1 / 37

Journal Club

Journal Club. Marfella R, Barbieri M, Grella R, Rizzo MR, Nicoletti GF, Paolisso G. Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-hour acute glucose fluctuations. J Diabetes Complications. 2009 Mar 3. [Epub ahead of print]

markfbrown
Download Presentation

Journal Club

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Journal Club Marfella R, Barbieri M, Grella R, Rizzo MR, Nicoletti GF, Paolisso G. Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-hour acute glucose fluctuations. J Diabetes Complications. 2009 Mar 3. [Epub ahead of print] Blaha J, Kopecky P, Matias M, Hovorka R, Kunstyr J, Kotulak T, Lips M, Rubes D, Stritesky M, Lindner J, Semrad M, Haluzik M. Comparison of three protocols for tight glycemic control in cardiac surgery patients. Diabetes Care. 2009 May;32(5):757-61. Epub 2009 Feb 5. 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 2009年5月21日　8:30-8:55 ８階　医局

  2. Mechanism of Action of OHA α-glucosidase inhibitor SU drugs, glinides Incretin (GLP-1, DDPIV inhibitor) Gut Pancreas CHO abserption Hyperglycemia Defect in insuiin secretion = Deficiency of Insulin  Rd of glucose Insulin resistance = • Hepatic glucose • production Muscle Liver Thiazolidinedione Biguanide

  3. Dipeptidyl peptidase-4 inhibitor Sitagliptin Alogliptin Vildagliptin

  4. Background and Aim There is increasing evidence that glycemic disorders such as rapid glucose fluctuations over a daily period might play an important role on diabetic complications. We evaluated the efficacy of sitagliptin 100 mg once daily vs. vildagliptin 50 mg twice daily on daily blood glucose fluctuations in patients with type 2 diabetes that was inadequately controlled by metformin.

  5. Methods Forty-eight-hour continuous subcutaneous glucose monitoring (CSGM) was performed in patients treated with metformin plus vildagliptin (n=18) or sitagliptin (n=20) over a period of 3 months. The mean amplitude of glycemic excursions (MAGE) was used for assessing glucose fluctuations during the day. During a standardized meal, glucagon-like peptide-1 (GLP-1), glucagon, and insulin were measured.

  6. Pharmaceutical Power Plasma DPP-4 activity is inhibited by almost 100% already at 15–30 min, and >80% inhibition lasts for almost 14 h after a single dose of sitagliptin at 100 mg (Herman et al., 2006); Vildagliptin at 50 mg bid inhibits DPP- 4 activity by almost 97% over a daily period (Mari et al., 2005).

  7. Fig. 1. Box plot (a plot type that displays the central line representing the median, the boxes span from the 25th to 75th percentiles, and the error bars extend from the 10th to 90th percentiles) showing the reductions of fasting glycemia (FPG), PPG levels, 24-hour mean plasma glucose (MPG) levels and MAGE in sitagliptin and vildagliptin groups (Panel A). Plasma levels of intact GLP-1(Panel B) and glucagon (Panel C) during 24-h sampling comprising three standardized meals after 3 months of treatment with vildagliptin (○, 50 mg, twice daily) or sitagliptin (■, 100 mg once daily) in type 2 diabetic patients. Values are the mean±S.D. ⁎P<.05 compared to the vildagliptin group. The parameter MAGE was designed to quantify major fluctuations of glycemia and to exclude minor ones. Calculation of the MAGE was obtained by measuring the arithmetic mean of the differences between consecutive peaks and nadirs.

  8. Summary CSGM shows large MAGE decrements in the vildagliptin group compared with the sitagliptin group (P<.01). A marked increase in GLP-1 occurred during interprandial period in vildagliptin bid-treated toward sitagliptin 100 mg once daily (Pb<.01). Glucagon was more suppressed during interprandial period in subjects receiving vildagliptin compared to those receiving sitagliptin (P<.01).

  9. Conclusion Since MAGE (mean amplitude of glycemic excursions ) is associated with an activation of oxidative stress, our data suggest that dipeptidyl peptidase IV inhibition therapy should target not only reducing HbA1c but also flattening acute glucose fluctuations over a daily period.

