Supplementary Data

SUPPLEMENTARY DATA

ICD_9 PROCEDURE CODES USED FOR PATIENT SELECTION

Valves 351_ Open heart valvuloplasty without replacement 352_ Replacement of heart valve 353_ Operations on structures adjacent to heart valves

Atrial septa 354_ Production of septal defect in heart 3551 Repair of atrial septa with prosthesis open technique 3561 Repair of atrial septa with tissue graft open technique 3571 Other and unspecified repair of atrial septa

Ventricles 3553 Repair of ventricular septa with prosthesis open technique 3562 Repair of ventricular septa with tissue graft open technique 3572 Other and unspecified repair of ventricular septa 358_ Total repair of certain congenital cardiac anomalies

Heart Revascularizations: 3603 Open chest coronary artery angioplasty 361_ Bypass anastomosis for heart revascularization 362_ Heart revascularization by arterial implant 3631 Open chest transmyocardial revascularization 3639 Other heart revascularization: 369_ Other operations on vessels of heart:

Incisions, Endarterectomies, Resection: 3805 Incision of thoracic vessel * 3815 Endarterectomy of thoracic vessels * 3845 Resection of thoracic vessel with replacement *

Other operations on vessels: 390_ Systemic to pulmonary artery shunt * 392_ Other shunt or vascular bypass *

Other operations on heart 3710 Cardiotomy not specified 3711 Cardiotomy 3731 Pericardiectomy 3732 Excision of aneurysm of heart 3733 Excision or destruction of other lesion of heart 3735 Partial ventriculectomy

* Only in combination with Cardiopulmonary bypass code: 3961

Infections Pneumonia: 00322, 01124, 01140, 01144, 01145, 01304, 01363, 02120, 03910, 05210, 05510, 07300, 07310, 11505, 11515, 11595, 480__, 481__, 482__, 483__, 484__, 485__, 486__, 99731. Surgical Site Infection: 9985_, 5192_, 9966_. Sepsis: 038__, 78552, 99591, 99592, 99800, 99859, 99931.

Respiratory failure 5184_, 5185_, 51881, 51882, 51884, 7991_

©2017 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc17-1554/-/DC1 SUPPLEMENTARY DATA Supplementary Table 1. Risk factors for mortality from 48 hours after surgery to discharge. HR: Hazard ratio; TWA: Time Weighted Average. The Lactate and Glucose time-weighted averages were calculated for the first 48 hours after surgery. The numerical values of Glucose-TWA and Lactate-TWA shown in the Table are the mean values of these parameters. A three way interaction among Glucose-TWA, Lactate-TWA and Diabetes, and an interaction between lactate-TWA and time after surgery are shown in the model. *: X indicates an interaction between variables. The interaction is illustrated by the subsections listed below. For example, the first entry shows the effect that a 1 mmol/L increase of time- weighted average lactate would have on the risk of mortality, in patients having no DM at a glucose-time weighted average = 124.3 mg/dl. #: 17 patients were excluded from the extended Cox proportional hazard regression model: 7 patients who died within 48 hours after surgery; 8 patients with only 1 lactate measurement and 2 patients who were discharged within 48 hours.

Variable No. of No. of HR 95% CI P Value Deaths subjects# Lactate-TWA X Glucose-TWA X Diabetes* 67 4081 0.0069 1 mmol/l Lactate-TWA in NODM at 2.33 1.964, 2.751 Glucose-TWA=124.3 mg/dl 1 mmol/l Lactate-TWA in DM at Glucose- 2.32 1.785, 2.901 TWA=124.3mg/dl 1 mg/dl Glucose-TWA inNODM at Lactate- 0.97 0.939, 1.004 TWA=1.71 mmol/l 1 mg/dl Glucose-TWA in DM at Lactate- 1.00 0.978, 1.025 TWA=1.71mmol/l DM at Glucose-TWA=124.3 mg/dl and 1.15 0.599, 2.296 Lactate-TWA=1.71 mmol/l Lactate-TWA X Time after surgery (1 day)* 0.98 0.972, 0.991 0.0002 Admission Type (vs. Elective) Urgent 5 288 0.40 0.110,1.189 0.1295 Emergent 6 394 0.67 0.211, 1.764 0.4545 Transfer 26 654 2.87 1.56, 3.634 0.0007 Not Available 7 202 2.09 0.794, 4.936 0.1077 Cancer 5 104 5.03 1.703, 11.928 0.0009

