METABOLIC SYNDROME

WHAT IS METABOLIC SYNDROME?

The term “metabolic syndrome” was coined in scientific literature by Hermann Haller in 1975, as a combination of certain variables that increased the risk of cardiovascular disease (1). In 1988, G. M. Reaven described a similar combination of factors that lead to coronary artery disease and labeled that combination as “Syndrome X” (2). Today, the term metabolic syndrome is most commonly used to describe this health problem.  Metabolic syndrome is a collection of metabolic abnormalities, that together, increase the risk of cardiovascular disease, diabetes, and stroke (3).

RISK FACTORS AND SYMPTOMS OF METABOLIC SYNDROME

• Central Obesity (increased waist circumference measuring ≥102 cm in men and ≥ 88 cm in women)
• Dyslipidemia (elevated triglycerides ≥150 mg/dl)
• Insulin Resistance (reduced HDL cholesterol <40 mg/dl in men and < 50 mg/dl in women)
• Hypertension (≥130/85 mm Hg or on treatment for hypertension)
• Hyperglycemia (≥100 mg/dl) (4)

Each of the five major risk factors that contribute to metabolic syndrome is serious conditions individually that should be paid attention to and treated. According to the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI), criteria for a diagnosis of metabolic syndrome includes at least three out of the five risk factors.  Furthermore, they stated that having metabolic syndrome does, in fact, increase chances of cardiovascular diseases more than having any of the variables individually (5,6).  The International Diabetes Federation (IDF) puts central obesity and insulin resistance as the most causative risk factors for metabolic syndrome (4,7). Various organizations agree that central obesity, specifically waist circumference would continue to be a preliminary screening tool for metabolic syndrome (8).

Research shows that there are further risk factors for metabolic syndrome that go beyond the five major variables. Some of these include:

• Lack of physical activity (9)
• Cigarette smoking (10,11)
• Increased age (12,13)
• Alcohol consumption (14,15)
• High fat and carbohydrate diet (16,17)

For more information on metabolic syndrome and diagnosis:  1. Talk to your doctor  2. Visit the American Heart Association website  3. Visit the Mayo Clinic website 

METABOLIC SYNDROME FACTS AND STATISTICS

In 2015, the American Heart Association reported that an estimated 34% of adults in the United States have metabolic syndrome (17).  According to a study performed in 2012, an estimated 50% of people in the United States over the age of 60 have metabolic syndrome (18).

Obesity

• Between 2011 and 2014, over 35% of adults in the United States were obese (19).

Diabetes (Insulin Resistance/Hyperglycemia)

• In 2015, 9.4% or over 30 million people in the United States had diabetes
• Type 2 diabetes accounts for 90% to 95% of all cases (20)

Hypertension

• Hypertension was responsible for over 400,000 deaths in 2014 in the United States.
• In 2016, 1 in 3 adults in the United States had pre-hypertension (21).

Dyslipidemia (High Cholesterol)

• In 2012, 37% of adults in the United States had elevated “bad” cholesterol or high LDL levels (22).
• Between 2011 and 2012, 7% of children and adolescents between 6 and 19 years old in the United States had high total cholesterol (22).

MEDICAL TREATMENT OF METABOLIC SYNDROME

Treatment of metabolic syndrome would be to treat each risk factor that contributes to it.

Fibrates

• Effective in reducing lipid abnormalities
• Low incidence side effects include skin reactions and blood clotting, rare nervous system or libido disturbances, gallstone (23,24)

Statins

• Effective in reducing lipid abnormalities in metabolic syndrome patients
• Marketed as Lipitor, Crestor
• Side effects include hypothyroidism, polypharmacy and alcohol abuse (25,26)

Metformin

• Enhances the action of insulin in the liver to reduce the rate of hepatic glucose production (27)
• Side effects include diarrhea and vitamin B12 deficiency and clinical neuropathy in type 2 diabetes patients (28,29)

Cholesterol Absorption Inhibitors

• Inhibits intestinal cholesterol absorption
• Side effects include headache, pharyngitis, upper respiratory tract concerns, nausea and chest pain (30)

Glucagon-Like Peptide-1 Receptor Agonists

• Controls blood glucose levels (31)
• Effective in treating type 2 diabetes, obesity and hyperglycemia (32)
• Side effects include nausea, vomiting, diarrhea, moderate injection site pruritus,  hypoglycemia (33,34,35,36,37,38,39,40,41)

NATURAL WAYS TO SUPPORT A HEALTHY CARDIOVASCULAR SYSTEM

Practices to Support a Healthy Cardiovascular System:

