Clinical Medicine Insights Received 25 Dec 2020 | Revised 20 Jan 2021 | Accepted 24 Feb 2021 | Published Online 30 Mar 2021 DOI: https://doi.org/10.52845/CMI/2021-2-1-3 CMI JOURNAL 2 (1), 64−79 (2021) ISSN (O) 2694-4626 REVIEW ARTICLE Obesity and Non-Communicable Diseases: Part I Cardiovascular Diseases, Respiratory Diseases, Depression, Liver Diseases Shashi K. Agarwal, MD ∗ 12227 US Highway 1, #309 North Brunswick, NJ 08902,USA Abstract Obesity has become a pandemic. Obesity is associated with a wide array of physical and emotional health ailments. It is associated with a reduced quality of life. Comorbid disorders often result in premature mortality. Although BMI is the widely used standard for defining overweight and obesity, abdominal or visceral obesity has a more significant association with several noncommunicable diseases.Weight loss is beneficial in halting the deleterious effects of excess body weight. Part I of thismanuscript, discusses the harmful effects of obesity on cardiovascular diseases, respiratory diseases, depression, and liver diseases. Keywords: obesity, non-communicable diseases, cardiovascular dis- eases, respiratory diseases, obesity, depression, liver diseases Copyright : © 2021 The Authors. Published by Medical Editor and Educational Research Publishers Ltd. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 INTRODUCTION Obesity is growing exponentially all over the world1. Obesity is recognized and classi- fied according to a person’s body mass index (BMI)2. BMI is a person’s weight [kilo- grams] divided by the square of his or her height [meters])2. According to theWorld Health Organiza- tion (WHO), a BMI between 20 and 25 kg/m2 is nor- mal, a BMI between 25 and 30 kg/m2 is considered overweight, while a BMI of >30 kg/m2 represents obesity3. These numbers are different for the Asian population (Asian people have a high risk of type 2 diabetes and CVD at a lower BMI) 3. Obesity is further divided into 3 classes (class 1, BMI > 30 and < 35; class 2, BMI > 35 and < 40; class 3, BMI > 40)4. In the USA in 2017-2018, 42.2% of all adults were obese5. Europe has the second highest proportion of overweight or obese people, with obe- sity rates of over 30% in most countries6. Several low- and middle-income countries, like China, India, and Brazil, have also seen a major rise in the preva- lence of obesity7−9. It has also been increasing at an alarming rate in African countries10. TheGlobal Bur- den of Disease Group reported in 2017 that “since 1980, the prevalence of obesity has doubled in more CMI JOURNAL 2 (1), 64−79 MEERP LTD 64 Open Access Journal https://doi.org/10.52845/CMI/2021-2-3-5 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/index.php/cmi MEERP LTD SHASHI K. AGARWAL, MD than 70 countries and has continuously increased in most other countries”11. Excessive weight gain is not limited to adults, it also affects children and adolescents12. This puts them at a higher risk to de- velopmajor noncommunicable diseases like diabetes and cardiovascular diseases at a younger age13. It is estimated that obesity will affect 1.12 billion people by 203014. BMI is unable to specify the type of collection of fat – subcutaneous adiposity or visceral adiposity15. The latter represents central obesity or abdominal obesity15. Abdominal fat is metabolically active16, unlike subcutaneous fat – it induces inflammation17, insulin resistance18, and a procoagulant state19, re- sulting in a high risk of several chronic diseases. Subcutaneous fat, on the other hand, protects the body from lipotoxicity15,20. Several anthropometric measurements are now routinely done to objectively diagnose central obesity21,22. These include the waist circumference (WC), waist hip ratio (WHR), and the weight height ratio (WHtR)21,22. WC is measured to the nearest 0.1 cm at the umbilical level while standing23. It should ideally be <102 cm inmales and <88 cm in females23. TheWHR is normal if it is 0.85 or less in women and 0.9 or less in men24. TheWHtR is calculated by dividing theWC by height (< 0.5 (no central obesity) and > 0.5 (central obesity)25. Besides the nine chronic diseases discussed in this two-part manuscript, obesity is also implicated in several other disorders, including gastroesophageal reflux disease26, pancreatitis27, osteoporosis28, infertility29,30, and can increase complications related to pregnancy31. It may lead to psycho- social distress and obese people may have low self-esteem and feelings of rejection32. They often have heightened anxiety, body image dissatisfaction, and may face weight bias and sigma33,34. Stigma Supplementary information The online version of this article (10.52845/CMI/2021-2-3-5) contains supplementary material, which is available to autho- rized users. Corresponding Author: Shashi K. Agarwal, MD Shashi K. Agarwal, MD 2227 US Highway 1, #309 North Brunswick, NJ 08902,USA Email: usacardiologist@gmail.com may also be exhibited by health care providers35. Obesity may also lead to disqualification from the US military36. It reduces the health quality of life37. It is associated with an increase in disability and mortality38,39. Most of the deaths attributable to obesity occur due to cardiovascular diseases40. According to the GBD 2015 Obesity Collaborators, obesity accounted for about four million deaths worldwide41. It is amajor cause of preventable death, second only after smoking42. Obesity care is also expensive43. In the US alone, obesity related health care is over $150 billion yearly44. The obesity paradox is a phenomenon where obe- sity is associated with increased survival, especially in hospitalized patients45. It has been observed in chronic diseases such as heart failure46, coronary artery disease47, and end-stage kidney disease48. It has also been observed in acute conditions such as pneumonia49, sepsis50, acute respiratory distress syn- drome (ARDS)51, and other critical illness52. Sev- eral hypotheses have been advanced to explain this phenomenon53−57. The health effects of obesity on common chronic medical conditions are discussed in this two-part manuscript. Part I discusses the relationship between obesity and cardiovascular diseases (CVD), chronic obstructive pulmonary disease (COPD), depression, and liver diseases. Part II discusses its impact on can- cer, diabetes mellitus, kidney diseases, Alzheimer’s disease, and arthritis. 