1型糖尿病患者外周血中CD4^＋CD25^＋与CD8^＋CD28^-调节性T细胞水平的研究

流式细胞仪检测1型糖尿病（T1DM）患者外周血CD4^＋CD25^＋与CD8^＋CD28^-调节性T细胞的水平,发现其外周血CD4^＋CD25^＋T淋巴细胞水平[（2．02±0．43）％]显著低于2型糖尿病（T2DM）组[（6．79±1．75）％]和健康对照（NC）组[（7．84±1．45）％],而CD8^＋CD28^-调节性T细胞水平三组间无差异。     

2型糖尿病肥胖与非肥胖血液流变学和血脂变化

2型糠尿病77例，分为肥胖与非肥胖组，测定空腹胰岛素，血流变学等检查。结果肥胖组胰岛素敏感性指数低于非肥胖组，空腹血胰岛素、血尿酸高于非肥胖组，肥胖的糖尿病患者，其血脂及血液流变学变化，TG及TC，均与非肥胖者比较有显著差异，但2组的APOA、APOB、LP（a）、LDL无显著差异。其全血粘度高切、低切，血浆粘度均高于肥胖者。而红细胞压积高于非肥胖者，差异显著。结论肥胖的2型糖尿病患者存在明显的胰岛素敏感性减低、高胰岛素血症、高尿酸血症、高粘血症及脂代谢紊乱，提示改善肥胖本身，降低血粘度以及针对脂毒性的治疗在2型糖尿病综合治疗中的重要地位。     

肥胖和非肥胖2型糖尿病患者的临床特点及影响其心功能的多因素探讨

目的 比较肥胖和非肥胖2型糖尿病患者的临床特点。探讨影响两组患者心功能的因素。方法 符合1999年糖尿病诊断标准的住院型糖尿病患者238例。根据有无肥胖将所有患者分为肥胖组和非肥胖组，胰岛素敏感指数采用QUICKI公式，用二维指导下的M型超声心动图检测患者在左心房大小，舒张末期左心室内径，左心室后壁厚度，室间隔厚度，射血分数，用超声多普勒检测E峰A峰比值，计算左心室质量指数。结果 （1）肥胖组胰岛素敏感指数较非肥胖组高，高密度脂蛋白胆固醇水平较非肥胖组低；（2）肥胖组左心房内径，舒张末期左心室内径，左心室后壁厚度，室间隔厚度，左心室质量指数均大于非肥胖组；（2）多元逐步回归分析显示；肥胖组射血分数与左心室质量指数，空腹C肽呈负相关；非肥胖组射血分数与左心室质量指数，收缩压，尿酸呈负相关，结论 肥胖糖尿病患者存在明显的左心肥大，并与低胰岛素敏感发性和低，高密度脂蛋白胆固醇并存；左心室肥大，无论在肥胖和非肥胖的糖尿病患者均影响左心室收缩功能；肥胖与非肥胖糖尿病患者还存在不同的收收缩功能有关的因素。     

MDA、SOD在肥胖与非肥胖2型糖尿病患者血清中的变化

受试者分为3组：肥胖与非肥胖2型DM组各50例,正常对照组50例,各组年龄、性别、种族均有可比性。禁食12—14h,空腹静脉取血,测定血清MDA含量及SOD活性水平。结果：肥胖2型DM患者的MDA含量明显高于非肥胖2型DM患者,而SOD活性明显低于非肥胖2型DM患者。结论：2型糖尿病肥胖患者比2型糖尿病非肥胖患者的氧化应激更显著。     

慢性阻塞性肺疾病并2型糖尿病患者的免疫功能分析

目的观察慢性阻塞性肺疾病（COPD）并2型糖尿病（T2DM）患者的免疫功能,探讨其临床意义。方法选择COPD稳定期的患者60例,其中COPD合并T2DM患者30例、单纯COPD患者30例,健康对照组20例。检测外周血IgA、IgG、CD3^＋、CD4^＋、CD8^＋及CD4^＋/CD8^＋水平,并进行统计学分析。结果 COPD患者与健康对照组相比,外周血CD3^＋、CD4^＋、CD4^＋/CD8^＋、IgA、IgG、IgM均低,CD8^＋水平较高,差异有统计学意义（P〈0.05）;其中COPD合并T2DM患者与单纯COPD组相比,差异有统计学意义（P〈0.05）。结论 COPD并T2DM患者稳定期存在免疫功能异常,给予免疫干预治疗可能会减少COPD患者急性加重次数,改善预后。     

