Clinical Medicine Insights Received 28 June 2021 | Revised 24 July 2021 | Accepted 19 Aug 2021 | Published Online 31 Aug 2021 DOI: https://doi.org/10.52845/CMI/2021-2-3-6 CMI JOURNAL 2 (3), 185−200 (2021) ISSN (O) 2694-4626 REVIEW ARTICLE Alcohol and Noncommunicable 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 Excessive alcohol consumption is common. It leads to the development of several NCDs and is associated with considerable disability and high mortality. Its intake has been linked with an increase in many cancers, including the common breast and prostate cancer. Light-to-moderate drinking is associated with a lower incidence of type 2 diabetes, but ex- cessive alcohol consumption leads to increased morbidity and mortality in these patients. Compared with no consumption, moderate consump- tion of alcohol-associated with a reduced risk of CKD. However, the association with heavy alcohol intake and CKD is not clear, although it also appears to be overall inverse in nature. Excessive alcohol intake also targets the brain and promotes AD – although mild to moderate intake may be safe. Alcohol consumption is negatively associated with the prevalence of knee OA. There appears to be an inverse association between alcohol consumption and RA incidence. Alcohol consumption, usually when taken in more than a moderate amount. may also trigger gout. In general, alcohol intake in low to moderate amounts appears to be safe for NCDs described in this communication, except for cancer, where no amount is a safe amount. Keywords: alcohol, non-communicable diseases, cancer, diabetes mel- litus, kidney diseases, Alzheimer’s disease, 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 A lcohol consumption is common in our society1. It is estimated that in 2016, 32.5% of the world’s population had at least one alcoholic drink in the past 12months2. Globally, men tend to drink more than women3. A standard drink contains 12–15 g of pure ethanol and this is found in 12 ounces of regular beer, 5 ounces of wine, and 1.5 ounces of distilled spirits4. In most European CMI JOURNAL 2 (3), 185−200 MEERP LTD 185 Open Access Journal https://doi.org/10.52845/CMI/2021-2-3-10 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/index.php/cmi/index ALCOHOL AND NONCOMMUNICABLE DISEASES: PART II CANCER, DIABETES MELLITUS, KIDNEY DISEASES, ALZHEIMER’S DISEASE, ARTHRITIS countries, alcoholic drinks are often referred to as by units, with one unit being equivalent to 8-10 grams of alcohol, with typical drinks containing 1–3 units of alcohol5. Moderate alcohol intake is considered as two standard drinks a day for men and one standard drink a day for women6,7. Heavy drinking is defined as a long-term, high-dose intake, of >60 g/day in men and >40 g/day in women8. Binge drinking is considered as 4 or more drinks for women and 5 or more drinks for men over a 2-hour period9,10. Compulsive excessive alcohol intake leads to alcohol use disorder11. It is estimated that 20% of patients seen by primary care physicians consume alcohol in amounts that are harmful to their health12. Alcohol was responsible for 8.9% in males and 2.3% in females for disability-adjusted life years in 2016, globally13. Griswold et al also calculated that in 2016, alcohol consumption was responsible for 6.8% of male deaths and 2.2% of female deaths all over the world13. Of these deaths in 2016, 21.3% were due to digestive diseases, 19% due to cardiovascular diseases and diabetes, 12.9% due to infectious dis- eases, and 12.6% due to cancers14. The health-related financial burden attributable to alcohol misuse is also extremely high, and in 2010, it cost the United States $249 billion15. The relationship between alcohol consumption and cardiovascular diseases (CVDs), respiratory dis- eases, depression, and liver diseases was discussed in Part I of this manuscript. 2 DISCUSSION Noncommunicable diseases (NCD) are common conditions affecting humans16. This part of the manuscript discusses the relationship between al- Supplementary information The online version of this article (10.52845/CMI/2021-2-3-6) 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 cohol and cancer, diabetes mellitus (DM), chronic kidney disease (CKD), Alzheimer’s disease (AD), and arthritis. Cancer is expected to replace CVDs as the number one killer in the world17. The most common global cancers are those involving the lung, colorectum, stomach, and liver18. However, many common cancers can be ‘cured’ if caught early19. Breast cancer, the most common nonskin cancer among women, if detected while still in localized form has a 5-year survival rate of 98%, compared with a survival rate of 72% by Stage III and just 22% by Stage IV20,21. Many other cancers demonstrate a similar prognosis depending on the time of their diagnosis22. Basal cell carcinoma and squamous cell carcinoma of the skin are the most common human cancers and are 100% treatable if found early. Di- agnosing cervical cancer in a pre-cancerous stage can assure a near 100% survival rate. However, if discovered in Sate III, the rate drops to just 32% and if diagnosed in Stage IV, it is a dismal 16%. Prostate cancer is 98% survivable for 5 or more years if it is diagnosed when it is limited to the prostate gland. while if diagnosed at Stage IV, the survival rate is only about 28%. Colon cancer can be 90% survivable if detected early; the survival drops to 39% if it is detected when it has spread22. DM is one of the most common metabolic disorders worldwide23. and its prevalence is rapidly rising in low- and middle- income countries24. According to the World Health Organization, the number of people with diabetes rose from 108 million in 1980 to 422 million in 201424. In the United States, 9.3% of Americans had diabetes (29.1 million persons) in 2014, with a life- time risk calculated at almost 40%25. It is caused by a combination of defective insulin secretion by pan- creatic β-cells and the inability of insulin-sensitive tissues to respond to insulin26. Diabetes mellitus is associated with significant microvascular (retinopa- thy, nephropathy, and neuropathy) and macrovascu- lar (coronary artery disease, stroke, peripheral artery disease complications27,28. DM reduces the life ex- pectancy of the affected individual by approximately six years29. CKD refers to kidney damage or an estimated glomerular filtration rate (eGFR) less than 60ml/min/1.73 mt2, persisting for 3 months or more, irrespective of the cause30. It is a