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Clinical Problems Caused by Obesity

, M.D., PhD, , MD, PhD, FRCP, , MD, PHD, , MD, FRCP, and , MD, FRCP.

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Last Update: January 11, 2018.

ABSTRACT

Obesity constitutes a worldwide epidemic with prevalence rates which are increasing in most Western societies and in the developing world. By 2025, if this trend continues, the global obesity prevalence will reach 18% in men and exceed 21% in women. Furthermore, it is now well-established that obesity (depending on the degree, duration, and distribution of the excess weight/adipose tissue) can progressively cause and/or exacerbate a wide spectrum of co-morbidities, including type 2 diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease, non-alcoholic fatty liver disease, reproductive dysfunction, respiratory abnormalities, psychiatric conditions, and even increase the risk for certain types of cancer. This chapter presents an overview of these links focusing on the most common obesity-related co-morbidities.

Introduction

During the past few decades, the prevalence rates of obesity [defined as body mass index (BMI) over 30 kg/m2] have been increasing at a rapid pace in both Western societies and the developing world (1), reaching 641 million adults being obese in 2014 [266 million men and 375 million women], compared to 105 million adults in 1975 [34 million men and 71 million women] (2). Notably, if this trend persists, the global obesity prevalence is predicted to rise to 18% in men and surpass 21% in women by 2025 (2). Overall, obesity can be considered a chronic relapsing and progressive disease (3) and a leading risk factor for global deaths. Furthermore, alarming trends of weight gain have also been documented for children and adolescents, undermining the present and future health status of the population (4-7). To highlight the related threat to public health, the World Health Organization (WHO) declared obesity a global epidemic, also stressing that in many cases it remains an under-recognized problem of the public health agenda (1, 8, 9).

Depending on the degree and duration of weight gain, obesity can progressively cause and/or exacerbate a wide spectrum of co-morbidities, including type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, cardiovascular disease (CVD), liver dysfunction, respiratory and musculoskeletal disorders, sub-fertility, psychosocial problems, and certain types of cancer (Figure 1).

Figure 1. Co-Morbidities Associated with Overweight and Obesity.

Image clin-prblms-obesity_figure1-1024x699.jpg

These chronic diseases have been shown to have strong correlations with BMI, and closely follow the prevalence patterns of excessive body weight in all studied populations (10, 11). Notably, the risk of developing a number of obesity-related co-morbidities rises exponentially with increasing BMI over 30 kg/m2, which is further associated with a graded increase in the relative risk of premature death, primarily from CVD (9, 10, 12). For individuals with BMI between 25 and 29.9 kg/m2 (pre-obesity) the risk of premature mortality is weaker and appears to be influenced mainly by fat distribution (Figure 2). Indeed, fat accumulation intra-abdominally and subcutaneously around the abdomen (central, abdominal, visceral, android, upper body or apple-shaped obesity) is associated with higher risk for cardiometabolic diseases, independent of BMI (13, 14). On the other hand, fat accumulation in the subcutaneous regions of hips, thighs and lower trunk (gluteofemoral, peripheral, gynoid, lower body or pear-shaped obesity) is considered less harmful or even protective against cardiometabolic complications (13, 15-17).

Figure 2. Relationship Between Body Mass Index (BMI) and Mortality (data from Calle et al. NEJM 1999 (12)).

Image clin-prblms-obesity_figure2-1024x891.jpg

Notably, individuals of certain ethnic backgrounds, regardless of the country of residence, are predisposed to central/abdominal obesity and more vulnerable to obesity-related complications (18-21). Indeed, studies in South Asian, Japanese, and Chinese populations have demonstrated significantly higher risk for insulin resistance, T2DM and CVD compared to matched overweight/obese Caucasians (22-24). Accordingly, rigorous cut-off points have been proposed for weight management among these populations, diagnosing obesity with BMI thresholds as low as 25 kg/m2 and defining central obesity based on ethnicity specific cut-off values of waist circumference (22-27).

