Correlation between simultaneous scintigraphic and ultrasonographic measurement of gastric emptying in patients with type 1 diabetes mellitus.

OBJECTIVE: To compare scintigraphic measurements of total stomach emptying of a semisolid meal with ultrasonographic measurements of changes in antral area as estimates of antral emptying in type 1 diabetic patients. METHODS: Eleven patients with insulin-dependent diabetes mellitus were studied with simultaneous measurements of gastric emptying by scintigraphy and ultrasonography. Patients were imaged immediately after ingestion (time 0) and every 15 minutes over 120 minutes. The gastric emptying rate was expressed as percent reduction in antral cross-sectional area from 15 to 90 minutes after meal ingestion. RESULTS: Ultrasonographic measurements showed a postprandial maximal antral area at 15 minutes, continuously decreasing with time, and reaching a plateau 45 to 90 minutes after the end of meal ingestion, whereas the scintigraphic counts attained their maximum immediately after the meal and began to fall thereafter. Between 15 and 90 minutes, the residual radioactivity and antral ultrasonographically measured distension curves were concordant. The curves then showed a tendency toward deviation for the last 15 minutes (median, 51% versus 59% at 105 minutes and 40% versus 57% at 120 minutes, respectively). A strong significant correlation could be seen between the ultrasonographic gastric emptying rate and scintigraphic half-time values (r = -0.94; P < .001). Comparing scintigraphic and ultrasonographic half-time values showed a systematic measurement error of 9.9 minutes and a random measurement error of 18.6 minutes. CONCLUSIONS: The use of standardized real-time ultrasonography to determine the gastric emptying rate of semisolid meals in diabetic patients, with the use of the change in gastric antral cross-sectional area in a single section of the stomach 15 and 90 minutes postprandially, offers a valid method for clinical practice.     

32例食管癌切除术后胃排空障碍

目的:探讨食管癌切除术后胃排空障碍并发症的临床特点、诊断及外科治疗。方法:对32 例食管癌术后胃排空障碍的临床资料进行回顾性分析。结果:全组有19例经保守治疗治愈,13例保守治疗无效行手术治疗,除1 例死亡外,其余治愈。结论:食管癌切除术后胃排空障碍大多数为功能性,与手术操作的细微环节有关,提高手术操作技巧、早期诊断、正确的处理措施可以阻止胃排空障碍的加重,对保守治疗无效的病例应选择手术治疗。     

Predictors of delayed gastric emptying in diabetes.

OBJECTIVE: To define the predictors of the rate of gastric emptying in patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 101 outpatients with diabetes (79 type 1 and 22 type 2) underwent measurements of gastric emptying of a solid/liquid meal (scintigraphy), upper gastrointestinal symptoms (questionnaire), glycemic control (blood glucose concentrations during gastric emptying measurement), and autonomic nerve function (cardiovascular reflexes). RESULTS: The gastric emptying of solid and/or liquid was delayed in 66 (65%) patients. Solid (retention at 100 min 64 +/- 3.2 vs. 50.2 +/- 3.6%, P < 0.005) and liquid (retention at 100 min 22.7 +/- 1.7 vs. 16.0 +/- 1.8%, P < 0.001) gastric emptying was slower in women than in men. Of all upper gastrointestinal symptoms (including nausea and vomiting), only abdominal bloating/fullness was associated with slower gastric emptying (P < 0.005). A multiple regression analysis demonstrated that both abdominal bloating/fullness and female sex were predictors of slower gastric emptying of both solids and liquids. CONCLUSIONS: We conclude that the presence of abdominal bloating/fullness but not any other upper gastrointestinal symptom is associated with diabetic gastroparesis and that gastric emptying is slower in diabetic women than in diabetic men.     

Delayed gastric emptying in conscious male rats following chronic estrogen and progesterone treatment

Several clinical observations and animal experiments have led to speculation concerning the possible effects of pregnancy and pregnancy-associated sex steroids on gastrointestinal function. It was reported that estrogen increases intestinal contractile activity, while progesterone or the combination of estrogen and progesterone decreases it. In order to measure gastric emptying, a methylcellulose test meal was given orally into the stomach of conscious rats. In progesteronetreated rats, at the dose of 0.2 mg/kg, gastric emptying was not significantly different from that of the control, but it was found to be significantly delayed at the dose of 10 mg/kg (P<0.05). Estrogen treatment at doses of 20 μg/kg and 600 μg/kg significantly delayed gastric emptying, when compared with controls (P<0.001). Combined therapy of estrogen and progesterone induced a significant delay in gastric emptying rate compared with the control group (P<0.001). In the animals with pseudopregnancy treatment (100 μg/kg estrogen+ 15 mg/kg progesterone; 7–12 days) the gastric empying rate was significantly different from that of the control (P<0.05). We conclude that both estrogen and progesterone exert inhibitory effects on gastric emptying, and this may account for the disturbances in gastrointestinal function that pregnant women frequently experience.     

