The Metabolic Syndrome - Doc Grimes

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					The Metabolic Syndrome

           Gil C. Grimes, MD
 Assistant Professor TAMU College of Medicine
 Scott & White Department of Family Medicine
Objectives
   Define Metabolic Syndrome
   Review the prevalence in our population
   Discuss the proposed pathophysiology
   Review associated morbidity and mortality
   Define treatment strategies
Definitions
World Health Organization Definition
   One of these
       Insulin resistance
       Impaired glucose regulation
            FPG ≥ 110 mg/dl and/or
            2 hour PG ≥ 140 mg/dl
   Two of these
       Hypertension SBP ≥ 140 DBP ≥ 90
       Elevated Triglycerides (≥ 150 mg/dl) and/or low HDL (≤35 mg/dl
        males and ≤39 mg/dl females)
       Central Obesity waist to hip ratio >0.90 males, >0.85 females, or
        BMI>33 kg/m2
       Microalbuminuria urinary albumin excretion rate ≥ 20 mg/min or
        albumin/creatinine ratio ≥ 30 mg/g


                             Albert KGMM et al Diabetic Med 1998;15:539-553 [Level 5]
National Cholesterol Education
Program (NCEP) Adult Treatment
Panel III (ATPIII) Definition
   Three of the following
   Abdominal circumference
       Men > 40 inches
       Women >35 inches
   Triglycerides > 150 mg/dl
   HDL Cholesterol
       Men < 40 mg/dl
       Women <50 mg/dl
   Blood Pressure > 130/85 mm Hg
   Glycemia >110mg/dl
                                Expert panel on Detection, Evaluation,
                                and Treatment of High Blood Cholesterol
                                in Adults, JAMA 2001;285:2486-2497
                                [Level 5]
Prevalence
Obesity US 1991




                  [Level 2b]
Obesity US 1992




                  [Level 2b]
Obesity US 1993




                  [Level 2b]
Obesity US 1994




                  [Level 2b]
Obesity US 1995




                  [Level 2b]
Obesity US 1996




                  [Level 2b]
Obesity US 1997




                  [Level 2b]
Obesity US 1998




                  [Level 2b]
Obesity US 1999




                  [Level 2b]
Obesity US 2000




                  [Level 2b]
Obesity US 2001




                  [Level 2b]
Texas 2001
Percentage Overweight and Obese




                                  45%

                                  40%

                                  35%

                                  30%

                                  25%                                                                        Overweight
                                  20%                                                                        Obese

                                  15%

                                  10%

                                  5%

                                  0%
                                        White        Black        Hispanic     Multiracial     Other



                                                Behavioral Risk Factor Surveillance System, 2001 CDC [Level 2b]
                                             Prevalence in FOS and SAHS
                                             populations
Percentage with Metabolic Syndrome




                                     35

                                     30

                                     25

                                     20
                                                                                                                NCEP ATPIII
                                                                                                                NCEP ATPIII BMI
                                     15
                                                                                                                WHO
                                     10

                                     5

                                     0
                                            Men       Women       Men      Women        Men         Women

                                                  White          Non-hispanic white    Mexican American

                                          Framingham Offspring          San Antonio Heart Studies

                                                                          Meigs J et al Diabetes 2003; 52:2160-7 [Level 2c]
Prevalence Metabolic Syndrome in
NHANES III




              Ford ES et al JAMA 2002;287:356-359 [Level 2 c]
Prevalence Metabolic Syndrome in
NHANES III by Race




                Ford ES et al JAMA 2002;287:356-359 [Level 2 c]
                                         Prevalence in Adolescents
                                         from NHANES III
Percentage with Metabolic Syndrome




                                     7
                                     6
                                     5
                                     4                                                                 Three Risk Factors
                                     3                                                                 Four Risk Factors
                                     2
                                     1
                                     0
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                                                             Cook S et al Arch Pediatric Adolec Med 2003;157:821-827 [Level 2c]
Pathophysiology
Proposed Pathophysiology
   Role of adipose tissue
    and inflammation
       IL-6 (pro-inflammatory
        compound)
            Produces 25% of IL-6
            Stimulate acute phase
             hepatic protein
             production
       Obesity associated with
        increased C-reactive
        protein
       Represents chronic low
        level inflammation
       More related to Waist to
        hip ratio than BMI Visser M et al JAMA 1999;282:2131-2135 [Level 2b]
                              CRP and BMI
                              1.8

                              1.6
Odds ratio for elevated CRP




                              1.4

                              1.2

                                                                   Per SD increment BMI
                               1

                              0.8                                  Per SD increment waist hip
                                                                   ratio
                              0.6

                              0.4

                              0.2

                               0
                                    Men       Women


                                            Visser M et al JAMA 1999;282:2131-2135 [Level 2b]
CRP, IL-6, and subsequent DM




            Pradhan AD et al JAMA 2001;286:327-334 [Level 2b]
Cartoon of mechanism of
disease
Associated Morbidity and Mortality
CHD Morbidity and Mortality
                                  4.5
Relative risk of death from CHD




