Glycemic Variability Correlates Strongly With Postprandialβ-Cell Dysfunction in a Segment of Type 2 Diabetic Patients Using Oral Hypoglycemic Agents Klaus-Dieter Kohnert , MD, PHD 1 , Petra Augstein , MD, PHD 1 , Eckhard Zander , MD 2 , Peter Heinke , MSC 1 , Karolina Peterson , MD 1 , Ernst-Joachim Freyse , MD, PHD 1 , Roman Hovorka , PHD 3 and Eckhard Salzsieder , PHD 1 1 Institute of Diabetes “Gerhardt Katsch,” Karlsburg, Germany; 2 Clinics for Diabetes and Metabolic Diseases, Karlsburg, Germany; 3 Institute of Metabolic Science, University of Cambridge, Cambridge, U.K. Corresponding author: Klaus-Dieter Kohnert, kohnert{at}diabetes-karlsburg.de . Abstract OBJECTIVE Glucose fluctuations trigger activation of oxidative stress, a main mechanism leading to secondary diabetes complications. We evaluated the relationship between glycemic variability and β-cell dysfunction. RESEARCH DESIGN AND METHODS We conducted a cross-sectional study in 59 patients with type 2 diabetes (aged 64.2 ± 8.6 years, A1C 6.5 ± 1.0%, and BMI 29.8 ± 3.8 kg/m 2 mean ± SD) using either oral hypoglycemic agents (OHAs) ( n = 34) or diet alone (nonusers). As a measure of glycemic variability, the mean amplitude of glycemic excursions (MAGE) was computed from continuous glucose monitoring data recorded over 3 consecutive days. The relationships between MAGE, β-cell function, and clinical parameters were assessed by including postprandial β-cell function (PBCF) and basal β-cell function (BBCF) obtained by a model-based method from plasma C-peptide and plasma glucose during a mixed-meal test as well as homeostasis model assessment of insulin sensitivity, clinical factors, carbohydrate intake, and type of OHA. RESULTS MAGE was nonlinearly correlated with PBCF ( r = 0.54, P < 0.001) and with BBCF ( r = 0.31, P = 0.025) in OHA users but failed to correlate with these parameters in nonusers (PBCF P = 0.21 and BBCF P = 0.07). The stepwise multiple regression analysis demonstrated that PBCF and OHA combination treatment were independent contributors to MAGE ( R 2 = 0.50, P < 0.010), whereas insulin sensitivity, carbohydrate intake, and nonglycemic parameters failed to contribute. CONCLUSIONS PBCF appears to be an important target to reduce glucose fluctuations in OHA-treated type 2 diabetes. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received October 29, 2008. Accepted February 20, 2009. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. © 2009 by the American Diabetes Association.