worldwide public health31. In 2017, CKD affected almost 700 million CMI JOURNAL 2 (3), 185−200 (2021) MEERP LTD 186 mailto:usacardiologist@gmail.com MEERP LTD SHASHI K. AGARWAL, MD people in the world32. Those affected with CKD exceed those with diabetes, osteoarthritis, COPD, asthma, or depressive disorders33. Hypertension and diabetes mellitus are the main causes34. CKD is a progressive disease, ultimately resulting in the need for peritoneal dialysis or hemodialysis, or kidney transplantation35. The major cause of morbidity and mortality in CKD is due to cardiovascular events36. CKD also leads to frequent hospitalization37and poor quality of life38. CKD results in more deaths than tuberculosis or HIV and is presently ranked as the 12th leading cause of death out of 133 conditions in the world33. Dementia is a common worldwide disease39, with ADbeing responsible for 50% to 70% of these cases40,41. It is characterized by pathologies: β-amyloid plaque deposition and neurofibrillary tan- gles of hyperphosphorylated tau42. This disorder continues to increase in low- and middle-income countries43. Its etiology is unclear but appears to be related to a complex interplay between genetic and environmental factors44. AD produces cognitive impairment and functional decline, often leading to institutionalization45,46. There is no cure for AD, and treatment remains symptomatic47. The QOL of these patients is markedly reduced and AD remains a major cause of death48. Arthritis is of many types, and osteoarthritis is the most common49. It is a major health concern, affecting about 240 million people globally50. It reduces the quality of life and results in considerable disability and mortality51. It usually af- fects the knees and the hip, resulting in chronic pain, stiffness, joint instability, and joint deformities52. It is associated with considerable disability53. Patho- logically, it is characterized by progressive cartilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis54. Osteoarthritis (OA) cases are predicted to rise in the coming decades due to the aging population, increasing obesity, and high rates of traumatic knee injuries55. Rheumatoid arthri- tis (RA) is autoimmune arthritis and is character- ized by symmetrical polyarthritis oftenwith systemic manifestations56,57. RA is often associated with per- sistent pain, deformity, and disability58. It also ac- celerates cardiovascular disease in these patients59. Gout is an autoinflammatory joint arthritis60, caused by the deposition ofmonosodium uratemicrocrystals in joints and tissues61. Hyperuricemia is central to its development62. In an acute flare-up, monoarthritis develops rapidly and affects the big toe in 50% of cases (other joints commonly affected include the ankle, midtarsal, knee, wrist, finger, and elbow)63. The affected joint is red, tender, hot, and tumid with extreme pain64. Diagnosis may be confirmed by finding monosodium urate crystals in synovial fluid or tophus aspirates65. 2.1 CANCER Alcohol is a known carcinogen66,67. Its consumption increases the risk of several cancers68,69, especially those affecting the mouth, throat, larynx, esophagus, liver, colorectal tissues, and breast70. Bagnardi et al. reviewed 222 articles in 2013, (comprising of about 92 000 light drinkers and 60 000 non-drinkers with cancer and concluded that light drinking increases the risk of oropharyngeal cancer by 17%; esophageal squamous cell carcinoma by 30% and breast cancer by 5%71. In a recent analysis, published in 2018, Islami et al. found that alcohol intake was the third- largest contributor to all cancer cases among women and the fourth largest contributor among men72. In women, besides causing 28.4% of esophageal can- cers, 27.4% of the oral cavity and pharyngeal can- cers and many breast cancers were associated with alcohol72. Alcohol was associated with 46.3% of all oral cavity and pharyngeal cancers in men72. They estimated that alcohol intake was responsible for 5.6% of cancer cases and 4.0% of all cancer-related deaths72. Alcohol intake has also been linked with an increase in other cancers, such as gastric cancer73, colo-rectal cancer74, prostate cancer75, and some skin cancers76. It also increases the risk of a second aerodigestive-tract cancer77. There may be a dose- response relationship between alcohol and cancer78. However, most people are unaware of the increased risk of cancer even after the first drink79. The Amer- ican Cancer Society recommends not drinking al- cohol to lower cancer risk80. Despite these recom- mendations, most people, including cancer survivors continue to drink81. Alcohol is an irritant to the upper aerodigestive tract82. Acetaldehyde is the first and primarymetabo- lite of alcohol and is strongly implicated in can- cer development83. Its intake is associated with ab- MEERP LTD CMI JOURNAL 2 (3), 185−200 (2021) 187 ALCOHOL AND NONCOMMUNICABLE DISEASES: PART II CANCER, DIABETES MELLITUS, KIDNEY DISEASES, ALZHEIMER’S DISEASE, ARTHRITIS normal production of reactive oxygen and nitrogen species, aberrant DNA methylation, altered folate metabolism, disturbed immune surveillance and in- flammatory response and increased estrogen levels in breast cancer cases84−86. 2.2 DIABETES MELLITUS Alcohol intake is generally considered beneficial for type 2 diabetes prevention, provided it is consumed in moderate amount87. In a large study involving 22,778 twins and 580 incident cases of type 2 di- abetes during 20 years of follow-up, Carlsson et al documented this phenomenon88. Some previous studies have estimated that moderate alcohol con- sumptionmay reduce the incidence of type 2 diabetes by 30%-40%89−91. In a recent meta-analysis of 20 observational studies, undertaken by Baliunas et al. in 2009, a peak reduction in risk for type 2 dia- betes mellitus (T2DM) was noted at 24 g/day among women and 22 g/day among men, relative to never drinkers, with risk increasing in a dose-dependent manner above these levels92. However, in a major meta-analysis of 38 studies representing 1,902,605 participants and 125,926 cases of type 2 diabetes, Knott et al found a risk reduction only inwomen (<71 g/day) when compared to current non-drinkers and never drinkers93. Irrespective of the level of alcohol consumption, no risk reduction was noted in men93. Several biological mechanisms have been proposed to explain the apparent reduction in risk of T2DM among moderate drinkers94. These include the anti- inflammatory hypothesis, which posits