Does insulin treatment during and after acute stress have ... a/hall a saturday... ·...
Transcript of Does insulin treatment during and after acute stress have ... a/hall a saturday... ·...
![Page 1: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/1.jpg)
Does insulin treatment during and after acute stress have
advantage beyond the lowering effect of blood glucose ?
Krzysztof Krzysztof StrojekStrojek
Department of Internal Diseases Diabetology and NephrologyDepartment of Internal Diseases Diabetology and Nephrology
Zabrze, Zabrze, PolandPoland
![Page 2: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/2.jpg)
Roper, N. A et al. BMJ 2001;322:1389-1393
Decreased survival in diabetic patientsDecreased survival in diabetic patients
![Page 3: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/3.jpg)
Consequences of diabetesConsequences of diabetesConsequences of diabetes
![Page 4: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/4.jpg)
Risk of perioperative complications in diabetic patientsRisk of perioperative complications in diabetic patients
�� HyperglycemiaHyperglycemia, , ketoacidosisketoacidosis
�� NeuroglycopoeniaNeuroglycopoenia ((drugsdrugs, , unadequateunadequate supervisionsupervision))
�� Perioperative complicationsPerioperative complications ((wounds’ infectionwounds’ infection, MI, , MI, healinghealing) )
![Page 5: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/5.jpg)
Metabolic deterioration at acute stress
� Hormonal disorders:
�↑ cortisol
�↑ somatotropin
�↑ catecholamines;
�↑ sympathetic overactivity;
�↓ endogenous insulin secretion;
�↓ peripheral insulin sensitivity;
� Metabolic disorders:
�↑ glicogenolisis
�↑ glukoneogenesis
�↑ proteolisis
�↑ lipolisis
�↑ ketogenesis
Metabolic deterioration at acute stress
� Hormonal disorders:
�↑ cortisol
�↑ somatotropin
�↑ catecholamines;
�↑ sympathetic overactivity;
�↓ endogenous insulin secretion;
�↓ peripheral insulin sensitivity;
� Metabolic disorders:
�↑ glicogenolisis
�↑ glukoneogenesis
�↑ proteolisis
�↑ lipolisis
�↑ ketogenesis
Elliott M Clin Anaesthesiol 1983;1: 527Elliott M Clin Anaesthesiol 1983;1: 527
![Page 6: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/6.jpg)
Van den Berghe, G. J. Clin. Invest. 2004;114:1187
Interaction between glucose toxicity and insulin deficiency in critical illness
![Page 7: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/7.jpg)
Van den Berghe J. Clin. Invest. 2004;114:1187Van den Berghe J. Clin. Invest. 2004;114:1187
Intensive insulin infusion at ICU (surgical)(goal 110 mg/dl)
![Page 8: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/8.jpg)
Insulin in critically ill (glycemia < 110 mg/dl)
Insulin in critically ill (glycemia < 110 mg/dl)
↓ 42% mortality
↓ 20% duration of intensive care
↓ 34% in-hospital mortality
↓ 46% septicemia
↓ 41% dialysis
↓ 50% red cell transfusion
↓ 44% critical illnes polyneuropathy
↓ 42% mortality
↓ 20% duration of intensive care
↓ 34% in-hospital mortality
↓ 46% septicemia
↓ 41% dialysis
↓ 50% red cell transfusion
↓ 44% critical illnes polyneuropathy
Van den Berghe N Eng J Med. 2001; 345: 1359Van den Berghe N Eng J Med. 2001; 345: 1359
![Page 9: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/9.jpg)
Intensive insulin infusion at ICU (medical)(goal 110 mg/dl)
Van den Berghe N Engl J Med 2006;354:449-461
![Page 10: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/10.jpg)
Additional metabolic effects of Additional metabolic effects of insulininsulin
� Anti-inflamatory effect
� preventing endothelial dysfunction
� preventing hypercoagulation
� anabolic effect
� improvement of dyslipidemia
� anti apoptotic effect
Van den Berghe J Clin Invest 2004;114:1187Van den Berghe J Clin Invest 2004;114:1187
![Page 11: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/11.jpg)
Ellger B Diabetes 2006; 55:1096
Subjects
Normal insulin / normoglycemia
High insulin / normoglycemia
Normal insulin / hyperglycemia
High insulin / hyperglycemia
Survival
Other parameters
?
