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Diabetes mellitus is a frequent transient or rare permanent complication of pregnancy. The role of autoimmune phenomena in this gestational form of diabetes is incompletely understood. We have examined sera from 312 pregnant women who had abnormal glucose tolerance (based on a screening examination during the second trimester) for the presence of islet cell surface antibodies or insulin autoantibodies. Fifty-eight of these women were lost to follow-up. Of the remaining subjects, 144 (57.1%) had gestational diabetes diagnosed by formal glucose tolerance testing and the others (42.9%) were normal. Sixty percent of the women with gestational diabetes eventually required insulin to control their blood glucose during pregnancy. One serum from the non-diabetic women was positive for insulin antibodies (0.9%);8 of the sera from the patients with gestational diabetes were positive (5.6%). Subsequent analysis revealed that all nine of the women whose sera were positive for insulin autoantibodies had been treated with insulin previously. Islet cell surface antibodies were strongly correlated with gestational diabetes. Forty-five of 144 gestational diabetic sera were positive (31.3%) whereas only 9 of 108 suspect control sera (8.3%) and 7 of 60 unknown sera (11.7%) were positive. These data suggest that a high percentage of pregnant women who screen positive for glucose intolerance have serological evidence of an autoimmune response against the pancreatic islets, in spite of the state of relative immune tolerance during pregnancy. These data suggest that autoimmune phenomena may play a role in gestational diabetes and that the presence of islet cell antibodies can predict insulin-requiring gestational diabetes. [ABSTRACT FROM AUTHOR]

Anti-B cell auto-immunity may play a role in the pathogenesis of diabetes in mice resulting from multiple subdiabetogenic doses of the pancreatic B cell toxin, streptozotocin. In the present study we have investigated the cytotoxic anti-B cell response in these mice. A major role for B lymphocytes, macrophages, or their products in the cytotoxic response originally detected in vitro was eliminated by passing splenocytes from the mice treated with multiple subdiabetogenic doses of streptozotocin over a nylon wool column. The removal of the adherent cells enhanced the cytotoxicity against a rat insulinoma cell line in vitro by that expected due to enrichment of T-lymphocytes by approximately twofold. The induction of diabetes after multiple subdiabetogenic doses of streptozotocin is strain dependent. Mice of five strains were immunized with rat insulinoma cells, but only splenocytes from the two strains susceptible to multiple subdiabetogenic doses of streptozotocin demonstrated a significant cytotoxic response against the rat insulinoma cells in vitro. Mice pre-immunized with either the rat insulinoma cells or with syngeneic islets labelled in vitro with the hapten trinitrophenol developed hyperglycaemia more rapidly than control mice after multiple subdiabetogenic doses of streptozotocin. In the latter experiment the control mice immunized with complete Freund's adjuvant alone also became hyperglycaemic after a modified multiple subdiabetogenic dose of streptozotocin that did not cause diabetes in non-immunized mice. In mice pre-treated with either adjuvant or cyclophosphamide and then given a modified multiple subdiabetogenic dose of streptozotocin (35 mg/kg × 5 rather than 40 mg/ kg) the degree of hyperglycaemia was reduced and there was no protective effect of cyclophosphamide. However, the mice pre-treated with adjuvant again developed hyperglycaemia more rapidly and to a much higher level than did the mice given multiple subdiabetogenic doses of streptozotocin only. These additional data further support the hypothesis that B-cell destruction after multiple subdiabetogenic doses of streptozotocin results from triggering of an immune response against these insulin-producing cells. [ABSTRACT FROM AUTHOR]

An increased prevalence of Type 1 (insulin-dependent) diabetes has been reported in patients with congenital rubella. Rubella virus multiplies in the pancreas, and we have hypothesized that studies of children with congenital rubella would be of great importance in following the development of Type 1 diabetes in a defined, susceptible population. Two hundred and forty-one children with congenital rubella (mean age 17.4±0.3 years; 65% black and hispanic) have been evaluated, 30 of whom already have diabetes and 17 of whom have borderline glucose tolerance. In these latter two groups, HLA-DR3 is significantly increased and HLA-DR2 significantly decreased. Pancreatic islet cell cytotoxic surface antibodies are found in 20% of the total congenital rubella population, including in more than 50% in the time period before they develop diabetes and are not related to any specific HLA type. In addition, anti-microsomal and anti-thyroglobulin antibodies are found in 34% of this population. The data demonstrate that Type 1 diabetes developing in congenital rubella patients has the genetic and immunological features of classical Type 1 diabetes, namely the presence of HLA-DR3, the absence of HLA-DR2, islet cell surface antibodies before decompensation and an increased prevalence of anti-thyroid antibodies. Patients with non-diabetic congenital rubella represent an easily identifiable group in whom other immunological factors associated with Type 1 diabetes can be elucidated and possibly modified. [ABSTRACT FROM AUTHOR]

Residual beta cell secretory capacity was assessed in short term (2 months to 2 years) and long term (5 to 8 years) insulin-dependent diabetics by measurement of serum C-peptide immunoreactivity during three provocative tests: glucose, tolbutamide, and glucagon. Minimal C-peptide secretion could be detected in only one out of seven long term diabetics by the stimulatory tests. All seven short-term diabetics responded to at least one provocative test of beta cell reserve, although these responses were blunted. The greatest C-peptide responses occurred after glucagon administration (mean increase 0.62 pmol/ml) in short-term responders. Patients who responded to one test did not necessarily respond to another stimulus. There was no correlation between basal C-peptide levels and the ability to provoke further C-peptide secretion by any of the three tests. C-peptide responses did not correlate with % Haemoglobin A1c, mean fasting blood glucose levels, or mean blood glucose concentrations during an oral glucose tolerance test. The data indicate that stimulation tests are only useful in assessing endogenous beta cell reserve in patients with diabetes of less than 5 years duration. In diabetics of longer duration there is little insulin reserve above basal levels.