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01-10-2008 | Ôriginal

Tight glycemic control does not affect asymmetric-dimethylarginine in septic patients

Authors: Gaetano Iapichino, Maura Albicini, Michele Umbrello, Francesca Sacconi, Isabella Fermo, Radmila Pavlovich, Rita Paroni, Giacomo Bellani, Giovanni Mistraletti, Massimo Cugno, Antonio Pesenti, Luciano Gattinoni

Published in: Intensive Care Medicine | Issue 10/2008

Abstract

Objective

We investigated whether preventing hyperglycemia in septic patients affected the plasma concentration of asymmetric-dimethylarginine and if this was associated with clinical benefit.

Design

A prospective, multicenter, randomized, controlled, clinical study.

Setting

Intensive care units (ICU) in three university hospitals.

Patients

A total of 72 patients admitted for severe sepsis or septic shock, who stayed at least 3 days in the ICU. At admission the patients were assigned to receive either tight or conventional glycemic control.

Interventions

Determination of circulating levels of asymmetric-dimethylarginine, arginine, interleukin-6, C-reactive-protein and tumor-necrosis-factor-α.

Measurements and results

Blood was sampled at admission (no differences between groups), and on the 3rd, 6th, 9th, and 12th (T12) days. Sequential organ failure assessment was scored at each sampling time. All the data were analyzed on an intention-to-treat basis. The control and treatment groups received the same energy intake, glycemia (110.4 ± 17.3 vs. 163.0 ± 28.9 mg/dL, P < 0.001) and insulin (P = 0.02) supply differed. No differences were found in high plasma levels of asymmetric-dimethylarginine (P = 0.812) at any time during the ICU stay. The clinical course, as indicated by markers of inflammation, average and maximum organ failure score, ICU stay and ICU and 90-day mortality, was the same.

Conclusions

Intensive insulin treatment, while achieving glucose control, did not reduce asymmetric-dimethylarginine in high-risk septic patients fed with no more than 25 kcal/kg per day to limit ventilatory demand and to simplify glucose control.

Descriptor

45 (SIRS/sepsis: clinical studies).

Kimoto M, Tsuji H, Ogawa T, Sasaoka K (1993) Detection of NG, NG-dimethylarginine dimethylaminohydrolase in the nitric oxide-generating systems of rats using monoclonal antibody. Arch Biochem Biophys 300:657–662PubMedCrossRef

Kimoto M, Whitley GS, Tsuji H, Ogawa T (1995) Detection of NG, NG-dimethylarginine dimethylaminohydrolase in human tissues using a monoclonal antibody. J Biochem 117:237–238PubMedCrossRef

Kielstein JT, Boger RH, Bode-Böger SM, Frolich JC, Haller H, Ritz E, Fliser D (2002) Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease. J Am Soc Nephrol 13:170–176PubMed

Marescau B, Nagels G, Possemiers I, De Broe ME, Becaus I, Billiouw JM, Lornoy W, De Deyn PP (1997) Guanidino compounds in serum and urine of nondialyzed patients with chronic renal insufficiency. Metabolism 46:1024–1031PubMedCrossRef

Closs EI, Basha FZ, Habermeier A, Forstermann U (1997) Interference of l-arginine analogues with l-arginine transport mediated by the y+ carrier hCAT-2B. Nitric Oxide 1:65–73PubMedCrossRef

Bode-Böger SM, Scalera F, Kielstein JT, Martens-Lobenhoffer J, Breithardt G, Fobker M, Reinecke H (2006) Symmetrical dimethylarginine: a new combined parameter for renal function and extent of coronary artery disease. J Am Soc Nephrol 17:1128–1134PubMedCrossRef

Vallance P, Leone A, Calver A, Collier J, Moncada S (1992) Endogenous dimethylarginine as an inibitor of nitric oxide synthesis. J Cardiovasc Pharmacol 20:S60–S62PubMed

Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP (1999) Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 99:3092–3095PubMed

Siroen MP, Teerlink T, Nijveldt RJ, Prins HA, Richir MC, van Leeuwen PA (2006) The clinical significance of asymmetric dimethylarginines. Annu Rev Nutr 26:203–228PubMedCrossRef

10.

Sydow K, Munzel T (2003) ADMA and oxidative stress. Atheroscler Suppl 4:41–51PubMedCrossRef

11.

Stühlinger MC, Oka RK, Graf EE, Schmölzer I, Upson BM, Kapoor O, Szuba A, Malinow MR, Wascher TC, Pachinger O, Cooke JP (2003) Endothelial dysfunction induced by hyperhomocysteinemia: role of asymmetric dimethylarginine. Circulation 108:933–938PubMedCrossRef

12.

Schnabel R, Blankenberg S, Lubos E, Lackner KJ, Rupprecht HJ, Espinola-Klein C, Jachmann N, Post F, Peetz D, Bickel C, Cambien F, Tiret L, Münzel T (2005) Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene Study. Circ Res 97:e53–e59PubMedCrossRef

13.

Kielstein JT, Bode-Böger SM, Hesse G, Martens-Lobenhoffer J, Takacs A, Fliser D, Hoeper MM (2005) Asymmetrical dimethylarginine in idiopathic pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol 25:1414–1418PubMedCrossRef

14.

