The Metabolic Syndrome (MetS) is a constellation of co-existent abnormalities sufficiently common to suggest a unifying underpinning pathology or genetic predisposition. The concept arose from the work and observations of Jean Vague who described the association of obesity, particularly when distributed “above the umbilicus”, with diabetes, hypertension and hyperuricaemia.12
Over the last few decades the increasing prevalence of obesity has raised awareness of the metabolic syndrome, leading to
There are three (overlapping) schools of thought regarding “unifying themes” or underpinning pathophysiology.
Insulin Resistance. This hypothesis argues that the primary abnormality in the MS is peripheral resistance to insulin action. However, insulin has multiple other actions, including interaction with other endocrine loops, and it is likely that these are impaired in MS patients also. There is a close relationship with obesity, particularly central, and insulin resistance, but they are not
Endocrine abnormalities in the MetS are common, and some are likely to contribute in a causative sense whilst others are likely to be consequential.17, 18 Major players include increased circulating glucose and FFA. Leptin is increased proportional to fat mass. Additionally obesity is characterised by leptin resistance at multiple levels, including transport into the brain, with resultant diminution in central actions (including appetite suppression). IR is initially characterised by high
The relevance of the presence of MetS at the time of admission to critical care is significant. Firstly, many features/components of the MS are similar to the metabolic disturbances observed in critical illness. These include dysregulation of the HPA axis and catecholamine regulation (“Stress” response), dyslipidaemia, suppression of many endocrine axes, BP and fluid dysregulation, inflammation and insulin resistance. The second concern is that a “pre-morbid’ diagnosis of MetS may influence or
Advances in the therapy of critical illness have allowed patients to survive well beyond the initial resuscitation phase with the result that increasing numbers of patients now go on to manifest the metabolic abnormalities noticed both in the acute and in the recovery phase. It has now become apparent that there are several parallels between the “traditional metabolic syndrome” and the abnormalities seen in critical illness. These include:
Insulin resistance of sepsis and critical illness and
Adiponectin is a protein produced and secreted almost exclusively by adipocytes.7 Adiponectin is an insulin sensitising, vascular protective, anti-inflammatory protein. In addition to its effect on glucose metabolism, higher levels of adiponectin are also associated with a more favourable lipoprotein subclass, with low HDL-cholesterol and hypertriglyceridaemia associated with low adiponectin.42 Circulating adiponectin is decreased in obesity43 and is considered a biomarker for the development
Attempts to manipulate the metabolic dysregulation of critical illness and the inflammatory response have largely focussed on glucose control, which is the subject of a separate review in this publication. In recent years two other approaches are being targeted: modulation of adiponectin and the use of statins for their lipid lowering and pleiotropic effects.
The authors report no ethical or financial conflicts of interest in the preparation of this document. The metabolic dysregulation in critical illness bears similarities to those seen in the metabolic syndrome. Compared to those without the metabolic syndrome, patients with this syndrome may be at a higher risk of morbidity and mortality if admitted with critical illness. Emerging data suggest that adiponectin, a key adipokine in the metabolic syndrome, may play an important role inPractice points
Additionally, the down regulation of ADPN receptor mRNA in white blood cells in endotoxemia [27], negative correlation between ADPN and Sequential Organ Failure Assessment (SOFA) score [25], and higher levels of ADPN during recovery compared to ICU stay [11] have been stated previously. These reports could advance the argument that ADPN modulation during critical illness might ameliorate the inflammatory responses, improve glucose tolerance and reduce need to vasopressors [28]. However, there are controversial data on metabolic role of ADPN in critically ill patients.
In septic shock, clinical studies have established a link between lipid metabolism (hypertriglyceridemia and decrease in HDL and LDL-cholesterol), insulin resistance and systemic inflammatory response syndrome (SIRS) [1–4].
The recent 2009 H1N1 pandemic showed once again that severe or fatal influenza in people of any age largely affects those with specific underlying high-risk conditions (Van Kerkhove et al., 2011). These conditions share one feature in common: chronic low-grade inflammation that is associated with what cardiovascular scientists call metabolic syndrome (Cornier et al., 2008; Robinson et al., 2011). Metabolic syndrome is found in patients with cardiopulmonary diseases (Kupeli et al., 2010; Minas et al., 2011), diabetes mellitus (Romeo et al., 2012), hepatic and renal diseases (Stepanova et al., 2010; Slee, 2012); obesity (Lumeng and Saltiel, 2011); and asthma (Agrawal et al., 2011).