Thyroid autoimmunity in children and adolescents with type 1 diabetes: a multicenter survey

OBJECTIVE: To investigate thyroid autoimmunity in a very large nationwide cohort of children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Data were analyzed from 17,749 patients with type 1 diabetes aged 0.1-20 years who were treated in 118 pediatric diabetes centers in Germany and Austria. Antibodies to thyroglobulin (anti-TG) and thyroperoxidase (anti-TPO) were measured and documented at least once in 7,097 patients. A total of 49.5% of these patients were boys, the mean age was 12.4 years (range 0.3-20.0 years), and the mean duration of diabetes was 4.5 years (range 0.0-19.5 years). A titer exceeding 100 units/ml or 1:100 was considered significantly elevated. RESULTS: In 1,530 patients, thyroid antibody levels were elevated on at least one occasion, whereas 5,567 were antibody-negative during the observation period. Patients with thyroid antibodies were significantly older (P < 0.001), had a longer duration of diabetes (P < 0.001), and developed diabetes later in life (P < 0.001) than those without antibodies. A total of 63% of patients with positive antibodies were girls, compared with 45% of patients without antibodies (P < 0.001). The prevalence of significant thyroid antibody titers increased with increasing age; the highest prevalence was in the 15- to 20-year age group (anti-TPO: 16.9%, P < 0.001; anti-TG: 12.8%, P < 0.001). Thyroid-stimulating hormone (TSH) levels were higher in patients with thyroid autoimmunity (3.34 microU/ml, range 0.0-615.0 microU/ml) than in control subjects (1.84 microU/ml, range 0.0-149.0 microU/ml) (P < 0.001). Even higher TSH levels were observed in patients with both anti-TPO and anti-TG (4.55 microU/ml, range 0.0-197.0 microU/ml). CONCLUSIONS: Thyroid autoimmunity seems to be particularly common in girls with diabetes during the second decade of life and may be associated with elevated TSH levels, indicating subclinical hypothyroidism.     

Male sex increases the risk of autoimmunity but not type 1 diabetes

OBJECTIVE: The goal of this study was to explore the role of sex on the prevalence of autoantibodies, protective genetic subtypes, beta-cell function, and the incidence of type 1 diabetes in a population of first- and second-degree relatives of patients with type 1 diabetes (probands). We examined both the effect of the sex of the individual screened as well as the effect of the sex of the individual's proband on diabetes risk variables tested. RESEARCH DESIGN AND METHODS: The Diabetes Prevention Trial-Type 1 has screened 93,188 relatives of type 1 diabetic patients from February 1994 to January 2002. After observing that more men than women were islet cell autoantibody (ICA) positive for the group as a whole, we further explored the role of sex by detailed analysis of variables in this population. RESULTS: Our data suggest only an influence of sex on the type 1 diabetes disease process. After adjustment for race, age, and relationship to proband, male sex was associated with the appearance of autoimmunity, i.e., the presence of ICA and having two or more antibodies. There was no effect of sex on the presence of other autoantibodies, insulin secretion, results of oral glucose tolerance test, or development of diabetes. CONCLUSIONS: Our finding that male sex conveys an independent increased risk for development of ICA and multiple antibodies, while at the same time finding no difference with respect to the development of diabetes, suggests that male relatives with the known risk factor of ICA are less likely than comparable female relatives to progress to overt disease, that the pathogenesis of type 1 diabetes among men is slower compared with women, or that women develop diabetes manifesting different antibody responses.     

老年糖尿病患者胃排空功能的评估

目的:用13C辛酸呼气试验方法检测老年2型糖尿病患者胃排空功能,并分析其相关因素。方法:2002-07/2003-01河北省人民医院老年病三科住院2型糖尿病患者共148例。纳入标准:符合WHO1999年糖尿病诊断标准;排除标准:胃肠道器质性病变、严重肝、肾、心脑血管疾病者。将符合上述标准的2糖尿病患者31例设为糖尿病组,年龄61～74岁。选择同期体检健康的老年自愿者19例为对照组,年龄60～73岁。给予糖尿病患者及对照组老年人13C辛酸试验餐,检测呼气样品,计算患者胃半排空时间(half-emptyingtime,T1/2)、延迟相时间(lagphasetime,Tlag);同时记录患者年龄、性别、病程、体质量指数(bodymassindex,BMI)、症状得分,检测患者空腹血糖、餐后血糖、糖化血红蛋白(HbA1c),并与T1/2进行相关分析。结果:糖尿病患者胃排空延迟发生率及胃T1/2,Tlag犤48%,(191.33±64.77),(124.56±55.63)min犦明显高于对照组犤10%,(111.58±22.66),(88.74±20.33)min犦(χ2=7.525,P=0.006;t=3.858,3.523,P<0.01);患者T1/2与空腹血糖、HbA1c,BMI有相关关系(r=0.54,0.16,0.43,P=0.006,0.024,0.036),而与年龄、病程、性别、症状得分、餐后血糖无明显相关性(P>0.05)。结论:老年2型糖尿病患者可能存在胃排空时间延迟;空腹血糖、HbA1c和BMI可能是胃排空延     

FCRL3 -169CT functional polymorphism in type 1 diabetes and autoimmunity traits.

