The transition from preclinical to clinical obesity: the importance of a borderline stage

Obesity is a multifactorial health condition influenced by genetic predisposition and environmental factors, identified as a condition of persistent, mild systemic inflammation marked by an abnormal buildup of fat tissue, becoming clinical when accompanied by functional impairment of organs. This review explores the role of hyperinsulinemia and hypertriglyceridemia in driving the transition from a preclinical to a clinical state of obesity. Insulin resistance leads to compensatory hyperinsulinemia, impairing glucose homeostasis in skeletal muscle, liver, and adipose tissue. Concurrently, excessive dietary fat intake contributes to elevated triglyceride levels, which promote systemic inflammation and facilitate the onset of endocrine and cardio vascular disorders. Early risk factors, such as childhood obesity, as well as other contributors, including chronic psychological stress, alterations in gut microbiota, sleep disturbances, and vitamin D deficiency, are discussed in the context of their role in disease progression. Critically, the concept of a 'borderline' stage is introduced-a transitional phase characterized by elevated triglycerides, insulin resistance, and low-grade chronic inflammation-representing a critical point in the progression toward clinical obesity. Identifying this intermediary stage, even present in other pathologies, offers a valuable window for early interven tion, potentially preventing the establishment of chronic degenerative diseases associated with advanced obesity. Current strategies aimed at controlling hyperinsulinemia and hypertriglyceridemia, including dietary interventions, physical activity, and pharmacological approaches such as GLP-1 receptor agonists and SGLT2 inhibitors, should be considered.