NIDDM患者24小时血压监测的临床意义

用无创性动态血压监测（ＡＢＰＭ）对３０例血压正常的ＮＩＤＤＭ患者进行２４小时动态血压监测，并探讨其与自主神经病变和肾病的关系。结果：ＮＩＤＤＭ患者２４小时平均收缩压（１６．５±２．６ｋＰａ）、夜间收缩压（１６．３±３．１ｋＰａ）均较对照组（分别为１４．６±１．１ｋＰａ和１４．０±１．６ｋＰａ）明显增高；夜间收缩压负荷值增高（有１７例，占５７％）；夜间收缩压下降百分率降低（５．７％±５．０％对１０．４％±５．７％）；有神经病变的ＮＩＤＤＭ患者夜间收缩压下降百分率（３．６％±３．３％）及昼－夜尿白蛋白排泄差值（８．８％±８．５％）均低于无神经病变患者（分别为９．９％±５．１％和２０．６％±１１．１％）。提示糖尿病患者血压昼夜节律减弱或消失以及夜间血压增高可能参与糖尿病肾病的发生。     

Glutamic acid decarboxylase antibodies,autonomic nerve antibodies and autonomic neuropathy in diabetic patients

Summary To clarify whether GAD-ab are associated with diabetic autonomic neuropathy and/or complement fixing antibodies against sympathetic ganglia, adrenal medulla, and vagus nerve, we examined 133 diabetic patients (95 with IDDM). GAD-ab were determined by a radioligand binding assay using in vitro expression of recombinant GAD-65 whereas sympathetic ganglia antibodies, adrenal medulla antibodies, vagus nerve, and ICA were evaluated by indirect immunofluorescence assays. Autonomic nerve function was evaluated by objective tests (heart rate reactions to deep breathing and to tilt). In the total material of 133 patients, GAD-ab were detected in 36 patients, all of whom had IDDM. The frequency of GADab was similar (38%) in IDDM patients with and without signs of autonomic neuropathy (21 of 55 vs 15 of 40). In addition, there were no significant associations between GAD-ab and autonomic nerve antibodies; GAD-ab were detected in 9 of 21 (43%) of patients with and in 27 of 112 (24%) of patients without sympathetic ganglia antibodies, in 5 of 15 (33%) of patients with and 31 of 118 (26%) without adrenal medulla antibodies, and in 5 of 15 (33%) with and 31 of 118 (26%) of patients without vagus nerve antibodies. The frequency of ICA, however, was significantly increased in patients with sympathetic ganglia antibodies compared with those without sympathetic ganglia antibodies (10 of 21 [48%] vs 21 of 112 [19%]; p<0.01). In conclusion, GAD-ab were neither associated with disturbed autonomic nerve function nor with antibodies against autonomic nerve structures.Abbreviations GAD Glutamic acid decarboxylase - ab antibodies - ICA islet cell antibodies - CF-ADM complement-fixing adrenal medulla antibodies - CF-SG complement-fixing sympathetic ganglia antibodies - CF-V complement-fixing vagal nerve antibodies - IDDM insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus - JDF Juvenile Diabetes Foundation     

IA-2 antibodies – a sensitive marker of IDDM with clinical onset in childhood and adolescence

Summary To study the relationship of IA-2 antibodies (IA-2A) to other autoantibodies and genetic risk markers in insulin-dependent diabetes mellitus (IDDM), 758 children and adolescents younger than 15 years of age (mean age 8.4 years) with newly diagnosed diabetes were analysed for IA-2A, GAD antibodies (GADA) and insulin autoantibodies (IAA) with radiobinding assays, for islet cell antibodies (ICA) with immunofluorescence and for HLA DR alleles by serology. IA-2A were detected in 85.9 % of cases with no association with gender or age. An overwhelming majority of the patients (71.3 %) tested positive for three or more antibodies, and 90.7 % for at least two. Fifty-four subjects (7.1 %) had one antibody detectable, whereas only 2.1 % of the patients tested negative for all four. A higher proportion of patients was positive for IA-2A and/or GADA than for ICA alone (95.5 vs 84.2 %, p < 0.001). The prevalence and level of IA-2A were increased in cases carrying HLA DR4/non-DR3 compared with other DR combinations. The results indicate that almost all patients with newly diagnosed childhood IDDM can be identified by screening with these four autoantibodies. The combination of IA-2A and/or GADA had a higher sensitivity for IDDM than ICA alone. The close association between IA-2A and HLA DR4, the strongest single allele predisposing to IDDM, suggests that IA-2A may be a more specific marker of beta-cell destruction than GADA, which have been shown to associate with the DR3 allele and thyroid autoimmunity. [Diabetologia (1998) 41: 424–429] Received: 20 August 1997 and in final revised form: 13 November 1997     

