Inflammation and insulin resistance genes are activated by surgery

Journal of Clinical Endocrinology & MetabolismThis interesting paper recently published in the Journal of Clinical Endocrinology & Metabolism describes one of the reasons why support when undergoing a surgical procedure is so important (and links to the risks for delirium and accelerated dementia after surgery in the elderly). The authors set out to investigate the…

“…mechanisms behind postoperative insulin resistance and impaired glucose utilization…”

They shrewdly analyzed the expression of 21 target genes in abdominal adipose (fat) tissue from samples taken at the beginning and end of patients undergoing abdominal surgery. What did the data show?

“After surgery, both sc [subcutaneous] and omental adipose tissue mRNA levels of genes involved in the IL6 and nicotinamide phosphoribosyltransferase pathways were increased, whereas mRNA levels of insulin receptor substrate 1 and adiponectin were reduced. TNF pathway genes were differently regulated between sc and omental adipose tissue, and glucose transporter 4 mRNA levels were decreased only in omental adipose tissue.”

In other words, surgery elicits a shift in genetic expression that favors insulin resistance and inflammation. The authors conclude:

“The transcriptional output of pivotal inflammatory and insulin signaling pathway genes is altered after surgery…This could be of importance for the metabolic aberrations associated to postsurgical complications…”

This helps to understand why patients who are lucky enough to receive adjunctive support for the insulin and inflammatory signaling pathways and receptors recover faster and with less complications.

The common danger of delirium and dementia after surgery, and pre-existing neurodegeneration

British Journal of SurgeryPerhaps you saw the recent New York Times article about the devastating experience of delirium in the hospitalized elderly. This is an important topic because it is associated with persistent diminished cognitive function, dementia and earlier death; and it is surprisingly common. As a number of studies point out, it is evidence of pre-existing neurodegeneration that puts brains ‘on the edge’. In a recent study published in the British Journal of Surgery the authors…

“…evaluated the incidence of postoperative delirium (POD) in elderly patients undergoing general surgery, the risk factors associated with POD, and its impact on hospital stay and mortality.”

Their data showed a huge difference between the study subjects with post-operative delirium and those without. The average length of hospital stay was 21 days with POD versus 8 days without. Moreover the mortality rate was 19% versus 8.4% respectively. Their conclusion is very important for both doctors and patients to bear in mind:

The incidence of POD is high in elderly patients for both emergency and elective surgery, leading to an increase in hospital stay and perioperative mortality. To minimize POD, associated risk factors of co-morbidity, cognitive impairment, psychopathology and abnormal glycaemic control must be identified and treated.

Note the comment on glycemic control—this will be expanded in a subsequent post.

British Journal of AnaesthesiaAlthough the danger is more marked in the elderly because there has been more time for neurodegeneration, it is not limited to the geriatric population. A recent paper in the British Journal of Anaesthesia warns that postoperative cognitive dysfunction (POCD, impaired cognition long after the surgery) must not be overlooked:

Postoperative delirium and cognitive dysfunction (POCD)…although not limited to geriatric patients, the incidence and impact of both are more profound in geriatric patients. Delirium has been shown to be associated with longer and more costly hospital course and higher likelihood of death within 6 months or postoperative institutionalization. POCD has been associated with increased mortality, risk of leaving the labour market prematurely, and dependency on social transfer payments.”

Practitioners take note:

“Delirium as a behavioural manifestation of cortical dysfunction is associated with characteristic signs. The EEG may show diffuse slowing of background activity. A wide variety of disturbances in neurotransmitter systems has been described. Serum anticholingeric activity has been associated with delirium and may be especially important, and also other mediators such as melatonin, norepinephrine, and lymphokinespostoperative chemokines have been found to be more elevated in patients who became delirious than in matched controls.”

Regarding postoperative cognitive dysfunction:

Increased inflammatory activity may play a role in early POCD. Elevated C-reactive protein is associated with impaired mental status in elderly hip fracture patients.”

How could we argue with what the authors assert in their conclusion:

Good basic care demands identification of at-risk patients, awareness of common perioperative aggravating factors, simple prevention interventions, recognition of the disease states, and basic treatments for patients with severe hyperactive manifestations.”

American Journal of Geriatric PsychiatryIt’s not just our British colleagues who are diligently investigating this devastating phenomenon. A fascinating study published recently in the American Journal of Geriatric Psychiatry reveals evidence that pre-existing white matter lesions are a risk factor for postoperative delirium:

“Delirium is a common and critical clinical syndrome in older persons. The authors examined whether any abnormalities in the white matter (WM) assessed by diffusion tensor imaging (DTI) predisposes patients to develop delirium…”

Their data clearly showed that damage to the white matter by accelerated neurodegeneration is an important risk factor:

“The abnormalities in the deep WMs and thalamus that were mainly accelerated by aging may account for the vulnerability to postoperative delirium…”

In other words, these are brains already ‘on the edge’ and predisposed to delirium and postoperative cognitive dysfunction from neurodegeneration that has been occurring for years. Now is the time, before more damage is done, to understand what you personally need to prevent unnecessary loss of brain function with age. Another paper published around the same time in the same journal focuses on the critical point of brain reserve. The authors provide…

“…a review of original articles on cognitive and brain reserve across many conditions affecting the central nervous system, with a focus on delirium…Reserve may be a potentially modifiable characteristic. Studying the role of reserve in delirium can advance prevention strategies for delirium and may advance knowledge of reserve and its role in aging and neuropsychiatric disease generally.”

I don’t think I can overemphasize this point. It is the brains that are low on reserve due to pre-existing neurodegeneration that are prone to delirium and postoperative cognitive dysfunction with all their depredations when challenged. How is your brain reserve? How easily do you experience cognitive (memory, focus, attention) or emotional (rage, irritability, depression, etc) dysfunction when stressed? There are objective, evidence-based ways to find out the contributing underlying causes and treat them from a functional perspective if we don’t wait too long.