脂蛋白(α)与非胰岛素依赖型糖尿病代谢控制的关系

为探讨非胰岛素依赖型糖尿病（ＮＩＤＤＭ）血糖控制对血清脂蛋白（α）浓度的影响，对１０６例ＮＩＤＤＭ和５４例正常对照者的脂蛋白（α）和其它血脂成分进行了分析，结果显示ＮＩＤＤＭ组脂蛋白（α）高于对照组（Ｐ＜０，０１）；根据糖化血红蛋白水平将ＮＬＤＤＭ组分成三组，三组间脂蛋白（α）无显著性差异；相关分析发现ＮＩＤＤＭ全组脂蛋白（α）与糖化血红蛋白和血糖无相关性（Ｐ均＞０．０５）。进一步用多元逐步回归分析显示，脂蛋白（α）与糖化血红蛋白无关联（Ｐ＞０．０５）。研究结果表明ＮＩＤＤＭ血糖控制对脂蛋白（α）无影响。     

非胰岛素依赖型糖尿病患者的胃排空和胃电研究

为了探讨非胰岛素依赖型糖尿病（ＮＩＤＤＭ）的胃排空和胃电特性以及它们之间的相关性，用双核素标记ＳＰＥＣＴ技术和胃电图对４９例非胰岛素依赖型糖尿病患者进行了研究。其中２３例血糖控制不良型作胃排空检测，全部病例接受胃电图检查。结果显示：ＮＩＤＤＭ血糖控制不良组和对照组液相排空曲线相似，半排空时间Ｔ５０二组差异无显著性；固相排空曲线差异明显，固相Ｔ５０较对照组显著延长。ＮＩＤＤＭ血糖正常和异常组胃电节律紊乱率、退化率和恢复时间均显著高于对照组。胃排空和胃电图之间无明显相关性。结论：糖尿病患者存在固相胃排空和胃电图异常。血糖水平与胃电节律紊乱无关。胃排空和胃电图无相关性，不能用异常胃电图预测延迟的胃排空。     

脂蛋白（a）与非胰岛素依赖型糖尿病代谢控制的关系

为探讨非胰岛素依赖型糖尿病血糖控制对血清脂蛋白浓度的影响，对１０６例ＮＩＤＤＭ和５４例正常对照者的脂蛋白和其它成分进行了分析，结果显示ＮＩＤＤＭ组脂蛋白（ａ）高于对照组。根据糖化血红蛋白水平将ＩＤＤＭ组成三组，三组间脂蛋白无显著性差异。相关分析发现ＮＩＤＤＭ全组脂蛋白与糖化血红蛋白和血糖无相关性。进一步用多元逐步回归分析显示，脂蛋白与糖化血红蛋白无关联。研究结果表明ＮＩＤＤＭ血糖控制对脂蛋白无影响     

长期血糖控制与早期糖尿病肾病的进展速度

０３１长期血糖控制与早期糖尿病肾病的进展速度［英］／ＲｉｃｈｒｄＥ…／／ＫｉｄｎｅｙＩｎｔ．－１９９３；４４．－８５５～８５９糖尿病肾病（ＤＮ）的自然史尚不完全清楚，Ⅰ型糖尿病（ＩＤＤＭ）患者大约３０％～４０％最终发生ＤＮ，Ⅱ型糖尿病（ＮＩＤＤＭ）患...     

载脂蛋白B基因多态性与I型糖尿病并冠心病关系的研究

应用聚合酶链反应（ＰＣＲ）技术对非胰岛素依赖型糖尿病（ＮＩＤＤＭ）４１例、ＮＩＤＤＭ合并冠心病５１例和正常对照组６０例进行载脂蛋白Ｂ基因ＥｃｏＲＩ和ＸｂａＩ酶切位点限制性片段长度多态性（ＲＦＬＰ）研究。结果显示少见等位基因频率在ＮＩＤＤＭ组及ＮＩＤＤＭ并冠心病组均升高。与对照组比较，Ｅ－等位基因频率在糖尿病患者显著升高。ｘ＋等位基因频率升高与ＮＩＤＤＭ并发冠心病明显相关     

IDDM患者白细胞介素2和白细胞介素6的研究

测定ＩＤＤＭ患者１６例、ＮＩＤＤＭ患者２０例和正常对照组２７例的外周血单个核细胞产生白细胞介素２（ＩＬ－２）和白细胞介素６（ＩＬ－６）的能力。结果：ＩＤＤＭ患者ＩＬ－２水平较正常对照组和ＮＩＤＤＭ患者显著降低（ｐ＜０．００１），ＩＬ－６的水平显著升高（Ｐ＜０．００１）。ＮＩＤＤＭ患者ＩＬ－２和ＩＬ－６与正常对照组差异无显著性。提示ＩＤＤＭ患者ＩＬ－２和ＩＬ－６异常改变导致免疫功能紊乱。     

