1. Journal Club 亀田メディカルセンター 糖尿病内分泌内科 Diabetes and Endocrine Department, Kameda Medical Center 松田 昌文 Matsuda, Masafumi 2008 年７月 24 日 8:20-8:50 B 棟８階 カンファレンス室 R. Ascione, C.A. Rogers, C. Rajakaruna and G.D. Angelini Inadequate Blood Glucose Control Is Associated With In-Hospital Mortality and Morbidity in Diabetic and Nondiabetic Patients Undergoing Cardiac Surgery Circulation 2008;118;113-123; originally published online Jun 30, 2008 Bazzano LA, Li TY, Joshipura KJ, Hu FB. Intake of fruit, vegetables, and fruit juices and risk of diabetes in women. Diabetes Care. 2008 Jul;31(7):1311-7. Epub 2008 Apr 4.

2. Bristol Heart Institute, University of Bristol, Bristol, United Kingdom

3. Aim Derangement of glucose metabolism after surgery is not specific to patients with diabetes mellitus. We investigated the effect of different degrees of blood glucose control (BGC) on clinical outcomes after cardiac surgery.

4. Methods We analyzed 8727 adults operated on between April 1996 and March 2004. The highest blood glucose level recorded over the first 60 hours postoperatively was used to classify patients as having good ( 250 mg/dL) BGC; 7547 patients (85%) had good, 905 (10%) had moderate, and 365 (4%) had poor BGC. Initially, data were collected on the basis of presumed consent, but since 2002, when a program of annual follow-up for all surviving patients was established, consent for the use of data has been sought.

5. Figure 1.Patient selection and classification process * 50 (14.8%) of the 337 excluded patients died following surgery: 30 (60%) on the day of surgery, 9 (18%) on day 1, 2 (4%) on day 2 and 2 (4%) on day 3. The remaining 7 deaths occurred more than 3 days after the operation. 72-198 mg/dl 200-245 245-

6. Figure 2. Protocol for sliding-scale insulin infusion. -72 mg/dl 72-108 108-162 162-198 198-306 306-

13. *The following variables were considered for inclusion in the adjustment: age >65 years, gender, body mass index (categorized as 90 minutes, operation performed (grouped as CABG, valve, CABG and valve, congenital and other), aortic procedure, and need for inotropic support after surgery; those variables significant at P<0.10 were chosen (see Methods). †Estimated from 200 bootstrap samples. ‡Uncorrected probability values estimated from 200 bootstrap samples; variables with a value of P<0.005 are significant at the 5% level after Bonferroni correction for multiple comparisons. §ORs suggest that DM is “protective” for patients whose blood glucose is poorly controlled (OR decreases with decreased BGC). This phenomenon is illustrated in Figure 3. In non-DM patients, the complication rate increases with decreasing BGC; in the DM group, the rate is similar across the 3 BGC groups. The difference in complication rates between DM and non-DM groups is greatest for patients with poor BGC, with the DM group having the lower rate in each case; hence the OR for DM is <1 and lowest for the poor BGC group.

14. *The following variables were considered for inclusion in the adjustment: age >65 years, gender, body mass index (categorized as 90 minutes, operation performed (grouped as CABG, valve, CABG and valve, congenital, and other), aortic procedure, and need for inotropic support after surgery; those variables significant at P<0.10 were chosen (see Methods). †Estimated from 200 bootstrap samples. ‡Test for an overall effect of blood glucose control on outcome. Uncorrected probability values estimated from 200 bootstrap samples. Variables with a value of P<0.0042 are significant at the 5% level after Bonferroni correction for multiple comparisons. §Uncorrected probability values estimated from 200 bootstrap samples. Variables with a value of P<0.005 are significant at the 5% level after Bonferroni correction for multiple comparisons.

15. Figure 4. Prevalence of complications by BGC and DM. Note: the scale of the y-axis varies across the four charts

17. Results Patients with inadequate BGC were more likely to present with advanced New York Heart Association class, congestive heart failure, hypertension, renal dysfunction, and ejection fraction <50% (P<0.001). We found that 52% of patients with poor, 31% with moderate, and 8% with good BGC had diabetes mellitus. Inadequate BGC, but not diabetes mellitus (P=0.79), was associated with in-hospital mortality (good, 1.8%; moderate, 4.2%; poor, 9.6%; adjusted odds ratio: poor versus good BGC, 3.90 [95% confidence interval, 2.47 to 6.15]; moderate versus good BGC, 1.68 [95% confidence interval, 1.25 to 2.25]). Inadequate BGC also was associated with postoperative myocardial infarction (eg, odds ratio, poor versus good BGC: 2.73 [95% confidence interval, 1.74 to 4.26]) and with pulmonary and renal complications in patients without known diabetes mellitus (eg, odds ratio, poor versus good BGC: 2.27 [95% confidence interval, 1.65 to 3.12] and 2.82 [95% confidence interval, 1.54 to 5.14] respectively).

18. Conclusion More than 50% of patients with moderate to poor BGC after cardiac surgery were not previously identified as diabetic. Inadequate postoperative BGC is a predictor of in-hospital mortality and morbidity.

19. Our study demonstrates that inadequate blood glucose control (BGC) after cardiac surgery is not specific to patients with diabetes mellitus (DM). Inadequate BGC, regardless of DM status, was independently associated with in-hospital mortality and morbidity. Our findings have epidemiological, clinical, academic, and financial implications. We suggest that DM patients represent only a fraction of those suffering derangement of glucose metabolism after surgery. The projected future number of adults with DM is an underestimate of the number likely to be affected by deranged glucose metabolism and its related complications. Inadequate BGC after surgery seems to represent a separate clinical entity that is explained only partially by undiagnosed and diet-controlled diabetes. Our data suggest that strict protocols to maintain BGC should be used for all patients. However, the efficacy of these protocols and the pathophysiologic mechanisms of this condition need further research. In addition, further research and guidelines as to how best to manage these patients are needed. Currently, important clinical decisions such as choice of screening test, strategy for maintaining adequate BGC, and the ideal target level of BGC are often left to the individual clinician. This has resulted in inconsistencies in the definition of undiagnosed DM, stress hyperglycemia, and inadequate BGC; marked variation in estimates of prevalence; and significant variation in treatment, the impact of which remains uncertain. Our findings also may apply to patients admitted for major noncardiac surgery. The impact on life expectancy and on hospital resources is potentially enormous. CLINICAL PERSPECTIVE

21. The Nurses’ Health Study 1976- 121700 Female RNs 1984- 2002 71346 Female RNs diet cohort 1Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana; the 2Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts; the 3Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, the University of Puerto Rico, Medical Sciences Campus, School of Dentistry, San Juan, Puerto Rico, and the Harvard School of Dental Medicine, Boston, Massachusetts; and the 4Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, and the Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts.

25. 28.4x8=227ml

26. Consumption of green leafy vegetables and fruit was associated with a lower hazard of diabetes, whereas consumption of fruit juices may be associated with an increased hazard among women. CONCLUSIONS