Type 2 diabetes mellitus (DM) is a disease commonly associated with obesity [13]. The incidence of developing type 2 DM increases with the degree of excess weight [13] with a prevalence rate as high as 49 % in patients who are obese [14]. It is a metabolic disorder primarily characterized by abnormal carbohydrate metabolism and the clinical presence of hyperglycemia. The disease may range from a relative defect in insulin secretion, insulin resistance at the cellular level, or varying degrees of both [6]. It is associated with many long-term macrovascular and microvascular complications affecting the eyes, kidneys, and nerves, as well as an increased risk for cardiovascular disease.

The relationship between obesity and thyroid disease is intertwined. Thyroid hormones regulate energy metabolism, which can affect body weight and composition. Both subclinical and overt hypothyroidism are frequently associated with weight gain [37]. Furthermore, evidence suggests that BMI has been positively associated with TSH level and negatively associated with serum free T4 (FT4) among euthyroid obese and overweight individuals [38, 39]. These alterations seem rather a consequence than a cause of obesity since weight loss leads to a normalization of elevated TSH [40, 41]. It has been hypothesized the correlation between TSH and BMI could be mediated by leptin through the following paths: (1) regulates energy homeostasis by informing the central nervous system about adipose tissue reserves [39]; (2) modulates the neuroendocrine and behavior responses to overfeeding; (3) has effects on hypothalamic–pituitary–thyroid axis [42]; and (4) affects thyroid deiodinase activities with activation of T4 to T3 conversion [43].

Obesity is a well-known cause of hypertension [8, 45, 46]. It is estimated that obesity accounts for 65–75 % of essential hypertension [46]. 50–60 % of obese persons have mild to moderate hypertension, while 5–10 % have severe hypertension [47]. Although the exact etiology is unknown, there are four suggestions to explain this causality: (1) a change in hemodynamics—obese persons require a greater total blood volume in order to perfuse extra adipose tissue [8, 46]. This increase in blood volume leads to a greater cardiac output and stroke volume [8]. When combined with increased peripheral vascular resistance, this may lead to greater intravascular pressures [8], (2) physical compression of the kidneys—intra-abdominal pressure caused by excess abdominal fat physically compresses the kidneys, renal veins, and ureters which can further increase blood pressure [46]. This pressure leads to impaired renal-pressure natriuresis and increased sodium reabsorption [47]; (3) changes in the renin–angiotensin–aldosterone system (RAAS) ; and (4) increased sympathetic nervous system activity [46]—obesity is associated with increased plasma renin activity, angiotensinogen, angiotensin-converting enzyme activity, angiotensin II, and aldosterone [46]. This leads to vasoconstriction, sodium and fluid retention, and an increase in the sympathetic nervous system [46].

Obesity is also a well-known cause of dyslipidemia [48]. Typically obese individuals display increased triglycerides and free fatty acids, decreased high-density lipoprotein (HDL) cholesterol, with normal or slightly increased low-density lipoprotein (LDL) cholesterol [48]. Persons with a BMI over 40 are almost twice as likely to develop hyperlipidemia [49]. The decision to prescribe cholesterol lowering medication may be informed by the patient’s Framingham Risk Score (FRS) , which equates to their 10 year estimated risk of developing cardiovascular disease [50]. This score takes into account age, gender, total cholesterol, HDL cholesterol, smoking, diabetes, and blood pressure [50].

Obesity and many of its comorbidities such as hypertension and dyslipidemia [51] accelerate the accumulation of intraluminal fatty plaques and therefore progression of atherosclerosis [52]. Plaques may cause stenosis, leading to angina or ischemia, or may also cause a thrombus or complete blockage leading to myocardial infarction or stroke [52]. Moreover, obese persons have increased levels of fibrinogen, factor VII, factor VIII, and plasminogen activator inhibitors, and decreased levels of antithrombin III and fibrinolytic activity [47]. This alteration in coagulation, when combined with increased abdominal pressures, venous stasis, valve incompetence, and decreased mobility, increases the risk for venous thromboembolism [8, 10] as well as dermatologic conditions in the lower extremities such as ulcers and cellulitis [10].

