role of proinsulin in gestational diabetes mellitus

To look for any increase in proinsulin or proinsulin/insulin ratio in women suffering GDM as an additional factor to their insulin resistance state during pregnancy; and to test for its reversibility in the post partum period. The study was conducted on 30 pregnant age matched women in their second or third trimester and 10 age matched non pregnant normoglycemic women as a reference group. The pregnant women were divided into 3 groups each of ten as follow: normoglycemic women with normal OGTT as a control group, obese women with GDM and lean women with GDM. All women were subjected to full history taking and complete clinical examination. The following parameters were measured: diagnostic OGTT using 100 gm glucose, fasting serum proinsulin, fasting serum insulin, serum C-peptide, proinsulin/insulin ratio and insulin sensitivity. All these tests were repeated 4-8 weeks postpartum. The results of the study revealed that the serum levels of proinsulin and the proinsulin/insulin ratio were significantly higher in obese and lean women with GDM than the control and reference groups during pregnancy and also after delivery. The insulin sensitivity index was significantly lower and the relative resistance for insulin was significantly higher in GDM women compared with normal glucose tolerant pregnant women during pregnancy, while after delivery the sensitivity index was significantly higher than during pregnancy in GDM women as well as pregnant women with normal OGTT. The mean values of C-peptide were significantly higher in GDM patients versus control and reference groups during pregnancy. After delivery these mean values of C-peptide were significantly lower than during pregnancy in the three pregnant studied groups. Women with GOM are characterized by elevated serum proinsulin concentrations and increased proinsulin/insulin ratio which reflect beta-cell decompensation. These precursors molecules might thus serve as a marker for the disease and potentially even identify the subjects of high risk for development of type 2 diabetes. Also, it may be possible to detect such beta-cell stress earlier in pregnancy and to use this phenomena in the assistance of better prediction of GDM

Study of islet cell autoantibodies in serum of siblings of type 1 diabetics

Type 1 diabetes is an autoimmune disease that accounts for approximately 15% of the diabetic population. The pathogenesis of Type 1 diabetes could be divided into six stages. Stage I is genetic susceptibility which requires the presence of a triggering event [stage Il] that initiate the development of autoimmunity [stage Ill] which is characterized by lymphocytic infiltration of the islet cells and production of anti-islet autoantibodies e.g. islet cell cytoplasmic autoantibodies [ICCA], insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], and autoantibodies against irisulinoma-associated-2 autoantigen [IA-2A]. In stage IV, there is progressive loss of insulin secretion despite normal blood glucose level. Stage V develops when overt diabetes is first recognized. In stage VI, there is complete beta cell destruction. Since the clinical onset of Type 1 diabetes does not occur until 80-90% of the insulin-producing pancreatic beta cells have been destroyed, this prediabetic stage may last for a long time during which the immunologic disease markers are present and measurable. The present study aimed to determine the prevalence of the islet cell autoantibodies in siblings of type I diabetics for the presence of islet autoantibodies in an attempt to allow the opportunity for prediction and/or the prevention the clinical onset of the disease. 108 healthy siblings of Type 1 diabetic children [group I] and 100 healthy control subjects [group II] of matched age and sex were enrolled in the present study. IAA, GADA, and IA-2A autoantibodies were assayed in serum of all subjects by radioimmunoassay. Eight of the control subjects had autoantibodies in their sera which were of the IAA type only. In siblings of Type 1 diabetic children, the prevalence of GADA seropositivity showed the highest percentage [25%], followed by IAA [14.81%], then IA-2A [2.78%]. There was significant association between the brotherhood to Type 1 diabetic children and the presence of GADA alone [i.e. no concomitance with any other autoantibody], total GADA [GADA alone and in combination with other autoantibodies], and GADA+IAA [P=0.000, 0.000, and 0.018 respectively]. IAA+GADA+IA-2A or for IAA+lA-2A combinations were not detected in sera of siblings of Type 1 diabetic children. None of the siblings of Type 1 diabetics had lA-2A autoantibodies alone in the serum. From the present results it could be concluded that some degree of islet cell autoimmunity might develop in siblings of type 1 diabetic children as evidenced by the significant association between the presence of GADA or GADA+IAA and the brotherhood to type 1 diabetics. The present results also revealed that GADA is the most frequent autoantibody in serum of siblings of type 1 diabetics. They also showed that the presence of GADA per se conferred the highest significant association with the brotherhood to Type I diabetic children. However, a larger prospective study is recommended to ascertain the importance of the assay of these immunologic markers for the prediction and possible prevention of type 1 diabetes in individuals at risk e.g. sibling, parents, and offspring of Type 1 diabetics