Hypothesis: Enhanced glucose availability and insulin resistance enhances an activated immune system and accounts for the obesity paradox

Abstract

Summary Many studies have demonstrated an ‘obesity paradox’ where people with obesity have reduced mortality in the context of acute critical illnesses compared to people of normal weight. In contrast, obesity is associated with reduced life expectancy in the population in general and is associated with an increased risk for type 2 diabetes, cardiovascular disease and other health problems. However, the absence of the metabolic syndrome is associated a lower mortality than when the metabolic syndrome is present regardless of body mass index status and the obesity paradox appears to only occur in association with the metabolic syndrome, but cardiorespiratory fitness modifies these outcomes. Enhanced glucose availability is important when the immune system is activated not only because it has an acute onset, a high consumption of glucose and is substantially an obligate glucose utilizer but also because it has priority over most other tissues and cells for the available glucose. Thus, for vulnerable populations, such as children with severe infections, this increases the risk of hypoglycaemia and death. The obesity paradox may be substantially a consequence of two features associated with obesity. One is endogenous glucose production (EGP). Obesity is associated with an increased capacity for EGP and thus is associated with enhanced glucose availability. Second is insulin resistance that reduces the amount of glucose metabolized by cells that are not obligate glucose utilizers and increases the release of fatty acids and glycerol from adipose stores that are alternative fuels for tissues and cells.

Correlation of TyG-BMI and TyG-WC with severity and short-term outcome in new-onset acute ischemic stroke

“…Previous experiments have shown that glucose prioritizes the immune system’s needs, sustains macrophage viability, and slows disease development ( 35 ). The other factor is insulin resistance, which limits the quantity of glucose that non-obligate glucose consumers can metabolize while increasing the production of glycerol and fatty acids through the fat pool as an alternate fuel source for tissues and cells ( 36 ). Although it is not clear whether IR is involved in the stroke-obesity paradox, IR theoretically contributes to this phenomenon.…”

<strong></strong>Thiamine and High Dose Insulin Treatment for Sepsis<strong> </strong>

“…Activation of the immune response (equivalent to the hyper inflammatory state of sepsis) in healthy adults results in a metabolic rate increase of 37-55% [4] which is equivalent to about 175-261 g of glucose because the immune system substantially uses glucose [5]. Core temperature also increases.…”

“…A negative of glycolysis is that it is unable to produce sufficient ATP on an ongoing basis for all the cells of the normal healthy organism. It is only a temporary measure for the urgent need to produce large amounts of ATP for immune cells to destroy pathogens quickly in relatively anaerobic or ischaemic tissues [5,12].…”

“…Evidence that death from sepsis is increased by a relative unavailability of glucose is also supported by the fact that patients who are hyperthermic are more likely to survive than those who are hypothermic [15]. Glucose is the dominant fuel of the activated immune system, and this system has priority for this fuel over other metabolic uses including thermoregulation [5]. Patients who can elevate body temperature during an infection have a relative excess of glucose above that needed for immune system needs.…”

Novel Pyrano[3,2-c]quinoline-1,2,3-triazole Hybrids as Potential Anti-Diabetic Agents: In Vitro α-Glucosidase Inhibition, Kinetic, and Molecular Dynamics Simulation

“…The bodies of people with DM do not produce enough insulin, which is responsible for lowering blood sugar levels . If diabetics are not treated, their blood glucose levels may increase significantly, , and this may lead to kidney failure, cardiovascular disease, blindness, and impaired wound healing. α-Glucosidase (EC 3.2.1.20) is a carbohydrate-hydrolyzing enzyme, and its catalytic activity, as an intestinal digestive enzyme, results in cleavage of poly- and disaccharides into monosaccharides (glucose), which in turn will raise blood sugar levels. , Therefore, several α-glucosidase inhibitors (AGIs) such as acarbose, voglibose, miglitol, and nojirimycin are widely used alone or in combination with insulin injection as treatment of diabetes.…”