2 DISCUSSION The Centers for Disease Control and Prevention (CDC) defines chronic diseases as “conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living or both”58. Most chronic diseases are noncommunicable dis- eases (NCDs) and are gradually replacing infectious diseases as the major health burden in developing countries59. Out of the 17 million premature deaths (under the age of 70) due to noncommunicable dis- eases in 2015, 82% were in low- and middle-income countries59. The NCDs discussed in this part include cardiovas- cular diseases (such as hypertension (HTN), coro- MEERP LTD CMI JOURNAL 2 (1), 64−79 (2021) 65 mailto:usacardiologist@gmail.com OBESITY AND NON-COMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES nary artery disease, stroke, and heart failure (HF)), chronic respiratory diseases (such as chronic ob- structive pulmonary disease (COPD), lung cancer, tuberculosis, lung infections, asthma, and interstitial lung diseases) depression, and liver diseases (such as nonalcoholic and alcoholic hepatitis, viral hepatitis, cirrhosis of liver). Cardiovascular diseases (CVD) are the leading cause of morbidity worldwide60. They are also the leading cause of global mortality and were responsible for 17.9 million deaths in 2016 (representing 31% of all global deaths)61. Of all the global deaths in 2015, 82% were in low- and middle-income countries61. CVDs were responsible for 37% of these deaths61. Men and women were nearly equally affected59. The most common un- derlying pathology is atherosclerosis (especially in myocardial infarction, ischemic stroke and periph- eral arterial disease)60. The most frequent chronic respiratory diseases encountered include chronic ob- structive pulmonary disease (COPD), lung cancer, tuberculosis, lung infections, asthma, and interstitial lung diseases (ILD). Chronic respiratory diseases are responsible for about 7.5 million deaths per year, and account for approximately 14% of annual deaths worldwide63,64. COPD is the most common cause, and is usually due to tobacco smoking65. These patients experience airflow limitation, and COPD can be diagnosed by the FEV1 /FVC ratio of less than 0.7066. Asthma is a chronic inflam- matory disorder of the airways67. Globally, one in two hundred and fifty deaths are due to ashtma68. The physical quality of life is impaired by bronchial symptoms69, while social life is also impaired by rhinitis co-morbidity70. Obstructive sleep apnea syn- drome results from upper airway obstruction71. Pe- riods of reduced or absent airflow through the nose or mouth cause loud snoring and the hypoxemia is usually terminated by arousal72. Sleep is espe- cially disturbed in these patients73. Major depressive disorder (MDD) is the primary cause of disability worldwide74. It can be diagnosed by the presence of at least five of the following symptoms occurring independently of physical illness, normal bereave- ment, alcohol or drugs: abnormal depressed mood; abnormal loss of interest and pleasure; appetite or weight disturbance; sleep disturbance; disturbance in activity (agitation or slowing); abnormal fatigue or loss of energy; abnormal self-reproach or inap- propriate guilt; poor concentration or indecisiveness; and morbid thoughts of death or suicide75. The five diagnostic symptoms, which should include abnor- mal depressed mood or loss of interest and pleasure, are present nearly every day for at least two weeks after the diagnosis75. TheWorldHealth Organization predicts that depression will generate the greatest global burden by 203076. Liver diseases affect more than 10% of the world population77. The leading liver disease globally (40% of all liver diseases) is nonalcoholic fatty liver disease (NAFLD). Other common liver diseases are Hepatitis B virus (HBV) (30%), Hepatitis C virus (HCV) (15%) and excessive consumption (11%)77. These patients may progress to cirrhosis of the liver or develop liver cancer78. 2.1 CARDIOVASCULAR DISEASES Obesity has a strong detrimental relationship with CVDs79,80. An increased CVD risk of 6% for each 1.1 kg/m2 increase in BMI was noted by Ember- son et al. among 6452 British men81. Weight loss, on the other hand, reduces CVDs82. In the Look AHEAD trial, with amedian follow-up of 10.2 years, weight loss decreased CVD outcomes82. A 10% body weight reduction in the first year of the study resulted in a 21% lower risk of the primary CVD out- come and a 24% reduced risk of the secondary out- come compared with individuals who were weight stable or gained weight82. Obesity has been associated with an in- creased risk of HTN83, coronary artery disease84,stroke85,86, HF87,cardiac arrhythmias88, and sudden cardiac death (SCD)89. It is estimated that obesity may result in a 3.5-fold increase in the likelihood of being hypertensive, and obesity may be responsible for about 70% of HTN in adults90,91. An increase in weight by 5% appears to increase the incidence of hypertension by 20–30%92. On the other hand, weight loss is effective in lowering blood pressure (BP)93. Studies indicated that a 10 Kg weight loss would result in a 6 mmHg in BP94. Obese patients are twice as likely to have coronary artery disease and their lesions are more complex95,96. They do not heal well after coronary artery bypass grafting97 and have a higher mortality98. Obesity is CMI JOURNAL 2 (1), 64−79 (2021) MEERP LTD 66 MEERP LTD SHASHI K. AGARWAL, MD an independent risk factor for heart failure (HF)99. In the Framingham Heart Study of 5881 patients,an increase in BMI of 1 kg/m2 increased the risk of heart failure by 5% in men and 7% in women100. They also do not do well after a left ventricular assist device implantation101 or heart transplant surgery102. Bariatric surgery induced weight loss in HF patients resulting in a significant reduction in their New York Heart Association classification103. Ischemic stroke risks are also increased in obese patients104. In the Physicians’ Health Study, men with BMI >30 kg/m2 had a >2- fold increase in risk for stroke105. In a prospective study of >39,000 healthy women, those with BMI >35 kg/m2 had a 3-fold increase in the risk of ischemic stroke compared with women with BMI <20 kg/m2106. It is estimated that for each 1-U increase in BMI, there is an increase of 4% in the risk of ischemic stroke107,108. Obese patients also have a higher risk of atrial fibrillation, with the risk being 1.52 times compared to that of the normal weight population109. Obesity increases the risk of SCD110. There is also a detrimental association noted between obesity and several other CVDs, including aortic stenosis111, peripheral artery disease112, erectile dysfunction113, and venous thromboembolism114. Obesity is also associated with diabetes mellitus, dyslipidemia, and sleep apnea syndrome – disorders that further increase the risk of cardiovascular disorders115. Obesity results in several pathophysiological mechanisms that damage the cardiovascular sys- tem. The adipose tissue releases proinflammatory adipokines, elevates free radicals, causes endothe- lial dysfunction, and activates macrophages, T cells, and B cells within fat deposits leading to atherosclerosis116. 