Core Curriculum

• Targeting Insulin Resistance for Vascular Protection

VBWG06_CORE_IR.pdf (17.0MB)VBWG06_CORE_IR.pdf (17.0MB)

Targeting Insulin Resistance for Vascular Protection

Download VBWG06_CORE_IR_Sec1.ppt (43 slides - 13.0MB)

Targeting Insulin Resistance for Vascular Protection Contents Vascular Consequences of Diabetes and Insulin Resistance One third of adults with diabetes are undiagnosed Rising prevalence of diabetes Parallel epidemics of diabetes and obesity 90% of patients with newly diagnosed diabetes are overweight or obese IFG/IGT: Challenge for prevention “Ticking clock” hypothesis: Glucose abnormalities increase CV risk DECODE: IGT increases mortality risk CHD risk appears to begin at low blood glucose levels Continuum of CV risk: Reason for early intervention in patients with IFG/IGT Even mild glucose elevations increase mortality in patients undergoing PCI IGT and undiagnosed DM2 are common in acute MI and stroke Risk of endothelial dysfunction increases at FG 110–125 mg/dL Impaired macrovascular reactivity in people at risk for type 2 diabetes Insulin resistance: Risk factor for CV disease Insulin resistance and atherosclerosis Who has insulin resistance? Insulin resistance is an independent predictor of HF Insulin resistance increases risk of chronic kidney disease (CKD) Development of insulin resistance in obesity-induced inflammation and stress Visceral obesity Visceral fat independently predicts mortality CRP levels show positive correlation with visceral obesity Shared CV risk between insulin resistance and visceral obesity Metabolically active molecules link obesity and atherosclerosis Antiatherogenic effects of adiponectin Visceral obesity and adiponectin Inverse relationship between baseline adiponectin level and MI risk Shared metabolic abnormalities with insulin resistance and endothelial dysfunction PPAR activation and atherosclerosis: A hypothesis Peroxisome proliferator-activator receptors (PPARs) PPARs: Overview Beyond fat and glucose: Potential for CV benefits with PPAR agonists Obesity induces inflammatory changes in adipose tissue Macrophage and adipocyte similarities PPAR signaling pathways influence macrophage gene expression and foam-cell formation PPAR agonists improve endothelial vasodilation and decrease inflammation PPAR agonists impact inflammatory markers and adiponectin Added benefit of BP reduction with PPAR agonists PPAR agonists increase collagen content – potentially improving plaque stability Potential vascular benefits of PPAR activation

CV Risk Reduction, Diabetes Prevention, and TZDs

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CV Risk Reduction, Diabetes Prevention, and TZDs UKPDS 34: Intensive glucose control andCV protection DCCT/EDIC: Lower glucose = lower long-term CV risk DCCT/EDIC: Intensive glucose control reduces long-term CV risk DCCT/EDIC: Intensive treatment slows renal changes Vascular effects of thiazolidinediones (TZDs) TZDs impact carotid IMT TZD impact on restenosis in type 2 diabetes TZDs consistently reduce restenosis after coronary stenting in patients with diabetes Surrogate outcome results driving major TZD trials Major TZD outcome trials Major TZD outcome trials PROactive: Study design PROactive: CV history at baseline PROactive: CV medications at baseline PROactive: Nonsignificant reduction in primary outcome PROactive: Significant reduction in secondary outcome PROactive: Subgroup analysis–Previous MI PROactive: HF hospitalization and mortality PROactive vs landmark clinical trials: Comparative benefit in patients with diabetes PROactive in perspective Fluid retention after TZD use tends to be peripheral Managing TZD-related fluid retention Collecting duct (CD) PPAR: Potential mechanism for volume expansion TZDs associated with lower mortality TZDs in type 2 diabetes and HF Major TZD outcome trials DREAM: Background and study objective RAAS modulation reduces new-onset diabetes TRIPOD: Treating insulin resistance reduces incidence of type 2 diabetes TZDs blunt diabetes progression DREAM: Study design DREAM: 2 x 2 factorial design DREAM: Inclusion criteria DREAM: Key exclusion criteria DREAM: Baseline characteristics DREAM: Baseline glucose status DREAM: Beyond diabetes prevention DREAM: Substudies ADOPT: Study objective ADOPT: Study design CHICAGO: Study objective CHICAGO: Study design

Clinical Imperatives When Treating Patients with Diabetes

Download VBWG06_CORE_IR_Sec3.ppt (34 slides - 1.6MB)

Clinical Imperatives When Treating Patients with Diabetes Diabetes, IFG, IGT: Diagnostic criteria AHA/ACC/ADA: Multiple risk reduction in diabetes AACE: Managing diabetes AHA/ACC secondary prevention guidelines:Diabetes management DPP: Benefit of diet/exercise or metformin on diabetes prevention in at-risk patients DPP: Benefit of diet/exercise or metformin on diabetes by race/ethnicity 3-Week diet + exercise yield favorable metabolic changes 3-Week diet + exercise reduce proatherogenic factors Beyond lifestyle: Aggressive medical therapy in diabetes Steno-2 supports aggressive multifactorial intervention in type 2 diabetes Steno-2: Multifactorial intervention on CV outcomes Steno-2: Better risk factor control with intensive therapy Steno-2: Effects of multifactorial intervention on microvascular and neuropathic outcomes Benefits of aggressive LDL-C lowering in diabetes HPS: Statin beneficial irrespective of baseline lipid level and diabetes status ASCOT-LLA: Atorvastatin reduces CV events in patients with diabetes and hypertension  MICRO-HOPE, PERSUADE: ACEI reduces CV events in diabetes TZD + statin: Favorable effects on inflammatory markers and adiponectin Principal mechanisms of action for oral diabetic agents Oral antihyperglycemic agents Beyond glucose lowering: Effects of antidiabetic agents TZD vs sulfonylurea: Glycemic control over time TZD + sulfonylurea efficacy in type 2 diabetes PROactive: Reduced requirement for insulin use Sulfonylurea + TZD or metformin: Comparison of lipid and renal effects TZDs and metformin reduce risk of MI Improving blood glucose control: Potential role of combination therapy DPP-IV inhibitors DPP-IV inhibitors, GLP-1 analogs: New classes of antidiabetic agents AMIGO trials: GLP-1 analog in type 2 diabetes Managing diabetes as a CHD equivalent: ABCs of coronary prevention Proatherogenic effects of insulin resistance Summary: Expanding risk factor control to enhance CV outcomes
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