Childhood obesity is associated with metabolic complications such as insulin resistance, hypertension, dyslipidemia and inflammation, which may eventually lead to the development of cardiovascular disease (CVD) and type 2 diabetes. Nonetheless, some obese children do not show any of these cardiometabolic disturbances, and they are called metabolically healthy obese (MHO).
It has been suggested that 30% of obese adult patients are metabolically healthy, and that this group have similar insulin sensitivity to lean individuals, lower visceral and liver fat and lower intima media thickness of the carotid artery (cIMT) compared with metabolically unhealthy obese (MUO) patients. Thus, MHO phenotype basically refers to obese individuals who might not be at an increased risk of CVD. Recently, however, several papers have focused on the dangers and long-term outcomes of the MHO phenotype. Indeed, it has been shown that a high number of subjects with MHO eventually develop metabolic unhealthiness or metabolic unhealthy obesity over time, that subjects with MHO still have an increased risk of CVD, particularly heart failure, and even coronary heart disease, and that MHO phenotype MHO is still associated with future risk of metabolic syndrome and CVD.
Whether MHO is associated with subclinical signs of organ damage, such as hepatic steatosis, subclinical atherosclerosis and LVH remains to be determined in childhood. This is an important issue in light of the role of fatty liver disease and subclinical cardiovascular changes (atherosclerosis and cardiac structural abnormalities) as predictors of CV events. Therefore the objectives of the present research will be to assess in a large population of overweight/obese youth, whether MHO is associated with signs of organ damage, in comparison with age- and gender-matched normal weight subjects.
As outlined in previous sections, MHO is a complex, emerging phenotype with risks intermediate between metabolically healthy individuals with normal-weight (MHNW) and individuals who are metabolically abnormal with obesity (MUO). Compared with metabolically healthy individuals with normal-weight, individuals with obesity are at an increased risk of all-cause and cause-specific mortality and cardiovascular disease events even in the absence of metabolic abnormalities, suggesting that there is no healthy pattern of increased weight. However, compared with their peers who are MUO, individuals with MHO have lower risk of of all-cause and cause-specific mortality. Furthermore, studies suggest that individuals with MHO have similar insulin sensitivity to lean individuals, as well as lower liver fat content and lower intimal-medial thickness of the carotid artery compared to subjects who are MUO. No study, however, has evaluated in the pediatric population whether a heathy phenotype is associated with unfavorable risk profile.
In particular, whether MHO is associated with subclinical signs of organ damage, such as hepatic steatosis, subclinical atherosclerosis and LVH remains to be determined in childhood. This is an important issue in light of the role of fatty liver disease and subclinical cardiovascular changes (atherosclerosis and cardiac structural abnormalities) as predictors of CV events.
To this end, a large population of overweight/obese youth will undergo a comprehensive and complete analysis of metabolic and cardiovascular abnormalities in comparison with age- and gender-matched normal weight subjects, an approach that has not been used so far. As matter of fact, only one study with a relatively small sample size have reported the adult cardiometabolic profile of individuals identified as MHO in childhood as compared to metabolically unhealthy normal weight (MUNW) subjects and healthy NW children.
Expected results
1) To clarify whether MHO phenotype can be a healthy prototype;
2) To examine the transition between MHO and MUO phenotypes and whether lifestyle factors play a part in both development and reversal of such phenotypes.
Early identification of children and adolescents with MHO provides an excellent opportunity for primary prevention at the population level, by instituting simple lifestyle changes, such as weight loss and regular physical exercise, that can prevent conversion to MUO and development of MetS and subsequent CVD. Indeed, such pediatric-wide healthy interventions are the only hope of preventing the oncoming tsunami of MetS, diabetes, and CVD in the adult population.