2.2 RESPIRATORY DISEASES Increased BMI results in reduced lung function, with reductions in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)117,118. Obesity is detrimentally associated with obstructive sleep ap- nea (OSA)119 and bronchial asthma120. Obesity pro- motes OSA by causing enlargement of soft tissue structures within and surrounding the airway121. An excess of fat deposition has also been observed under the mandible and in the tongue, soft palate, and uvula122. Further, obesity may reduce lung volumes by a combination of increased abdominal fat mass123 and disturbed neuroanatomic interactions124. Several longitudinal epidemiological studies have shown that obesity is a major risk factor for asthma in children125,126. Obesity and weight gain during preg- nancy in the mother are both associated with an increased risk of asthma in the offspring127. Several prospective studies in adults have also found a rela- tionship between obesity and incident asthma128,129. Obesity in adults with asthma has been associated with reduced response to asthma medications, result- ing in worse disease control, higher risk of hospital- ization and lower quality of life, when compared to lean asthma patients130,131. Weight loss intervention by caloric restriction132 or bariatric surgery leads to an improvement in asthma outcomes133. Abdominal or central obesity, even with a normal BMI, appears to be linked with an increased risk of lung cancer134. Yu et al estimated this increased risk to be 40% greater in these patients 135. Carreras-Torres et al, using Mendelian randomization, recently reported that genetically predicted BMI,WHR, and insulin re- sistance increased the risk of lung cancer, especially for squamous cell and small cell lung cancer136. An obesity paradox has been noted in COPD patients, especially those with severe disease137. Patients with a higher BMI survive longer when compared to those with low or normal BMI138. It has been suggested that the severity of COPD may be overestimated in obese patients, as when CO2 levels and muscle mass and exercise capacity are looked at, there appears to be no obesity paradox139. 2.3 DEPRESSION Several studies have found that obesity and mental health problems are linked140−142. Si- mon et al concluded that there was an approx- imately 25% increase in mood disorders and anxiety in obese patients143. Obesity and depres- sion also frequently co-exist144,145 and the pres- ence of one not only increases the risk of the other, but also causes significant adverse health outcomes when they co-occur146,147. The preva- MEERP LTD CMI JOURNAL 2 (1), 64−79 (2021) 67 OBESITY AND NON-COMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES lence of depression in obese individuals is esti- mated to be twice as high as in those of normal weight148. Negative body image, and low self- esteemare common in obese patients149. They also face stigma in social and professional lives150,151. These factors contribute to the development and maintenance of depression152,153. Other patho- physiological processesmay also play a role in this connection154,155. Depression also increases weight gain and obesity156−160. Depressed individuals may be less physically active and indulge in excessive ‘comfort’ eating156−158. Certain antidepressant med- ications can also contribute to weight gain159,160. The relationship between obesity and depres- sion is therefore bidirectional161. The biological pathways include genetic influence162, HPA axis disturbances163,164, immuno-inflammatory dys- regulation166, and insulin abnormalities167. 2.4 LIVER DISEASES NAFLD is prevalent in obese individuals168. Obese individuals have a prevalence of 30% to 37% of NAFLD169. In those who have undergone bariatric surgery, the prevalence rises to 84% to 96%170. Li et al. estimated that obesity produced a 3.5-fold increased risk of developing NAFLD171 and is more closely related to waist circumference172. Pang et al. in a meta-analysis, concluded that for each 1 unit increase in waist circumference, the odds ratio of NAFLD increased by 1.07, and for each 1 unit increase in BMI, the odds ratio increased by 1.25173. Obesity also worsens the prognosis in patients with hepatitis174. Obese patients with alcoholic hepatitis, are twice as likely to die in the short term, com- pared to those who are nonobese174. Obesity is also common in chronic HCV infected individuals175. This increases their risk of developing serious liver related complications and dying early176. Antiviral treatment in these patients may sometimes result in weight gain177. 3 CONCLUSIONS The increasing epidemic of obesity has resulted in a greater development, aggressive progression, and poor outcomes for many common chronic diseases and ailments. The evidence for the preventive and therapeutic effects of a BMI of 25 or more on NCDs is strong. Weight loss, including that with bariatric surgery, helps most obesity related conditions. Acknowledgment: None Funding: None Conflict of interest: None REFERENCES 1. Kolahi AA, Moghisi A, Soleiman Ekhtiari Y. Socio-demographic determinants of obe- sity indexes in Iran: findings from a nation- wide STEPS survey. Health Promot Perspect. 2018;8(3):187–194. 2. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Com- mittee. World Health Organ Tech Rep Ser. 1995;854:1–452. 3. WHO Expert Consultation: Appropriate body- mass index for Asian populations and its im- plications for policy and intervention strategies. Lancet 363: 157–163, 2004. 4. Aronne LJ. Classification of obesity and assess- ment of obesity-related health risks. Obes Res. 2002;10(Suppl 2):105S–115S. 5. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of Obesity and Severe Obe- sity Among Adults: United States, 2017-2018. NCHS Data Brief. 2020 Feb;(360):1-8. PMID: 32487284. 6. Nittari G, Scuri S, Petrelli F, Pirillo I, di Luca NM, Grappasonni I. Fighting obesity in children from European World Health Orga- nization member states. Epidemiological data, medical-social aspects, and prevention pro- grams. Clin Ter. 2019 May-Jun;170(3):e223- e230. doi: 10.7417/CT.2019.2137. 7. Yu Z, Han S, Chu J, Xu Z, Zhu C, Guo X: Trends in overweight and obesity among chil- dren and adolescents in China from 1981 to 2010: A meta-analysis. PLoS One 7: e51949, 2012. CMI JOURNAL 2 (1), 64−79 (2021) MEERP LTD 68 MEERP LTD SHASHI K. AGARWAL, MD 8. Gupta R, Sharma KK, Gupta A, Agrawal A, Mohan I, Gupta VP, Khedar RS, Guptha S: Per- sistent high prevalence of cardiovascular risk factors in the urban middle class in India: Jaipur Heart Watch-5. J Assoc Physicians India 60: 11–16, 2012. 