The metabolic syndrome is defined by a cluster of interconnected biochemical and clinical parameters associated with visceral obesity, which increase the risk of mortality for all causes. The main factors that contribute to the syndrome are insulin resistance, dyslipidemia, endothelial dysfunction, elevated blood pressure, a hypercoagulable and inflammatory state. Several definitions of MetS have been proposed (Table 4.1) [1–6], many of them being focused on insulin resistance. The ATPIII and IDF definitions employ measures that are readily available to physicians, thus facilitating their clinical application, although discrepancies may arise when the definition is applied to different ethnic groups [7]. In particular, the risk of type 2 diabetes mellitus (T2DM) increases at much lower levels of obesity in Asians compared to Europeans. Therefore, a new set of criteria with ethnic/racial specific cutoffs has been recently proposed [8].

The obese status is associated with a spectrum of cardiovascular disorders ranging from a hyperdynamic circulation with subclinical myocardial structural changes to overt heart failure. Occurrence of obesity cardiomyopathy as a distinct entity has been proposed. Obesity cardiomyopathy may result from a complex interaction between functional, metabolic, and toxic factors, including an expansion of the blood volume, insulin resistance, activation of the sympathetic nervous system, and cardiac lipotoxicity.

Study performed by ultrasonic tissue characterization in a series of severely obese healthy subjects showed early myocardial structural and functional alterations that were almost completely normalized after weight loss achieved by bariatric surgery [19, 20].

Increasing evidence suggests that NAFLD represents the hepatic component of the metabolic syndrome and the most common cause of abnormal liver tests in the adult population of Western countries. NAFLD is a consequence of visceral fat accumulation and is defined by a lipid accumulation >5 % in hepatic tissue in the absence of chronic alcohol consumption [21]. NAFLD is characterized by a wide spectrum of liver damage ranging from simple steatosis to advanced fibrosis and to cryptogenic cirrhosis through steatohepatitis (NASH), and, ultimately, to hepatocellular carcinoma [22, 23]. The prevalence and severity of NAFLD increases with increments of body mass index. NAFLD is usually asymptomatic, and hepatomegaly can be the only objective sign. No combination of clinical or biochemical abnormalities can accurately differentiate the spectrum of NAFLD, and only liver biopsy can establish the diagnosis. Whole hepatic enlargement is proportional to the severity of the metabolic syndrome, and various imaging methodologies can be used for the estimation of liver volume. Recently, an ultrasound technique has been introduced, which measures the hepatic left lobe volume (HLLV) [24, 25]. HLLV was tightly correlated to intra-abdominal fat and an excellent indicator of visceral adiposity, clustering with the parameters defining the metabolic syndrome. Furthermore, after weight loss achieved by gastric banding, reduction of the HLLV was the best single predictor of improvement of various cardiometabolic risk factors.

Obesity hypoventilation syndrome (OHS) and obstructive sleep apnea syndrome (OSAS) are the main pulmonary dysfunctions associated with obesity [26]. Fat accumulation in the upper site of the body leads to reduction in chest wall compliance and respiratory muscle performance, with consequent hypoxemia and progressively worsening disability. OHS is defined as the combined presence of obesity and awake arterial hypercapnia (PaCO₂ >45 mmHg) in the absence of other causes of hypoventilation.

OSAS is characterized by repetitive upper airway occlusion episodes leading to apnea with arousal being required to reestablish airway patency. OSAS affects up to 7 % of the adult male population, and its prevalence increases with age. The apnea/hypopnea index (AHI) that indicates the frequency of the apnea/hypopnea episodes per hour of sleep, is commonly used to quantify the severity of OSAS. The pathophysiology of OSAS is mainly based on the imbalance between the collapsing forces of the upper airway during inspiration and the counteracting forces of the upper airway dilating muscles [27]. Obesity and male gender are the most important risk factors for sleep apnea [28]. The OSAS prevalence is 12- to 30-fold higher among morbidly obese patients than in the general population [29] with visceral obesity being more strictly associated to OSAS; the accumulation of adipose tissue in the neck and in the pharyngeal structures is one of the main mechanisms involved in this association. Noteworthy, OSAS itself may predispose individuals to worsening obesity because of sleep deprivation, daytime somnolence, and disrupted metabolism [30]. Sleep fragmentation and chronic intermittent hypoxia are likely to play a prevalent role in causing the increased morbidity and mortality in comparison with simple obesity [31], and OSAS is indeed associated [32] with an increased prevalence of metabolic syndrome, hypertension, insulin resistance and T2DM, and cardiovascular illness, such as transient ischemic attacks, stroke, cardiac arhythmias, myocardial infarction, and pulmonary hypertension [33, 34].

Major depression, binge eating disorder (BED), and night eating syndrome (NES) are commonly associated with obesity. Current evidence suggests that there is a temporal association between obesity and depression, which would make obesity a risk factor for the development of the disease. However, a temporal depression to obesity relationship has also been observed, which may be due to eating and sleeping disturbances as well as the use of antidepressant medications [35].

Early-onset obesity is associated with the development of eating disorders, body-dysmorphic disorders, and low self-esteem. In a recent study including 280 obese subjects, patients with early onset obesity displayed a higher burden of depressive spectrum symptomatology than patients who developed obesity only during adulthood [36].

BED, defined as the ingestion of large amount of food in a short period of time (>2H) accompanied by a sense of loss of control over eating, is another psychiatric disorder independently associated with obesity and depression. Its prevalence increases with severity of the obese state. NES is characterized by evening hyperphagia, meaning that at least 25 % of the daily caloric intake is consumed after the last evening meal or that two or more nocturnal eating episodes occur per week. NES is more common among obese persons although it is not exclusive to them [37]. About one in five obese subjects assessed for eligibility for bariatric surgery present with mood and/or personality disorders [38, 39]. A careful psychological and/or psychiatric assessment and treatment should always be provided to establish the eligibility for bariatric surgery, to improve the postoperative outcome and to reduce the risk of complications.

Osteoarthritis (OA) is the most important musculoskeletal disease associated with obesity [40]. It is a disabling degenerative joint disorder characterized by pain, limitation of mobility, and an overall negative impact on quality of life. The incidence and progression of OA in obese subjects is increased both in weight-bearing and non-weight-bearing joints. Weight loss contribute to improve symptoms and to delay the progression of joint disease. The pathogenesis of obesity-related OA is multifactorial: Both mechanical factors as well as metabolic factors appear to be involved, including the low-grade inflammatory state associated with obesity and the abnormal expression of adypokines. Weight loss may improve both pain and joint function, and osteoarthritis should be considered when assessing the indications of obese candidates to bariatric surgery.

The International Agency for Research into Cancer and the World Cancer Research Fund (WCRF) [41] have reported a strong association of obesity with the endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal cancers, whereas other types of malignancies such as leukemia, non-Hodgkin’s lymphoma, multiple myeloma, malignant melanoma, and thyroid tumors are less frequent [42]. The main pathogenic mechanisms include BMI, excess weight, particularly visceral fat accumulation, diet, and lifestyle factors. Furthemore, biological mechanisms appear to be involved, such as hyperinsulinemia and insulin resistance, the activities of IGFs and IGF binding proteins, sex hormones and SHBG, low-grade inflammation, changes in adipose tissue production of adipokines and vascular growth factors, oxidative stress, endocrine disruptors, and alterations in immune function.