Seroconversion of reticulin autoantibodies predicts coeliac disease in insulin dependent diabetes mellitus.

Serum IgA class reticulin autoantibody test was performed prospectively once a year on 238 children and adolescents with insulin dependent diabetes mellitus (IDDM). At the initial testing, within one year after onset of IDDM, five were positive and 233 were negative. During follow up a further 11 of the initially antibody negative children became positive (6.7%). Jejunal biopsy was performed at the appearance of the autoantibodies and silent coeliac disease was shown in nine (3.8%). One of these children showed on initial biopsy after the onset of IDDM to have normal jejunal mucosal architecture deteriorating later to a flat lesion. Jejunal immunohistochemical studies of another of the patients positive for reticulin autoantibodies but normal on routine biopsy showed an increased density of intraepithelially located gamma/delta T cells and aberrant HLA-DR expression in the crypts pointing to ongoing mucosal inflammation and potential coeliac disease. This study shows that in IDDM patients, reticulin autoantibody negative subjects become antibody positive, which may be followed by coeliac disease. Repeated serological screening and rebiopsy should be considered to detect late developing clinically silent coeliac disease among patients with IDDM.     

HLA antigens and insulin dependent diabetes mellitus. A family study.

Sixteen insulin dependent diabetic patients (age at onset less than 35 years) and their families were tissue typed for HLA antigens. Glucose tolerance of relatives was also tested. Among diabetic patients two HLA antigens were found with increased frequency: B8 (31 percent, control 15 percent) and Bw35 (38 percent, control 23 percent). Among normal relatives B8 and Bw35 had the same frequency as the control group. Bw15 frequency was not increased in either group. In relatives, no correlation between HLA antigens (B8 or Bw35) and abnormal glucose tolerance, obesity and over-weight at birth was found. Present data confirm previous reports of high B8 frequency in early onset diabetic patients, but fail to demonstrate a raised frequency of abnormal glucose tolerance among relatives bearing B8 (or, in our cases, Bw35). B8 may be considered a genetic indicator for susceptibility to juvenile diabetes. On the basis of present results in families, however non genetic factors clearly also play a determinant role. Furthermore, that diabetogenesis arises from a link between Ir-genes and HLA-B8 antigen should only be considered a suggestive hypothesis.     

胰岛素依赖型糖尿病的视网膜病变的观察

对５１例病程３年以上的胰岛素依赖型糖尿病（ＩＤＤＭ）患者进行荧光眼底血管造影检查，发现儿童时期发病的糖尿病视网膜病变（ＤＲ）发生率为２５．５％，全部为单纯型视网膜病变。糖尿病病程在３年以上即可并发ＤＲ病。结果表明，ＤＲ的发生率及严重程度与病程及血糖控制的好坏有明显的相关性（Ｐ〈０．０１）。严格控制高血糖，正确治疗可使已发生的轻度ＤＲ病变好转或消失。     

胰岛素依赖型糖尿病大截面血小板超微结构的立体计量学研究

本文采用立体计量学方法定量分析１０例胰岛素依赖型糖尿病（ＩＤＤＭ）患者大截面和非大截面血小板，以及６例健康对照者非大截面血小板超微结构的变化，发现糖尿病患者大截面血小板存在膜分化障碍，各种细胞器含量增多，并相对集中于不同区域，揭示糖尿病骨髓巨核细胞膜分化障碍，是造成细胞器丰富的大血小板增多的原因。微血管病变组大截面血小板存在早期激活的结构变化，表明微血管病变可作为血小板激活的因素之一。     

Concurrent onset of adult onset Still''s disease and insulin dependent diabetes mellitus.

Within two weeks after symptoms of an upper respiratory tract infection a 32 year old man developed Still's disease and insulin dependent diabetes mellitus, both of which have persisted for 24 months. Investigations failed to confirm acute infection but did show isolated persistent increase of serum antibodies to rubella virus. The simultaneous onset of these two diseases suggests a shared cause, possible associated with rubella infection.     

