1. Journal Club 埼玉医科大学 総合医療センター 内分泌・糖尿病内科 Department of Endocrinology and Diabetes, Saitama Medical Center, Saitama Medical University 松田 昌文 Matsuda, Masafumi 2010 年 7 月 1 日 8:30-8:55 ８階 医局 Ralph A DeFronzo, Masafumi Matsuda Reduced Time Points to Calculate the Composite Index DIABETES CARE, 33,(7):e93, 2010

2. http://mmatsuda.diabetes-smc.jp/english.html

3. RALPH A. DEFRONZO, MD 1, MASAFUMI MATSUDA, MD, PHD 2 1 Department of Medicine, Diabetes Division, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 2 Saitama Medical Center, Saitama Medical University, Saitama, Japan. DOI: 10.2337/dc10-0646 DIABETES CARE, 33(7):e93, 2010

4. Since the original publication of the composite (Matsuda) index for the measurement of insulin sensitivity from plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT), this index has been widely used by investigators throughout the world. According to Scopus, more than 1,000 articles have cited the original article during the last 10 years, and several modifications of this index have been published. Although the basic idea is to use the plasma insulin and glucose areas under the curve (AUCs), the actual time points at which plasma insulin and glucose levels are measured during the OGTT may be few and the time intervals may not be equal. Background

5. We show here that calculation of the composite index using these fewer time points agrees well with the original calculation, which was based on five plasma glucose and insulin measurements. Although it is difficult to imagine a reasonable AUC when samples from only 0 and 120 min are available, the simple index below works quite well. Aim

6. Using the data from the original publication (N = 153), correlation coefficients were calculated relating whole-body ISI(composite) to 1) the rate of insulin stimulated glucose disposal (Rd) during the euglycemic insulin clamp and 2) hepatic insulin sensitivity (His) measured with tritiated glucose: His=1,000/HGP×FPI, where HGP is hepatic glucose production, the primary determinant of fasting plasma glucose level, and FPI is fasting plasma insulin. Methods

7. ISI(composite) = k/sqrt （ G 0 × I 0 × G 120 × I 120 ) ISI(composite) = k/sqrt （ G 0 × I 0 × × ) where ISI(composite) is the insulin sensitivity index, k (= 10,000) is a constant that provides numbers that are easy to deal with, and represent the average plasma glucose and insulin concentrations after oral glucose load G 0 and G 120 represent the plasma glucose concentrations at times 0 and 120 min, I 0 and I 120 represent the plasma insulin concentrations at times 0 and 120 min, and sqrt is the mathematical function to calculate the square root.

8. ISI(composite) = k/sqrt （ G 0 × I 0 × G 120 × I 120 ) ≒ G 120 ， ≒ I 120 Table 1 Correlation coefficients (n=153) relating whole body insulin sensitivity index [ISI(comp)] (i) to the rate of insulin- stimulated glucose disposal [Rd] during the euglycemic insulin clamp and (ii) to hepatic insulin sensitivity measured with tritiated glucose (1000/HGP x FPI), where HGP is the primary determinant of the FPG.

9. Results Rd (or His) and an ISI(composite) calculated from 0, 30, 60, 90, and 120 min (set A); 0, 60, and 120 min (set B); and 0 and 120 min (set C) were significantly (P < 0.01) correlated with r = 0.732 (r = 0.670) in set A, r = 0.741 (r = 0.680) in set B, and r = 0.772 (r = 0.651) in set C.

10. Conclusion Although ISI(composite) calculated using different time points cannot be compared between different studies, within any given study the index provides a reasonable index of whole- body insulin sensitivity.

11. http://mmatsuda.diabetes-smc.jp/newpage115.html

12. De-convolusion technique to calculate glucose sensitivity (insulin secretion) ブドウ糖負荷試験の血中グルコース濃度，血中インスリン濃度は数式化す ればインスリン分泌が評価できる。

13. Message Matsuda Index は非常によく用いられているが，概念 的には基礎状態の血中グルコースとインスリン濃度， ブドウ糖負荷試験のグルコースとインスリン濃度の平 均値が計算に必要である。 ブドウ糖負荷後の反応の平均は 0,60,120 分や 0,120 分 の値からでも計算は十分に可能である。 ( インスリン感受性の強い集団では 0,60,120 分を使っ た方がよい ) 他にも患者さんのデータが無駄にならず世の中の為に なります！ ⇒ OGTT では 0,30,60,90,120 分を測定してください

14. Must Review! The HEALTHY Study Group. A School-Based Intervention for Diabetes Risk Reduction. N Engl J Med. 2010 Jun 27. [Epub ahead of print] The ACCORD Study Group and ACCORD Eye Study Group* Effects of Medical Therapies on Retinopathy Progression in Type 2 Diabetes 10.1056/NEJMoa1001288 Richard M. Bergenstal, M.D., William V. Tamborlane, M.D., Andrew Ahmann, M.D., John B. Buse, M.D., Ph.D., George Dailey, M.D., Stephen N. Davis, M.D., Carol Joyce, M.D., Tim Peoples, M.A., Bruce A. Perkins, M.D., M.P.H., John B. Welsh, M.D., Ph.D., Steven M. Willi, M.D., and Michael A. Wood, M.D., for the STAR 3 Study Group* Effectiveness of Sensor-Augmented Insulin-Pump Therapy in Type 1 Diabetes 10.1056/NEJMoa1002853 Bergenstal RM, Wysham C, Macconell L, Malloy J, Walsh B, Yan P, Wilhelm K, Malone J, Porter LE; for the DURATION-2 Study Group. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010 Jun 25. [Epub ahead of print] Michaela Diamant, Luc Van Gaal, Stephen Stranks, Justin Northrup, Dachuang Cao, Kristin Taylor, Michael Trautmann Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial Lancet 2010; 375: 2234–43 Julio Rosenstock, Daniel L Lorber, Luigi Gnudi, Campbell P Howard, David W Bilheimer, P-C Chang, Richard E Petrucci, Anders H Boss, Peter C Richardson Prandial inhaled insulin plus basal insulin glargine versus twice daily biaspart insulin for type 2 diabetes: a multicentre randomised trial Lancet 2010; 375: 2244–53 The Emerging Risk Factors Collaboration* Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies Lancet 2010; 375: 2215–22 Cliff ord J Bailey, Jorge L Gross, Anne Pieters, Arnaud Bastien, James F List Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double- blind, placebo-controlled trial Lancet 2010; 375: 2223–33