Metabolic Syndrome

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Metabolic Syndrome
Metabolic Syndrome
MAJ(P) J. Scott Earwood
MAJ(P) J. Scott Earwood
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Goals

• Define Metabolic Syndrome
• Emphasize that visceral obesity is an indicator
  of the syndrome and an independent marker for CVD
• Review current and some potential future
  treatment options

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An estimated 47 million people have metabolic
syndrome in the U.S.
NHANES III 1988-94, JAMA 2002
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ATP III Clinical Identification of the Metabolic
Syndrome

• Waist circumference
• Mengt102 cm (gt40 in)
• Womengt88 cm (gt35 in)
• Triglycerides gt150 mg/dL
• HDL cholesterol 
• Menlt40 mg/dL  
• Womenlt50 mg/dL
• Blood pressure 130/ 85 mm Hg
• Fasting glucose gt110 mg/dL

New ADA guidelines suggest gt100mg/dl increases
risk for Metabolic Syndrome
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International Diabetes Federation (IDF) Definition

• Modified ATPIII definition
• Fasting Glucose gt 100mg/dl
• Adjusted waist circumference based on ethnicity
  (i.e. asians with lower waist circumference
  threshold than pacific islanders)

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Ethnic specific values for waist circumference
(IDF)

• Europids Male 94 cm Female 80 cm
• South Asians Male 90 cm Female 80 cm
• Chinese Male 90 cm Female 80 cm
• Japanese Male 85 cm Female 90 cm
• Ethnic South and Central Use South Asian
  recommendations until more specific
• Americans data are available (ATPIII)
• Sub-Saharan Africans Use European data until more
  specific data are available
• Eastern Mediterranean and Middle East (Arab)
  populations Use European data until more specific
  data are available

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Lahey Clinic Study--50-60 of Pts lt45yo who
suffered MI had Metabolic Syndrome, a mean BMI of
approximately 32, and relatively normal LDL(The
Framingham Risk scores of these patients is
typically very lowbecause age is low)
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Obesity is a Cardiovascular Risk Factor

• Linear Increase in Risk for Cardiovascular
  Disease with increase in BMI from 25 to 35
  (unrelated to HDL, and LDL)

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Specifically, Visceral Obesity

• Elevated waist circumference
• TGlt150 probably normal metabolic risk (CVD)
• TG150 excess visceral fat and increased risk
  (CVD)
• Waist-to-Hip ratio (peripheral fat, protective)
• No specific measurement (hip circumferencegtWaist
  circumference)

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Look at your patients shape
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Other Indicators of Metabolic Syndrome and CV Risk

• CRP
• Borderline LDL

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EBM Recommendations

• Any person at high risk or moderately high risk
  who has lifestyle-related risk factors (e.g.,
  obesity, physical inactivity, elevated
  triglyceride, low HDL-C, or metabolic syndrome)
  is a candidate for therapeutic lifestyle changes
  to modify these risk factors regardless of LDL-C
  level.

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EBM Recommendations (cont.)

• There is some evidence that insulin sensitizing
  agents such as metformin are effective in
  treating features of metabolic syndrome.

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Current Treatments

• Weight reduction
• TLC Diet and Exercise
• Lower BP goals
• Lower LDL goals
• Statins
• Metformin
• Aspirin therapy

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Possible New Markers

• Adiponectin (cytokine released from peripheral
  adipose tissue) low levels associated with
  increased risk for MI

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Possible New Therapies

• Endocannabinoid system
• Phospholipid derivatives over-produced in obese
  patients
• CB1 receptor

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Possible New Therapies (Cont.)

• CB1 receptorsanimal studies
• Hypothalamusregulates energy metabolism
• Liverlipogenesis
• Adipose tissues
• Lipogenesis
• Fat accumulation
• Inhibition of adiponectin

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Possible New Therapies (Cont.) RIO-LIPID trial
(2005 NEJM)

• Placebo group
• ? weight
• 2kg
• 4kg
• ? Abdominal circumference
• 2.5cm
• 4.5cm
• ? HDL-C
• 15

• CB1 receptor blocker
• ? weight
• 8kg
• ? Abdominal circumference
• 9cm
• ? HDL-C
• 25
• ? CRP 27
• ? Adiponectin 46

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Summary

• The definition for metabolic syndrome is straight
  forward
• We see these patients every day in our practices
• Weight reduction is the key to preventing CVD
• There are some new exciting treatments on the
  horizon

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Question?
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References

• Third report of the National Cholesterol
  Education Program (NCEP) Expert Panel on
  Detection, Evaluation, and Treatment of High
  Blood Cholesterol in Adults (Adult Treatment
  Panel III). (2)Implications of recent clinical
  trials for the National Cholesterol Education
  Program Adult Treatment Panel III Guidelines.
• International Diabetes Federation
• Insulin-sensitising drugs, The Cochrane Database
  of Systematic Reviews Date of last Substantial
  Update December 31. 2002
• Effects of Rimonabant on Metabolic Risk Factors
  in Overweight Patients with Dyslipidemia, NEJM.
  Nov 2005