that alcohol may beneficially alter the expression of inflamma- tory proteins94 and a possible stimulatory effect of alcohol upon the synthesis of HDL95. After an anal- ysis of results reported by 14 intervention studies, alcohol consumption was associated with reduced fasting insulin concentrations and improved insulin sensitivity among women96. Reduced duration of drinking, or initiating alcohol intake at a later age, also appears to decrease the risk of T2DM97. Heavy alcohol intake has been associated with a higher risk for DM in many studies98,99. In a study of 2366 Koreans monitored over 10 years, consumption of more than 2 units of alcohol per day was associated with an increase in the risk of T2DM100. A reduction in the maximum intake of alcoholic beverages not only decreases the risk of development of T2DM but also improves survival among established diabetic subjects especially if this reduction is done in early adulthood101,102. Several mechanisms may cause this harm, in- cluding alcohol-related increase in metabolic syndrome103,104. The increase in alcohol-related hypertension tends to aggravate cardiovascular complications103. Long-term alcohol intake also re- sults in pancreatic islet dysfunction and apoptosis104. Overall, the relationship between alcohol consump- tion and risk of T2DM appears to be J- or U-shaped association105. 2.3 KIDNEY DISEASES Comparedwith no consumption,moderate consump- tion of alcohol may be associated with a reduced risk of CKD106. Moderate alcohol use was associated with a lower risk of CKD or end-stage kidney disease (ESKD) in several previous reports107−110. In ameta- analysis of prospective cohorts. not only moderate but also high amounts of alcohol use have been asso- ciatedwith a lower risk of incident CKDor ESKD111. However, heavy alcohol consumption or chronic alcohol consumption is positively associated with CKD112−116. A Mendelian randomization study also found a causal link between heavy alcohol intake and an increased risk of end-stage kidney disease117. In another Mendelian randomization study, Park et al also confirmed the deleterious role of alcohol on the risk of ESKD118. Mechanisms of alcohol-induced kidney damage in- clude oxidative stress injury, increase in blood pressure, and activation of the renin-angiotensin- aldosterone pathway119−121. Further alcohol and other substances in alcohol may also influence kid- ney function by effects on other body systems122,123. Bottom line – alcohol is a double-edged sword in CKD. It may be safe to drink to a low or moderate degree with CKD but heavy or binge drinking is harmful124. CMI JOURNAL 2 (3), 185−200 (2021) MEERP LTD 188 MEERP LTD SHASHI K. AGARWAL, MD 2.4 ALZHEIMER'S DISEASE Several studies have documented the protective ef- fects of low to moderate amounts of alcohol on dementia125−127. Epidemiological studies have also reported a similar effect in AD128. In a recent large meta-analysis of 91 articles on AD, Anstey et al confirmed this association129. Animal and cell cul- ture studies also show that low or moderate con- centrations of ethanol exhibit a protective effect on AD in vitro and in vivo130-133. Heavy drinking is however harmful to the brain134−138. In a 5- year follow-up study of 13,342 men and women, Piumati et al reported that reaction time declined more with alcohol intake of 12 units per week when compared to those who drank less134. In a large study (of 31 million people over 5 years), researchers found that alcohol use disorders were associated with increased dementia risk135. Heavy alcohol in- take induces harmful brain changes, cognitive im- pairment, and dementia136,137. Similar deleterious findings have been noted in AD patients with higher alcohol intake138. Changes consistent with increased cognitive deficits have also been noted in AD mice models 1-month post alcohol drinking139. In the 23- year UK Whitehall study (9087 participants), absti- nence or heavy drinking were both associated with a higher risk of dementia140. Overall, the association between alcohol intake and dementia appears to be U-shaped with low or moderate amounts of alcohol being protective against Aβ toxicity in hippocampal neurons and high intake increasing neuronal cell death and neurodegeneration141. However, alcohol drinking is not recommended for AD protection142. 2.5 ARTHRITIS There is no concrete evidence of an association, ben- eficial or otherwise, between moderate alcohol con- sumption and OA143,144. This has been noted in the Finnish cohort studywith an observation period of 22 years143 and the Nurses’ Health Study144. Moderate amounts of alcohol intake are associated with anti- inflammatory effects145. Zhang et al found no evi- dence of alcohol consumption with hsCRP or knee OA146. Some studies have found that chronic and ex- cessive intake of alcohol raises inflammation147,148. Kc et al noted pathological OA-like changes in ani- mals with chronic alcohol intake149. A similar radi- ological knee OA effect, rather than a symptomatic effect, was seen in Korea in patients with alcohol consumption150. The clinical implications of the re- lationship between alcohol intake and OA. There- fore. remain unclear. The 2009 the Swedish EIRA study (Epidemiological Investigation of Rheumatoid Arthritis) and the Danish CACORA study (Case- Control Study on Rheumatoid Arthritis) found that limited amounts of alcohol decrease the risk of RA incidence151. Lu et al concluded that moderate alco- hol intake was associated with a better functional sta- tus in RA patients152. Another study found that low levels of alcohol consumption (about three drinks per week) over at least ten years lowered the risk of RA incidence by half compared with non-drinkers153. However, increased frequency of alcohol consump- tion may be harmful in RA154. In the Västerbotten Intervention Program cohort of 386 individuals, no association was seen between alcohol intake and the risk of RA155. Baker et al reported that RA patients tend to reduce alcohol intake with higher disease activity, disability, comorbidity, and poor quality of life156. Overall, there appears to be no clear benefit of alcohol consumption in RA. Alcohol may pre- cipitate gout at lower urate levels157. Beer intake appears to be more associated with gout than spirits, and spirits more than wine158,159. Chronic alcohol intake also is also harmful to gout patients160,161. High alcohol intake may impair the production of oxypurinol and stimulate urate production in the body160,161. 