9. Schmitt AC, Cardoso MR, Lopes H, et al. Prevalence of metabolic syndrome and associ- ated factors in women aged 35 to 65 years who were enrolled in a family health program in Brazil. Menopause 20: 470–476, 2013. 10. Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, et al. The global obesity pandemic: Shaped by global drivers and local environments. Lancet. 2011;378: 804– 814. doi: 10.1016/S0140-6736(11)60813-1. 11. GBD 2015Obesity Collaborators Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 2017;377(1):13–27. 12. Fryar CD, Carroll MD, Ogden PD. Preva- lence of overweight, obesity, and severe obe- sity among children and adolescents aged 2–19 years: United States, 1963–1965 through 2015– 2016. Natl Cent Heal Stat (US) Div Heal Nutr Exam Surv. 2018;.93–95. 13. Juonala M., Magnussen C.G., Berenson G.S., et al. Childhood Adiposity, Adult Adiposity, and Cardiovascular Risk Factors. N. Engl. J. Med. 2011;365:1876–1885. 14. Kolahi AA, Moghisi A, Soleiman Ekhtiari Y. Socio-demographic determinants of obe- sity indexes in Iran: findings from a nation- wide STEPS survey. Health Promot Perspect. 2018;8(3):187–194. 15. Piché ME, Poirier P, Lemieux I, et al. Overview of epidemiology and contribution of obesity and body fat distribution to cardiovascular disease: an update. Prog Cardiovasc Dis. 2018;61:103– 113. 16. Bays H, Blonde L, Rosenson R. Adiposopathy: how do diet, exercise and weight loss drug therapies improve metabolic disease in over- weight patients? Expert Rev Cardiovasc Ther. 2006;4(6):871–95. 17. Smitka K, Marešová D. Adipose Tissue as an Endocrine Organ: An Update on Pro- inflammatory and Anti-inflammatory Microen- vironment. Prague Med Rep. 2015;116(2):87- 111. doi: 10.14712/23362936.2015.49. 18. Frayn KN. Adipose tissue and the insulin resis- tance syndrome. Proc Nutr Soc. 2001;60:375– 380. 19. Candeloro M, Di Nisio M, Valeriani E, et al. Effects of body composition on the procoagulant imbalance in obese patients. J Thromb Thrombolysis. 2021 May;51(4):1036- 1042. doi: 10.1007/s11239-020-02287-1. 20. Neeland IJ, Poirier P, Despres JP (2018) Car- diovascular andmetabolic heterogeneity of obe- sity: clinical challenges and implications for management. Circulation 137:1391–1406. 21. Wakabayashi Ichiro. Necessity of Both Waist Circumference and Waist-to-Height Ratio for Better Evaluation of Central Obesity. Metabolic Syndrome and Re- lated Disorders. 2013;11(3):189–194. doi: 10.1089/met.2012.0131. 22. Hsieh S D, Yoshinaga H, Muto T. Waist-to- height ratio, a simple and practical index for assessing central fat distribution and metabolic risk in Japanese men and women. International Journal of Obesity. 2003;27(5):610–616. doi: 10.1038/sj.ijo.0802259. 23. World Health Organization. Waist Circumfer- ence and Waist-Hip Ration: Report of a WHO Expert Consultation. World Health Organiza- tion; Geneva, Switzerland: 2008. 24. Klingberg S, Draper CE, Micklesfield LK, et al. Childhood obesity prevention in Africa: a systematic review of intervention effec- tiveness and implementation. Int J Envi- ron Res Public Health 2019;16:1212. doi: 10.3390/ijerph16071212. MEERP LTD CMI JOURNAL 2 (1), 64−79 (2021) 69 OBESITY AND NON-COMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES 25. Hsieh S D, Yoshinaga H, Muto T. Waist-to- height ratio, a simple and practical index for assessing central fat distribution and metabolic risk in Japanese men and women. International Journal of Obesity. 2003;27(5):610–616. doi: 10.1038/sj.ijo.0802259. 26. Camilleri M, Malhi H, Acosta A. Gastroin- testinal Complications of Obesity. Gastroen- terology. 2017 May;152(7):1656-1670. doi: 10.1053/j.gastro.2016.12.052. 27. Khatua B, El-Kurdi B, Singh VP. Obe- sity and pancreatitis. Curr Opin Gas- troenterol. 2017 Sep;33(5):374-382. doi: 10.1097/MOG.0000000000000386. 28. Kim KC, Shin DH, Lee SY, Im JA, Lee DC. Relation between obesity and bone mineral density and vertebral fractures in Korean postmenopausal women. Yon- sei Med J. 2010 Nov;51(6):857-63. doi: 10.3349/ymj.2010.51.6.857. 29. Talmor A, Dunphy B. Female obesity and infertility. Best Pract Res Clin Obstet Gynaecol. 2015 May;29(4):498-506. doi: 10.1016/j.bpobgyn.2014.10.014. 30. Kahn BE, Brannigan RE. Obesity and male infertility. Curr Opin Urol. 2017 Sep;27(5):441- 445. doi: 10.1097/MOU.0000000000000417. 31. Catalano PM, Shankar K. Obesity and preg- nancy: mechanisms of short term and long term adverse consequences for mother and child. BMJ. 2017 Feb 8;356:j1. doi: 10.1136/bmj.j1. 32. Sarwer DB, Polonsky HM. The Psy- chosocial Burden of Obesity. Endocrinol Metab Clin North Am. 2016;45(3):677-688. doi:10.1016/j.ecl.2016.04.016. 33. Weinberger NA, Kersting A, Riedel-Heller SG, Luck-Sikorski C. Body Dissatisfaction in In- dividuals with Obesity Compared to Normal- Weight Individuals: A Systematic Review and Meta-Analysis. Obes Facts. 2016;9(6):424-441. doi: 10.1159/000454837. 34. Pont SJ, Puhl R, Cook SR, Slusser W; SECTION ON OBESITY; OBESITY SO- CIETY. Stigma Experienced by Chil- dren and Adolescents With Obesity. Pe- diatrics. 2017 Dec;140(6):e20173034. doi: 10.1542/peds.2017-3034. 35. Puhl RM, Heuer CA. The stigma of obe- sity: a review and update. Obesity (Sil- ver Spring). 2009 May;17(5):941-64. doi: 10.1038/oby.2008.636. 36. Maxey H, Bishop S, Goodman B, Browning D. Breaking Point: Child malnutrition imperils America’s national security. Mission: Readi- ness Council for a Strong America; 2020. 37. Sirtori A, Brunani A, Villa V, Berselli ME, Croci M, Leonardi M, Raggi A. Obesity is a marker of reduction in QoL and disability. Sci- entificWorldJournal. 2012;2012:167520. doi: 10.1100/2012/167520. 38. Capodaglio P, Brunani A, Giustini A, Negrini S, Saraceni VM, Akyüz G, Imamura M. Disability in obesity with comorbidities. A perspective from the PRM Societies. Eur J Phys Rehabil Med. 2014 Apr;50(2):129-32. 39. GBD 2015Obesity Collaborators Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 2017;377(1):13–27. 40. The Global BMI Mortality Collaboration. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Volune 388, Issue 10046, P776-786, August 20, 2016. 2016 DOI:https://doi.org/10.1016/S0 140-6736(16)30175-1 41. GBD 2015 Obesity Collaborators. Afshin A., Forouzanfar M.H., Reitsma M.B., Sur P., Estep K., Lee A., Marczak L., Mokdad A.H., Moradi- Lakeh M., et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N. Engl. J. Med. 2017;377:13–27. CMI JOURNAL 2 (1), 64−79 (2021) MEERP LTD 70 MEERP LTD SHASHI K. AGARWAL, MD 42. Panuganti KK, Nguyen M, Kshirsagar RK. Obesity. 2020 Dec 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. 43. Withrow D, Alter DA. The economic bur- den of obesity worldwide: a systematic re- view of the direct costs of obesity. Obes Rev. 2011 Feb;12(2):131-41. doi: 10.1111/j.1467- 789X.2009.00712.x. 44. Finkelstein EA1, Trogdon JG, Cohen JW, Dietz W. Annual medical spending at- tributable to obesity: payer-and service- specific estimates. Health Aff (Mill- wood). 