Frequently encountered during hospitalization secondary to increases in circulating stress hormones.

Effects of hyperglycemia are multifactorial, and include activation of the renin-angiotensin-aldosterone system, and pro-inflammatory pathways, increased production of reactive, oxygen species, and activation of their receptors.

Estimated that 1/3 of hospitalized patients will experience significant hyperglycemia and the cost associated with hospitalization for patients with diabetes accounts for half of all health expenditures for this disease.

Uncontrolled hyperglycemia in hospitalized patients associated with adverse outcomes and longer lengths of stay.

Acute hyperglycemia defined as a random blood glucose of 140 mg/dL.

Elevated fasting plasma glucose level is an independent risk factor for adverse cardiovascular outcomes.

Basal insulin secretion is required to maintain fasting plasma glucose levels below 100 mg/dL

Elevated fasting plasma glucose levels indicates an insufficient endogenous insulin secretion to overcome underlying insulin resistance.

Causes symptoms from hyperosmolality of the blood.

Causes glycosuria when the renal capacity for glucose reabsorption is exceeded.

Glycosuria, the excretion of osmotically active glucose molecules permits the loss of large amounts of water, ref2242ed to osmotic diuresis.

With osmotic diuresis dehydration occurs and leads to polydipsia.

With induction osmotic diuresis Na+ and K+ losses are significant.

For every gram of glucose lost via the urine 4.1 kcal is lost from the body, and replacing this lost with oral intake of calories further raises blood sugar and therefore glycosuria, in turn: overall resulting in mobilization of protein and fat stores along with weight loss.

Energy requirements met by catabolism of fat and protein with formation of ketones.

Leads to small amounts of hemoglobin A to nonenzymatically glycated to form HbA1c.

Commonly seen in ICU patients with increase in counter regulated hormones cortisol and glucagon.

In critically ill patients on IV insulin, blood glucose levels should be maintained 140 and 180 mg/dL.

In critical ill patients targets BS of <110 mg/dL is not recommended.

An independent risk factor for mortality and morbidity in patients in intensive care units including medical, surgical, neurological and cardiac facilities.

Studies an association between glucose control and cardiovascular disease.

A 10 year follow-up patients with type two diabetes assigned to intensive glucose control for 5.6 years had 8.6 fewer major cardiovascular events for 1000 person-years than those assigned to standard therapy, and no improvement was seen in the rate of overall survival (VA DT).

A predictor of survival in patients with acute coronary syndromes.

Circumstantial evidence for tight control in the ICU seems compelling and glucose can be seen as a marker of the function of overall metabolism and the anabolic effects of insulin.

Blood glucose concentrations on admission, during a postoperative period, or the mean glucose concentration in the hospitalized patient are directly related to adverse outcomes including prolonged hospital stay, readmission and mortality.

Increased morbidity and mortality for postoperative cardiac and general surgery patients, myocardial infarct, stroke and general medical patients.

An increased fasting plasma glucose level is associated with a relatively higher risk of in-hospital mortality in men but not in women (Yang SW et al).

There is a U. shaped relationship between fasting plasma glucose levels and in-hospital and three-year mortality for acute myocardial infarction (Yang SW et al).

Postprandial glycemia is a risk factor for cardiovascular disease in diabetic and non-diabetic persons.

Stress hyperglycemia refers to elevated blood glucose in the presence of acute illness (Dungan KM et al).

Stress hyperglycemia in critical illness related to release of stress hormones such as cortisol and epinephrine, the use of glucocorticoid and catecholamine medications, and the release of mediators with sepsis or surgery: these factors inhibit release of insulin and inhibit insulin action with enhanced gluconeogenesis, inhibition of glycogen synthesis and impair insulin mediated uptake of glucose by tissues.

Hyperglycemia in the ICU setting increased by the use of intravenous solutions and parenteral nutrition.

Hyperglycemia in the ICU does not consistently portend a worse prognosis for individuals with known diabetes, but is associated with worse prognoses in patients admitted to the ICU without previously diagnosed diabetes, particularly for patients with acute coronary syndromes and stroke (Egi M et al).

Correlates with vasculopathies involving the CNS and the onset of stroke: the worse the hyperglycemia the greater the risk of stroke downstream (Sui X et al).

In the presence of brain ischemia, elevated blood and brain glucose exacerbates ischemic neurologic injury, turning subclinical injury into apparent injury, and mild clinical injury into potentially debilitating or morbid illness (Wass CT et al).

Patients with nonketotic hyperglycemia can develop hemiballismus as a complication to the disease through the development of a subthalamic nucleus lesion, and is the second most common reported cause of hemiballismus. 

Observational data suggests prolonged hyperglycemia inversely associated with survival in acutely ill patients (Eli M et al).

Suspected that hyperglycemia associated with increased susceptibility to sepsis is hypothesized the harm from hyperglycemia in critically ill patients.

