Effects of glucose-dependent insulinotropic polypeptide on gastric emptying, glycaemia and insulinaemia during critical illness: a prospective, double blind, randomised, crossover study

详细信息    查看全文

• 作者：Palash Kar (1)
  Caroline E Cousins (1)
  Christopher E Annink (1)
  Karen L Jones (2) (3)
  Marianne J Chapman (1) (4)
  Juris J Meier (5)
  Michael A Nauck (6)
  Michael Horowitz (2) (3)
  Adam M Deane (1) (4)
  
  1. Intensive Care Unit ; Level 4 ; Emergency Services Building ; Royal Adelaide Hospital ; North Terrace ; Adelaide ; South Australia ; 5000 ; Australia
  2. Discipline of Medicine ; The University of Adelaide ; Royal Adelaide Hospital ; Level 6 Eleanor Harrald Building ; North Terrace ; Adelaide ; South Australia ; 5000 ; Australia
  3. Centre of Research Excellence in Translating Nutritional Science to Good Health ; The University of Adelaide ; Level 6 ; Eleanor Harrald Building ; North Terrace ; Adelaide ; South Australia ; 5000 ; Australia
  4. Discipline of Acute Care Medicine ; The University of Adelaide ; North Terrace ; Adelaide ; South Australia ; 5000 ; Australia
  5. Diabetes Division ; Department of Medicine I ; St. Josef-Hospital ; Ruhr-University Bochum ; Gudrunstra脽e 56 ; Bochum ; 44791 ; Germany
  6. Diabetes Centre ; Bad Lauterberg ; Kirchberg 21 ; Bad Lauterberg ; Harz ; 37431 ; Germany
  