• Reduce or quit smoking (42)
• Exercise for weight loss (43,44)
• Balanced diet with calorie restrictions (44)
• Maintain healthy blood pressure (45)
• Regular doctor check-ups (45)

Natural Supplements That Support a Healthy Cardiovascular System:

• Cinnamon (46,47)
• Fenugreek (48,49)
• Gymnema sylvestre (50,51)
• Ginseng (52,53)
• Momordica charantia (bitter melon) (54,55)
• Allium sativa (garlic) (56,57)
• Ocimum sanctum (tulsi, holy basil) (58)

REFERENCES

1. Haller H. [Epidermiology and associated risk factors of hyperlipoproteinemia]. Zeitschrift für die gesamte Inn Medizin und ihre Grenzgebiete. 1977;32(8):124-128.
2. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595-1607. doi:10.2337/diab.37.12.1595
3. Srikanthan K, Feyh A, Visweshwar H, Shapiro JI, Sodhi K. Systematic review of metabolic syndrome biomarkers: A panel for early detection, management, and risk stratification in the West Virginian population. Int J Med Sci. 2016;13(1):25-38. doi:10.7150/ijms.13800
4. Emanuela F, Grazia M, Marco DR, Maria Paola L, Giorgio F, Marco B. Inflammation as a link between obesity and metabolic syndrome. J Nutr Metab. 2012;2012. doi:10.1155/2012/476380
5. Hutcheson R, Rocic P. The metabolic syndrome, oxidative stress, environment, and cardiovascular disease: The great exploration. Exp Diabetes Res. 2012;2012. doi:10.1155/2012/271028
6. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation. 2005;112(17):2735-2752.
7. Consensus statements. Idforg. 2018. https://www.idf.org/e-library/consensus-statements/60-idfconsensus-worldwide-definitionof-the-metabolic-syndrome. Accessed March 17, 2018.
8. Alberti KGMM, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640-1645. doi:10.1161/CIRCULATIONAHA.109.192644
9. Ford ES, Kohl HW, Mokdad AH, Ajani UA. Sedentary behavior, physical activity, and the metabolic syndrome among U.S. adults. Obes Res. 2005;13(3):608-614. doi:10.1038/oby.2005.65
10. Balhara YPS, Article R, Balhara YPS. Tobacco and metabolic syndrome. Indian J Endocrinol Metab. 2012;16(1):81-87. doi:10.4103/2230-8210.91197
11. Calo WA, Ortiz AP, Suárez E, Guzmán M, Pérez CM, Pérez CM. Association of cigarette smoking and metabolic syndrome in a Puerto Rican adult population. J Immigr Minor Health. 2013;15(4):810-816. doi:10.1007/s10903-012-9660-0
12. Suastika K, Dwipayana P, Ratna Saraswati IM, et al. Relationship between age and metabolic disorders in the population of Bali. J Clin Gerontol Geriatr. 2011;2(2):47-52. doi:10.1016/j.jcgg.2011.03.001
13. Hildrum B, Mykletun A, Hole T, Midthjell K, Dahl AA. Age-specific prevalence of the metabolic syndrome defined by the International Diabetes Federation and the National Cholesterol Education Program: the Norwegian HUNT 2 study 1349. BMCPublic Heal. 2007;7(1471-2458 (Electronic)):220.
14. Baik I, Shin C. Prospective study of alcohol consumption and metabolic syndrome. Am J Clin Nutr. 2008;87(5):1455-1463.
15. Vieira BA, Luft VC, Schmidt MI, et al. Timing and type of alcohol consumption and the metabolic syndrome – ELSA-Brasil. PLoS One. 2016;11(9). doi:10.1371/journal.pone.0163044
16. Pitsavos C, Panagiotakos D, Weinem M, Stefanadis C. Diet, exercise and the metabolic syndrome. Rev Diabet Stud. 2006;3(3):118-126. doi:10.1900/RDS.2006.3.118
17. Heart.org. 2018. https://www.heart.org/idc/groups/heart-public/@wcm/@hcm/documents/downloadable/ucm_300322.pdf. Accessed March 17, 2018.
18. Maria Aguilar, Taft Bhuket, Sharon Torres, Benny Liu, Robert J. Wong. Prevalence of the Metabolic Syndrome in the United States, 2003-2012. JAMA, 2015; 313 (19): 1973 DOI: 10.1001/jama.2015.4260
19. Chronic Disease Overview | Publications | Chronic Disease Prevention and Health Promotion | CDC. Cdcgov. 2018. https://www.cdc.gov/chronicdisease/overview/index.htm. Accessed March 17, 2018.