载脂蛋白B基因多态性与Ⅱ型糖尿病并冠心病关系的研究

应用聚合酶链反应（ＰＣＲ）技术对非胰岛屿纱依赖型糖尿病（ＮＩＤＤＭ）４１例、ＮＩＤＤＭ合并冠心病５１例和正常对照组６０例进行载脂蛋白Ｂ基因ＥｃｏＲ和ＸｂａＩ酶切位点限制性片段长度多态性（ＲＦＬＰ）研究。结果显示少见等位基因频率在ＮＩＤＤＭ组及ＮＩＤＤＭ并冠心病均升高。与对照组比较，Ｅ等位基因频率在糖尿病患者显著升高，等位基因频率升高与ＮＩＤＤＭ并发冠心病明显相关。     

Ⅱ型糖尿病血管并发症与血浆脂蛋白及体液免疫水平的关系

本文测定了５４例Ⅱ型糖尿病（ＮＩＤＤＭ）病人（２０例有微血管病变、１８例有大血管病变、１６例无血管病变）及３３例正常人的血浆脂蛋白（ａ）［Ｌｐ（ａ）］、低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）、循环免疫复合物（ＣＩＣ）、补体Ｃ３（Ｃ３）和免疫球蛋白。ＮＩＤＤＭ各组与正常对照组比较，ＬＤＬ－Ｃ、ＤＩＣ、Ｃ３、ＩｇＧ、ＩｇＡ水平均显著升高，ＩｇＭ显著下降。Ｌｐ（ａ）、ＣＩＣ在ＮＩＤＤＭ并发血管病变组均显著高于无血管病变组．ＮＩＤ－ＤＭ并发微血管病变组的ＣＩＣ水平又显著高于其大血管病变组。另外ＮＩＤＤＭ病人血浆Ｌｐ（ａ）、ＬＤＬ－Ｃ与ＣＩＣ水平呈显著正相关。提示ＮＩＤＤＭ病人的脂代谢异常及免疫异常与其血管并发症关系密切，脂代谢与免疫异常有内在联系。     

Ⅱ型糖尿病患者记忆功能障碍的临床研究

利用临床记忆量表测定了４４例Ⅱ型糖尿病（ＮＩＤＤＭ）患者、１１例其中合并腔隙性脑梗塞（ＬＩ）患者和３０例正常人的记忆功能。结果发现ＮＩＤＤＭ患者的指向记忆、联想学习、图像自由回忆、无意义图形再认识、人像特点联想回忆、记忆商（ＭＱ）等明显低于正常人；合并ＬＩ的ＮＩＤＤＭ患者ＭＱ也明显低于无ＬＩ的ＮＩＤＤＭ患者。ＭＱ与病程、血浆比粘度、糖化血红蛋白（ＨｂＡ１）、血糖呈负相关，与血胰岛素（ＢＩｎ）呈正相关。结果提示ＮＩＤＤＭ患者的语言、学习、抽象思维能力降低，并与病情控制程度有关。     

血糖控制不良的非胰岛素依赖型糖尿病患者胃排空时间测定

本文以双核素标记试餐ＳＰＥＣＴ显像技术，检测了１５例血糖控制不良的非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者的胃排空时间，结果显示：ＮＩＤＤＭ组液体排空曲线与对照组相似，呈指数相排空；固体排空曲线则不同于正常人的双相性曲线，而类似于液体排空曲线。１２例（８０％）无延迟时间（Ｐ＜０．００５）。９例（６０％）ＮＩＤＤＭ患者胃排空时间异常，其中固体半排空时间（Ｔ５０）延长者７例，固、液体Ｔ５０均延长和均缩短者各１例。固体Ｔ５０延长者归为一亚组，病程和血糖与固体Ｔ５０均有显著相关性。因此，ＮＩＤＤＭ患者以固体胃排空异常为主；对于那些长期血糖控制不良者有必要研究其胃排空功能；双核素标记试餐ＳＰＥＣＴ显像技术是较敏感的检测手段。     

