A prospective observational study of the relationship of critical illness associated hyperglycaemia in medical ICU patients and subsequent development of type 2 diabetes

Ivan Gornik, Ana Vujaklija-Brajkovic, Ivana Pavlic Renar, Vladimir Gasparovic, Ivan Gornik, Ana Vujaklija-Brajkovic, Ivana Pavlic Renar, Vladimir Gasparovic

Abstract

Introduction: Critical illness is commonly complicated by hyperglycaemia caused by mediators of stress and inflammation. Severity of disease is the main risk factor for development of hyperglycaemia, but not all severely ill develop hyperglycemia and some do even in mild disease. We hypothesised that acute disease only exposes a latent disturbance of glucose metabolism which puts those patients at higher risk for developing diabetes.

Methods: Medical patients with no history of impaired glucose metabolism or other endocrine disorder admitted to an intensive care unit between July 1998 and June 2004 were considered for inclusion. Glucose was measured at least two times a day, and patients were divided into the hyperglycaemia group (glucose ≥7.8 mmol/l) and normoglycaemia group. An oral glucose tolerance test was performed within six weeks after discharge to disclose patients with unknown diabetes or pre-diabetes who were excluded. Patients treated with corticosteroids and those terminally ill were also excluded from the follow-up which lasted for a minimum of five years with annual oral glucose tolerance tests.

Results: A five-year follow-up was completed for 398 patients in the normoglycaemia group, of which 14 (3.5%) developed type 2 diabetes. In the hyperglycaemia group 193 patients finished follow-up and 33 (17.1%) developed type 2 diabetes. The relative risk for type 2 diabetes during five years after the acute illness was 5.6 (95% confidence interval (CI) 3.1 to 10.2).

Conclusions: Patients with hyperglycaemia during acute illness who are not diagnosed with diabetes before or during the hospitalization should be considered a population at increased risk for developing diabetes. They should, therefore, be followed-up, in order to be timely diagnosed and treated.

Figures

Figure 1
Figure 1
Flow diagram showing the loss of patients from initial screening to the end of five-year follow-up.
Figure 2
Figure 2
Cumulative incidence of diabetes in patients with hyperglycaemia and normoglycaemia during critical illness.

