Glycemia influences on glucose metabolism in sepsis during hyperinsulinemic clamp.
BACKGROUND
We investigated glucose metabolism in septic patients during hyperglycemic clamps and compared the different levels of insulinemia and glycemia.


METHODS
In 10 non-diabetic stable septic patients on mechanical ventilation with baseline glycemia >6 mmol/L and continuous insulin infusion, 3 steps of hyperinsulinemic clamp were performed after 8 hours without caloric intake. In step 1, the targets were insulinemia of 250 mIU/L and glycemia of 5 mmol/L; in step 2, insulinemia of 250 mIU/L and glycemia of 10 mmol/L; in step 3, insulinemia of 1250 mIU/L and glycemia of 5 mmol/L. Glucose uptake was calculated as the amount of glucose per time needed to maintain the target level of glycemia. Glucose oxidation was calculated from indirect calorimetry and urinary nitrogen losses. Values are provided as means +/- SD. A two-way analysis of variance and Scheffe's method were used for statistical analysis and p < .05 was considered significant.


RESULTS
At step 1, glucose uptake was lower than at step 2 (3.8 +/- 2.48 mg/kg/min and 7.9 +/- 3.45 mg/kg/min, respectively; p < .001). Glucose oxidation was also lower at step 1 (2.6 +/- 0.98 and 4.2 +/- 1.85 mg/kg/min, respectively; p < .01). Glucose storage was low at step 1 (0.7 +/- 1.39) and increased at step 2 (3.5 +/- 2.18; p < .05). In step 3, glucose uptake was 7.0 +/- 2.1, oxidation was 3.6 +/- 1.37, and storage was 2.9 +/- 2.79. There was no significant difference in all these parameters between steps 2 and 3. Energy expenditure between steps 1, 2 and 3 did not change (2294 + 307.42, 2334 + 341.53, and 2342 + 426.67 kcal/day, respectively). Alanine in plasma dropped significantly (p < .05): 10 mmol/L (311 +/- 55.88 mmol/L) at glycemia compared with 5 mmol/L (390 +/- 76 micromol/L) at insulinemia 250 mIU/L. It did not differ significantly from the values obtained at glycemia 5 mmol/L and insulinemia 1250 mIU/L (348 +/- 70.68 mmol/L). Even if the level of cytokines in sepsis was higher, there was no correlation between the insulin level in plasma (250 and 1250 mIU/L), glycemia (5 and 10 mmol/L) and cytokine level (IL-1beta, IL-2, IL-6, IL-8 and TNFalpha).


CONCLUSIONS
At insulinemia 250 mIU/L, a glucose level of 10 mmol/L seems to increase glucose uptake, oxidation, and storage compared with glycemia 5 mmol/L. This glucose uptake and oxidation at glycemia 10 mmol/L is comparable with the effect of extremely high insulinemia (1250 mIU/L) clamped at glycemia 5 mmol/L. A higher level of blood glucose or a high level of insulinemia significantly increases glucose uptake but not energy expenditure.
Rusavy
Zdenek
Z
Department of Medicine I, University Hospital Plzen, Alej Svobody 80, 304 60 Plzen, Czech Republic. rusavy@fnplzen.cz
Macdonald
Ian A
IA
Sramek
Vladimir
V
Lacigova
Silvie
S
Tesinsky
Pavel
P
Novak
Ivan
I
D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism*; D002153:Calorimetry, Indirect; D016207:Cytokines / Q000096:biosynthesis; D004734:Energy Metabolism / Q000502:physiology*; D015309:Glucose Clamp Technique; D006801:Humans; D007263:Infusions, Parenteral; D007328:Insulin / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D009584:Nitrogen / Q000652:urine; D018805:Sepsis / Q000097:blood / Q000378:metabolism*; D012720:Severity of Illness Index
D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D009584:Nitrogen