2009 Sep-Oct;28(5):w822-31. doi: 10.1377/hlthaff.28.5.w822. 45. Hainer V, Aldhoon-Hainerová I. Obesity para- dox does exist. Diabetes Care. 2013;36 Suppl 2(Suppl 2):S276-S281. doi:10.2337/dcS13- 2023. 46. Sharma A, Lavie CJ, Borer JS, Vallakati A, Goel S, Lopez-Jimenez F, Arbab-Zadeh A, Mukherjee D, Lazar JM (2015) Meta-analysis of the relation of body mass index to all-cause and cardiovascular mortality and hospitaliza- tion in patients with chronic heart failure. Am J Cardiol 115:1428–1434. 47. Romero-Corral A, Montori VM, Somers VK, Korinek J, Thomas RJ, Allison TG, Mookadam F, Lopez-Jimenez F (2006) Association of bodyweight with total mortality and with car- diovascular events in coronary artery disease: a systematic review of cohort studies. Lancet 368:666–678. 48. Naderi N, Kleine CE, Park C, Hsiung JT, Soohoo M, Tantisattamo E, Streja E, Kalantar- Zadeh K, Moradi H (2018) Obesity paradox in advanced kidney disease: from bedside to the bench. Prog Cardiovasc Dis 61:168–181. 49. Nie W, Zhang Y, Jee SH, Jung KJ, Li B, Xiu Q (2014) Obesity survival paradox in pneumonia: a meta-analysis. BMC Med 12:61. 50. Pepper DJ, Sun J, Welsh J, Cui X, Suffredini AF, Eichacker PQ (2016) Increased body mass index and adjusted mortality in ICU patients with sepsis or septic shock: a systematic review and meta-analysis. Crit Care 20:181. 51. Ni YN, Luo J, Yu H, Wang YW, Hu YH, Liu D, Liang BM, Liang ZA (2017) Can body mass index predict clinical outcomes for patients with acute lung injury/acute respiratory distress syn- drome? A meta-analysis. Crit Care 21:36. 52. Hogue CW, Stearns JD, Colantuoni E, Robin- son KA, Stierer T, Mitter N, Pronovost PJ, Needham DM (2009) The impact of obesity on outcomes after critical illness: a meta-analysis. Intensive Care Med 35:1152–1170. 53. Marques MB, Langouche L (2013) Endocrine, metabolic, and morphologic alterations of adi- pose tissue during critical illness. Crit CareMed 41:317–325. 54. Alipoor E, Mohammad Hosseinzadeh F, Hosseinzadeh-Attar MJ (2018) Adipokines in critical illness: a review of the evidence and knowledge gaps. Biomed Pharmacother 108:1739–1750. 55. Fantuzzi G (2005) Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 115:911–919. 56. Stapleton RD, Dixon AE, Parsons PE, Ware LB, Suratt BT (2010) The association between BMI and plasma cytokine levels in patients with acute lung injury. Chest 138:568–577. 57. Murch O, Collin M, Hinds CJ, Thiemermann C (2007) Lipoproteins in inflammation and sepsis. I. Basic science. Intensive Care Med 33:13–24. 58. https://www.cdc.gov/chronicdisease/about/ind ex.htm. Accessed January 2, 2021. 59. WorldHealth Organization Cardiovascular Dis- ease. [(accessed on 13November 2019)]; Avail- able online: https://www.who.int/cardiovascula r_diseases/about_cvd/en/. MEERP LTD CMI JOURNAL 2 (1), 64−79 (2021) 71 OBESITY AND NON-COMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES 60. Hogas S., Bilha S.C., Branisteanu D., Hogas M., Gaipov A., Kanbay M., Covic A. Potential novel biomarkers of cardiovascular dysfunction and disease: Cardiotrophin-1, adipokines and galectin-3. Arch. Med. Sci. 2017;4:897–913. doi: 10.5114/aoms.2016.58664. 61. World Health Organization. World Health Statistics 2018: Monitoring Health for the SDGs: Sustainable Development Goals. World Health Organization; Geneva, Switzerland: 2018. Licence: CC BY-NC-SA 3.0 IGO. 62. Rahman MS, Woollard K. Atherosclerosis. Adv Exp Med Biol. 2017;1003:121-144. doi: 10.1007/978-3-319-57613-8_7. 63. Noncommunicable Diseases Country Profiles 2018. Geneva: World Health Organization; 2018, 223. Available online: https://www.who .int/nmh/publications/ncd-profiles-2018/en. 64. GBD Chronic Respiratory Disease Collabora- tors. Prevalence and attributable health bur- den of chronic respiratory diseases, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir Med. 2020 Jun;8(6):585-596. doi: 10.1016/S2213- 2600(20)30105-3. 65. Salvi S. Tobacco smoking and environmental risk factors for chronic obstructive pulmonary disease. Clin Chest Med. 2014 Mar;35(1):17- 27. doi: 10.1016/j.ccm.2013.09.011. 66. Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347– 65. ht tp://dx.doi.org/10.1164/rccm.201204-0596PP PMID:22878278. 67. Mims JW. Asthma: definitions and pathophys- iology. Int Forum Allergy Rhinol. 2015 Sep;5 Suppl 1:S2-6. doi: 10.1002/alr.21609. 68. Fergeson JE, Patel SS, Lockey RF. Acute asthma, prognosis, and treatment. J Allergy Clin Immunol. 2017 Feb;139(2):438-447. doi: 10.1016/j.jaci.2016.06.054. 69. Wilson SR, Rand CS, Cabana MD, Foggs MB, Halterman JS, Olson L, et al. Asthma out- comes: Quality of life. J Allergy Clin Immunol. 2012;129:S88–123. 70. Boulet LP, Boulay MÈ. Asthma-related co- morbidities. Expert Rev Respir Med. 2011 Jun;5(3):377-93. doi: 10.1586/ers.11.34. 71. Qaseem A, et al. Diagnosis of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014;161(3):210–220. 72. Maspero C, Giannini L, Galbiati G, Rosso G, Farronato G. Obstructive sleep apnea syn- drome: a literature review. Minerva Stomatol. 2015 Apr;64(2):97-109. 73. Patel SR. Obstructive Sleep Apnea. Ann Intern Med. 2019 Dec 3;171(11):ITC81-ITC96. doi: 10.7326/AITC201912030. 74. Friedrich MJ. Depression is the leading cause of disability around the world. JAMA. 2017;317(15):1517. 75. American Psychiatric Association Diagnostic and statistical manual of mental disorders: 5th Edn. Washington, DC: (2013) 76. .Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):2011–2030. 77. Muriel P. Liver Pathophysiology. Elsevier; Am- sterdam, The Netherlands: 2017. The Liver: General Aspects and Epidemiology; pp. 3–22. 78. https://medlineplus.gov/liverdiseases.html - ac- cessed August 4, 2021. 79. Kenchaiah S , Evans JC, Levy D, Wilson PWF, Benjamin EJ, Larson MG, Kannel WB, Vasan RS. Obesity and the risk of heart failure. N Engl J Med. 2002;347(5):305–313. CMI JOURNAL 2 (1), 64−79 (2021) MEERP LTD 72 MEERP LTD SHASHI K. AGARWAL, MD 80. Canoy D , Cairns BJ, Balkwill A, Wright FL, Green J, Reeves G, Beral V; Million Women Study Collaborators. Body mass index and in- cident coronary heart disease in women: a population-based prospective study. BMCMed. 2013;11(1):87. 81. Emberson JR , Whincup PH, Morris RW, Wan- namethee SG, Shaper AG. Lifestyle and car- diovascular disease in middle-aged British men: the effect of adjusting for within-person varia- tion. Eur Heart J. 2005;26(17):1774–1782. 82. Gregg EW , Jakicic JM, Blackburn G, et al. Look AHEAD Research Group. Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial. Lancet Diabetes Endocrinol. 2016;4(11):913–921. 83. Shariq OA, McKenzie TJ. Obesity-related hypertension: a review of pathophysiology, management, and the role of metabolic surgery. Gland Surg. 2020;9(1):80-93. doi:10.21037/gs.2019.12.03. 