20. Diabetes.org. 2018. http://www.diabetes.org/assets/pdfs/basics/cdc-statistics-report-2017.pdf. Accessed March 17, 2018.
21. High Blood Pressure Fact Sheet|Data & Statistics|DHDSP|CDC. Cdcgov. 2018. https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_bloodpressure.htm. Accessed March 17, 2018.
22. High Cholesterol Facts. Centers for Disease Control and Prevention. 2018. https://www.cdc.gov/cholesterol/facts.htm. Accessed March 17, 2018.
23. Roberts WC. Safety of fenofibrate-us and worldwide experience. Cardiol. 1989;76(3):169-179. doi:10.1159/000174488
24. Sgro C, Escousse A. Side Effects of Fibrates (except liver and muscle). Therapie. 1991;46(5):351-354.
25. Ramkumar S, Raghunath A, Raghunath S. Statin therapy: Review of safety and potential side effects. Acta Cardiol Sin. 2016;32(6):631-639. doi:10.6515/ACS20160611A
26. Maji D, Shaikh S, Solanki D, Gaurav K. Safety of statins. Indian J Endocrinol Metab. 2013;17(4):636. doi:10.4103/2230-8210.113754
27. Natali A, Ferrannini E. Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: A systematic review. Diabetologia. 2006;49(3):434-441. doi:10.1007/s00125-006-0141-7
28. Hostalek U, Gwilt M, Hildemann S. Therapeutic Use of Metformin in Prediabetes and Diabetes Prevention. Drugs. 2015;75(10):1071-1094. doi:10.1007/s40265-015-0416-8
29. Singh a K, Kumar a, Karmakar D, Jha RK. Association of B12 deficiency and clinical neuropathy with metformin use in type 2 diabetes patients. J Postgrad Med. 2013;59(4):253-257. doi:10.4103/0022-3859.123143
30. Gagné C, Gaudet D, Bruckert E. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation. 2002;105(21):2469-2475. doi:10.1161/01.CIR.0000018744.58460.62
31. Drucker DJ. Biologic actions and therapeutic potential of the proglucagon-derived peptides. Nat Clin Pract Endocrinol Metab. 2005;1(1):22-31. doi:10.1038/ncpendmet0017
32. Tran KL, Park YI, Pandya S, et al. Overview of glucagon-like peptide-1 receptor agonists for the treatment of patients with type 2 diabetes. Am Heal Drug Benefits. 2017;10(4):178-188.
33. Buse JB, Drucker DJ, Taylor KL, et al. DURATION-1: Exenatide once weekly produces sustained glycemic control and weight loss over 52 weeks. Diabetes Care. 2010;33(6):1255-1261. doi:10.2337/dc09-1914
34. Blevins T, Pullman J, Malloy J, et al. DURATION-5: Exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011;96(5):1301-1310. doi:10.1210/jc.2010-2081
35. Diamant M, Van Gaal L, Guerci B, et al. Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial. lancet Diabetes Endocrinol. 2014;2(6):464-473. doi:10.1016/S2213-8587(14)70029-4
36. Montanya E, Sesti G. A review of efficacy and safety data regarding the use of liraglutide, a once-daily human glucagon-like peptide 1 analogue, in the treatment of type 2 diabetes mellitus. Clin Ther. 2009;31(11):2472-2488.
37. Nauck MA, Stewart MW, Perkins C, et al. Efficacy and safety of once-weekly GLP-1 receptor agonist albiglutide (HARMONY 2): 52 week primary endpoint results from a randomised, placebo-controlled trial in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetologia. 2016;59(2):266-274. doi:10.1007/s00125-015-3795-1
38. Ahrén B, Johnson SL, Stewart M, et al. HARMONY 3: 104-week randomized, double-blind, placebo- and active-controlled trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin. Diabetes Care. 2014;37(8):2141-2148. doi:10.2337/dc14-0024
39. Bolli GB, Munteanu M, Dotsenko S, et al. Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin (GetGoal-F1). Diabet Med. 2014;31(2):176-184. doi:10.1111/dme.12328
40. Wysham C, Blevins T, Arakaki R, et al. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes Care. 2014;37(8):2159-2167. doi:10.2337/dc13-2760
41. Giorgino F, Benroubi M, Sun J-H, Zimmermann AG, Pechtner V. Efficacy and Safety of Once-Weekly Dulaglutide Versus Insulin Glargine in Patients With Type 2 Diabetes on Metformin and Glimepiride (AWARD-2). Diabetes Care. 2015;38(12):2241-2249. doi:10.2337/dc14-1625