In any case, obesity should be recognized by the treating physician as a key risk factor for the health of the patient, and appropriate weight loss treatments should be offered to patients with obesity, independently of other related co-morbidities (28-30). Weight management is crucial and should be suggested promptly even when these individuals are otherwise healthy (e.g. metabolically healthy patients with obesity) to prevent and/or delay the onset of obesity-related complications. Interestingly, recent advances in treatment options for CVD risk factors and acute coronary syndromes are now offering improved cardio-protection outcomes and appear to prolong life expectancy in patients with obesity. Indeed, epidemiologic data support the notion that, in developed societies increasing numbers of these patients are expected to live more than previously predicted, despite failing to reduce their excessive body weight (31, 32). As such, it is estimated that growing and progressively ageing populations in Western societies will continue to develop an increasing burden of obesity-related disease, including complications (e.g. chronic liver disease, respiratory or mobility problems) which were previously under-diagnosed or under-expressed due to earlier mortality (expansion of obesity-related morbidity) (31, 33, 34). Subsequently, the economic impact of obesity on health care costs is profound and will continue to increase, while the additional indirect costs (e.g. absence from work, reduced productivity and disability benefits) are also substantial. National surveys in the UK have shown that obesity is directly responsible for almost 7% of the overall morbidity and mortality, with a direct cost to the Neational Health System (NHS) that currently exceeds five billion pounds per year and could potentially rise to more than nine billion pounds by 2050 (35-37).

Childhood obesity also poses a significant burden due to a spectrum of complications both in the short term and later in life, highlighting the need for early intervention and prevention of obesity in children and adolescents (5, 38, 39). It should be noted that the absolute BMI is not an appropriate screen index to identify children with elevated body fat mass since BMI normative values differ based on age and gender. Hence, in the pediatric population BMI should be plotted on the Centers for Disease Control and Prevention’s percentile curves to identify the corresponding BMI percentile category (www.cdc.gov/growthcharts) [obesity in children and adolescents will be reviewed in detail in the EndoText chapter dedicated to Pediatric Obesity].

Conclusion

In this chapter, we have discussed major disorders/diseases that are associated with obesity and are caused, at least in part, by adipose tissue accumulation. These include disturbances of glucose metabolism, manifestations of the metabolic syndrome, non-alcoholic fatty liver disease, gallbladder disease, osteoarthritis, obstructive sleep apnea, and various types of cancer, as well as unfavorable outcomes regarding reproduction, stress levels, and psychiatric disorders.

In clinical practice it should be noted that individuals with obesity often vary significantly regarding clinical manifestations of obesity-related morbidity, and it appears that patterns of lipid partitioning are a major determinant of their metabolic profile (65). Distribution of body fat plays an important role in this context (65, 641). As such, visceral accumulation of excess body fat is shown to be strongly associated with most of the obesity-related disorders including insulin resistance (642), and T2DM (643), as well as with all-cause mortality (644). On the other hand, increased subcutaneous fat depots can even have protective metabolic effects (645-647). Although not all previous studies have shown an independent effect of the subcutaneous abdominal fat on insulin sensitivity (646) and controversial findings have also been reported (648), data suggest that an expanded fat mass, particularly of subcutaneous adipose tissue, may function as a sink for glucose uptake and triglyceride accumulation resulting in compensatory improvement of insulin sensitivity (647). In agreement with this hypothesis, it has been shown that enabling a massive expansion of the subcutaneous adipose tissue mass in the ob/ob mouse model potently counteracts the development of insulin resistance associated with excess caloric intake (649). Importantly, evidence from rodent models of obesity and research into the genetic basis of human obesity have started to provide novel insight into the predisposition to weight gain and the pathophysiology of obesity-associated co-morbidity [rodent models of obesity and the genetics of obesity in humans will be reviewed in detail in the corresponding EndoText chapters].

In conclusion, obesity constitutes a complex, multifactorial disease associated with a wide spectrum of comorbidities due to both a deleterious endocrine/metabolic profile of the expanded/accumulated adipose tissue, and an increased physical burden imposed on various body sites/organs. Thus, even in cases of “metabolically healthy” obese individuals (presenting with a predominantly female type of fat distribution and absence of metabolic abnormalities) multiple other parameters and the risk of long-term adverse outcomes (e.g. risk of CVD, osteoarthritis, disability, psychological comorbidity) need to be seriously considered when discussing the benefits of various weight management interventions (28, 650, 651).

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