The beta cell glucokinase promoter variant is an unlikely risk factor for diabetes mellitus

Summary Glucokinase plays an important role in the regulation of insulin secretion and is therefore an attractive candidate gene for both insulin dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. A single G-A nucleotide polymorphism at the –30 position of the beta-cell specific promoter region of the glucokinase gene was previously associated with reduced beta-cell function. In the present study we analysed 268 consecutive newly diagnosed Swedish patients classified with either IDDM (n = 205), NIDDM (n = 31) or unclassifiable (n = 32) diabetes between the ages of 15 and 35 years along with a group of 158 age- and sex-matched control subjects. The beta-cell promoter region was amplified by the polymerase chain reaction and the G-A variant identified by single strand conformational polymorphism. There was no significant difference in allele frequencies of G and A between any of the subject groups and likewise, no significant difference in the frequencies of the G/G, G/A, or A/A genotypes. Eight subjects were homozygous for the less common A allele, five had IDDM and three were control subjects. Our results suggest that the –30 beta-cell glucokinase promoter variant is not associated with IDDM. [Diabetologia (1997) 40: 959–962) Received: 3 February 1997 and in revised form: 29 April 1997     

The frequency and severity of retinopathy are related to HbA1c values after, but not at, the diagnosis of NIDDM

OBJECTIVES: To examine the relationship between previous glycaemic exposure and prevalence of retinopathy 8 years after diagnosis of diabetes in 58 islet cell antibodies (ICA)-negative noninsulin-dependent diabetes mellitus (NIDDM) patients and in a group of 14 ICA-positive 'NIDDM' and insulin-dependent diabetes mellitus (IDDM) patients. DESIGN AND METHODS: The Wisconsin retinopathy scale was used to assess the retinopathy which was graded into mild, moderate and severe nonproliferative diabetic retinopathy (NPDR), or proliferative retinopathy (PDR). The frequency and severity of retinopathy was related to HbA1c levels at diagnosis, and 3 and 5 years later. RESULTS: Thirty of the 58 ICA-negative NIDDM patients (52%) but only 2 of the 14 ICA-positive 'NIDDM' or IDDM patients (14%) had mild-moderate-severe NPDR 8 years after diagnosis (P = 0.02). None had PDR. Retinopathy 8 years after diagnosis in NIDDM (= 58 ICA-negative patients) was correlated with the degree of glycaemic control (HbA1c levels) at 3 and 5 years after diagnosis, but not to HbA1c levels at diagnosis. The relative risk for a higher average HbA1c (per percentage) at 3 and 5 years was 1.56 for any retinopathy vs. no retinopathy (95% confidence interval 1.1-2.2; P = 0.01) and 1.68 for moderate to severe NPDR in comparison with no DR and mild NPDR (95% confidence interval 1.0-2.8; P = 0.04). CONCLUSIONS: Retinopathy after 8 years of diabetes in NIDDM patients was associated with impaired glycaemic control during previous years but not with glycaemic control at baseline. Good glycaemic control may prevent retinopathy in patients with NIDDM.     