老年2型糖尿病胰岛素抵抗与非酒精性脂肪肝相关分析

研究表明,胰岛素抵抗(IR)是2型糖尿病(T2DM)、代谢综合征(MS)、动脉粥样硬化(AS)的共同发病基础。近期研究发现IR在脂肪肝的发生中亦起着极其重要的作用[1-2]。流行病学研究表明,在欧美国家以酒精性脂肪肝为多见,而在我国则以非酒精性脂肪肝(NAFLD)为主,并且已成为发病率仅次于     

No association between rheumatoid arthritis and insulin dependent diabetes mellitus: an epidemiologic and immunogenetic study.

To acquire more information on the controversial question of a possible association between rheumatoid arthritis (RA) and insulin dependent diabetes mellitus we searched for insulin dependent diabetes mellitus among patients hospitalized due to RA in 2 rheumatism hospitals in Finland. Nine subjects with insulin dependent diabetes mellitus were found among an annual number of 1460 patients admitted to one of the hospitals due to RA. These figures give a frequency of insulin dependent diabetes mellitus in patients with RA of 0.6% (95% confidence interval 0.2-1.0%), which does not exceed the prevalence of insulin dependent diabetes mellitus among the middle aged population of Finland in general (0.5-0.6%). Accordingly, no overrepresentation of homozygosity for HLA-DR4 was found among the total number of 25 patients with RA as well as insulin dependent diabetes mellitus, though the opposite might be expected as these diseases have a common DR4 association--RA with DR4 and DR1 and insulin dependent diabetes mellitus with DR4 and DR3. Instead, an increased frequency of DR1 (p less than 0.0002) and the antigen combination DR1/4 (p less than 0.01) was found in the subjects with both RA and insulin dependent diabetes mellitus compared with the subjects with insulin dependent diabetes mellitus alone.     

Highly variable gastric emptying in patients with insulin dependent diabetes mellitus.

Some diabetic patients--particularly those with nausea and vomiting--frequently have evidence of delayed gastric emptying while other diabetic patients may in fact exhibit accelerated gastric emptying. Whether the presence or absence of symptoms of upper gastrointestinal dysfunction correlated with objective measures of gastric emptying in insulin dependent diabetic subjects was investigated. Twenty one insulin dependent diabetic patients underwent a solid phase gastric emptying scintiscan using in vivo labelled chicken liver. Thirteen patients had symptoms suggestive of gastrointestinal dysfunction (nausea, vomiting, early satiety, or constipation), while eight patients had no gastrointestinal symptoms. Eleven patients had orthostatic hypotension. All patients had been diabetic since childhood or adolescence. As a group, the diabetic patients showed a half time (T50) of gastric emptying (mean (SD) 150.0 min (163.7) that was not significantly different from that of 12 healthy control subjects (148.1 min (62.4)). Those diabetic patients without gastrointestinal symptoms and without orthostatic hypotension, however, showed a gastric emptying half time (70.1 min (41.6)) that was significantly faster than that of the control subjects. Conversely, those diabetic patients with nausea, vomiting, and early satiety (or early satiety alone) showed T50 values that were significantly greater than those of the diabetic patients without these symptoms. No correlation was found between the T50 value and the duration of diabetes, the fasting blood glucose at the time of study, or the respiratory variation in heart rate (E:I ratio). These observations indicate that highly variable rates of gastric emptying occur in insulin dependent diabetic patients, and that accelerated gastric emptying may occur in diabetic patients who have no symptoms of gastrointestinal dysfunction.     

老年人非胰岛素依赖型糖尿病与脂蛋白（a）的关系

目的了解老年非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者及其慢性并发症和并存症者血清脂蛋白（ａ）〔Ｌｐ（ａ）〕变化情况。方法测定８９例老年ＮＩＤＤＭ和６１例非老年ＮＩＤＤＭ患者并以６２例老年非糖尿病健康者作对照的血清Ｌｐ（ａ）和其它血脂水平，并分析了老年ＮＩＤＤＭ组并发症及并存症对血清Ｌｐ（ａ）的影响。结果３组血清Ｌｐ（ａ）浓度差异无显著性（Ｐ＞０．０５），Ｌｐ（ａ）与血清总胆固醇、甘油三酯、高密度脂蛋白－胆固醇及其亚型、低密度脂蛋白－胆固醇、载脂蛋白Ａ１和Ｂ水平无明显相关性（ｒ＝－０．０４１～０．１９７，均为Ｐ＞０．１）。老年ＮＩＤＤＭ组合并高血压、糖尿病性视网膜病变和肾病变者的血清Ｌｐ（ａ）浓度明显高于无合并相应疾病者（Ｐ＜０．０５或Ｐ＜０．００１）；血清尿素氮、肌酐、尿微量白蛋白排泄率升高、尿蛋白定性阳性者血清Ｌｐ（ａ）明显高于肾功能正常者（均为Ｐ＜０．００５）；血糖化血红蛋白Ａ１ｃ≥８％者其Ｌｐ（ａ）明显高于＜８％者（Ｐ＜０．００５）。结论老年ＮＩＤＤＭ患者血清Ｌｐ（ａ）浓度与对照组差异无显著性；合并高血压、糖尿病性视网膜病变和肾病变及肾功能异常、糖化血红蛋白Ａ１ｃ≥８％者血清Ｌｐ（ａ）明显升高。     