A functional variant located in the promoter region of the Fc receptor like 3 gene (FCRL3, -169CT variant) has been recently shown to be associated with several autoimmune diseases in the Japanese population. Following the concept of shared genetic determinants between autoimmune diseases, we tested this variant for association to Type 1 diabetes (T1D) and T1D-related phenotypes in two independent settings: a family-based association study (French and US families) and a case-control study (French population). We found suggestive evidence for association of the FCRL3 -169CC genotype, corresponding to the susceptibility genotype for rheumatoid arthritis, with an increased risk of additional autoimmunity markers (OR=1.97, P=0.01) and of other autoimmune diseases (OR=1.75, P=0.05). However, there was no evidence of association of this variant with T1D in these cohorts, separately and combined, nor in subgroups of patients defined based on their major T1D risk factors at HLA-DRB1, insulin and PTPN22. Hence, this variant may help define subgroups of T1D patients with contrasted risk of other autoimmune diseases.     

Clinical presentation and early course of type 1 diabetes in patients with and without thyroid autoimmunity

OBJECTIVE: To evaluate the prevalence of thyroid autoimmunity (TAI) in patients with recent-onset type 1 diabetes and to determine the influence of TAI on the clinical presentation and evolution of type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied 111 newly diagnosed type 1 diabetes patients > 13 years old. The diagnosis of TAI was based on medical history and measurement of thyroid peroxidase (microsomal) antibodies (TPOAs). Clinical presentation of diabetes, beta-cell autoimmune markers (GADAs and 1A2As), and evolution of insulin-secretory reserves and metabolic control during the first 2 years of follow-up were analyzed. Differences between groups were evaluated by Student's t test or the chi 2 test. The influence of TAI on follow-up data was evaluated by multiple logistic regression analysis. RESULTS: TAI was present in 31 patients (14 TPOA+ patients with normal thyroid function, 12 TPOA+ patients with thyroid dysfunction, and 5 patients with previously diagnosed TAI). TAI was more prevalent in women than in men (43.7 vs. 15.9%, P = 0.001). beta-Cell autoimmunity was more prevalent in patients with TAI than in those without TAI (93.5 vs. 76.3%, P = 0.03). The evolution of insulin requirements, metabolic control, and insulin-secretory reserves was comparable in the two groups. CONCLUSIONS: TAI is present in many type 1 diabetes patients at the time of diagnosis and is associated with a high prevalence of thyroid dysfunction. The clinical presentation of diabetes and the evolution of metabolic control and insulin-secretory reserves are not influenced by the presence of TAI. Patients with type 1 diabetes should be screened for TAI at diagnosis.     

Soluble transferrin receptor level: a new marker of iron deficiency anemia, a common manifestation of gastric autoimmunity in type 1 diabetes

OBJECTIVE: A total of 15-20% of type 1 diabetic patients have parietal cell antibodies (PCAs). PCA+ subjects are at increased risk for iron deficiency anemia and atrophic gastritis. Recently, soluble transferrin receptor (sTfR) levels have proven to be a sensitive indicator for iron deficiency They are, in contrast with ferritin levels, independent of inflammation, liver and hormonal status, and sex. We are the first to evaluate sTfR levels in type 1 diabetes and tested the hypothesis of higher sTfR levels in patients with PCAs and/or autoimmune gastritis. RESEARCH DESIGN AND METHODS: We examined 148 type 1 diabetic patients (85 men and 63 women; 50 were PCA+) and 59 sex- and age-matched control subjects (30 men and 29 women). The main outcome measures were sTfR levels, iron deficiency anemia, and atrophic gastritis. Logistical regression analysis tested risk factors for iron deficiency RESULTS: Iron deficiency was present in 38 subjects. Iron (P<0.0001) and ferritin (P<0.0001) levels but not sTfR levels were lower in women. sTfR levels were similar in diabetic and control subjects but were higher in PCA+ subjects (P = 0.015). In diabetic subjects, iron deficiency anemia was more prevalent in PCA+ than in PCA- patients (odds ratio 3.07, P = 0.013) and was associated with sex (P = 0.0001), age (P = 0.046), and sTfR (P = 0.0008) levels. Atrophic gastritis was present in 15 of 28 PCA+ and in 1 of 11 PCA diabetic subjects (P = 0.014). sTfR levels tended to be higher in patients with atrophic gastritis (P = 0.062). CONCLUSIONS: In type 1 diabetes, sTfR levels can be used to diagnose iron deficiency anemia, which is more prevalent in PCA+ subjects. sTfR levels are higher in PCA+ individuals who are at risk for developing atrophic gastritis.     

