B-cell function and islet cell and other organ-specific autoantibodies in relatives to insulin-dependent diabetic patients

The pancreatic B-cell function (glucose tolerance, C-peptide release) and organ-specific autoantibodies, including islet cell cytoplasmic and cell surface (mouse), were studied in 45 first-degree relatives of patients with insulin-dependent diabetes mellitus diagnosed before the age of 30 years. Compared to 107 healthy persons without any family history of either insulin-dependent or non-insulin-dependent diabetes mellitus, the prevalence of autoantibodies was increased among the relatives. The prevalence of islet cell antibodies did not differ between relatives and controls and none of the individuals had complement-fixing islet cell antibodies. There was no difference in glucose tolerance or C-peptide release between relatives and controls, whether they had autoantibodies or not. At a three-year follow-up, none of the individuals had developed insulin-dependent diabetes.     

A prospective study of the development of diabetes in relatives of patients with insulin-dependent diabetes

BACKGROUND. The presence of cytoplasmic islet-cell autoantibodies has been recognized as a risk factor for the development of diabetes mellitus in relatives of patients with insulin-dependent diabetes mellitus (IDDM), but the magnitude of the risk is unknown, as is the influence of other factors, such as age, sex, and race. METHODS. From 1979 through 1989, we studied 4015 initially nondiabetic relatives of 1590 probands with IDDM to determine the risk of IDDM according to the presence and titer of autoantibodies, as well as other factors. RESULTS. Of the 4015 nondiabetic relatives, 125 (3.1 percent) had islet-cell antibodies in their initial serum samples, and 40 contracted IDDM. Islet-cell antibodies were most frequent (4.3 percent) in relatives who were under 20 years of age (P = 0.001) and in those (4.8 percent) from families with more than one affected member (a multiplex pedigree) (P = 0.003). Independent risk factors for the development of diabetes in the relatives included age of less than 10 years at the time of the initial study (P = 0.001), membership in a multiplex pedigree (P = 0.02), and a positive test for islet-cell antibodies in the initial serum sample (P = 0.0001). Twenty-seven of the relatives in whom diabetes developed (67.5 percent) had positive tests for islet-cell antibodies before the diagnosis of IDDM, giving a relative risk of IDDM of 68 (95 percent confidence interval, 34 to 134) for antibody-positive relatives. Islet-cell-antibody titers of 20 Juvenile Diabetes Foundation units or higher were associated with an increasing risk of diabetes. CONCLUSIONS. Nondiabetic relatives of probands with IDDM who are in the first two decades of life, are members of multiplex pedigrees, and have increased titers of islet-cell antibodies are the most likely to contract IDDM themselves.     

Risk of progression to diabetes of low titer ICA-positive first-degree relatives of type I diabetics in southern Germany

In a prospective study to evaluate the prevalence and predictive potential of circulating cytoplasmatic islet cell antibodies (ICA) and competitive insulin autoantibodies (CIAA), we screened 406 non-diabetic first-degree relatives of patients with Type I diabetes mellitus (n = 154 for CIAA). The prevalence of ICA was 2.5% (10/406) and of CIAA 0.6% (1/154) in ICA- and 10% (1/10) in ICA+ relatives at initial screening. The titer of ICA positivity in all relatives varied between 1:1 and 1:4. Values of elevated CIAA were 256 nU/ml of the CIAA+/ICA+, and 97 nU/ml of the CIAA+/ICA- relatives (normal range less than or equal to 39 nU/ml). Sera for repeat ICA and CIAA determination was obtained, and 70% of relatives were found to be again ICA+ after 1.5 years, 40% after 3 years, and 10% after 5.7 years. Both CIAA+ relatives were found to be again CIAA+ on follow-up. Intravenous glucose tolerance tests (IVGTT) were performed in all antibody-positive relatives. No decrease in first-phase insulin secretion (1 + 3 min) below the 1st percentile was observed in any of the ICA+ relatives during follow-up. No ICA+, but one CIAA+/ICA- relative had developed Type I diabetes after 5.6 years of follow-up. In summary, these results indicate that low titer ICA (less than 40 JDF units) are often transient and relatives with low titer ICA rarely progress to Type I diabetes. Elevated CIAA appear to be constant over time and associated with increased progression to overt diabetes.     

