Literature Review: Key Guidelines and Studies for Hyperglycemia in Hospitalized Patients

American Diabetes Association (ADA) and American Association of Clinical Endocrinologists (AACE)

• ICU Setting:
  • Initiate insulin therapy for persistent hyperglycemia (>180 mg/dL or >10 mmol/L).
  • Target glucose level between 140 – 180 mg/dL (7.8 – 10.0 mmol/L) for most ICU patients.
  • More stringent goals (110 – 140 mg/dL or 6.1 – 7.8 mmol/L) may be appropriate for selected ICU patients, such as cardiac surgical patients, or those with stable glycemic control without hypoglycemia.

• Non-ICU Setting:
  • Pre-meal glucose targets should generally be <140 mg/dL (<7.8 mmol/L), and random glucose levels <180 mg/dL (<10.0 mmol/L).
  • Less stringent targets may be appropriate for patients with severe comorbidities.

Clinical Practice Guideline of the Endocrine Society

• Non-ICU Setting:
  • Pre-meal glucose target of <140 mg/dL (<7.8 mmol/L) and random blood glucose <180 mg/dL (<10.0 mmol/L).
  • Lower target ranges may be appropriate for individuals who can achieve and maintain glycemic control without hypoglycemia.

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Select Clinical Trials

1. Leuven Surgical ICU Study (Van den Berghe, 2001)

• Setting: Surgical ICU
• Population: Mixed, with a majority being cardiac cases.
• Key Outcomes:
  • Those in the intensive therapy group (target glucose between 80-110 mg/dL) had significantly fewer complications such as bacteremia, reduced antibiotic requirements, lower length of ventilator dependency, fewer ICU days, and a 34% reduction in mortality compared to conventional therapy.

2. Medical ICU Study (Van den Berghe, 2006)

• Setting: Medical ICU
• Population: Mixed population, 18% with diabetes.
• Key Outcomes:
  • Intensive insulin therapy resulted in fewer ICU and total hospital complications for those receiving at least 3 days of insulin treatment.

3. Glucontrol Trial

• Setting: Multi-center, Medical and Surgical ICUs
• Key Outcomes:
  • No significant difference in mortality between the intensive (80-110 mg/dL) and conventional glycemic control groups (140-180 mg/dL).

4. VISEP Study

• Setting: Medical ICU, patients with sepsis.
• Key Outcomes:
  • No difference in 28- or 90-day mortality, but a significantly higher rate of severe hypoglycemia in the intensive treatment group.

5. NICE-SUGAR Trial

• Setting: Multi-center, Medical and Surgical ICUs
• Key Outcomes:
  • No difference in hospital mortality, but a higher 90-day mortality and increased hypoglycemia in the intensive treatment group.

6. GLUCO-CABG Trial

• Setting: Cardiac Surgery, ICU
• Key Outcomes:
  • Intensive glucose treatment resulted in a 20% reduction in perioperative complications compared to conservative treatment. The cost of hospitalization was also lower in the intensive group.

7. Observational and Randomized Trials in General Medical and Surgical Patients

• Key Outcomes:
  • Improved glucose control with a basal-bolus regimen led to a significant reduction in complications such as postoperative wound infection, pneumonia, bacteremia, and acute renal and respiratory failure. It also reduced average total inpatient costs per day by 14%.

These trials present a nuanced view of glycemic control in both ICU and non-ICU settings. While earlier studies like the Leuven trials suggested benefits from intensive glycemic control, later studies such as NICE-SUGAR and VISEP showed the risks associated with such an approach, particularly the risk of severe hypoglycemia.

The GLUCO-CABG trial and observational studies in general medical and surgical patients suggest that a more balanced approach, such as a basal-bolus regimen, may offer benefits in terms of reduced complications and cost.

 

Non-ICU settings

Study	Setting	Population	% with Diabetes	Intervention	Clinical Outcome
Leuven Surgical ICU Study (Van den Berghe, 2001)	Surgical ICU	Mixed, majority cardiac cases	13%	Target glucose between 80-110 mg/dL	34% reduction in mortality, fewer complications like bacteremia, reduced ICU days
Medical ICU Study (Van den Berghe, 2006)	Medical ICU	Mixed	18%	Intensive insulin therapy	Fewer ICU and total hospital complications for those on 3+ days of insulin
Glucontrol Trial	Multi-center, Medical and Surgical ICUs	Mixed	18%	Target glucose 80-110 mg/dL vs. 140-180 mg/dL	No significant difference in 28-day mortality
VISEP Study	Medical ICU, Sepsis Patients	Mixed	30%	Target glucose 180-200 mg/dL vs. 80-110 mg/dL	No difference in 28- or 90-day mortality, but higher rate of severe hypoglycemia in intensive group
NICE-SUGAR Trial	Multi-center, Medical and Surgical ICUs	Mixed	20%	Target glucose <180 mg/dL vs. 81-108 mg/dL	No difference in hospital mortality, but higher 90-day mortality and increased hypoglycemia in intensive group
GLUCO-CABG Trial	Cardiac Surgery, ICU	Mixed, undergoing CABG	Unknown	Target glucose 100-140 mg/dL vs. 141-180 mg/dL	20% reduction in perioperative complications and lower hospitalization costs in the intensive group