Inpatient Diabetes Control
Approaches to treatment
- APP, acute-phase protein
- CRP, C-reactive protein
- DIGAMI, Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction
- FFA, free fatty acid
- HGP, hepatic glucose production
- ICU, intensive care unit
- IL, interleukin
- IRS, insulin receptor substrate
- LOS, length of stay
- NF-κB, nuclear factor-κB
- PAI-1, plasminogen activator inhibitor-1
- PI3K, phosphatidylinositol-3-hydroxy kinase
- TNF, tumor necrosis factor
- VSMC, vascular smooth muscle cell
This is the second of two articles on the Consensus Development Conference on Inpatient Diabetes Control, which was sponsored by the American College of Endocrinology and held in Washington, DC, 14–15 December 2003.
Mechanisms of adverse effect of hyperglycemia
Derek LeRoith (Bethesda, MD) and Irl Hirsch (Seattle, WA) discussed mechanisms by which metabolic control may improve outcomes. Both speakers reviewed physiological and cellular aspects of normal insulin action and glucose homeostasis and molecular aspects of insulin resistance in relation to situations of stress. Insulin has classic actions such as increased glucose uptake, decreased hepatic glucose production (HGP), and antilipolytic effects in skeletal muscle, liver, and adipose tissue, as well as nonclassical vasodilatory effects, proliferative actions on vascular smooth muscle cells (VSMCs), effects on the brain (perhaps related to learning and memory), β-cell actions, and general effects increasing growth and differentiation and decreasing apoptosis. Insulin levels range from <10 to 30–50 μU/ml in the fasting versus fed state. The liver is exposed to portal vein insulin levels triple that in the periphery, with HGP inhibited at levels of 20–25 μU/ml. Lipolysis increases during fasting and is inhibited at levels of 30–50 μU/ml, so that in the fasting state, free fatty acids (FFAs) are available for fuel. A doubling of insulin levels inhibits HGP by 80% and increases glucose utilization by 20%.
The insulin-signaling pathway involves stimulation of cascades of intracellular kinases leading to insulin action. The insulin receptor substrates (IRSs) have metabolic as well as antiapoptotic effects, particularly due to IRS-1 phosphorylation via the phosphatidylinositol-3-hydroxy kinase (PI3K) pathway after activation of the insulin receptor—a process inhibited in situations of insulin resistance. The mitogen-activated protein kinase pathway is involved in gene expression, cell proliferation, and a variety of other anabolic actions. When insulin stimulates glucose uptake, particularly occurring in muscle, which mediates ∼80% of insulin-stimulated glucose uptake, PI3K …
