Feasibility of hyperinsulinemic normoglycemia strategy in critically ill patients_West China Medical Journal

Authors：

LI Yunwei ¹ , ZUO Yanyan ² ,  KANG Yan ³

1. Department of Emergency Medicine, the Fourth People’s Hospital of Langfang, the Affiliated Hospital of Chengde Medical University, Langfang, Heibei 065700, P. R. China;
2. Department of Anesthesiology, the Fourth People’s Hospital of Langfang, the Affiliated Hospital of Chengde Medical University, Langfang, Heibei 065700, P. R. China;
3. Department of Critical Care Medicine, West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

KANG Yan, Email: kang_yan_123@163.com

Keywords：

Hyperglycemia; critically ill patient; hyperinsulinemic normoglycemia strategy; glycemic control

DOI：

10.7507/1002-0179.202201106

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Objective To evaluate the feasibility of hyperinsulinemic normoglycemia strategy in critically ill patients. Methods Between January 2020 and October 2021, the critically ill patients with stress hyperglycemia in the Emergency Intensive Care Unit of the Fourth People’s Hospital of Langfang were randomly assigned into a trial group or a control group. The trial group adopted hyperinsulinemic normoglycemia therapy, while the control group adopted conventional glucose control therapy. The mean and variability (standard deviation) of blood glucose, incidences of severe hypoglycemia and abnormal hyperglycemia, as well as the percentage of blood glucose values within the target range were compared between the two groups, to evaluate the feasibility of hyperinsulinemic normoglycemia strategy in critically ill patients from the perspective of safety and effectiveness. The non-normally distributed measurement data were presented as median (lower quartile, upper quartile). Results A total of eighty patients were included, with forty cases in each group. The mean blood glucose level [6.00 (5.74, 6.70) vs. 9.51 (8.74, 10.01) mmol/L, P<0.001], the standard deviation of glucose level [1.58 (1.11, 2.15) vs. 2.20 (1.21, 2.76) mmol/L, P=0.028], and the glycemic lability index [175.52 (100.51, 346.69) vs. 408.51 (205.56, 651.91) mmol²/(L²·h·d), P<0.001] were all smaller in the trial group than those in the control group. The percentage of blood glucose values within the target range was 77.34% in the trial group and 5.33% in the control group, respectively, and the difference was statistically significant (P<0.001). No patients experienced severe hypoglycemia. There was a significant difference in the incidence of abnormal hyperglycemia between the two groups (5.08% vs. 36.16%, P<0.001). Conclusions Hyperinsulinemic normoglycemia strategy can effectively and safely provide normoglycemia, reduce glycemic variability, and achieve good glycemic control in critically ill patients. Hyperinsulinemic normoglycemia strategy may be a new approach to glycemic control in critically ill patients.

Citation： LI Yunwei, ZUO Yanyan, KANG Yan. Feasibility of hyperinsulinemic normoglycemia strategy in critically ill patients. West China Medical Journal, 2022, 37(6): 875-879. doi: 10.7507/1002-0179.202201106 Copy

1.	Van Den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med, 2001, 345(19): 1359-1367.
2.	Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med, 2008, 358(2): 125-139.
3.	Preiser JC, Devos P, Ruiz-Santana S, et al. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med, 2009, 35(10): 1738-1748.
4.	Yamada T, Shojima N, Noma H, et al. Glycemic control, mortality, and hypoglycemia in critically ill patients: a systematic review and network meta-analysis of randomized controlled trials. Intensive Care Med, 2017, 43(1): 1-15.
5.	Fu Y, Sun Y, Zhang J, et al. Intensive glucose control for critically ill patients: an updated meta-analysis. Endocr Connect, 2018, 7(12): 1288-1298.
6.	Hermanides J, Vriesendorp TM, Bosman RJ, et al. Glucose variability is associated with intensive care unit mortality. Crit Care Med, 2010, 38(3): 838-842.
7.	Egi M, Bellomo R, Reade MC. Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?. Crit Care, 2009, 13(2): 302.
8.	Zhou Z, Sun B, Huang S, et al. Glycemic variability: adverse clinical outcomes and how to improve it?. Cardiovasc Diabetol, 2020, 19(1): 102.
9.	Atamna A, Ayada G, Akirov A, et al. High blood glucose variability is associated with bacteremia and mortality in patients hospitalized with acute infection. QJM, 2019, 112(2): 101-106.
10.	Akirov A, Diker-Cohen T, Masri-Iraqi H, et al. High glucose variability increases mortality risk in hospitalized patients. J Clin Endocrinol Metab, 2017, 102(7): 2230-2241.
11.	Carvalho G, Lattermann R, Codere-Maruyama T, et al. Glucose and insulin administration while maintaining normoglycemia: the GIN concept. Minerva Anestesiol, 2013, 79(1): 74-82.
12.	Sato H, Carvalho G, Sato T, et al. Perioperative tight glucose control with hyperinsulinemic-normoglycemic clamp technique in cardiac surgery. Nutrition, 2010, 26(11/12): 1122-1129.
13.	Abd-Elsayed A, Mascha EJ, Yang D, et al. Hyperinsulinemic normoglycemia decreases glucose variability during cardiac surgery. J Anesth, 2017, 31(2): 185-192.
14.	Sato H, Lattermann R, Carvalho G, et al. Perioperative glucose and insulin administration while maintaining normoglycemia (GIN therapy) in patients undergoing major liver resection. Anesth Analg, 2010, 110(6): 1711-1718.
15.	Ryan EA, Shandro T, Green K, et al. Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes, 2004, 53(4): 955-962.
16.	Blixt C, Larsson M, Isaksson B, et al. The effect of glucose control in liver surgery on glucose kinetics and insulin resistance. Clin Nutr, 2021, 40(7): 4526-4534.
17.	谭惠文, 余叶蓉, 李秀钧. 正常血糖-高胰岛素钳夹技术在胰岛素制剂药物代谢动力学研究中的应用进展. 华西医学, 2017, 32(11): 1801-1804.
18.	Duncan AE, Sessler D, Sato H, et al. Hyperinsulinemic normoglycemia during cardiac surgery reduces a composite of 30-day mortality and serious in-hospital complications: a randomized clinical trial. Anesthesiology, 2018, 128(6): 1125-1139.
19.	Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med, 2008, 358(24): 2545-2559.
20.	Gunst J, De Bruyn A, Van den Berghe G. Glucose control in the ICU. Curr Opin Anaesthesiol, 2019, 32(2): 156-162.