• 刊名：Critical Care
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：19
• 期：1
• 全文大小：898 KB
• 参考文献：1. Dungan, KM, Braithwaite, SS, Preiser, JC (2009) Stress hyperglycaemia. Lancet 373: pp. 1798-807 CrossRef
  2. Umpierrez, GE, Isaacs, SD, Bazargan, N, You, X, Thaler, LM, Kitabchi, AE (2002) Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab 87: pp. 978-82 CrossRef
  3. Egi, M, Bellomo, R, Stachowski, E, French, CJ, Hart, GK, Hegarty, C (2008) Blood glucose concentration and outcome of critical illness: the impact of diabetes. Crit Care Med 36: pp. 2249-55 CrossRef
  4. Deane, AM, Horowitz, M (2013) Dysglycaemia in the critically ill 鈥?significance and management. Diabetes Obes Metab 15: pp. 792-801 CrossRef
  5. Krinsley, JS, Meyfroidt, G, Berghe, G, Egi, M, Bellomo, R (2012) The impact of premorbid diabetic status on the relationship between the three domains of glycemic control and mortality in critically ill patients. Curr Opin Clin Nutr Metab Care 15: pp. 151-60 CrossRef
  6. Plummer, MP, Bellomo, R, Cousins, CE, Annink, CE, Sundararajan, K, Reddi, BA (2014) Dysglycaemia in the critically ill and the interaction of chronic and acute glycaemia with mortality. Intensive Care Med 40: pp. 973-80 CrossRef
  7. Investigators, N-SS, Finfer, S, Liu, B, Chittock, DR, Norton, R, Myburgh, JA (2012) Hypoglycemia and risk of death in critically ill patients. N Engl J Med 367: pp. 1108-18 CrossRef
  8. Iersel, FM, Slooter, AJ, Vroegop, R, Wolters, AE, Tiemessen, CA, Rosken, RH (2012) Risk factors for hypoglycaemia in neurocritical care patients. Intensive Care Med 38: pp. 1999-2006 CrossRef
  9. Egi, M, Bellomo, R, Stachowski, E, French, CJ, Hart, G (2006) Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology 105: pp. 244-52 CrossRef
  10. Krinsley, JS (2008) Glycemic variability: a strong independent predictor of mortality in critically ill patients. Crit Care Med 36: pp. 3008-13 CrossRef
  11. Krinsley, J, Schultz, MJ, Spronk, PE, Braam, HF, Sluijs, JP, Melot, C (2011) Mild hypoglycemia is strongly associated with increased intensive care unit length of stay. Ann Intensive Care 1: pp. 49 CrossRef
  12. Krinsley, JS, Egi, M, Kiss, A, Devendra, AN, Schuetz, P, Maurer, PM (2013) Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study. Crit Care 17: pp. R37 CrossRef
  13. Vilsboll, T, Krarup, T, Madsbad, S, Holst, JJ (2003) Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul Pept 114: pp. 115-21 CrossRef
  14. Ahren, B (2011) The future of incretin-based therapy: novel avenues鈥搉ovel targets. Diabetes Obes Metab 13: pp. 158-66 CrossRef
  15. Inzucchi, SE, Bergenstal, RM, Buse, JB, Diamant, M, Ferrannini, E, Nauck, M (2012) Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 35: pp. 1364-79 CrossRef
  16. Deane, AM, Chapman, MJ, Fraser, RJ, Burgstad, CM, Besanko, LK, Horowitz, M (2009) The effect of exogenous glucagon-like peptide-1 on the glycaemic response to small intestinal nutrient in the critically ill: a randomised double-blind placebo-controlled cross over study. Crit Care 13: pp. R67 CrossRef
  17. Deane, AM, Chapman, MJ, Fraser, RJ, Summers, MJ, Zaknic, AV, Storey, JP (2010) Effects of exogenous glucagon-like peptide-1 on gastric emptying and glucose absorption in the critically ill: relationship to glycemia. Crit Care Med 38: pp. 1261-9
  18. Deane, AM, Summers, MJ, Zaknic, AV, Chapman, MJ, Fraser, RJ, Bartolomeo, AE (2011) Exogenous glucagon-like peptide-1 attenuates the glycaemic response to postpyloric nutrient infusion in critically ill patients with type-2 diabetes. Crit Care 15: pp. R35 CrossRef
  19. Singer, P, Pichard, C, Heidegger, CP, Wernerman, J (2010) Considering energy deficit in the intensive care unit. Curr Opin Clin Nutr Metab Care 13: pp. 170-6 CrossRef
  20. Lee, MY, Fraser, JD, Chapman, MJ, Sundararajan, K, Umapathysivam, MM, Summers, MJ (2013) The effect of exogenous glucose-dependent insulinotropic polypeptide in combination with glucagon-like peptide-1 on glycemia in the critically ill. Diabetes Care 36: pp. 3333-6 CrossRef
  21. Edholm, T, Degerblad, M, Gryback, P, Hilsted, L, Holst, JJ, Jacobsson, H (2010) Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin鈥揼lucose homeostasis. Neurogastroenterol Motil 22: pp. 1191-200.e1315 CrossRef
  22. Christensen, M, Vedtofte, L, Holst, JJ, Vilsboll, T, Knop, FK (2011) Glucose-dependent insulinotropic polypeptide: a bifunctional glucose-dependent regulator of glucagon and insulin secretion in humans. Diabetes 60: pp. 3103-9 CrossRef
  23. Vilsboll, T, Knop, FK, Krarup, T, Johansen, A, Madsbad, S, Larsen, S (2003) The pathophysiology of diabetes involves a defective amplification of the late-phase insulin response to glucose by glucose-dependent insulinotropic polypeptide-regardless of etiology and phenotype. J Clin Endocrinol Metab 88: pp. 4897-903 CrossRef
  24. Chia, CW, Carlson, OD, Kim, W, Shin, YK, Charles, CP, Kim, HS (2009) Exogenous glucose-dependent insulinotropic polypeptide worsens post prandial hyperglycemia in type 2 diabetes. Diabetes 58: pp. 1342-9 CrossRef
  25. Singh, SK, Bartoo, AC, Krishnan, S, Boylan, MO, Schwartz, JH, Michael Wolfe, M (2008) Glucose-dependent insulinotropic polypeptide (GIP) stimulates transepithelial glucose transport. Obesity 16: pp. 2412-6 CrossRef
  26. Meier, JJ, Gallwitz, B, Siepmann, N, Holst, JJ, Deacon, CF, Schmidt, WE (2003) Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia 46: pp. 798-801 CrossRef
  27. Christensen, M, Calanna, S, Holst, JJ, Vilsboll, T, Knop, FK (2013) Glucose-dependent insulinotropic polypeptide: blood glucose stabilizing effects in patients with type 2 diabetes. J Clin Endocrinol Metab 99: pp. jc20133644 CrossRef
  28. Deane, AM, Wong, GL, Horowitz, M, Zaknic, AV, Summers, MJ, Bartolomeo, AE (2012) Randomized double-blind crossover study to determine the effects of erythromycin on small intestinal nutrient absorption and transit in the critically ill. Am J Clin Nutr 95: pp. 1396-402 CrossRef
  29. Deane, AM, Rayner, CK, Keeshan, A, Cvijanovic, N, Marino, Z, Nguyen, NQ (2014) The effects of critical illness on intestinal glucose sensing, transporters, and absorption. Crit Care Med 42: pp. 57-65 CrossRef
  30. Knop, FK, Vilsboll, T, Hojberg, PV, Larsen, S, Madsbad, S, Holst, JJ (2007) The insulinotropic effect of GIP is impaired in patients with chronic pancreatitis and secondary diabetes mellitus as compared to patients with chronic pancreatitis and normal glucose tolerance. Regul Pept 144: pp. 123-30 CrossRef
  31. Mentis, N, Vardarli, I, Kothe, LD, Holst, JJ, Deacon, CF, Theodorakis, M (2011) GIP does not potentiate the antidiabetic effects of GLP-1 in hyperglycemic patients with type 2 diabetes. Diabetes 60: pp. 1270-6 CrossRef
  32. Hojberg, PV, Vilsboll, T, Rabol, R, Knop, FK, Bache, M, Krarup, T (2009) Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia 52: pp. 199-207 CrossRef
  33. Zhou, J, Livak, MF, Bernier, M, Muller, DC, Carlson, OD, Elahi, D (2007) Ubiquitination is involved in glucose-mediated downregulation of GIP receptors in islets. Am J Physiol Endocrinol Metab 293: pp. E538-47 CrossRef
  34. Schvarcz, E, Palmer, M, Aman, J, Horowitz, M, Stridsberg, M, Berne, C (1997) Physiological hyperglycemia slows gastric emptying in normal subjects and patients with insulin-dependent diabetes mellitus. Gastroenterology 113: pp. 60-6 CrossRef
  35. Deane, AM, Summers, MJ, Zaknic, AV, Chapman, MJ, Bartolomeo, AE, Bellon, M (2011) Glucose absorption and small intestinal transit in critical illness. Crit Care Med 39: pp. 1282-8 CrossRef
  36. Vilsboll, T, Krarup, T, Sonne, J, Madsbad, S, Volund, A, Juul, AG (2003) Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab 88: pp. 2706-13 CrossRef
  37. Christensen, MB, Calanna, S, Holst, JJ, Vilsboll, T, Knop, FK (2014) Glucose-dependent insulinotropic polypeptide: blood glucose stabilizing effects in patients with type 2 diabetes. J Clin Endocrinol Metab 99: pp. E418-26 CrossRef
  38. Galiatsatos, P, Gibson, BR, Rabiee, A, Carlson, O, Egan, JM, Shannon, RP (2014) The glucoregulatory benefits of glucagon-like peptide-1 (7鈥?6) amide infusion during intensive insulin therapy in critically ill surgical patients: a pilot study. Crit Care Med 42: pp. 638-45 CrossRef
  39. Abuannadi, M, Kosiborod, M, Riggs, L, House, JA, Hamburg, MS, Kennedy, KF (2013) Management of hyperglycemia with the administration of intravenous exenatide to patients in the cardiac intensive care unit. Endocr Pract 19: pp. 81-90 CrossRef
  40. D'Alessio, DA (2011) What if gut hormones aren鈥檛 really hormones: DPP-4 inhibition and local action of GLP-1 in the gastrointestinal tract. Endocrinology 152: pp. 2925-6 CrossRef
  
