Data & Rationale

A Review of the Basic Science: Understanding the Mechanisms of Hyperglycemia for the Inpatient with Diabetes

In this section you will find:

• Slide presentation - describing the basic science rationale for the beneficial effects of glucose control and use of insulin, including the interactions between insulin, the nuclear transcription factor NF-κB, the various cytokines, adhesion molecules, nitric oxide, and acute phase proteins.
• Reference list - and suggested key readings
• Selected published literature and abstracts

Key Points:

• Hyperglycemia and insulin regulation play both a direct and indirect role in the cellular mechanisms underlying inflammation and oxidative stress
• Free fatty acids generated by hyperglycemia and insulin deficiency result in endothelial dysfunction and the generation of reactive oxygen species
• Hyperglycemia consistently promotes inflammation
• Role of insulin in mediating inflammation is more complicated
• In some studies, cytokines appear to be generated in the inflammatory process in the presence of insulin - in other studies, cytokines appear to be suppressed by insulin
• Resolution of this apparent conflict:  insulin and glucose co-modulate inflammation 

  • With euglycemia, insulin suppresses inflammatory processes
  • However, in the presence of hyperglycemia, insulin promotes inflammation
• This may explain apparently discrepant results in some clinical trials, especially when hyperglycemia has not been controlled meticulously

Finally:

Glycemic variability is an important concept—relevant to both outpatient and inpatient outcomes.  Glucose fluctuations fuel formation of reactive oxygen species, specifically superoxide, which in turn promotes the four known cellular mechanisms of diabetic vasculopathy. Oxidative stress resulting from glycemic spikes and troughs may create acute vascular flow problems, resulting in poor outcomes for acutely ill patients. While not yet proven, such cellular mechanisms may have important relevance for chronic complications.  In fact, they may be the most important reason to avoid the use of sliding scale insulin therapy for inpatients with hyperglycemia.