Clinical Medicine Insights Received 25 Dec 2020 | Revised 22 Jan 2021 | Accepted 28 Feb 2021 | Published Online 30 Mar 2021 DOI: https://doi.org/10.52845/CMI/2021-2-1-4 CMI JOURNAL 2 (1), 80−97 (2021) ISSN (O) 2694-4626 REVIEW ARTICLE Obesity and Non-Communicable Diseases: Part II Cancer, Diabetes Mellitus, Kidney Diseases, Alzheimer’s Disease, Arthritis Shashi K. Agarwal, MD ∗ 12227 US Highway 1, #309 North Brunswick, NJ 08902,USA Abstract Obesity is increasing all over the world. An excess body weight, as recognized by a body mass index of more than 25, is associated with several chronic diseases, increased disability, and early mortality. Its main impact is on non-communicable diseases, such as cancer, diabetes mellitus, kidney diseases, Alzheimer’s disease, and arthritis. Successful weight loss strategies through healthy lifestyle behaviors and bariatric surgery have been associated with a decrease in morbidity, an improved quality of life, an increase in disease-free years, and improved longevity. Keywords: obesity, non-communicable diseases, cancer, diabetes mel- litus, chronic kidney disease, dementia, arthritis 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 The prevalence of overweight and obesity is increasing globally and is expected to reach 1.35 billion and 573 million respectively by 20301. Major health organizations recommend that a healthy lifestyle should include adherence to a normal body weight (a body mass index or BMI of 18.5–24.9 kg/m2), regular physical activity (150 min/week of moderate to vigorous physical activity), and a healthy diet (ideally 32 g/day of dietary fiber, 400 g/day of fruit and non-starchy vegetables, 0 g/week of processed meat, and <500 g/week of red meat), and avoidance of smoking and moderation in alcohol intake2. Healthy lifestyles help not only prevent but also help decrease the undesirable impact of several diseases3−5. Besides a reduction in mor- bidity, the overall health quality of life is improved in these patients and mortality is decreased6−8. Li et al. using data from the Nurses’ Health Study and the Health Professionals Follow-up Study (total of 123,219 participants), estimated that adherence to all five healthy lifestyles increases the lifespan at age 50 by 14 years in females and 12.2 years in males, when compared with those with zero low-risk factors9. A normal body weight is a major lifestyle factor in the prevention of noncommunicable diseases10. As mentioned in Part I of this manuscript, a BMI be- CMI JOURNAL 2 (1), 80−97 MEERP LTD 80 Open Access Jpurnal 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 tween 25 and 29.9 kg/m2 is considered overweight, while a BMI of >30 kg/m2 is considered obese11. The Global Burden of Disease project, in a metanalysis of 239 prospective studies in four continents, reported a J shaped relationship between BMI and all-cause mortality12. This research included >10 million peo- ple and recorded 385,879 deaths during amedian fol- low up of 13.7 years12. The lowest mortality was in individuals with a BMI of 20.0 to 25.0 kg/m212. All- cause mortality increased both below and above this BMI range12. The most dramatic increase in mor- bidity and mortality was noted in individuals who became obese12. Obesity is further divided into class 1 (30.0-34.9 kg/m2), class 2 (35.0-39.9 kg/m2), and class 3 (40 kg/m2 or greater)13. Mortality increases as the class of obesity increases12. The Global Burden of Disease project reported that mortality increased by 45% for grade I obesity, by 94% for grade 2 obesity, and 176% for grade-3 obesity12. The ben- eficial effect of weight loss has also been reported14. The Swedish Obese Subjects Study showed a 29% reduction in overall mortality (after 10.9 years of monitoring) in obese patients who underwent surgi- cal intervention for obesity14. The problems associated with obesity in several chronic medical conditions are discussed in this two- part manuscript. Part I discussed the role of obesity in cardiovascular diseases (CVD), chronic respiratory diseases, depression, and liver diseases. This part dis- cusses its effect on cancer, diabetes mellitus, kidney diseases, Alzheimer’s disease, and arthritis. 2 DISCUSSION Noncommunicable diseases (NCD) are common conditions affecting humans15. Cancer has become Supplementary information The online version of this article (10.52845/CMI/2021-2-1-4) 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 the king of all maladies and is on its way to replacing CVDs as the number one killer in the world16. It is es- timated that 1 in 5 men and 1 in 6 women developed cancer in 2016, resulting in the deaths of 1 in 8 men and 1 in 10 women17. The most common global can- cers are those involving the lung, colorectum, stom- ach, breast, prostate and liver17. Type 2 Diabetes Mellitus (DM) is one of the most common metabolic disorders worldwide18. It results from a combina- tion of reduced insulin secretion by pancreatic β- cells and peripheral insulin resistance19. Prediabetes is associated with an increased risk of developing DM20. This disease is associated with significant microvascular (retinopathy, nephropathy, and neu- ropathy) andmacrovascular (coronary artery disease, stroke, peripheral artery disease) pathology21. It re- duces the life expectancy of the affected individual by approximately six years22. Cardiovascular disease is extremely common in diabetics and cardiovascular complications are responsible for more than 50% of diabetes related deaths23. Diabetes is now considered an independent risk factor for CVD24. Prediabetes is also associated with a higher risk of atherosclerotic cardiovascular disease and all-cause mortality25. Chronic kidney disease (CKD) is defined by the pres- ence of kidney damage or an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 mt2, persisting for 3 months or more, irrespective of the cause26. It has become a worldwide public health problem27. DM is the leading cause28. CKD is a progressive disease, and as it worsens, the affected individuals need peritoneal dialysis or hemodialysis or kidney transplantation29. It affects most systems of the body and often leads to atherosclerotic car- diac disease, poor cognitive dysfunction, and a poor quality of life30−32. Dementia is a common world- wide disease33. Alzheimer’s disease (AD) is themost common form of dementia and is responsible for about 70% of the cases34. AD is a progressive and irreversible neurodegenerative disease, asso- ciated with amyloid plaques and neurofibrillary tangles in the brain35. The World Alzheimer Re- port estimates that 50 million people worldwide have dementia, and this number is projected to increase to 82 million by 2030 and to 152 million by 205036. It leads to loss of independence, poor quality of life, and premature institutionalization37. MEERP LTD CMI JOURNAL 2 (1), 80−97 (2021) 81 mailto:usacardiologist@gmail.com OBESITY AND NON-COMMUNICABLE DISEASES: PART II CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES It is also a major cause of death38. Treatment re- mains symptomatic, as a definitive cure is lacking39. Arthritis is of many types40. Osteoarthritis (OA) is the most common type and a major global cause of disability41. It is characterized by progressive car- tilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis42. It usually affects the knees and the hip and is associated with consid- erable pain and disability43,44. Rheumatoid arthritis (RA) is an autoimmune arthritis and is character- ized by symmetrical polyarthritis oftenwith systemic manifestations45. Gout is an autoinflammatory joint arthritis, induced by monosodium urate crystals that are deposited in joints (and soft tissues)46. Hype- ruricemia is usually the underlying abnormality47. Gout and hyperuricemia are both rising globally48,49. 