References

    1. Bernard C. Laçons sur les phenomenes de la vie communs aux animaux et aux vegetaux. p. 1878.
    1. Benfield T, Jensen JS, Nordestgaard BG. Influence of diabetes and hyperglycaemia on infectious disease hospitalisation and outcome. Diabetologia. 2007;50:549–554. doi: 10.1007/s00125-006-0570-3.
    1. Christiansen C, Toft P, Jorgensen HS, Andersen SK, Tonnesen E. Hyperglycaemia and mortality in critically ill patients. A prospective study. Intensive Care Med. 2004;30:1685–1688. doi: 10.1007/s00134-004-2325-2.
    1. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359–1367. doi: 10.1056/NEJMoa011300.
    1. 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 Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study. Circulation. 1999;99:2626–2632.
    1. Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hebert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1283–1297. doi: 10.1056/NEJMoa0810625.
    1. Preiser JC. NICE-SUGAR: the end of a sweet dream? Crit Care. 2009;13:143. doi: 10.1186/cc7790.
    1. Inzucchi SE, Siegel MD. Glucose control in the ICU--how tight is too tight? N Engl J Med. 2009;360:1346–1349. doi: 10.1056/NEJMe0901507.
    1. Dungan KM, Braithwaite SS, Preiser JC. Stress hyperglycaemia. Lancet. 2009;373:1798–1807. doi: 10.1016/S0140-6736(09)60553-5.
    1. Van den Berghe G. Neuroendocrine pathobiology of chronic critical illness. Crit Care Clin. 2002;18:509–528. doi: 10.1016/S0749-0704(02)00007-6.
    1. Langouche L, Van den Berghe G. The dynamic neuroendocrine response to critical illness. Endocrinol Metab Clin North Am. 2006;35:777–791. doi: 10.1016/j.ecl.2006.09.007. ix.
    1. McCowen KC, Malhotra A, Bistrian BR. Stress-induced hyperglycemia. Crit Care Clin. 2001;17:107–124. doi: 10.1016/S0749-0704(05)70154-8.
    1. Grimble RF. Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care. 2002;5:551–559. doi: 10.1097/00075197-200209000-00015.
    1. Marette A. Mediators of cytokine-induced insulin resistance in obesity and other inflammatory settings. Curr Opin Clin Nutr Metab Care. 2002;5:377–383. doi: 10.1097/00075197-200207000-00005.
    1. Marik PE, Raghavan M. Stress-hyperglycemia, insulin and immunomodulation in sepsis. Intensive Care Med. 2004;30:748–756. doi: 10.1007/s00134-004-2167-y.
    1. Aljada A, Ghanim H, Assian E, Dandona P. Tumor necrosis factor-alpha inhibits insulin-induced increase in endothelial nitric oxide synthase and reduces insulin receptor content and phosphorylation in human aortic endothelial cells. Metabolism. 2002;51:487–491. doi: 10.1053/meta.2002.31339.
    1. Mizock BA. Alterations in fuel metabolism in critical illness: hyperglycaemia. Best Pract Res Clin Endocrinol Metab. 2001;15:533–551. doi: 10.1053/beem.2001.0168.
    1. Clowes GH Jr, Martin H, Walji S, Hirsch E, Gazitua R, Goodfellow R. Blood insulin responses to blood glucose levels in high output sepsis and spetic shock. Am J Surg. 1978;135:577–583. doi: 10.1016/0002-9610(78)90040-5.
    1. Dahn MS, Jacobs LA, Smith S, Hans B, Lange MP, Mitchell RA, Kirkpatrick JR. The relationship of insulin production to glucose metabolism in severe sepsis. Arch Surg. 1985;120:166–172.
    1. Metso AJ, Murros K. Hyperglycaemia and the outcome of stroke. Brain. 2007;130:e85. doi: 10.1093/brain/awm158. author reply e86.
    1. Cubbon RM, Rajwani A, Abbas A, Gale CP, Grant PJ, Wheatcroft SB, Barth JH, Kearney MT, Hall AS. Hyperglycaemia, in relation to sex, and mortality after acute coronary syndrome. Eur J Cardiovasc Prev Rehabil. 2007;14:666–671. doi: 10.1097/HJR.0b013e32827ab6c1.
    1. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20:864–874. doi: 10.1097/00003246-199206000-00025.
    1. Krishnan JA, Parce PB, Martinez A, Diette GB, Brower RG. Caloric intake in medical ICU patients: consistency of care with guidelines and relationship to clinical outcomes. Chest. 2003;124:297–305. doi: 10.1378/chest.124.1.297.
    1. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2008;31:S55–60. doi: 10.2337/dc08-S055.
    1. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med. 2003;29:530–538.
    1. Pollack CV Jr, Braunwald E. 2007 update to the ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: implications for emergency department practice. Ann Emerg Med. 2008;51:591–606. doi: 10.1016/j.annemergmed.2007.09.004.
    1. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE, Steward DE, Theroux P, Alpert JS, Eagle KA, Faxon DP, Fuster V, Gardner TJ, Gregoratos G, Russell RO, Smith SC Jr. ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina) J Am Coll Cardiol. 2000;36:970–1062. doi: 10.1016/S0735-1097(00)00889-5.
    1. Thorell A, Nygren J, Ljungqvist O. Insulin resistance: a marker of surgical stress. Curr Opin Clin Nutr Metab Care. 1999;2:69–78. doi: 10.1097/00075197-199901000-00012.
    1. Esteghamati A, Khalilzadeh O, Anvari M, Ahadi MS, Abbasi M, Rashidi A. Metabolic syndrome and insulin resistance significantly correlate with body mass index. Arch Med Res. 2008;39:803–808. doi: 10.1016/j.arcmed.2008.08.004.
