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Benzodiazepines induce hyperglycemia in rats by affecting peripheral disposal of glucose
Critical Care volume 17, Article number: P385 (2013)
In light of the interest in the relationship between glycemia control in critically ill subjects and outcome, we set up a study to investigate whether benzodiazepine, commonly used in anesthesia and ICUs, interferes with glucose metabolism and to explore the mechanism.
A total of 40 sedated and paralyzed Sprague-Dawley rats (301 ± 55 g) were investigated in four consecutive studies. (1) To investigate the effects of diazepam on blood glucose, 15 rats were randomly assigned to intraperitoneal anesthesia with tiopenthal 80 mg/kg (DZP0), tiopenthal 40 mg/kg + diazepam 5 mg/kg (DPZ5) or tiopenthal 40 mg/kg + diazepam 15 mg/kg (DZP15). Blood levels of glucose (GEM premier 3000; IL) were measured at time intervals over 2 hours. (2) Ten animals randomized to DZP0 or DZP5 underwent an intravenous glucose tolerance test with glucose bolus (0.5 g/kg). Acute insulin response, the mean value of blood insulin (Insulin ELISA kit; Millipore) from 2 to 10 minutes after glucose bolus, was measured as index of insulin secretion. (3) A hyperinsulinemic euglycemic clamp obtained by a continuous intravenous infusion of insulin (130 mUI/kg/minute) was run in 10 animals randomized to DZP0 or DZP5 and the glucose infusion rate (GIR, mg/kg/minute) was assessed . (4) The effect of midazolam on blood glucose was tested in five additional animals (M5: tiophental 40 mg/kg + midazolam 5 mg/kg). Data are presented as mean ± SEM. Statistical analysis (ANOVA, t test) was conducted with Sigma Stat 3.1 (Systat Software).
(1) Diazepam was associated with higher levels of blood glucose in a dose-response fashion: DZP0 128 ± 7 mg/dl, DZP5 166 ± 7.3, DZP15 197 ± 7 (P < 0.05). (2) The acute insulin response to intravenous glucose tolerance test was similar in DZP0 and DZP5 (DZP0 3.97 ± 0.42 ng/ml, DZP5 3.68 ± 0.44, P = 0.68), while blood glucose levels were different (DZP0 192 ± 5 mg/dl, DZP5 217 ± 5, P < 0.05). (3) During hyperinsulinemic euglycemic clamp, blood glucose levels were similar (109 ± 3 mg/dl, P = 0.2), but the DZP5 group showed a trend through lower values of GIR (DZP0 30.8 ± 2 mg/kg/minute, DZP5 24.7 ± 2, P = 0.08). (4) Infusion of midazolam was associated with higher blood glucose levels (DZP0 128 ± 5 mg/dl, M5 151 ± 6, P < 0.05).
Both diazepam and midazolam significantly alter plasma glucose levels in rats. Peripheral disposal of glucose rather than altered pancreas secretion of insulin explains the benzodiazepine-associated hyperglycemia.
DeFronzo: Am J Physiol. 1979, 273: E214-E223.
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Salice, V., Valenza, F., Pizzocri, M. et al. Benzodiazepines induce hyperglycemia in rats by affecting peripheral disposal of glucose. Crit Care 17, P385 (2013). https://doi.org/10.1186/cc12323
- Blood Glucose Level
- High Blood Glucose
- Glucose Infusion Rate