2.1 CANCER Obesity has been linked to an increased risk for several cancers, including those of the breast (post- menopausal), colon and rectum, corpus uteri (en- dometrium), esophagus (adenocarcinoma), gallblad- der, kidney, liver, meningioma, multiple myeloma, ovary, pancreas, stomach (cardia), and thyroid50. A recent report from the World Cancer Research Fund and the American Institute for Cancer Research also indicated a potential link between body fatness and advanced prostate cancer and cancers of the mouth, pharynx, and larynx51. Excess body weight and can- cer is more than twice as high in women (368,500 cases) as in men (175,800 cases)52. Males demon- strate an increased risk for neoplasms of the colon, rectum, and prostate, while women have an increased risk for cancers of the breast, endometrium, and gallbladder53. Islami et al estimated that excess body weight was associated with 60.3% of uterine cancers, 33.9% of liver cancers, 11.3% of breast cancers in women, and 5.2% of colorectal cancers54. Lauby- Secretan et al. estimated that an increase of every 5 kg/m2 rise in body mass index resulted in a 5% increase in the risk of colorectal cancer and a 50% increase in the risk of endometrial cancer55. Central obesity is also positively associated with cancer56. Obesity induces a more rapid cancer progression57,58 and is associated with reduced efficacy of certain drugs59. Obese patients also have more cancer recur- rences and tend to develop secondary primary can- cers more often60. Obesity cancer survivors report a reduced quality of life61,62. Obesity is also associ- ated with decreased survival, both in children63 and adults64. Morbidly obese patients (BMI >40) exhibit a 52% higher mortality rate in men and a 62% higher mortality rate in women, when compared to those with normal weight65. Obesity contributes to a pro-carcinogenic environ- ment by producing a pro-inflammatory state66, ini- tiating several sex and growth hormonal changes67, increasing blood levels of insulin and insulin- like growth factor-168, promoting oxidative stress69, cell proliferation and angiogenesis70, and inhibiting apoptosis/cell death71. Mechanical effects of excess fat may also play a role in some cancers72. 2.2 DIABETES MELLITUS Studies indicate that more than 85% of people with DM are overweight or obese73. This number is on the increase, and it is estimated that by 2025, more than 300 million people worldwide will have DM associated with obesity74. Scientific data reveals that an increase in BMI, central obesity and an increase in body weight prognosticate the development of DM75−77. A study from the UK found that the risk of developing future DM was four times higher in obese children and obese adolescents78. Weight loss helps79. In the Diabetes Prevention Program, a median weight loss of 5.5% over 2.8 years reduced the risk of converting from prediabetes to diabetes by 58%80. Bariatric surgery not only results in a weight loss of 20% to 30% but also induces DM remission rates ranging from 23% to 60%81. In the Look AHEAD (Action for Health in Diabetics) trial, besides a lower AIC and a reduced need for diabetic medications, patients also reduced their hospitaliza- tions and health care costs, besides experiencing a reduction in sleep apnea, improved mobility, and a better quality of life82,83. Weight reduction is asso- ciated with an improvement in cardiovascular mor- bidity and mortality in these patients84. In a more recent DIRECT trial, weight loss was associated with sustained remissions of DM in more than a third of people at 24 months85. Obesity causes chronic inflammation, biotoxicity and adipocyte induced loss CMI JOURNAL 2 (1), 80−97 (2021) MEERP LTD 82 MEERP LTD SHASHI K. AGARWAL, MD of insulin sensitivity, and these factors contribute to the development of DM86. 2.3 KIDNEY DISEASES Obesity is a major cause of chronic kidney disease CKD87−94. A high BMI is often associated with the presence of proteinuria in individuals without kidney disease95−98. Furthermore, in numerous large population-based studies, high BMI appears to be associated with the development of low eGFR99,100. Obesity is also associated with a more rapid pro- gression of the disease. often leading to end stage renal disease (ESRD)101−109. Obese patients have a higher risk of complications during and after renal transplantation surgery110. As noted with CVDs and DM, central obesity seems to be more important than BMI as a risk factor for CKD in several cross- sectional studies111. A waist circumference (WC) >102 cm and a waist hip ratio (WHR) of 0.9 in females, and a WC >88 cm and WHR >0.8 in males, is associated with an increased risk of CKD, even if the BMI is normal112. Higher abdominal girth has been associated with albuminuria113,114, decreased eGFR115, and a higher incidence of ESRD116, in- dependent of BMI level. Visceral obesity (BMI- independent) also predicts poorer renal outcomes, including mortality in patients with ESRD117 and after kidney transplant118. Weight loss helps kidney disease119−125. In obesity related glomerulopathy, a weight loss of 12% re- sulted in a decrease in proteinuria by >80%119. Weight loss with bariatric surgery also results in improvement in kidney function120−125. An asso- ciation between obesity and nephrolithiasis has also been described, particularly with uric acid and calcium oxalate calculi126−129. Obesity is also associated with an increased risk of cancer of the kidney130,131. In a meta-analysis, Guh et al estimated that this increased risk was 1.82 for men and 2.64 for women132. Despite the deleterious effects of obesity on CKD and its progression, several studies have noted that obesity may result in lower mortality rates in patients with advanced CKD and ESRD133−136. This obesity paradox in these individuals may reduce mortality by providing better protein and energy reserves, a higher muscle mass with enhanced an- tioxidant capacity, and lower circulating actin and higher plasma gelsolin levels137,138. Obesity impacts the kidneys via production of adiponectin, leptin and resistin139−141. There are more inflammatory cytokines141, increased oxida- tive stress142, abnormal lipid metabolism143, activa- tion of the renin-angiotensin-aldosterone system144, and increased production of insulin with insulin resistance145,146. There may be a direct pressure effect of the increased perirenal fat also.147 Obe- sity is also closely associated with DMs, HTN, and atherosclerosis, which are also important risk factors for CKD148,149. 