Glucose control therapies in the perioperative period
My PhD thesis, defended at the University of Amsterdam, covering two lines of work: how diabetes is managed around the time of surgery, and whether GLP-1 receptor agonists can safely replace insulin for perioperative glucose control — the research that became the GLOBE trial.
Funding. Novo Nordisk provided funding through its Investigator Initiated Study programme for the studies making up Chapters 5, 6 and 7 — the GLOBE trial protocol, its main results, and the cardiac substudy. No other funding sources applied to the contents of this thesis.
Summary
The thesis is in two parts. Part I looks at how patients with diabetes are actually managed around surgery: a nationwide survey found treatment goals and insulin dosing varied widely between Dutch hospitals, patients with type 1 diabetes had worse glucose control than those with type 2 despite identical protocols, and — in a randomised trial — continuing metformin through the perioperative period didn’t improve glucose control over withholding it, though it also didn’t raise lactate to a concerning degree.
Part II turns to GLP-1 receptor agonists as an alternative to insulin. A systematic review of incretin-based therapy in perioperative and intensive care found it lowered glucose and reduced insulin use without more hypoglycaemia. That groundwork led to the GLOBE trial: a multicentre, placebo-controlled study of preoperative liraglutide in cardiac surgery patients. The main result confirmed the hypothesis — liraglutide reduced the need for intraoperative insulin and improved glycaemic control throughout, with no difference in complication rates. A secondary analysis found a higher rate of normal postoperative left-ventricular function in the liraglutide group, a hypothesis-generating signal for cardioprotection worth testing further. The closing chapter discusses the newer once-weekly GLP-1 formulations and argues, on balance, for continuing them perioperatively in patients already on them.
The concluding chapter argues that the next step is a larger, complication-powered trial — the line of work that continues through the Rubicon fellowship, the Marie Skłodowska-Curie ELECTRIC fellowship, and the MERCURI programme.
Committee & supervisors
prof. dr. B. Preckel
Promotor · Amsterdam UMC, University of Amsterdam
prof. dr. M.W. Hollmann
Promotor · Amsterdam UMC, University of Amsterdam
prof. dr. J.H. de Vries
Copromotor · Amsterdam UMC, University of Amsterdam
dr. J. Hermanides
Copromotor · Amsterdam UMC, University of Amsterdam
prof. dr. W.S. Schlack
Committee · Amsterdam UMC, University of Amsterdam
prof. dr. R.J.M. Klautz
Committee · Amsterdam UMC, University of Amsterdam
prof. dr. O.R.C. Busch
Committee · Amsterdam UMC, University of Amsterdam
prof. dr. N.P. Juffermans
Committee · Amsterdam UMC, University of Amsterdam
prof. dr. B.J.M. van der Meer
Committee · Tilburg University
dr. D.H. van Raalte
Committee · VU medisch centrum
Publications included in this thesis
Same layout as the full publications page — title, authors, then journal and year linking to the open-access version or DOI where available.
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Peri-operative management of patients with diabetes mellitus in Dutch hospitals, a nation-wide survey of protocolsNed Tijdschr Anesthesiol 2019
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Lack of consensus on the peri-operative management of patients with diabetes mellitus
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Comparison of perioperative glucose regulation in patients with type 1 vs type 2 diabetes mellitus: A retrospective cross-sectional study
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Perioperative continuation of metformin does not improve glycemic control in patients with type 2 diabetes; a randomized controlled trial
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In response to: Metformin for the management of peri-operative hyperglycaemia
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Preoperative Continuation of Oral Hypoglycemic Drugs
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Potential Benefits of Sodium-Glucose Cotransporter-2 Inhibitors in the Perioperative Period
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Systematic review of incretin therapy during peri-operative and intensive care
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Study protocol of the randomised placebo-controlled GLOBE trial: GLP-1 for bridging of hyperglycaemia during cardiac surgery
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Liraglutide for perioperative management of hyperglycaemia in cardiac surgery patients: a multicentre randomized superiority trial
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Effects of Liraglutide on Myocardial Function After Cardiac Surgery: A Secondary Analysis of the Randomised Controlled GLOBE Trial
Where this leads
The GLOBE trial and its findings are the starting point for the kidney-protection and glucose-regulation work described on the main research programme, and for the full record of everything published since.