Both obesity as well as type 2 diabetes mellitus (T2D) and other metabolic disorders are causing a huge impact on global health but is in epidemic proportions right through the world. Thus, the term diabesity had to be coined. Earlier we have reviewed various therapies that can be used to treat both obesity and T2D medically including various combination therapies like topiramate with phentermine, bupropion and naltrexone, GLP1 agonists like luraglutide ,thylakoids and different plant products like monoterpenes, PTP Inhibitors etc although permanent efficacy not maintained other than by bariatric surgery .Further we discussed the use of weight neutral antidiabetic drugs once DM develops like liraglutide ,role of empagliflozin in CVOT trials .Here we discuss more of prevention along with treatment of both obesity and diabetes and once DM has developed how to treat by targeting macrophages with a lot of insight in the bioenergetics ,detailed classification of macrophages beyond M1 ,M2 dichotomy and detailed transcriptional and epigenetic regulation of macrophages. A crucial player in dysmetabolism is chronic low grade inflammation in ,that by definition is the inability to maintain homeostasis leading to loss of lipid regulation ,oxidative stress and insulin resistance .We have further reviewed role of macrophages in non-alcoholic fatty liver disease(NAFLD) and in obesity and DM .Here we further emphasize on how we can target macrophages by the newer insight on macrophage metabolism, transcriptional factors that regulate macrophages like IGF 1,HIF 1,AP,NFκB along with trying to understand the microglial control .Further emphasis on metabolism of proinflammatory macrophages utilizing glycolytic cycles whereas anti-inflammatory macrophages utilizing Oxidative phosphorylation that we have earlier reviewed in nutrients role in immuno metabolism and how deficiencies get created within the body with the vicious cycle of these metabolic features and how we need to target inflammation right at the initiation of obesity and T2DM to prevent it further worsening without affecting the immune role of these macrophages in infections.