                                   4
                                  3.5
                                   3
                                  2.5
                                   2
                                  1.5
                                   1
                                  0.5
                                   0
                                        NCEP With Waist   NCEP with Waist >94     WHO Waist to Hip   WHO Waist >94 cm
                                           >102 cm                cm                  >0.90
                                          Age Adjusted

                                          Age, LDL, Smoking, FHx Adjusted

                                          Age, LDL, Smoking, FHx, Socioeconomic
                                          Adjusted

                                                                       Lakka H et al JAMA 2002; 288:2709-2016 [Level 1b]
                     Metabolic Syndrome as a Risk
                     for CHD and Diabetes
                4

               3.5

                3
Hazard Ratio




               2.5
                                                                              CHD Univariate
                2                                                             CHD Multivariate
                                                                              Diabetes Univariate
               1.5

                1

               0.5

                0
                     Metabolic   Age 10 yr       Smoker     Pravastatin
                     Syndrome
                                 Predictors of CHD and DM             Sattar N et al Circulation
                                                                      2003:108:414-9 [Level 2b]
Risks for CHD and CVA
Morbidity
                       10.00%

                        9.00%

                        8.00%
Prevalence Morbidity




                        7.00%

                        6.00%
                                                                                                 CHD
                        5.00%
                                                                                                 CVA
                        4.00%

                        3.00%

                        2.00%

                        1.00%

                        0.00%
                                With Metabolic Syndrome         Without Metabolic Synd.



                                                   Isomaa B et al Diabetes Care 2001;24:683-689 [Level 2b]
Risk for CHD Mortality
                        20%

                        18%

                        16%
 Prevalence Mortality




                        14%

                        12%
                                                                                          Total Mortality
                        10%
                                                                                          CHD Mortality
                        8%

                        6%

                        4%

                        2%

                        0%

                              With Metabolic Syndrome      Without Metabolic Synd.


                                                  Isomaa B et al Diabetes Care 2001;24:683-689 [Level 1a]
Risk for CHD and Diabetes
                25                                                     24.4




                20
 Hazard Ratio




                15
                                                                                 CHD
                                                                                 Diabetes
                10
                                                            7.26


                 5                              4.5                 3.65
                                                       3.19
                                           2.25
                               1.792.36
                     1
                         1
                 0
                     0          1           2           3           >4
                             Number of Metabolic Risk Factors


                                                                   Sattar N et al Circulation
                                                                   2003:108:414-9 [Level 2b]
Risk for DM from Kuopio IHD
Risk Factor Study
   Presence of Metabolic Syndrome
       Odds Ratio of developing DM 10
       4 fold increased risk for DM
       WHO Definition with Waist Hip Ratio >0.90
            Sensitivity 0.83
            Specificity 0.78
       NCEP Definition
            Sensitivity 0.57
            Specificity 0.90

                     Laaksonen D et al Am J Epidemiol 2002;156:1070-1077 [Level 2b]
Treatment
Treatment
   Prevention is the Key
       Diminish the adipose poisoning
       Must extrapolate from other studies
       Diabetes Prevention Program
            Goal 150 minutes of exercise weekly
            Low fat diet
                 Nutrition counseling every 90 days
            NNT 8 people for 3 years to prevent 1 new DM
            Absolute Risk Reduction 12.77%

                               Tuomilheto J et al NEJM 2001;344:1343-1350 [Level 1a]
Treatment Lifestyle vs.
Metformin
   Similar design
   NNT for 3 years to prevent on case of
    DM
       Lifestyle 6.9
       Metformin 13.9




              Diabetes Prevention Program Group NEJM 2002;346:393-403 [Level 1a]
Treatment Lifestyle vs. Xenical
   Subgroup analysis of Xenical trial
   40% of patients positive for Metabolic
    syndrome
       Type II DM 13.9% lifestyle group
       Type II DM 9.8% Xenical group
       Industry sponsored study


                Torgerson J et al 12th European Congress on Obesity 2003 [Level 2b ?]
Statins et al
   Presence of Metabolic Syndrome indicates at
    least 2 risk factors
       LDL goal <100 mg/dl
       Statins reduce LDL on average 18-55%
       Fenofibrate reduce Triglycerides 20-50% and raise
        HDL 10-35%
       Niacin reduce LDL 5-25% Triglycerides 20-50%
        and raise HDL 15-35%
       Combinations work well, caution for increased risk
        of adverse events

                           O‘Mara NB Prescriber’s Letter 2003;19:191001
Control the Pressure
   JNC 7 guidelines and ALLHAT tell us to
    lower the pressure
       Intensive lifestyle modification
       HOPE trial 32% reduction in new onset DM
        for ramipril
       LIFE trial
            Losartan 6% developed DM
            Atenolol 8% developed DM
Aspirin Therapy
   Routine recommendation for those at
    increased risk for cardiovascular disease
   Unclear if it decreases progression of
    Metabolic Syndrome
   Use based on High Risk status of these
    patients
Sample Patient
                  38 year old male
                  Weight 250 lbs

                  Height 72 inches

                  BMI 34

                  BP 140/86

                 Screen Glucose?
                 Screen Lipids?
                 Therapy?
Take Home
   It is common in our patients
   The prevalence is expected to increase
   The process starts early
   The intervention needs to start early
   Get your patients up and moving

				
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