3 CONCLUSION Low to moderate alcohol intake appears to be safe, and even protective in DM, CKD, and AD. There may be no “safe” level of alcohol use when it comes to cancer. No definite association can be gleaned from published studies between alcohol and OA and RA. Gout suffers may consider abstaining from alcohol. High levels of alcohol intake are in general, harmful for NCDs. The 2015 U.S. Dietary Guide- lines for Americans strongly suggest restricting con- sumption to≤2 drinks/day for men and≤1 drink/day MEERP LTD CMI JOURNAL 2 (3), 185−200 (2021) 189 ALCOHOL AND NONCOMMUNICABLE DISEASES: PART II CANCER, DIABETES MELLITUS, KIDNEY DISEASES, ALZHEIMER’S DISEASE, ARTHRITIS for women. Alcohol consumption can lead to ad- verse outcomes and therefore, non-drinkers should not start drinking for health reasons. Acknowledgment: None Funding: None Conflict of interest: None REFERENCES 1. World Health Organization -WHO. Global Sta- tus Report: alcohol policy. https://www.who.i nt/substance_abuse/facts/alcohol/en/ - accessed March 3, 2021. 2. Griswold M.G., Fullman N., Hawley C., et al. Alcohol use and burden for 195 coun- tries and territories, 1990–2016: A system- atic analysis for the Global Burden of Disease Study 2016. Lancet. 2018;392:1015–1035. doi: 10.1016/S0140-6736(18)31310-2. 3. Testino G. Are patients with alcohol use dis- orders at increased risk for Covid-19 infec- tion? Alcohol Alcoholism (Oxford, Oxford- shire) 2020. 4. https://www.niaaa.nih.gov/alcohols-effects-he alth/overview-alcohol-consumption/what-stan dard-drink - accessed August 3, 2021. 5. https://www.letithapyn.eu/data-si/file/Report% 20on%20the%20alcohol%20laws%20in%20E U.pdf – accessed August 3, 2021. 6. Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: A state- ment by the American Society of Hypertension and the International Society of Hypertension. Journal of Clinical Hypertension (Greenwich) 2014;16(1):14–26. 7. Xi B., Veeranki S.P., Zhao M., Ma C., Yan Y., Mi J. Relationship of Alcohol Con- sumption to All-Cause, Cardiovascular, and Cancer-Related Mortality in U.S. Adults. J. Am. Coll. Cardiol. 2017;70:913–922. doi: 10.1016/j.jacc.2017.06.054. 8. Fernández-Solà J. Cardiovascular risks and benefits of moderate and heavy alcohol con- sumption. Nat. Rev. Cardiol. 2015;12:576–587. doi: 10.1038/nrcardio.2015.91. 9. Kuntsche E., Kuntsche S., Thrul J., Gmel G. Binge drinking: Health impact, preva- lence, correlates and interventions. Psy- chol. Health. 2017;32:976–1017. doi: 10.1080/08870446.2017.1325889. 10. Fillmore M.T., Jude R. Defining “binge” drink- ing as five drinks per occasion or drinking to a .08% BAC: Which is more sensitive to risk? Am. J. Addict. 2011;20:468–475. doi: 10.1111/j.1521-0391.2011.00156.x. 11. Esser MB, Hedden SL, Kanny D, Brewer RD, Gfroerer JC, Naimi TS. Prevalence of Alcohol Dependence Among US Adult Drinkers, 2009– 2011. Prev Chronic Dis 2014;11:140329. 12. World Health Organization - WHO. Global Status Report on Alcohol. 2004. Available from: http://www.who.int/substance_abuse/p ublications/global_status_report_2004_overvie w.pdf?ua=1». 13. Griswold M.G., Fullman N., Hawley C., Arian N., Zimsen S.R., Tymeson H.D., Venkateswaran V., Tapp A.D., Forouzan- far M.H., Salama J.S. Alcohol use and burden for 195 countries and territories, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2018;392:1015–1035. 14. World Health Organization (2018). Global Status Report on Alcohol and Health. 15. Sacks J. J., Gonzales K. R., Bouchery E. E., Tomedi L. E., Brewer R. D. (2015). 2010 National and state costs of excessive alcohol consumption. Am. J. Prev. Med. 49, e73–e79. 10.1016/j.amepre.2015.05.031. 16. NCD Countdown 2030 collaborators. NCD Countdown 2030: worldwide trends in non-communicable disease mortal- ity and progress towards Sustainable CMI JOURNAL 2 (3), 185−200 (2021) MEERP LTD 190 MEERP LTD SHASHI K. AGARWAL, MD Development Goal target 3.4. Lancet. 2018 Sep 22;392(10152):1072-1088. doi: 10.1016/S0140-6736(18)31992-5. 17. 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 countries. CA Cancer J Clin. 2018;68:394-424. 18. The Global Cancer Observatory (IARC). GLOBOCAN 2018. gco.iarc.fr/. Accessed March 1, 2019. 19. Roy PS, Saikia BJ. Cancer and cure: A critical analysis. Indian J Cancer. 2016 Jul-Sep;53(3):441-442. doi: 10.4103/0019- 509X.200658. 20. Reeves GK, Beral V, Green J, Gathani T, Bull D; Million Women Study Collabora- tors. Hormonal therapy for menopause and breast-cancer risk by histological type: A co- hort study and meta-analysis. Lancet Oncol 2006;7:910-8. 21. Cuzick J, DeCensi A, Arun B, Brown PH, Castiglione M, Dunn B, et al. Preventive therapy for breast cancer: A consensus state- ment. Lancet Oncol 2011;12:496-503. 22. Mackay J, Jemal A, Lee NC, Parkin DM. The Cancer Atlas. Atlanta: American Cancer Society; 2006. 23. 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. 24. https://www.who.int/news-room/fact-sheet s/detail/diabetes. 25. https://www.niddk.nih.gov/health-informat ion/health-communication-programs/ndep/ health-care-professionals/game-plan/facts-st atistics/Pages/index.aspx. 26. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Os- tolaza H, Martín C. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci. 2020 Aug 30;21(17):6275. doi: 10.3390/ijms21176275. 27. 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. 28. Almdal T, Scharling H, Jensen JS, Vester- gaard H. The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population- based study of 13,000 men and women with 20 years of follow-up. Arch Intern Med. 2004;164:1422–1426. 10.1001/arch- inte.164.13.1422. 29. 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. 30. Chapter 1: Definition and classification of CKD. Kidney Int Suppl (2011). 2013 Jan;3(1):19-62. 31. 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. 32. GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a system- atic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395:709–733. doi: 10.1016/S0140-6736(20)30045-3. 33. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, re- gional, and national incidence, prevalence, MEERP LTD CMI JOURNAL 2 (3), 185−200 (2021) 191 ALCOHOL AND NONCOMMUNICABLE DISEASES: PART II CANCER, DIABETES MELLITUS, KIDNEY DISEASES, ALZHEIMER’S DISEASE, ARTHRITIS and years lived with disability for 354 dis- eases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018; 392: 1789-1858. 34. Couser WG, Remuzzi G, Mendis S, Tonelli M. The contribution of chronic kidney dis- ease to the global burden of major noncom- municable diseases. Kidney Int. 2011; 80: 1258-1270. 