2.4 ALZHEIMER'S DISEASE The relationship between increased BMI and de- mentia is well established150,151. In a review of 19 longitudinal studies including 589,649 people aged 35 to 65 years, followed up for up to 42 years, obesity was associated with late life dementia150. This was also reported in another metanalysis (1.3 million adults aged ≥18 years) where a higher body mass increased the dementia risk by a RR of 1.3151. A systematic review and a meta-analysis also re- ported a link between obesity and AD152,153. Xu et al. reported that obese individuals at midlife de- veloped dementia at a mean odds ratio of 3.88154. Visceral obesity is also pathogenic for AD155,156. In a longitudinal study of 6,583 individuals, those with the largest abdominal diameter appeared to have a three-fold risk of developing demen- tia, when compared with those with the small- est diameter155. Another study observed that a larger waist-hip ratio was associated with de- creased hippocampal volume156, the latter often seen in patients with AD157. Although some stud- ies have noted that older people often have low body weight when they exhibit dementia, this low body weight is often deceptive as a causative factor158,159. It seems that dementia often takes 10 years to set in and during this time, BMI may de- cline in these individuals due to comorbidities and otherwise poor health160. Although other lifestyle changes help, weight loss also plays an important preventive and therapeutic role in AD161. It has been projected by an Australian study that in MEERP LTD CMI JOURNAL 2 (1), 80−97 (2021) 83 OBESITY AND NON-COMMUNICABLE DISEASES: PART II CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES 2050, dementia in old age can be reduced by 10% by decreasing midlife obesity by 20%162. A meta- analysis of seven RCTs (468 participants) and 13 longitudinal studies (551 participants) of overweight and obese adults without dementia, (mean age 50 years), reported that weight loss of 2 kg or more in people with BMI greater than 25 was associ- ated with a significant improvement in attention and memory163. Obesity is also a well-known risk factor for DM164, dyslipidemia165, cardiovascular diseases166, and cerebrovascular diseases167 - all known risk factors for AD. Obesity induces adipokine dys- regulation leading to central nervous system inflammation168−172. The resultant increase in microglia causes reduced synaptic plasticity and impaired neurogenesis173. Microglia also interfere with insulin action and can result in Aβ accumulation and reduce the tau protein degradation seen in AD173. 2.5 ARTHRITIS Obesity is commonly seen in patients with knee and hip osteoarthritis174.Obesity is traumatic to the knees175. The excessive joint loading in obese patients is thought to alter gait and movement strategies, resulting in joint malalignment and cartilage degeneration176. Obese patients under- going total knee arthroplasty experience increased revision rates, lower functional scores, and in- creased complications, including infection, when compared to non-obese patients177−179. Obese indi- viduals also suffer from increased osteo-arthritis of non-weight bearing joints180. The actions of pro-inflammatory adipokines and cytokines are implicated in this181. Obesity is also significantly associated with RA182−184.A meta-analysis of 11 studies concluded that obese patients had a rel- ative risk of 1.31 for RA185. Females are at a higher risk when compared to males186,187. Cen- tral obesity, even with normal BMI, appears to be worse in this relationship188. Obesity also dele- teriously impacts RA progression throughout the course of the disease189,190. In a meta-analysis, Liu et al found that obese patients had decreased remission during therapy and overall experienced poorer outcomes191. Interventions to prevent and re- verse obesity help improve the outcomes and quality of life in RA patients191. Obese patients with RA also exhibit higher comorbidity rates, negatively affecting RA prognosis192. The major damage is conveyed by adiposity related adipocytokines, which exert pro-inflammatory effects193,194. Sev- eral other potential mechanisms, such as vitamin D deficiency, sex hormone differences, and in- sulin resistance, may also play a role195. Gouty arthritis is also causally connectedwith obesity196. In an evaluation of 10 prospective studies, in- volving 27,944 cases with a median follow-up of 10.5 years, Aune et al. found that the relative risks for gouty arthritis were 2.67, 3.62, and 4.64 for people with a BMI of 30, 35, and 40 kg/m2, respectively, compared with people with a BMI of 20 kg/m2196. 3 CONCLUSION Obesity has a causal relationship with most major NCDs197. Obese children usually end up being obese in their adult life198. The increasing prevalence of obesity in children and adolescents portends an in- crease an increase in NCDs during adulthood in these individuals199. The evidence for the preventive and therapeutic effects of maintaining a normal BMI is persuasive200. Most studies also reveal the benefits of weight loss on NCDs, including via bariatric surgery79,120,162. It is therefore clear that obesity is an important lifestyle that needs to be targeted to decrease the NCD burden, both in children, adoles- cents, and adults. Acknowledgment: None Funding: None Conflict of interest: None REFERENCES 1. Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projec- tions to 2030. Int J Obes (Lond) 2008;32:1431– 1437. 2. https://www.wcrf.org/dietandcancer/cancer-pr evention-recommendations. Accessed October 11, 2020. CMI JOURNAL 2 (1), 80−97 (2021) MEERP LTD 84 MEERP LTD SHASHI K. AGARWAL, MD 3. LoConte NK, Gershenwald JE, Thomson CA, Crane TE, Harmon GE, Rechis R. Lifestyle Modifications and Policy Implications for Pri- mary and Secondary Cancer Prevention: Diet, Exercise, Sun Safety, and Alcohol Reduction. Am Soc Clin Oncol Educ Book. 2018 May 23;38:88-100. doi: 10.1200/EDBK_200093. PMID: 30231343. 4. Holme L, Haaheim S, Tonstad I, Hjermann I. Effect of dietary and antismoking advice on the incidence of myocardial infarction: A 16-year follow-up of the Oslo Diet and Antismoking Study after its close. Nutr Metab Cardiovasc. 2006;16:330–338. doi: 10.1016/j.numecd.2005.04.007. 5. Lindstrom J, Ilanne-Parikka P, Peltonen M, et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Preven- tion Study. Lancet. 2006;368:1673–1679. doi: 10.1016/S0140-6736(06)69701-8. 6. Chen X, Sekine M, Hamanishi S, Wang H, Gaina A, Yamagami T, Kagamimori S. Lifestyles and health-related quality of life in Japanese school children: a cross-sectional study. Prev Med. 2005 Jun;40(6):668-78. doi: 10.1016/j.ypmed.2004.09.034. 7. Zhang SC, Tao FB, Ueda A, Wei CN, Fang J. The influence of health-promoting lifestyles on the quality of life of retired workers in a medium-sized city of Northeastern China. Env- iron Health Prev Med. 2013 Nov;18(6):458-65. doi: 10.1007/s12199-013-0342-x. 8. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with over- weight and obesity using standard body mass index categories: a systematic review and meta- analysis. JAMA. 2013 Jan 2;309(1):71-82. doi: 10.1001/jama.2012.113905. 9. Li Y, Pan A, Wang DD, et al. Impact of Healthy Lifestyle Factors on Life Expectan- cies in the US Population. Circulation. 2018 Jul 24;138(4):345-355. doi: 10.1161/CIRCU- LATIONAHA.117.032047. 10. Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019 May;15(5):288-298. doi: 10.1038/s41574-019- 0176-8. 11. WHO Expert Consultation: Appropriate body- mass index for Asian populations and its im- plications for policy and intervention strategies. Lancet 363: 157–163, 2004. 12. Di Angelantonio E , Bhupathiraju S, Wormser D, et al. The Global Mortality Collabora- tion. Body-mass index and all-cause mortal- ity: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 2016;388:776–786. 13. Aronne LJ. Classification of obesity and assess- ment of obesity-related health risks. Obes Res. 2002;10(Suppl 2):105S–115S. 14. Sjöström L , Narbro K, Sjöström CD, et al. Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741–752. 15. NCD Countdown 2030 collaborators. NCD Countdown 2030: worldwide trends in non- communicable disease mortality and progress towards Sustainable Development Goal target 3.4. Lancet. 2018 Sep 22;392(10152):1072- 1088. doi: 10.1016/S0140-6736(18)31992-5. 16. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 coun- tries. CA Cancer J Clin. 2018;68:394-424. 17. The Global Cancer Observatory (IARC). GLOBOCAN 2018. Accessed March 1, 2019. gco.iarc.fr/. 18. Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet. 2017 Jun 3;389(10085):2239- 2251. doi: 10.1016/S0140-6736(17)30058-2. 19. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Osto- laza H, Martín C. Pathophysiology of Type 2 MEERP LTD CMI JOURNAL 2 (1), 80−97 (2021) 85 OBESITY AND NON-COMMUNICABLE DISEASES: PART II CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES Diabetes Mellitus. Int J Mol Sci. 2020 Aug 30;21(17):6275. doi: 10.3390/ijms21176275. 20. Tabák AG, Herder C, Rathmann W, Brunner EJ, Kivimäki M. Prediabetes: a high-risk state for diabetes development. Lancet. 2012 Jun 16;379(9833):2279-90. doi: 10.1016/S0140- 6736(12)60283-9. 21. Emerging Risk Factors Collaboration, Sar- war N, Gao P, Seshasai SR, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collabora- tive meta-analysis of 102 prospective studies. Lancet. 2010 Jun 26;375(9733):2215-22. doi: 10.1016/S0140-6736(10)60484-9. 22. Seshasai S.R.K., Kaptoge S., Thompson A., et al. Emerging Risk Factors Collaboration. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N. Engl. J. Med. 2011;364:829–8415. 23. Strain WD, Paldánius PM. Diabetes, cardio- vascular disease and the microcirculation [pub- lished correction appears in Cardiovasc Dia- betol. 2021 Jun 11;20(1):120]. Cardiovasc Di- abetol. 2018;17(1):57. Published 2018 Apr 18. doi:10.1186/s12933-018-0703-2 24. Fox CS, Golden SH, Anderson C, et al. Up- date on prevention of cardiovascular disease in adults with type 2 diabetes mellitus in light of recent evidence: a scientific statement from the American Heart Association and the American Diabetes Association. Circulation. 2015;132:691–718. 25. Huang D, Refaat M, Mohammedi K, Jayyousi A, Al Suwaidi J, Abi Khalil C. Macrovascular Complications in Pa- tients with Diabetes and Prediabetes. Biomed Res Int. 2017;2017:7839101. doi: 10.1155/2017/7839101 26. Chapter 1: Definition and classification of CKD. Kidney Int Suppl (2011). 2013 Jan;3(1):19-62. 27. Eckardt KU, Coresh J, Devuyst O, Johnson RJ, Kottgen A, Levey AS, et al. Evolving importance of kidney disease: from sub- specialty to global health burden. Lancet. 2013;382(9887):158–69. 10.1016/S0140- 6736(13)60439-0. 28. GBD Chronic Kidney Disease Collaboration Global, regional, and national burden of chronic kidney disease, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395:709–733. doi: 10.1016/S0140-6736(20)30045-3. 29. Tsai WC, Wu HY, Peng YS, et al. Risk Factors for Development and Progression of Chronic Kidney Disease: A Systematic Review and Exploratory Meta-Analysis. Medicine (Baltimore). 2016 Mar;95(11):e3013. doi: 10.1097/MD.0000000000003013. 30. Van Biesen W, De Bacquer D, Verbeke F, Delanghe J, Lameire N, Vanholder R. The glomerular filtration rate in an apparently healthy population and its relation with cardio- vascular mortality during 10 years. European heart journal. 2007;28(4):478–83. 31. Etgen T, Chonchol M, Forstl H, Sander D. Chronic Kidney Disease and Cognitive Impairment: A Systematic Review and Meta- Analysis. American journal of nephrol- ogy. 2012;35(5):474–82. Epub 2012/05/05. 10.1159/000338135. 32. Perlman RL, Finkelstein FO, Liu L, Roys E, Kiser M, Eisele G, et al. Quality of life in chronic kidney disease (CKD): a cross-sectional analysis in the Renal Research Institute-CKD study. Am J Kidney Dis. 2005;45(4):658–66. 33. Patterson C. Alzheimer’s Disease International; London: 2018. World Alzheimer report 2018) and Alzheimers disease is responsible for 50% to 70% of these cases. https://www.dementia.c om/causes.html - accessed July 9, 2021. 34. Reitz C, Mayeux R. Alzheimer disease: epi- demiology, diagnostic criteria, risk factors and CMI JOURNAL 2 (1), 80−97 (2021) MEERP LTD 86 MEERP LTD SHASHI K. AGARWAL, MD biomarkers. Biochem Pharmacol. 2014 Apr 15;88(4):640-51. 35. Yiannopoulou KG, Papageorgiou SG. Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013 Jan;6(1):19-33. doi: 10.1177/1756285612461679. 36. Wimo A., Ali G.-C., Guerchet M., Prince M., Prina M., Wu Y.-T., World Alzheimer Report 2015 The Global Impact of Dementia. An Anal- ysis of Prevalence, Incidence, Cost and Trends. [(accessed on 30 January 2021. 37. Yu F, Kolanowski A, Strumpf N, Eslinger P. Improving cognition and function through exercise intervention in Alzheimer’s disease. J Nurs Scholarsh. 2006;38(4):358–365. doi: 10.1111/j.1547-5069.2006.00127.x. 38. Alzheimer’s Association. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 2016 Apr;12(4):459-509. doi: 10.1016/j.jalz.2016.03.001. 39. Yiannopoulou K.G., Papageorgiou S.G. Cur- rent and future treatments in Alzheimer disease: An update. J. Cent. Nerv. Syst. Dis. 2020:12. doi: 10.1177/1179573520907397. 40. Bortoluzzi A, Furini F, Scirè CA. Osteoarthritis and its management - Epidemiology, nutritional aspects and environmental factors. Autoimmun Rev. 2018 Nov;17(11):1097-1104. 41. JBortoluzzi A, Furini F, Scirè CA. Osteoarthri- tis and its management - Epidemiology, nutri- tional aspects and environmental factors. Au- toimmun Rev. 2018 Nov;17(11):1097-1104. 42. Harrell C. R.,Markovic B. S., FellabaumC., Ar- senijevic A., Volarevic V. (2019). Mesenchy- mal stem cell-based therapy of osteoarthri- tis: current knowledge and future perspec- tives. Biomed. Pharmacother. 109, 2318–2326. 10.1016/j.biopha.2018.11.099. 43. Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, Heyse SP, Hirsch R, Hochberg MC, Hunder GG, Liang MH, Pillemer SR, Steen VD, Wolfe F. Estimates of the prevalence of arthritis and selected muscu- loskeletal disorders in the United States. Arthri- tis Rheum. 1998. 44. Guccione AA, Felson DT, Anderson JJ, An- thony JM, Zhang Y, Wilson PW, Kelly-Hayes M, Wolf PA, Kreger BE, Kannel WB. The ef- fects of specific medical conditions on the func- tional limitations of elders in the Framingham study. Am J Public Health. 1994;84:351–358. doi: 10.2105/AJPH.84.3.351. 45. van derWoude D, van der Helm-vanMil AHM. Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2018;32:174–187. 46. Kuo CF, Grainge MJ, Zhang W, Doherty M. Global epidemiology of gout: prevalence, in- cidence and risk factors. Nat Rev Rheumatol. 2015;11:649–662. 47. Li Q, Li X, Wang J, Liu H, Kwong JS, Chen H, Li L, Chung SC, Shah A, Chen Y, An Z, Sun X, Hemingway H, Tian H, Li S. Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements. BMJ Open. 2019 Aug 24;9(8):e026677. doi: 10.1136/bmjopen- 2018-026677. 48. Kuo C-F, Grainge MJ, Zhang W, et al.. Global epidemiology of gout: prevalence, in- cidence and risk factors. Nat Rev Rheumatol 2015;11:649–62. 10.1038/nrrheum.2015.91. 49. Kuo C-F, Grainge MJ, Mallen C, et al. Ris- ing burden of gout in the UK but continuing suboptimal management: a nationwide popu- lation study. Ann Rheum Dis 2015;74:661–7. 10.1136/annrheumdis-2013-204463. 50. Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body fatness and cancer — viewpoint of the IARC Working Group. N Engl J Med. 2016; 375: 794- 798. MEERP LTD CMI JOURNAL 2 (1), 80−97 (2021) 87 OBESITY AND NON-COMMUNICABLE DISEASES: PART II CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES 51. World Cancer Research Fund/American Insti- tute for Cancer Research. Continuous Update Project Report 2018. Body Fatness and Weight Gain and the Risk of Cancer. London, UK: World Cancer Research Fund International; 2018. 52. Pearson-Stuttard J, Zhou B, Kontis V, Bentham J, Gunter MJ, Ezzati M. Worldwide burden of cancer attributable to diabetes and high body- mass index: a comparative risk assessment. Lancet Diabetes Endocrinol. 2018;6:e6-e15. 53. JBrawer R , Brisbon N, Plumb J. Obesity and cancer. Prim Care. 2009;36(3):509–531.; Calle EE , Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625– 1638. 