with type 2 diabetes not using insulin.

Methods

We performed an incremental cost-effectiveness analysis of the self-monitoring of blood glucose in adults with type 2 diabetes not taking insulin. We used the United Kingdom Prospective Diabetes Study (UKPDS) model to forecast diabetes-related complications, corresponding quality-adjusted life years and costs. Clinical data were obtained from a systematic review comparing self-monitoring with no self-monitoring. Costs and utility decrements were derived from published sources. We performed sensitivity analyses to examine the robustness of the results.

Results

Based on a clinically modest reduction in hemoglobin A_1C of 0.25% (95% confidence interval 0.15–0.36) estimated from the systematic review, the UKPDS model predicted that self-monitoring performed 7 or more times per week reduced the lifetime incidence of diabetes-related complications compared with no self-monitoring, albeit at a higher cost (incremental cost per quality-adjusted life year $113 643). The results were largely unchanged in the sensitivity analysis, although the incremental cost per quality-adjusted life year fell within widely cited cost-effectiveness thresholds when testing frequency or the price per test strip was substantially reduced from the current levels.

Interpretation

For most patients with type 2 diabetes not using insulin, use of blood glucose test strips for frequent self-monitoring (≥ 7 times per week) is unlikely to represent efficient use of finite health care resources, although periodic testing (e.g., 1 or 2 times per week) may be cost-effective. Reduced test strip price would likely also improve cost-effectiveness.Self-monitoring of blood glucose in patients with diabetes who use insulin may contribute to improved glycemic control and reduced hypoglycemia by allowing for self-adjustments in insulin dose to be made based on meter readings.¹ Self-monitoring may also allow for appropriate changes in diet and physical activity to be made. However, the benefits of self-monitoring of blood glucose for patients not using insulin are less clear. Hypoglycemia is less frequent in this population² and is confined mainly to those taking secretagogues. The degree to which patients can adjust the dose of oral antidiabetes drugs in response to readings is limited.Nevertheless, self-monitoring of blood glucose is routinely recommended for patients who are not using insulin.¹ This results in major investments in this technology by patients and payers.³ In 2006, $250 million was spent on blood glucose test strips in 8 publicly funded drugs plans in Newfoundland and Labrador, Nova Scotia, Quebec, Ontario, Manitoba, Saskatchewan and British Columbia, while over $120 million was spent in privately funded drug plans in Canada.⁴ In some publicly funded drug plans in Canada, blood glucose test strips are among the top 5 classes in terms of total expenditure,⁵ with costs exceeding those for all oral antidiabetes drugs combined.^4,6 It is estimated that more than 50% of the total expenditure on blood glucose test strips is for patients with type 2 diabetes who are not using insulin.³ Costs related to test strips are expected to rise steadily^5,7 because of the increasing prevalence of type 2 diabetes.⁸Decisions about the prescribing and reimbursement of blood glucose test strips require consideration of information about the costs and clinical benefits.^9,10 As part of a larger initiative to determine the optimal use of this technology, we sought to determine the cost-effectiveness of self-monitoring of blood glucose for patients with type 2 diabetes who do not use insulin, based on data from our systematic review¹¹ of the available clinical evidence.     

Chromium determinations in blood cells: clinical relevance demonstrated in patients with diabetes mellitus type 2

As an essential nutrient involved in carbohydrate and lipid metabolism, chromium is of extraordinary importance for patients with diabetes. Plasma concentrations do not reflect the chromium supply; thus, we determined the element’s content in blood cells in order to evaluate the body status. We investigated 86 blood donors (C) and 35 diabetics type 2 (Dm2). After the isolation of the blood cells by using a density centrifugation, the chromium concentrations were determined by electrothermal atomic absorption spectrometry. Compared to C, Dm2 had higher values in plasma, erythrocytes, and platelets (248%, 61%, and 91%, respectively) and lower contents in polymorphonuclear and mononuclear leukocytes (each −35%, age- and sex-matched groups with n=35, each p<0.01). The poorer the metabolic control assessed by HbA1c, the higher were the chromium concentrations in plasma (r=+0.46, n=33, p=0.007, increase 11.1% per %HbA1c) and the lower were the values in mononuclear leukocytes (r=−0.45, n=33, p=0.008, decrease 17.8% per %HbA1c). The changed amounts in plasma and in mononuclear cells in increasing hyperglycemia could be the result of an intracellular/extracellular redistribution of the element. High plasma levels might explain the renal chromium losses of diabetics, whereas the lymphocytes could reflect a decreasing chromium body state.     

