30061 - Evidence Supporting Aggressive Glycemic Control...

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Evidence Supporting Aggressive Glycemic Control
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Treatment of Type 2 Diabetes
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Sites of Action of Therapeutic Options for Type 2 Diabetes
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DCCT: Effects of Intensive vs Conventional Glycemic Control
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UKPDS: Design
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UKPDS: Effects of Intensive (Sulfonylurea/Insulin) Treatment
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UKPDS: Effects of Intensive (Metformin) Treatment*
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UKPDS: Effects of Glycemia Exposure Over Time
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UKPDS: Risk Reduction in Diabetes- Related Complications (A 1c )
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D iabetes P revention P rogram: Protocol Design
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D iabetes P revention P rogram: Reduction in Diabetes Incidence
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Structures of Thiazolidinediones
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Thiazolidinediones: Mechanism of Insulin Sensitization
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PPAR α vs. gamma PPAR α (fibrates) work mostly in the liver and lower VLDL triglycerides and increase HDL-C but do not affect FFA, glucose, or insulin sensitivity PPAR gammas (TZDs such as rosiglitazone or pioglitazone) promote new fat cells in subcutaneous tissue and decrease intramuscular and visceral fat.
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Thiazolidinediones: Rationale for Type 2 Diabetes Therapy
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ACTOS, an Insulin Sensitizer
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Reduced Insulin Resistance Suggested by HOMA Analysis of Pioglitazone Therapy
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Improved β-Cell Response Suggested by HOMA Analysis of Pioglitazone Therapy
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Changes in A 1c From Baseline in All Treated Patients
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Endpoint Changes in Patients With Lower Baseline A 1c (Mean 9.0%)*
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Change in FPG From Baseline in All Treated Patients
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Change in Lipid Profile at Endpoint: ACTOS 26-Week Monotherapy
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DREAM Study for Prevention of Diabetes 5,269 persons with pre-diabetes randomized to rosiglitazone (8 mg daily) vs. placebo and ramipril vs. placebo for median of 3 years 10.6% of those on rosiglitazone progressed to type 2 diabetes vs. 25% on placebo, a 62% risk reduction (p<0.0001). Primary endpoint of development of diabetes or death from any cause reduced by 60% 51% of those on rosiglitazone vs. 30% on placebo returned to normal blood sugar No significant difference in future cardiovascular events, but higher rate of new heart failure in those on rosiglitazone (0.5%) vs. placebo (0.1%). Body weight increased 2.2kg more in the rosiglitazone vs. placebo group.
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PROACTIVE Study: Secondary Prevention of Macrovascular Events in Persons with Diabetes from Pioglitazone 5238 patients with type 2 diabetes who had evidence of macrovascular disease assigned to oral pioglitazone titrated from 15 mg to 45 mg (n=2605) or matching placebo (n=2633), taken w/existing drugs. Primary endpoint:
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30061 - Evidence Supporting Aggressive Glycemic Control...

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