54. Islami, F., Goding Sauer, A., Miller, K.D., Siegel, R.L., Fedewa, S.A., Jacobs, E.J., Mc- Cullough, M.L., Patel, A.V., Ma, J., Soerjo- mataram, I., Flanders, W.D., Brawley, O.W., Gapstur, S.M. and Jemal, A. (2018), Propor- tion and number of cancer cases and deaths at- tributable to potentially modifiable risk factors in the United States. CA: A Cancer Journal for Clinicians, 68: 31-54. doi:10.3322/caac.21440. 55. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, International Agency for Research on Cancer Handbook Working Group Body fatness and cancer– viewpoint of the IARC Working Group. N Engl J Med 2016;375:794-8. 10.1056/NE- JMsr1606602. 56. Freisling, H., Arnold, M., Soerjomataram, I. et al. Comparison of general obesity and measures of body fat distribution in older adults in rela- tion to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe. Br J Cancer 116, 1486–1497 (2017). h ttps://doi.org/10.1038/bjc.2017.106. 57. Candace A. Gilbert and Joyce M. Slingerland. Cytokines, Obesity, and Cancer: New Insights onMechanisms Linking Obesity to Cancer Risk and Progression. Annual Review of Medicine 2013 64:1, 45-57. 58. Ringel AE, Drijvers JM, Baker GJ, et al. Obe- sity Shapes Metabolism in the Tumor Microen- vironment to Suppress Anti-Tumor Immunity. Cell. 2020 Dec 23;183(7):1848-1866.e26. doi: 10.1016/j.cell.2020.11.009. 59. Christine Desmedt, Marco Fornili, Florian Clatot, et al. Differential Benefit of Adjuvant Docetaxel-Based Chemotherapy in Patients With Early Breast Cancer According to Baseline Body Mass Index. Journal of Clinical Oncology 2020 38:25, 2883-2891. 60. Sang Min Park, Young Ho Yun, Young Ae Kim, Minkyung Jo, Young-Joo Won, Joung Hwan Back, and Eun-Sook Lee. Prediagno- sis Body Mass Index and Risk of Secondary Primary Cancer in Male Cancer Survivors: A Large Cohort Study. Journal of Clinical Oncol- ogy 2016 34:34, 4116-4124. 61. Rock CL, Doyle C, Demark-Wahnefried W, et al. Nutrition and physical activity guide- lines for cancer survivors. CA Cancer J Clin. 2012;62:243–274. 62. Firkins J, Hansen L, Driessnack M, Dieckmann N. Quality of life in ”chronic” cancer sur- vivors: a meta-analysis. J Cancer Surviv. 2020 Aug;14(4):504-517. doi: 10.1007/s11764-020- 00869-9. 63. Orgel E, Sposto R, Malvar J, Seibel NL, Ladas E, Gaynon PS, et al. Impact on survival and toxicity by duration of weight extremes dur- ing treatment for pediatric acute lymphoblastic leukemia: A report from the Children’s Oncol- ogy Group. J Clin Oncol 2014;32:1331–7. 64. E.E. Calle, C. Rodriguez, K. Walker- Thurmond, M.J. Thun. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med, 348 (2003), pp. 1625-1638. CMI JOURNAL 2 (1), 80−97(2021) MEERP LTD 88 MEERP LTD SHASHI K. AGARWAL, MD 65. E.E. Calle, C. Rodriguez, K. Walker- Thurmond, M.J. Thun. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med, 348 (2003), pp. 1625-1638. 66. Kolb R, Sutterwala FS, Zhang W. Obesity and cancer: inflammation bridges the two. Curr Opin Pharmacol. 2016 Aug;29:77-89. doi: 10.1016/j.coph.2016.07.005. 67. Zimta AA, Tigu AB, Muntean M, Cenariu D, Slaby O, Berindan-Neagoe I. Molecular Links between Central Obesity and Breast Cancer. Int J Mol Sci. 2019 Oct 28;20(21):5364. doi: 10.3390/ijms20215364. 68. Perry RJ, Shulman GI. Mechanistic Links between Obesity, Insulin, and Cancer. Trends Cancer. 2020 Feb;6(2):75-78. doi: 10.1016/j.trecan.2019.12.003. 69. Manna P, Jain SK. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies. Metab Syndr Re- lat Disord. 2015 Dec;13(10):423-44. doi: 10.1089/met.2015.0095 70. Kolb R, Kluz P, Tan ZW, et al. Obesity- associated inflammation promotes angiogene- sis and breast cancer via angiopoietin-like 4. Oncogene. 2019 Mar;38(13):2351-2363. doi: 10.1038/s41388-018-0592-6. 71. Sergeev IN. Regulation of apoptosis in adipocytes and breast cancer cells by 1,25- dihydroxyvitamin D3: a link between obesity and breast cancer. HormMol Biol Clin Investig. 2013 Aug;14(3):99-106. doi: 10.1515/hmbci- 2013-0012. 72. Long E, Beales IL. The role of obesity in oesophageal cancer development. Therap Adv Gastroenterol. 2014 Nov;7(6):247-68. doi: 10.1177/1756283X14538689. 73. Zimmet P., Alberti K.G.M.M., Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001;414:782–787. doi: 10.1038/414782a. 74. Bhupathiraju S.N., Hu F.B. Epidemiol- ogy of Obesity and Diabetes and Their Cardiovascular Complications. Circ. Res. 2016;118:1723–1735. doi: 10.1161/CIRCRE- SAHA.115.306825. 75. QiaoQ., Nyamdorj R. The optimal cutoff values and their performance of waist circumference and waist-to-hip ratio for diagnosing type II diabetes. Eur. J. Clin. Nutr. 2009;64:23–29. 76. DeFronzo RA , Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, Hu FB, Kahn CR, Raz I, Shulman GI, Simonson DC, Testa MA, Weiss R. Type 2 diabetes mellitus. Nat Rev Dis Primers. 2015;1:15019. 77. Galassi A , Reynolds K, He J. Metabolic syn- drome and risk of cardiovascular disease: a meta-analysis. Am J Med. 2006;119(10):812– 819. 78. Ali Abbasi, Dorota Juszczyk, Cornelia H. M. van Jaarsveld, Martin C. Gulliford, Body Mass Index and Incident Type 1 and Type 2 Diabetes in Children and Young Adults: A Retrospective Cohort Study, Journal of the Endocrine Society, Volume 1, Issue 5, 1May 2017, Pages 524–537, https://doi.org/10.1210/js.2017-00044. 79. Lean MEJ, Leslie WS, Barnes AC, et al. Dura- bility of a primary care-led weight-management intervention for remission of type 2 diabetes: 2- year results of the DiRECT open-label, cluster- randomised trial. Lancet Diabetes Endocrinol. 2019 May;7(5):344-355. doi: 10.1016/S2213- 8587(19)30068-3. 80. Knowler WC , Fowler SE, Hamman RF, Christophi CA, Hoffman HJ, Brenneman AT, Brown-Friday JO, Goldberg R, Venditti E, Nathan DM; Diabetes Prevention Program Re- search Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374(9702):1677–1686. 81. Hanipah ZN, Schauer PR. Bariatric Surgery as a Long-Term Treatment for Type 2 Di- abetes/Metabolic Syndrome. Annu Rev Med. MEERP LTD CMI JOURNAL 2 (1), 80−97 (2021) 89 OBESITY AND NON-COMMUNICABLE DISEASES: PART II CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES 2020 Jan 27;71:1-15. doi: 10.1146/annurev- med-053117-123246. 82. Pi-Sunyer X. The Look AHEAD trial: a review and discussion of its outcomes. Curr Nutr Rep 2014;3:387–39. 83. Espeland MA, Glick HA, Bertoni A, et al; Look AHEAD Research Group. Impact of an intensive lifestyle intervention on use and cost of medical services among overweight and obese adults with type 2 diabetes: the Ac- tion for Health in Diabetes. Diabetes Care 2014;37:2548–2556. 84. Look AHEAD Research Group; Gregg EW, Jakicic JM, Blackburn G, et al. 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;4:913–921. 85. Lean MEJ, Leslie WS, Barnes AC, et al. Dura- bility of a primary care-led weight-management intervention for remission of type 2 diabetes: 2- year results of the DiRECT open-label, cluster- randomised trial. Lancet Diabetes Endocrinol. 2019 May;7(5):344-355. doi: 10.1016/S2213- 8587(19)30068-3. 86. Dyson PA. The therapeutics of lifestyle man- agement on obesity. Diabetes Obes Metab. 2010 Nov;12(11):941-6. doi: 10.1111/j.1463- 1326.2010.01256.x. 87. Hall JE, Henegar JR, Dwyer TM, Liu J, Silva AA, Kuo JJ, et al. Is obesity a major cause of chronic kidney disease? Adv Ren Replace Ther 2004;11:41-54. 88. Kopple JD, Feroze U. The effect of obesity on chronic kidney disease. J Ren Nutr 2011;21:66- 71. DOI: http://dx.doi.org/10.1053/j.jrn.2010.1 0.009. 89. Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA 2005;293:455-62. PMID: 15671430 DOI: http://dx.doi.org/10.1001/jama.293.4.45 5. http://dx.doi.org/10.1001/jama.293.4.455. 