Prevalence of cytoplasmatic islet cell antibodies and insulin autoantibodies is increased in subjects with genetically defined high risk for insulin-dependent diabetes mellitus

Summary The presence of cytoplasmatic islet cell antibodies (ICA) and IgG insulin autoantibodies (IgG-IAA) has been observed in the prediabetic state of type 1 (insulin-dependent) diabetes (IDDM). We therefore analyzed the prevalence of these markers in sera from 1117 healthy HLA-typed first-degree relatives (1° Rel) of IDDM patients. ICA was determined by indirect immunofluorescence on cryostat sections of human pancreas. For IgG-IAA measurement a competitive solid-phase ELISA was used. ICA were present in 3.5% of 1° Rel vs 0.4% of controls (P<0.025). The highest frequencies of ICA were found in individuals of IDDM multiplex families (7.7%) and HLA-DR1,3 (5.4%), -DR1,4 (5.8%), and -DR3,4 (6.7%) positive subjects. We therefore conclude that the prevalence of ICA is increased in 1° Rel with high genetic risk for diabetes. IgG-IAA occurred in 9.9% of 1° Rel vs 1.4% of controls (P<0.01). Like ICA, IgG-IAA were significantly increased in a group of subjects being positive for either HLA-DR1,3-DR1,4, or -DR3,4 (16.5%,P<0.01). In multiplex families, however, prevalence of IgG-IAA was not increased. In contrast to ICA there was an additional influence of age and sex: IgG-IAA were found more often in siblings (mean age, 16.6 years; prevalence, 15.0%) than in parents (mean age, 44.1 years; prevalence, 8.3%) of IDDM patients (P<0.01). In brothers the prevalence of IgG-IAA is higher than in other 1° Rel. Only a weak association between ICA and IgG-IAA was observed in subjects (n=810) tested for both antibodies. IgG-IAA occurred in 6/35 (17%) ICA positive 1°Rel, while ICA were found in 6/79 (8%) IgG-IAA positive relatives.Abbreviations ICA islet cell antibodies - IgG-IAA immunoglobulin G-insulin autoantibodies - IDDM type 1 (insulin-dependent) diabetes mellitus - 1° Rel first-degree relatives - JDF Juvenile Diabetes Foundation - WHO World Health Organization - OD delta optical density     

Low interleukin-2 receptor levels in serum of patients with insulin-dependent diabetes

Interleukin-2 receptors are released in the circulation in response to antigenic or mytogenic stimulation of T-lymphocytes. Abnormal serum interleukin-2 receptor levels have been found in young children with type 1 diabetes and prediabetes. We measured interleukin-2 receptor levels in 17 patients with newly diagnosed type 1 diabetes, 21 patients with long-standing type 1 diabetes, 19 patients with long-standing type 2 diabetes, 19 islet-cell antibody positive nondiabetic polyendocrine patients, 12 islet-cell antibody-positive first-degree relatives of patients with type 1 diabetes and compared the results to age- and sex-matched normal controls. We found significantly lower interleukin-2 receptor levels in patients with newly diagnosed and long-standing type 1 diabetes compared to normal controls (87 ± 11 and 93 ± 11 vs. 142 ± 25 and 132 ± 40 U/ml, P < 0.001 and P < 0.01). There were no significant differences in interleukin-2 receptor levels between prediabetic groups and normal controls or patients with long-standing type 1 or type 2 diabetes. There was no correlation between glycosylated hemoglobin, blood glucose levels, and interleukin-2 receptor in the groups with long-standing type 1 or type 2 diabetes. We conclude that patients with type 1 diabetes have low interleukin-2 receptor serum levels. This phenomenon is acquired close to disease onset and is unlikely to be an early markers of type 1 diabetes.Abbreviations JDf Juvenile Diabetes foundation - ICA⁺ islet-cell antibody positive - IDDM insulin-dependent diabetes mellitus - IL-2R® interleukin-2 receptors - NIDDM non-insulin-dependent diabetes mellitus Correspondence to: R. Wagner     

Insulin-dependent diabetes mellitus secondary to chronic pancreatitis is not associated with HLA or the occurrence of islet-cell antibodies

We assessed HLA-DR types and investigated serum samples for islet-cell cytoplasmic antibodies (ICA) in 31 Danish patients with chronic pancreatitis. The antigen frequencies were compared with those in 1177 unrelated healthy Danish controls. Twenty patients had insulin-dependent diabetes and 11 had normal intravenous glucose tolerance. No significant differences in the frequencies of DR3, DR4, or DR2 were found between patients with insulin-dependent diabetes and patients with normal glucose tolerance or between any of these groups and controls. ICA were negative in all patients with chronic pancreatitis. It is concluded that the beta-cell dysfunction in insulin-dependent diabetes in chronic pancreatitis differs from that of classical insulin-dependent diabetes.     

