**3. Adiponectin and the risk of developing co‐morbidities**

Some contradiction exists in literature regarding adiponectin levels in young OB patients. Total adiponectin levels are generally accepted to be lower in OB children and adolescents when compared with CT and overweight (OW) subjects [25, 32]. However, contradictory data have also been reported [12, 33].

Cardiometabolic risk factors, such as dyslipidaemia, hyperglycaemia, hypertension, central obesity and IR, tend to cluster and are associated with increased risk for cardiovascular diseases (CVDs) [1, 2]. These risk factors are already altered in early ages in OB individuals, and changes in adiponectin levels may underlie such risk. Indeed, an association of adiponectin with metabolic risk factors [1, 34] has been reported, leading to the proposal of adiponectin as a marker of cardiometabolic risk [24, 35], and as a potential predictor of obesity‐related co‐morbidities [36, 37]. An association between adiponectin levels in childhood and the probability of developing co‐morbidities in the future has been also raised [21]. In agreement, a study by Morrison et al. showed that lower levels of adiponectin in 16‐year‐ old females were related with the development of cardiometabolic risk features at the age of 23 years [38]. Another study also showed adiponectin as a predictor of cardiometabolic risk, in OW children, even when adjusted for age, gender, Tanner stage, BMI, visceral fat and IR [34].

In T2D OB adolescents, adiponectin levels were found to be lower than in normal individuals, and even lower than in OB individuals without T2D. In this population, IR appeared as a main determinant of adiponectin concentrations, more than BMI itself [2]. There are, however, controversial data about the changes in adiponectin, in OB adolescents with and without T2D [23].

In obesity, it is important to consider body fat distribution, besides weight excess. Indeed, increased abdominal obesity has been associated with lower levels of adiponectin [1, 25, 39, 40] and adiponectin was negatively associated with visceral‐to‐subcutaneous fat ratio [41]. The association between hypoadiponectinaemia and increased visceral adipose tissue (VAT) seems to appear early in life [33].

Younger age of adiposity rebound (AAR) associates with increased adiposity later in life [42, 43]. Nevertheless, no association was found between AAR and adiponectin in 10‐year‐old children, whereas an association was found between AAR and leptin [44]. A preferential relationship of AAR with increased subcutaneous adipose tissue, rather than with VAT, might partially explain why no association was found with hypoadiponectinaemia [43].

In adolescents, the increased abdominal obesity and reduced adiponectin levels are accompanied by enhanced TG and decreased levels of high‐density lipoprotein cholesterol (HDLc) [1], suggesting that central body fat distribution is also associated with a worse control on lipid metabolism.

The inverse relation of adiponectin with cardiometabolic risk appears to be accepted, especially in pubertal subjects. It is important to highlight that the diagnosis of metabolic syndrome (MS) in young children (under 10 years) should be avoided, as recommended by the International Diabetes Federation, considering the lack of age‐ and gender‐adjusted cut‐offs for MS components and the ambiguous causality evidence in such young ages relating MS and increased risk of CVD later in life [45].