In a study of critically ill surgical ICU patients treated with tight glucose control versus standard management resulted in a 42% reduction in mortality rate among the intensively treated patients who remained in the ICU for more than 5 days: attributed to by a decrease in multiorgan failure and sepsis (Van de Berghe).

In sick patients observational studies indicate that for those values between the range of 79 to 200 mg per deciliter the duration of exposure to higher glucose concentrations is inversely associated with survival (Egi M et al).

In medical ICU patients treated with tight glucose control versus a standard approach a reduction in mortality was not appreciated, as seen with surgical ICU patients, but there was a decrease in morbidity (Van den Berghe).

In a study of 1604 patients (Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation) admitted to an ICU for critical illness undergoing randomization to intensive glucose control vs. conventional glucose control (target of 180 mg or less per deciliter) with a primary endpoint of death from any cause within 90 days of randomization: severe hypoglycemia occurred in the intensive group 6.8% of cases and in 0.5% of cases in the conventional group, no significant difference in the groups in median days in the ICU, or hospital, or median number of days on mechanical ventilation or renal replacement therapy, 27.5% in the intensive group died and 24.9% in the conventional group died (NICE-SUGAR study).

Conclusion of the NICE-SUGAR study is that intensive glucose control increased mortality among adult patients in the ICU.

Despite the NICE-SUGAR study indicating that intense glycemic control may increase harm and mortality in ICU care the deadoption of such care has not occurred in the U.S.(Niven DJ et al).

In 4 additional studies of 2600 patients with both medical and surgical patients intensive insulin treatment had no significant effect on mortality but was associated with higher levels, 8-28%, of hypoglycemia, and no improvement in renal impairment, duration of mechanical ventilation or length of stay (Arabi YM et al, Brunkhorst FM et al, DELa Rosa GDC et al).

A multi center, randomized trial showed that tight glycemic control in critically ill children had no significant effect on major clinical outcomes, although hypoglycemic episodes were higher with tight glucose control them with conventional glucose control (CHIP investigators).

Increased sugar in ill patients due to hormone changes, decreased physical activity and insulin resistance.

About one in five deaths from ischemic disease and one in eight from stroke worldwide attributable to higher than optimum blood glucose levels.

Severe changes associated with deleterious abnormalities of vascular, hemodynamic and immune systems.

Postoperative sugar levels predict for infection rate after cardiac surgery.

Elevated glucose levels at the time of acute myocardial infarction predict for in hospital and 1 year mortality.

Associated with adverse outcomes for patients in ICU’s, general postoperative surgical patients, acute cardiovascular events including stroke.

Increased morbidity and mortality among hospitalized individuals with acute illness and diabetes, and in patients with hyperglycemia without known diabetes.

With tight diabetic control in the ICU may decrease morbidity and mortality, but may be associated with higher levels of hypoglycemic episodes.

The first randomized large clinical trial demonstrated type glycemic control to predominately surgical patients admitted to the ICU compared with conventional glucose management resulted in 1 life saved for every 29 patients treated (Leuven I et al).

ACCORD trial randomly assigned patients with type 2 diabetes and cardiovascular disease received intensive therapy, Hgb A1C target <6.0 or standard therapy Hgb A1C 7-7.9-follow up after termination of the study at 5 years revealed reduced nonfatal myocardial infarctions but increased 5 year mortality (ACCORD Study Group).

In the ACCORD trial, and in the ADVANCE trial, and in the veterans Affars Diabetes Trial (DDDT) have shown that no cardiovascular benefit is associated with tight control of glycemia: with the hemoglobin A-1 C of 6.4%, 6.4%, and 6.9% for the ACCORD, ADVANCE, and VADT, respectively compared with control arms of 7.5%, 7%, and 8.4%, respectively.

In the ACCORD study an increased mortality in the intensive control group prematurely closed the study.

An increase in mortality was not found in ADVANCE or VADT study.

Severe hypoglycemia was seen in the intensive control groups in all three studies.

The National Committee for Quality Insurance Health care Effectiveness Data and Information Set (HEDIS) suggests hemoglobin A-1 C Gold to listen 7% for persons younger than 65 years of age without cardiovascular disease or in stage complications and diabetes and establish the new goal of less than 8% for persons 65 to 74 years of age.

Electrolyte abnormalities are common with hyperglyycemia due to osmotic fluid shifts of of total body deficits brought about by osmotic diuresis.

Increase in glucose concentration increases plasma tonicity, creating an osmotic driving force that moves water from the intracellular space to the extracellular space, diluting the extracellular concentration of sodium.

With hyperglycemia plasma sodium concentration is usually low as a result of osmotic influx  of water.

Typically, oral anti-diabetic agents have limited role in inpatient hospital setting, and should be discontinued during an acute illness, unless a very brief hospitalization occurs.

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