Association between diabetes mellitus and gastroesophageal reflux disease:A meta-analysis

AIM:To investigate whether there is a link between diabetes mellitus(DM) and gastroesophageal reflux disease(GERD).METHODS:We conducted a systematic search of Pub Med and Web of Science databases,from their respective inceptions until December 31,2013,for articles evaluating the relationship between DM andGERD.Studies were selected for analysis based on certain inclusion and exclusion criteria.Data were extracted from each study on the basis of predefined items.A meta-analysis was performed to compare the odds ratio(OR)in DM between individuals with and without GERD using a fixed effect or random effect model,depending on the absence or presence of significant heterogeneity.Subgroup analyses were used to identify sources of heterogeneity.Publication bias was assessed by Begg’s test.To evaluate the results,we also performed a sensitivity analysis.RESULTS:When the electronic database and hand searches were combined,a total of nine eligible articles involving 9067 cases and 81 968 controls were included in our meta-analysis.Based on the randomeffects model,these studies identified a significant association between DM and the risk of GERD(overall OR=1.61;95%CI:1.36-1.91;P=0.003).Subgroup analyses indicated that this result persisted in studies on populations from Eastern countries(OR=1.71;9 5%C I:1.3 8-2.1 2;P=0.0 0 3)a n d i n y o u n g e r patients(mean age50 years)(OR=1.70;95%CI:1.22-2.37;P=0.001).No significant publication bias was observed in this meta-analysis using Begg’s test(P=0.175).The sensitivity analysis also confirmed the stability of our results.CONCLUSION:This meta-analysis suggests that patients with DM are at greater risk of GERD than those who do not have DM.     

Ⅰ型糖尿病患者外周血NK细胞活性降低

以改良铬（５１Ｃｒ）释放法检测３４例Ⅱ型糖尿病（ＮＩＤＤＭ）、２３例Ｉ型糖尿病（ＩＤＤＭ）和２８例正常人外周血ＮＫ细胞对Ｋ５６２靶细胞的杀伤活性。结果显示：①ＩＤＤＭ组患者ＮＫ细胞活性显著低于ＮＩＤＤＭ组及正常对照组，经正规治疗血糖控制以后，ＮＫ细胞活性恢复正常。②ＮＩＤＤＭ组患者血ＮＫ细胞活性在血糖控制前后无显著变化，与正常对照组比较亦无统计学差异。提示ＩＤＤＭ与机体免疫异常密切关联。     

冠心病并发Ⅱ型糖尿病患者高凝状态的临床研究

目的探讨冠心病（CHD）并发非胰岛素依赖糖尿病（NIDDM）患者体内凝血功能的变化及临床意义。方法选择病例组CHD并发NIDDM患者24例,CHD患者32例,以及正常对照组20例,分别测定血浆D-二聚体（D-D im er）、纤维蛋白原（Fbg）含量,同时分析Fbg与冠脉病变支数的相关性。结果CHD并发NIDDM患者血浆D-D im er、Fbg水平显著高于CHD患者和正常对照者（P<0.05或P<0.01）,并且CHD患者也显著高于对照者（P<0.05）;冠脉病变严重者血浆Fbg含量显著高于冠脉病变较轻患者（P<0.01）。结论CHD并发NIDDM患者体内存在明显的高凝状态,并与冠状动脉病变程度有关。     