Complications of mumps infection, islet-cell antibodies, and HLA

To investigate whether the development of islet-cell antibodies (ICA) in the course of mumps infection is associated with a "diabetes-like" immunogenetic condition, 45 children with mumps complications as well as 56 children with insulin-dependent diabetes mellitus (IDDM) were typed for HLA ABC and DR antigens. ICA were detected in 14 out of 35 mumps patients. In the IDDM group, significant deviations from antigen frequencies of normal controls were observed for HLA Bw39, DR2, DR3, and DR4. In contrast, in ICA positive mumps patients, the frequency of these antigens was normal, but Aw24 was significantly increased. Thus, no immunogenetic similarities of both groups of patients could be detected.     

T-Cell Response to Proinsulin and Insulin in Type 1 and Pretype 1 Diabetes

Insulin-dependent diabetes mellitus (IDDM) results from the selective destruction of pancreatic cells by a T cell-mediated autoimmune process. Insulin and proinsulin are the only known cell-specific autoantigens. Using short-term cultures of freshly isolated peripheral blood mononuclear cells, we evaluated T-cell responses to proinsulin and to insulin in IDDM patients and individuals at risk for IDDM. A proliferative T-cell response to proinsulin was observed in only 2 of 26 recent-onset IDDM subjects and 2 of 12 long-standing IDDM subjects and was associated with a proliferative response to insulin. In contrast, 5 of 13 islet cell autoantibody-positive first-degree relatives of IDDM patients showed a proliferative response to proinsulin alone, 3 of 13 to insulin alone, and 1 of 13 to both insulin and proinsulin. Overall, 9 of 13 ICA-positive first-degree relatives responded to either proinsulin or insulin. We observed an inverse relationship between antiinsulin antibodies and T-cell responses to insulin in ICA-positive first-degree relatives but not in long-standing IDDM patients. Our data indicate that proinsulin is a major antigen in IDDM and, further, illustrate the difference between the autoimmune response to insulin and the immune response to exogenous insulin.     

Macrophages from high-risk HLA-DQB1*0201/*0302 type 1 diabetes mellitus patients are hypersensitive to lipopolysaccharide stimulation

Levels of nonantigen-induced pro-inflammatory cytokines and prostaglandin in macrophages isolated from human leucocyte antigen (HLA)-matched type 1 diabetes mellitus patients, first-degree relatives and healthy controls were determined. We hypothesize that monocytes isolated from patients are sensitized or preactivated and therefore, have an altered response to in vitro stimulus compared with control groups as measured by levels of pro- and anti-inflammatory mediators. In this study, peripheral blood monocytes were differentiated to macrophages with macrophage-colony stimulating factor (M-CSF) to determine lipopolysaccharide (LPS)-stimulated tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-12 and prostaglandin E-2 (PGE-2) secretion from hetero- or homozygous HLA DQB1*0201 and *0302 type 1 diabetes mellitus patients, first-degree relatives and homozygous HLA DQB1*0602 healthy controls. LPS-stimulated secretion of TNF-alpha, IL-1beta and IL-6 was immediate and markedly higher in the HLA-DQB1*0201/*0302 type 1 diabetes patients compared with all other groups including HLA-matched healthy first-degree relatives. In DQB1*0201/*0302 diabetes patients PGE-2 secretion was delayed but increased by LPS stimulation compared with HLA-matched healthy relatives. IL-12 was not detected at any condition. These data suggest that macrophages from DQB1*0201/*0302 type 1 diabetes patients are sensitized to secrete both cytokines and PGE-2 following nonantigenic stimulation. Sensitized macrophages may be important to high-risk DQB1*0201/*0302-associated type 1 diabetes.     

