title: Mild hypoglycemia is independently associated with increased mortality in the critically ill.
abstract: BACKGROUND
  Severe hypoglycemia (blood glucose concentration (BG) < 40 mg/dL) is independently associated with an increased risk of mortality in critically ill patients. The association of milder hypoglycemia (BG < 70 mg/dL) with mortality is less clear.
  
  
  METHODS
  Prospectively collected data from two observational cohorts in the USA and in The Netherlands, and from the prospective GLUCONTROL trial were analyzed. Hospital mortality was the primary endpoint.
  
  
  RESULTS
  We analyzed data from 6,240 patients: 3,263 admitted to Stamford Hospital (ST), 2,063 admitted to three institutions in The Netherlands (NL) and 914 who participated in the GLUCONTROL trial (GL). The percentage of patients with hypoglycemia varied from 18% to 65% among the different cohorts. Patients with hypoglycemia experienced higher mortality than did those without hypoglycemia even after stratification by severity of illness, diagnostic category, diabetic status, mean BG during intensive care unit (ICU) admission and coefficient of variation (CV) as a reflection of glycemic variability. The relative risk (RR, 95% confidence interval) of mortality associated with minimum BG < 40, 40 to 54 and 55 to 69 mg/dL compared to patients with minimum BG 80 to 109 mg/dL was 3.55 (3.02 to 4.17), 2.70 (2.31 to 3.14) and 2.18 (1.87 to 2.53), respectively (all P < 0.0001). The RR of mortality associated with any hypoglycemia < 70 mg/dL was 3.28 (2.78 to 3.87) (P < 0.0001), 1.30 (1.12 to 1.50) (P = 0.0005) and 2.11 (1.62 to 2.74) (P < 0.0001) for the ST, NL and GL cohorts, respectively. Multivariate regression analysis demonstrated that minimum BG < 70 mg/dL, 40 to 69 mg/dL and < 40 mg/dL were independently associated with increased risk of mortality for the entire cohort of 6,240 patients (odds ratio (OR) (95% confidence interval (CI)) 1.78 (1.39 to 2.27) P < 0.0001), 1.29 (1.11 to 1.51) P = 0.0011 and 1.87 (1.46 to 2.40) P < 0.0001) respectively.
  
  
  CONCLUSIONS
  Mild hypoglycemia was associated with a significantly increased risk of mortality in an international cohort of critically ill patients. Efforts to reduce the occurrence of hypoglycemia in critically ill patients may reduce mortality.
authors.affiliation: Division of Critical Care, Stamford Hospital, Columbia University College of Physicians and Surgeons, 190 West Broad Street, Stamford, CT 06902, USA. james.krinsley@gmail.com
authors.forename: James S
authors.initials: JS
authors.lastname: Krinsley
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: Peter E
authors.initials: PE
authors.lastname: Spronk
authors.forename: Robin E
authors.initials: RE
authors.lastname: Harmsen
authors.forename: Floris
authors.initials: F
authors.lastname: van Braam Houckgeest
authors.forename: Johannes P
authors.initials: JP
authors.lastname: van der Sluijs
authors.forename: Christian
authors.initials: C
authors.lastname: Mélot
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Preiser
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D002140:California / Q000453:epidemiology; D015331:Cohort Studies; D016638:Critical Illness / Q000401:mortality*; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D007003:Hypoglycemia / Q000401:mortality* / Q000503:physiopathology; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D001786:Blood Glucose