Effect of Chronic Disease-Related Symptoms and Impairments on Universal Health Outcomes in Older Adults; Journal of American Geriatric Society

Metabolic SyndromeEvaluation and treatment strategies John HyerUniversity of Georgia College of PharmacyDoctor of Pharmacy Candidate, 2012Preceptor: Ali R. Rahimi, MD, FACP, AGSF

ObjectivesDefine metabolic syndrome (MetS)Examine the risk and prevalence associated with Metabolic syndrome (MetS)Evaluate current treatment strategies for efficacy Our role in prevention

EpidemiologyApproximately 25% of the worlds population has metabolic syndromeInterestingly enough (but not surprisingly), more than half of the adults in U.S. are overweight or obeseSame or greater primary risk factor as smoking for CVD (cardiovascular disease)Numbers will increase with aging population and increasing rates of childhood obesityPeaks in mid to late 60sEpidemiologyMost common in men and HispanicsIncreases with ageNative Americans have highest recorded prevalence of MetS60% or women aged 45-4945% of men aged 45-49Cardio-Metabolic Syndrome risk is based on global risk of metabolic syndrome

Risk factorsCentral adiposity (waist circumference)Better association with MetS than BMIPeripheral adiposity is a weaker predictor of MetSObesitySedentary lifestyleType 2 diabetes mellitus (T2DM)Est. that up to 75% of patients with T2DM or impaired glucose tolerance have MetSLipodystrophyGenetic or HAART inducedAgingPostmenopausal statusSmokingLow household incomeAntipsychotic medicationsClozapineOlanzapine

Pathophysiology of MetSWidely debatedMost accepted hypothesis is insulin resistanceInsulin resistance precluded by:Postprandial hyperinsulinemia followed by Fasting hyperinsulinemia and hyperglycemia

Insulin resistance Increases with increasing body fatExcess adipose tissue releasesNonesterified fatty acids (NEFA)High level overloads muscle and liver with lipidsCytokines Increase glucose and VLDL-C production by liverPlasminogen activator inhibitor-1 (PAI-1)High levels contribute to a prothrombotic stateAdiponectinPlays a role as an anti-inflammatory and insulin sensitizing agentReducedInterleukin (IL)-6 elevationStimulate insulin resistance and lypolysis of adipose tissue TGC-reactive protein (CRP)Signifies cytokine excess and a proinflammatory state

9Insulin resistanceFree fatty acids - contributorReleased from enlarged adipose tissue massInsulin responsible forAntilipolysis Most sensitive pathway of insulin actionStimulation of hormone sensitive lipoprotein lipaseMobilizes fatty acids from triglyceride rich stores Insulin resistance = increased lipolysis produces more FFA= further decreases antipolytic effect of insulinInsulin resistance -FFAsIn muscleHigh NEFA levels in muscle are diverted to the liver Promoting fatty liver and atherogenic dyslipidemiaIn the liver increases production ofGlucoseTriglyceridesSecretion of very-low-density lipoproteins

Insulin resistanceIn muscleFFAs reduce insulin sensitivity by inhibiting insulin-mediated glucose uptakeLeads to increased circulating glucoseIncreases pancreatic insulin secretion hyperinsulinemiaResults in enhanced sodium reabsorption and increased sympathetic nervous system activityHypertension?Take home Point!!!Insulin resistance leads to oxidative stress which leads to endothelial cell dysfunction, promoting vascular damage and atheroma formation

Diagnosing Metabolic Syndrome

Metabolic Syndrome DefinedAccording to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) presence 0f 3 of the following:

ATP III CriteriaAbdominal ObesityWaist circumference > 40 inches in men and 35 inches in femaleFasting plasma glucose (FPG)FPG 100 mg/dL or drug treatment for elevated blood glucoseBlood pressure (BP)BP > 130/85 mmHg or drug treatment for blood pressureSerum high-density lipoprotein cholesterol (HDL-C)HDL-C < 40 mg/dL in men and < 50 mg/dL in womenSerum triglycerides 150 mg/dL or drug treatment for elevated triglyceridesEvaluation The American Heart AssociationRecommends measurement of high-sensitivity CRP for risk stratification in patients at high risk of CVDIs patient ready to make therapeutic lifestyle modifications? (i.e. reduce dietary fat)Fasting glucose Fasting lipid panelWaist circumferenceHeight and weight (BMI)Frammingham Risk Assessment for 10 Year CVD riskCoronary Artery Calcium (CAC) scan (AHA/ACC)Good in asymptomatic low-risk patients

Clinical ConsequencesMetS CVD and T2DMCardiovascular Disease (CVD)High risk for developing CVDMetS and the Framingham Risk ScoreWhich is better at predicting CVD?Evidence for both camps in the literatureRelative risk for CVD events or death is 1.78 in patients with MetS

Clinical ConsequencesType II Diabetes Mellitus (T2DM)Presence of MetS is highly predictive of developing new-onset T2DM75-85% of patients with MetS will progress to T2DMRelative risk of 3.53-5.17 for development of diabetes

TherapyDifficultNo randomized controlled trials for specific treatment optionsGoalReduce the risk for or preventing CVD and T2DMNCEP ATP III Major Therapeutic Goals in Patients with MetSTreat underlying causes (overweight/obesity and physical inactivity) by intensifying weight management and increasing physical activityTreating cardiovascular risk factors if they persist despite lifestyle modification*** lifestyle modifications, pharmacologic therapy, and bariatric surgery***Lifestyle Modifications

Lifestyle ModificationsDietEven a modest weight loss significantly reduced prevalence of MetS Diet rich in complex, unrefined carbs, high in fiber (14 g/1000 cal consumed daily), and low in added sugar (