In order to select a population at risk for the development of diabetes for a prospective study of the relationship of islet cell antibodies (ICA), islet cell surface antibodies ( ICSA ), and glucose tolerance after mumps infection, we carried out a screening program for diabetes. A diabetic survey was conducted among 1581 children (less than 16 yr of age) with mumps infection 14 mo before the survey, using a brief questionnaire combined with urinary glucose analysis. Responses to the screening program were obtained from 68.4% (N = 1080) of the children. Out of a total of 1080 subjects, 1069 (99%) had no diabetes mellitus, diabetic symptoms, or glucosuria. A "positive urine glucose screen" was obtained in 11 subjects (1%) of the study group. These individuals all had a normal oral glucose tolerance test according to the new WHO definition. A group of 86 children was randomly selected from the total group of 1080 children for follow-up glucose tolerance, ICA, and ICSA . Irrespective of the negative urine glucose screen impaired glucose tolerance was diagnosed in 3.5% (N = 3) of the 86 children. The prevalence of ICA and ICSA was 78% and 36%, respectively. The simultaneous prevalence of ICA and ICSA was 33%. The pathogenetic role of mumps infection and ICA/ ICSA and their possible relationship to slow progressive beta cell destruction remain to be elucidated.

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The purpose of the present cross-sectional clinical study was to evaluate the prevalence of retinopathy in Type 1 diabetic patients without nephropathy and with different degrees of nephropathy. In addition we investigated the association between retinopathy, nephropathy, and other variables, and studied the importance of cardiovascular autonomic dysfunction to these conditions. 76 Type 1 diabetic patients were investigated. All patients were initially selected on the basis of body weight, and 47 proteinuric patients were further selected for age, diabetes duration and the duration of insulin treatment (see Table 1). Proteinuric diabetic patients were categorized by degree of nephropathy, i.e. for incipient nephropathy (proteinuria of less than 0.5 g/day), for overt nephropathy (proteinuria of more than 0.5 g/day), and for renal failure (serum creatinine of more than 103 mumol/l). Retinopathy was assessed by ophthalmoscopy. Cardiovascular autonomic dysfunction (CAD) was assessed by heart rate variations, 30:15 ratios, the Valsalva maneuver, and systolic blood pressure fall upon standing. Our findings revealed increased prevalence of retinopathy in patients with more advanced stages of nephropathy. CAD abnormalities exhibited increased prevalence among proteinuric patients. Our data clearly revealed differences between proteinuric and non-proteinuric patients. In both proteinuric and non-proteinuric patients there were found correlations of retinopathy with diabetes duration, and only in proteinurics was retinopathy correlated with kidney function, systolic blood pressure and CAD findings. In patients in identical stages of nephropathy, increased prevalence of CAD abnormalities was shown in patients suffering from proliferative retinopathy. Thus our data suggest that CAD abnormalities might be related in some way to both the proliferative retinopathy and to diabetic nephropathy.

Islet cell cytoplasmic antibodies (ICA), islet cell surface ( ICSA ) antibodies, HLA phenotypes, glucose tolerance, insulin secretion, and insulin sensitivity were studied in 16 twins of insulin-dependent diabetics as well as in 21 subjects with impaired glucose tolerance (IGT). 60% of the identical twins and 40% of the non-identical twins were ICSA -positive. The prevalence of ICSA in control persons was only 5%. ICA were found in all identical twins and in half of the non-identical twins. However, ICSA and ICA results were concordant in only 46% of the whole group of twins. There was no correlation between ICSA and either insulin secretion or insulin sensitivity. In the IGT subjects exhibiting low and normal insulin responses ICSA were observed in 67% and 23%, respectively. A high proportion of twins, but not of IGT subjects, had HLA DR3 or DR4 antigens which seem to confer genetic susceptibility to the development of IDDM. In the majority of DR3/DR4 twins, ICSA were also present. This might support the hypothesis of genetically-based autoimmunity, although the precise relationship between HLA and islet cell antibodies has to be clarified in a prospective study.

Since mumps virus seems to be one of the most likely candidates in viral etiology of insulin-dependent diabetes (IDDM) we studied the possible relationship of glucose tolerance (75 g oGTT), beta cell function, diabetes associated HLA antigens, haptoglobin phenotype, islet cell antibodies (ICA) and islet cell surface antibodies (ICSA) in 125 subjects with antecedent mumps infection. Impaired glucose tolerance (IGT) was diagnosed in 3.2% (n = 4) but onset of diabetes did not appear within 14 months after mumps infection. There was no relationship between glucose tolerance and complications of antecedent mumps infection (e.g. pancreatitis, meningitis, orchitis). The prevalence rate of ICA was 76%. ICSA were detectable in about 36% of children and 62% of the adults tested (p less than 0.01). There was no relationship between ICA/ICSA and diabetes-associated HLA antigens, haptoglobin phenotype or beta cell function (fasting C-peptide and insulin response to 75 g oGTT). However, adults with circulating ICA were characterized by a significantly lower insulin response to glucose. Fifty two "risk" subjects characterized by IGT, diabetes associated HLA antigen(s), ICA or ICSA either alone or combined were studied again 26 months after mumps infection. No symptomatic diabetes appeared and IGT was diagnosed in one case only. ICA and ICSA persisted in more than 50% of subjects in whom ICA or ICSA were present 14 months after mumps infection. Since the used immunological techniques do not clearly distinguish organ-specific from non-organ-specific antibodies the results must be interpreted with caution. To summarize, the preliminary results do not support a close temporal relationship between mumps infection and the onset of IDDM. The pathogenetic role of mumps virus and ICA/ICSA and their possible relation to a slow progressive beta cell destruction has still to be determined.