It is estimated that the risk for congestive heart failure increases by 5 % for men and 7 % for women for every 1 unit increase in BMI [8]. As mentioned above, obese persons have a greater total blood volume and cardiac output [45, 47]. Since the heart rate remains unchanged, this increase in cardiac output is mainly a result of an increase in stroke volume [43, 47]. The left ventricle becomes dilated and hypertrophic because it ejects more blood with each contraction [10, 45]. This leads to irreversible damage [10], impaired function, and an increased risk for cardiac failure [8, 10, 45]. To further complicate this problem, adipocytes may gradually infiltrate the cardiac myocytes and cause dysfunction and pressure-induced atrophy of cardiac muscle [8].

The risk for sudden cardiac death is 40 times higher in the obese population [8]. This increase in risk is most commonly as a result of coronary atherosclerosis [53] or arrhythmias related to cardiomyopathies [8, 51]. Autopsy studies indicate that up to 2/3 of sudden deaths are the result of cardiac dysfunction, 60 % of which are caused by coronary artery disease (CAD) or ischemic heart disease [53]. About 70 % of sudden cardiac deaths also show cardiomegaly, sometimes in the absence of CAD, which indicates left ventricular hypertrophy may cause sudden cardiac death related to arrhythmias [53].

Asthma is a chronic airway disease characterized by airway inflammation, hypersensitivity, and reversible air flow obstruction [60]. There is growing evidence that links obesity and asthma [61]. Asthma symptoms in the obese individual can be more severe and difficult to treat as there is decreased responsiveness to traditional treatments [62]. According to Mokdad et al. [49], the risk of developing asthma for those with a BMI of 40 or greater is almost threefold. Although the exact mechanism is unknown, the following causes of asthma have been hypothesized: systemic inflammation due to increased adipose tissue; structural changes to the lungs due to decreased lung volumes; an increased genetic predisposition to the development of atopic allergies; the impact of pro-inflammatory markers such as leptin and adiponectin ; and the effects of excessive macronutrients intake [61–63].

There is little data on the prevalence of pulmonary hypertension (PH) in obesity; however, one study showed that 38 % of patients with primary PH were obese [64]. PH is a potentially fatal condition. It results from an increase in pulmonary artery pressure which impedes blood flow to the lungs. Proposed mechanisms for the development of PH in obesity include obstructive sleep apnea (OSA) , obesity hypoventilation syndrome (OHS) , cardiomyopathy , pulmonary thromboembolic disease , endothelial dysfunction , hyperuricemia , and the use of appetite suppressants [65]. Patients with PH present with shortness of breath on exertion, chest pain, dizziness, and swelling of the legs [65].

OSA is a sleep disorder that is characterized by episodes of breathing cessation interspersed with disordered breathing and snoring [57, 66]. Estimates are that 50 to 60 % of obese individuals have some degree of OSA [67]. A high BMI, hypertension, and male gender are several of the risk factors associated with the development of OSA (see Table 5.3 for screening criteria). Research has demonstrated that obese patients with OSA have excess fat around the soft and hard palate and tongue leading to a narrowing of the upper airway and increased airway resistance [69]. In addition to fragmented sleep, untreated OSA predisposes individuals to cardiac arrhythmias, CHF, hypertension, DM, and motor vehicle collisions [57, 70].

OHS is characterized by a trio of features: obesity, low daytime blood oxygen levels (hypoxemia), and high serum concentration of carbon dioxide (hypercapnia ) in the absence of an underlying cardiorespiratory cause [71]. The exact prevalence of OHS is unknown; however, one study estimated that OHS was present in approximately 31 % of hospitalized obese patients and the mortality rate was estimated to be 2.5 times higher at 18 months post discharge [72].

It is difficult to distinguish OHS from OSA because the clinical presentations of daytime somnolence, irritability, and mood disturbance are similar. As a result, many patients go undiagnosed until they have an episode of severe respiratory failure requiring ventilatory support in an intensive care unit setting [71]. The chronic effects of hypoxia and hypercapnia are polycythemia, PH, cardiac disturbances, and CHF, which contribute to increased mortality in this population [57].