Glycated haemoglobin and the risk of postoperative complications in people without diabetes: a prospective population-based study in UK Biobank

Abstract

The aim of our study was to clarify the association between glycated haemoglobin (HbA_1c ) and postoperative outcomes in people without an existing diagnosis of diabetes. Half a million adults were recruited into the UK Biobank prospective cohort study between March 2006 and October 2010. We divided participants into three groups: no diagnosis of diabetes and HbA_1c < 42 mmol.mol^-1 ; no diagnosis of diabetes and elevated HbA_1c (≥ 42 mmol.mol^-1 with no upper limit); and prevalent diabetes (regardless of HbA_1c concentration) at recruitment. We followed up participants by linkage with routinely collected hospital data to determine any surgical procedures undertaken after recruitment and the associated postoperative outcomes. Our main outcome measure was a composite primary outcome of 30-day major postoperative complications and 90-day all-cause mortality. We used logistic regression to estimate the odds of the primary outcome by group. We limited analyses to those who underwent surgery within one year of recruitment (n = 26,653). In a combined effects logistic regression model, participants not known to have diabetes with HbA_1c ≥ 42 mmol.mol^-1 had increased odds of the primary outcome (OR [95% CI] 1.43 [1.02-2.02]; p = 0.04), when compared with those without diabetes and HbA_1c < 42 mmol.mol^-1 . This effect was attenuated and no longer statistically significant in a direct effects model with adjustment for hyperglycaemia-related comorbidity (OR [95% CI] 1.37 [0.97-1.93]; p = 0.07). Elevated pre-operative HbA_1c in people without diabetes may be associated with an increased risk of complications, but the association is likely confounded by end-organ comorbidity. In contrast to previous evidence, our findings suggest that to prevent adverse postoperative outcomes, optimisation of pre-existing morbidity should take precedence over reducing HbA_1c in people without diabetes.

Keywords: glycated haemoglobin; postoperative complications; pre-diabetic state.

Figure 1

Directed acyclic graph representing the casual relationship between HbA_1c and postoperative complications. HbA_1c, glycated haemoglobin; MI, myocardial infarction; CCF, congestive cardiac disease; PVD, peripheral vascular disease; and Composite, 30‐day major postoperative complication and 90‐day all‐cause mortality. The green line from HbA_1c to the composite outcome represents the direct casual pathway of HbA_1c (direct effect). The blue risk factors represent mediators through which HbA_1c also acts. If, after adjustment of mediators, an association is found between HbA_1c and the composite outcome, this would suggest that HbA_1c is not dependent on the mediators, that is, has a direct effect on the composite outcome. A direct effect would support optimisation of HbA_1c before surgery. No direct effect would support optimisation of the mediators before surgery. [Colour figure can be viewed at wileyonlinelibrary.com]