INTRODUCTION
cardiovascular disease, MetS, TG, metabolic syndrome, T2DM, chronic progressive disease
TYPE 2 DIABETES MELLITUS, LUNG, CARDIOVASCULAR DISEASE, BLOOD, INSULIN RESISTANCE, SYNDROME, ELEVATED GLUCOSE, METABOLIC SYNDROME, HEART, HYPERTENSION, INFLAMMATORY RESPONSE
Type 2 diabetes mellitus (T2DM) is well known as a chronic progressive disease. Despite the existing variant drug classes in clinics, patients eventually fail to respond to most oral antidiabetic drugs and rely on insulin. The key issue is that T2DM patients express long‐standing insulin resistance (IR) and accompanying metabolic syndrome (MetS).The concept and meaning of MetS have been constantly evolving. In 1998, the World Health Organization recommended the use of the term “metabolic syndrome.” The National Cholesterol Education Program Adult Treatment Panel III (ATP III) devised a definition for MetS in 2001, and the American Heart Association and the National Heart, Lung, and Blood Institute updated the definition in 2005. In the updated definition, MetS is diagnosed if three or more of the following criteria are met: waist circumference ≥102 cm (men) or 88 cm (women), systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥85 mm Hg or on antihypertensive drug treatment for hypertension, fasting triglyceride (TG) level ≥1.7 mmol/L or on drug treatment for elevated TG, fasting high‐density lipoprotein cholesterol (HDL‐C) level <1.03 mmol/L (men) or 1.3 mmol/L (women) or on drug treatment for reduced HDL‐C, fasting plasma glucose (FPG) ≥5.6 mmol/L or on drug treatment for elevated glucose.Most studies have shown that MetS is associated with an approximate doubling of cardiovascular disease risk and that the risk for incident T2DM is more than five times higher in individuals with MetS compared with those without the syndrome.Peroxisome proliferator‐activated receptors (PPARs) belong to nuclear hormone receptors family, encompassing three isotypes of PPARα, PPARδ, and PPARγ. These isotypes act as key regulators of lipid and glucose metabolism, playing a central role in maintaining energy homeostasis and modulating inflammatory response.Chiglitazar is designed with a configuration‐restricted non‐thiazolidinedione chemical structure and acts as a moderately potent and well‐balanced PPAR pan‐agonist, exhibiting unique molecular mechanisms of action in vitro and in vivo,