35. Liyanage T, Ninomiya T, Jha V, Neal B, Patrice HM, Okpechi I, Zhao MH, Lv J, Garg AX, Knight J, Rodgers A, Gallagher M, Kotwal S, Cass A, Perkovic V. Worldwide access to treatment for end-stage kidney dis- ease: a systematic review. Lancet. 2015 May 16;385(9981):1975-82. doi: 10.1016/S0140- 6736(14)61601-9. 36. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. The New England journal of medicine. 2004;351(13):1296–305. Epub 2004/09/24. 10.1056/NEJMoa041031. 37. Gansevoort RT, Correa-Rotter R, Hemmel- garn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and cardio- vascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013. 10.1016/S0140- 6736(13)60595-4. 38. 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. 39. Patterson C. Alzheimer’s Disease Interna- tional; London: 2018. World Alzheimer re- port 2018. 40. https://www.dementia.com/causes.html - accessed July 9, 2021. 41. Crous-Bou M, Minguillón C, Gramunt N, et al. : Alzheimer’s disease prevention: from risk factors to early intervention. Alzheimers Res Ther. 2017;9(1):71. 10.1186/s13195-017- 0297-z. 42. Yiannopoulou KG, Papageorgiou SG. Current and future treatments for Alzheimer’s disease. Ther Adv Neu- rol Disord. 2013 Jan;6(1):19-33. doi: 10.1177/1756285612461679. 43. Prince M, Albanese E, Guerchet M, et al. World Alzheimer Report 2014: Dementia and Risk Reduction an Analysis of Protective and Modifiable Factors, 2014. 44. Karch CM, Goate AM. Alzheimer’s Dis- ease Risk Genes and Mechanisms of Disease Pathogenesis. Biol. Psychiatry 2015;77:43–51. 45. American Psychiatric Association . Diag- nostic and Statistical Manual of Mental Disorders (4th ed.) text revision (DSM-IV- TRTM) Washington, DC: American Psychi- atric Association; 2000. 46. 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. 47. Yiannopoulou K.G., Papageorgiou S.G. Cur- rent and future treatments in alzheimer dis- ease: An update. J. Cent. Nerv. Syst. Dis. 2020:12. doi: 10.1177/1179573520907397. 48. 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. 49. Bortoluzzi A, Furini F, Scirè CA. Os- teoarthritis and its management - Epi- demiology, nutritional aspects and envi- ronmental factors. Autoimmun Rev. 2018 Nov;17(11):1097-1104. CMI JOURNAL 2 (3), 185−200 (2021) MEERP LTD 192 MEERP LTD SHASHI K. AGARWAL, MD 50. Osteoarthritis Research Society Interna- tional. Osteoarthritis: A Serious Disease. Os- teoarthritis Research Society International; 2016. pp. 1–103. 51. Vitaloni M, Botto-van Bemden A, Sciortino Contreras RM, et al. Global management of patients with knee osteoarthritis begins with quality of life assessment: a systematic review. BMC Musculoskelet Disord. 2019 Oct 27;20(1):493. doi: 10.1186/s12891-019- 2895-3 52. Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998. 53. Guccione AA, Felson DT, Anderson JJ, et al. The effects of specific medical conditions on the functional limitations of elders in the Framingham study. Am J Public Health. 1994;84:351–358. doi: 10.2105/AJPH.84.3.351. 54. Harrell C. R., Markovic B. S., Fellabaum C., Arsenijevic A., Volarevic V. (2019). Mes- enchymal stem cell-based therapy of os- teoarthritis: current knowledge and future perspectives. Biomed. Pharmacother. 109, 2318–2326. 10.1016/j.biopha.2018.11.099. 55. Mandl LA. Osteoarthritis year in re- view 2018: clinical. Osteoarthritis Car- tilage. 2019 Mar;27(3):359-364. doi: 10.1016/j.joca.2018.11.001. 56. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011 Dec 8;365(23):2205-19. doi: 10.1056/NE- JMra1004965. 57. van der Woude D, van der Helm-van Mil AHM. Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2018;32:174–187. 58. Smolen JS, Aletaha D, McInnes IB Rheuma- toid arthritis. Lancet. 2016;388(10055):2023- 2038. 59. Meyer PW, Anderson R, Ker JA, Ally MT. Rheumatoid arthritis and risk of cardiovascular disease. Cardiovasc J Afr. 2018 Sep/Oct 23;29(5):317-321. doi: 10.5830/CVJA-2018-018. 60. Kuo CF, Grainge MJ, Zhang W, Doherty M. Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheuma- tol. 2015;11:649–662. 61. Scuiller A, Pascart T, Bernard A, Oehler E. La maladie goutteuse [Gout]. Rev Med Interne. 2020 Jun;41(6):396-403. French. doi: 10.1016/j.revmed.2020.02.014. 62. Chhana A. Lee G. Dalbeth N. Factors in- fluencing the crystallization of monosodium urate: a systematic literature review. BMC Musculoskelet Disord. 2015;16:296. 63. Grassi W, De Angelis R. Clinical features of gout. Reumatismo. 2012 Jan 19;63(4):238- 45. doi: 10.4081/reumatismo.2011.238. 64. Perez-Ruiz F, Castillo E, Chinchilla SP, Herrero-Beites AM. Clinical manifestations and diagnosis of gout. Rheum Dis Clin North Am. 2014 May;40(2):193-206. doi: 10.1016/j.rdc.2014.01.003. 65. Richette P, Doherty M, Pascual E, et al. 2018 updated European League Against Rheuma- tism evidence-based recommendations for the diagnosis of gout. Ann Rheum Dis. 2020 Jan;79(1):31-38. doi: 10.1136/annrheumdis- 2019-215315. 66. IARC Working Group . IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Alcohol Drinking. International Agency for Research on Cancer: Lyon; 1988. 67. Secretan B, Straif K, Baan R, et al. A review of human carcinogens–Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol. 2009;10(11):1033–1034. 68. Boffetta P, Hashibe M. Alcohol and cancer. Lancet Oncol. 2006;7(2):149-156. doi:10.1016/S1470-2045(06)70577-0. MEERP LTD CMI JOURNAL 2 (3), 185−200 (2021) 193 ALCOHOL AND NONCOMMUNICABLE DISEASES: PART II CANCER, DIABETES MELLITUS, KIDNEY DISEASES, ALZHEIMER’S DISEASE, ARTHRITIS 69. Bagnardi V, Rota M, Botteri E, et al. Al- cohol consumption and site-specific cancer risk: a comprehensive dose-response meta- analysis. Br J Cancer. 2015;112(3):580-593. doi:10.1038/bjc.2014.579. 70. Alcohol Use and Cancer. Accessed May 21, 2020. https://www.cancer.org/cancer/cance r-causes/diet-physical-activity/alcohol-use-a nd-cancer.html. 71. Bagnardi V, Rota M, Botteri E, et al. Light alcohol drinking and cancer: a meta-analysis. Ann. Oncol. 2013;24(2):301–308. 72. Islami, F., Goding Sauer, A., Miller K.M., et al. (2018), Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States. CA: A Cancer Journal for Clinicians, 68: 31-54. https://doi.org/10.3322/caac.21440 – accessed August 4, 2021. 73. Tramacere I, Negri E, Pelucchi C, Bagnardi V, Rota M, Scotti L, et al. A meta-analysis on alcohol drinking and gastric cancer risk. Ann Oncol. 2011:mdr135. 