2型糖尿病外周血内皮祖细胞增殖、分化及细胞周期变化

目的观察2型糖尿病（T2DM）患者外周血内皮祖细胞（EPC）增殖、分化能力及细胞周期分布。方法T2DM患者（DM组）和非T2DM患者（Con组）各20例，离心法获取外周血单个核细胞，培养7天后，鉴定EPC，检测EPC增殖能力、EPC分化及细胞周期分布。结果DM组外周血EPC数量及增殖能力明显降低；EPC数量、增殖能力与HbA1c水平和DM病程呈负相关；EPC表达CD14^＋、CD64^＋明显高于Con组，而表达vWF^＋明显低于Con组；EPC在S期的比例明显减少，在G0／G1期的比例增高。结论T2DM患者外周血EPC数量减少、增殖能力受损、向内皮细胞系分化减少。     

强直性脊柱炎患者外周血T细胞亚群的变化及意义

目的探讨强直性脊柱炎（AS）患者外周血中T细胞亚群的变化及其意义。方法采用流式细胞仪（FCM）检测外周血淋巴细胞表面CD3、CD4、CD8及其胞质内细胞因子IFN-γ和IL-4的表达。结果与正常对照组相比,As患者外周血Th细胞（CD;CD4＋）百分率无显著差异,Tc细胞（CD;CD;）明显升高（P〈0．05）;Th1细胞（CD3^＋CD4^＋IFN-γ^＋）百分率明显升高,Th2细胞（CD3^＋CD4^＋IL4^＋）无显著性差异;Te1细胞（CD3^＋CD8^＋IFN-γ^＋）百分率明显降低,T02细胞（CD3^＋CD8^＋IL4^＋）无显著性差异。结论AS患者外周血T细胞Th1／Th2、Tcl／Tc2亚群比例失衡,呈Th1、Tc2优势型。     

2型糖尿病肥胖与非肥胖血液流变学和血脂变化

2型糠尿病77例,分为肥胖与非肥胖组,测定空腹胰岛素,血流变学等检查.结果肥胖组胰岛素敏感性指数低于非肥胖组,空腹血胰岛素、血尿酸高于非肥胖组,肥胖的糖尿病患者,其血脂及血液流变学变化,TG及TC,均与非肥胖者比较有显著差异,但2组的APOA、APOB、LP(a)、LDL无显著差异.其全血粘度高切、低切,血浆粘度均高于肥胖者,而红细胞压积高于非肥胖者,差异显著.结论肥胖的2型糖尿病患者存在明显的胰岛素敏感性减低、高胰岛素血症、高尿酸血症、高粘血症及脂代谢紊乱,提示改善肥胖本身,降低血粘度以及针对脂毒性的治疗在2型糖尿病综合治疗中的重要地位.     

肥胖合并糖尿病的临床表现及诊断进展

肥胖症是指体内脂肪堆积过多和(或)分布异常,通常伴有体重增加.肥胖与糖尿病密切相关,均已成为世界范围内的流行病,严重危害人类健康.肥胖和糖尿病均为异质性疾病,肥胖合并糖尿病的临床表现亦呈多种表现. 肥胖合并糖尿病的临床表现 1.原发性肥胖合并2型糖尿病:通常所说的肥胖合并糖尿病即为此种类型.与非肥胖2型糖尿病患者相比,肥胖2型糖尿病患者存在更严重的胰岛素抵抗,但是胰岛素分泌能力优于非肥胖者[1,2];肥胖2型糖尿病患者体内血清抵抗素、视黄醇结合蛋白4、丝氨酸蛋白酶抑制剂水平均显著升高[3-5].肥胖是代谢综合征的重要组成成分,除易合并糖尿病外,亦常与高血压、血脂代谢异常、高尿酸血症等合并存在,因此肥胖合并2型糖尿病的患者在临床上常表现为代谢综合征.     

2型糖尿病患者肥胖与胰岛素抵抗的关系

目的观察照2型糖尿病患者肥胖和胰岛素抵抗的关系.方法对正常对照组20例,肥胖2型糖尿病患者41例,非肥胖2型糖尿病患者17例,分别检测体重指数（BMI）、腰围、臀围、空腹血糖（FBG）、胰岛素（INS）,计算腰臀比（WHR）和胰岛素敏感指数（ISI）,并进行对比分析.结果肥胖2型糖尿病患者较非肥胖者FBG、BMI、WHR均显著升高（P＜0.05）,但ISI显著降低（P＜0.01）.结论肥胖的2型糖尿病患者存在更为严重的胰岛素抵抗.     

Sleep-disordered breathing in nonobese diabetic subjects with autonomic neuropathy.

