Lower estimated insulin sensitivity was associated with risk for hyperfiltration over time, whereas increased albumin excretion was associated with hyperglycemia in youth-onset T2DM.

Adrenal secretory rates of cortisol and arterial concentrations of adrenocorticotropin (ACTH) were measured in conscious trained dogs subjected to intravenous infusion of ACTH. To investigate the causal relation of ACTH to the secretion of cortisol, a mechanistic mathematical model based on current hypotheses of adrenocortical function was constructed and tested. It is widely believed that ACTH stimulates cortisol secretion through adenosine 3',5'-cyclic monophosphate (cAMP), which provides substrate cholesterol by activating cholesterol ester hydrolase and facilitating transport of cholesterol to the side-chain cleavage enzyme. In addition, cholesterol modulates its own synthesis by inhibiting beta-hydroxy-beta-methylglutaryl (HMG)-CoA reductase in the adrenocortical cell. These and other steps in the biosynthetic reaction sequence were described using differential equations subject to the additional constraints imposed by available measurements of intracellular quantities. The resulting model is consistent with many of the known characteristics of the canine adrenal response to ACTH. In this model, steady-state nonlinearities arise from cooperative binding of cAMP to its receptor protein and saturation of mitochondrial pregnenolone transport. The transient response is dominated by a depletable pool of intracellular free cholesterol. Other inferences based on the model are presented, and a quantifiable cellular basis for increased adrenal sensitivity to ACTH is proposed.

Adrenal secretory rates of cortisol and corticosterone and arterial concentrations of ACTH and cortisol were measured in conscious trained dogs subjected to 10 ml/(kg . 3 min) or 20 ml/(kg . 3 min) hemorrhage. All four variables increased substantially after 20 ml/(kg . 3 min) hemorrhage. Secretion rates of cortisol and corticosterone increased significantly after 10 ml/(kg . 3 min) hemorrhage, without a change in ACTH. The responses of ACTH and the secretion rates of cortisol to 10 ml/(kg . 3 min) hemorrhage and iv infusion of ACTH were compared. Infusions of ACTH required to match the secretory response of cortisol after 10 ml/(kg . 3 min) hemorrhage resulted in concentrations of ACTH significantly higher than those observed after 10 ml/(kg . 3 min) hemorrhage. These results suggest that 10 ml/(kg . 3 min) hemorrhage induces an acute increase in adrenocortical sensitivity to ACTH.