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e Definition 1999: Based on Clinical Criteria ? Insulin resistance (type 2 diabetes, IFG, IGT)* ? Plus any 2 of the following: ? Elevated BP (?140/90 or drug Rx) ? Plasma TG ?150 mg/dl ? HDL 35 mg/dl (men)。 40 mg/dl (women) ? BMI 30 and/or W/H (men), (women) ? Urinary albumin 20 mg/min。 Alb/Cr 30 mg/g * Note that 1999 WHO uses hyperinsulinemic euglycemic clamp whereas 1998 WHO and EGIR use HOMAIR. Must Insulin Resistance be Present for a Patient to Have the Metabolic Syndrome? ? WHO 1999 clinical definition ? Yes ? ATP III 2021 clinical definition ? No, but it is usually present ? Multiple metabolic risk factors are sufficient ? Obesity can produce the metabolic syndrome without insulin resistance WHO. Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications: Report of a WHO Consultation. Geneva: WHO, 1999. | Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2021。285:24862497. WHO Metabolic Syndrome Definition 1999: Therapeutic Implications ? Focus on insulin resistance as the underlying cause of the metabolic syndrome ? More emphasis on the geic basis of the metabolic syndrome rather than obesity ? Leads to increased thinking about the use of drugs to treat insulin resistance in patients with the metabolic syndrome Therapeutic Implications of Definition of Metabolic Syndrome ? If focus is on obesity as underlying cause ? Prevent and treat obesity ? If focus is on insulin resistance as underlying cause ? Treat insulin resistance ? If focus is on metabolic risk factors ? Treat individual risk factors Criteria for Comparing Different Definitions of Metabolic Syndrome ? Risk of: ? CHD ? DM ? Relation to: ? Insulin resistance ? Obesity ? Prevalence in munity could differ by race ? How simple is the definition? Intensity of Therapy Should be Proportionate to Level of Risk ? What is the impact of the metabolic syndrome on health outes? ?Cardiovascular disease ?Type 2 diabetes Cardiovascular Disease Mortality Increased in the Metabolic Syndrome: Kuopio Ischaemic Heart Disease Risk Factor Study Lakka HM et al. JAMA 2021。288:27092716. Cumulative Hazard, % 0 2 6 8 12 Followup, y YES Metabolic Syndrome: NO Cardiovascular Disease Mortality RR (95% CI), (–) 4 10 051015NCEP MetS WHO MetS Total Population All Cause (–) (–) CVD (–) (–) Disease Free* All Cause (–) (–) CVD (–) (–) Cox Proportional Hazard Ratios (and 95% Confidence Intervals) Predicting AllCause and Cardiovascular Mortality: San Antonio Heart Study 14Year Followup Hunt KJ et al. Diabetes 2021。52:A221A222. * Those without diabetes, cardiovascular disease, or cancer. Adjusted for age, gender, and ethnic group. Comparison of NCEP and 1999 WHO Metabolic Syndrome to Identify InsulinResistant Subjects: IRAS % in Lowest Quartile of Si Hanley AJ et al. Diabetes 2021。52:27402747. Neither NCEP Only WHO Only Both Overall Hispanics NonHispanic w