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Doktorsavhandling vid Karolinska Institutet |
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Nygren, JonasThe sites and mechanisms of postoperative insulin resistanceFredagen den 10 oktober 1997, kl. 9.00. Kirurgiska klinikens föreläsningssal, plan 4, Karolinska sjukhuset. |
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| ISBN: 91-628-2695-6 |
Abstract:
The Sites and Mechanisms of Postoperative Insulin Resistance
by Jonas Nygren, M.D.
Departments of Surgery and Endocrinology and Diabetes,
Karolinska Hospital and Institute, SE-171 76, Stockholm, Sweden
In Sweden with nine million inhabitants, 450,000 operations
(outpatients excluded) are performed every year resulting in
2,250,000 treatment days in hospital. Surgical operations are part of
the treatment for 44% of all patients admitted to hospital care
occupying 24% of all hospital beds. The majority of these patients
undergo an elective surgical procedure. Therefore, it is important to
reduce the side effects of surgery, such as the catabolic response.
Insulin is a key anabolic hormone which regulates not only the
metabolism of glucose, but also the metabolism of fat and protein.
Insulin resistance is a main feature of the catabolic response to
surgery and other trauma. However, the sites and mechanisms of the
postoperative insulin resistance remain to be clearly defined.
Furthermore, it is not known whether changes in postoperative insulin
sensitivity have any impact on patient outcome. Therefore, insulin
sensitivity and glucose kinetics ([6,6,2H2]-D-glucose) were
determined using hyperinsulinemic, normoglycemic clamps and indirect
calorimetry, before and after elective surgery in patients undergoing
abdominal surgery (n = 18) or total hip replacement (n = 13). The
patients were undergoing surgery after the traditional overnight fast
(n = 17) or in a carbohydrate fed state. The carbohydrate fed state
was achieved by infusions of glucose and insulin 3-4 hours before and
during surgery (n = 7) or by intake of a carbohydrate drink (400 ml,
50 g carbohydrates) 2-3 hours before surgery (n = 7).
Glucose infusion rates required to maintain normoglycemia during
clamps (M-value) were reduced after surgery in the overnight fasted
patients, indicating the development of postoperative insulin
resistance. Endogenous glucose production was moderately increased
after surgery. The suppressibility of endogenous glucose production
by insulin was preserved postoperatively. Thus, most of the reduction
in insulin sensitivity after surgery was due to a defect in glucose
disposal. Since postoperatively, a similar reduction in both glucose
oxidation and nonoxidative glucose disposal was observed, a defect in
glucose transport probably underlies a decrease in insulin
sensitivity. Energy expenditure increased after surgery and fat
oxidation rates were less suppressed by insulin infusions. Only
moderate changes were found in glucagon and cortisol levels aher
surgery. To single out the effects of surgery from the effects of the
common perioperative treatment with bed rest and hypocaloric
nutntion, insulin sensitivity was measured in healthy subjects (n =
6), before and after a 24 hour period of hypocaloric nutrition and/or
bed rest. Insulin sensitivity was reduced after 24 hours hypocalonc
nutrition alone while the same period of immobilization had no
effect.
One group of patients was treated with infusions of insulin and
glucose before and during total hip replacement and compared to
controls. In the insulin and glucose treated patients, insulin
sensitivity remained unaffected immediately after surgery while
insulin sensitivity was reduced in the control patients, undergoing
the same operation after an ovemight fast.
A more convenient way to administer carbohydrates would be as a
beverage instead of an intravenous infusion. To test the possibility
of administrating carbohydrates orally before the operation, gastric
emptying of an isoosmolar carbohydrate rich drink (400 ml, 12%
carbohydrates) was detenmined using gamma camera technique (99Tcm).
Despite increased anxiety preoperatively, gastric emptying of the
drink was completed 90 minutes after intake in patients in the
morning of surgery. When the carbohydrate drink was given to patients
2-3 hours before elective colorectal surgery, postoperative insulin
sensitivity was markedly improved as compared to patients undergoing
similar surgical procedures after an overnight fast.
Multiple regression analysis showed that 72% of the variability in
the relative reduction in insulin sensitivity after elective
abdominal surgery could be predicted by the duration of surgery (p =
0.0002) and the carbohyd rate access preoperatively (p = 0.0005).
Furthermore, the length of hospital stay was related to the degree of
postoperative insulin resistance (relative change in M-values
postoperatively vs hospital stay in postoperative days, r = -0.60, p
= 0.018).
In addition, 64% of the vanability in hospital stay was predicted by
the type of surgery (hip or abdominal) (p = 0.0001), duration of
surgery (p = 0.010) and whether the patients were fasted or
carbohydrate fed before surgery (p = 0.004). Thus, carbohydrate
feeding seems to be a better preparation than overnight fasting
before surgery by improving postoperative insulin sensitivity and
patient recovery following elective surgery.
Key words: Surgery, Insulin resistance, Glucose metabolism, Glucose clamping technique, Gastric emptying, Immobilization, Preoperative fasting, ICF-I, Hospital stay, Stable isotopes
ISBN 91-628-2695-6 Stockholm 1997
Keywords: Surgery, Insulin resistance, Glucose metabolism, Glucose clamping technique, Gastric emptying, Immobilization, Preoperative fasting, ICF-I, Hospital stay, Stable isotopes ISBN 9
