<p> Page 1 of 13</p><p>ONLINE ONLY APPENDIX</p><p>Appendix 1: OptumLabs Data Warehouse OptumLabs Data Warehouse (OLDW) is a national administrative database of more than 100 million privately insured and Medicare Advantage enrollees throughout the U.S.1,2 The database includes medical (both professional and facility) claims with International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes, ICD-9 procedure codes, Current Procedural Terminology, Version 4 (CPT-4) procedure codes, Healthcare Common Procedure Coding System (HCPCS) procedure codes, site of service codes, and provider specialty codes. The database also includes pharmacy claims with medications dispensed, prescription quantity, and fill date. 1 Included individuals span all ages, are of diverse races/ethnicities, and reside in all 50 States with greater representation of Southern and Midwestern states. Page 2 of 13</p><p>Table 1. ICD-9-CM principal diagnosis codes signifying severe dysglycemia events.3-5 These diagnoses are different from the CCS classification of “Diabetes mellitus with complications” </p><p>(CCS 50), which includes ICD-9-CM codes for secondary diabetes (249.01, 249.10, 249.11, </p><p>249.20, 249.21, 249.30, 249.31, 249.40, 249.41, 249.50, 249.51, 249.60, 249.61, 249.70, 249.71,</p><p>249.80, 249.81, 249.90, 249.91), uncontrolled diabetes without designation of an acute metabolic event (250.02, 250.03, 250.10, 250.40, 250.41, 250.42, 250.43, 250.50, 250.51, 250.52, 250.53, </p><p>250.60, 250.61, 250.62, 250.63, 250.70, 250.71, 250.72, 250.73), as well as codes designed as severe dysglycemic events below (250.11, 250.12, 250.13, 250.20, 250.21, 250.22, 250.23, </p><p>250.30, 250.31, 250.32, 250.33, 250.80 250.81, 250.82, 250.83, 250.90, 250.91, 250.92, 250.93). a Codes pertaining to hypoglycemia that are missing from the CCS 50 grouper.</p><p>Designation ICD-9-CM code Hyperglycemia 250.10, 250.11, 250.12, 250.13 Diabetes with ketoacidosis 250.20, 250.21, 250.22, 250.23 Diabetes with hyperosmolarity 250.30, 250.31, 250.32, 250.33 Diabetes with other coma </p><p>Hypoglycemia 250.80, 250.81, 250.82, 250.83 Diabetes with other specified manifestations of diabetic hypoglycemia NOS or hypoglycemic shock NOS UNLESS 259.8, 272.7, 681, 682, 686.9, 707.1, 707.8, 707.9, 709.3, 730.0, 730.1, 730.2, 731.8 251.0 Hypoglycemic coma 251.1 Other unspecified hypoglycemia 251.2 Unspecified hypoglycemia 962.3, E858.0, E932.3, E950.4, E962.0, E980.4 Poisoning by insulins/ anti-diabetic drugs a</p><p>Unspecified 250.90, 250.91, 250.92, 250.93 Diabetes with unspecified complication Page 3 of 13</p><p>Table 2. Index hospitalization diagnosis categories, exclusive of severe dysglycemic events, that are strongest predictors of all-cause readmission. These are the index hospitalization diagnoses that have the highest rate of 30-day all-cause hospital readmission. Twenty of 46 index hospitalization CCS principal diagnoses categories with overall prevalence ≥0.5% are presented in descending order of all-cause 30-day readmission rates. These diagnoses were included in logistic regression models examining readmission risk for severe dysglycemia and other causes.