74. Fedirko V, Tramacere I, Bagnardi V, Rota M, Scotti L, Islami F, et al. Alcohol drinking and colorectal cancer risk: an overall and dose–response meta-analysis of published studies. Ann Oncol. 2011;22:1958–1972. doi: 10.1093/annonc/mdq653. 75. Watters JL, Park Y, Hollenbeck A, et al. Alcoholic beverages and prostate cancer in a prospective US cohort study. American Jour- nal of Epidemiology. 2010;172(7):773–780. 76. Rota M. Evidence for an association be- tween alcohol intake and an increased risk of nonmelanoma skin cancer. Br J Dermatol. 2017;177(3):611-612. doi:10.1111/bjd.15790. 77. Day GL, Blot WJ, Shore RE, et al. Sec- ond cancers following oral and pharyn- geal cancers: Role of tobacco and alcohol. Journal of the National Cancer Institute. 1994;86(2):131–137. 78. Bagnardi V, Rota M, Botteri E, Tra- macere I, Islami F, Fedirko V, et al. Al- cohol consumption and site-specific cancer risk: a comprehensive dose–response meta- analysis. Br J Cancer. 2015;112(3):580–93. 10.1038/bjc.2014.579. 79. Buykx P, Li J, Gavens L, Hooper L, Lovatt M, Gomes de Matos E, et al. Public aware- ness of the link between alcohol and cancer in England in 2015: a population-based sur- vey. BMC Public Health. 2016;16(1):1194. 10.1186/s12889-016-3855-6. 80. American Cancer Society Updates Guideline for Diet and Physical Activity. Accessed June 15, 2020. https://www.cancer.org/latest-ne ws/american-cancer-society-updates-guideli ne-for-diet-and-physical-activity.html. 81. Bellizzi KM, Rowland JH, Jeffery DD, McNeel T. Health behaviors of can- cer survivors: examining opportuni- ties for cancer control intervention. J Clin Oncol. 2005;23(34):8884–8893. doi: 10.1200/JCO.2005.02.2343. 82. Organization WH. IARC Monographs on the Evaluation of Carcinogenic Risks to Hu- mans: Alcohol Drinking Lyon: IARC Press, International Agency for Research on Can- cer, 1988. 83. Seitz HK, Stickel F. Acetaldehyde as an un- derestimated risk factor for cancer develop- ment: role of genetics in ethanol metabolism. Genes Nutr. 2010; 5: 121- 128. 84. Pöschl G, Seitz HK. Alcohol and cancer. Alcohol Alcoholism 2004;39:155–165.; Seitz HK, Stickel F. Molecular mechanisms of alcohol-mediated carcinogenesis. Nat Rev Cancer. 2007; 7: 599- 612. 85. Boffetta P, Hashibe M. Alcohol and can- cer. Lancet Oncol. 2006 Feb;7(2):149-56. doi: 10.1016/S1470-2045(06)70577-0. CMI JOURNAL 2 (3), 185−200 (2021) MEERP LTD 194 MEERP LTD SHASHI K. AGARWAL, MD 86. Varela-Rey M, Woodhoo A, Martinez- Chantar ML, Mato JM, Lu SC. Alcohol, DNA methylation, and cancer. Alcohol Res. 2013;35(1):25-35. 87. Nyberg S.T., Singh-Manoux A., Pentti J., Madsen I.E.H., Sabia S., Alfredsson L., Bjorner J.B., Borritz M., Burr H., Gold- berg M., et al. Association of Healthy Lifestyle With Years Lived Without Ma- jor Chronic Diseases. JAMA Intern. Med. 2020;180:760–768. doi: 10.1001/jamaintern- med.2020.0618. 88. Sofia Carlsson, Niklas Hammar, Valdemar Grill,Jaakko Kaprio, Alcohol Consumption and the Incidence of Type 2 DiabetesDia- betes Care 2003 Oct; 26(10): 2785-2790. htt ps://doi.org/10.2337/diacare.26.10.2785. 89. Nakanishi N, Suzuki K, Tatara K: Alcohol consumption and risk for development of impaired fasting glucose or type 2 diabetes in middle-aged Japanese men. Diabetes Care 26:48–54, 2003. 90. de Vegt F, Dekker JM, Groeneveld WJ, Nijpels G, Stehouwer CD, Bouter LM, Heine RJ: Moderate alcohol consumption is asso- ciated with lower risk for incident diabetes and mortality: the Hoorn study. Diabetes Res Clin Pract 57:53–60, 2002. 91. Conigrave KM, Hu BF, Camargo CA, Stampfer MJ, Willett WC, Rimm EB: A prospective study of drinking patterns in relation to risk of type 2 diabetes among men. Diabetes 50:2390–2395, 2001. 92. Baliunas DO, Taylor BJ, Irving H, et al. Alcohol as a risk factor for type 2 diabetes: a systematic re- view and meta-analysis. Diabetes Care 2009;32:2123–2132pmid:19875607. 93. Craig Knott 94. Akash MS, Rehman K, Chen S. Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus. J Cell Biochem 2013;114:525–531pmid:22991242. 95. Brien SE, Ronksley PE, Turner BJ, Mukamal KJ, Ghali WA. Effect of al- cohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta- analysis of interventional studies. BMJ 2011;342:d636pmid:21343206. 96. Schrieks IC, Heil AL, Hendriks HF, Muka- mal KJ, Beulens JW. The effect of alco- hol consumption on insulin sensitivity and glycemic status: a systematic review and meta-analysis of intervention studies. Dia- betes Care 2015;38:723–732. 97. Li H., Lv J., Yu C., Guo Y., Bian Z., Fan J., Yang L., Chen Y., Du H., Long H., et al. The Association Between Age at Initiation of Alcohol Consumption and Type 2 Diabetes Mellitus: A Cohort Study of 0.5 Million Persons in China. Am. J. Epidemiol. 2020;189:1478–1491. doi: 10.1093/aje/kwaa119. 98. Sofia Carlsson, Niklas Hammar, Valdemar Grill,Jaakko Kaprio, Alcohol Consumption and the Incidence of Type 2 Diabetes. Di- abetes Care 2003 Oct; 26(10): 2785-2790. ht tps://doi.org/10.2337/diacare.26.10.2785. 99. Lin Y., Ying Y.Y., Li S.X., Wang S.J., Gong Q.H., Li H. Association be- tween alcohol consumption and metabolic syndrome among Chinese adults. Pub- lic Health Nutr. 2020;10:1–23. doi: 10.1017/S1368980020004449. 100. Baik I., Park S.I. Associations of alcohol consumption and physical activity with lean type 2 diabetes mellitus among Korean adults: A prospective cohort study. PLoS ONE. 2020;15:e0238641. doi: 10.1371/jour- nal.pone.0238641. 101. Schlesinger S., Neuenschwander M., Ballon A., Nöthlings U., Barbaresko J. Adherence to healthy lifestyles and incidence of dia- betes and mortality among individuals with MEERP LTD CMI JOURNAL 2 (3), 185−200 (2021) 195 ALCOHOL AND NONCOMMUNICABLE DISEASES: PART II CANCER, DIABETES MELLITUS, KIDNEY DISEASES, ALZHEIMER’S DISEASE, ARTHRITIS diabetes: A systematic review and meta- analysis of prospective studies. J. Epidemiol. Community Health. 2020;74:481–487. doi: 10.1136/jech-2019-213415. 102. Han T, Zhang S, Duan W, Ren X, Wei C, Sun C, Li Y. Eighteen-year alcohol consump- tion trajectories and their association with risk of type 2 diabetes and its related fac- tors: the China Health and Nutrition Survey. Diabetologia. 2019 Jun;62(6):970-980. doi: 10.1007/s00125-019-4851-z. 103. Mayl JJ, German CA, Bertoni AG, Upad- hya B, Bhave PD, Yeboah J, Singleton MJ. Association of Alcohol Intake With Hypertension in Type 2 Diabetes Melli- tus: The ACCORD Trial. J Am Heart Assoc. 2020 Sep 15;9(18):e017334. doi: 10.1161/JAHA.120.017334. 104. Yang B.C., Wu S.Y., Leung P.S. Alcohol ingestion induces pancreatic islet dysfunc- tion and apoptosis via mediation of FGF21 resistance. Ann. Transl. Med. 2020;8:310. doi: 10.21037/atm.2020.02.129. 