![Page 12: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/12.jpg)
INSULIN OR HYPERGLYCEMIAINSULIN OR HYPERGLYCEMIA
Ellger B Diabetes 2006;55:1096
NI/NG
HI/NG
NI/HG
HI/HG
![Page 13: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/13.jpg)
INSULIN OR HYPERGLYCEMIAINSULIN OR HYPERGLYCEMIA
� Maintaining normoglycemia, independent of insulin levels, prevented
endothelial dysfunction, liver and kidney injury.
� Benefits of intensive insulin therapy required mainly maintenance of
normoglycemia
� Glycemia-independent actions of insulin exerted only minor, organ-
specific impact.
Ellger B Diabetes 2006;55:1096
![Page 14: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/14.jpg)
INSULIN TREATMENT IN ACUTE MIINSULIN TREATMENT IN ACUTE MI((aimaim: insulin : insulin infusioninfusion))
� ECLA- Cirulation 1998; 98:2227
� CREATE-ECLA JAMA; 2005:293:435
� Pol-GIK Caremużyński Cardiosurg Drugs Ther 1999;13:191
� Dutch GIK J Am Cardiol 2003:42: 784
Glucose/Insulin constant proportion irrespective of glycemia
No terapeutic effect
![Page 15: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/15.jpg)
INSULIN TREATMENT IN ACUTE MIINSULIN TREATMENT IN ACUTE MI((aimaim: : glucoseglucose controlcontrol))
� DIGAMI- Am J Cardiol 1995; 26:57-65- 29% reduction of mortality
� DIGAMI-2 Eur Heart J 2005; 26:650- no effect
![Page 16: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/16.jpg)
Diabetes Care 2006; 29: 765-770
![Page 17: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/17.jpg)
Malmberg K et al. BMJ 1997;314:1512-1515.Malmberg K et al. BMJ 1997;314:1512-1515.
No insulin before
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Mortality
Overall
Yrs Yrs
Control
Insulin iv
0 1 2 3 4 5 0 1 2 3 4 5
Control
p = .0111 p = .004
n=133
n=139
n=314
n=306
Insulin iv
INSULIN in acute MIINSULIN in acute MI
![Page 18: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/18.jpg)
Malmberg, K. et al. Eur Heart J 2005 26:650-661Malmberg, K. et al. Eur Heart J 2005 26:650-661
Mortality in Digami Mortality in Digami 22
![Page 19: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/19.jpg)
Insulin use in DIGAMI 2Insulin use in DIGAMI 2
44 (14,4)44 (14,4)444 (93,9)444 (93,9)446 (94,1)446 (94,1)Insulin iv Insulin iv in acute phasein acute phase
GroupGroup 33
N=306N=306
GroupGroup 22
N=473N=473
GroupGroup 11
N=474N=474
Malmberg, K. et al. Eur Heart J 2005 26:650Malmberg, K. et al. Eur Heart J 2005 26:650
124 (40,5)124 (40,5)154 (32,6)154 (32,6)Insulin Insulin sc in hospitalsc in hospital
GroupGroup 33
N=306N=306
GroupGroup 22
N=473N=473
393945458484Insulin Insulin at discharge at discharge (%)(%)
57 57 ±± 424246 46 ±± 303036 36 ±± 2222IU (IU (meanmean ±± SD)SD)
GroupGroup 33
N=306N=306
GroupGroup 22
N=473N=473
GroupGroup 11
N=474N=474
![Page 20: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/20.jpg)
Postprandial hyperglycemia and macroangiopathy
(CVD, CHD, stroke)
Postprandial hyperglycemia and macroangiopathy
(CVD, CHD, stroke)
DECODE Arch Int Med., 2001, 161DECODE Arch Int Med., 2001, 161
FPG 2 h
![Page 21: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/21.jpg)
POSTPRANDIAL HYPERGLYCEMIA AND CV RISK
HEART2D Study
POSTPRANDIAL HYPERGLYCEMIA AND CV RISK
HEART2D Study
Milicevic, Raz, Strojek: J Diabtic Compl 2005; 19:80Milicevic, Raz, Strojek: J Diabtic Compl 2005; 19:80
Acute MI
Acute MI
Type 2 diabetes(n=1355)
Type 2 diabetes(n=1355)
18 days18 days
LysPro preprandiallyLysPro preprandially
18 months18 months
