Islet cell antibodies (ICA), complement fixing islet cell antibodies, immune complexes and thyro-gastric autoantibodies were studied in newly diagnosed diabetic patients not requiring insulin at diagnosis. Particular attention was focussed on that minority of patients who are initially treated with diet or oral agents but show ICA in their serum. One hundred and six non-insulin-requiring patients were studied at clinical diagnosis. Seventeen who had ICA in their serum were compared with a control group of 89 who did not. The 17 ICA-positive diabetic patients were followed serologically for approximately 1 year from diagnosis. Patients were followed clinically for 3 years. Forty-seven percent of ICA-positive and 19% of ICA-negative patients had immune complexes in their serum. Eleven of the 17 ICA-positive patients also had serum complement fixing islet cell antibodies. Thyro-gastric antibodies were found in 29% of ICA-positive and 18% of ICA-negative diabetic patients. ICA, complement fixing antibody and immune complex positivity declined with time. Ten of the 7 ICA-positive and two of the 89 ICA-negative patients required insulin within 3 years of diagnosis. There was a positive trend for the presence of complement fixing islet cell antibodies at diagnosis to be associated with the early development of insulin dependency. The type of diabetes in ICA-positive patients not requiring insulin at diagnosis has strong immunological and clinical similarities to classical Type 1 (insulin-dependent) diabetes.

Abstract. An investigation on circulating immune complexes (AgAb) was carried out in 80 diabetics with severe microangiopathy and in 71 diabetics without microvascular lesions. The duration of the disease, the type of diabetes, the type of treatment and the main localization of microangiopathy (retinopathy and nephropathy) were taken into account. AgAb were detected by two different methods: the solid phase Clq binding test (ClqSP) and the conglutinin binding test (KgBt). AgAb detected by ClqSP were increased both in prevalence and quantities in diabetics with severe microangiopathy regardless of the duration of the disease and the type of diabetes. Long standing diabetics without microangiopathy had similar prevalence of AgAb as normal controls. The presence of AgAb was not in correlation with the type of treatment and was similar in diabetics with retinopathy and in those with nephropathy. When AgAb were detected by KgBt, they were found with higher prevalence in diabetics than in normal controls but no correlation with microangiopathy was observed. AgAb, detected by KgBt, were higher in long standing type I diabetics. Since the two methods detect different AgAb it is concluded that AgAb present in diabetics seem to be heterogenous and part of them are related to the presence of microangiopathy.

An increase in circulating immune complexes (AgAb) of medium size has been observed in diabetics with late complications. This increase may be related either to an increased formation or reduced clearance. Alternatively, both mechanisms may be involved. As medium-sized AgAb determined by the C1q solid phase method are mainly removed from circulation by the fixed phagocytes of the reticulo-endothelial system, we investigated the function of these cells using a colloid clearance test in diabetics with various degrees of microangiopathy. Microaggregated iodinated human serum albumin was injected into 30 diabetic volunteers with severe (group 1), moderate (group 2), and absent (group 3) microangiopathy, and into 40 normal volunteers. The colloid clearance was significantly reduced in diabetics with severe microangiopathy in comparison with patients who had no sign of microangiopathy, or with normal subjects. A significant correlation was found between reduced colloid clearance and increased levels of circulating AgAb determined by C1q solid phase method. Results of this study suggest that the increase in circulating AgAb observed in patients with severe microangiopathy may result from an impaired function of mixed phagocytes.

In 41 Type 1 (insulin-dependent) diabetic patients, islet cell antibodies, anti-insulin antibodies, and immune complexes measured by two different methods (the C1q solid phase assay and the conglutinin binding test) were studied at diagnosis, and the influence of treatment with insulins of different purity was investigated during the first year of treatment. Twenty subjects were treated with conventional insulins (group 1) while 21 were treated with monocomponent porcine insulins (group 2). The prevalence of islet cell antibodies significantly decreased during the 12-month study period in the 41 patients. From the first month anti-insulin antibodies were always significantly higher in group 1 than in group 2. At diagnosis the prevalence of both types of immune complexes in the 41 patients was higher than in normal subjects. The immune complexes measured by the C1q solid phase method showed a significant and progressive reduction during the follow-up period, whereas the immune complexes assayed by conglutinin showed no significant variation in the same period. The presence of C1q immune complexes was found to correlate with the occurrence of islet cell antibodies both at diagnosis and during the follow-up period. The presence of conglutinin immune complexes, on the other hand, tended to parallel the increase of anti-insulin antibody levels.