Causes, Characteristics, and Consequences of Metabolically Unhealthy Normal Weight in Humans

Abstract

A BMI in the normal range associates with a decreased risk of cardiometabolic disease and all-cause mortality. However, not all subjects in this BMI range have this low risk. Compared to people who are of normal weight and metabolically healthy, subjects who are of normal weight but metabolically unhealthy (∼20% of the normal weight adult population) have a greater than 3-fold higher risk of all-cause mortality and/or cardiovascular events. Here we address to what extent major risk phenotypes determine metabolic health in lean compared to overweight and obese people and provide support for the existence of a lipodystrophy-like phenotype in the general population. Furthermore, we highlight the molecular mechanisms that induce this phenotype. Finally, we propose strategies as to how this knowledge could be implemented in the prevention and treatment of cardiometabolic diseases in different stages of adiposity in routine clinical practice.

Procollagen‐III peptide identifies adipose tissue‐associated inflammation in type 2 diabetes with or without nonalcoholic liver disease

“…Indeed, our findings suggest that, in presence of dysmetabolic conditions, such as T2DM and overweight/obesity, circulating PIIINP levels are mostly associated with systemic proinflammatory profile likely associated with AT expansion rather than by fat deposition into the hepatic parenchyma. Notably, these results applied to different BMI categories, identifying a phenotype at increased cardiometabolic risk likely correlated with visceral fat and AT inflammation, as also suggested by other reports …”

“…Notably, these results applied to different BMI categories, identifying a phenotype at increased cardiometabolic risk likely correlated with visceral fat and AT inflammation, as also suggested by other reports. 41,42 Thus, in absence of clinical advanced liver damage, PIIINP may not represent a useful tool for NAFLD detection and risk stratification, particularly.…”

Cardiometabolic risk factors in Thai individuals with prediabetes treated in a high‐risk, prevention clinic: Unexpected relationship between high‐density lipoprotein cholesterol and glycemia in men

“…This might have led to disruption in the expected relationships between glycemia and individual characteristics; for example, the lack of a relationship between BMI and the unexpected reduction in waist circumference with increasing HbA1c in men. In this high-risk clinic population, it is possible that there was some degree of lipodystrophy, with redistribution of fat to ectopic areas and an accompanying increase in insulin resistance 34 . However, in the absence of regional body fat measurements, we were unable to fully explore this possibility.…”

Obesity and impaired metabolic health in patients with COVID-19

“…Furthermore, the impaired metabolic health (characterized by hypertension, dyslipidaemia and hyperglycaemia) associated with obesity might also be present in those with normal weight or overweight 5 . Prediabetes, which is present in 38% of the adult population in the USA, was identified as an important risk factor for CVD and renal disease 5 . To what extent these cardiometabolic risk factors predispose individuals to severe disease independently of BMI remains to be determined.…”