  10. 院内血糖管理ガイドライン VIII. DIABETES CARE IN SPECIFIC SETTINGS A. Diabetes care in the hospital Recommendations ● All patients with diabetes admitted to the hospital should have their diabetes clearly identified in the medical record. (E) ● Goals for blood glucose levels: Critically ill surgical patients’ blood glucose levels should be kept as close to 110 mg/dl (6.1 mmol/l) as possible and generally 140 mg/dl (7.8 mmol/l). (A) These patientsrequire an intravenous insulin protocol that has demonstrated efficacy and safety in achieving the desired glucose Critically ill nonsurgical patients’ glycemic targets are less well defined. DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S13

  11. 院内血糖管理ガイドライン VIII. DIABETES CARE IN SPECIFIC SETTINGS A. Diabetes care in the hospital Recommendations ● Scheduled prandial insulin doses should be appropriately timed in relation to meals and should be adjusted according to point-of-care glucose levels. The traditional sliding-scale insulin regimens are ineffective as monotherapy and are generally not recommended. (C) ● Using correction dose or "supplemental" insulin to correct premeal hyperglycemia in addition to scheduled prandial and basal insulin is recommended. (E) DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S13

  12. POINT OF CARE TESTING POCT（Point of Care Testing）は、患者さんがいるその場で、簡便・迅速に実施する臨床検査[薬] SMBG=self monitoring of blood glucose （測定ではない！ISO 15197で誤差は血糖が75mg/dl以上で±20%ならOK）

  13. Surgical ICUでのインスリン強化療法による 死亡率減少 周術期（主に術後）には、 血糖を200mg/dl程度にする治療に比較し100mg/dl前後にすると死亡率が半減する。

  14. 重症入院患者へのインスリン治療：死亡率 （無作為ランダム化研究のメタ解析） 周術期（主に術後）には、 血糖を200mg/dl程度にする治療に比較し100mg/dl前後にすると死亡率が半減する。 心筋梗塞ではそれほどの差はない。 35publications, n=8478

  15. 12のプロトコールとの比較 Graphic Protocol variable Y N Both Y Y NA NA NA/Y adjustable Diabetes Care 30:1005, 2007 に追加

  16. Yale大学プロトコール／若干の修正 Diabetes Care 27:461, 2004　を改変

  17. Yale 大学プロトコールの実施例 67 y.o. male, 外傷による多発骨折，臓器損傷

  18. Evaluation of insulin sensitivity (Graphic example)

  19. Glucose Control Summary(All subjectsKameda Medical Center 2006-2008) Partly presented at the 44th EASD, Sep. 8-11, 2008, Rome, Italy, Diabetologia 51(Supplement 1): S440, 2008

  20. 1Department of Anaesthesia, Resuscitation and Intensive Medicine, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic; the 2Institute of Metabolic Science, University of Cambridge, Cambridge, U.K., the 3Department of Anaesthesiology and Resuscitation, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; the 4Department of Cardiothoracic Surgery, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic; and the 53rd Department of Medicine, Charles University in Prague, and 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic. Diabetes Care 32:757–761, 2009

  21. Aim We performed a randomized trial to compare three insulin-titration protocols for tight glycemic control (TGC) in a surgical intensive care unit: an absolute glucose (Matias) protocol, a relative glucose change (Bath) protocol, and an enhanced model predictive control (eMPC) algorithm.

  22. Methods A total of 120 consecutive patients after cardiac surgery were randomly assigned to the three protocols with a target glycemia range from 4.4 to 6.1 mmol/l. Intravenous insulin was administered continuously or in combination with insulin boluses (Matias protocol). Blood glucose was measured in 1- to 4-h intervals as requested by the protocols.

  23. Matias J Clin Endocrinol Metab 92: 2960–2964, 2007

  24. Bath Anaesth Intensive Care 2004; 32:311–316

  25. eMPC Intensive Care Med (2008) 34:1224–1230

  26. Figure 1— Blood glucose concentrations and time to target range, expressed as means ± SEM, in patients after cardiac surgery controlled by the Matias, Bath, and eMPC protocols.

  27. Results The eMPC algorithm gave the best performance as assessed by time to target (8.8 ± 2.2 vs. 10.9 ± 1.0 vs. 12.3 ± 1.9 h; eMPC vs. Matias vs. Bath, respectively; P < 0.05), average blood glucose after reaching the target (5.2 ± 0.1 vs. 6.2 ± 0.1 vs. 5.8 ± 0.1 mmol/l; P< 0.01), time in target (62.8 ± 4.4 vs. 48.4 ± 3.28 vs. 55.5 ± 3.2%; P < 0.05), time in hyperglycemia >8.3 mmol/l (1.3 ± 1.2 vs. 12.8 ± 2.2 vs. 6.5 ± 2.0%; P < 0.05), and sampling interval (2.3 ± 0.1 vs. 2.1 ± 0.1 vs. 1.8 ± 0.1 h; P<0.05). However, time in hypoglycemia risk range (2.9–4.3 mmol/l) in the eMPC group was the longest (22.2 ± 1.9 vs. 10.9 ± 1.5 vs. 13.1 ± 1.6; P < 0.05). No severe hypoglycemic episode (<2.3 mmol/l) occurred in the eMPC group compared with one in the Matias group and two in the Bath group.

  28. Conclusion The eMPC algorithm provided the best TGC without increasing the risk of severe hypoglycemia while requiring the fewest glucose measurements. Overall, all protocols were safe and effective in the maintenance of TGC in cardiac surgery patients.

More Related