Abstract
There is a strong association between obesity, insulin resistance and type 2 diabetes mellitus. Abdominal obesity appears to be a major mediator of insulin resistance and hyperinsulinemia. Insulin resistance is a pathological condition in which cells fail to respond normally to the hormone insulin. leading to high blood sugar (impaired glucose uptake in peripheral tissues, particularly in skeletal muscle.) The more life-threatening problems fall into four main areas: type 2 diabetes, cardiovascular diseases (CVD), dyslipidemia and certain types of cancers and musculoskeletal disorders. There is considerable evidence that inflammation is a primary mediator of obesity induced insulin resistance and related co-morbidities, including diabetes and CVD whereby pro-inflammatory substances and other chemokines produced by adipocytes and macrophages are able to cause insulin resistance. The major inflammatory factors include pro-inflammatory interleukins (IL-1 & IL-6) and signaling intermediate-nuclear factor kappa B cells (NF-kB), chemokines and cytokines, tumor necrosis factor alpha (TNF-α), adiponectin (ADN), circulating C-reactive protein (CRP) concentrations, toll-like receptors (Tlr), free fatty acids (FFA), oxidative stress and dietary fatty acids. Considering this viewpoint, in the present review, we have selected ten well designed clinical studies with salsalates, thiazolidinediones (TZD) and TNF-α–antagonists to discuss and analyze these emerging therapeutic approaches for the treatment of obesity induced insulin resistance and type 2 diabetes mellitus. These therapeutics provide sufficient evidence of improved glycemic control post treatment in obese patients by targeting the state of chronic inflammation that characterizes obesity and resulted in improved insulin sensitivity by reducing adipocyte pro-inflammatory cytokine expression, adipose tissue macrophage content and immune cell infiltration into adipose tissue and other inflammatory markers. Even with looking at only few studies, analyzing each pathway, the hypothesis that targeting pro-inflammatory pathways in adipocytes with TZD and salicylates as a novel approach remains supported for reducing chronic inflammation-induced insulin resistance in obese patients, with TZD emerging with the strongest effects.
Highlights
Since 1980, the global incidence of overweight and obesity has risen to the extent that almost one-third of the world population is considered being overweight or obese [1]
These studies provide evidence of reduced adipose tissue-induced inflammation after salsalate treatment and increased ADN levels, which further add to its antiinflammatory and glycaemia-controlling effects in obese patients
Group II studies [135,136,137] more strongly confirm the hypothesis of a strong therapeutic agent, as Thiazolidine diones (TZD) result in improved insulin sensitivity and decrease obesity-induced inflammation by reducing adipocyte pro-inflammatory cytokine expression, adipose tissue macrophage content and immune cell infiltration into adipose tissue
Summary
Since 1980, the global incidence of overweight and obesity has risen to the extent that almost one-third of the world population is considered being overweight or obese [1]. Abdominal obesity serves as a major contributing factor for the development of insulin resistance and hyperglycemia that characterizes diabetes, metabolic syndrome and nonalcoholic fatty liver [16,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41]. There is considerable evidence that inflammation is a primary mediator of obesity induced insulin resistance and related health problems, including diabetes and CVD [46,47,48,49,50,51,52]. The major inflammatory factors include proinflammatory cytokines (interleukins-IL) such as IL1 & IL-6 [63,64,65,66,67], chemokines and cytokines such as MCP-1 [67,68,69], tumor necrosis factor-alpha (TNF-α)
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