</p><p>Index hospitalization principal diagnosis Discharges Readmission rate (%) CCS group Asthma 6,697 12.2% Acute myocardial infarction 17,133 12.2% Gastrointestinal hemorrhage 9,273 12.3% Circulatory disease, other 3,311 12.4% Peripheral and visceral atherosclerosis 5,913 12.4% Urinary tract infections 14,730 12.7% Nervous system disorders, other 4,961 12.7% Complications of surgical procedure 7,671 12.8% Pneumonia 23,074 13.1% Complication of device, implant, or graft 15,576 13.7% Fluid and electrolyte disorders 9,428 13.8% Gastrointestinal disorders, other 4,214 14.1% Intestinal infection 4,496 14.8% Sepsis 26,516 15.3% Hypertension with complications 7,862 15.7% Anemia 5,235 16.0% Chronic obstructive pulmonary disease 18,622 16.0% Acute and unspecified renal failure 17,464 16.4% Congestive heart failure 32,415 17.4% Respiratory failure 8,382 18.5% Page 4 of 13 Page 5 of 13</p><p>Table 3: Most prevalent CCS diagnosis categories at index hospitalization. The 20 most prevalent index hospitalization principal diagnosis CCS group diagnoses.</p><p>Index hospitalization principal diagnosis N (%) Congestive heart failure 32,415 (5.5) Osteoarthritis 29,368 (4.9) Sepsis 26,516 (4.5) Pneumonia 23,074 (3.9) Coronary atherosclerosis 20,958 (3.5) Cardiac dysrhythmias 19,695 (3.3) Chronic obstructive pulmonary disease 18,622 (3.1) Acute renal failure 17,464 (2.9) Acute myocardial infarction 17,133 (2.9) Skin and subcutaneous tissue infection 15,903 (2.7) Severe dysglycemia* 15,644 (2.6) Hyperglycemia 7,886 (1.3) Hypoglycemia 7,528 (1.3) Unspecified 230 (0.0) Complication of device, implant, or graft 15,576 (2.6) Spondylosis 15,343 (2.6) Urinary tract infections 14,730 (2.5) Acute cerebrovascular disease 13,353 (2.2) Diabetes mellitus with complications* 12,267 (2.1) Nonspecific chest pain 11,707 (2.0) Fluid and electrolyte disorders 9,428 (1.6) Gastrointestinal hemorrhage 9,273 (1.6) Biliary tract disease 8,481 (1.4) Page 6 of 13</p><p>* Severe dysglycemia diagnoses are different from the CCS classification of “Diabetes mellitus with complications” (CCS 50), which includes ICD-9-CM codes for secondary diabetes (249.01, 249.10, 249.11, 249.20, 249.21, 249.30, 249.31, 249.40, 249.41, 249.50, 249.51, 249.60, 249.61, 249.70, 249.71, 249.80, 249.81, 249.90, 249.91), uncontrolled diabetes without designation of severe dysglycemia (250.02, 250.03, 250.10, 250.40, 250.41, 250.42, 250.43, 250.50, 250.51, 250.52, 250.53, 250.60, 250.61, 250.62, 250.63, 250.70, 250.71, 250.72, 250.73); and codes designated as severe dysglycemia events (250.11, 250.12, 250.13, 250.20, 250.21, 250.22, 250.23, 250.30, 250.31, 250.32, 250.33, 250.80 250.81, 250.82, 250.83, 250.90, 250.91, 250.92, 250.93). Codes pertaining to hypoglycemia are missing from the CCS 50 grouper but are included in the severe dysglycemia classification. Page 7 of 13</p><p>Table 4. Most prevalent principal diagnoses upon readmission following index hospitalization for severe dysglycemia. Shown are both the (a) rate of readmission for the specific diagnosis following index hospitalization for severe dysglycemia (N = 15,644); and (b) proportion of all readmissions (N = 1,744) following an index hospitalization for severe dysglycemia that are for that diagnosis.