Nijveldt RJ, Teerlink T, Van Der Hoven B, Siroen MP, Kuik DJ, Rauwerda JA, van Leeuwen PA (2003) Asymmetrical dimethylarginine (ADMA) in critically ill patients: high plasma ADMA concentration is an independent risk factor of ICU mortality. Clin Nutr 22:23–30PubMedCrossRef

15.

Siroen MP, Van Leeuven PAM, Nijveldt RJ, Teerlink T, Wouters PJ, Van den Berghe G (2005) Modulation of asymmetric dimethylarginine in critically ill patients receiving intensive insulin treatment: a possible explanation of reduced morbidity and mortality? Crit Care Med 33:504–510PubMedCrossRef

16.

O’Dwyer MJ, Dempsey F, Crowley V, Kelleher DP, McManus R, Ryan T (2006) Septic shock is correlated with asymmetrical dimethylarginine levels, which may be influenced by a polymorphism in the dimethylarginine dimethylaminohydrolase II gene: a prospective observational study. Crit Care 10:R139PubMedCrossRef

17.

Maas R, Dentz L, Schwedhelm E, Thoms W, Kuss O, Hitmeyer N, Hdden M, Koss T, Standl T, Boger RH (2007) Elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine predict adverse events in patients undergoing noncardiac surgery. Crit Care Med 35:1876–1881PubMedCrossRef

18.

Zoccali C, Bode-Böger SM, Mallamaci F, Benedetto F, Tripepi G, Malatino L, Cataliotti A, Bellanuova I, Fermo I, Frölich J, Böger RH (2001) Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet 358:2113–2117PubMedCrossRef

19.

Valkonen VP, Paiva H, Salonen JT, Lakka TA, Lehtimaki T, Laakso J, Laaksonen R (2001) Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. Lancet 358:2127–2128PubMedCrossRef

20.

Lu TM, Ding YA, Lin SJ, Lee WS, Tai HC (2003) Plasma levels of asymmetric dimethylarginine and adverse cardiovascular events after percutaneous coronary intervention. Eur Heart J 24:1912–1919PubMedCrossRef

21.

Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874CrossRef

22.

Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345:1359–1367PubMedCrossRef

23.

Le Gall JR, Lemeshow S, Saulnier F (1993) A new Simplified Acute Physiology Score (Simplified Acute Physiology Score II) based on a European/North American multicenter study. JAMA 270:2957–2963PubMedCrossRef

24.

Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med 22:707–710PubMedCrossRef

25.

Paroni R, Fermo I, Fiorina P, Cighetti G (2005) Determination of asymmetric and symmetric dimethylarginines in plasma of hyperhomocysteinemic subjects. Amino Acids 28:389–394PubMedCrossRef

26.

Iapichino G, Radrizzani D, Solca M, Bonetti G, Leoni L, Ferro A (1985) Influence of total parenteral nutrition on protein metabolism following acute injury: assessment by urinary 3-methylhistidine excretion and nitrogen balance. J Parentr Enteral Nutr 9:42–46CrossRef

27.

Mann GE, Yudilevich DL, Sobrevia L (2003) Regulation of amino acid and glucose transporters in endothelial and smooth muscle cells. Physiol Rev 83:183–252PubMed

28.

Sobrevia L, Nadal A, Yudilevich DL, Mann GE (1996) Activation of l-arginine transport (system y+) and nitric oxide synthase by elevated glucose and insulin in human endothelial cells. J Physiol 490:775–781PubMed

29.

Lin KY, Ito A, Asagami T, Tsao PS, Adimoolam S, Kimoto M, Tsuji H, Reaven GM, Cooke JP (2002) Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 106:987–992PubMedCrossRef

30.

Nijveldt RJ, Teerlink T, Siroen MP, van Lambalgen AA, Rauwerda JA, van Leeuwen PA (2003) The liver is an important organ in the metabolism of asymmetrical dimethylarginine (ADMA). Clin Nutr 22:17–22PubMedCrossRef

31.

Liu J, Hatzoglou M (1998) Control of expression of the gene for the arginine transporter Cat-1 in rat liver cells by glucocorticoids and insulin. Amino Acids 15:321–337PubMedCrossRef

32.

Radrizzani D, Iapichino G (1998) Nutrition and lung function in the critically ill patient. Clin Nutr 17:7–10PubMedCrossRef

33.

Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natansori C, Loeffler M, Reinhart K, German Competence Network Sepsis (SepNet) (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358:125–139PubMedCrossRef

34.

Devos P, Preiser JC, Melot C (2007) Impact of tight glucose control by Intensive insulin therapy on ICU mortality and the rate of hypoglycaemia: final results of the Glucocontrol study. Intensive Care Med 33(Suppl 2):S189

Title: Tight glycemic control does not affect asymmetric-dimethylarginine in septic patients
Authors: Gaetano Iapichino
Maura Albicini
Michele Umbrello
Francesca Sacconi
Isabella Fermo
Radmila Pavlovich
Rita Paroni
Giacomo Bellani
Giovanni Mistraletti
Massimo Cugno
Antonio Pesenti
Luciano Gattinoni
Publication date: 01-10-2008
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 10/2008
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-008-1158-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Tight glycemic control does not affect asymmetric-dimethylarginine in septic patients

Abstract

Objective

Design

Setting

Patients

Interventions

Measurements and results

Conclusions

Descriptor

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Design

Setting

Patients

Interventions

Measurements and results

Conclusions

Descriptor

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