Long-acting1 – 2 daily
Long-acting1 – 2 daily
Mortality
CV events
other events
metabolic control
Mortality
CV events
other events
metabolic control
![Page 22: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/22.jpg)
Ann Thorac Surg 1999; 67: 352-360Ann Thorac Surg 1999; 67: 352-360
![Page 23: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/23.jpg)
J Thorac Cardiovasc Surg 2003;125:1007J Thorac Cardiovasc Surg 2003;125:1007
Insulin infusion vs subcutanous in cardiosurgery
Ann Thorac Surg, 1999, 67; 352-362Ann Thorac Surg, 1999, 67; 352-362
![Page 24: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/24.jpg)
Scott J. et al. Stroke 1999; 30: 793-799
The Glucose Insulin in Stroke Trial (GIST)
![Page 25: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/25.jpg)
![Page 26: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/26.jpg)
Goldberg, Diabetes Care 2004; 27: 461
![Page 27: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/27.jpg)
Goldberg , Diabetes Care 2004; 27: 461Goldberg , Diabetes Care 2004; 27: 461
Efficacy of insulin infusionEfficacy of insulin infusion
![Page 28: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/28.jpg)
73
86
75
0
20
40
60
80
100
easy effective overall
improvement
[%]
MICU nursing reaction(anonymus survey)
MICU nursing reaction(anonymus survey)
Goldberg, Diabetes Care 2004; 27: 461Goldberg, Diabetes Care 2004; 27: 461
![Page 29: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/29.jpg)
Cost effectiveness Cost effectiveness by insulin by insulin useuse
-30
-25
-20
-15
-10
-5
0
Laboratory Pharmacy Imaging Total
Krinsley Chest 2006;129:644Krinsley Chest 2006;129:644
% r
eductio
n
p<0.001p<0.001
p<0.003
p<0.099
![Page 30: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/30.jpg)
Diabetes Care 2006; 29:1750–1756
![Page 31: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/31.jpg)
Diabetes Care 2006;29:1750–1756
Continuous glucose monitoring at ICU
![Page 32: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/32.jpg)
Summary
� Acute stress induced by criticall illnes causes complex metabolic and hormonal disorders
� Maintenance blood glucose in critically ill patients (both diabetic and non-diabetic)
improves survival and other outcomes
� Intrvenous infusion has an advantage over subcutaneous injections
� Trained staff and precise protocol for dose titration is necessary
� Insulin application is cost effective
� Novel (end expensive) continuous glucose monitoring devices are similarly effective as
standard methods
� Acute stress induced by criticall illnes causes complex metabolic and hormonal disorders
� Maintenance blood glucose in critically ill patients (both diabetic and non-diabetic)
improves survival and other outcomes
� Intrvenous infusion has an advantage over subcutaneous injections
� Trained staff and precise protocol for dose titration is necessary
� Insulin application is cost effective
� Novel (end expensive) continuous glucose monitoring devices are similarly effective as
standard methods
![Page 33: Does insulin treatment during and after acute stress have ... a/hall a saturday... · ↑glukoneogenesis ↑proteolisis ... Insulin iv INSULIN in acute MI. ... Microsoft PowerPoint](https://reader034.fdocuments.net/reader034/viewer/2022051722/5a95ff477f8b9aba4a8c943b/html5/thumbnails/33.jpg)
... an umbiased opinion
is always absolutely valueless
... an umbiased opinion
is always absolutely valueless
Oscar Wilde „ The Critic as Artist” 1890