84. Garcia-Labbé D, Ruka E, Bertrand OF, Voisine P, Costerousse O, Poirier P. Obesity and coro- nary artery disease: evaluation and treatment. Can J Cardiol. 2015 Feb;31(2):184-94. 85. Kurth T, Gaziano JM, Berger K, Kase CS, Rexrode KM, Cook NR, Buring JE, Manson JE. Body mass index and the risk of stroke in men. Arch Intern Med. 2002; 162: 2557–2562. 86. Kurth T, Gaziano JM, Rexrode KM, Kase CS, Cook NR, Manson JE, Buring JE. Prospective study of body mass index and risk of stroke in apparently healthy women. Circulation. 2005 Apr 19;111(15):1992-8. doi: 10.1161/01.CIR.0000161822.83163.B6. 87. Aune D , Sen A, Prasad M, Norat T, Jan- szky I, Tonstad S, Romundstad P, Vatten LJ. BMI and all cause mortality: systematic review and non-linear dose-response meta- analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants. BMJ. 2016;353:i2156. 88. N. Wanahita, F.H. Messerli, S. Bangalore, et al. Atrial fibrillation and obesity—results of a meta-analysis. AmHeart J, 155 (2008), pp. 310- 31552. 89. Nunez, H.O. Ventura, D.W. Snyder. Over- weight and sudden death: increased ventricular ectopy in cardiomyopathy of obesity. Arch In- tern Med, 147 (1987), pp. 1725-1728. 90. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden as- sociated with overweight and obesity. JAMA. 1999;282:1523–9. 91. Garrison RJ, Kannel WB, Stokes J, 3rd, et al. Incidence and precursors of hypertension in young adults: the FraminghamOffspring Study. Prev Med 1987;16:235-51. 10.1016/0091- 7435(87)90087-9. 92. Vasan RS, Larson MG, Leip EP, et al. Assessment of frequency of progression to hypertension in non-hypertensive participants in the Framingham Heart Study: a cohort study. Lancet 2001;358:1682-6. 10.1016/S0140- 6736(01)06710-1. 93. C.J. Lavie, R.V. Milani. Obesity and cardiovas- cular disease: the Hippocrates paradox? J Am Coll Cardiol, 42 (2003), pp. 677-679. 94. Shariq OA, McKenzie TJ. Obesity-related hypertension: a review of pathophysiology, management, and the role of metabolic surgery. Gland Surg. 2020;9(1):80-93. doi:10.21037/gs.2019.12.03. 95. Ndumele CE, Matsushita K, Lazo M, Bello N, Blumenthal RS, Gerstenblith G, Nambi V, Ballantyne CM, Solomon SD, Selvin E, Fol- som AR, Coresh J. Obesity and Subtypes of Incident Cardiovascular Disease. J Am Heart Assoc. 2016 Jul 28;5(8). MEERP LTD CMI JOURNAL 2 (1), 64−79 (2021) 73 OBESITY AND NON-COMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES 96. Garcia-Labbé D, Ruka E, Bertrand OF, Voisine P, Costerousse O, Poirier P. Obesity and coro- nary artery disease: evaluation and treatment. Can J Cardiol. 2015 Feb;31(2):184-94. 97. Buschmann K, Wrobel J, Chaban R, et al. Body Mass Index (BMI) and Its Influence on the Cardiovascular and Operative Risk Profile in Coronary Artery Bypass Grafting Patients: Im- pact of Inflammation and Leptin. Oxid Med Cell Longev. 2020 Jun 23;2020:5724024. doi: 10.1155/2020/5724024. 98. Yarnell JW, Patterson CC, Thomas HF, Sweet- nam PM. Comparison of weight in middle age, weight at 18 years, and weight change between, in predicting subsequent 14 year mortality and coronary events: Caerphilly Prospective Study. J Epidemiol Community Health 2000;54:344-8. 99. Hagg S, Fall T, Ploner A, Magi R, Fischer K, et al. European Network for Genetic and Genomic Epidemiology Consorium. Adiposity as a cause of cardiovascular disease: aMendelian random- ization study. Int J Epidemiol 2015;44:578– 586. 100. Kenchaiah S., Evans J. C., Levy D., et al. Obe- sity and the risk of heart failure. New Eng- land Journal of Medicine. 2002;347(5):305– 313. doi: 10.1056/NEJMoa020245. 101. Lee A.Y., Tecson K.M., Lima B. Durable left ventricular assist device implantation in extremely obese heart failure patients. Artif Organs. 2019;43(3):234–241. doi: 10.1111/aor.13380. 102. Lavie C.J., Mehra M.R., Ventura H.O. Body composition and advanced heart failure ther- apy: Weighing the options and outcomes. JACC Hear Fail. 2016;4(10):769–771. doi: 10.1016/j.jchf.2016.07.007. 103. Yang T.W.W., Johari Y., Burton P.R. Bariatric surgery in patients with severe heart failure. Obes Surg. 2020 doi: 10.1007/s11695-020- 04612-2. 104. Rexrode KM, Hennekens CH, Willett WC, Colditz GA, Stampfer MJ, Rich-Edwards JW, Speizer FE, Manson JE. A prospective study of body mass index, weight change, and risk of stroke in women. JAMA. 1997; 277: 1539– 1545. 105. Kurth T, Gaziano JM, Berger K, Kase CS, Rexrode KM, Cook NR, Buring JE, Manson JE. Body mass index and the risk of stroke in men. Arch Intern Med. 2002; 162: 2557–2562. 106. Kurth T, Gaziano JM, Rexrode KM, Kase CS, Cook NR, Manson JE, Buring JE. Prospective study of body mass index and risk of stroke in apparently healthy women. Circulation. 2005 Apr 19;111(15):1992-8. doi: 10.1161/01.CIR.0000161822.83163.B6. PMID: 15837954. 107. P. Poirier, T.D. Giles, G.A. Bray, et al. Obe- sity and cardiovascular disease: pathophysiol- ogy, evaluation, and effect of weight loss: an update of the 1997 American Heart Association scientific statement on obesity and heart dis- ease from the obesity committee of the council on nutrition, physical activity, and metabolism. Circulation, 113 (2006), pp. 898-9181. 108. Kurth T, Gaziano JM, Berger K, Kase CS, Rexrode KM, Cook NR, Buring JE, Manson JE. Body mass index and the risk of stroke in men. Arch Intern Med. 2002; 162: 2557–2562. 109. Tedrow U. B., Conen D., Ridker P. M., et al. The long- and short-term impact of elevated body mass index on the risk of new atrial fibrillation: the WHS (women’s health study) Journal of the American College of Cardiology. 2010;55(21):2319–2327. doi: 10.1016/j.jacc.2010.02.029. 110. Jouven X., Desnos M., Guerot C., Ducimetiere P. Predicting sudden death in the pop- ulation: the Paris Prospective Study I. Circulation. 1999;99(15):1978–1983. doi: 10.1161/01.CIR.99.15.1978. CMI JOURNAL 2 (1), 64−79 (2021) MEERP LTD 74 MEERP LTD SHASHI K. AGARWAL, MD 111. Larsson SC, Wolk A, Håkansson N, Bäck M.. Overall and abdominal obesity and incident aortic valve stenosis: two prospective cohort studies. Eur Heart J 2017;38:2192–2197. 112. Huang Y, Xu M, Xie L, et al. Obesity and peripheral arterial disease: a Mendelian randomization analysis. Atherosclerosis 2016;247:218–224. 113. Han TS, Tajar A, O’Neill TW, Jiang M, Bartfai G, et al. Impaired quality of life and sexual function in overweight and obese men: the Eu- ropean Male Ageing Study. Eur J Endocrinol. 2011;164:1003–11. 114. Lindstrom S, Germain M, Crous-Bou M, et al. Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study. Hum Genet 2017;136:897–902. 115. Poirier P., Giles T. D., Bray G. A., et al. Obesity and cardiovascular disease: patho- physiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Com- mittee of the Council on Nutrition, Physi- cal Activity, and Metabolism. Circulation. 