Early endotoxemia increases peripheral and hepatic insulin sensitivity in healthy humans.
BACKGROUND
Sepsis-induced hypoglycemia is a well known, but rare, event of unknown origin.


OBJECTIVE
The aim of the study was to obtain insight into the mechanism of sepsis-induced hypoglycemia, focusing on glucose kinetics and insulin sensitivity measured with stable isotopes by using the model of human endotoxemia.


METHODS
Glucose metabolism was measured during two hyperinsulinemic [insulin levels of 100 pmol/liter (low-dose clamp) and 400 pmol/liter (medium-dose clamp)] euglycemic (5 mmol/liter) clamps on two occasions: without or with lipopolysaccharide (LPS).


METHODS
The study was conducted at the Academic Medical Center, Metabolic and Clinical Research Unit (Amsterdam, The Netherlands).


METHODS
Eighteen healthy male volunteers participated in the study.


METHODS
A hyperinsulinemic euglycemic (5 mmol/liter) clamp with LPS (two groups of six subjects; insulin infusion at rates of either 10 or 40 mU.m(-2).min(-1)) or without LPS (n = 6; both insulin infusions in same subjects).


METHODS
We measured hepatic and peripheral insulin sensitivity.


RESULTS
Hepatic insulin sensitivity, defined as a decrease in endogenous glucose production during hyperinsulinemia (100 pmol/liter), was higher in the LPS group compared to the control group (P = 0.010). Insulin-stimulated peripheral glucose uptake was higher in both clamps after LPS compared to the control setting (P = 0.006 and 0.010), despite a significant increase in the plasma concentrations of norepinephrine and cytokines in the LPS group during both clamps.


CONCLUSIONS
These data indicate that shortly (2 h) after administration of LPS, peripheral and hepatic insulin sensitivity increase. This may contribute to the hypoglycemia occurring in some patients with critical illness, especially in the setting of intensive insulin therapy.
van der Crabben
Saskia N
SN
Department of Endocrinology and Metabolism, Academic Medial Center, Amsterdam, The Netherlands. s.n.vandercrabben@umcutrecht.nl
Blümer
Regje M E
RM
Stegenga
Michiel E
ME
Ackermans
Mariëtte T
MT
Endert
Erik
E
Tanck
Michael W T
MW
Serlie
Mireille J
MJ
van der Poll
Tom
T
Sauerwein
Hans P
HP
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D015309:Glucose Clamp Technique / Q000379:methods; D006262:Health; D006728:Hormones / Q000097:blood; D006801:Humans; D007260:Infusion Pumps; D007328:Insulin / Q000097:blood* / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D013997:Time Factors; D055815:Young Adult
D001786:Blood Glucose; D016207:Cytokines; D006728:Hormones; D007328:Insulin; D008070:Lipopolysaccharides