</p><p>Readmission principal diagnosis N (readmission rate)a Proportion of readmissions b Severe dysglycemia* 483 (3.1%) 28.9% Hyperglycemia 350 (2.2%) 20.1% Hypoglycemia 128 (0.8%) 7.3% Unspecified 5 (0.0%) 0.3% Diabetes mellitus with complications* 118 (0.8%) 7.0% Sepsis 92 (0.6%) 5.5% Congestive heart failure 88 (0.6%) 5.3% Acute renal failure 74 (0.5%) 4.4% Skin and subcutaneous tissue infection 49 (0.3%) 2.9% Complication of device, implant, or graft 45 (0.3%) 2.7% Pneumonia 34 (0.2%) 2.0% Complications of surgical procedures 34 (0.2%) 2.0% Fluid and electrolyte disorders 31 (0.2%) 1.9% Urinary tract infections 26 (0.2%) 1.6% Hypertension 24 (0.2%) 1.4% Acute cerebrovascular disease 22 (0.1%) 1.3% Respiratory failure 22 (0.1%) 1.3% Pancreatic disorders 18 (0.1%) 1.1% Gastrointestinal hemorrhage 17 (0.1%) 1.0% Mood disorders 17 (0.1%) 1.0% Anemia 16 (0.1%) 1.0% Nonspecific chest pain 16 (0.1%) 1.0% Cardiac dysrhythmias 16 (0.1%) 1.0%</p><p>* Severe dysglycemia diagnoses are different from the CCS classification of “Diabetes mellitus with complications” (CCS 50), which includes ICD-9-CM codes for secondary diabetes (249.01, 249.10, 249.11, 249.20, 249.21, 249.30, 249.31, 249.40, 249.41, 249.50, 249.51, 249.60, 249.61, 249.70, 249.71, 249.80, 249.81, 249.90, 249.91), uncontrolled diabetes without designation of severe dysglycemia (250.02, 250.03, 250.10, 250.40, 250.41, 250.42, 250.43, 250.50, 250.51, 250.52, 250.53, 250.60, 250.61, 250.62, 250.63, 250.70, 250.71, 250.72, 250.73); and codes designated as severe dysglycemic events (250.11, 250.12, 250.13, 250.20, 250.21, 250.22, 250.23, 250.30, 250.31, 250.32, 250.33, 250.80 250.81, 250.82, 250.83, 250.90, 250.91, 250.92, 250.93). Codes pertaining to hypoglycemia are missing from the CCS 50 grouper but are included in the severe dysglycemia classification. Page 8 of 13</p><p>Table 5. Most prevalent principal diagnoses upon readmission following index hospitalizations for reasons other than severe dysglycemia. Shown are both the (a) rate of readmission for the specific diagnosis following all index hospitalizations for reasons other than severe dysglycemia (N = 578,502); and (b) proportion of all readmissions (N = 68,212) following an index hospitalization for causes other than severe dysglycemia that are for that diagnosis.</p><p>Readmission principal diagnosis N (readmission rate)a Proportion of readmissionsb Congestive heart failure 6164 (1.1%) 9.0% Sepsis 4687 (0.8%) 6.9% Complications of surgical procedures 3464 (0.6%) 5.1% Acute renal failure 3331 (0.6%) 4.9% Pneumonia 2811 (0.5%) 4.1% Complication of device, implant, or graft 2743 (0.5%) 4.0% Chronic obstructive pulmonary disease 2481 (0.4%) 3.6% Cardiac dysrhythmias 1851 (0.3%) 2.7% Respiratory failure 1796 (0.3%) 2.6% Urinary tract infections 1762 (0.3%) 2.6% Gastrointestinal hemorrhage 1561 (0.3%) 2.3% Fluid and electrolyte disorders 1557 (0.3%) 2.3% Skin and subcutaneous tissue infection 1411 (0.2%) 2.1% Severe dysglycemia* 1261 (0.2%) 1.8% Hyperglycemia 936 (0.2%) 1.4% Hypoglycemia 318 (0.1%) 0.5% Unspecified 7 (0.0%) 0.0% Acute cerebrovascular disease 1218 (0.2%) 1.8% Acute myocardial infarction 1205 (0.2%) 1.8% Hypertension with complications 1133 (0.2%) 1.7% Diabetes mellitus with complications* 988 (0.2%) 1.4% Intestinal infection 