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Diabetes Mellitus 101 for Cardiologists (and Alike): 2015

This article explores an aggressive pathophysiologic approach to the therapy of type 2 diabetes in cardiometabolic patients. It specifically focuses on looking at diabetes medications with a cardiologist's perspective. The study examines the mean change in common carotid artery intima-media thickness (CIMT) and percent atheroma volume (PAV) in patients treated with Pioglitazone and Glimepiride.

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Diabetes Mellitus 101 for Cardiologists (and Alike): 2015

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  1. Diabetes Mellitus 101 for Cardiologists (and Alike): 2015 An Aggressive Pathophysiologic Approach to Therapy of Type 2 Diabetes in Cardiometabolic Patients: Looking at Diabetes Medications with a Cardiologists Eye Part 9 Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical Associate Professor of Medicine, U of Pa. 6105472000

  2. Mean Change in CIMT-Pioglitazone stopped progression 0.020 Glimepiride Pioglitazone 0.015 0.012 0.010 LS Mean Change From Baseline Posterior Wall CIMT (mm) 0.005 0.000 -0.001 -0.005 -0.010 Baseline CIMTLeast squares (LS) mean (standard error) Glimepiride (n=186) 0.779 (0.0085) mm Pioglitazone (n=175) 0.771 (0.0085) mm Treatment group difference (final visit) -0.013 (95% CI: -0.024, -0.002) P=0.017

  3. Primary Endpoint:Change in Percent Atheroma Volume (%) 0.9 P < 0.001 Glimepiride (n=181) 0.7 Pioglitazone (n=179) 0.73 0.5 P = 0.002 Change in PAV (%) 0.3 0.1 -0.16 -0.1 P = 0.44 -0.3 Presented at: American College of Cardiology March 29-April 1, 2008; Chicago, IL

  4. PROactive in the Context of Other Landmark Clinical Trials in Diabetic Patients HPS CARE Placebo Placebo 30 40 CHD death, MI, revasc (%) 22% RRR P < 0.0001 25% RRR P = 0.05 30 Vascular events (%) 20 20 Pravastatin Simvastatin 10 10 0 0 0 1 2 3 4 5 0 1 2 3 4 5 6 Years Years Lancet. 2003;361. Circulation. 1998;98. MICRO-HOPE PROactive 25 Cardiac death, MI,coronary revasc, ACS(%) 20 Placebo Placebo 25% RRR P = 0.0004 20 16% RRR P = 0.034 15 MI, stroke, CV death (%) 15 10 10 Ramipril Pioglitazone 5 5 0 0 0 1 2 3 4 5 0 1 2 3 Years Years 4 Lancet. 2000;355. Lancet. 2005;366.

  5. Stroke Reduction: Proactive vs SPARCL

  6. Sent home after CHF episode: TZD patients do no worse than Metformin patients; And Do BEST if sent home on BOTH

  7. AFTER AMI; Patients sent home on TZD =Mortality vs. metformin And if on both, do better!!

  8. Synthesis- Edema / CHF • Fluid retention- • Several mechanisms may underlie the development of peripheral oedema. • 1. TZDs exhibit some properties of L-type calcium channel antagonism like calcium- channel blockers,  • 2. increase expression of vascular endothelial growth factor (VEGF), •  3. improvement in insulin sensitivity associated • a. actions on sodium reabsorption at the level of the kidney, • b. augmenting insulin-mediated vasodilatation. 4.renal effectPPARγ-Induced Stimulation of Amiloride-Sensitive Sodium Current in Renal Collecting Duct Principal Cells is Serum and Insulin Dependent (DOI:10.1159/000358636) • Not Cardiac issue • Increase CHF likely due to salt retention in patients with Diastolic Dysfunction

  9. Implications for Therapy • Treat Central Mechanisms IR • Treat Peripheral IR- fat, liver, muscle • Treat Inflammation • Treat Biome

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