2006;113(6):898–918. doi: 10.1161/CIRCU- LATIONAHA.106.171016. 116. Lovren F, Teoh H, Verma S. Obe- sity and atherosclerosis: mechanistic in- sights.Can J Cardiol. 2015; 31:177–183. doi: 10.1016/j.cjca.2014.11.031. 117. Thyagarajan B., Jacobs D.R., Apostol G.G., Smith L.J., Jensen R.L., Crapo R.O., Barr R.G., Lewis C.E., Williams O.D. Longitudinal asso- ciation of body mass index with lung function: The CARDIA study. Respir. Res. 2008;9:31. doi: 10.1186/1465-9921-9-31. 118. Steele R.M., Finucane F.M., Griffin S.J., Ware- hamN.J., Ekelund U. Obesity is associated with altered lung function independently of physical activity and fitness. Obesity. 2009;17:578–584. doi: 10.1038/oby.2008.584. 119. Foster GD , Sanders MH, Millman R, Zam- mit G, Borradaile KE, Newman AB, Wad- den TA, Kelley D, Wing RR, Sunyer FX, Darcey V, Kuna ST; Sleep AHEAD Research Group. Obstructive sleep apnea among obese patients with type 2 diabetes. Diabetes Care. 2009;32(6):1017–1019. 120. Peters U, Dixon AE, Forno E. Obe- sity and asthma. J Allergy Clin Im- munol. 2018 Apr;141(4):1169-1179. doi: 10.1016/j.jaci.2018.02.004. 121. Resta O, Foschino-Barbaro MP, Legari G, et al. Sleep-related breathing disorders, loud snoring and excessive daytime sleepiness in obese subjects. Int J Obes Relat Metab Disord. 2001;25:669–75. 122. Kim AM, Keenan BT, Jackson N, Chan EL, Staley B, Poptani H, Torigian DA, Pack AI, Schwab RJ. Tongue fat and its relationship to obstructive sleep apnea. Sleep. 2014 Oct 1;37(10):1639-48. doi: 10.5665/sleep.4072. 123. Isono S. Obesity and obstructive sleep ap- noea: mechanisms for increased collapsibility of the passive pharyngeal airway. Respirology. 2012;17:32–42. 124. Polotsky M, Elsayed-Ahmed AS, Pichard L, et al. Effects of leptin and obesity on the upper air- way function. J Appl Physiol. 2012;112:1637– 43. 125. Mamun A.A., Lawlor D.A., Alati R., O’Callaghan M.J., Williams G.M., Najman J.M. Increasing body mass index from age 5 to 14 years predicts asthma among adolescents: Evidence from a birth cohort study. Int. J. Obes. 2007;31:578–583. doi: 10.1038/sj.ijo.0803571. 126. Weinmayr G., Forastiere F., Buchele G., Jaensch A., Strachan D.P., Nagel G., The ISAAC Phase Two Study Group Over- weight/obesity and respiratory and allergic disease in children: International study of asthma and allergies in childhood (ISAAC) phase two. PLoS ONE. 2014;9:e113996. doi: 10.1371/journal.pone.0113996. MEERP LTD CMI JOURNAL 2 (1), 64−79 (2021) 75 OBESITY AND NON-COMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES 127. Dumas O., Varraso R., Gillman M.W., Field A.E., Camargo C.A., Jr. Longitudinal study of maternal body mass index, gestational weight gain, and offspring asthma. Allergy. 2016;71:1295–1304. doi: 10.1111/all.12876. 128. Ronmark E., Andersson C., Nystrom L., Fors- berg B., Jarvholm B., Lundback B. Obesity increases the risk of incident asthma among adults. Eur. Respir. J. 2005;25:282–288. doi: 10.1183/09031936.05.00054304. 129. Peters U, Dixon AE, Forno E. Obe- sity and asthma. J Allergy Clin Im- munol. 2018 Apr;141(4):1169-1179. doi: 10.1016/j.jaci.2018.02.004. 130. Boulet L.P., Franssen E. Influence of obe- sity on response to fluticasone with or without salmeterol in moderate asthma. Respir. Med. 2007;101:2240–2247. doi: 10.1016/j.rmed.2007.06.031. 131. Scott H.A., Gibson P.G., Garg M.L., Pretto J.J., Morgan P.J., Callister R., Wood L.G. Dietary restriction and exercise improve air- way inflammation and clinical outcomes in overweight and obese asthma: A randomized trial. Clin. Exp. Allergy. 2013;43:36–49. doi: 10.1111/cea.12004. 132. Scott H.A., Gibson P.G., Garg M.L., Pretto J.J., Morgan P.J., Callister R., Wood L.G. Dietary restriction and exercise improve air- way inflammation and clinical outcomes in overweight and obese asthma: A randomized trial. Clin. Exp. Allergy. 2013;43:36–49. doi: 10.1111/cea.12004. 133. Van Huisstede A., Rudolphus A., Cabezas M.C., Biter L.U., Van De Geijn G.-J., Taube C., Hiemstra P.S., Braunstahl G.-J., Van Schadewijk A. Effect of bariatric surgery on asthma control, lung function and bronchial and systemic inflammation in morbidly obese subjects with asthma. Thorax. 2015;70:659– 667. doi: 10.1136/thoraxjnl-2014-206712. 134. Dewi NU, Boshuizen HC, Johansson M, et al. Anthropometry and the Risk of Lung Cancer in EPIC. Am J Epidemiol. 2016 Jul 15;184(2):129-39. doi: 10.1093/aje/kwv298. 135. Yu D, Zheng W, Johansson M, et al. Overall and Central Obesity and Risk of Lung Can- cer: A Pooled Analysis. J Natl Cancer Inst. 2018;110(8):831-842. doi:10.1093/jnci/djx286. 136. Carreras-Torres R, Johansson M, Haycock PC,. et al. Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study. PLoS One. 2017;126:e0177875. 137. Huber MB, Kurz C, Kirsch F, Schwarzkopf L, Schramm A, Leidl R. The relationship between body mass index and health-related quality of life in COPD: real-world evidence based on claims and survey data. Respir Res. 2020;21(1):291. Published 2020 Nov 3. doi:10.1186/s12931-020-01556-0. 138. Cao C,Wang R,Wang J, et al. Body mass index and mortality in chronic obstructive pulmonary disease: a meta-analysis. PLoS One 2012; 7(8): e43892. 139. Marquis K, Debigare R, Lacasse Y, et al. Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002; 166(6): 809–813. 140. Stunkard AJ, Faith MS, Allison KC. De- pression and obesity. Biol Psychiatry. 2003; 10.1016/S0006-3223(03)00608-5. 141. Carpenter KM, Hasin DS, Allison DB, Faith MS. Relationships between obesity and DSM- IV major depressive disorder, suicide ideation, and suicide attempts: results from a general population study. Am J Public Health. 2000; 10.2105/AJPH.90.2.251. 142. McElroy SL, Kotwal R,Malhotra S, Nelson EB, Keck PE, Nemeroff CB. Are mood disorders and obesity related? A review for the mental CMI JOURNAL 2 (1), 64−79 (2021) MEERP LTD 76 MEERP LTD SHASHI K. AGARWAL, MD health professional. J Clin Psychiatry. 2004; 10.4088/JCP.v65n0507. 143. Simon GE, et al. Association between obesity and psychiatric disorders in the US adult population. Arch Gen Psychiatry. 2006; 10.1001/archpsyc.63.7.824. 144. Schwenke M, Löbner M, Riedel-Heller S, Luppa M. Adipositas und Depression in der Primärversorgung [Obesity and Depression in Primary Care - Results from the INTERACT Study]. Psychiatr Prax. 2020 Oct;47(7):388- 391. 145. German. doi: 10.1055/a-1144-7035; Quinn D.M., Puhl R.M., Reinka M.A. Trying again (and again): Weight cycling and de- pressive symptoms in U.S. adults. PLoS ONE. 2020;15:e0239004. doi: 10.1371/jour- nal.pone.0239004. 146. Luppino F.S., de Wit L.M., Bouvy P.F., et al. Overweight, Obesity, and Depression. Arch. Gen. Psychiatry. 2010;67:220. doi: 10.1001/archgenpsychiatry.2010.2. 