FP Essentials™

Metabolic Syndrome

Call for Authors

This edition of FP Essentials™ will cover recent updates on metabolic syndrome. The content should include: impaired glucose tolerance; hyperlipidemia; nonalcoholic steatohepatitis; and polycystic ovarian syndrome. The content should emphasize recent, relevant literature rather than provide a general review of these four topics.

This edition of FP Essentials should be approximately 10,000 words in length, divided into four sections of approximately 2,500 words each, plus an abstract of no more than 200 words for each section, key practice recommendations, a maximum of 15 tables and figures, recommended readings, and references. This edition should focus on what is new in each topic and should answer the key questions listed for each section. Each section should begin with an illustrative case, similar to the examples provided, with modifications to emphasize key points; each case should have a conclusion that demonstrates resolution of the clinical situation. The references suggested here include information that should be considered in preparation of this FP Essentials. However, these references are only a useful starting point that should be used to identify additional information to review.

Section 1: Metabolic Syndrome and Impaired Glucose Tolerance

Example case: Kara, a 34-year-old obese woman, was found after obtaining blood work to have a random glucose level of 174 mg/dL. She has a family history of diabetes in her mother and sister, and her father had a myocardial infarction at age 60 years. She does not smoke. You obtain a fasting blood sugar, and it is 124 mg/dL. Kara is otherwise in good health. She returns to the office to discuss the test results and a treatment plan.

Key questions to consider:

  • How is metabolic syndrome defined?
  • How is impaired glucose tolerance (IGT) defined?
  • How is IGT diagnosed?
  • What is the prevalence and the consequences, including the economic consequences, of untreated IGT? Are there differences in the prevalence of IGT among various ethnic groups?
  • What is the role of IGT in metabolic syndrome?
  • How is IGT prevented and/or managed? Do weight loss or certain diets reduce the risk of IGT, reduce its progression to diabetes, or reverse it? Is exercise beneficial?
  • What lifestyle interventions are beneficial for metabolic syndrome (eg, diet, exercise)?
  • What is the role of diet foods and drinks in development of metabolic syndrome?
  • When is drug therapy indicated? What drugs should be used and when? Can they reduce the progression of IGT to diabetes? Can they reduce the rate of adverse outcomes?

Initial references to consider:

  • Gillett M, Royle P, Snaith A, et al. Non-pharmacological interventions to reduce the risk of diabetes in people with impaired glucose regulation: a systematic review and economic evaluation. Health Technol Assess. 2012;16(1):1-236, iii-iv.
  • Bianchi C, Miccoli R, Trombetta M, et al. Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired β-cell function, insulin resistance, and worse cardiovascular risk profile: the GENFIEV study. J Clin Endocrinol Metab. 2013;98(5):2100-2105.
  • Malin SK, Nightingale J, Choi SE, Chipkin SE, Braun B. Metformin modifies the exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adults. Obesity (Silver Spring). 2013;21(1):93-100.
  • Hagman E, Reinehr T, Kowalski J, Ekbom A, Marcus C, Holl RW. Impaired fasting glucose prevalence in two nationwide cohorts of obese children and adolescents. Int J Obes (Lond). 2014;38(1):40-45.
  • Viscogliosi G, Cipriani E, Liquori ML, et al. Mediterranean dietary pattern adherence: associations with prediabetes, metabolic syndrome, and related microinflammation. Metab Syndr Relat Disord. 2013;11(3):210-216.
  • Schellenberg ES, Dryden DM, Vandermeer B, Ha C, Koroenyk C. Lifestyle interventions for patients with and at risk for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159(8):543-551.
  • Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH, Lau J. Long-term non-pharmacological weight loss interventions for adults with prediabetes. Cochrane Database Syst Rev. 2005;(2):CD005270.
  • Van de Laar FA, Luccasen PI, Akkermans RP, Van de Lisdonk EH, De Grauw WJ. Alpha-glucosidase inhibitors for people with impaired glucose tolerance or impaired fasting blood glucose. Cochrane Database Syst Rev. 2006;(4):CD005061.
  • Sorkin JD, Muller DC, Fleg JL, Andres R. The relation of fasting and 2-h postchallenge plasma glucose concentration to mortality: data from the Baltimore Longitudinal Study of Aging with a critical review of the literature. Diabetes Care. 2005;28(11):2626-2632.
  • Rodriguez F, Naderi S, Wang Y, Johnson CE, Foody JM. High prevalence of metabolic syndrome in young Hispanic women: findings from the national Sister to Sister campaign. Metab Syndr Relat Disord. 2013;11(2):81-86.
  • Shen L, Shah BR, Reyes EM, et al. Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study. BMJ. 2013;347:f6745. Erratum in BMJ. 2014;348:f1339.