Autoantibodies associated with presymptomatic insulin-dependent diabetes mellitus in women

Presymptomatic autoantibody markers of insulin-dependent (Type 1) diabetes mellitus (IDDM) are less well characterized in adults than in children. We quantitated anti-GAD, anti-ICA512 and ICA by titration to endpoint and compared frequencies and levels in 139 Finnish women from whom 390 serum samples had been archived during antecedent pregnancies for 10 years before and up to 1 year after diagnosis of diabetes. Also, we compared the autoantibody status in adults with IDDM with that of children with newly diagnosed IDDM. Of the 35 women seropositive for 1 or more autoantibodies, 77 % developed IDDM, 11 % non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), 9 % gestational diabetes mellitus requiring insulin (GDM-ins) and 3 % GDM controlled by diet. The frequency of antibodies during the 10-year presymptomatic period was 83 % for anti-glutamic acid decarboxylase (GAD), 52 % for anti-ICA512 and 41 % for islet cell antibodies (ICA) for those who developed IDDM, 25 %, 17 %, and 0 % for NIDDM, 12 %, 4 %, and 8 % for GDM-ins and 1 %, 0 %, and 1 % for GDM-diet. Anti-GAD was found most consistently in early samples; 13 of 15 with a single autoantibody at their first test had anti-GAD. Among those who developed IDDM, the frequency of anti-GAD was constant, anti-ICA512 increased threefold, and ICA increased slightly before diagnosis. Levels of the autoantibodies varied between subjects, but were relatively stable in individual subjects. Comparison of tests on the women, and children after diagnosis of IDDM, showed the frequencies and levels to be the same for anti-GAD but lower for anti-ICA512 and ICA in adults. Our observations show in women the long latency of seropositivity before overt IDDM, the predominance of anti-GAD among these three serological markers, and the presence of these markers in NIDDM presumably representing a NIDDM phase of autoimmune insulitis. © 1997 by John Wiley & Sons, Ltd.     

Systemic levels of cytokines and GAD-specific autoantibodies isotypes in Chinese IDDM patients

It is not clear if a Th1/Th2 imbalance in Type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) would lead to a particular antigen-specific IgG subclass dominant as had been shown in the mouse model. In new-onset Type 1 diabetics, an autoantibody response to glutamate decarboxylase (GADab) is frequently observed but the GADab subclass repertoire is not well-established. We determined the systemic levels of representative Th1 and Th2 cytokines and the GADab IgG subclass distribution in 41 Chinese IDDM patients of whom 26 were recently diagnosed (< or = 1 year) and 32 had GADab, to ascertain a likely association of antigen-specific antibody isotype and the Th1/Th2 dichotomy. With high-sensitivity ELISA systems that measure sub-picogram cytokine concentrations, 26 of the 41 patients (63.4%) had at least one of the pro-inflammatory Th1 cytokines (TNF-alpha, IFN-gamma and IL-12) detected. Fewer patients (4/41) had the anti-inflammatory Th2 cytokine IL-4 detected. For IL-10, all subjects had measurable quantities but only three diabetics had levels above the upper limit for healthy subjects (n = 20). Grouped according to the profile of detectable cytokines, there were 24 Th1, 2 Th2 and 2 Th0 patterns. GAD-specific IgG1 antibody was more frequently expressed; 22 of 32 GADab[+] patients. The rank order for the GADab subclasses was IgG1 > 4 > 3 > 2; IgG2 was found in 11 GADab[+] patients. Recent-onset diabetics have a similar ranking of the GAD-specific IgG subclasses. In human Type 1 diabetes, a predominance of GAD-specific IgG1 antibody response is observed together with a dominant Th1 cytokine pattern.     

Latent autoimmune diabetes mellitus in adult humans with non-insulin-dependent diabetes: isPsammomys obesus a suitable animal model?

Recent data suggest that in a proportion of NIDDM patients there is a slowly evolving insulitis which results in a latent autoimmune diabetes leading to full insulin-dependence. Many animal models exist of NIDDM but none have reported the spontaneous existence of a similar phenomenon. We have re-examined the histology of pancreata from a few Psammomys obesus who had become insulin-dependent in the late stages of NIDDM. We report here the unexpected finding of the presence of insulitis in these animals and suggest that they could be a model for the clinical observation of latent IDDM in NIDDM patients.     

