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94 Stress Hyperglycemia or Diabetes - Which is bad in ICU?

pathways are under the direct control of insulin and Management of stress induced
glucagon. Insulin is primarily secreted after meals or hyperglycemia
when blood glucose levels rise, it is also secreted at
basal levels in between meal times. Glucagon se- New data suggests that new onset stress hypergly-
cretion happens mostly in between meals or when cemia in hospital may be more dangerous than hy-
blood glucose levels get too low to maintain glycog- perglycemia in a patient with pre-existing diabetes(1,
enolysis and gluconeogenesis. Both these hormones 4). The treatment of stress hyperglycemia depends
maintain blood glucose levels within a close normal on the primary condition being treated, need for in-
range. After a meal, glucose enters the liver and the creased substrate or in conditions where there is no
muscle, adipose tissue and other tissues take the increase in calorie need. In patients with severe hy-
rest. Glucose utilizes a carrier mediated transport sys- povolemic or hypotensive states such as severe cere-
tem entry to cells and the most important isoform is brovascular or low cardiac output states maintenance
GLUT4, which is predominantly present in skeletal, of glucose levels at a higher level may be needed. In
cardiac muscle and adipocytes. Under physiological conditions such as burns or severe trauma increas-
conditions, when blood glucose rises after a meal, ing glucose turnover by infusing glucose and insulin
insulin is secreted from the beta-cells initiates a mul- may improve glucose utilization by glucose sensitive
titude of signaling pathways leading to recruitment tissues.
of GLUT4 to translocate to the cell membrane. This The number of patients admitted to hospital with hy-
leads to uptake of glucose leading to maintenance perglycemia is increasing. There is a large group of
of normal blood glucose. patients with high glucose levels ,during hospitaliza-
tion due to disease related stress and reverts to nor-
Stress and Metabolism mal glucose tolerance post-discharge. There is evolv-

The main role of metabolic response to stress is to ing evidence that poorly controlled glucose levels are
maintain influx of substrates to vital tissues. Brain associated with increased hospital related mortality,
is the major user of glucose in the fasting state and increased length of stay and excessive health care
is independent of insulin. Hence maintenance of costs. Data from one particular study showed that
glucose delivery to central nervous system is de- patients with new onset hyperglycemia had an 18
pendent on plasma glucose concentration and ce- fold increased in-hospital mortality, 2.7 fold risk in
rebral blood flow. In situations of prolonged fasting patients with pre-existing diabetes when compared
with normal blood flow, the central nervous system with normo-glycemic patients(1). There are guidelines
is programmed to utilize ketone bodies from the liver suggesting that hyperglycemia is very common prob-
and reduce up to 50 % of the obligatory carbohydrate lem in an inpatient setting and early identification
need .Tissue damage contributes to hyperglycemia and aggressive management approach is needed to
in a variety of ways. The important contributor is the improve patient outcomes.
release of stress hormones such as adrenaline, nor- The initial data originated from the DIGAMI trial where
adrenaline, cortisol, growth hormone, interleukin-1 insulin-glucose infusion was used to treat hypergly-
and tumor necrosis factor-alpha. Sepsis and other cemia in acute ST-segment elevation myocardial in-
factors also aggravate pre-existing insulin resistance, farction. This showed a significant reduction of mor-
which worsens hyperglycemia. It is also postulated tality of 27 % at the end of the first year. Unfortu-
that stress hyperglycemia is regulated by central nately DIGAMI 2 couldn’t replicate the previous study
mechanisms. Afferent inputs to the central nervous results, which was disappointing. The early evidence
system can signal the need for increased carbo- in critical care originated from the study done by Van
hydrate flux to the brain. These afferent inputs are den Berghe et al in post-operative patients. Intensive
from chemoreceptors in the carotid bodies, pressure post-operative insulin therapy in surgical ICU setting
sensors in the carotid sinus & aortic arch, tempera- reduced mortality and morbidity(5, 6). This same
ture receptors and glucose receptors in the liver and study group failed to replicate reduction in mortality
the brain. These signals are integrated in the high- by insulin infusion in a medical ITU setting. A large
er centers including the hypothalamus, which then multicenter, international trial was designed to con-
integrates the efferent responses leading to stress firm these findings. In NICE-SUGAR trial (The Normo-
hyperglycemia. Upto 25 % of patients with an acute glycemia in Intensive Care Evaluation – Survival using
MI or stroke when being admitted to hospital fulfill Glucose Algorithm Regulation), over 6000 patients
the criteria for diabetes (2, 3). were randomized to receive either strict glycemic
control (glucose target 81-108 mg/dl) or conventional
treatment (glucose target < 180 mmol/l) comparing

GCDC 2017