90. Chang A, van Horn L, Jacobs DR Jr, Liu K, Muntner P, Newsome B, et al. Lifestyle-related factors, obesity, and incidentmicroalbuminuria: The CARDIA (Coronary Artery Risk Develop- ment in Young Adults) study. Am J Kidney Dis 2013;62:267-75. DOI: http://dx.doi.org/10.105 3/j.ajkd.2013.02.363. 91. Lee KB, Hyun YY, Kim H. DASH dietary pattern and chronic kidney disease in elderly Korean population. Nephrol Dial Transplant 2015;30:iii504-iii505. 92. SongYM, Sung J, Lee K. Longitudinal relation- ships of metabolic syndrome and obesity with kidney function: Healthy Twin Study. Clin Exp Nephrol 2015;19:887-94. DOI: http://dx.doi.or g/10.1053/j.ajkd.2013.02.363. 93. WangY, ChenX, SongY, Caballero B, Cheskin LJ: Association between obesity and kidney disease: A systematic review andmeta-analysis. Kidney Int 73: 19–33, 2008. 94. Kopple JD, Feroze U. The effect of obesity on chronic kidney disease. J Ren Nutr 2011;21:66- 71. DOI: http://dx.doi.org/10.1053/j.jrn.2010.1 0.009. 95. Pinto-Sietsma SJ, Navis G, Janssen WM, de Zeeuw D, Gans RO, de Jong PE, et al. A central body fat distribution is related to re- nal function impairment, even in lean sub- jects. Am J Kidney Dis. 2003;41:733–741. doi: 10.1016/S0272-6386(03)00020-9. 96. Foster MC, Hwang SJ, Larson MG, Licht- man JH, Parikh NI, Vasan RS, Levy et al. Overweight, obesity, and the development of stage 3 CKD: the Framingham Heart Study. Am J Kidney Dis. 2008;52:39–48. doi: 10.1053/j.ajkd.2008.03.003. 97. Kramer H, Luke A, Bidani A, Cao G, Cooper R, McGee D. Obesity and prevalent and incident CKD: the Hypertension Detection and Follow- Up Program. Am J Kidney Dis. 2005;46:587– 594. doi: 10.1053/j.ajkd.2005.06.007. CMI JOURNAL 2 (1), 80−97 (2021) MEERP LTD 90 MEERP LTD SHASHI K. AGARWAL, MD 98. Chang A, Van HL, Jacobs DR, Jr, Liu K, Muntner P, Newsome B, et al. Lifestyle- related factors, obesity, and incident microal- buminuria: the CARDIA (Coronary Artery Risk Development in Young Adults) study. Am J Kidney Dis. 2013;62:267–275. doi: 10.1053/j.ajkd.2013.02.363. 99. Ejerblad E, Fored CM, Lindblad P, Fryzek J, McLaughlin JK, Nyren O. Obesity and risk for chronic renal failure. J Am Soc Nephrol. 2006;17:1695–1702. doi: 10.1681/ASN.2005060638. 100. Gelber RP, Kurth T, Kausz AT, Manson JE, Buring JE, Levey AS, et al. Association be- tween body mass index and CKD in apparently healthy men. Am J Kidney Dis. 2005;46:871– 880. doi: 10.1053/j.ajkd.2005.08.015. 101. Lu JL, Kalantar-Zadeh K, Ma JZ, Quarles LD, Kovesdy CP. Association of body mass index with outcomes in patients with CKD. J Am Soc Nephrol. 2014;25:2088–2096. doi: 10.1681/ASN.2013070754. 102. Evangelista LS, Cho W-K, Kim Y (2018) Obe- sity and chronic kidney disease: A population- based study among South Koreans. PLoS ONE 13(2): e0193559. https://doi.org/10.1371/journ al.pone.0193559. 103. HerringtonW.G., Smith M., Bankhead C., Mat- sushita K., Stevens S., Jolt T., Hobbs F.R., Coresh J., Woodward M. Body-mass index and risk of advanced chronic kidney disease: Prospective analyses from a primary care co- hort of 1.4 million adults in England. PLoS ONE. 2017;12:e0173515. doi: 10.1371/jour- nal.pone.0173515. 104. Lu JL, Molnar MZ, Naseer A, Mikkelsen MK, Kalantar-Zadeh K. Kovesdy CP: Association of age and BMI with kidney function and mortality: a cohort study. Lancet Diabetes En- docrinol. 2015;3:704–714. doi: 10.1016/S2213- 8587(15)00128-X. 105. Munkhaugen J, Lydersen S, Wideroe TE, Hallan S. Prehypertension, obesity, and risk of kidney disease: 20-year follow- up of the HUNT I study in Norway. Am J Kidney Dis. 2009;54:638–646. doi: 10.1053/j.ajkd.2009.03.023. 106. Iseki K, Ikemiya Y, Kinjo K, Inoue T, Iseki C, Takishita S. Body mass index and the risk of development of end-stage renal disease in a screened cohort. Kidney Int. 2004;65:1870– 1876. doi: 10.1111/j.1523-1755.2004.00582.x. 107. Vivante A, Golan E, Tzur D, Leiba A, Tirosh A, Skorecki K, et al. Body mass index in 1.2 million adolescents and risk for end-stage re- nal disease. Arch Intern Med. 2012;172:1644– 1650. doi: 10.1001/2013.jamainternmed.85. 108. Hsu C, McCulloch C, Iribarren C, Darbinian J. Go A.: Body mass index and risk for end-stage renal disease. Ann Intern Med. 2006;144:21– 28. doi: 10.7326/0003-4819-144-1-200601030- 00006. 109. Lu JL, Kalantar-Zadeh K, Ma JZ, Quarles LD, Kovesdy CP. Association of body mass in- dex with outcomes in patients with CKD. J Am Soc Nephrol. 2014 Sep;25(9):2088-96. doi: 10.1681/ASN.2013070754. 110. Molnar MZ, Kovesdy CP, Mucsi I, Bun- napradist S, Streja E, Krishnan M, Kalantar- Zadeh K: Higher recipient body mass index is associated with post-transplant delayed kidney graft function. Kidney Int 80: 218–224, 2011. 111. Kopple JD, Feroze U. The effect of obesity on chronic kidney disease. J Ren Nutr 2011;21:66- 71. DOI: http://dx.doi.org/10.1053/j.jrn.2010.1 0.009. 112. Zoccali C, Torino C, Tripepi G, Mallamaci F: Assessment of obesity in chronic kidney dis- ease: What is the best measure? Curr Opin Nephrol Hypertens 21: 641–646, 2012. 113. Thoenes M, Reil JC, Khan BV, Bramlage P, Volpe M, Kirch W, et al. Abdominal obesity MEERP LTD CMI JOURNAL 2 (1), 80−97 (2021) 91 OBESITY AND NON-COMMUNICABLE DISEASES: PART II CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES is associated with microalbuminuria and an el- evated cardiovascular risk profile in patients with hypertension. Vasc Health Risk Manag. 2009;5:577–585. 114. Foster MC, Hwang SJ, Massaro JM, Hoff- mann U, DeBoer IH, Robins SJ, et al. Association of subcutaneous and visceral adiposity with albuminuria: the Framingham Heart Study. Obesity. 2011;19:1284–289. doi: 10.1038/oby.2010.308. 115. Pinto-Sietsma SJ, Navis G, Janssen WM, de ZD, Gans RO, de Jong PE. A central body fat distribution is related to renal function impair- ment, even in lean subjects. Am J Kidney Dis. 2003;41:733-741. 116. Kramer H, Gutierrez OM, Judd SE, Muntner P, Warnock DG, Tanner RM, et al. Waist circumference, body mass index, and ESRD in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study. Am J Kidney Dis. 2016;67:62–69. doi: 10.1053/j.ajkd.2015.05.023. 117. Postorino M, Marino C, Tripepi G, Zoccali C. Abdominal obesity and all-cause and cardio- vascular mortality in end-stage renal disease. J Am Coll Cardiol. 2009;53:1265–1272. doi: 10.1016/j.jacc.2008.12.040. 118. Kovesdy CP, Czira ME, Rudas A, Ujszaszi A, Rosivall L, Novak M, et al. Body mass index, waist circumference and mortality in kidney transplant recipients. Am J Transplant. 2010;10:2644–2651. doi: 10.1111/j.1600- 6143.2010.03330.x. 119. Praga M. Hernamndez E. Andres A. et al. Ef- fects of body-weight loss and captopril treat- ment on proteinuria associated with obesity. Nephron. 1995; 70: 35-41. 120. Alexander JW, Goodman HR, Hawver LR, Cardi MA: Improvement and stabilization of chronic kidney disease after gastric bypass. Surg Obes Relat Dis 5: 237–241, 2009. 121. Hou CC, Shyu RS, Lee WJ, Ser KH, Lee YC, Chen SC: Improved renal function 12 months after bariatric surgery. Surg Obes Relat Dis 9: 202–206, 2013. 122. Tafti BA, Haghdoost M, Alvarez L, Curet M, Melcher ML: Recovery of renal function in a dialysis-dependent patient following gastric by- pass surgery. Obes Surg 19: 1335–1339, 2009. 123. Bueter M, Dubb SS, Gill A, Joannou L, Ahmed A, Frankel AH, Tam FW, le Roux CW: Renal cytokines improve early after bariatric surgery. Br J Surg 97: 1838–1844, 2010. 124. Amor A, Jiménez A, Moizé V, Ibarzabal A, Flores L, Lacy AM, Vidal J: Weight loss in- dependently predicts urinary albumin excretion normalization in morbidly obese type 2 diabetic patients undergoing bariatric surgery. Surg En- dosc 27: 2046–2051, 2013. 