Type I (insulin dependent) diabetes mellitus

Summary A recent investigation of families containing two and three consecutive generations affected with Type I (insulin dependent) diabetes mellitus has led to speculation that there is a second susceptibility gene, not linked to the major histocompatibility complex. These families differ in important respects from families which have provided the strongest evidence for HLA linkage, namely, families with two or more affected siblings. Computer simulations were designed to test the hypothesis that these two types of families were drawn from the same population of insulin dependent patients. The results indicate that this hypothesis is tenable and that the consecutive generation families probably failed to yield strong evidence for an HLA linked susceptibility gene because of ascertainment bias combined with probable incorrect specifications of the mode of inheritance of insulin dependent diabetes.     

Platelet hyperreactivity and vasculopathy in insulin dependent diabetes mellitus

Platelet functions were studied in 10 patients with insulin dependent diabetes mellitus (IDDM) with vasculopathy, and in age and sex-matched normal controls. The patient group at presentation showed increased circulating platelet aggregates, greater platelet factor III availability and increased aggregation of platelets in response to various agonists (shorter latent period, greater rate of aggregation, greater degree of aggregation, p < 0.05- < 0.001). This platelet hyperreactivity remained unchanged even after normalisation of blood glucose. In contrast, similar platelet hyperreactivity seen by us earlier in patients with uncontrolled IDDM without vasculopathy reversed to normal after metabolic control. In view of the postulated role of hyperreactivity of platelets in the pathogenesis of vasculopathy in IDDM, our results imply that once vasculopathy sets in, a vicious cycle starts between platelet hyperreactivity and vasculopathy. Proper and early treatment of IDDM at a stage when vasculopathy is not present, would therefore be important in reversing the platelet hyper-function and may possibly delay the development of vasculopathy.     

Effect of metformin on peripheral insulin sensitivity in non insulin dependent diabetes mellitus

To test whether metformin treatment might improve peripheral insulin sensitivity in non insulin dependent diabetes, we measured peripheral glucose uptake in 12 non insulin dependent diabetics before (A) and after 4 weeks (B) of metformin therapy (2 X 850 mg/day) by the hyperinsulinemic clamp technique (80 mU/m2/min). In addition, insulin binding to monocytes was compared between A and B. Diabetic control, evaluated by measurement of fasting blood glucose and glycosylated hemoglobin, was significantly improved by metformin treatment (P less than 0.01). Insulin binding to monocytes was not significantly influenced by metformin (A-4.53% vs. B-5.12%, n.s. at insulin tracer concentration). Peripheral glucose utilisation improved slightly, but significantly after 4 weeks of metformin therapy (A: 4.4 +/- 0.6 mg/kg/min, B: 5.4 +/- 0.8 mg/kg/min, p less than 0.01). Improvement in peripheral glucose utilisation correlated significantly with improved metabolic control, estimated by fasting blood glucose measurements (p less than 0.01).     

Effects of alpha 2-adrenergic blockade on renal hemodynamics in patients with insulin dependent diabetes mellitus.

The role of renal alpha 2-adrenoceptors in the regulation of glomerular filtration and renal perfusion is unknown. We studied the effects of alpha 2-adrenergic blockade on renal hemodynamics in six patients with insulin-dependent diabetes mellitus (IDDM) and in six healthy subjects. At the basal state, glomerular filtration rate (GFR) was higher in IDDM although the difference from control levels was not statistically significant. Volume expansion, achieved by infusion of isotonic sodium chloride solution, during placebo infusion induced a significant drop in GFR in healthy subjects but not in IDDM patients. Infusion of the alpha 2-adrenoceptor antagonist idazoxan did not further modify the effect of volume expansion on GFR. Renal plasma and blood flow as well as filtration fraction were not significantly changed by volume expansion or idazoxan infusion. Plasma renin activity and plasma aldosterone levels decreased during volume expansion in both IDDM and control subjects. In conclusion, volume expansion induced decreased GFR in healthy controls but not in IDDM patients. Since infusion of idazoxan did not affect GFR or other parameters of renal hemodynamics, renal alpha 2-adrenoceptors do not seem to be involved in the regulation of renal function. Hence, enhanced renal alpha 2-adrenoceptor activity is not likely to underlie hyperfiltration as seen in IDDM.