Insulin sensitivity in critically ill patients: are women more insulin resistant?

Glycaemic control (GC) in intensive care unit is challenging due to significant inter- and intra-patient variability, leading to increased risk of hypoglycaemia. Recent work showed higher insulin resistance in female preterm neonates. This study aims to determine if there are differences in inter- and intra-patient metabolic variability between sexes in adults, to gain in insight into any differences in metabolic response to injury. Any significant difference would suggest GC and randomised trial design should consider sex differences to personalise care.

Insulin sensitivity (SI) levels and variability are identified from retrospective clinical data for men and women. Data are divided using 6-h blocks to capture metabolic evolution over time. In total, 91 male and 54 female patient GC episodes of minimum 24 h are analysed. Hypothesis testing is used to determine whether differences are significant (P < 0.05), and equivalence testing is used to assess whether these differences can be considered equivalent at a clinical level. Data are assessed for the raw cohort and in 100 Monte Carlo simulations analyses where the number of men and women are equal.

Demographic data between females and males were all similar, including GC outcomes (safety from hypoglycaemia and high (> 50%) time in target band). Females had consistently significantly lower SI levels than males, and this difference was not clinically equivalent. However, metabolic variability between sexes was never significantly different and always clinically equivalent. Thus, inter-patient variability was significantly different between males and females, but intra-patient variability was equivalent.

Given equivalent intra-patient variability and significantly greater insulin resistance, females can receive the same benefit from safe, effective GC as males, but may require higher insulin doses to achieve the same glycaemia. Clinical trials should consider sex differences in protocol design and outcome analyses.