Geographical variation in risk HLA-DQB1 genotypes for type 1 diabetes and signs of beta-cell autoimmunity in a high-incidence country

OBJECTIVE: To assess possible differences in the frequency of HLA-DQB1 risk genotypes and the emergence of signs of beta-cell autoimmunity among three geographical regions in Finland. RESEARCH DESIGN AND METHODS: The series comprised 4,642 children with increased HLA-DQB1-defined genetic risk of type 1 diabetes from the Diabetes Prediction and Prevention (DIPP) study: 1,793 (38.6%) born in Turku, 1,646 (35.5%) in Oulu, and 1,203 (25.9%) in Tampere. These children were examined frequently for the emergence of signs of beta-cell autoimmunity, for the primary screening of which islet cell antibodies (ICA) were used. If the child developed ICA, all samples were also analyzed for insulin autoantibodies (IAA), GAD65 antibodies (GADA), and antibodies to the IA-2 molecule (IA-2A). RESULTS: The high- and moderate-risk genotypes were unevenly distributed among the three areas (P<0.001); the high-risk genotype was less frequent in the Oulu region (20.4%) than in the Turku (28.4%; P<0.001) or Tampere regions (27.2%; P<0.001). This genotype was associated with an increased frequency of ICA seroconversion relative to the moderate risk genotypes (hazard ratio 1.89, 95% CI 1.36-2.62). Seroconversions to ICA positivity occurred less commonly in Tampere than in Turku (0.47, 0.28-0.75), whereas the seroconversion rate in Oulu did not differ from that in Turku (0.72, 0.51-1.03). The Tampere-Turku difference persisted after adjustment for risk genotypes, sex, and time of birth (before January 1998 versus later). Seroconversion for at least one additional autoantibody was also less frequent in Tampere than in Turku (0.39, 0.16-0.82). CONCLUSIONS: These data show that in Finland, the country with the highest incidence of type 1 diabetes in the world, both the frequency of the high-risk HLA-DQB1 genotype and the risk of seroconversion to autoantibody positivity show geographical variation. The difference in seroconversion rate could not be explained by the difference in HLA-DQB1-defined disease susceptibility, implying that the impact of environmental triggers of diabetes-associated autoimmunity may differ between the three regions studied.     

Autoantibody "subspecificity" in type 1 diabetes: risk for organ-specific autoimmunity clusters in distinct groups

OBJECTIVE: Autoimmune thyroid disease (AIT), celiac disease, and Addison's disease are characterized by the presence of autoantibodies: thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in AIT, tissue transglutaminase antibody (TTGAb) in celiac disease, and 21-hydroxylase antibody (21-OHAb) in Addison's disease. The objective of this study was to define the prevalence of these autoantibodies and clinical disease in a population with type 1 diabetes. RESEARCH DESIGN AND METHODS: We screened 814 individuals with type 1 diabetes for TPOAb, TGAb, TTGAb, and 21-OHAb. Clinical disease was defined by chart review. Factors related to the presence of autoimmunity and clinical disease including age at onset of type 1 diabetes, duration of diabetes, age at screening, sex, and the presence of autoantibodies were reviewed. RESULTS: The most common autoantibodies expressed were TPOAb and/or TGAb (29%), followed by TTGAb (10.1%) and 21-OHAb (1.6%). Specific HLA DR/DQ genotypes were associated with the highest risk for expression of 21-OHAb (DRB1*0404-DQ8, DR3-DQ2) and TTGAb (DR3-DQ2- DR3-DQ2). The expression of thyroid autoantibodies was related to 21-OHAb but not to TTGAb. The presence of autoantibodies was associated with and predictive of disease. CONCLUSIONS: In this large cohort of individuals with type 1 diabetes, the expression of organ-specific autoantibodies was very high. The grouping of autoantibody expression suggests common factors contributing to the clustering.     

Gene therapy for type 1 diabetes: a novel approach for targeted treatment of autoimmunity

It has been difficult to develop therapies that target those T cells initiating and mediating the pathogenesis of autoimmune disease. Indeed, most current treatments indiscriminately affect both the autoreactive T cells and the "good" T cells, putting the patient at risk of compromised immune function. A new approach raises the possibility of targeted therapy for autoimmunity. Transplantation of hematopoietic stem cells modified to express a protective form of MHC class II corrects a defect in central tolerance. This method contrasts with other targeted therapies that attempt to modify peripheral tolerance, which is also defective in type 1 diabetes mellitus.