©2017 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc17-1554/-/DC1 SUPPLEMENTARY DATA Supplementary Table 2. Risk Factors of pulmonary failure. TWA: Time-Weighted Average. The time-weighted averages were calculated for the first 48 hours after surgery. The numerical values of glucose and Lactate-TWA shown in the Table are the mean values of these parameters. The model includes a three way interaction among glucose-TWA, Lactate-TWA and Diabetes. Data were analyzed using logistic regression. *: X indicates an interaction between variables. The interaction is illustrated by the subsections listed below. For example, the 3rd entry shows the effect that a 1 mmol/L increase of time- weighted average lactate would have on the risk of mortality, in patients having no DM at a glucose-time weighted average = 124.3 mg/dl. #: 17 patients were excluded from the logistic regression model: 7 patients who died within 48 hours after surgery; 8 patients with only 1 lactate measurement and 2 patients who were discharged within 48 hours.

No. of No. of Odds Variable 95% CI P-value Pulm. F. subjects# Ratio Glucose-TWA X Lactate-TWA X Diabetes* 672 4081 0.0426 Glu-TWA (10 mg/dl) 0.914 0.817 1.023 at Lac-TWA =1.71 mmol/l, NODM Glu-TWA (10 mg/dl) 0.862 0.796 0.932 at Lac-TWA =1.71 mmol/l, DM Lac-TWA (1 mmol/l) 1.302 1.110 1.527 at Glu-TWA =124.3 mg/dl, NODM Lac-TWA (1 mmol/l) 1.225 1.088 1.380 at Glu-TWA =124.3 mg/dl, DM DM at Lac-TWA =1.71 mmol/l, 1.626 1.313 2.014 Glu-TWA =124.3 mg/dl Hypoglycemia 89 307 1.616 1.215 2.147 0.0010 Surgery Duration (per 10 minutes) 1.003 1.002 1.003 <.0001 Hospital days before surgery (per day) 1.042 1.008 1.076 0.0135 Insurance (vs. Private Insurance) Medicaid 100 664 0.984 0.744 1.303 0.9130 Medicare 366 1874 1.337 1.090 1.641 0.0054 Other 11 45 2.440 1.201 4.955 0.0136 Pulmonary Circulation Disorder 183 781 1.405 1.133 1.742 0.0019 Smoking (vs. No Smoker) EX Smoker 266 1522 1.186 0.979 1.437 0.0813 Current Smoker 82 412 1.505 1.127 2.011 0.0056 Unknown 45 185 1.710 1.167 2.506 0.0059 Surgery (vs. CABG) Thoracic Aortic Aneurysm 31 91 2.139 1.288 3.551 0.0033 CABG & Valve 94 521 0.792 0.585 1.073 0.1323 Valve 346 2202 0.945 0.748 1.194 0.6381 Other 14 85 1.223 0.634 2.357 0.5482 Renal Failure 174 695 1.337 1.069 1.672 0.0110 Weight Loss 64 199 2.364 1.695 3.298 <.0001 Fluid & Electrolyte Disorder 33 267 0.531 0.356 0.794 0.0020

©2017 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc17-1554/-/DC1 SUPPLEMENTARY DATA Supplementary Table 3. Risk Factors of Infection. TWA: Time Weighted Average. CV: Coefficient of Variation. TWAs and CV were calculated for the first 48 hours after surgery. Data were analyzed using logistic regression. #: 17 patients were excluded from the logistic regression model: 7 patients who died within 48 hours after surgery; 8 patients with only 1 lactate measurement and 2 patients who were discharged within 48 hours.

Variable No. of No. of Odds 95% CI P-value Infections subjects# Ratio Lactate TWA (1 mmol/l) 217 4081 1.400 1.245 1.579 <.0001 Glucose TWA (10 mg/dl) 0.987 0.977 0.998 0.0189 Glucose C V (1 unit) 1.025 1.006 1.045 0.0113 Diabetes 105 1507 1.665 1.206 2.295 0.0019 Surgery Duration (10 minutes) 1.041 1.027 1.054 <.0001 Hospital days before surgery (day) 1.148 1.094 1.204 <.0001 Smoking (vs. No Smoker) EX Smoker 86 1522 1.452 1.042 2.029 0.0280 Current Smoker 33 412 2.026 1.268 3.175 0.0025 Unknown 22 185 2.419 1.350 4.177 0.0021 Admission Type (vs. Elective) Emergent 32 400 1.163 0.688 1.913 0.5629 Urgent 21 293 1.548 0.888 2.581 0.1067 Transfer 66 680 1.583 1.056 2.359 0.0249 Missing 14 209 2.195 1.142 3.934 0.0122 Weight Loss 28 199 2.486 1.521 3.928 0.0002 Other Neurological Disease 15 94 2.711 1.383 5.001 0.0022