College Answer

a) Define S.I.H
Transient hyperglycaemia during acute illness –usually restricted to patients without prior evidence of diabetes with reversion to normal after discharge.

b) Outline the mechanisms thought important in the pathogenesis of S.I.H.

•    S.I.H is thought to develop due to complex interplay between counter regulatory hormones such as catecholamines, GH, cortisol and cytokines.
•    The   underlying   illness   and   treatments   (TPN,   enteral   feed,   steroids,   and vasopressors) might affect the scale of these derangements.
•    The   key   contributor   would   appear   to   be   high   hepatic   glucose   output   via gluconeogenesis  driven by glucagon,  adrenaline  and cortisol.  Cytokines  such as TNFα interact to enhance this response.
•    Insulin resistance plays a role.
•    Underlying abnormalities in glucose regulation may be present.

c) Outline clinical implications and treatment of S.I.H.

•    Recent  data  suggests  that  S.I.H  and  diabetic  hyperglycaemia  are  two  different phenomena with differing clinical outcomes.
•    Patients with S.I.H have been shown in several studies to have increased risk of mortality, adverse events, and greater organ failure scores compared to those with diabetes.
•    Whether S.I.H per se causes harm or instead is a marker of severity of counter regulatory response and degree of illness is unknown.
•    Management  of S.I.H cannot be distinguished  from hyperglycaemia  due to other causes.  In  most  cases  it  is  not  generally  predictable  or  preventable.   Early recognition and interception might prevent persistence and exacerbation. Recommendations include insulin therapy with more conservative glucose targets.
•    Candidates mentioning recent data from RCTs were given credit.

Discussion

Stress-induced hyperglycaemia is discussed elsewhere. In brief, one would define it as hyperglycaemis which occurs in the presence of severe illness and in the absence of pre-existing diabetes. Marik & Bellomo have a nice review of this from 2013.

One could summarise the mechanisms as follows:

• Increased glucose synthesis is due to the following mechanisms:
  • Increased lipolysis due to catecholamine activity
  • Increased gluconeogenesis due to catecholamine activity
  • Increased glycogenolysis due to catecholamine activity
• Increased insulin resistance is due to the decreased sensitivity of skeletal muscle to insulin, via the effects of the following hormones:
  • Catecholamines
  • Growth hormone
  • Cortisol
  • TNF-α
• Additional effects are the direct inhibition of insulin release by adrenaline, and the activation of hepatic glycolysis by glucagon.

Clinical implications of stress-induced hyperglycaemia and its treatment are detailed in the chapter on glycaemic conrol in critical illness.

The key points can be summarised as a list:

• Increased mortality
• Pro-inflammatory effects
• Increased susceptibility to infection

The college points out that association with mortality is not evidence of causation. Glucose may just be another acute phase reactant.

And as for management? In short, keep the BSL between 5 and 8. Finfer et al have demonstrated (NICE-SUGAR) that tight glycaemic control hurts more people than it helps.