Metabolic Syndrome

Aka: Metabolic Syndrome, Metabolic Syndrome X, Insulin Resistance Syndrome, Impaired Glucose Tolerance, Impaired Fasting Glucose, Insulin Resistance, Glucose Intolerance, Prediabetes, Prediabetic, Diabetes Risk Factors

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II. Definitions

  1. Prediabetes (Impaired Fasting Glucose, Impaired Glucose Tolerance)
    1. Inadequate Carbohydrate Metabolism to process intake, but not meeting Diabetes Mellitus criteria
  2. Insulin Resistance
    1. Insulin with decreased effectiveness in lowering Blood Sugar levels
  3. Metabolic Syndrome
    1. Collection of multiple metabolic risk factors
      1. Risks include abdominal Obesity, sedentary, Family History, Hyperlipidemia, Hypertension
    2. Associated with Insulin Resistance, prothrombotic and proinflammatory states
      1. Increased risk of Diabetes Mellitus and cardiovascular disease (CAD, CVA)

III. Epidemiology

  1. Prevalence in U.S. of Metabolic Syndrome or Prediabetes
    1. Total estimated at 86 million
    2. Affects 33% of adults and 4% of teens (90% of adults are unaware of diagnosis)

IV. Pathophysiology

  1. Diminished Insulin response results in hyperinsulinemia
    1. Fewer Insulin receptors on cells
    2. Less Glucose transporter (Glut 4) in cells
  2. Hyperinsulinemia predisposes to cardiovascular disease
  3. Precursor to Type II Diabetes Mellitus

V. Risk Factors

  1. Strong Family History of Diabetes Mellitus
  2. Prior Gestational Diabetes Mellitus or Fetal Macrosomia
  3. Metabolic Syndrome associated conditions (see below)
  4. Obesity
    1. Body Mass Index 30 kg/m2 or higher
    2. Waist to hip ratio increased
      1. Men: 1.0 or higher
      2. Women: 0.8 or higher
    3. Waist Circumference
      1. Men: >40 inches or 102 cm
      2. Women: >35 inches or 88 cm
  5. High Risk Ethnic Groups
    1. African American
    2. Latino
    3. Native American
    4. Asian American
    5. Pacific Islander

VI. Diagnosis: Metabolic Syndrome - Three or more conditions below

  1. Insulin Resistance (see labs below)
  2. Hypertension (Blood Pressure 130/85 or higher)
    1. Seen in up to 40% of Metabolic Syndrome patients
  3. Hyperlipidemia (see labs below)
  4. Coronary Artery Disease
  5. Polycystic Ovary Syndrome
  6. Acanthosis Nigricans
  7. HAIR-AN Syndrome
  8. Abdominal Obesity
    1. Men with Waist Circumference >40 inches or 102 cm
    2. Women with Waist Circumference >35 inches or 88 cm

VII. Labs: Screening Indications (repeat every 3 years)

  1. See Risk Factors above
  2. Age over 35 years and Body Mass Index >25 kg/m2 (>23 kg/m2 in asian patients)
  3. Family History of Diabetes Mellitus or high risk ethnic group (see above)
  4. Prior history of Gestational Diabetes
  5. HDL Cholesterol <35 mg/dl
  6. Serum Triglycerides >250 mg/dl
  7. Polycystic Ovary Syndrome
  8. Hypertension
  9. Overweight Teens (Puberty or over age 10 years old) with at least one other risk (e.g. diabetes Family History)

VIII. Labs: Diagnosis

  1. Impaired Glucose Metabolism Criteria
    1. Hemoglobin A1C 5.7 to 6.4%
    2. Fasting Glucose: 100 to 125 mg/dl
      1. Known as Impaired Fasting Glucose
      2. New guidelines suggest bottom cut-off of 100 mg/dl
      3. Metabolic Syndrome defined as 110 mg/dl or higher
    3. Two hour Glucose Tolerance Test (75 g): 140-199 mg/dl
      1. Known as Impaired Glucose Tolerance
  2. Lipid Profile
    1. Serum Triglycerides >150 mg/dl
    2. Serum Very Low Density Lipoprotein (VLDL) increased
    3. Serum HDL Cholesterol decreased
      1. Men <40 mg/dl
      2. Women <50 mg/dl
  3. Best lab markers for Insulin Resistance
    1. Plasma Insulin level (or Glucose to Insulin Ratio)
    2. Plasma Triglyceride levels
    3. Triglyceride to HDL ratio
    4. McLaughlin (2003) Ann Intern Med 139:802-9 [PubMed]