Section 2: Metabolic Syndrome and Hyperlipidemia

Example case: John is a 35-year-old obese man. He has a waist circumference of 110 cm (43.3 in), and laboratory test results have shown impaired glucose tolerance. You obtain a fasting lipid profile that shows total cholesterol of 260 mg/dL, low-density lipoprotein level of 200 mg/dL, high-density lipoprotein level of 35 mg/dL, and triglycerides levels of 250 mg/dL. Although his father died of a myocardial infraction at age 45 years, John is reluctant to start drug therapy for treatment of these lipid abnormalities.

Key questions to consider:

  • What lipid disorders are commonly seen in adults with metabolic syndrome? Are these lipid disorders required for the diagnosis of metabolic syndrome?
  • Regarding etiology or consequences, is there anything different about the lipid disorders that occur in metabolic syndrome compared to those that occur in individuals without metabolic syndrome?
  • Should management of lipid disorders in patients with metabolic syndrome differ from that in other patients with lipid disorders? If so, how should it differ?
  • What interventions are effective for improving lipid profiles in patients with metabolic syndrome? Comment on nonpharmacologic (eg, diet, weight loss, exercise) and pharmacologic interventions (statins and other drugs). Do any of those management strategies reduce morbidity or mortality rates, or do they just improve lipid profiles? Do they reduce health care costs?
  • Does managing metabolic syndrome without specifically targeting lipids levels affect the lipid profile?
  • Are there effective herbal therapies?
  • To what extent can a lipid profile be improved by avoiding or ingesting alcohol?
  • What is the relationship between hypertriglyceridemia and cardiovascular disease when hypertriglyceridemia is the only lipid abnormality? How well established is that relationship?
  • What is the best clinical approach to managing mild to moderate hypertriglyceridemia when it occurs as an isolated lipid abnormality?
  • Have the 2013 American College of Cardiology/American Heart Association lipid guidelines changed the recommended management of lipid abnormalities in patients with metabolic syndrome? If so, what has changed?

Initial references to consider:

  • De la Iglesia R, Lopez-Legarrea P, Abete I, et al. A new dietary strategy for long-term treatment of the metabolic syndrome is compared with the American Heart Association (AHA) guidelines: the MEtabolic Syndrome REduction in NAvarra (RESMENA) project. Br J Nutr. 2014;111(4):643-652.
  • Rees K, Dyakova M, Wilson N, Ward K, Thorogood M, Brunner E. Dietary advice for reducing cardiovascular risk. Cochrane Database Syst Rev. 2013;(12):CD002128.
  • Elbarasi EA, Goodman SG, Yan RT, et al; Guidelines Oriented Approach in Lipid Lowering (GOALL) Registry and Vascular Protection (VP) Registry Investigators. Management of risk factors among ambulatory patients at high cardiovascular risk in Canada: a follow-up study. Can J Cardiol. 2013;29(12):1586-1592.
  • Adams SP, Tsang M, Wright JM. Lipid lowering efficacy of atorvastatin. Cochrane Database Syst Rev. 2012;(12):CD008226.
  • Bays HE, Avema M, Majul C, et al. Efficacy and safety of ezetimibe added to atorvastatin versus atorvastatin uptitration or switching to rosuvastatin in patients with primary hypercholesterolemia. Am J Cardiol. 2013;112(12):1885-1895.
  • Mampuya WM, Frid D, Rocco M, et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience. Am Heart J. 2013;166(3):597-603.
  • McKenny JM, Jenks BH, Shneyvas E, et al. A softgel dietary supplement containing esterified plant sterols and stanols improves the blood lipid profile of adults with primary hypercholesterolemia: a randomized, double-blind, placebo-controlled replication study. J Acad Nutr Diet. 2014;114(2):244-249.
  • Liu ZL, Liu JP, Zhang AL, et al. Chinese herbal medicines for hypercholesterolemia. Cochrane Database Syst Rev. 2011;(7):CD008305.
  • Ried K, Toben C, Fakler P. Effect of garlic on serum lipids: an updated meta-analysis. Nutr Rev. 2013; 71(5):282-299.
  • Wider B, Pittler MH, Thompson-Coon J, Ernst E. Artichoke leaf extract for treating hypercholesterolemia. Cochrane Database Syst Rev. 2013;(3):CD003335.
  • Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Nov 12 [Epub ahead of print]. Available at http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437738.63853.7a.citation(circ.ahajournals.org).