938 (0.2%) 1.4% Nonspecific chest pain 932 (0.2%) 1.4%</p><p>* Severe dysglycemia diagnoses are different from the CCS classification of “Diabetes mellitus with complications” (CCS 50), which includes ICD-9-CM codes for secondary diabetes (249.01, 249.10, 249.11, 249.20, 249.21, 249.30, 249.31, 249.40, 249.41, 249.50, 249.51, 249.60, 249.61, 249.70, 249.71, 249.80, 249.81, 249.90, 249.91), uncontrolled diabetes without designation of severe dysglycemia (250.02, 250.03, 250.10, 250.40, 250.41, 250.42, 250.43, 250.50, 250.51, 250.52, 250.53, 250.60, 250.61, 250.62, 250.63, 250.70, 250.71, 250.72, 250.73); and codes designated as severe dysglycemic events (250.11, 250.12, 250.13, 250.20, 250.21, 250.22, 250.23, 250.30, 250.31, 250.32, 250.33, 250.80 250.81, 250.82, 250.83, 250.90, 250.91, 250.92, 250.93). Codes pertaining to hypoglycemia are missing from the CCS 50 grouper but are included in the severe dysglycemia classification. Page 9 of 13</p><p>Table 6: Risk factors for severe dysglycemia vs. other readmissions following index hospitalization for severe dysglycemia. Adjusted multinomial logit regression model showing the relative risk ratios (RRRs) for severe dysglycemia and other cause 30-day readmissions compared to no readmission. The severe dysglycemia/other ratio is a ratio of the RRRs of severe dysglycemia and other cause readmissions. Specifically, an severe dysglycemia/other ratio >1 signifies greater impact of the covariate on readmissions for severe dysglycemia readmission than other causes; and vice versa. The model was adjusted for the Charlson comorbidities </p><p>(dementia, chronic obstructive pulmonary disease, rheumatologic disease, peptic ulcer disease, liver disease, hemiplegia/paraplegia, cancer, and AIDS/HIV), the discharge year, and the 20 principal diagnosis CCS categories from the index discharge with the highest risk of all-cause </p><p>30-day readmission (Online Appendix Table 2).</p><p>Readmission for Severe Readmission for Other Ratio of Severe Wald Pa Dysglycemia Causes Dysglycemia/Otherb RRR (95% CI) P RRR (95% CI) P P Patient characteristics Age, years 0.002 < 45 Ref Ref Ref 45-64 0.76 (0.57,1.02) 0.07 1.29 (1.04,1.62) 0.02 0.59 <0.001 65-74 0.89 (0.64,1.23) 0.47 1.47 (1.14,1.89) 0.003 0.60 <0.001 <0.00 ≥ 75 0.67 (0.46,0.96) 0.03 1.57 (1.22,2.02) 0.42 <0.001 1 Sex 0.49 Male Ref Ref Ref Female 1.05 (0.85,1.30) 0.65 1.08 (0.95,1.22) 0.25 0.98 0.84 Race 0.37 White Ref Ref Ref Black 1.05 (0.81,1.37) 0.69 0.94 (0.81,1.09) 0.42 1.12 0.46 Asian 1.03 (0.48,2.22) 0.95 0.88 (0.50,1.54) 0.66 1.17 0.77 Hispanic 0.87 (0.60,1.27) 0.47 0.98 (0.78,1.23) 0.87 0.89 0.56 Other/unknown 0.44 (0.17,1.09) 0.08 0.65 (0.43,0.99) 0.04 0.67 0.34 Annual income (US$) <0.001 <$40,000 Ref Ref Ref $40,000-$49,000 1.00 (0.65,1.52) 0.98 0.99 (0.81,1.22) 0.95 1.00 0.99 $50,000-$59,000 1.26 (0.92,1.74) 0.16 0.96 (0.76,1.21) 0.75 1.31 0.23 Page 10 of 13</p><p>$60,000-$74,000 0.96 (0.64,1.43) 0.83 0.95 (0.77,1.17) 0.63 1.01 0.97 $75,000-$99,000 0.67 (0.48,0.94) 0.02 0.97 (0.79,1.20) 0.78 0.69 0.03 ≥$100,000 0.71 (0.52,0.98) 0.04 0.90 (0.73,1.10) 0.30 0.80 0.17 Index hospitalization characteristics Type of severe dysglycemic event (vs. no) <0.001 Hypoglycemia 0.87 (0.30,2.47) 0.79 1.33 (0.74,2.38) 0.34 0.65 0.37 Hyperglycemia 1.93 (0.69,5.42) 0.21 1.12 (0.62,2.03) 0.70 1.71 0.48 Unspecified ------Planned status <0.001 Unplanned Ref Ref Ref Planned 0.63 (0.36,1.08) 0.09 0.87 (0.70,1.08) 0.2 0.72 0.18 Length of stay <0.001 <0.00 1 day 0.87 (0.67,1.14) 0.31 0.67 (0.54,0.83) 1.30 0.17 1 2-4 days Ref Ref <0.00 5-7 days 0.94 (0.71,1.26) 0.69 1.65 (1.42,1.92) 0.57 <0.001 1 <0.00 8-14 days 0.96 (0.64,1.44) 0.86 1.76 (1.45,2.15) 0.55 <0.001 1 <0.00 ≥ 15 days 1.20 (0.57,2.49) 0.63 2.55 (1.85,3.51) 0.47 0.004 1 Prior hospitalizations (vs. none) <0.001 <0.00 Other causes only 2.16 (1.66,2.82) <0.001 1.68 (1.46,1.94) 1.29 0.14 1 Severe 6.16 (4.79,7.91) <0.001 1.41 (1.13,1.76) 0.002 4.36 <0.001 dysglycemia Diabetes characteristics Diabetes complications severity index <0.001 0 Ref Ref Ref 1-2 1.09 (0.74,1.63) 0.66 1.00 (0.77,1.28) 0.97 1.1 0.70 3-6 1.58 (1.08,2.30) 0.02 1.32 (1.04,1.67) 0.02 1.20 0.47 <0.00 7-29 1.91 (1.27,2.88) 0.002 2.01 (1.58,2.56) 0.95 0.84 1 Diabetes treatment 0.13 Non-insulin only Ref Ref Ref Insulin 1.25 (1.00,1.57) 0.047 0.99 (0.87,1.12) 0.89 1.27 0.10 a The Wald p-value is a test of overall (joint) effect of multi-category variables. b P-value for a two-sided test of the severe dysglycemia/other RRR ratio being different from 1. Page 11 of 13</p><p>Table 7: Risk factors for severe dysglycemia vs. other readmission following index hospitalizations for causes other than severe dysglycemia. Adjusted multinomial logit regression model showing the relative risk ratios (RRRs) for severe dysglycemia and other cause </p><p>30-day readmissions compared to no readmission. The severe dysglycemia/other ratio is a ratio of the RRRs of severe dysglycemia and other cause readmissions. Specifically, an severe dysglycemia/other ratio >1 signifies greater impact of the covariate on readmissions for severe dysglycemia readmission than other causes; and vice versa. The model was adjusted for the </p><p>Charlson comorbidities (dementia, chronic obstructive pulmonary disease, rheumatologic disease, peptic ulcer disease, liver disease, hemiplegia/paraplegia, cancer, and AIDS/HIV), the discharge year, and the 20 principal diagnosis CCS categories from the index discharge with the highest risk of all-cause 30-day readmission (Online Appendix Table 2).</p><p>Readmission for Severe Readmission for Other Ratio of Severe Wald Pa Dysglycemia Causes Dysglycemia/Otherb RRR (95% CI) P RRR (95% CI) P P Patient characteristics Age, years <0.001 < 45 Ref Ref Ref 45-64 0.37 (0.30,0.46) <0.001 0.96 (0.91,1.00) 0.065 0.39 <0.001 65-74 0.41 (0.33,0.51) <0.001 0.98 (0.93,1.03) 0.355 0.42 <0.001 ≥ 75 0.47 (0.37,0.59) <0.001 1.03 (0.98,1.09) 0.242 0.46 <0.001 Sex 0.80 Male Ref Ref Ref Female 0.96 (0.86,1.08) 0.52 1.00 (0.98,1.02) 0.87 0.96 0.53 Race <0.001 White Ref Ref Ref <0.00 Black 1.24 (1.09,1.42) 0.002 1.09 (1.06,1.12) 1.14 0.07 1 Asian 1.36 (0.97,1.89) 0.072 1.05 (0.98,1.11) 0.141 1.29 0.18 Hispanic 1.00 (0.81,1.23) 0.991 1.05 (1.01,1.09) 0.014 0.95 0.65 Other/unknown 0.78 (0.55,1.10) 0.16 1.01 (0.96,1.06) 0.606 0.77 0.09 Annual income (US$) <0.001 <$40,000 Ref Ref Ref <0.00 $40,000-$49,000 0.71 (0.57,0.87) 0.001 0.94 (0.91,0.96) 0.75 0.002 1 $50,000-$59,000 0.83 (0.67,1.02) 0.07 0.98 (0.95,1.01) 