To assess the occurrence and nature of sleep-disordered breathing (SDB) in 26 adult, nonobese diabetics (18 with autonomic neuropathy (DAN+) (age 45 (41-50) yrs; body mass index (BMI) 24.1 (22-26) kg x m(-2)) and eight without autonomic neuropathy (DAN-) (age 45 (35-55) yrs; BMI 24.8 (23-26) kg x m(-2))) overnight full sleep studies and measurements of central and peripheral carbon dioxide (CO2) chemosensitivity were performed. DAN+ were divided in two subgroups, according to the presence (DAN+PH+; n=10) or absence (DAN+PH-; n=8) of postural hypotension. Ten normal subjects were studied as controls (age 42 (36-48) yrs; BMI 24.4 (23-25) kg x m(-2)). In contrast to DAN- and controls, who did not show SDB, five DAN+ (four DAN+PH- and one DAN+PH+) had an apnoea/hypopnoea index > or = 10 and four DAN+ (two DAN+PH- and two DAN+PH+) had an apnoea index > or = 5. All the events were obstructive, occurring mainly during rapid eye movement (REM) sleep. Ten DAN+ exhibited a mean lowest oxygen saturation < 90% during REM sleep. No periodic breathing or central sleep apnoeas were found in DAN+PH+, although they had an enhanced central chemoresponsiveness to CO2. Both DAN+ subgroups showed a marked reduction in peripheral CO2 chemosensitivity. In conclusion, adult nonobese diabetics with autonomic neuropathy, independent of the severity of their dysautonomy, have obstructive sleep apnoea/hypopnoea with a frequency > 30%. A decrease in peripheral carbon dioxide chemosensitivity prevents adult nonobese diabetics with autonomic neuropathy and postural hypotension from experiencing posthyperventilatory central sleep apnoea, despite an increased hypercapnic central drive.     

急性冠状动脉综合征患者外周血CD31~(bright)/Annexin V~+内皮微粒水平增高

目的 观察急性冠状动脉综合征患者与非冠心病患者外周血内皮微粒水平,探讨CD31bright/AnnexinV+内皮微粒与心血管危险因素的相关性.方法 急性冠状动脉综合征患者56例,非冠心病患者26例,采用流式细胞仪检测外周血CD31bright/Annexin V+内皮微粒水平.结果 与非冠心病患者比较,急性冠状动脉综合征患者外周血CD31bright/Annexin V+内皮微粒显著增加(P<0.01),而急性心肌梗死与不稳定型心绞痛亚组之间外周血CD31bright/Annexin V+内皮微粒水平无显著性差异(P>0.05).所有入选患者中,2型糖尿病患者外周血CD31bright/Annexin V+内皮微粒水平较非糖尿病患者显著升高(P<0.05);多因素回归分析显示,血清甘油三酯水平与外周血CD31bright/Annexin V+内皮微粒数量独立正相关(r=0.28,P<0.05).急性冠状动脉综合征组血清高敏C反应蛋白水平与外周血CD31bright/Annexin V+内皮微粒数量呈正相关(r=0.31,P<0.05).结论 急性冠状动脉综合征患者和糖尿病患者外周血CD31bright/Annexin V+内皮微粒增多,提示急性冠状动脉综合征患者和2型糖尿病患者内皮损伤严重.CD31bright/Annexin V+内皮微粒水平增高可能与血清甘油三酯和血清高敏C反应蛋白水平增高有关.     

The role of CD4+ and CD8+ T cells in the destruction of islet grafts by spontaneously diabetic mice.

Spontaneous development of diabetes in the nonobese diabetic (NOD) mouse is mediated by an immunological process. In disease-transfer experiments, the activation of diabetes has been reported to require participation of both CD4+ and CD8+ T-cell subsets. These findings seem to indicate that the CD4+ cells are the helper cells for the activation of cytotoxic CD8+ cells that directly destroy islet beta cells in type I diabetes. In this report we challenge this interpretation because of two observations: (i) Destruction of syngeneic islet grafts by spontaneously diabetic NOD mice (disease recurrence) is CD4+ and not CD8+ T-cell dependent. (ii) Disease recurrence in islet tissue grafted to diabetic NOD mice is not restricted by islet major histocompatibility complex antigens. From these observations we propose that islet destruction depends on CD4+ effector T cells that are restricted by major histocompatibility complex antigens expressed on NOD antigen-presenting cells. Both of these findings argue against the CD8+ T cell as a mediator of direct islet damage. We postulate that islet damage in the NOD mouse results from a CD4+ T-cell-dependent inflammatory response.     