105. Wei M, Gibbons LW, Mitchell TL, Kampert JB, Blair SN. Alcohol intake and incidence of type 2 diabetes in men. Diabetes Care. 2000;23:18–22. 10.2337/diacare.23.1.18. 106. Kelly JT, Su G, Zhang L, Qin X, Marshall S, González-Ortiz A, Clase CM, Campbell KL, Xu H, Carrero JJ. Modifiable Lifestyle Factors for Primary Prevention of CKD: A Systematic Review and Meta-Analysis. J Am Soc Nephrol. 2021 Jan;32(1):239-253. doi: 10.1681/ASN.2020030384. 107. Reynolds K, Gu D, Chen J, et al. Alcohol consumption and the risk of end-stage renal disease among Chinese men. Kidney Int. 2008;73:870–876. 108. White SL, Polkinghorne KR, Cass A, Shaw JE, Atkins RC, Chadban SJ. Alcohol con- sumption and 5-year onset of chronic kidney disease: the AusDiab study. Nephrol Dial Transplant. 2009;24:2464–2472. 109. Schaeffner ES, Kurth T, de Jong PE, Glynn RJ, Buring JE, Gaziano JM. Alcohol con- sumption and the risk of renal dysfunction in apparently healthy men. Arch Intern Med. 2005;165:1048–1053. 110. Hsu YH, Pai HC, Chang YM, Liu WH, Hsu CC. Alcohol consumption is inversely associ- ated with stage 3 chronic kidney disease in middle-aged Taiwanese men. BMC Nephrol. 2013;14:254. 111. Li D, Xu J, Liu F, Wang X, Yang H, Li X. Alcohol drinking and the risk of chronic kid- ney damage: a meta-analysis of 15 prospec- tive cohort studies. Alcohol Clin Exp Res. 2019;43:1360–1372. 112. Inoue Y, Howard AG, Thompson AL, et al. The association between urbanization and reduced renal function: findings from the China Health and Nutrition Survey. BMC Nephrol. 2017;18(1):160. 113. White SL, Polkinghorne KR, Cass A, et al. Alcohol consumption and 5-year onset of chronic kidney disease: the AusDiab study. Nephrol Dial Transplant. 2009;24(8):2464–72. 114. Shankar A, Klein R, Klein BEK. The as- sociation among smoking, heavy drinking, and chronic kidney disease. Am J Epidemiol. 2006;164(3):263–71. 115. Savdie E, Grosslight GM, Adena MA. Rela- tion of alcohol and cigarette consumption to blood pressure and serum creatinine levels. J Chronic Dis. 1984;37(8):617–23. 116. Perneger TV, Whelton PK, Puddey IB, et al. Risk of end-stage renal disease associated with alcohol consumption. Am J Epidemiol. 1999;150(12):1275–81. 117. Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. CMI JOURNAL 2 (3), 185−200 (2021) MEERP LTD 196 MEERP LTD SHASHI K. AGARWAL, MD 118. Park S, Lee S, Kim Y, et al. Causal ef- fect of alcohol use on the risk of end- stage kidney disease and related comor- bidities: a Mendelian randomization study. Kidney Res Clin Pract. 2021;40(2):282-293. doi:10.23876/j.krcp.20.186. 119. Latchoumycandane C, Nagy LE, McIntyre TM. Myeloperoxidase formation of PAF receptor ligands induces PAF receptor- dependent kidney injury during ethanol consumption. Free Radic Biol Med. 2015;86:179–190. 120. Hamrahian SM, Falkner B. Hyperten- sion in Chronic Kidney Disease. Adv Exp Med Biol. 2017;956:307-325. doi: 10.1007/5584_2016_84. 121. Leal S, Ricardo Jorge DO, Joana B, Maria SS, Isabel SS. Heavy alcohol consumption effects on blood pressure and on kidney structure persist after long-term withdrawal. Kidney Blood Press Res. 2017;42:664–675. 122. Hipolito UV, Callera GE, Simplicio JA, et al. Vitamin C prevents the endothelial dysfunc- tion induced by acute ethanol intake. Life Sci. 2015;141:99–107. 123. Yuan Q, Hong S, Han S, et al. Precondi- tioning with physiological levels of ethanol protect kidney against ischemia/reperfusion injury by modulating oxidative stress. PLoS One. 2011;6(10):e25811. 124. Fan Z, Yun J, Yu S, Yang Q, Song L. Alcohol Consumption Can be a "Double-Edged Sword" for Chronic Kidney Disease Patients. Med Sci Monit. 2019 Sep 20;25:7059-7072. doi: 10.12659/MSM.916121.;https://www. kidney.org/atoz/content/alcohol -accessed August 2, 2021. 125. Ilomaki J, Jokanovic N, Tan ECK, Lon- nroos E. Alcohol consumption, demen- tia, and cognitive decline: an overview of systematic reviews. Curr Clin Pharmacol. 2015;10:204–212. 126. Koch M, Fitzpatrick AL, Rapp SR. Alco- hol Consumption and risk of dementia and cognitive decline among older adults with or without mild cognitive impairment. JAMA Netw Open. 2019;2. 127. Piumatti G, Moore SC, Berridge DM, Sarkar C, Gallacher J. The relationship between alcohol use and long-term cognitive decline in middle and late life: a longitudinal analysis using UK Biobank. J Public Health (Oxf) 2018;40:304–311. 128. Munoz G., Urrutia J.C., Burgos C.F., Silva V., Aguilar F., Sama M., Yeh H.H., Opazo C., Aguayo L.G. Low concentra- tions of ethanol protect against synapto- toxicity induced by Abeta in hippocampal neurons. Neurobiol. Aging. 2015;36:845–856. doi: 10.1016/j.neurobiolaging.2014.10.017. 129. Anstey K.J., Ee N., Eramudugolla R., Jagger C., Peters R. A Systematic Review of Meta- Analyses that Evaluate Risk Factors for De- mentia to Evaluate the Quantity, Quality, and Global Representativeness of Evidence. J. Alzheimer’s Dis. 2019;70:S165–S186. doi: 10.3233/JAD-190181. 130. Munoz G., Urrutia J.C., Burgos C.F., Silva V., Aguilar F., Sama M., Yeh H.H., Opazo C., Aguayo L.G. Low concentra- tions of ethanol protect against synapto- toxicity induced by Abeta in hippocampal neurons. Neurobiol. Aging. 2015;36:845–856. doi: 10.1016/j.neurobiolaging.2014.10.017. 131. Munoz G., Urrutia J.C., Burgos C.F., Silva V., Aguilar F., Sama M., Yeh H.H., Opazo C., Aguayo L.G. Low concentra- tions of ethanol protect against synapto- toxicity induced by Abeta in hippocampal neurons. Neurobiol. Aging. 2015;36:845–856. doi: 10.1016/j.neurobiolaging.2014.10.017. 132. Huang D., Yu M., Yang S., Lou D., Zhou W., Zheng L., Wang Z., Cai F., Zhou W., Li T., et al. Ethanol Alters APP Processing MEERP LTD CMI JOURNAL 2 (3), 185−200 (2021) 197 ALCOHOL AND NONCOMMUNICABLE DISEASES: PART II CANCER, DIABETES MELLITUS, KIDNEY DISEASES, ALZHEIMER’S DISEASE, ARTHRITIS and Aggravates Alzheimer-Associated Phe- notypes. Mol. Neurobiol. 2018;55:5006–5018. doi: 10.1007/s12035-017-0703-3. 133. Hoffman J.L., Faccidomo S., Kim M., Taylor S.M., Agoglia A.E., May A.M., Smith E.N., Wong L.C., Hodge C.W. Alcohol drinking exacerbates neural and behavioral pathology in the 3xTg-AD mouse model of Alzheimer’s disease. Int. Rev. Neurobiol. 2019;148:169–230. doi: 10.1016/bs.irn.2019.10.017. 134. Piumatti G, Moore SC, Berridge DM, Sarkar C, Gallacher J. The relationship between alcohol use and long-term cognitive decline in middle and late life: a longitudinal analysis using UK Biobank. J Public Health (Oxf) 2018;40:304–311. 