Sage Journals: Discover world-class research

Abstract

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 >6mmol/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 5mmol/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 umol/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-1β_, IL-2, IL-6, IL-8 and TNFα). Conclusion: 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.

This study describes the influence of glycemia on glucose metabolism in septic patients during hyperglycemic clamp.

Get full access to this article

View all access options for this article.

References

Brandi LS, Santoro D, Natali A, et al. Insulin resistance of stress: sites and mechanisms. Clin Sci. 1993 ;85:525– 535.

Gore DC, Wolf SE, Herndon DN, Wolfe RR. Relative influence of glucose and insulin on peripheral amino acid metabolism in severely burned patients. JPEN J Parenter Enteral Nutr. 2002;26 : 271–277.

Ling PR, Bistrian BR, Mendez B, Istfan NW. Effects of systemic infusions of endotoxin, tumor necrosis factor and interleukin-1 on glucose metabolism in the rat: relationship to endogenous glucose production and peripheral tissue glucose uptake. Metabolism. 1994 ;43:279– 284.

Tappy L, Cayeux M, Schneiter P, et al. Effects of lactate on glucose metabolism in healthy subjects and in severely injured hyperglycemic patients. Am J Physiol. 1995 ;431:E630– E635.

Berg S, Sappington PL, Guzik LJ, Delude RL, Fink MP. Proinflammatory cytokines increase the rate of glycolysis and adenosine–5′-triphosphate turnover in cultured rat enterocytes.Crit Care Med. 2003;31:1203– 1212.

Iscra F, Gullo A, Biolo G. Bench-to-bedside review: lactate and the lung. Crit Care Med 2002;6:327– 329.

Mandarino LJ, Consoli A, Jain A, Kelley DE. Differential regulation of intracellular glucose metabolism by glucose and insulin in human muscle.Am J Physiol. 1993;265:E878– E905.

Henry RR, Gumbiner B, Flynn T, Thorburn AW. Metabolic effects of hyperglycemia and hyperinsulinemia on fate of intracellular glucose in NIDDM.Diabetes. 1990;39:149– 156.

Pilz G, Appel R, Gurniak T, Bujdoso O, Werdan K. APACHE II und Elebute Score-Berechnung und Sepsisbeurteilung auf der Intensivstation anhand eines BASIC Computerprogramms. Intensivmed. 1992 ;29:81– 89.

10.

DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistence. Am J Physiol. 1979 ;237:E214– E223.

11.

Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated cost of care. Crit Care Med 2001 ;29:1303– 1310.

12.

van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001 ;345:1359– 1367.

13.

Malmberg K, Norhammar A, Wedel H, Ryden L. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the DIGAMI study. Circulation. 1999 ;99:2626– 2632.

14.

Das UN. Is insulin an anti-inflammatory molecule?Nutrition 2001;17:409– 413.

15.

Gore DC, Wolf SE, Herndon DN, Wolfe RR. Relative influence of glucose and insulin on peripheral amino acid metabolism in severely burned patients. JPEN J Parenter Enteral Nutr 2002;26 : 271–277.

16.

Rovlias A, Kotsou S. The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery 2000 ;46:335– 342.

17.

Preiser JCH, Devos P, van den Berghe G. Tight control of glycemia in critically ill patients. Curr Opin Clin Nutr Metab Care. 2002 ;5:533– 537.

18.

Tappy L, Chioléro R, Berger M. Autoregulation of glucose production in health and disease. Curr Opin Clin Nutr Metab Care. 1999;2:161– 164.

19.

Wolfe RR, Martini WZ. Changes in intermediary metabolism in severe surgical illness. World J Surg. 2000 ;24:639– 647.

20.

Saeed M, Carlson GL, Little RA, Irving MH: Selective impairment of glucose storage in human sepsis. Brit J Surg. 1999 ;86:813– 821.

21.

Shangraw RE, Jahoor F, Miyoshi H, Neff WA, Stuart CA. Differentiation between septic and postburn insulin resistance.Metabolism. 1989;38:983– 989.

22.

Campbell IT. Limitations in nutrient intake. The effect of stressors: trauma sepsis and multiple organ failure. Eur J Clin Nutr. 1999; 53:143– 147.

23.

Arnold J, Campbell IT, Hipkin LJ, Keegan M. Manipulation of substrate utilization with somatostatin in patients with secondary multiple organ dysfunction syndrome. Crit Care Med 1995;23 : 71–77.

24.

Valarini R, Sousa MF, Kalil R, Abumrad NN, Riella MC. Anabolic effects of insulin and amino acids in promoting nitrogen accretion in postoperative patients. JPEN J Parenter Enteral Nutr 1994 ;18:214– 218.

25.

Jeevanandam M, Shamos RF, Petersen SR. Substrate efficacy in early nutrition support of critically ill multiple trauma victims. JPEN J Parenter Enteral Nutr 1992;16:511– 520.

26.

Zaloga GP, Roberts P. Permissive underfeeding. New Horizons 1994;2:257– 263.

27.

Katz JA, Lowry SF. Substrate use in hypermetabolism. In: Fein AM, ed. Sepsis and Multiorgan Failure. Baltimore, MD: Williams and Wilkins, 1997.

28.

Yu WK, Li WQ, Li A, Li JS. Influence of acute hyperglycemia in human sepsis on inflammatory cytokine and contra-regulatory hormone concentrations. World J Gastroenterol 2003 ;9:1824– 1827.

Glycemia Influences on Glucose Metabolism in Sepsis During Hyperinsulinemic Clamp

Abstract

Get full access to this article

References