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Effects of high-dose glucose–insulin–potassium on myocardial metabolism after coronary surgery in patients with Type II diabetes
Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
Department of Thoracic Physiology, Karolinska Hospital, Stockholm, Sweden.
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2001 (English)In: Clinical Science, ISSN 0143-5221, Vol. 101, no 1, 37-43 p.Article in journal (Refereed) Published
Abstract [en]

The effects of glucose–insulin–potassium (GIK) on cardiac metabolism have been studied previously in non-diabetic patients after cardiac surgery. Although patients with diabetes mellitus can be expected to benefit most from such treatment, the impact of GIK in diabetic patients undergoing cardiac surgery remains unexplored. Therefore the present study investigates the effects of high-dose GIK on myocardial substrate utilization after coronary surgery in patients with Type II diabetes. A total of 20 patients with Type II diabetes undergoing elective coronary surgery were randomly allocated to either post-operative high-dose GIK or standard post-operative care, including insulin infusion if necessary to keep blood glucose below 10 mmol/l. Myocardial substrate utilization was studied using the coronary sinus catheter technique. Haemodynamic state was assessed with the aid of Swan–Ganz catheters. High-dose GIK caused a shift towards carbohydrate utilization, with significant lactate uptake throughout the study period and significant uptake of glucose after 4 h. Arterial levels of non-esterified fatty acids and b-hydroxybutyric acid decreased, and after 1 h no significant uptake of these substrates was found. Increases in the cardiac index and stroke volume index were found in patients treated with high-dose GIK. A decrease in systemic vascular resistance was found both in the control group and in the high-dose GIK group. We conclude that high-dose GIK can be used in diabetic patients after cardiac surgery to promote carbohydrate uptake at the expense of non-esterified fatty acids and b-hydroxybutyric acid. This could have implications for treatment of the diabetic heart in association with surgery and ischaemia.

Place, publisher, year, edition, pages
2001. Vol. 101, no 1, 37-43 p.
Keyword [en]
coronary surgery, diabetes, glucose, b-hydroxybutyric acid, insulin, lactate, myocardial metabolism, non-esterified fatty acids, potassium
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-13694DOI: 10.1042/CS20010005OAI: oai:DiVA.org:liu-13694DiVA: diva2:21170
Available from: 2001-10-11 Created: 2001-10-11 Last updated: 2009-08-21
In thesis
1. Diabetes and Coronary Surgery: Metabolic and clinical studies on diabetic patients after coronary surgery with special reference to cardiac metabolism and high-dose GIK
Open this publication in new window or tab >>Diabetes and Coronary Surgery: Metabolic and clinical studies on diabetic patients after coronary surgery with special reference to cardiac metabolism and high-dose GIK
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction An increasing proportion of the patients undergoing cardiac surgery have diabetes mellitus, in particular type II diabetes. In spite of this, diabetic patients have received limited attention in this setting. Although diabetes is a metabolic disease cardiac metabolism in association with surgery has previously not been explored in diabetics. This investigation was carried out to describe the metabolic state of the heart in diabetics after cardiac surgery and to study if it is accessible to metabolic intervention with high-dose GIK. Also, the potential hazards associated with such a regime in clinical practice were evaluated. Furthermore, a comparison of the outcome in diabetic and nondiabetic patients after coronary surgery was done.

Methods Myocardial metabolism and how it was influenced by high-dose GIK was assessed with coronary sinus catheter technique in a prospective randomized study on 20 type II diabetic patients undergoing CABG (paper I, II). Safety issues concerning high-dose GIK were assessed in two retrospective studies. The potential role of metabolic interventions for neurological injury was assessed in a cohort of 775 consecutive patients undergoing CABG or combined CABG + valve surgery, in whom metabolic interventions gradually replaced traditional treatment for postoperative heart failure (paper III). A detailed analysis of blood glucose and electrolyte control was done in all cases (n=89) receiving high-dose GIK during one year (paper IV). The hemodynamic impact of highdose GIK was assessed with standard postoperative monitoring including Swan-Ganz catheters (paper II, IV). Outcome and prognosis after CABG in diabetic patients (n=540) were compared with nondiabetics (n=2239) with the aid of the institutional database comprising all isolated CABG procedures from 1995-1999 (paper V).

Results The metabolism of the diabetic heart after CABG was characterized by predominant uptake of FFA and restricted uptake of carbohydrate substrates. A high extraction rate of beta-hydroxybutyric acid and glutamate was also found. Alanine was released from the heart (paper I). High-dose GIK induced a shift towards uptake of carbohydrates, in particular lactate, at the expense of FFA and betahydroxybutyric acid (paper II). A substantial systemic glucose uptake was found during high-dose GIK treatment but the uptake tended to be lower and blood glucose higher if adrenergic drugs were used or/and if the patient was a diabetic (paper IV). High-dose GIK was associated with beneficial effects on cardiac output both in the prospective and retrospective analyses (paper II, IV). No evidence for untoward neurological effects associated with GIK treatment was found. History of cerebrovascular disease was the most important risk factor for postoperative cerebral complications and in general markers for advanced atherosclerotic disease were found to be of importance (paper III). High-dose GIK in clinical practice was associated with acceptable blood glucose and electrolyte control and no serious adverse events were recorded (paper IV). Patients with diabetes undergoing CABG had an acceptable short-term mortality that did not differ significantly from non-diabetic patients. However, diabetic patients had a higher early postoperative morbidity particularly with regard to stroke, renal- and infectious complications. Also, long-term survival was markedly reduced in diabetic patients, particularly in insulin treated patients (paper V).

Comments FFA were the main source of energy for the heart in type II diabetics after CABG whereas the uptake of carbohydrates was restricted. The high extraction rates of beta-hydroxybutyric acid and glutamate may represent an adaptation to the unfavorable metabolic situation of the post-ischemic diabetic heart. High-dose GIK can be used in type II diabetic patients after cardiac surgery to promote carbohydrate uptake at the expense of FFA and beta-hydroxybutyric acid. The magnitude of this shift was sufficient to account for the entire myocardial oxygen consumption assuming that the substrates extracted were oxidized. This could have implications for the treatment of the diabetic heart in association with surgery and ischemia. Provided careful monitoring high-dose GIK can be safely used in clinical practice and this treatment deserves further evaluation in the treatment of postoperative heart failure. High-dose GIK also provides a means for strict blood glucose control and as substantial amounts of glucose can be infused even in critically ill patients, it may prove useful for nutrition in critical care. Several of the risk factors for neurological injury identified constitute markers for advanced atherosclerotic disease, thus, also providing an explanation for the increased risk of neurological injury in diabetics after cardiac surgery. Short-term mortality was acceptable in diabetics after CABG. However, further efforts are warranted to address postoperative morbidity and late outcome. This represents a challenge as diabetic patients are accounting for an increasing proportion of the patients undergoing CABG.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2001. 64 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 687
Keyword
diabetes, heart, coronary surgery, cardiac surgery, myocardial metabolism, free fatty
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-5219 (URN)91-7219-982-2 (ISBN)
Public defence
2001-09-28, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
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Note
On the day of the public defence the status of article IV was: Submitted and the title of article IV was in the printed version: High-dose GIK in cardiac surgery - clinical safety issues and lessons learned.Available from: 2001-10-11 Created: 2001-10-11 Last updated: 2012-01-24Bibliographically approved

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Szabó, ZoltánArnqvist, HansHåkanson, ErikSvedjeholm, Rolf

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Thoracic SurgeryFaculty of Health SciencesDepartment of Thoracic and Vascular SurgeryCell BiologyDepartment of Endocrinology and Gastroenterology UHL
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