• 刊物主题：Intensive / Critical Care Medicine; Emergency Medicine;
• 出版者：BioMed Central
• ISSN：1364-8535

文摘

Introduction Insulin is used to treat hyperglycaemia in critically ill patients but can cause hypoglycaemia, which is associated with poorer outcomes. In health glucose-dependent insulinotropic polypeptide (GIP) is a potent glucose-lowering peptide that does not cause hypoglycaemia. The objectives of this study were to determine the effects of exogenous GIP infusion on blood glucose concentrations, glucose absorption, insulinaemia and gastric emptying in critically ill patients without known diabetes. Methods A total of 20 ventilated patients (Median age 61 (range: 22 to 79) years, APACHE II 21.5 (17 to 26), BMI 28 (21 to 40) kg/m2) without known diabetes were studied on two consecutive days in a randomised, double blind, placebo controlled, cross-over fashion. Intravenous GIP (4 pmol/kg/min) or placebo (0.9% saline) was infused between T鈥?鈥夆垝60 to 300聽minutes. At T0, 100聽ml of liquid nutrient (2聽kcal/ml) containing 3-O-Methylglucose (3-OMG), 100 mcg of Octanoic acid and 20聽MBq Tc-99聽m Calcium Phytate, was administered via a nasogastric tube. Blood glucose and serum 3-OMG (an index of glucose absorption) concentrations were measured. Gastric emptying, insulin and glucagon levels and plasma GIP concentrations were also measured. Results While administration of GIP increased plasma GIP concentrations three- to four-fold (T鈥?鈥夆垝60 23.9 (16.5 to 36.7) versus T鈥?鈥? 84.2 (65.3 to 111.1); P 300 4217 (1891 to 7715) versus 1232 (293 to 4545) pg/ml.300聽minutes; P鈥?鈥?.04), there were no effects on postprandial blood glucose (AUC300 2843 (2568 to 3338) versus 2819 (2550 to 3497) mmol/L.300聽minutes; P鈥?鈥?.86), gastric emptying (AUC300 15611 (10993 to 18062) versus 15660 (9694 to 22618) %.300聽minutes; P鈥?鈥?.61), glucose absorption (AUC300 50.6 (22.3 to 74.2) versus 64.3 (9.9 to 96.3) mmol/L.300聽minutes; P鈥?鈥?.62) or plasma insulin (AUC300 3945 (2280 to 6731) versus 3479 (2316 to 6081) mU/L.300聽minutes; P鈥?鈥?.76). Conclusions In contrast to its profound insulinotropic effect in health, the administration of GIP at pharmacological doses does not appear to affect glycaemia, gastric emptying, glucose absorption or insulinaemia in the critically ill patient. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12612000488808. Registered 3 May 2012.