Could type 2 diabetes be a component of the post-intensive care syndrome?

The current definition of the post-intensive care syndrome (PICS) includes new or worsening impairments in physical, cognitive and/or mental health [1]. This list can encompass a broad number of dysfunctions, syndromes or specific diseases. In addition to muscular weakness and post-trauma stress disorder cognitive, behavioral or mental changes, other disorders may arise as a result of the pathophysiological events of the acute phase of critical illness, including physiological changes or the effects of therapies. We here suggest that type 2 diabetes mellitus can be acquired during a stay in an intensive care unit (ICUacquired diabetes (ICU-AD)) as an additional component of PICS. ICU-AD will increase the risks of long-term complications and increase the burden of critical illness. Regarding the pathogenesis of ICU-AD, persisting insulin resistance (IR) is the most likely candidate because IR develops rapidly during the acute phase of critical illness, with stress hyperglycemia (SHG) representing its commonest expression [2–4]. In contrast to the hyperglycemia in type 2 diabetes, which results from the combination of progressive IR developing over years and eventually culminates in betacell secretory defect, the pathogenesis of SHG involves a much quicker and more dramatic interplay of counterregulatory hormones such as catecholamines, growth hormone, cortisol and cytokine, resulting in IR and raised hepatic glucose production (from gluconeogenesis and glycogenolysis) [3]. The adaptive mechanisms developed to survive a stress (sympathetic activity, release of pituitary hormones, inflammatory mediators) all result in a resistance to anabolic signals, including insulin [2, 3]. Teleologically, IR is considered an evolutionary preserved mechanism designed to supply higher amounts of glucose to insulin-independent tissues than to insulindependent tissues [2]. In the presence of IR, the flow of glucose will rise during the acute post-injury phase, triggering SHG [4]. The magnitude of IR should be confirmed by accurate assessments using isoglycemic hyperinsulinemic clamps. Because this technique can hardly be used in daily clinical practice, the use of physiological modeling including the determination of insulin sensitivity can be very helpful and may help to improve the quality of glycemic control. In addition to IR, other stress-related pathophysiological derangements can also contribute to the development of ICU-AD. Among other potential mechanisms, a partial inhibition of the incretin effect could be involved. Such inhibition results in a lesser release of insulin in response to enterohormones released by the duodenum, small intestine or colon in response to oral or enteral food ingestion than in healthy conditions. Finally, a role of adipokines in the modulation of IR is suspected but not convincingly supported. By analogy with gestational diabetes, a normalization of the sensitivity to insulin is expected after the resolution of the underlying condition. Contrasting with this belief, cohort studies have described the acquisition of type 2 diabetes, sometimes diagnosed very late after the resolution of the critical illness. Of note, the British National Institute for Health and Clinical Excellence [5] already recommended in 2011 screening for diabetes in patients who developed SHG after an acute coronary syndrome. Abdelhamid et al. [6] reported recently in Critical Care the results of a systematic review of the incidence of diabetes of prediabetes diagnosed at least 3 months after hospital discharge of critically ill patients. Overall, this meta-analysis supports SHG as a risk factor for incident diabetes, when the risk of subsequent diabetes in patients who experienced SHG was multiplied by 3.5 [6]. Even though these data are quite convincing, the incidence of ICU-AD might be overestimated in some studies because diabetes might be preexisting in some patients [7, 8]. Taken together, these findings underline * Correspondence: jean-charles.preiser@erasme.ulb.ac.be Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, 808 route de Lennik, 1070 Brussels, Belgium