Section 3: Metabolic Syndrome and Nonalcoholic Steatohepatitis

Example case: Kathy is a 45-year-old obese woman who has been diagnosed with metabolic syndrome based on waist circumference, impaired glucose tolerance, and hyperlipidemia. She presented with abdominal pain and you obtained a chemistry profile, which showed elevated levels of aspartate transaminase and alanine transaminase. She denies any alcohol use and is not taking a statin or other drug that could cause elevated liver enzymes.

Key questions to consider:

  • What are the definitions of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)? How do these conditions differ?
  • What is the prevalence of NAFLD and NASH in patients with metabolic syndrome? Has the prevalence changed in recent years? What ethnic groups are more likely to have NAFLD and NASH, and to have comorbid metabolic syndrome?
  • How are NAFLD and NASH diagnosed? What is the differential diagnosis?
  • Is it important to diagnose NASH and NAFLD? If so, why?
  • Are NAFLD and NASH only found in obese patients? What influence does waist circumference and body mass index have on diagnosis and management?
  • What are thought to be the causes of NAFLD and NASH? Are these causes modifiable or reversible?
  • What are the roles of adipokines and vitamin D in NAFLD and NASH?
  • Does liver fat content predict impaired glucose tolerance? If so, how is liver fat content measured?
  • What are the consequences of NAFLD and NASH? How often do they progress to cirrhosis and can progression be prevented?
  • What nonpharmacologic and pharmacologic treatments should be recommended for patients with NAFLD and NASH? Are they effective in reversing or preventing progression of these conditions?  Are there other recommendations to consider, such as immunizations or avoidance of certain drugs?

Initial references to consider:

  • Williams CD, Stengel J, Asike MI, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140(1):124-131.
  • Kotronen A, Yki-Jarvinen H. Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2008;28(1):27-38.
  • Angulo P. Nonalcoholic fatty liver disease. N Eng J Med. 2002;346(16):1221-1231.
  • De Alwis NMW, Day CP. Non alcoholic fatty liver disease: the mist gradually clears. J Hepatol. 2008;48(Supp 1):S104-S112.
  • Adams LA, Waters OR, Knuiman MW, Elliott RR, Olynyk JK. NAFLD as a risk factor for the development of diabetes and the metabolic syndrome: an eleven year follow-up study. Am J Gastroenterol. 2009;104(4):861-867.
  • Bae JC, Cho YK, Lee WY, et al. Impact of nonalcoholic fatty liver disease on insulin resistance in relation to HbA1c levels in nondiabetic subjects. Am J Gastroenterol. 2010;105(11):2389-2395.
  • Bhat G, Baba CS, Pandey A, Kumari N, Choudhuri G. Insulin resistance and metabolic syndrome in nonobese Indian patients with non-alcoholic fatty liver disease. Trop Gastroenterol. 2013;34(1):18-24.
  • Ju CY, Choe YG, Cho YK, et al. The influence of waist circumference on insulin resistance and nonalcoholic fatty liver disease in apparently healthy Korean adults. Clin Mol Hepatol. 2013;19(2):140-147.
  • Karoll R. Fatima J, Chandra A, et al. Prevalence of hepatic steatosis in women with polycystic ovary syndrome. J Hum Reprod Sci. 2013;6(1):9-14.
  • Rhee EJ, Kim MK, Park SE, et al. High serum vitamin D levels reduce the risk for nonalcoholic fatty liver disease in healthy men independent of metabolic syndrome. Endocr J. 2013;60(6):743-752.