Several different enterovirus serotypes can be associated with prediabetic autoimmune episodes and onset of overt IDDM

In a prospective multicentre study described previously on prediabetic events in siblings of index cases with insulin-dependent diabetes mellitus, 31 children developed clinical diabetes during the observation period and 51 children seroconverted for islet cell antibodies or insulin autoantibodies. By using nonserotype specific EIA and RIA, it has shown recently that enterovirus infections in both groups were frequently associated with increases of islet cell antibody and/or insulin autoantibody titres. Serum specimens sequentially collected from 12 children during the prediabetic period were still available and were then tested for serotype-specific neutralizing antibodies. Plaque-neutralization assays were carried out for coxsackievirus A9, coxsackievirus B types 1 to 6, and echovirus types 1 and 11. An unequivocal monotypic increase in neutralizing antibodies was observed on seven occasions in six children, on one occasion with coxsackievirus A9, one with coxsackievirus B1, two with coxsackievirus B2, two with coxsackievirus B3, and one with coxsackievirus B5. In four patients, the infection was associated temporally with increases in the levels of islet cell antibodies, insulin autoantibodies and/or antibodies to glutamic acid decarboxylase, and in three other patients, it coincided with the clinical onset of insulin-dependent diabetes mellitus. These results suggest that the association of enterovirus infections with insulin-dependent diabetes mellitus is not restricted to serotype 4 of coxsackie B viruses suspected previously, but that several different serotypes might play a role in the pathogenesis of the disease. J. Med. Virol. 56:74–78, 1998. © 1998 Wiley-Liss, Inc.     

Psychiatric disorder in patients with insulin-dependent diabetes mellitus attending a general hospital clinic: (i) two-stage screening and (ii) detection by physicians

Two-stage screening for psychiatric disorder was carried out with a sample of 99 male and 95 female outpatients with insulin-dependent diabetes mellitus, using the General Health Questionnaire and the Clinical Interview Schedule. The estimated prevalence of psychiatric disorder in this sample was 18%: only 28% of the psychiatric morbidity so identified was detected by physicians. In contrast, physicians rated 10% of the sample as psychiatric 'cases' using a simple 6-point scale.     

"Diabetic rosettes": a cellular immunity marker in subjects at risk for type I diabetes

The authors have previously described a marker of cell-mediated, called "diabetic rosettes", revealed by the increased binding of CD3 CD4 lymphocytes from type I diabetic patients to beta-cell membrane antigens, as compared to lymphocytes from control subjects. In the present study, they have detected such "diabetic rosettes" in some subjects at risk for type I diabetes. The mean value of lymphocytes adhering to beta (RINm5F)-cells (beta-CL) was statistically higher in those subjects at risk than in control blood bank donors (p = 0.003). When a positive test was arbitrarily defined as a value of beta-CL higher than the 95th percentile of controls, 20 p. cent of the subjects at risk were classified as beta-CL+. No difference was observed between two subgroups of subjects at risk: first degree relatives of type I diabetic patients, and non-diabetic subjects with transient hyperglycaemia. "Diabetic rosettes" were associated with HLA DR 3/4 heterozygosity (p less than 0.04) and with a "low" acute insulin release to IV glucose (p = 0.05). They were not associated with islet-cell antibodies, insulin autoantibodies, or "activated" (HLA DR+) T-lymphocytes. The authors suggest that "diabetic rosettes" represent a marker of cellular immunity in some subjects at risk for type I diabetes.     

Suppressor cell function and anti-DNA antibody idiotypes in the serum of SLE patients and their first-degree relatives

Sixteen-six (16/6) is a major cross-reactive idiotype of monoclonal anti-DNA antibodies, which was derived from the fusion of lymphocytes of a patient with systemic lupus erythematosus (SLE). Antibodies with the 16/6 idiotype (16/6 Id) are increased in the sera of patients with SLE and deposited in their gomeruli and skin. Since stimulated lymphocytes from healthy persons have the capacity to produce 16/6 Id, the mechanisms controlling its expression in health and their possible failure in SLE are of considerable interest. A defect in suppressor cell function was found in a high proportion of patients with SLE and in some of their first-degree relatives. Suppressor cell function in 15 SLE patients and in 53 relatives was compared with the level of 16/6 Id as well as with immunoglobulin levels and anti-DNA antibodies. Ten of 15 SLE patients and 26 of 53 first-degree relatives had increased serum 16/6 levels, which was found in only 1 of 35 healthy controls and household members. Of the 10 SLE patients with increased 16/6, six had a suppressor cell defect (P less than 0.1). Among the 26 first-degree relatives with elevated 16/6 Id levels, 12 had associated suppressor defect and in only two cases was a suppressor cell defect unaccompanied by increased 16/6 (P less than 0.005). For the group of 18 patients and relatives showing concomitant suppressor cell defect and increased 16/6, a correlation was found between the severity of the suppressor cell defect and the level of 16/6 Id in the serum. The increased 16/6 in the relatives was not associated with hypergammaglobulinemia or with measurable anti-DNA activity in the serum. We conclude that the suppressor cell defect in relatives of SLE patients is often associated with increased expression of antibodies with the 16/6 idiotype. However, additional mechanisms are involved in the regulation of 16/6 Id and the development of clinical SLE, since increased 16/6 was commonly found in the presence of a normal suppressor T-cell function.     