125. Heneghan HM, Cetin D, Navaneethan SD, OrzechN, Brethauer SA, Schauer PR: Effects of bariatric surgery on diabetic nephropathy after 5 years of follow-up. Surg Obes Relat Dis 9: 7– 14, 2013. 126. Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA 2005;293:455-62. DOI: http://dx.doi.or g/10.1001/jama.293.4.455. 127. Scales CD, Jr, Smith AC, Hanley JM, Sai- gal CS. Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160–165. doi: 10.1016/j.eururo.2012.03.052. 128. Curhan GC, Willett WC, Rimm EB, Speizer FE, Stampfer MJ. Body size and risk of kidney stones. J Am Soc Nephrol. 1998;9:1645–1652. 129. Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kid- ney stones. JAMA. 2005;293:455–46. doi: 10.1001/jama.293.4.455. 130. Arnold M, Pandeya N, Byrnes G, Renehan AG, Stevens GA, Ezzati M, et al. Global burden CMI JOURNAL 2 (1), 80−97 (2021) MEERP LTD 92 MEERP LTD SHASHI K. AGARWAL, MD of cancer attributable to high body-mass in- dex in 2012: a population-based study. Lancet Oncol. 2015;16:36–46. doi: 10.1016/S1470- 2045(14)71123-4. 131. Kopple JD, Feroze U. The effect of obesity on chronic kidney disease. J Ren Nutr 2011;21:66- 71. DOI: http://dx.doi.org/10.1053/j.jrn.2010.1 0.009. 132. Guh DP, Zhang W, Bansback N, Amarsi Z, BirminghamCL, Anis AH. The incidence of co- morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health. 2009;9:88. Published 2009 Mar 25. doi:10.1186/1471-2458-9-88. 133. Lu JL, Kalantar-Zadeh K, Ma JZ, Quarles LD, Kovesdy CP. Association of body mass index with outcomes in patients with CKD. J Am Soc Nephrol. 2014;25:2088–2096. doi: 10.1681/ASN.2013070754. 134. Kovesdy CP, Anderson JE, Kalantar-Zadeh K. Paradoxical association between body mass in- dex and mortality in men with CKD not yet on dialysis. Am J Kidney Dis. 2007;49:581–591. doi: 10.1053/j.ajkd.2007.02.277. 135. Kalantar-Zadeh K, Kuwae N,WuDY, Shantouf RS, Fouque D, Anker SD, et al. Associations of body fat and its changes over time with quality of life and prospective mortality in hemodialy- sis patients. Am J Clin Nutr. 2006;83:202–210. 136. Beddhu S, Pappas LM, Ramkumar N, Samore M. Effects of body size and body compo- sition on survival in hemodialysis patients. J Am Soc Nephrol. 2003;14:2366–2372. doi: 10.1097/01.ASN.0000083905.72794.E6. 137. Beddhu S, Pappas LM, Ramkumar N, Samore M. Effects of body size and body compo- sition on survival in hemodialysis patients. J Am Soc Nephrol. 2003;14:2366–2372. doi: 10.1097/01.ASN.0000083905.72794.E6. 138. Lee PS, Sampath K, Karumanchi SA, Tamez H, Bhan I, Isakova T, et al. Plasma gelsolin and circulating actin correlate with hemodialysis mortality. J Am Soc Nephrol. 2009;20:1140– 1148. doi: 10.1681/ASN.2008091008. 139. Sharma K. The link between obesity and albuminuria: adiponectin and podocyte dys- function. Kidney Int. 2009;76:145–148. doi: 10.1038/ki.2009.137. 140. Wolf G, Ziyadeh FN. Leptin and renal fibro- sis. Contrib Nephrol. 2006;151:175–183. doi: 10.1159/000095328. 141. Ellington AA, Malik AR, Klee GG, Turner ST, Rule AD, Mosley TH, Jr, et al. Association of plasma resistin with glomerular filtration rate and albuminuria in hypertensive adults. Hyper- tension. 2007;50:708–714. doi: 10.1161/HY- PERTENSIONAHA.107.095257. 142. Kwaifa IK, Bahari H, Yong YK, Noor SM. Endothelial Dysfunction in Obesity-Induced Inflammation: Molecular Mechanisms and Clinical Implications. Biomolecules. 2020 Feb 13;10(2):291. doi: 10.3390/biom10020291. 143. Ruan XZ, Varghese Z, Moorhead JF. An update on the lipid nephrotoxicity hypothe- sis. Nat Rev Nephrol. 2009;5:713–721. doi: 10.1038/nrneph.2009.184. 144. Ruster C, Wolf G. The role of the renin- angiotensin-aldosterone system in obesity- related renal diseases. Semin Nephrol. 2013;33:44–53. doi: 10.1016/j.semnephrol. 20 12.12.002. 145. Oterdoom LH, de Vries AP, Gansevoort RT, de Jong PE, Gans RO, Bakker SJ. Fast- ing insulin modifies the relation between age and renal function. Nephrol Dial Transplant. 2007;22:1587–1592. doi: 10.1093/ndt/gfm037. 146. Reaven GM. Banting lecture 1988. Role of insulin resistance in human dis- ease. Diabetes. 1988;37:1595–1607. doi: 10.2337/diab.37.12.1595. 147. D’Marco L, Salazar J, Cortez M, et al. Perirenal fat thickness is associated with metabolic risk factors in patients with chronic kidney disease. Kidney Res Clin Pract. 2019; doi.org/10.23876/j.krcp.18.0155. MEERP LTD CMI JOURNAL 2 (1), 80−97 (2021) 93 OBESITY AND NON-COMMUNICABLE DISEASES: PART II CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES 148. Wickman C, Kramer H. Obesity and kidney disease: potential mechanisms. Semin Nephrol. 2013 Jan;33(1):14-22. doi: 10.1016/j.semnephrol.2012.12.006. 149. Silva Junior GB, Bentes AC, Daher EF, Matos SM. Obesity and kidney disease. J Bras Ne- frol. 2017 Mar;39(1):65-69. Portuguese, En- glish. doi: 10.5935/0101-2800.20170011. 150. Albanese E, Launer LJ, EggerM. Bodymass in- dex in midlife and dementia: systematic review and meta-regression analysis of 589,649 men and women followed in longitudinal studies. Alzheimers Dement (Amst) 2017;8:165–178. 151. Kivimäki M, Luukkonen R, Batty GD. Body mass index and risk of dementia: analysis of individual-level data from 1·3 million individ- uals. Alzheimers Dement. 2018;14:601–609. 152. Beydoun MA, Beydoun HA, Wang Y. Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis. Obes Rev. 2008;9:204–18. 153. Profenno LA, Porsteinsson AP, Faraone SV. Meta-analysis of Alzheimer’s disease risk with obesity, diabetes, and related disorders. Biolog- ical psychiatry. 2010;67:505–12. 154. Xu WL, Atti AR, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. Midlife overweight and obesity increase late-life dementia risk: a population-based twin study. Neurology. 2011;76:1568–1574. 155. Whitmer RA, Gustafson DR, Barrett-Connor E, Haan MN, Gunderson EP, Yaffe K. Cen- tral obesity and increased risk of demen- tia more than three decades later. Neurology. 2008;71:1057–1064. 156. Jagust W, Harvey D, Mungas D, Haan M. Cen- tral obesity and the aging brain. Arch Neurol. 2005;62:1545–1548. 157. Braak H, Braak E. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol. 1991;82:239–259. doi: 10.1007/BF00308809. 158. Qizilbash N, Gregson J, JohnsonME, Pearce N, Douglas I, Wing K, Evans SJ, Pocock SJ. BMI and risk of dementia in two million people over two decades: a retrospective cohort study. The lancet. Diabetes & endocrinology. 2015;3:431– 436. 159. Pugazhenthi S, Qin L, Reddy PH. Common neurodegenerative pathways in obesity, dia- betes, and Alzheimer’s disease. Biochim Bio- phys Acta Mol Basis Dis. 2017;1863(5):1037- 1045. doi:10.1016/j.bbadis.2016.04.017. 160. Knopman DS, Edland SD, Cha RH, Petersen RC, Rocca WA. Incident dementia in women is preceded by weight loss by at least a decade. Neurology. 2007;69:739–46. 161. Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol. 2011;10(9):819- 828. doi:10.1016/S1474-4422(11)70072-2. 162. Nepal B, Brown LJ, Anstey KJ. Rising midlife obesitywill worsen future prevalence of demen- tia. PLoS One. 2014;9:e99305. 163. Veronese N, Facchini S, Stubbs B. Weight loss is associated with improvements in cognitive function among overweight and obese people: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2017;72:87–94. 164. Maggio CA, Pi-Sunyer FX. Obesity and type 2 diabetes. Endocrinol Metab Clin North Am. 2003 Dec;32(4):805-22, viii. doi: 10.1016/s0889-8529(03)00071-9. 165. Popp J, Meichsner S, Kolsch H, Lewczuk P, et al. Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer’s disease. Biochem Pharmacol. 2013;86(1):37– 42. doi: 10.1016/j.bcp.2012.12.007. 166. Jokinen E. Obesity and cardiovascular disease. Minerva Pediatr. 