Effect of insulin therapy on plasma leptin and body weight in patients with type 2 diabetes.

AIMS: This study set out to define relationships between changes in plasma leptin and changes in body weight, plasma insulin and blood glucose control during a 12-month crossover study of once-daily Ultratard or twice-daily Insulatard insulin. PATIENTS AND METHODS: Fasting plasma leptin and insulin were measured during a multicentre cross-over study involving 60 subjects with type 2 diabetes (fasting glucose > 8 mM). After a 2-month run-in, there were two 6-month periods of treatment with Insulatard or Ultratard insulin. RESULTS: Mean plasma leptin increased significantly in both groups after insulin therapy was instigated (12.8 +/- 8.1 to 22.9 +/- 13.1 ng/ml in the Insulatard group; 12.1 +/- 7.2 to 19.2 +/- 12.3 ng/ml in the Ultratard group). Weight also increased significantly in both groups (82.4 +/- 14.3 kg to 88.8 +/- 14.3 kg and 82.2 +/- 15.3 kg to 85.3 +/- 15.2 kg respectively). The increase in plasma leptin correlated well with the increase in weight (R = 0.416, p = 0.001), and this correlation continued after the crossover point. Plasma leptin correlated with BMI throughout the study (R = 0.540, p = 0.000). CONCLUSION: The sustained rise in body weight despite a substantial increase in plasma leptin suggests that either resistance to the hypothalamic action of leptin develops when insulin therapy is begun in type 2 diabetes, or that resetting of the set point for body weight occurs such that a larger body mass is tolerated for a given level of plasma leptin.     

动态血糖监测在老年2 型糖尿病患者降糖治疗中的应用价值

目的：通过对老年2 型糖尿病患者进行动态血糖监测了解降糖治疗的疗效,评价动态血糖监测系统的应用价值,确定其在 治疗老年2 型糖尿病患者中的地位。方法：选取2008 年8 月至2013 年8 月住院的老年2 型糖尿病患者95 例,随机分为对照组 48 例和观察组47 例,对照组行予常规的指尖血糖监测,观察组行动态血糖监测,比较两组患者血糖的控制情况。结果：观察组患 者治疗后平均血糖、高血糖持续时间、低血糖持续时间、血糖最大波波动幅度、平均血糖波动幅度、血清糖化白蛋白及餐后2h 血 糖等与治疗前相比较比较,差异均有统计学意义,P＜0.05。对照组患者治疗后平均血糖、高血糖持续时间、低血糖持续时间、血糖 最大波波动幅度、平均血糖波动幅度、血清糖化白蛋白及餐后2h血糖等与治疗前相比较比较,差异均无统计学意义,P＞0.05。两 组患者空腹血糖治疗前、后差异均无统计学意义,P＞0.05。结论：动态血糖监测系统用于监测老年2 型糖尿病患者的降糖治疗疗 效优于常规血糖检测。     

动态血糖监测在老年2型糖尿病患者降糖治疗中的应用价值

目的：通过对老年2型糖尿病患者进行动态血糖监测了解降糖治疗的疗效,评价动态血糖监测系统的应用价值,确定其在治疗老年2型糖尿病患者中的地位。方法：选取2008年8月至2013年8月住院的老年2型糖尿病患者95例,随机分为对照组48例和观察组47例,对照组行予常规的指尖血糖监测,观察组行动态血糖监测,比较两组患者血糖的控制情况。结果：观察组患者治疗后平均血糖、高血糖持续时间、低血糖持续时间、血糖最大波波动幅度、平均血糖波动幅度、血清糖化白蛋白及餐后2h血糖等与治疗前相比较比较,差异均有统计学意义,P〈0.05。对照组患者治疗后平均血糖、高血糖持续时间、低血糖持续时间、血糖最大波波动幅度、平均血糖波动幅度、血清糖化白蛋白及餐后2h血糖等与治疗前相比较比较,差异均无统计学意义,P〉0.05。两组患者空腹血糖治疗前、后差异均无统计学意义,P〉0.05。结论：动态血糖监测系统用于监测老年2型糖尿病患者的降糖治疗疗效优于常规血糖检测。