147. Baldini I, Casagrande BP, Estadella D. De- pression and obesity among females, are sex specificities considered? Arch Womens Ment Health. 2021 Apr 20. doi: 10.1007/s00737-021- 01123-6. 148. Pereira-Miranda E., Costa P.R.F., Queiroz V.A.O., Pereira-Santos M., Santana M.L.P. Overweight and Obesity Associated with Higher Depression Prevalence in Adults: A Systematic Review and Meta-Analysis. J. Am. Coll. Nutr. 2017;36:223–233. doi: 10.1080/07315724.2016.1261053. 149. Strauss RS. Childhood obesity and self-esteem. Pediatrics. 2000; 10.1542/peds.105.1.e15. 150. Carr D., Friedman M.A. Is obesity stigmatiz- ing? Body weight, perceived discrimination, and psychological well-being in the United States. J. Health. Soc. Behav. 2005;46:244–259. doi: 10.1177/002214650504600303. 151. Schwartz M.B., Chambliss H.O.N., Brownell K.D., Blair S.N., Billington C. Weight Bias among Health Professionals Specializing in Obesity. Obes. Res. 2003;11:1033–1039. doi: 10.1038/oby.2003.142. 152. Minkwitz J., Scheipl F., Cartwright L., Campbell I.C., Chittka T., Thormann J., Hegerl U., Sander C., Himmerich H. Why some obese people become depressed whilst others do not: Exploring links between cognitive reactivity, depression and obesity. Psychol. Health Med. 2019;24:362–373. doi: 10.1080/13548506.2018.1524153. 153. Thormann J., Chittka T., Minkwitz J., Kluge M., Himmerich H. Obesity and depression: An overview on the complex interactions of two diseases. Fortschr. Neurol. Psychiatr. 2013;81:145–153. 154. Vagena E., Ryu J. K., Baeza-Raja B., et al. A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA sig- naling. Translational Psychiatry. 2019;9(1):p. 141. doi: 10.1038/s41398-019-0470-1. 155. Sharma S., Fulton S. Diet-induced obesity pro- motes depressive-like behaviour that is asso- ciated with neural adaptations in brain re- ward circuitry. International Journal of Obesity. 2013;37(3):382–389. doi: 10.1038/ijo.2012.48. 156. Wise L.A., Adams-Campbell L.L., Palmer J.R., Rosenberg L. Leisure time physical activity in relation to depressive symp- toms in the Black Women’s Health Study. Ann. Behav. Med. 2006;32:68–76. doi: 10.1207/s15324796abm3201_8. 157. Oliver G., Wardle J. Perceived effects of stress on food choice. Physiol. Behav. 1999;66:511– 515. doi: 10.1016/S0031-9384(98)00322-9. 158. Dallman M.F., Pecoraro N.C., La Fleur S.E. Chronic stress and comfort foods: Self-medication and abdominal obesity. Brain Behav. Immun. 2005;19:275–280. doi: 10.1016/j.bbi.2004.11.004. MEERP LTD CMI JOURNAL 2 (1), 64−79 (2021) 77 OBESITY AND NON-COMMUNICABLE DISEASES: PART I CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES 159. Himmerich H., Minkwitz J., Kirkby K.C. Weight Gain and Metabolic Changes Dur- ing Treatment with Antipsychotics and An- tidepressants. Endocr. Metab. Immune Dis- ord. Drug Targets. 2015;15:252–260. doi: 10.2174/1871530315666150623092031. 160. Serretti A., Mandelli L. Antidepressants and Body Weight. J. Clin. Psychiatry. 2010;71:1259–1272. doi: 10.4088/JCP.09r05346blu. 161. Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, Zitman FG. Over- weight, obesity, and depression: a systematic review and meta-analysis of longitudinal stud- ies. Arch Gen Psychiatry. 2010 Mar;67(3):220- 9. doi: 10.1001/archgenpsychiatry.2010.2. 162. Milaneschi Y, Simmons WK, van Rossum EFC, Penninx BW. Depression and obesity: evidence of shared biological mechanisms. Mol Psychiatry. 2019 Jan;24(1):18-33. doi: 10.1038/s41380-018-0017-5 163. Bornstein S.R., Schuppenies A., Wong M.L., Licinio J. Approaching the shared biology of obesity and depression: The stress axis as the locus of gene-environment interac- tions. Mol. Psychiatry. 2006;11:892–902. doi: 10.1038/sj.mp.4001873. 164. Gibbons J.L., McHugh P.R. Plasma cor- tisol in depressive illness. J. Psychiatr. Res. 1962;1:162–171. doi: 10.1016/0022- 3956(62)90006-7. 165. Sachar E.J., Hellman L., Fukushima D.K., Gal- lagher T.F. Cortisol Production in Depressive Illness: A Clinical and Biochemical Clarifica- tion. Arch. Gen. Psychiatry. 1970;23:289–298. doi: 10.1001/archpsyc.1970.01750040001001. 166. Raison C., Miller A. Is depression an in- flammatory disorder? Curr. Psychiatry Rep. 2011;13:467–475. doi: 10.1007/s11920-011- 0232-0. 167. Hryhorczuk C., Sharma S. Metabolic dis- turbances connecting obesity and depres- sion. Front. Neurosci. 2013;7:177. doi: 10.3389/fnins.2013.00177. 168. Clark JM . The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroen- terol. 2006;40(Suppl 1):S5–S10.; Than NN , Newsome PN. A concise review of non- alcoholic fatty liver disease. Atherosclerosis. 2015;239(1):192–202. 169. Vernon G, Baranova A, Younossi ZM. Sys- tematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34:274–285. 170. Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gas- troenterol. 2006 Mar;40 Suppl 1:S5-10. doi: 10.1097/01.mcg.0000168638.84840.ff. 171. Li L , Gan Y, Li W, Wu C, Lu Z. Overweight, obesity and the risk of gallbladder and extra- hepatic bile duct cancers: a meta-analysis of observational studies. Obesity (Silver Spring). 2016;24(8):1786–1802. 172. Farrell GC. The liver and the waistline: Fifty years of growth. J Gastroenterol Hepatol. 2009;24 Suppl 3:S105–S118. 173. Pang Q , Zhang JY, Song SD, et al. Central obesity and nonalcoholic fatty liver disease risk after adjusting for body mass index. World J Gastroenterol. 2015;21(5):1650–1662. 174. Parker R, Kim SJ, Im GY, et al. Obesity in acute alcoholic hepatitis increases morbidity and mortality. EBioMedicine. 2019 Jul;45:511- 518. doi: 10.1016/j.ebiom.2019.03.046. 175. Watts T, Lauver D, Sethi AK, Snedden T, Zahner S. Hepatitis C virus infections among people aged 15-44, United States, 2009-2018. Public Health Nurs. 2021 Mar;38(2):167-175. doi: 10.1111/phn.12808. 176. Benhammou JN, Moon AM, Pisegna JR, Su F, Vutien P, Moylan CA, Ioannou GN. Non- alcoholic Fatty Liver Disease Risk Factors Affect Liver-Related Outcomes After Direct- Acting Antiviral Treatment for Hepatitis C. Dig Dis Sci. 2021 Jul;66(7):2394-2406. doi: 10.1007/s10620-020-06457-2. CMI JOURNAL 2 (1), 64−79 (2021) MEERP LTD 78 MEERP LTD SHASHI K. AGARWAL, MD 177. Do A, Esserman DA, Krishnan S, Lim JK, Taddei TH, Hauser RG 3rd, Tate JP, Re VL 3rd, Justice AC. ExcessWeight Gain After Cure of Hepatitis C Infection with Direct-Acting An- tivirals. J Gen InternMed. 2020 Jul;35(7):2025- 2034. doi: 10.1007/s11606-020-05782-6. How to cite this article: Agarwal S.K,, MD, OBESITY AND NON-COMMUNICABLE DISEASES: PART I Cardiovascular Diseases, Respiratory Diseases, Depression, Liver Diseases. Clinical Medicine Insights. 2021;64−79. https://doi.org/ 10.52845/CMI/2021-2-1-3 MEERP LTD CMI JOURNAL 2 (1), 64−79 (2021) 79 Introduction Discussion CARDIOVASCULAR DISEASES RESPIRATORY DISEASES DEPRESSION LIVER DISEASES Conclusions