key to lower the burden of CVD in the society (Kundu et al. 2019b).
2.5.8 Obesity, a Major Risk Factor for Prevalent Metabolic Syndrome in Women
Firstly, maternal obesity, overweight, and gestational weight gain in women aggravate many conditions such as PCOS (polycystic ovary syndrome) which associate with increased incidence of diseases falling under metabolic abnormalities including dyslipidaemia, hypertension, glucose intolerance, and also major reproductive complications including infertility, pregnancy complications, gestational diabetes mellitus (GDM), gestational hypertension, pre‐eclampsia, and delivery of a preterm or growth‐restricted baby (Osibogun et al. 2020).
Prior studies have found that women with increased pathogenesis of PCOS are more likely to have increased subclinical CVD markers and clinical outcomes of insulin resistance. This worsens the reproductive, metabolic, and psychological behaviour of women greatly including anxiety, depression, OCD (obsessive–compulsive disorder), and poor quality of life. PCOS and its strong link with infertility and obesity (~80%) could be managed by lifestyle management of proper nutritional intake and physical activity, which is always the advised first line of treatment. A small percentage (5–10%) of weight loss has led to improved PCOS conditions in women (Chella Krishnan et al. 2018).
Secondly, the pathology of the disruption of metabolic homeostasis between men and women is different due to differences in the normal adipose physiology. The location of the white adipose tissue could be under the skin as subcutaneous adipose tissue (SAT) or in the deep abdominal region as visceral adipose tissue (VAT). It is reported that VAT depots confers more cardiometabolic risk and are higher in adult men in comparison to premenopausal women who possess more SAT depots for the storage of fat (Chella Krishnan et al. 2018). On the other hand, increased risk of cardiometabolic syndrome in middle‐aged women above 50 years of age as compared to men has been attributed to the loss of this cardiometabolic protection in postmenopausal women (Chella Krishnan et al. 2018).
Another major and most common cardiometabolic deregulation diagnosed frequently in pregnant women is GDM which involves a degree of glucose intolerance. GDM affects 5–25% of all pregnant women worldwide and is the largest group of cardiometabolic disorders in pregnant women followed by a higher risk of developing hypertension, hypercholesterolemia, and cancers of nasopharynx, lung kidney, breast, and thyroid glands (Peng et al. 2019; Han et al. 2018) (Figure 2.8). Thus, the dysregulations in cardiometabolic factors are the most common pathway for potential interrelatedness between preterm birth and CVD. It is crucial for women to control overweight through lifestyle changes to prevent the incidence of cardiometabolic disorder and potential multiple comorbidities during pregnancy and beyond (Grieger et al. 2021).
Also, cardiometabolic syndrome in women linked with obesity is due to social problems and socio‐economic cultures in many underdeveloped and developing countries where there are security and safety issues that restrict the free movement, social interactions, and physical activity of children, particularly women leading to increased weight during childhood. All these varied reasons culminate in a nearly 15% higher rate of the risk of cardiometabolic disorders, mental and physical stress facilitated by obesity in women as compared to men.
2.5.9 Childhood Obesity, a Growing Concern
Another prevailing concern worldwide is childhood obesity in both developing and developed countries. The data from NHANES (National Health and Nutrition Examination Survey) in the year 2015 and 2016 highlighted that there was gradual increase in the overall prevalence of obesity from childhood, adolescents, and youth to adults from nearly 14 to 19% and 40%, respectively. Recently, childhood obesity has seen a considerable spike and the environment around the home of the child is the most prevalent cause. Along with the prevalence of obesity, 70% of the children had a minimum of one cardiometabolic risk factor (WHO 2019a). Insulin resistance due to obesity was more prevalent in young girls than boys. In terms of number, it is alarming that around 38 million children worldwide under the age of five years were reported to be overweight in 2019 (WHO 2019b). Childhood obesity leads to breathing difficulties, increased bone injuries, and psychological breakdown. Obese children have a predisposition for premature death, insulin resistance, adult obesity, and chronic inflammation. Various studies suggest the shared link between early markers of CVD, NAFLD with paediatric obesity. Therefore, paediatric obesity and its striking association of comorbidities such as asthma, fatty liver, sleep apnea, hypertension, orthopaedic problems, and type 2 diabetes in children bear economic and psychological burden on the children as well as their families along with the health issues (Corvalán et al. 2010).
2.5.10 Cardiometabolic Syndrome Associated Cancer Facilitated by Inflammation and Obesity
The relationship between metabolic syndrome and cancer is also one of growing concerns in the last few decades. Cardiometabolic syndrome and cancer are the major contributors to the burden of chronic disease and mortality worldwide (Koene et al. 2016). There is emerging evidence for possible interaction between the two with shared risk factors suggesting a similar underlying mechanism of the pathologies (Table 2.1) (O'Neill and O'Driscoll 2015). Additionally, each individual risk factor for metabolic syndrome has also an association with cancer. While inflammation is attributed to be the one of the major amalgamating factors in the onset and progression of the diseases, additional mechanisms or factors have also been identified, which mainly includes diabetes, insulin sensitivity, and obesity (Figure 2.8). It has been reported along with other factors sharing biological roles, phosphatase and tensin homolog (PTEN) is a crucial gene involved in regulating the Akt pathway (Arora et al. 2018) and PTEN mutations are linked to regulating insulin sensitivity and obesity (Mitchell 2012). Thereby, tracking back one of the major causes of cardiometabolic syndrome is obesity. Therefore, it becomes important to understand if cancer, CVD, and obesity have a shared biology. Studies in the United States in the later nineteenth century on cancer reported the association of BMI index and cancer deaths. It was observed that men with a BMI ≥ 40 had a 52% higher death rate from all cancer, while women with a BMI ≥ 40 had a 62% higher death rate from all cancers than men and women of normal weight, respectively. Thereby, if obesity is prevented in individuals, around 10–20% of cancer deaths in the United States could be prevented.
Scientific evidence shows that metabolic syndrome and obesity are contributors to an estimated 6% of all cancers (4% in men, 7% in women) diagnosed in 2007. Beyond being a major risk factor for diabetes, which itself is a risk factor for most cancers, obesity has long been understood to be associated with increased risk of oesophageal, colon, pancreatic, postmenopausal breast, endometrial, and renal cancers. More recently, evidence has accumulated that overweight and/or obesity raise the risk of cancers of the gallbladder, liver, ovaries (epithelial), and advanced prostate cancer, as well as leukaemia (Esposito et al. 2012). The complex relation between all three can be mediated by several factors including diet, physical activity and hormonal signalling (insulin‐like growth factor signalling), oxidative stress (Dara Hope and Derek 2012). Pro‐inflammatory cytokines predominantly secreted by immune cells and also other cell types like endothelial and adipocytes affect all tissues and organ systems including the vasculature system (Dinarello and Pomerantz 2001). The aetiology of cardiometabolic syndrome involves accumulation of visceral fat. This promotes the synthesis and release of pro‐inflammatory cytokines leading to enhanced oxidative stress. Infiltration of immune cells particularly inflammatory macrophages in the adipose tissues further enhance the cytokine burden causing chronic inflammation (DeMarco et al. 2010). Pro‐inflammatory cytokines produced within adipose tissues are also found to be elevated in the serum of obese people. Inflammatory cytokines such as IL‐6, TNF‐α, leptin have been extensively associated with obesity, CVD (upto 20%), and cancer (Grivennikov and Karin 2011; Bielecka‐Dabrowa et al. 2007). Therefore, IL‐6 and TNF‐α and other potential pro‐inflammatory cytokines