血清胰岛细胞抗体的测定及临床意义

作者采用Ｏ型血人新鲜胰腺冰冻切片作抗原，建立了血清胰岛细胞胞浆抗体（ＩＣＡ）的间接免疫荧光测定方法。对１５７例糖尿病患者（其中ＩＤＤＭ８２例、ＮＩＤＤＭ７５例）和８４例正常人进行了血清ＩＣＡ检测。结果，ＩＤＤＭ组、ＮＩＤＤＭ组和对照组的ＩＣＡ阳性率分别为３１．５％、１３．３％和１．１％，３组间差异有非常显著性（Ｐ＜０．００５）。ＩＤＤＭ组中，病程６个月以内者ＩＣＡ阳性率为４１．７％，病程超过６个月者为２２．６％，差异无显著性。１０例ＩＣＡ阳性的ＮＩＤＤＭ病人中，４例为口服降糖药继发失效者。提示ＩＣＡ是ＩＤＤＭ的自身免疫血清学标志，对糖尿病的病因学诊断分型及判断ＮＩＤＤＭ口服降糖药继发失效有重要意义。     

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.     

Age of onset and type of Japanese younger diabetics in Tokyo

The age of onset of diabetes and the type of diabetes were examined in 1408 Japanese patients who were initially diagnosed as having diabetes under the age of 30 and were registered in our Diabetes Center between 1980 and 1989. Of the 1408 patients, 538 (38.2%) had insulin-dependent diabetes mellitus (IDDM) (male/female ratio of 2:3), and 870 (61.8%) had non-insulin-dependent diabetes mellitus (NIDDM) (male/female ratio of 5:4). There were significant differences of the sex ratio in both IDDM and NIDDM. The age at which the numbers in both the IDDM and NIDDM groups were almost equal was 13–14 (26 for IDDM and 23 for NIDDM at 13; 28 for IDDM and 30 for NIDDM at 14). A total of 58% of IDDM patients (22% of all patients) and only 6% of NIDDM patients (4% of all patients) were diagnosed under the age of 14 (P < 0.01). Of the patients with IDDM, 42% (16% of all patients) were diagnosed over the age of 14, as were 94% of NIDDM (58% of all patients). The percentage of NIDDM cases increased even more over the age of 28, and no NIDDM patients developed diabetes under the age of 9.     

Antibodies to Glutamic Acid Decarboxylase in Japanese Diabetic Patients with Secondary Failure of Oral Hypoglycaemic Therapy

Some patients with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) are positive for antibodies to glutamic acid decarboxylase (anti-GAD), which have been shown to be a useful marker for the diagnosis and prediction of insulin-dependent (Type 1) diabetes mellitus (IDDM). Anti-GAD positive NIDDM patients tend to develop insulin deficiency. We investigated the prevalence of anti-GAD in 200 NIDDM with secondary failure of oral hypoglycaemic therapy (SF) and 200 NIDDM well controlled by diet and/or sulphonylurea agents (NSF). Twenty-two of 200 (11 %, p < 0.05) SF patients and 6 of 200 (3 %) NSF patients were anti-GAD positive. The positive rate for anti-GAD was as high as 23.8 % in the non-obese and insulin deficient SF patients. The SF patients with anti-GAD tended to be non-obese and to have an impaired release of endogenous insulin. The interval before development of secondary failure was not associated with the presence of anti-GAD in this study. In conclusion we found that anti-GAD was positive in as many as 11 % of the SF patients, suggesting that autoimmune mechanisms may play an important role in the pathogenesis of secondary failure of sulphonylurea therapy. © 1997 by John Wiley & Sons, Ltd.     

人类白细胞相关抗原HLA DQB1基因与IDDM的关联

利用ＰＣＲ／ＳＳＯ方法对ＩＤＤＭ病人，ＬＡＤＡ病人，ＮＩＤＤＭ病人以及健康对照者进行ＨＬＡ ＤＱＢ１基因分型。结果发现ＤＱＢ１＊０２０１及ＤＱＢ１＊０３０２在ＬＡＤＡ组显著增高，分别为５３．４％，６６．７％比正常组的１９．５％和３４．２％。与正常组相比，ＤＱＢ１＊０３０２在ＩＤＤＭ组显著增高，为９１．１％比３４．２％。     

