REN and obesity due to melanocortin 4 receptor deficiency: Other issues that may be important for critical illness outcomes include vitamin D related effects on vascular endothelial growth factor, endothelin and the renin-angiotensin-aldosterone system.38–40 Further, comorbidities including incident hypertension, glucose intolerance, the metabolic syndrome, obesity and cardiovascular disease are all associated with low 25(OH)D and higher mortality.41–45