0.29 0.84 0.07 Page 12 of 13</p><p>$60,000-$74,000 0.86 (0.71,1.05) 0.15 0.95 (0.92,0.98) 0.001 0.91 0.34 <0.00 $75,000-$99,000 0.86 (0.70,1.05) 0.14 0.94 (0.91,0.97) 0.91 0.35 1 <0.00 ≥ 0.80 (0.66,0.98) 0.3 0.90 (0.87,0.93) 0.89 0.21 $100,000 1 Index hospitalization characteristics Planned status <0.001 Unplanned Ref Ref Ref <0.00 Planned 0.57 (0.47,0.70) <0.001 0.78 (0.76,0.81) 0.73 <0.001 1 Length of stay <0.001 <0.00 1 day 0.75 (0.61,0.94) 0.012 0.77 (0.75,0.80) 0.98 0.83 1 2-4 days Ref Ref Ref <0.00 5-7 days 1.59 (1.38,1.84) <0.001 1.34 (1.32,1.37) 1.18 0.04 1 <0.00 8-14 days 2.09 (1.78,2.46) <0.001 1.78 (1.74,1.83) 1.17 0.07 1 <0.00 ≥ 15 days 2.72 (2.10,3.52) <0.001 2.44 (2.34,2.55) 1.12 0.44 1 Prior hospitalizations (vs. none) <0.001 <0.00 Other causes only 1.15 (1.01,1.30) 0.039 1.57 (1.54,1.60) 0.73 <0.001 1 Severe <0.00 6.28 (4.97,7.92) <0.001 1.46 (1.34,1.58) 4.31 <0.001 dysglycemia 1 Diabetes characteristics Diabetes complications severity index <0.001 0 Ref Ref Ref <0.00 1-2 1.68 (1.34,2.11) <0.001 1.19 (1.16,1.23) 1.41 0.01 1 <0.00 3-6 2.59 (2.07,3.23) <0.001 1.41 (1.38,1.45) 1.83 <0.001 1 <0.00 7-29 3.66 (2.87,4.66) <0.001 1.77 (1.71,1.82) 2.07 <0.001 1 Diabetes treatment 0.1344 Non-insulin only Ref Ref Ref <0.00 Insulin 1.92 (1.71,2.16) <0.001 1.07 (1.04,1.09) 1.80 <0.001 1 a The Wald p-value is a test of overall (joint) effect of multi-category variables. b P-value for a two-sided test of the severe dysglycemia/other RRR ratio being different from 1. Page 13 of 13</p><p>References 1. Optum. Optum Research Data Assets. 2015; June </p><p>2015:https://www.optum.com/content/dam/optum/resources/productSheets/5302_Data_A</p><p> ssets_Chart_Sheet_ISPOR.pdf. Accessed May 18, 2017.</p><p>2. Wallace PJ, Shah ND, Dennen T, Bleicher PA, Crown WH. Optum Labs: Building A </p><p>Novel Node In The Learning Health Care System. Health Aff (Millwood). July 1, 2014 </p><p>2014;33(7):1187-1194.</p><p>3. National Quality Measures Clearinghouse (NQMC). Measure summary: Diabetes short </p><p> term complications admission: percentage of admissions for a principal diagnosis of </p><p> diabetes with short-term complications per 100,000 population, ages 18 years and older. </p><p>In: National Quality Measures Clearinghouse (NQMC) [Web site]. Rockville (MD): </p><p>Agency for Healthcare Research and Quality (AHRQ); March 1, 2015. Available at: </p><p> https://www.qualitymeasures.ahrq.gov/summaries/summary/49498. Accessed on May 18,</p><p>2017.</p><p>4. National Quality Measures Clearinghouse (NQMC). Measure summary: Uncontrolled </p><p> diabetes admission: percentage of admissions for a principal diagnosis of diabetes </p><p> without mention of short-term or long-term complications per 100,000 population, ages </p><p>18 years and older. In: National Quality Measures Clearinghouse (NQMC) [Web site]. </p><p>Rockville (MD): Agency for Healthcare Research and Quality (AHRQ); March 1, 2015. </p><p>Avaialble at https://www.qualitymeasures.ahrq.gov/summaries/summary/49503. </p><p>Accessed on May 18, 2017.</p><p>5. Ginde AA, Blanc PG, Lieberman RM, Camargo CA, Jr. Validation of ICD-9-CM coding </p><p> algorithm for improved identification of hypoglycemia visits. BMC Endocr Disord. </p><p>2008;8:4.</p>