2型糖尿病家系非糖尿病一级亲属胰岛β细胞功能状态的研究

目的:探讨2型糖尿病(T2DM)家系非糖尿病一级亲属在不同糖耐量时胰岛素分泌第一时相的变化,及其在2型糖尿病发生、发展中的作用。方法:收集T2DM一级亲属正常糖耐量(NGT)组30例、糖耐量异常(IGT)组32例及新诊断T2DM组38例,并以无糖尿病家族史的30例健康成人(NC)为对照组,进行25 g静脉葡萄糖耐量试验(IVGTT),计算各组第一时相胰岛素分泌功能指数(AIR3-5)及胰岛素敏感指数(ISI)并进行比较。结果:新诊断的T2DM人群中,Homaβ、FPG、AIR3-5和ISI异常最为明显;而T2DM家系非糖尿病一级亲属的AIR3-5(53.67±2.36)mU/L和正常对照人群相比(80.85±1.43)mU/L出现下降;而ISI显著低于正常组均(P<0.01),但所有指标均处在正常人群和新诊断T2DM患者之间。结论:与正常对照人群相比,T2DM一级亲属NGT人群的胰岛β细胞第一时相胰岛素分泌减低,且存在胰岛素抵抗。     

Insulin-dependent diabetes mellitus following pentamidine therapy in a patient with AIDS

Pentamidine is known to cause severe dysglycaemia by damaging -cell function of the pancreas. The exact mechanism still remains unclear. We report the case of a 53-year-old man infected with the human immunodeficiency virus who developed insulin-dependent permanent diabetes mellitus 3 days after starting intravenous treatment with pentamidine for pneumocystis carinii pneumonia. Discharged from hospital the daily need of insulin increased continuously over one year now requiring an average dose of 80 units per day. So far, a number of cases of insulin-dependent diabetes mellitus following pentamidine therapy has been reported, but long-term observations are rare.Abbreviations AIDS acquired immune-deficiency syndrome - HIV human immunodeficiency virus - IDDM insulin-dependent diabetes mellitus Correspondence to: U. Liegl     

Autoantibodies and High-Risk HLA Susceptibility Markers in First-Degree Relatives of Brazilian Patients with Type 1 Diabetes Mellitus: A Progression to Disease Based Study

Purpose

The objective of this study was to determine the frequencies of autoantibodies to heterogeneous islet-cell cytoplasmic antigens (ICA), glutamic acid decarboxylase₆₅ (GAD₆₅A), insulinoma-associated antigen-2 (IA-2A) and insulin (IAA)–and human leukocyte antigen (HLA) class II markers (HLA-DR and -DQ) in first degree relatives of heterogeneous Brazilian patients with type I diabetes(T1DM). A major focus of this study was to determine the influence of age, gender, proband characteristics and ancestry on the prevalence of autoantibodies and HLA-DR and -DQ alleles on disease progression and genetic predisposition to T1DM among the first-degree relatives.

Methods

IAA, ICA, GAD₆₅A, IA-2A and HLA- class II alleles were determined in 546 first-degree-relatives, 244 siblings, 55 offspring and 233 parents of 178 Brazilian patients with T1DM.

Results

Overall, 8.9% of the relatives were positive for one or more autoantibodies. IAA was the only antibody detected in parents. GAD₆₅ was the most prevalent antibody in offspring and siblings as compared to parents and it was the sole antibody detected in offspring. Five siblings were positive for the IA-2 antibody. A significant number (62.1%) of siblings had 1 or 2 high risk HLA haplotypes. During a 4-year follow-up study, 5 siblings (expressing HLA-DR3 or –DR4 alleles) and 1 offspring positive for GAD₆₅A progressed to diabetes.

Conclusions

The data indicated that the GAD₆₅ and IA-2 antibodies were the strongest predictors of T1DM in our study population. The high risk HLA haplotypes alone were not predictive of progression to overt diabetes.     