Section 4: Metabolic Syndrome and Polycystic Ovarian Syndrome

Example case: Grace is a 25-year-old woman who has been trying to get pregnant for 2 years. She says her menstrual periods have always been irregular, and she frequently goes several months without a period. On examination, you notice acne and mild hirsutism.

Key questions to consider:

  • What is the definition of polycystic ovarian syndrome (PCOS)? What are the defining criteria?
  • What is the prevalence of PCOS?
  • What are the typical presentations of PCOS? Which symptoms are more common, and how often does each symptom occur?
  • Does PCOS ever occur in isolation, without an association with metabolic syndrome and/or its related conditions?
  • How is PCOS diagnosed? Is the finding of cysts on the ovaries necessary or sufficient to diagnose PCOS?
  • What are the consequences of untreated PCOS? Are there consequences other than those related to cosmetics (eg, hirsutism, acne) or fertility?
  • What are the risks of developing impaired glucose tolerance, type 2 diabetes, and dyslipidemia in women with PCOS? What is the long-term risk of cardiovascular disease?
  • What lifestyle changes are considered first-line interventions for women with PCOS? How effective are they? Are different treatments warranted for difference symptoms?
  • What medical management strategies are effective for symptoms and for subfertility due to PCOS?
  • How does metformin affect PCOS, and how does it compare with oral contraceptive pills to regulate menses?
  • What drugs or other approaches induce ovulation in women with PCOS? Which are most effective?
  • What effect does acupuncture have on PCOS?
  • What interventions are effective for the management of hirsutism in PCOS?

Initial references to consider:

  • Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2010;16(4):347-363.
  • Michaliszyn SF, Lee S, Tfayli H, Arslanian S. Polycystic ovary syndrome and nonalcoholic fatty liver in obese adolescents: association with metabolic risk profile. Fertil Steril. 2013;100(6):1745-1751.
  • Moran LJ, Hutchison SK, Norman RJ, Teede HJ. Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2011;(7):CD007506.
  • Haqq L, McFarlane J, Dieberg G, Smart N. Effect of lifestyle intervention on the reproductive endocrine profile in women with polycystic ovary syndrome: a systematic review and meta-analysis. Endocr Connect. 2014;3(1):36-46.
  • Costello M, Shrestha B, Eden J, Sjoblom P, Johnson N. Insulin-sensitizing drugs versus the combined oral contraceptive pill for hirsutism, acne, and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome. Cochrane Database Syst Rev. 2007;(1):CD005552.
  • Farquhar C, Brown J, Marjoribanks J. Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2012;(6):CD001122.
  • Ganie MA, Khurana ML, Nisar S, et al. Improved efficacy of low-dose spironolactone and metformin combination than either drug alone in the management of women with polycystic ovary syndrome(PCOS): a six-month, open-label randomized study. J Clin Endocrinol Metab. 2013;98(9):3599-3607.
  • Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitizing drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 2012;(5):CD003053.
  • Franik S, Kremer JA, Nelen WI, Farquhar C. Aromatase inhibitors for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2014;(2):CD010287.
  • Jedel E, Labrie F, Oden A, et al. Impact of electro-acupuncture and physical exercise on hyperandrogenism and oligo/amenorrhea in women with polycystic ovary syndrome: a randomized controlled trial. Am J Physiol Endocrinol Metab. 2011;300(1):E37-E45.
  • Stener-Victorin E, Holm G, Janson PO, Gustafson D, Waern M. Acupuncture and physical exercise for affective symptoms and health related quality of life in polycystic ovary syndrome: secondary analysis from a randomized controlled trial. BMC Complement Altern Med. 2013;13(1):131 [Epub ahead of print].