2015 Feb;67(1):25-32. 167. Marini S, Merino J, Montgomery BE, et al. International Stroke Genetics Con- sortium. Mendelian Randomization Study CMI JOURNAL 2 (1), 80−97 (2021) MEERP LTD 94 MEERP LTD SHASHI K. AGARWAL, MD of Obesity and Cerebrovascular Disease. Ann Neurol. 2020 Apr;87(4):516-524. doi: 10.1002/ana.25686. 168. Mendiola-Precoma J, Berumen LC, Padilla K, Garcia-Alcocer G. Therapies for Preven- tion and Treatment of Alzheimer’s Disease. Biomed Res Int. 2016;2016:2589276. doi: 10.1155/2016/2589276. 169. Jayaraman A., Lent-Schochet D., Pike C. J. Diet-induced obesity and low testosterone increase neuroinflammation and impair neu- ral function. Journal of Neuroinflammation. 2014;11, article 162 doi: 1.0.1186/s12974-014- 0162-y. 170. Mendiola-Precoma J, Berumen LC, Padilla K, Garcia-Alcocer G. Therapies for Preven- tion and Treatment of Alzheimer’s Disease. Biomed Res Int. 2016;2016:2589276. doi: 10.1155/2016/2589276. 171. Thaler J. P., Yi C.-X., Schur E. A., et al. Obesity is associated with hypothalamic injury in rodents and humans. The Journal of Clin- ical Investigation. 2012;122(1):153–162. doi: 10.1172/jci59660. 172. Bonda D. J., Stone J. G., Torres S. L., et al. Dysregulation of leptin signaling in Alzheimer disease: evidence for neuronal leptin resistance. Journal of Neurochemistry. 2014;128(1):162– 172. doi: 10.1111/jnc.12380. 173. Breijyeh Z, Karaman R. Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules. 2020;25(24):5789. Pub- lished 2020Dec 8. doi:10.3390/molecules25245789. 174. Singer SP, Dammerer D, Krismer M, Lieben- steiner MC. Maximum lifetime body mass in- dex is the appropriate predictor of knee and hip osteoarthritis. Arch Orthop Trauma Surg. 2018;138(1):99–103. 175. Felson DT , Anderson JJ, Naimark A, Walker AM, Meenan RF. Obesity and knee osteoarthri- tis. The Framingham Study. Ann Intern Med. 1988;109(1):18–24. 176. Runhaar J, Koes BW, Clockaerts S, Bierma- Zeinstra SMA. A systematic review on changed biomechanics of lower extremities in obese in- dividuals: a possible role in development of osteoarthritis. Obes Rev. 2011;12(12):1071– 1082. 177. Järvenpää J, Kettunen J, Kröger H,Miettinen H. Obesity may impair the early outcome of total knee arthroplasty. A prospective study of 100 patients. Scand J Surg. 2010;99:45–49. 178. Malinzak RA, Ritter MA, Berend ME, Meding JB, Olberding EM, Davis KE. Morbidly obese, diabetic, younger, and unilateral joint arthro- plasty patients have elevated total joint arthro- plasty infection rates. J Arthroplasty. 2009;24(6 suppl):84–88. 179. Amin AK, Clayton RAE, Patton JT, Gaston M, Cook RE, Brenkel IJ. Total knee replace- ment in morbidly obese patients. Results of a prospective, matched study. J Bone Jt Surg [Br] 2006;8888(10):1321–1326. 180. Wang T, He C. Pro-inflammatory cytokines: The link between obesity and osteoarthritis. Cy- tokine Growth Factor Rev. 2018 Dec;44:38-50. doi: 10.1016/j.cytogfr.2018.10.002. 181. Thijssen E, Van Caam A, Van Der Kraan PM. Obesity and osteoarthritis, more than just wear and tear: pivotal roles for inflamed adipose tis- sue and dyslipidaemia in obesity-induced os- teoarthritis. Rheumatology (United Kingdom) 2014;54:588–600. 182. Dar L, Tiosano S, Watad A, Bragazzi NL, Zisman D, Comaneshter D, Cohen A, Amital H. Are obesity and rheumatoid arthritis inter- related? Int J Clin Pract. 2018 Jan;72(1). doi: 10.1111/ijcp.13045. 183. Albrecht K, Richter A, Callhoff J, Huscher D, Schett G, Strangfeld A, Zink A. Body mass index distribution in rheumatoid arthritis: a collaborative analysis from three large German rheumatoid arthritis databases. Arthri- tis Res Ther. 2016 Jun 23;18:149. doi: 10.1186/s13075-016-1043-9. MEERP LTD CMI JOURNAL 2 (1), 80−97 (2021) 95 OBESITY AND NON-COMMUNICABLE DISEASES: PART II CARDIOVASCULAR DISEASES, RESPIRATORY DISEASES, DEPRESSION, LIVER DISEASES 184. Crowson CS, Matteson EL, Davis JM 3rd, Gabriel SE. Contribution of obesity to the rise in incidence of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013 Jan;65(1):71-7. doi: 10.1002/acr.21660. 185. Qin B, Yang M, Fu H, Ma N, Wei T, Tang Q, et al. Body mass index and the risk of rheuma- toid arthritis: a systematic review and dose- response meta-analysis. Arthritis Res Ther. 2015;17(1):86. 186. Lu B, Hiraki LT, Sparks JA, et al. Being over- weight or obese and risk of developing rheuma- toid arthritis among women: a prospective co- hort study. Ann Rheum Dis. 2014;73:1914–22. doi: 10.1136/annrheumdis-2014-205459. 187. Crowson CS, Matteson EL, Davis JM, III, et al. Contribution of obesity to the rise in incidence of rheumatoid arthritis. Arthri- tis Care Res (Hoboken) 2013;65:71–7. doi: 10.1002/acr.21660. 188. Elkan AC, Engvall IL, Cederholm T, et al. Rheumatoid cachexia, central obesity and mal- nutrition in patients with low-active rheuma- toid arthritis: feasibility of anthropometry, Mini Nutritional Assessment and body composition techniques. Eur J Nutr. 2009;48:315–22. doi: 10.1007/s00394-009-0017-y. 189. Finckh A, Turesson C. The impact of obesity on the development and progression of rheumatoid arthritis. Ann RheumDis. 2014;73:1911–3. doi: 10.1136/annrheumdis-2014-205741. 190. Wolfe F, Michaud K. Effect of body mass in- dex on mortality and clinical status in rheuma- toid arthritis. Arthritis Care Res (Hoboken) 2012;64:1471–9. doi: 10.1002/acr.21627. 191. Liu Y, Hazlewood GS, Kaplan GG, Eksteen B, Barnabe C. Impact of Obesity on Remission andDiseaseActivity in RheumatoidArthritis: A Systematic Review and Meta-Analysis. Arthri- tis Care Res (Hoboken). 2017 Feb;69(2):157- 165. doi: 10.1002/acr.22932. 192. Vidal C, Barnetche T, Morel J, et al. Associ- ation of body mass index categories with dis- ease activity and radiographic joint damage in rheumatoid arthritis: a systematic review and metaanalysis. J Rheumatol. 2015;42:2261–9. doi: 10.3899/jrheum.150224. 193. Versini M, Jeandel P-Y, Rosenthal E, Shoen- feld Y. Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev. 2014;13(9):981–1000. 194. Gómez R, Conde J, Scotece M, Gómez- Reino JJ, Lago F, Gualillo O. What’s new in our understanding of the role of adipokines in rheumatic diseases? Nat Rev Rheumatol. 2011;7(9):528–36. 195. Chung CP, Oeser A, Solus JF, Gebretsadik T, Shintani A, Avalos I, et al. Inflammation- associated insulin resistance: differential ef- fects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. Arthritis Rheum. 2008;58(7):2105–12. 196. Aune D , Norat T, Vatten LJ. Body mass in- dex and the risk of gout: a systematic review and dose-response meta-analysis of prospective studies. Eur J Nutr. 2014;53(8):1591–1601. 197. Dhawan D, Sharma S. Abdominal Obesity, Adipokines and Non-communicable Diseases. J Steroid BiochemMol Biol. 2020;203:105737. doi:10.1016/j.jsbmb.2020.105737. 198. Krassas GE, Tzotzas T. Do obese children become obese adults: childhood predictors of adult disease. Pediatr Endocrinol Rev. 2004 Aug;1 Suppl 3:455-9. 199. 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. 200. Forouzanfar M.H., Alexander L., Anderson H.R., et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, CMI JOURNAL 2 (1), 80−97 (2021) MEERP LTD 96 MEERP LTD SHASHI K. AGARWAL, MD 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386:2287–2323. How to cite this article: Agarwal S.K,, MD. OBESITY AND NON-COMMUNICABLE DISEASES: PART II Cancer, Diabetes Mellitus, Kidney Dis-eases, Alzheimer’s Disease, Arthritis. Clinical Medicine Insights. 2021;80 −97. https://doi.org/ 10.52845/CMI/2021-2-1-4 MEERP LTD CMI JOURNAL 2 (1), 80−97 (2021) 97 Introduction Discussion CANCER DIABETES MELLITUS KIDNEY DISEASES ALZHEIMER'S DISEASE ARTHRITIS CONCLUSION