1. Van Den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med, 2001, 345(19): 1359-1367.
2. Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med, 2008, 358(2): 125-139.
3. Preiser JC, Devos P, Ruiz-Santana S, et al. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med, 2009, 35(10): 1738-1748.
4. Yamada T, Shojima N, Noma H, et al. Glycemic control, mortality, and hypoglycemia in critically ill patients: a systematic review and network meta-analysis of randomized controlled trials. Intensive Care Med, 2017, 43(1): 1-15.
5. Fu Y, Sun Y, Zhang J, et al. Intensive glucose control for critically ill patients: an updated meta-analysis. Endocr Connect, 2018, 7(12): 1288-1298.
6. Hermanides J, Vriesendorp TM, Bosman RJ, et al. Glucose variability is associated with intensive care unit mortality. Crit Care Med, 2010, 38(3): 838-842.
7. Egi M, Bellomo R, Reade MC. Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?. Crit Care, 2009, 13(2): 302.
8. Zhou Z, Sun B, Huang S, et al. Glycemic variability: adverse clinical outcomes and how to improve it?. Cardiovasc Diabetol, 2020, 19(1): 102.
9. Atamna A, Ayada G, Akirov A, et al. High blood glucose variability is associated with bacteremia and mortality in patients hospitalized with acute infection. QJM, 2019, 112(2): 101-106.
10. Akirov A, Diker-Cohen T, Masri-Iraqi H, et al. High glucose variability increases mortality risk in hospitalized patients. J Clin Endocrinol Metab, 2017, 102(7): 2230-2241.
11. Carvalho G, Lattermann R, Codere-Maruyama T, et al. Glucose and insulin administration while maintaining normoglycemia: the GIN concept. Minerva Anestesiol, 2013, 79(1): 74-82.
12. Sato H, Carvalho G, Sato T, et al. Perioperative tight glucose control with hyperinsulinemic-normoglycemic clamp technique in cardiac surgery. Nutrition, 2010, 26(11/12): 1122-1129.
13. Abd-Elsayed A, Mascha EJ, Yang D, et al. Hyperinsulinemic normoglycemia decreases glucose variability during cardiac surgery. J Anesth, 2017, 31(2): 185-192.
14. Sato H, Lattermann R, Carvalho G, et al. Perioperative glucose and insulin administration while maintaining normoglycemia (GIN therapy) in patients undergoing major liver resection. Anesth Analg, 2010, 110(6): 1711-1718.
15. Ryan EA, Shandro T, Green K, et al. Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes, 2004, 53(4): 955-962.
16. Blixt C, Larsson M, Isaksson B, et al. The effect of glucose control in liver surgery on glucose kinetics and insulin resistance. Clin Nutr, 2021, 40(7): 4526-4534.
17. 谭惠文, 余叶蓉, 李秀钧. 正常血糖-高胰岛素钳夹技术在胰岛素制剂药物代谢动力学研究中的应用进展. 华西医学, 2017, 32(11): 1801-1804.
18. Duncan AE, Sessler D, Sato H, et al. Hyperinsulinemic normoglycemia during cardiac surgery reduces a composite of 30-day mortality and serious in-hospital complications: a randomized clinical trial. Anesthesiology, 2018, 128(6): 1125-1139.
19. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med, 2008, 358(24): 2545-2559.
20. Gunst J, De Bruyn A, Van den Berghe G. Glucose control in the ICU. Curr Opin Anaesthesiol, 2019, 32(2): 156-162.

West China Medical Journal

Feasibility of hyperinsulinemic normoglycemia strategy in critically ill patients

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