A Comparative Study of Epicardial Fat Thickness and its Association with Abdominal Visceral Fat Thickness in Obese and Nonobese Type 2 Diabetes Subjects

Context:

The concept of visceral fat and its role in various metabolic disorders is well-known. Epicardial fat (EF) is also visceral fat, and very few studies are done, especially in the Indian subcontinent.

Aims:

To study and establish the relationship of EF thickness (EFT) and abdominal visceral fat thickness (VAT) in obese and nonobese type 2 diabetics and to evaluate the usefulness of EFT as a marker of visceral adiposity.

Settings and Designs:

This cross-sectional study was carried out in the Department of Medicine, JSS Hospital, Mysore, India, between October 2012 and October 2014.

Materials and Methods:

A total of 68 patients were studied. Patients underwent transthoracic echocardiography and ultrasound abdomen. EFT and VAT were measured.

Statistical Analysis:

SPSS version 17.0 (SPSS Inc., Chicago, IL, USA) was used. T-test used for comparing quantitative variables. Correlation analysis was done using Pearson correlation test. P ≤ 0.05 was considered statistically significant. Kruskal-Wallis and Mann-Whitney test were used for analysis.

Results:

The mean value of EFT was 5.92 mm, 7.43 mm, 12.97 mm, 11.27 mm, and 13.8 mm for nonobese, obesity Grade I, II, III, and morbid, respectively (P < 0.0001). The mean EFT between nonobese and obese diabetics was 5.92 mm and 10.2 mm, respectively (P < 0.0001). The mean VAT between nonobese and obese diabetics was 16.58 mm and 38.53 mm, respectively. EFT was significantly correlating with VAT in obese diabetics.

Conclusion:

EFT and VAT were significantly correlated among obese diabetics while not significantly correlated among nonobese diabetics, suggesting obesity is an independent risk factor for visceral adipose tissue deposition both in abdomen as well as in epicardial surface.     

The fatty acid transporter FAT/CD36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes

BACKGROUND: Long-chain fatty acids (LCFAs) cross the plasma membrane via a protein-mediated mechanism involving one or more LCFA-binding proteins. Among these, FAT/CD36 has been identified as key LCFA transporter in the heart and skeletal muscle, where it is regulated acutely and chronically by insulin. In skeletal muscle, FAT/CD36 expression and/or subcellular distribution is altered in obesity and type 2 diabetes. There is limited information as to whether the expression of this protein is also altered in subcutaneous and/or visceral adipose tissue depots in human obesity or type 2 diabetes. OBJECTIVES: To compare (a) the expression of FAT/CD36 in subcutaneous and visceral adipose tissue depots in lean, overweight, and obese individuals and in type 2 diabetics, (b) to determine whether the protein expression of FAT/CD36 in these depots is associated with the severity of insulin resistance (type 2 diabetes>obese>overweight/lean) and (c) whether FAT/CD36 protein expression in these adipose tissue depots is associated with alterations in circulating substrates and hormones. SUBJECTS: Subjects who were undergoing abdominal surgery and who were lean (n=10; three men, seven women), overweight (n=10; three men, seven women) or obese (n=7; one man, six women), or who had been diagnosed with type 2 diabetes (n=5; one man, four women) participated in this study. MEASUREMENTS: Subcutaneous and visceral adipose tissue samples, as well as blood samples, were obtained from the subjects while under general anesthesia. Adipose tissue samples were analyzed for FAT/CD36 using Western blotting. Serum samples were analyzed for glucose, insulin, FFA and leptin. BMI was also calculated. RESULTS: Subcutaneous adipose tissue FAT/CD36 expression was upregulated by +58, +76 and +150% in overweight, obese and type 2 diabetics, respectively. Relative to subcutaneous adipose tissue, visceral adipose tissue FAT/CD36 expression was upregulated in lean (+52%) and overweight subjects (+30%). In contrast, in obese subjects and type 2 diabetics, no difference in FAT/CD36 protein expression was observed between their subcutaneous and visceral adipose tissue depots (P>0.05). The subcutaneous adipose tissue FAT/CD36 expression (R=0.85) and the visceral adipose tissue FAT/CD36 expression (R=0.77) were associated with alteration in BMI and circulating glucose and insulin. CONCLUSIONS: Subcutaneous adipose tissue FAT/CD36 expression is upregulated in obesity and type 2 diabetes. As FAT/CD36 expression is not different in lean, overweight and obese subjects, and was only increased in type 2 diabetics, it appears that visceral adipose tissue FAT/CD36 may respond in a less dynamic manner to metabolic disturbances than subcutaneous adipose tissue FAT/CD36.     