    1. Preissig CM, Rigby MR. Hyperglycaemia results from beta-cell dysfunction in critically ill children with respiratory and cardiovascular failure: a prospective observational study. Crit Care. 2009;13:R27. doi: 10.1186/cc7732.
    1. Goran KP. The consensus is clearly needed for the definition of stress hyperglycaemia in acute myocardial infarction. Eur Heart J. 2007;28:2042. doi: 10.1093/eurheartj/ehm231. author reply 2042-2043.
    1. Timmer JR, Ottervanger JP, Bilo HJ, Dambrink JH, Miedema K, Hoorntje JC, Zijlstra F. Prognostic value of admission glucose and glycosylated haemoglobin levels in acute coronary syndromes. QJM. 2006;99:237–243. doi: 10.1093/qjmed/hcl028.
    1. Schiele F, Descotes-Genon V, Seronde MF, Blonde MC, Legalery P, Meneveau N, Ecarnot F, Mercier M, Penfornis A, Thebault L, Boumal D, Bassand JP. Predictive value of admission hyperglycaemia on mortality in patients with acute myocardial infarction. Diabet Med. 2006;23:1370–1376. doi: 10.1111/j.1464-5491.2006.02000.x.
    1. Ishihara M, Inoue I, Kawagoe T, Shimatani Y, Kurisu S, Hata T, Nakama Y, Kijima Y, Kagawa E. Is admission hyperglycaemia in non-diabetic patients with acute myocardial infarction a surrogate for previously undiagnosed abnormal glucose tolerance? Eur Heart J. 2006;27:2413–2419. doi: 10.1093/eurheartj/ehl271.
    1. Deedwania P, Kosiborod M, Barrett E, Ceriello A, Isley W, Mazzone T, Raskin P. Hyperglycemia and acute coronary syndrome: a scientific statement from the American Heart Association Diabetes Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2008;117:1610–1619. doi: 10.1161/CIRCULATIONAHA.107.188629.
    1. Inzucchi SE, Rosenstock J. Counterpoint: Inpatient glucose management: a premature call to arms? Diabetes Care. 2005;28:976–979. doi: 10.2337/diacare.28.4.976.
    1. Bryer-Ash M, Garber AJ. Point: Inpatient glucose management: the emperor finally has clothes. Diabetes Care. 2005;28:973–975. doi: 10.2337/diacare.28.4.973.
    1. Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman R, Hirsch IB, Inzucchi SE, Ismail-Beigi F, Kirkman MS, Umpierrez GE. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care. 2009;32:1119–1131. doi: 10.2337/dc09-9029.
    1. Waeschle RM, Moerer O, Hilgers R, Herrmann P, Neumann P, Quintel M. The impact of the severity of sepsis on the risk of hypoglycaemia and glycaemic variability. Crit Care. 2008;12:R129. doi: 10.1186/cc7097.
    1. Rattanataweeboon P, Vilaichone W, Vannasaeng S. Stress hyperglycemia in patients with sepsis. J Med Assoc Thai. 2009;92:S88–94.
    1. Leonidou L, Michalaki M, Leonardou A, Polyzogopoulou E, Fouka K, Gerolymos M, Leonardos P, Psirogiannis A, Kyriazopoulou V, Gogos CA. Stress-induced hyperglycemia in patients with severe sepsis: a compromising factor for survival. Am J Med Sci. 2008;336:467–471. doi: 10.1097/MAJ.0b013e318176abb4.
    1. Griesdale DE, Tremblay MH, McEwen J, Chittock DR. Glucose Control and Mortality in Patients with Severe Traumatic Brain Injury. Neurocrit Care. 2009.
    1. Sen K, Mukherjee AK, Dharchowdhury L, Chatterjee A. A study to find out the proportion of prediabetes in patients with acute coronary syndrome in a medical college of Kolkata. J Indian Med Assoc. 2008;106:776–778.
    1. Nakamura T, Ako J, Kadowaki T, Funayama H, Sugawara Y, Kubo N, Momomura S. Impact of acute hyperglycemia during primary stent implantation in patients with ST-elevation myocardial infarction. J Cardiol. 2009;53:272–277. doi: 10.1016/j.jjcc.2008.11.011.
    1. Saudek CD, Herman WH, Sacks DB, Bergenstal RM, Edelman D, Davidson MB. A new look at screening and diagnosing diabetes mellitus. J Clin Endocrinol Metab. 2008;93:2447–2453. doi: 10.1210/jc.2007-2174.
    1. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009;32:1327–1334. doi: 10.2337/dc09-9033.
    1. Proceedings of the 4th International Workshop-Conference on Gestational Diabetes Mellitus. Chicago, Illinois, USA. 14-16 March 1997. Diabetes Care. 1998;21 Suppl 2:B1–B167.
    1. Kaaja RJ, Greer IA. Manifestations of chronic disease during pregnancy. Jama. 2005;294:2751–2757. doi: 10.1001/jama.294.21.2751.
    1. Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care. 2002;25:1862–1868. doi: 10.2337/diacare.25.10.1862.
    1. Ben-Haroush A, Yogev Y, Hod M. Epidemiology of gestational diabetes mellitus and its association with Type 2 diabetes. Diabet Med. 2004;21:103–113. doi: 10.1046/j.1464-5491.2003.00985.x.
    1. Ratner RE, Christophi CA, Metzger BE, Dabelea D, Bennett PH, Pi-Sunyer X, Fowler S, Kahn SE. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab. 2008;93:4774–4779. doi: 10.1210/jc.2008-0772.
    1. Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009;373:1773–1779. doi: 10.1016/S0140-6736(09)60731-5.
    1. Cowie CC, Rust KF, Ford ES, Eberhardt MS, Byrd-Holt DD, Li C, Williams DE, Gregg EW, Bainbridge KE, Saydah SH, Geiss LS. Full accounting of diabetes and pre-diabetes in the U.S. population in 1988-1994 and 2005-2006. Diabetes Care. 2009;32:287–294. doi: 10.2337/dc08-1296.

Source: PubMed

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