The obesity paradox and hypoglycemia in critically ill patients

Background: A high body mass index (BMI) has been associated with decreased mortality in critically ill patients. This association may, in part, relate to the impact of BMI on glycemia. We aimed to study the relationship between BMI, glycemia and hospital mortality. Methods: We included all patients with a recorded BMI from four large international clinical databases (n = 259,177). We investigated the unadjusted association of BMI with average glucose levels, mortality and hypoglycemia rate. We applied multivariate analysis to investigate the impact of BMI on hypoglycemia rate, after adjusting for glycemia-relevant treatments (insulin, dextrose, corticosteroids, enteral and parenteral nutrition) and key physiological parameters (previous blood glucose level, blood lactate, shock state, SOFA score). Results: We analyzed 5,544,366 glucose measurements. On unadjusted analysis, increasing BMI was associated with increasing glucose levels (average increase of 5 and 10 mg/dL for the 25-30, 30-35 kg/m(2) BMI groups compared to normal BMI (18.5-25 kg/m(2)) patients). Despite greater hyperglycemia, increasing BMI was associated with lower hospital mortality (average decrease of 2% and 3.25% for the 25-30, 30-35 kg/m(2) groups compared to normal BMI patients) and lower hypoglycemia rate (average decrease of 2.5% and 3.5% for the 25-30, 30-35 kg/m(2) groups compared to normal BMI patients). Increasing BMI was significantly independently associated with reduced hypoglycemia rate, with odds ratio (OR) 0.72 and 0.65, respectively (95% CIs 0.67-0.77 and 0.60-0.71, both p < 0.001) when compared with normal BMI. Low BMI patients showed greater hypoglycemia rate, with OR 1.6 (CI 1.43-1.79, p < 0.001). The association of high BMI and decreased mortality did not apply to diabetic patients. Although diabetic patients had higher rates of hypoglycemia overall and higher glucose variability (p < 0.001), they also had a reduced risk of hypoglycemia with higher BMI levels (p < 0.001). Conclusions: Increasing BMI is independently associated with decreased risk of hypoglycemia. It is also associated with increasing hyperglycemia and yet with lower mortality. Lower risk of hypoglycemia might contribute to decreased mortality and might partly explain the obesity paradox. These associations, however, were markedly modified by the presence of diabetes.