红细胞山梨醇水平与糖尿病患者糖代谢控制

采用山梨醇脱氢酶法测定了正常人23例及糖尿病66例的红细胞山梨醇水平。发现血糖控制差的Ⅰ型及Ⅱ型糖尿病的红细胞山梨醇水平显著高于正常对照组,且与同时测定的空腹血糖、24小时尿糖以及HbAic之间存在着显著的正相关;血糖控制好的Ⅱ型糖尿病组的红细胞山梨醇水平与正常对照组无显著差异且与空腹血糖不相关;血糖控制差的Ⅰ型与Ⅱ型糖尿病组之间空腹血糖差异无显著性,但红细胞山梨醇水平差异却有显著性。提示红细胞山梨醇水平可以作为糖尿病患者糖代谢控制好坏的一个指标。     

Glucose tolerance and insulin response in parents of patients with insulin-dependent and juvenile-onset non-insulin-dependent diabetes mellitus.

Glucose tolerance and insulin response were examined using a 100 g oral glucose tolerance test (OGTT) in 108 parents of 23 patients with insulin-dependent (IDDM) and 31 patients with non-insulin-dependent diabetes mellitus (NIDDM), whose age of onset of diabetes was less than 35 years. Thirty-two age-matched healthy volunteers without a family history of diabetes were also examined as a control group. Diabetes and impaired glucose tolerance (IGT) were significantly more frequent in parents of NIDDM (diabetes 34%, IGT 27%) than in parents of IDDM (diabetes 7%, IGT 13%) (P less than 0.001). At least one parent had diabetes or IGT in 30% of IDDM and 84% of NIDDM patients (P less than 0.001), and both parents had diabetes or IGT in 9% of IDDM and 39% of NIDDM patients (P less than 0.02). Even in cases with 'normal' glucose tolerance, the mean plasma glucose was higher in parents of NIDDM than in control subjects, suggesting a high prevalence of abnormal glucose tolerance including the marginal degree of abnormality in the families of NIDDM. The early phase insulin response was decreased more among parents of NIDDM with the greater impairment of glucose tolerance. However, among those with 'normal' glucose tolerance, early phase insulin response did not differ between parents of IDDM and NIDDM, and control subjects. The results confirmed a stronger familial background in NIDDM patients of younger onset than in IDDM. The different patterns of glucose tolerance among two parents of young-onset NIDDM patients suggest heterogeneity of the mode of inheritance of NIDDM among families.     

Phosphodiesterase activity in human subcutaneous adipose tissue in insulin- and noninsulin-dependent diabetes mellitus

The influence of diabetes mellitus on phosphodiesterase (PDE) activity in human sc adipose tissue was investigated in 8 patients with insulin-dependent (IDDM) and 9 with noninsulin-dependent (NIDDM) diabetes mellitus. The results were compared with data from 10 healthy normal weight subjects. The apparent maximal PDE activity (Vmax) of the low Km form of PDE was 60% lower (P less than 0.01) in untreated IDDM and NIDDM than in the control state. After treatment of IDDM and NIDDM, the Vmax of the low Km PDE was normalized. In untreated IDDM and NIDDM, the Vmax of the low Km PDE was correlated to the cAMP level (r = 0.8). This correlation was not observed after antidiabetic treatment or in the control state. The apparent Vmax values of the high Km form of PDE were similar in the diabetic states and in control subjects. The results suggest that the low Km PDE is inhibited in untreated IDDM and NIDDM. In these conditions, PDE may be one factor responsible for regulation of the cAMP level.     

Islet cell surface antibodies preferentially inhibit glucose-stimulated insulin release in vitro

The effect of islet surface antibodies (ICSA) on in vitro insulin release was studied. Isolated rat islets were incubated in the presence of immunoglobulin preparations from patients with insulin-dependent and non-insulin-dependent diabetes mellitus (IDDM, NIDDM) and healthy subjects, and stimulated with D-glucose, L-arginine or tolbutamide. After incubation, the amount of insulin release from the rat islets was determined. The immunoglobulin preparations from 5 newly diagnosed IDDM patients who were positive for ICSA, and from 5 age-matched healthy subjects were examined. Even in the absence of complement or lymphocytes, immunoglobulin fractions positive for ICSA significantly inhibited low and high concentrations of glucose-stimulated insulin release compared with normal control (P less than 0.02), but had little influence on insulin release after stimulation with tolbutamide. Arginine-stimulated insulin release was almost the same in ICSA-positive immunoglobulin fractions and the control. Immunoglobulin fractions negative for ICSA either from four patients with recently diagnosed IDDM or from four newly diagnosed NIDDM patients had only negligible effect on insulin release after stimulation with glucose. These results suggest that ICSA in IDDM patients, even in the absence of complement or lymphocytes, may preferentially interfere with the mechanisms of glucose-stimulated insulin release in the pancreatic B cells.     