IX. Management: Prevention of progression to Diabetes

  1. Key goals: 7% weight loss and 150 min/week Exercise
    1. Consider referral to intensive lifestyle intervention program
      1. Example: National Diabetes Prevention Program
        1. https://www.cdc.gov/diabetes/prevention/index.html
      2. May delay type 2 diabetes by 4 years and decrease overall diabetes Incidence 34% in 10 years
        1. Knowler (2009) Lancet 374(9702):1677-86 [PubMed]
    2. Weight Reduction of 5-10% (if Overweight)
      1. Lose 7% of body weight
    3. Moderate aerobic Exercise for 30 minutes every day
      1. Example: Brisk walking for total of 150 min/week
      2. Encourage 60 minutes of Physical Activity in children and teens per day (and less Screen Time)
  2. Decreased Caloric Intake
    1. See Healthy Eating Plate
    2. Consider Mediterranean Diet, DASH Diet or Plant Forward or Vegetarian Diet
    3. Keep fat intake <30% with saturated fat <10%
    4. Salad, vegetables, fruits
    5. Whole grains and legumes
    6. Fish high in Omega-3 Fatty Acids and lean meats
    7. Reduce intake of Simple Sugars
  3. Foods associated with improved Insulin sensitivity
    1. Dietary Fiber
      1. Increase to15 gram per 1000 calories
    2. Coffee
      1. Salazar-Martinez (2004) Ann Intern Med 140:1-8 [PubMed]
      2. Tuomilehto (2004) JAMA 291:1213-9 [PubMed]
    3. Cinnamon (1/2 teaspoon per day)
      1. Studies used 1-3 g/day of cassia cinnamon (chinese cinnamon, C. aromaticum, C. cassia)
      2. Appears to have Insulin-like activity, may increase Insulin sensitivity and may improve lipid profile
      3. May decrease Fasting Glucose by up to 25 mg/dl
      4. (2017) Presc Lett 24(12): 71
      5. Costello (2016) J Acad Nutr Diet 116(11):1794-1802 [PubMed]
      6. Khan (2003) Diabetes Care 26(12):3215-8 +PMID:14633804 [PubMed]
    4. Moderate Alcohol consumption
      1. Howard (2004) Ann Intern Med 140:211-9 [PubMed]
  4. Consider pharmacologic agents for Glucose control
    1. Indications
      1. Hemoglobin A1C >5.7% despite 3-6 months of lifestyle changes
      2. Factors with greatest benefit for Metformin addition to lifestyle changes
        1. Body Mass Index >35 kg/m2
        2. Age <60 years old
        3. High Fasting Glucose or Hemoglobin A1C
        4. Gestational Diabetes history
        5. Madsen (2019) Cochrane Database Syst Rev (12): CD008558 [PubMed]
    2. First-line (preferred)
      1. Metformin (Glucophage)
        1. Initial: 500 mg Glucophage XR orally daily
        2. Next: 1000 mg Glucophage XR orally daily (indicated if Hemoglobin A1C>5.7% after 3 months)
        3. Hostalek (2015) Drugs 75(10): 1071-94 +PMID:26059289 [PubMed]
    3. Second-line (indicated if Glucophage contraindicated or not tolerated)
      1. Pioglitazone (Actos)
      2. Acarbose (Precose)
      3. GLP1 Agonist (e.g. Ozempic)

X. Management: Cardiac Risk Management

  1. Same as Diabetes Mellitus and Coronary Artery Disease
  2. Tobacco Cessation!
  3. Aspirin 81 mg orally daily
  4. Hyperlipidemia
    1. LDL Cholesterol <100 mg/dl
    2. HDL Cholesterol >40 mg/dl (50 mg/dl in women)
    3. Triglycerides <150 mg/dl
    4. Statins are preferred agents
      1. Sowers (2003) Am J Cardiol 91:14B-22B [PubMed]
  5. Hypertension
    1. Goal Blood Pressure < 125/75 mmhg
    2. Consider ACE Inhibitor or Angiotensin Blocker

XI. Course

  1. Metabolic Syndrome or Prediabetes is high risk for progression to Type II Diabetes Mellitus
    1. Up to 15-30% of Prediabetes patients will develop Diabetes Mellitus within 5 years
    2. However, with sustained lifestyle change, 27 to 43% avoid Diabetes Mellitus diagnosis in the longterm
  2. Older adults (mean 75 years old) with Prediabetes do not progress to diabetes in 90% of cases over 6.5 years
    1. Rooney (2021) JAMA Intern Med 181(4):511-19 [PubMed]
  3. Diabetes Prevention Program (DPP)
    1. Basic diet and Exercise: 11% develop diabetes per year
      1. Diet, Exercise, and weight loss maintained for 3 years prevents Diabetes Mellitus (NNT 7)
    2. Metformin
      1. Metformin 850 twice daily with diet and Exercise: 7.8% develop DM per year
      2. Metformin maintained for 3 years prevents Diabetes Mellitus (NNT 14)
    3. Intensive diet, Exercise: 4.8% develop diabetes per year
      1. Classes and coaches
      2. Weight Reduction of 7%
  4. Reference
    1. (1999) Diabetes Care 22:623-34 [PubMed]

XII. Resources

  1. CDC Prediabetes Basics
    1. https://www.cdc.gov/diabetes/basics/prediabetes.html

XIII. References

  1. (2021) Presc Lett 28(3): 16-7
  2. Koenigsberg (2017) Am Fam Physician 96(6):362-70 [PubMed]
  3. (2021) Diabetes Care 44(suppl 1): S34-9 +PMID: 33298414 [PubMed]
  4. (2015) Diabetes Care 38(suppl):S4 +PMID:25537706 [PubMed]
  5. (1997) Diabetes Care 21:310-4 [PubMed]
  6. (2001) JAMA 285:2486-97 [PubMed]
  7. (2002) N Engl J Med 346:393-403 [PubMed]
  8. (2006) Lancet 368:1096-105 [PubMed]
  9. Goutham (2001) Am Fam Physician 63(6): 1159-66 [PubMed]
  10. Scott (2003) Am J Cardiol 92(2 suppl):35i-42i [PubMed]

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