NADPH-forming dehydrogenases in the adipose tissue of obese and nonobese diabetics

The activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) of adipose tissue was markedly decreased, both on a protein and on a fat cell number basis, in nonobese diabetics compared to control subjects, but was unchanged in obese diabetics. Average value in the obese diabetics was about fourfold higher than in nonobese diabetics. On the other hand, the activity of malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40) was reduced by about 50% in both groups of diabetics.These findings suggest that in obese diabetics NADPH-generation in the adipose tissue, necessary for several biosynthetic processes, might be less severely depressed than in lean diabetics.     

Abnormal glucoregulation during exercise in type II (non-insulin-dependent) diabetes

We studied the effects of exercise on the levels of plasma glucose and glucoregulatory hormones before and after 6 weeks of thrice-weekly physical training in 20 sedentary type II (non-insulin-dependent) diabetic patients and 11 control subjects matched for previous physical activity. Parameters were measured at rest, after 30 minutes of bicycle exercise at 70% to 75% of maximal oxygen uptake, and after 30 minutes of recovery. In the untrained state exercise resulted in a decrease in plasma glucose levels in diabetics but not in controls (-12 +/- 5 v + 4 +/- 2 mg/dL, P less than .01) and the expected drop in plasma insulin level was absent in diabetics. These differences in glucose and insulin response persisted after physical training. There was a tendency for patients with diabetes to have a smaller R-R interval variation during deep breathing, an abnormal resting heart rate response to physical training, and a lesser increment in plasma epinephrine levels following exercise, findings consistent with autonomic dysfunction. Physical training resulted in a blunting of the exercise-induced increment of plasma epinephrine, growth hormone, and lactate levels in control subjects, but not in diabetics. Our data demonstrate a hypoglycemic effect of exercise in mildly hyperglycemic nonobese type II diabetics. Possible causative factors include: hyperglycemia per se, a lack of physiologic suppression of plasma insulin, and abnormalities of autonomic or hypothalamic regulatory function.     

Identification of the beta cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes

Type 1 diabetes is an autoimmune disease in which autoreactive T cells attack and destroy the insulin-producing pancreatic beta cells. CD8+ T cells are essential for this beta cell destruction, yet their specific antigenic targets are largely unknown. Here, we reveal that the autoantigen targeted by a prevalent population of pathogenic CD8+ T cells in nonobese diabetic mice is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Through tetramer technology, IGRP-reactive T cells are readily detected in islets and peripheral blood directly ex vivo. The human IGRP gene maps to a diabetes susceptibility locus, suggesting that IGRP also may be an antigen for pathogenic T cells in human type 1 diabetes and, thus, a new, potential target for diagnostic and therapeutic approaches.     

The role of CD8+ cells, cell degeneration, and Fas ligand in insulitis after intraperitoneal transfer of NOD splenocytes

Cells expressing CD4, CD8, CD18, CD49d/CD29, CD44, CD54, CD80, CD86, CD106, CD11b/CD18 or DNA breaks were stained in the pancreases of female or male scid/ scid mice after adoptive transfer of lymphocytes from older than 12-week female nonobese diabetic (NOD) or Balb/c mice. After intraperitoneal adoptive transfer of NOD splenocytes to female severe combined immunodeficiency (scid)/scid mice, in situ end labeling (ISEL)+ as well as CD80+ and CD86+ cell infiltrates appeared first in the blood vessel walls and pancreatic interstitial tissue at 2-3 weeks after transfer. CD4+, CD8+, CD18+, CD44+, CD54+, and CD106+ cells then encircled and invaded some islets of the scid/scid mice 2 to 7 weeks after transfer. Cells expressing these surface components, except CD8, were present also in the Balb/c mice, but as individual cells, not as infiltrates. CD8+ cells were observed in the pancreases of all NOD splenocyte-injected scid mice at 2, 3, 4, 6, and 7 weeks after transfer, but in none of the Balb/c splenocyte-injected scid mice. Some scid/scid mice injected with NOD splenocytes also developed severe noninfectious diarrhea and cachexia 4 weeks after transfer. ISEL+ cells were observed in the pancreases of NOD splenocyte-injected female scid mice at all times after transfer, especially in the blood vessel walls and in the islets. Fas ligand was not present in Western blotting. It is proposed that apoptosis commonly occurs in islet-infiltrating lymphocytes and that in the scid/scid adoptive-transfer model, the first islet-infiltrating cells are destroyed by programmed cell death independent of Fas ligand. Further, CD8+ T lymphocytes inevitably play a central role in intraperitoneal adoptive transfer of insulitis.