Diurnal variation of blood ketone bodies in insulin-dependent diabetes mellitus and noninsulin-dependent diabetes mellitus patients: the relationship to serum C-peptide immunoreactivity and free insulin

We examined whether the rise in ketone body concentration around midnight and in the early morning was due to the lack of free insulin (IRI) or excess of insulin counterregulatory hormones such as human growth hormone (hGH), cortisol and glucagon in noninsulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) patients and whether the monitoring of blood ketone body concentration was clinically useful as an index of metabolic control for deciding to increase or decrease the insulin dose in the treatment of diabetes mellitus. Serum levels of 3-hydroxybutyrate (3-OHBA), acetoacetate (AcAc) and 3-OHBA/AcAc ratio before breakfast were significantly increased in insulin-treated NIDDM patients with well-controlled fasting plasma glucose levels and IDDM patients compared to those in normal subjects. Mirror image diurnal changes were found between serum concentrations of 3-OHBA and serum C-peptide or free IRI in normal subjects and NIDDM patients treated with diet alone or sulfonylurea during the 24-hour daily profiles. However, there were no correlations between 3-OHBA and free IRI in the NIDDM patients treated with insulin and IDDM patients who had a much larger increase in the mean concentration of serum 3-OHBA at 6 a.m. caused by a low concentration of free IRI. Counterregulatory hormones were not increased in IDDM patients compared to normal subjects in the early morning. Cortisol/free IRI and hGH/free IRI molar ratios were significantly increased in NIDDM and IDDM patients compared to normal subjects in the early morning, but glucagon/free IRI molar ratio was not changed between IDDM and normal subjects. In conclusion, the early morning rising of ketone body concentration in insulin-treated diabetic patients, particularly IDDM patients, is due to the absolute lack of free IRI and/or the relative lack of free IRI to the levels of hGH or cortisol, and the monitoring of 3-OHBA is clinically useful as a more sensitive index of metabolic control.     

Presence of anti-DNA antibody in diabetes mellitus: its relation to the duration of diabetes and diabetic complications

In seven patients with insulin-dependent diabetes mellitus (IDDM) and 86 patients with non-insulin-dependent diabetes mellitus (NIDDM), serum anti-DNA antibody was measured by a semiquantitative radioimmunoassay (RIA) method. Prevalence of positive anti-DNA antibody (more than 20 U/mL) was five of seven in IDDM patients, 15 of 36 in NIDDM patients with insulin therapy, and seven of 50 in NIDDM patients without insulin therapy. None of normal subjects or patients with impaired glucose tolerance (IGT) showed positive anti-DNA antibody. The titer of anti-DNA antibody was higher in IDDM patients than in age-matched normal subjects (mean +/- SD; 22.1 +/- 15.3 v 6.5 +/- 2.2 U/mL, P less than .05). In patients with NIDDM, the antibody titer regardless of insulin treatment, was higher than in age-matched subjects with IGT (18.5 +/- 13.1 U/mL in NIDDM patients receiving insulin, 14.8 +/- 8.1 U/mL in NIDDM patients not receiving insulin, and 8.8 +/- 3.9 U/mL in IGT patients [P less than .001] for either of NIDDM groups v IGT). The titer of anti-DNA antibody was positively correlated with the duration of diabetes (r = .413, P less than .001) and with the postprandial blood glucose level (r = .311, P less than .01) in NIDDM patients when all of them were combined and analyzed as a group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevated levels of soluble E-selectin in patients with IDDM and NIDDM: relation to metabolic control

Summary The adhesion of leucocytes to the endothelium, an early step in atherogenesis, is mediated by cell adhesion molecules. In this study we evaluated the concentration of soluble adhesion molecules in patients with insulin-dependent (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) and studied its relation to glycaemic control. Soluble adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) were measured in 31 diabetic patients (18 with IDDM and 13 with NIDDM), 20 hyperlipoproteinaemic patients (10 with type IIa and 10 with type IIb) and 20 healthy subjects. Increased E-selectin concentrations were found in the patients with IDDM and NIDDM and in the hyperlipoproteinaemic patients when compared to the control subjects (p<0.01 for all the groups). ICAM-1 was found to be elevated only in the patients with NIDDM (p<0.01). No significant differences in VCAM-1 concentration were found in the different groups of subjects. The concentration of plasma E-selectin was positively correlated with the glycated haemoglobin (r=0.54, p<0.01) in patients with IDDM and NIDDM. In the same patients E-selectin was not related to the concentrations of plasma lipids in spite of the fact that it was found to be elevated in hyperlipoproteinaemic subjects. The results though preliminary suggest that in diabetic patients the concentration of soluble adhesion molecules and especially of E-selectin may be related to metabolic control.Abbreviations IDDM insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus - ICAM-1 intercellular adhesion molecule-1 - VCAM-1 vascular adhesion molecule-1 - AGE advanced glycation end products     

