The aim of this study was to stratify risk for postpartum diabetes in women who have gestational diabetes. Women with gestational diabetes were recruited between 1989 and 1999, and 302 were followed with oral glucose tolerance tests at 9 months and 2, 5, 8, and 11 years postpregnancy. The 8-year postpartum diabetes risk was 52.7% (130 diabetic cases). Risk was increased in women with autoantibodies to GAD and/or insulinoma antigen-2 (adjusted hazard ratio 4.1; P < 0.0001), women who required insulin during pregnancy (4.7; P < 0.0001), women with BMI >30 kg/m 2 (1.5; P ‫؍‬ 0.04), and women with more than two prior pregnancies (2.5; P ‫؍‬ 0.02). Women without these risk factors had a postpartum diabetes risk of 14% by 8 years, and risk rose incrementally to 96% by 8 years in autoantibody-positive women. Parity status, C-reactive protein concentration, a diabetes family history, maternal age, weeks of gestation, and the child's birth weight did not significantly affect risk in multivariate analysis. Prospective diabetes assessment is indicated and intervention should be considered in women with gestational diabetes who are autoantibody positive, require insulin treatment during pregnancy, or are obese. Diabetes 55:792-797, 2006 G estational diabetes mellitus (GDM) complicates ϳ4% of pregnancies and is defined as glucose intolerance with onset or first diagnosis during pregnancy (1). GDM substantially increases the risk to develop postpartum diabetes and thus identifies a high-risk population for the development of both type 1 and type 2 diabetes. Risk estimates of type 2 diabetes after GDM vary from 17 to 63% within 5-16 years after pregnancy, depending upon the ethnic background of the study population and the detection method for GDM and glucose intolerance (2-4). Like type 2 diabetes, the incidence of postpartum diabetes appears to be increasing (5). Reported risk factors for postpartum diabetes include the detection of islet autoantibodies (6,7), insulin treatment during pregnancy, BMI, and age at delivery (3).The German GDM study has prospectively followed patients with GDM for up to 11 years for the purpose of estimating diabetes risk and identifying factors that modify risk. Here we report diabetes risk with respect to anthropometric markers such as BMI, insulin requirement during pregnancy, family history of diabetes, the number of previous pregnancies, age at delivery, duration of gestation, or birth weight of child and serological markers such as the presence of islet autoantibodies and serum concentrations of C-reactive protein (CRP) in this cohort. RESEARCH DESIGN AND METHODSThe German GDM prospective study follows women with GDM from delivery (6,8). Between 1989 and 1999, 302 patients with GDM were recruited from hospitals in Germany and participated in at least one follow-up contact after delivery. GDM was diagnosed following the criteria of the German Diabetes Association using an oral glucose tolerance test (OGTT) with 75-g glucose load. Women were considered to have GDM if two of three capillary bl...

Successful islet transplantation is dependent on the quality and quantity of islets infused. Islets are purified on density gradients, but procedures currently used have limited capacity for pancreatic digests, islet yield, and viability. We aimed to improve islet purification with a modified gradient medium. Biocoll was diluted in University of Wisconsin solution to create linear density gradients of 1.065 to 1.095 g/mL. Properties of islets purified from 22 human pancreas digests with modified medium were compared with 15 preparations using standard medium. The modification increased the capacity of gradients for pancreatic digests from 20 to 60 mL, islet yield increased from 218,000 to 435,318 per isolation, and viability increased from 65.4% to 92.1%. Islet fractions contained greater than 95% of recovered insulin. Islets showed good physiologic responses to secretagogues and restored normoglycemia in streptozotocin-induced diabetic severe combined immunodeficiency disease mice. The new medium enhances yield, purity, and viability of human islet preparations for clinical islet transplantation.

1IA-2 and phogrin are tyrosine phosphatase-like proteins that may mediate interactions between secretory granules and cytoskeleton in islets and neuroendocrine tissues. We investigated factors that regulate IA-2 and phogrin expression and their relationship to maturation of insulin secretory responses that occur after birth. Islet content of IA-2, but not phogrin, increased during the first 10 days of life in rats, when insulin secretion in response to glucose increased to adult levels. In cultured 5-day-old rat islets, IA-2 protein and mRNA was increased by glucose and agents that potentiate insulin secretion by the cAMP pathway. Addition of insulin increased IA-2 protein levels and insulin biosynthesis without affecting IA-2 mRNA. Blocking insulin secretion with diazoxide or insulin action with insulin receptor antibodies inhibited glucose-induced increases in IA-2 protein, but not those of mRNA. Phogrin expression was unchanged by all agents. Thus, IA-2 is regulated at the mRNA level by glucose and elevated cAMP, whereas locally secreted insulin modulates IA-2 protein levels by stimulating biosynthesis. In contrast, phogrin expression is insensitive to factors that modify ␤-cell function. These results demonstrate differential regulation of two closely related secretory granule components and identify IA-2 as a granule membrane protein subject to autocrine regulation by insulin. Diabetes 51:2982-2988, 2002

A tyrosine phosphatase-like protein, IA-2, is a major autoantigen in Type 1 diabetes but its role in islet function is unclear. Tyrosine phosphorylation mediates regulation of cellular processes such as exocytosis, cell growth, and cell differentiation. To investigate the potential involvement of IA-2 in islet differentiation and insulin secretion, we analyzed by immunohistochemistry expression of IA-2 during islet development in fetal rats and during the maturation of insulin secretory responses after birth. In the fetus, IA-2 immunoreactivity was detected in primitive islets positive for insulin and glucagon at 12 days' gestation. Subsequently, IA-2 was only weakly detectable in the fetal pancreas. In neonatal rat, a progressive increase in IA-2 immunoreactivity was observed in islets from very low levels at 1 day of age to moderate labeling at 10 days. In the adult, relatively high levels of IA-2 were detected in islets, with heterogeneous expression in individual cells within each islet. IA-2 marks a population of endocrine cells that transiently appear early in pancreatic ontogeny. Islet IA-2 expression reappears after birth concomitant with the development of mature insulin secretory responses, consistent with a role for this protein in regulated hormone secretion.