Autoimmune markers in slow type 1 diabetes: confrontation to type 1 diabetes

Slow onset type 1 diabetes is an heterogeneous entity. Its clinical features may mimick type 2 diabetes but its pathophysiological mechanisms are close to type 1 diabetes. AIM OF THE STUDY: To find out the frequencies, levels and associations of ICA, GADab and IA-2ab in type 2 diabetic patients with atypical phenotype. To compare it to type 1 diabetes. PATIENTS AND METHODS: ICA, GADab and IA-2ab were determined in: - 61 patients (age at diagnosis 48.2 +/- 10, range 36-73 years) with an initial diagnosis of type 2 diabetes but having at least one symptom suggesting a slow type 1 diabetes (loss of weight, absence of obesity at diagnosis or secondary failure of oral hypoglycaemic agents). - 70 patients with type 1 diabetes (age 18 +/- 8.9, range 2-35 years). Clinical data evaluated in slow type 1 were maximal BMI, BMI and loss of weight at diagnosis and autoimmune disease. Fasting C-peptide and insulinemia were also assessed. RESULTS: (Slow type 1 diabetes versus type 1 diabetes). ICA (43% vs 70%; p <0.01) and IA-2ab (16% vs 75%; p <0.01) were more frequent in type 1. GADab were as frequent (62% vs 74%). Association of the three antibodies (15.7% vs 58.5%; p <0.05) were more frequent in type 1. Prevalence of GADab alone (27.5% vs 7.5%; p <0.05) was higher in slow type 1 diabetes and with higher levels (median 55.5 UI/ml vs 17 UI/ml; p <0.01). There was no difference for levels of ICA (25.5 UJDF/ml vs 28 UJDF/ml) or IA-2ab (11.5 UI/ml vs 38.5 UI/ml). BMI of GADab positive patients was lower. Delay of insulinotherapy was shorter in GADab or ICA positive patients. We did not find any relationship between antibodies presence and fasting C-peptide or insulinemia. CONCLUSION: Slow type 1 diabetes should be evoked in atypical type 2 diabetes. Slow onset type 1 diabetic patients have different autoimmune patterns suggesting a different pathophysiological process. GADab and ICA are useful markers to predict future insulinopenia.     

胰岛细胞抗体ABC法检测及临床意义初步探讨

胰岛素依赖型糖尿病（ＩＤＤＭ）与机体的免疫功能紊乱有密切的关系。胰岛细胞抗体（ＩＣＡ）是ＩＤＤＭ患者主要的免疫学标志之一。可采用免疫组织化学技术作ＩＣＡ定性检测。我们首次应用“Ｏ”型血正常人胰腺石蜡切片作为抗原，ＡＢＣ法（卵白素－生物素化过氧化物酶复合物法）检测血清中ＩＣＡ。结果：１７例ＩＤＤＭ患者，阳性检出率５２．９４％；２０例ＮＩＤＤＭ及２０例非糖尿病患者无阳性反应。与国外报道比较，其方法的可     

Analysis of islet cell surface antigen reactions with islet cell surface antibodies (ICSA)

