Metabolic Syndrome Metabolic Syndrome

MAJ(P) J. Scott Earwood

MAJ(P) J. Scott Earwood

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

An estimated 47 million people have metabolic syndrome in the U.S.

NHANES III 1988-94, JAMA 2002

ATP III Clinical Identification of the Metabolic Syndrome

 Waist circumference:
 Men>102 cm (>40 in)


Women>88 cm (>35 in)

 Triglycerides >150 mg/dL  HDL cholesterol:

 

Men<40 mg/dL Women<50 mg/dL

 Blood pressure 130/ 85 mm Hg  Fasting glucose >110 mg/dL*

* New ADA guidelines suggest >100mg/dl increases risk for Metabolic Syndrome

International Diabetes Federation (IDF) Definition

 Modified ATPIII definition
 

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

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
    

Lahey Clinic Study--50-60% of Pts <45yo 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)

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)

Specifically, Visceral Obesity

 Elevated waist circumference
 

TG<150 probably normal metabolic risk (CVD) TG150 excess visceral fat and increased risk (CVD)

 Waist-to-Hip ratio (peripheral fat, protective)  No specific measurement (hip circumference>Waist circumference)

Look at your patients shape

Other Indicators of Metabolic Syndrome and CV Risk

 CRP  Borderline LDL

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.

EBM Recommendations (cont.)

 There is some evidence that insulin

sensitizing agents such as metformin are effective in treating features of metabolic syndrome.

Current Treatments
 Weight reduction  TLC: Diet and Exercise  Lower BP goals  Lower LDL goals  Statins  Metformin  Aspirin therapy

Possible New Markers

 Adiponectin (cytokine released from

peripheral adipose tissue) low levels associated with increased risk for MI

Possible New Therapies

 Endocannabinoid system


Phospholipid derivatives over-produced in obese patients CB1 receptor

Possible New Therapies (Cont.)

 CB1 receptorsanimal studies
  

Hypothalamusregulates energy metabolism Liverlipogenesis Adipose tissues

  

Lipogenesis Fat accumulation Inhibition of adiponectin

Possible New Therapies (Cont.)

RIO-LIPID trial (2005 NEJM)
 Placebo group


 CB1 receptor blocker

    

weight  2kg  4kg Abdominal circumference  2.5cm  4.5cm HDL-C  15%

weight  8kg Abdominal circumference  9cm HDL-C  25% CRP 27% Adiponectin 46%

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

Question?

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