A comparison of childhood and adult type I diabetes mellitus

The incidence rate of insulin-dependent (Type I) diabetes mellitus is bimodal: one peak occurs close to puberty, and the other in the fifth decade. To evaluate possible differences in these forms of the disease, we examined the clinical, biochemical, autoimmune, and genetic features of 82 children and adolescents (1.3 to 18.2 years old) and 44 adults (20.0 to 55.8 years old) when they presented with Type I diabetes. The mean (+/- SEM) duration of symptoms before diagnosis was longer in the adults (7.5 +/- 1.0 vs. 3.9 +/- 0.4 weeks; P less than 0.001), and their serum C-peptide concentrations at diagnosis were higher (0.29 +/- 0.03 vs. 0.17 +/- 0.01 nmol per liter; P less than 0.001), suggesting that they had more residual beta-cell function. There were no significant differences between the two groups in sex ratio, blood glucose levels, hemoglobin A1 values, degree of metabolic decompensation, or frequency of Type I diabetes in first-degree relatives. Thirty-four of 80 children tested (42.5 percent) were positive for insulin autoantibodies, as compared with only 1 of 26 adults (3.8 percent; P less than 0.001). However, the frequencies of islet-cell autoantibodies were similar in the adults and children (conventional autoantibodies, both 81 percent; complement-fixing autoantibodies, 46.2 percent and 60 percent). More children than adults were heterozygous for both HLA-Dw3/4 antigens (26.6 percent vs. 9.8 percent; P less than 0.05) and HLA-DR3/4 antigens (36.6 percent vs. 12.5 percent; P less than 0.05). We conclude that Type I diabetes that begins in adulthood is characterized by a longer symptomatic period before diagnosis, better preservation of residual beta-cell function, and lower frequencies of insulin autoantibodies and HLA-D3/D4 heterozygosity than Type I diabetes that begins in childhood or adolescence.     

Co-occurrence of celiac disease and other autoimmune diseases in celiacs and their first-degree relatives

The occurrence of other autoimmune diseases in celiac disease families has not been previously reported in a North American population. We investigated the familial aggregation of rheumatoid arthritis (RA), juvenile rheumatoid arthritis/juvenile idiopathic arthritis (JRA/JIA), hypothyroidism, insulin dependent diabetes mellitus (IDDM), and alopecia areata (AA) among individuals in families with celiac disease (CD). Family history information, obtained from questionnaires from the University of California Irvine Celiac Disease study, was reviewed for reports of RA, JRA/JIA, hypothyroidism, IDDM, and AA in celiac disease cases and their first-degree relatives. Reports of disease were compared with prevalence data from the literature and analyzed by calculating the standardized ratio (SR) with 95% confidence limits. We analyzed: (1) subjects with confirmed celiac disease or dermatitis herpetiformis (205 probands and 203 affected first-degree relatives) and (2) first-degree relatives of celiac disease cases (n=1272). We found a significantly increased number of cases, relative to the expected number, of IDDM in both groups and hypothyroidism among subjects with celiac disease. JRA/JIA was increased among first-degree relatives of celiacs. These results indicate that the presence of IDDM within our celiac disease families may be due to shared genetic susceptibility predisposing to these diseases or autoimmune diseases in general.     

A case for immune response genes?

Diabetes is not a single disease. Some patients develop insulin deficiency fairly rapidly and these are usually young, have lymphocytic infiltration of their pancreatic islets, possess circulating islet-cell antibody, and show a strong association with certain HLA phenotypes. This form of the disease is designated type I (juvenile onset or insulin-dependent diabetes mellitus, IDDM). The key factors involved in its pathogenesis were recently reviewed at the fourth of a series of international meetings on the immunology of diabetes'. This meeting was held in memory of Andrew Cudworth whose standing was pre-eminent in the immunogenetics of diabetes and whose untimely death is keenly felt.     

A population survey of pancreatic islet cell antibodies.

A population study on pancreatic islet cell antibodies (pica) among 3766 people from the town of Busselton, Western Australia showed that such antibodies were infrequent, the ''classical'' insulin-dependent diabetes associated islet cell antibody being present in less than 0.01%. Pancreatic islet cell antibodies in this population were not associated with insulin-dependent diabetes mellitus, and ten known insulin-dependent diabetics did not have these antibodies. These results for an unselected population are in sharp contrast with those derived from studies on highly selected hospital patients.