Islet cell surface antibodies (ICSA) have been detected in the sera of many patients with insulin-dependent diabetes mellitus (IDDM). They have also been demonstrated to affect the plasma membranes of beta-cells in vitro. To determine the pathogenetic role of ICSA in IDDM, we studied their prevalence and their relationship to lymphoblastogenesis (LBG) in diabetes as well as in other autoimmune diseases. Furthermore, islet cell antigens (IAg) were characterized from rat pancreatic islet cells, using an affinity column consisting of human IgGs including ICSA. ICSA titers were measured by indirect immunofluorescence. Sera were determined as ICSA-positive when they reacted to more than 10% of 50-100 cells. The LBG investigation was carried out after a 4-day incubation with phytohemagglutinin (PHA), pokeweed mitogen (PWM), or concanavalin A (Con A). The LBG induced by IAg was investigated after an 8-day incubation. Lymphocytes included 75% CD3-positive cells and 5% CD20-positive cells. IAg were purified from ICSA-positive IgG coupled to CNBr-activated sepharose 4B. The prevalence of ICSA was 39% in patients with IDDM (11/28), 15% in non-insulin dependent diabetes mellitus (NIDDM) (16/109), 14% in Graves' disease (3/22), 29% in Hashimoto's disease (5/17), 12% in rheumatoid arthritis (3/25), 20% in systemic lupus erythematosus (SLE) (7/35), and 33% in Sj?gren's syndrome (2/6). No ICSA were detected in 27 normal subjects. Although sera from the patients with autoimmune diseases contained antinuclear antibodies, antithyroid antibodies and/or rheumatoid factor, there was no relationship between the prevalence of such antibodies in patients with ICSA and those without it. In 3 patients (60%) with ICSA-positive IDDM, the lymphoblastogenic responses to PHA and PWM were decreased. A similar decrease was observed when comparing ICSA-positive NIDDM to ICSA-negative NIDDM (PHA: p less than 0.05; PWM: p less than 0.01). However, there was no relationship between HbA1 and the LBG response or between HbA1 and the presence of ICSA. The relative molecular weights (Mr.) of the IAg reacting with ICSA-positive IgG were around 67, 64, 55, and 20K in all but three patients with diabetes mellitus. IAg with a Mr. around 30K or less than 14K were also demonstrated in some patients with diabetes mellitus. The Mr. of IAg was the same in three patients with autoimmune disease as in diabetes mellitus, but it differed in three other similar patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Islet autoantibody markers in IDDM: risk assessment strategies yielding high sensitivity

Summary Identification of islet autoantigens offers the possibility that antibody tests other than islet cell antibodies may be used for assessing risk of insulin-dependent diabetes mellitus (IDDM). The aim of this study was to determine the combination of islet autoantibody markers that could identify most future cases of IDDM. Islet cell antibodies, antibodies to glutamic acid decarboxylase (GAD)₆₅, 37,000/40,000 M_r islet tryptic fragments, carboxypeptidase-H, and islet cell autoantigen (ICA)69 were measured in sera from 100 newly-diagnosed IDDM patients, 27 individuals prior to onset of IDDM, and 83 control subjects. Islet cell antibodies were detected in 88 % of IDDM patients and 81 % with pre-IDDM, GAD₆₅ antibodies in 70 % of IDDM patients and 89 % with pre-IDDM, and antibodies to 37,000/40,000 M_r islet tryptic fragments in 54 % of IDDM patients and in 48 % with pre-IDDM. The latter were found only in conjunction with islet cell antibodies and were more frequent in young onset cases. All 20 IDDM patients and the 3 pre-IDDM subjects who had islet cell antibodies without GAD₆₅ antibodies had antibodies to 37,000/40,000 M_r islet tryptic fragments, and all but one had disease onset before age 15 years. No sera strongly immunoprecipitated in vitro translated ICA69 or carboxypeptidase-H; 4 % of patients had anti-ICA69 and 11 % anti-carboxypeptidase-H levels above those of the control subjects. The findings suggest that none of the single antibody specificities are as sensitive as islet cell antibodies, but that a combination of GAD₆₅ antibodies and antibodies to 37,000/40,000 M_r islet tryptic fragments has the potential to identify more than 90 % of future cases of IDDM. Such a strategy could eventually replace islet cell antibodies in population screening for IDDM risk assessment. [Diabetologia (1995) 38: 816–822] Received: 17 October 1994 and in revised form: 29 December 1994     

D6S2420与1型糖尿病和LADA的相关性研究

目的 了解1型糖尿病（IDDM）的易感位点IDDM5与中国人群IDDM和成人迟发IDDM（LADA）的关系。方法 应用PCR－PAGE结合产物直接测序的技术，在105例无亲缘关系的成都地区正常汉族人，48例1型糖尿病患者以及22例成人迟发型1型糖尿病LADA患者中，对1型糖尿病易感位点IDDM5的连锁标记D6S2420的多态性进行分析。结果 D6S2420位点的等位基因A4的频率在1型糖尿病组中显著高于正常对照组，为26．04％vs12.86%、P＜0．0385；在LADA组中，各等位基因的频率分布与正常对照组相比无显著性差异，P值均＞0．05。结论 1型糖尿病的易感位点IDDM5与中国人群的1型糖尿病相关，但与LADA不相关；1型糖尿病与LADA发病的遗传因素可能存在差异。