42. Gepner AD, Piper ME, Johnson HM, Fiore MC, Baker TB, Stein JH. Effects of smoking and smoking cessation on lipids and lipoproteins: Outcomes from a randomized clinical trial. Am Heart J. 2011;161(1):145-151. doi:10.1016/j.ahj.2010.09.023
43. Unick JL, Beavers D, Bond DS, et al. The long-term effectiveness of a lifestyle intervention in severely obese individuals. Am J Med. 2013;126(3):236-242. doi:10.1016/j.amjmed.2012.10.010
44. Information H, Overview D, Diabetes? W, Resistance P, Resistance P. Prediabetes & Insulin Resistance | NIDDK. National Institute of Diabetes and Digestive and Kidney Diseases. 2018. https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-resistance. Accessed March 21, 2018.
45. Mouri Mi, Bhimji SS. Hyperglycemia.; 2017. http://www.ncbi.nlm.nih.gov/pubmed/28613650.
46. Ranasinghe P, Gunatilake M, Gunapala N et al. Effects of Cinnamomum zeylanicum(Ceylon cinnamon) on blood glucose and lipids in a diabetic and healthy rat model. Pharmacognosy Res. 2012;4(2):73. doi:10.4103/0974-8490.94719.
47. SHEN Y, FUKUSHIMA M, ITO Y et al. Verification of the Antidiabetic Effects of Cinnamon (Cinnamomum zeylanicum) Using Insulin-Uncontrolled Type 1 Diabetic Rats and Cultured Adipocytes. Biosci Biotechnol Biochem. 2010;74(12):2418-2425. doi:10.1271/bbb.100453.
48. Muraki E, Chiba H, Tsunoda N, Kasono K. Fenugreek Improves Diet-induced Metabolic Disorders in Rats. Hormone and Metabolic Research. 2011;43(13):950-955. doi:10.1055/s-0031-1291345.
49. Rafraf M, Malekiyan M, Asghari-Jafarabadi M, Aliasgarzadeh A. Effect of Fenugreek Seeds on Serum Metabolic Factors and Adiponectin Levels in Type 2 Diabetic Patients. International Journal for Vitamin and Nutrition Research. 2015;84(3-4):0196-0205. doi:10.1024/0300-9831/a000206.
50. Zuñiga L, González-Ortiz M, Martínez-Abundis E. Effect of Gymnema sylvestre Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion. J Med Food. 2017;20(8):750-754. doi:10.1089/jmf.2017.0001.
51. Kumar V, Bhandari U, Tripathi C, Khanna G. Anti-obesity Effect of Gymnema sylvestre Extract on High Fat Diet-induced Obesity in Wistar Rats. Drug Res (Stuttg). 2013;63(12):625-632. doi:10.1055/s-0033-1349852.
52. Sotaniemi E, Haapakoski E, Rautio A. Ginseng Therapy in Non-Insulin-Dependent Diabetic Patients: Effects on psychophysical performance, glucose homeostasis, serum lipids, serum aminoterminal propeptide concentration, and body weight. Diabetes Care. 1995;18(10):1373-1375. doi:10.2337/diacare.18.10.1373.
53. Shishtar E, Sievenpiper J, Djedovic V et al. The Effect of Ginseng (The Genus Panax) on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. PLoS ONE. 2014;9(9):e107391. doi: 10.1371/journal.pone.0107391.
54. Alam M, Uddin R, Subhan N, Rahman M, Jain P, Reza H. Beneficial Role of Bitter Melon Supplementation in Obesity and Related Complications in Metabolic Syndrome. J Lipids. 2015; 2015:1-18. doi:10.1155/2015/496169.
55. Tsai C, Chen E, Tsay H, Huang C. Wild bitter gourd improves metabolic syndrome: A preliminary dietary supplementation trial. Nutr J. 2012;11(1). doi:10.1186/1475-2891-11-4.
56. Choudhary P, Jani R, Sharma M. Effect of Raw Crushed Garlic (Allium sativum L.) on Components of Metabolic Syndrome. J Diet Suppl. 2017:1-8. doi:10.1080/19390211.2017.1358233.
57. Zeng Y, Li Y, Yang J et al. Therapeutic Role of Functional Components in Alliums for Preventive Chronic Disease in Human Being. Evidence-Based Complementary and Alternative Medicine. 2017; 2017:1-13. doi:10.1155/2017/9402849.
58. Satapathy S, Das N, Bandyopadhyay D, Mahapatra S, Sahu D, Meda M. Effect of Tulsi (Ocimum sanctum Linn.) Supplementation on Metabolic Parameters and Liver Enzymes in Young Overweight and Obese Subjects. Indian Journal of Clinical Biochemistry. 2016;32(3):357-363. doi:10.1007/s12291-016-0615-4.