HYPERGLYCEMIA : WHY ARE WE WORRIED ?

Hyperglycemia - why are you worried?
•    1. Hyperglycemia causes dehydration due to osmotic diuretic effect of glycosuria.
•    2. It leads to acidemia because of accumulation of ketoacids and lactic acids.
•    3. Glycosuria begins at the blood glucose of 180mg/dl causing fluid shifts, dehydration and electrolyte abnormalities.
•    4. Electrolyte imbalance mainly potassium and magnesium imbalance which may cause arrhythmias.
•    5. It blunts the protective action of insulin against ischaemic reperfusion injury.
•    6. Hyperglycemia and Brain-

During normal aerobic metabolism,glucose is converted to pyruvate which then enters the Kreb’s cycle as a source of energy(ATP).When the supply of oxygen is limited,pyruvate is reduced to lactate. Increased lactate and low pH damage brain cells.

The mechanisms for increased ischaemic damage to brain in presence of hyperglycemia are (1) anaerobic metabolism in which glucose is converted to lactate rather than pyruvate.(2) increased levels of glucose, available for lactate production that leads to neuronal damage due to lactate accumulation.

Hyperglycemia also adversely affects the ischemic brain by disrupting the blood-brain barrier and promoting cerebral edema. Also, hyperglycemia-induced brain injury resulted in increased free radical formation. In turn, the increased amount of free ras idical formation increased blood-brain barrier permeability and brain edema.
•    7. Hyperglycemia triggers inflammatory responses via increased mitochondrial superoxide production and endoplasmic reticulum stress. This  inflammation leads to insulin resistance and b-cell dysfunction which further aggravates hyperglycemia. Inflammation and activation of proinflammatory cytokines is also induced by hyperglycemia such as tumor necrosis factor- interleukin 1, and interleukin 6.
•    8. The molecular pathways that integrate hyperglycemia, oxidative stress, and diabetic vascular complications are described in the pathogenesis of endothelial dysfunction and endothelial dysfunction represents the first step of atherogenesis.
•    9. Acute hyperglycemia rapidly attenuates endothelium-dependent vasodilation and reduces myocardial perfusion.
•    10. Thus, direct effects of glucotoxicity, oxidative stress, and low grade inflammation act in a vicious circle that impairs insulin sensitivity, accelerates and escalates loss of b-cells, impairs endothelial function, and leads to microvascular and macrovascular disease.
•    11. Hyperglycemia hinders immune function leading to increased risk of infection. The risk of infection is increased because of abnormalities of monocyte and polymorphonuclear function, decreased intracellular bactericidal activity, glycosylation of immunoglobulins.
•    12. It promotes prothrombotic state due to increased platelet aggregation and adhesiveness in the setting of endothelial dysfunction and impairs wound healing. Blood coagulation is activated by hyperglycemia as circulating prothrombin fragments and D-dimers are increased and platelet aggregation and thrombosis occur.
- Perioperative hyperglycemia increases risk of perioperative mortality,cardiovascular,respiratory ,neurologic and infectious morbidity.

-Surgical patients develop hyperglycemia due to hypermetabolic stress response which increases glucose production and causes insulin resistance.

-Hyperglycemia is an independent risk factor for mortality in diabetic and non-diabetics.
 

- by Dr Amarja