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Diabetes Management
Table 1: Glycemic Targets in Hospitalized Patients
80–110mg/dl).
3–5,13
Severe hypoglycemia is a significant risk in the
intensive insulin therapy of critically ill patients and is an independent
Surgical critical care patients 140–180mg/dl risk factor for increased morbidity and mortality.
4,22
A potential problem
Medical critical care patients 140–180mg/dl in published large trials is the utilization of the Leuven insulin infusion
General medical–surgical patients 100–180mg/dl
protocol. In the original van den Berghe paper, the protocol reported an
Pre-meal <140mg/dl
incidence of hypoglycemia (≤40mg/dl) in the IIT group of 5.1 versus 0.8%
Random <180mg/dl
in the conventional group.
3
Other studies utilizing the same IIT protocol
16
Sources: Diabetes Care, 2009;32:1119–31, and Endocrine Practice, 2009;15(4):353–69.
demonstrated an increased incidence of hypoglycemia ranging from 5.1
to 24% in the intensively treated group.
3,4,23
All protocols need to be
literature.
3–5
Perhaps the seminal study was that of Van den Berghe and appropriately applied, but in the literature the Leuven insulin protocol
colleagues published in 2001.
3
This was a prospective RCT of 1,548 utilization and others have the disadvantage of lack of standardization
patients treated with intravenous insulin in the surgical ICU of University in application.
23–25
It is unknown whether utilization or application of the
Hospital in Leuven, Belgium. In the group treated with intensive insulin Leuven protocol influenced hypoglycemic risk in the reported studies.
therapy (IIT) to accomplish tight glycemic control (TGC), defined as a Although a standard protocol was utilized in NICE-SUGAR, problems
glucose goal of 80–110mg/dl, there was a 34% decrease of in-hospital with protocol application accounted for a significant number of patients
mortality compared with the conventionally treated group with a who experienced hypoglycemia.
26
Following review of the literature
glucose goal of 180–200mg/dl. Other measures of morbidity, including and pertinent available data, the American Association of Clinical
sepsis, acute renal failure requiring dialysis, need for blood transfusions, Endocrinologists (AACE) and the American Diabetes Association (ADA)
and polyneuropathy, were improved in the IIT group. However, in this issued a consensus statement on inpatient glycemic control.
16
The
study, hypoglycemia (blood glucose levels ≤40mg/dl) occurred in 5.1% of resultant goals for inpatient glucose control and previous goals are seen
the intensive insulin group and 0.8% of the conventional group. in Table 1. The committee predicated the basis of the guidelines as:
“until further information becomes available, to continue to emphasize
In 2006, the same group of investigators using the same treatment the importance of glycemic control in hospitalized patients with critical
protocol published their results in 1,200 patients treated in the medical and non-critical illness while aiming at targets that are less stringent
ICU. Unlike the initial study, conducted in a surgical ICU, there was no than 80 to 110 mg/dl.”
16
decrease in hospital mortality during the first three days in ICU in the
intensive group (glucose goal 80–110mg/dl). Hypoglycemia, which Additional areas of discussion in the evaluation of glucose control and in
occurred in 18.7% of patients in the intensive treatment group and the methods utilized to attain that control in the critically ill patient involve:
3.1% of the conventional group, was independently associated with a
poor prognosis.
4
• point-of-care (POC) testing of blood glucose;
• the use or non-use of supplemental caloric administration during IIT; and
In May 2009, the Normoglycemia in Intensive Care Evaluation and • the influence of glucose variability on morbidity and mortality.
15,27–29
Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study was
published in the New England Journal of Medicine.
5
This was a Reliability of POC blood glucose testing is extremely important to patient
randomized, controlled, unblinded study of 6,104 adult patients safety in the hospital setting. Accuracy of POC devices and an
admitted to medical and surgical ICUs in 42 hospitals, primarily in understanding of differences in whole blood and plasma glucose
Australia and New Zealand. The group treated with IIT (glucose goal measurements are essential. The hospital environment presents the
81–108mg/dl) achieved a mean glucose level of 115mg/dl, whereas the opportunity for multiple confounding factors to be present at once.
group treated conventionally (glucose goal 144–180mg/dl) achieved a Variables unique to the patient must be considered, particularly in
mean glucose level of 144mg/dl. Hypoglycemia (blood glucose levels situations where discrepancies arise between bedside glucose
≤40mg/dl) was seen in 6.8% of the intensive group and 0.5% of the measurement and the clinical presentation.
15
conventional group. The primary end-point, mortality at or before 90
days, was 27.5% in the intensive group versus 24.9% in the conventional The use or non-use of IIT with supplemental calories can significantly
group (p=0.02). The NICE-SUGAR investigators concluded that intensive affect metabolism in the critical care setting as well as blood glucose
glucose control increased mortality among adults in the ICU. A blood levels and the amount of infused insulin necessary to attain glucose
glucose target of 180mg/dl or less resulted in lower mortality than did a goals. The cardioprotective, neuroprotective, and antiapoptotic effect
target of 81–108mg/dl. Contrary to the previous Leuven surgical ICU of intravenous insulin is realized primarily in the setting of euglycemia
study,
3
and compatible with the medical ICU study of patients treated for versus hyperglycemia.
30
Therefore, this potential variable in critical
three days or less,
4
the NICE-SUGAR mortality at 90 days was increased care therapy must be addressed in treatment and in evaluation of the
in the group treated with IIT, with no decrease in morbidity when published literature.
compared with the conventional group.
Blood glucose variability in critically ill patients has been identified as a
Other smaller studies and meta-analyses have found conflicting results strong independent risk factor for increased mortality in the ICU
related to mortality and morbidity in ICU IIT-treated (glucose goal setting.
27–29
This particular metric is important in the selection of the type
80–110mg/dl) patients.
6,7,13
A consistent observation in these studies is of insulin therapy utilized in the ICU and must be considered when
an increase in hypoglycemia in the group treated with IIT (glucose goal evaluating treatment protocols and outcomes.
46 US ENDOCRINOLOGY
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