Soros Arlette, Zadik Zvi, Chalew Stuart
Pediatric Endocrinology, Department of Pediatrics, Louisiana State University Health Sciences Center and the Children's Hospital of New Orleans, New Orleans, LA 70118, United States.
Med Hypotheses. 2008 Sep;71(3):394-8. doi: 10.1016/j.mehy.2008.04.020. Epub 2008 Jun 10.
The recent unprecedented increase of childhood obesity has led to an alarming rise in type 2 diabetes mellitus (T2D) among these children. The process underlying the progression from simple obesity to T2D is not well understood. Cortisol is a candidate factor in the pathogenesis of T2D, as it can exacerbate insulin resistance and provoke other disturbances of the metabolic syndrome. The 24-h integrated concentration (IC) of cortisol is suppressed in non-diabetic obese children compared to lean children. This difference in IC-cortisol is not due to changes in cortisol binding globulin or plasma cortisol to cortisone ratio between groups. In obese individuals, IC-cortisol suppression disappears with age after adolescence, which corresponds with increasing occurrence of T2D and other metabolic disorders of obesity. We consider the IC-cortisol levels of lean insulin sensitive children to be metabolically inappropriate for obese insulin resistant children. Thus, we hypothesize that suppression of IC-cortisol is an important adaptive response to obesity (cortisol adaptive suppression) in childhood that prevents pediatric T2D while failure to suppress IC-cortisol (cortisol suppression failure) exacerbates insulin resistance and contributes to the development of T2D. In further support of this hypothesis is early pilot data suggesting that cortisol suppression failure occurs in obese children with impaired fasting glucose levels. The mechanism(s) underlying cortisol adaptive suppression, how and why these mechanism(s) fail are unknown. Elucidation of these mechanisms may lead to interventions to prevent the development of T2D and its complications in obese individuals.
近期儿童肥胖率前所未有的上升导致这些儿童中2型糖尿病（T2D）的发病率惊人地增加。从单纯肥胖发展到T2D的潜在过程尚未完全了解。皮质醇是T2D发病机制中的一个候选因素，因为它会加剧胰岛素抵抗并引发代谢综合征的其他紊乱。与瘦儿童相比，非糖尿病肥胖儿童的24小时皮质醇综合浓度（IC）受到抑制。IC-皮质醇的这种差异并非由于各组之间皮质醇结合球蛋白或血浆皮质醇与可的松比值的变化。在肥胖个体中，青春期后IC-皮质醇抑制随着年龄的增长而消失，这与T2D和其他肥胖代谢紊乱的发生率增加相对应。我们认为，瘦的胰岛素敏感儿童的IC-皮质醇水平对于肥胖的胰岛素抵抗儿童来说在代谢上是不适当的。因此，我们假设IC-皮质醇的抑制是儿童期对肥胖的一种重要适应性反应（皮质醇适应性抑制），可预防儿童T2D，而未能抑制IC-皮质醇（皮质醇抑制失败）会加剧胰岛素抵抗并促进T2D的发展。早期的初步数据进一步支持了这一假设，表明空腹血糖水平受损的肥胖儿童存在皮质醇抑制失败的情况。皮质醇适应性抑制的潜在机制、这些机制如何以及为何失败尚不清楚。阐明这些机制可能会带来预防肥胖个体中T2D及其并发症发展的干预措施。
