Research Highlights
During the past decade, type II diabetes mellitus has increased dramatically in American teenagers, with a prevalence rate now approaching 1:1000. The disease in adolescents affects all ethnic groups and now accounts for about 20% of newly diagnosed diabetes in teenagers. The accelerated prevalence parallels the epidemic of childhood obesity and may be the most significant consequence of increased adiposity in young people. Because type II diabetes mellitus results in striking increases in morbidity and mortality, the recent epidemic of the disease in adolescents constitutes a major public health problem.
While dysfunction of the pancreatic beta cell and insulin resistance are critical factors in the development of type II diabetes in adults, relatively little is known about the pathophysiology of the disease in adolescents and young adults. Consequently, it is unclear whether the disease in adolescents represents a distinct form of diabetes or is simply an early manifestation of the condition seen in adults. Recently, Dr. Deborah Elder, in collaborations with Dr. Larry Dolan and Dr. David D'Allesio (Division of Endocrinology, Department of Medicine, University of Cincinnati), studied glucose, insulin and glucagons dynamics in a cohort adolescent patients with type II diabetes and non-diabetic lean and obese controls. The major diabetes patients were severely insulin resistant compared to the lean and obese controls and had impaired insulin secretion relative to the degree of insulin resistance. However, in contrast to adult subjects with type II diabetes, the adolescent diabetic subjects had a first phase insulin response to intravenous glucose comparable to lean controls, and did not have hyperproinsulinemia (the precursor form of insulin) or hyperglucagonemia (another measure of beta cell function). This islet phenotype is in marked contrast to the classical findings in adults with T2DM, in whom first phase insulin secretion is very low; the proinsulin/insulin ratio is markedly elevated and glucagon secretion is excessive. These results therefore suggest that the pathophysiology of type II diabetes in youth is different than that in adults. The findings also suggest that the optimal therapy for the disease in adolescent patients may be distinct from that for adult patients.
Drs. You-Hong Cheng and Stuart Handwerger continued their investigations of the regulation of human placental development. They cloned and partially characterized the promoter for a newly-described gene called syncytin that codes for a glycoprotein that is critical early in placental differentiation when mononuclear cytotrophoblast cells fuse to form syncytiotrophoblast cells. In recently completed investigations, they identified a region of the promoter that is essential for placenta-specific expression of the syncytin gene and showed that the activity of the region requires intact binding sites for GATA-2, GATA-3 and Sp1 transcription factors. These studies are of clinical importance since markedly decreased syncytin expression has been observed in placentas from women with pre-eclampsia, a common pathologic condition of pregnancy that is associated with a marked increase in fetal and neonatal morbidity and mortality. An understanding of the regulation of key genes involved in placental development may lead to new therapies for pre-eclampsia and other diseases associated with abnormalities in placental development and function.