The Role of Insulin Resistance in the Natural History of Type 1 Diabetes

It is well established that peripheral insulin sensitivity is a critical factor in the aetiology of non-insulin dependent (Type 2) diabetes mellitus (NIDDM). Insulin resistance may also play a role at various stages in the natural history of insulin dependent (Type 1) diabetes (IDDM) and this was the topic of a workshop held in London on Friday 14 July 1995. The mechanisms of insulin resistance in IDDM are ill-defined but probably include ‘glucose toxicity’. In the pre-diabetic period, insulin resistance may affect rates of progression to frank hyperglycaemia. Following the clinical onset of IDDM, insulin resistance could influence the length of the ‘honeymoon period’, diabetic control and patterns of growth during puberty, insulin requirements and blood glucose control at any time, the birth weight of infants born to diabetic mothers, and, through an effect on lipid metabolism and hypertension, ultimately contribute to the excess mortality associated with IDDM. In NIDDM, insulin resistance could influence rates of progression to insulin dependence. Treatment using insulin enhancers in NIDDM patients with autoimmune changes might delay or arrest their usual high-risk of progression to insulin dependence. As it is likely that insulin resistance has a wide-ranging influence on the natural history of diabetes in IDDM patients we suggest that treatment with insulin enhancers may prove beneficial in selected patients. © 1997 by John Wiley & Sons, Ltd.     

Analysis of diabetic family connection in subjects with insulin-dependent diabetes mellitus (IDDM)

The family connection of diabetes was examined from the clinical records of 3,372 subjects who were seen, as an out patient population, within the frame of a Regional Health Program in Taranto, South Italy. The family connection of diabetes resulted from a questionnaire in which the subjects had to give informations about their disease, if present, and degrees of relationship that were directly verified by us with the examination (clinic and laboratory) of relatives said to have diabetes. From the analysis of records, it emerged that 112 patients were affected by insulin-dependent-diabetes mellitus (IDDM): 54 of them were related with at least one subject suffering from noninsulin-dependent diabetes mellitus (NIDDM), 13 with at least one subject affected by IDDM and the remaining 45 did not show any family connection. The corresponding figures found in a group of healthy control subjects, matched to IDDM patients for age, sex and BMI, were 19, 2 and 84, respectively (p less than 0.001). 34 IDDM patients were related with a first degree of relationship (parents, sons, sibs) to diabetic subjects (IDDM or NIDDM), but only 4 controls showed such a degree (p less than 0.001). These results seem to indicate that patients with IDDM have an increased family history of NIDDM.     

The predictive capability of the glycaemic response to spaghetti in non-insulin dependent (NIDDM) and insulin dependent (IDDM) diabetic subjects

To evaluate the predictive capability of the postprandial blood glucose response after consumption of a starch-rich meal, we compared the glycaemic effects of spaghetti (60 g) taken alone and with bolognese sauce (167 g). The study was carried out in both NIDDM (n = 6) and IDDM (n = 6) subjects. The latter had achieved normoglycaemia 120 min prior to the test meal by means of an artificial pancreas (Biostator) which provided constant insulinaemia during the observation period of 4 h. We found that the areas of blood glucose (above basal) were identical irrespective of whether spaghetti was taken alone or as part of a mixed meal in both NIDDM (484 +/- 154 mmol l-1 240 min-1 vs. 393 +/- 126 mmol l-1 240 min-1) and IDDM subjects (610 +/- 143 mmol l-1 240 min-1 vs. 770 +/- 135 mmol l-1 240 min-1). The insulin levels were identical in the IDDM diabetics. By contrast, the mixed meal caused a more marked insulinaemic response than spaghetti per se in the NIDDM subjects (3187 +/- 637 mU l-1 240 min-1 vs. 1940 +/- 235 mU l-1 240 min-1; P less than 0.05). In conclusion, the predictive capability of the glycaemic response to spaghetti was good in both IDDM and NIDDM diabetic subjects, at least under the conditions of the present study.