Understanding the Ups and Downs of Blood Glucose Irl B Hirsch, M.D University of Washington Question ♦ Who has the greatest risk of proliferative diabetic retinopathy (PDR) over the next 10 years ♦ A 55 y/o man with type diabetes for years, on oral agents, A1c = 9.0% ♦ An 18 y/o man with years of type diabetes, on BID NPH/R, A1c = 9.0% ♦ An 18 y/o man with years of type diabetes, on CSII, A1c = 9.0% Why are the risks of PDR different? Postprandial hyperglycemia ≠ glycemic variability Don’t forget about the “ups” and “downs”! “Oxidative Stress” What Should You Know? • Oxygen is critical for life: respiration and energy • Oxygen is also implicated in many disease processes, ranging from arthritis, cancer, Lou Gehrig’s disease as well as aging – This dangerous form of oxygen is from the formation of “free radicals” or “reactive oxygen species”, or pro-oxidants – Normally, pro-oxidants are neutralized by antioxidants “Oxidative Stress”: What You Should Know Oxidative Stress = Imbalance between pro-oxidants (free radicals, reactive oxygen species) and anti-oxidants Oxidative Stress: Why is it Important? Free radicals (reactive oxygen species) are known to fuel diabetic vascular complications OK, What Turns On Oxidative Stress, Free Radicals, and Reactive Oxygen Species ♦ High blood glucose ♦ Science is confirmed on this point ♦ Variability in blood glucose ♦ Science is highly suggestive on this point How Does One Measure…? ♦ Oxidative Stress ♦ Urinary isoprostanes: best marker of oxidative stress in total body ♦ “HbA1c of oxidative stress” ♦ Glycemic variability ♦ Mean Amplitude of Glycemic Excursions (MAGE) ♦ Standard deviation on SMBG meter download I Hirsch Urinary 8-SO-PGF2 alpha Excretion Rates (pg/mg creatinine) Correlation Between Urinary 8-iso-PGF2 alpha and MAGE in T2DM 1200 1000 800 R=0.86, p