135. Schwarzinger M, Pollock BG, Hasan OSM. Contribution of alcohol use disorders to the burden of dementia in France 2008–13: a na- tionwide retrospective cohort study. Lancet Public Health. 2018;3:e124–e132. 136. Topiwala A, Allan CL, Valkanova V. Moder- ate alcohol consumption as risk factor for ad- verse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017;357. 137. Rehm J, Hasan OSM, Black SE, Shield KD, Schwarzinger M. Alcohol use and dementia: a systematic scoping review. Alzheimers Res Ther. 2019;11:1. 138. Huang D., Yu M., Yang S., Lou D., Zhou W., Zheng L., Wang Z., Cai F., Zhou W., Li T., et al. Ethanol Alters APP Processing and Aggravates Alzheimer-Associated Phe- notypes. Mol. Neurobiol. 2018;55:5006–5018. doi: 10.1007/s12035-017-0703-3. 139. Hoffman J.L., Faccidomo S., Kim M., Taylor S.M., Agoglia A.E., May A.M., Smith E.N., Wong L.C., Hodge C.W. Alcohol drinking exacerbates neural and behavioral pathology in the 3xTg-AD mouse model of Alzheimer’s disease. Int. Rev. Neurobiol. 2019;148:169–230. doi: 10.1016/bs.irn.2019.10.017. 140. Sabia S, Fayosse A, Dumurgier J. Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study. BMJ. 2018;362. 141. Anttila T., Helkala E.L., Viitanen M., Kare- holt I., Fratiglioni L., Winblad B., Soininen H., Tuomilehto J., Nissinen A., Kivipelto M. Alcohol drinking in middle age and subse- quent risk of mild cognitive impairment and dementia in old age: A prospective popula- tion based study. BMJ. 2004;329:539. doi: 10.1136/bmj.38181.418958.BE. 142. WHO . Risk Reduction of Cognitive Decline and Dementia: WHO Guidelines. WHO; Geneva, Switzerland: 2019. 143. Juhakoski R, Heliövaara M, Impivaara O, Kröger H, Knekt P, Lauren H, Arokoski JP. Risk factors for the development of hip os- teoarthritis: a population-based prospective study. Rheumatol. 2009;48(1):83–87. doi: 10.1093/rheumatology/ken427. 144. Karlson EW, Mandl LA, Aweh GN, Sangha O, Liang MH, Grodstein F. Total hip re- placement due to osteoarthritis: the impor- tance of age, obesity, and other modifiable risk factors. Am J Med. 2003;114(2):93–98. doi: 10.1016/S0002-9343(02)01447-X. 145. Mandrekar P, Catalano D, White B, Szabo G. Moderate alcohol intake in humans at- tenuates monocyte inflammatory responses: inhibition of nuclear regulatory factor kappa B and induction of interleukin 10. Alco- hol Clin Exp Res. 2006;30(1):135–139. doi: 10.1111/j.1530-0277.2006.00012.x. 146. Zhang Y, Zeng C, Wei J, Li H, Yang T, Yang Y, et al. Associations of cigarette smoking, betel quid chewing and alcohol consump- tion with high-sensitivity C-reactive pro- tein in early radiographic knee osteoarthri- tis: a cross-sectional study. BMJ Open. CMI JOURNAL 2 (3), 185−200 (2021) MEERP LTD 198 MEERP LTD SHASHI K. AGARWAL, MD 2016;6(3):e010763. doi: 10.1136/bmjopen- 2015-010763, 147. McClain CJ, Barve S, Deaciuc I, Kugelmas M, Hill D. Cytokines in alcoholic liver dis- ease. Semin Liver Dis. 1999;19(2):205–219. doi: 10.1055/s-2007-1007110. 148. Haugen IK, Slatkowsky-Christensen B, Bøyesen P, Sesseng S, van der Heijde D, Kvien TK. MRI findings predict ra- diographic progression and development of erosions in hand osteoarthritis. Ann Rheum Dis. 2014;75(1):117–123. doi: 10.1136/annrheumdis-2014-205949. 149. Kc R, Voigt R, Li X, Forsyth CB, Ell- man MB, Summa KC, et al. Induction of osteoarthritis-like pathologic changes by chronic alcohol consumption in an experi- mental mouse model. Arthritis Rheumatol. 2015;67:1678–1680. doi: 10.1002/art.39090. 150. Kang AH, Kim MR, Shin JS, et al. As- sociation between alcohol consumption and osteoarthritis prevalence in Korea as as- sessed by the alcohol use disorders iden- tification test (AUDIT): a cross-sectional study. BMC Public Health. 2020;20(1):227. Published 2020 Feb 13. doi:10.1186/s12889- 020-8326-4. 151. Rosell M, Wesley AM, Rydin K, et al. Dietary fish and fish oil and the risk of rheumatoid arthritis. Epidemiology. 2009;20:896–901.;, Di Giuseppe D, Alfreds- son L, Bottai M, et al. Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study. BMJ. 2012;345:e4230. 152. Lu B, Rho YH, Cui J, Iannaccone CK, Frits ML, Karlson EW, Shadick NA. Associations of smoking and alcohol consumption with disease activity and functional status in rheumatoid arthritis. J Rheumatol. 2014 Jan;41(1):24-30. doi: 10.3899/jrheum.130074. 153. Di Giuseppe D, Alfredsson L, Bottai M, et al. Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study. BMJ. 2012;345:e4230. 154. Maxwell J.R., Gowers I.R., Moore D.J., Wilson A.G. Alcohol consumption is in- versely associated with risk and sever- ity of rheumatoid arthritis. Rheumatol- ogy (Oxford) 2010;49(11):2140–2146. doi: 10.1093/rheumatology/keq202. 155. Sundström B., Johansson I., Rantapää- Dahlqvist S. Diet and alcohol as risk factors for rheumatoid arthritis: A nested case-control study. Rheumatol. Int. 2015;35(3):533–539. doi: 10.1007/s00296- 014-3185-x. 156. Baker JF, England BR, Mikuls TR, Hsu JY, George MD, Pedro S, Sayles H, Michaud K. Changes in Alcohol Use and Associations With Disease Activity, Health Status, and Mortality in Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2020 Mar;72(3):301- 308. doi: 10.1002/acr.23847. 157. Vandenberg MK, Moxley G, Breitbach SA, Roberts WN. Gout attacks in chronic al- coholics occur at lower serum urate lev- els than in non-alcoholic. J Rheumatol 1994;21:700–4. 158. Zeng QY. Drinking alcohol and gout. [Edito- rial]. Lancet 2004;363:1251–2. 159. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Alcohol intake and risk of incident gout in men: a prospective study. Lancet 2004;363:1277–81. 160. Ralston SH, Capell HA, Sturrock RD. Alco- hol and response to treatment of gout. BMJ 1988;296:1641–2. 161. Faller J, Fox IH. Ethanol-induced hyper- uricemia: evidence for increased urate pro- duction by activation of adenine nucleotide turnover. N Engl J Med 1982;307:1598–602. MEERP LTD CMI JOURNAL 2 (3), 185−200 (2021) 199 ALCOHOL AND NONCOMMUNICABLE DISEASES: PART II CANCER, DIABETES MELLITUS, KIDNEY DISEASES, ALZHEIMER’S DISEASE, ARTHRITIS How to cite this article: Agarwal S.K,, MD. Alco- hol and Noncommunicable Diseases: Part II Cancer, Diabetes Mellitus, Kidney Dis-eases, Alzheimer’s Disease, Arthritis. Clinical Medicine Insights. 2021;185−200. https://doi.org/10.5284 5/CMI/2021-2-3-6 CMI JOURNAL 2 (3), 185−200 (2021) MEERP LTD 200 Introduction Discussion CANCER DIABETES MELLITUS KIDNEY DISEASES ALZHEIMER'S DISEASE ARTHRITIS CONCLUSION