Prior infection-related hospitalization in the case 
of pneumonia; older age, peripheral neuropathy and prior hospitalization for any infection for cellulitis; and fasting serum glucose and retinopathy for septicemia/bacteremia.Effect of statin use on hospitalization for pneumonia in diabetic patientsWe were able to identify a subset of 52 case-control pairs of FDS1 participants in whom statin use was confirmed for pneumonia-related or closely contemporaneous non-infectionrelated Fruquintinib chemical information admissions in cases and controls, respectively. Coding for pneumonia was confirmed by chart review in all the cases. There was no significant difference in the proportion of patients using statin therapy amongst FDS1 patients admitted with pneumonia compared to those hospitalized for indications other than infection (23.1 vs 13.5 , P = 0.27).Serious Bacterial Infections in Type 2 
DiabetesTable 2. Bivariate baseline associates of hospitalization for any infection after study entry.No hospitalizationNumber ( ) Age (years) Male ( ) Age at diabetes diagnosis (years) Diabetes duration (years) Body mass index (kg/m2) Ethnic background: Anglo-Celt Southern European Other European Asian Mixed/other Aboriginal Fasting serum glucose (mmol/L) HbA1c ( ) Diabetes treatment: Diet Oral agents Insulin 6 oral agents Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) On blood pressure-lowering medication ( ) Total serum cholesterol (mmol/L) Serum HDL-cholesterol (mmol/L) Serum triglycerides (mmol/L) On lipid-lowering medication ( ) Taking statin therapy ( ) Taking 75 mg/day aspirin ( ) Urinary albumin:creatinine (mg/mmol) Estimated glomerular filtration rate ,60 mL/min/1.73 m2 ( ) Any retinopathy ( ) Peripheral neuropathy ( ) Peripheral arterial disease ( ) Cerebrovascular disease ( ) Ischemic heart disease ( ) Any exercise in past two weeks ( ) Smoking status ( ): Never Ex-smoker Current Alcohol use (average standard drinks/day) Prior hospitalization for any infection ( )* 1043 (80.6) 63.6611.4 47.6 57.7611.6 4.0 [0.9?.0] 29.465.4 61.5 17.4 8.2 3.8 7.9 1.2 8.4 [6.8?0.7] 7.4 [6.4?.7] 32.9 55.4 11.7 150624 80611 49.9 5.561.1 1.0760.32 1.9 (1.1?.2) 11.1 6.9 20.8 3.0 (0.7?2.6) 41.4 15.1 29.4 29.1 9.3 28.3 73.1 46.2 38.9 14.9 0 [0?.3] 5.Hospitalization 251 (19.4) 66.1610.6 53.8 58.9611.5 4.1 [1.5?1.0] 30.365.6 61.8 19.1 9.6 1.2 6.0 2.4 8.6 [7.1?1.3] 7.6 [6.5?.1] 28.0 58.8 13.2 155623 81611 55.8 5.561.0 1.0460.34 2.0 (1.2?.5) 8.0 6.0 25.6 3.8 (0.8?7.9) 51.8 22.1 37.0 30.2 12.7 35.1 67.5 38.4 46.0 15.6 0 [0?.8] 10.P-value0.001 0.08 0.13 0.012 0.012 0.0.16 0.07 0.,0.001 0.53 0.11 0.45 0.21 0.016 0.17 0.68 0.11 0.012 0.003 0.011 0.028 0.76 0.10 0.038 0.08 0.0.12 0.Data are , mean 6 SD, median [IQR] or 1485-00-3 biological activity geometric mean (SD range);*between January 1982 and study entry doi:10.1371/journal.pone.0060502.twas increased by 23 in Danish diabetic patients [27,28], while studies from the US [29] and UK [30] have shown a diabetesassociated relative risk for UTI of 2.1 to 2.2. There are a variety of mechanisms by which diabetic patients are at increased risk of bacterial infection. These include hyperglycemia-related impairment of immune function and the adverse effects of the vascular and neuropathic complications of diabetes on tissue structure and function [5]. The relationship between glycemic control and infection in previous studies hasbeen strongest for skin infections and periodontal disease and relatively weak in the case of respiratory tract and genitourinary infections [5].Prior infection-related hospitalization in the case of pneumonia; older age, peripheral neuropathy and prior hospitalization for any infection for cellulitis; and fasting serum glucose and retinopathy for septicemia/bacteremia.Effect of statin use on hospitalization for pneumonia in diabetic patientsWe were able to identify a subset of 52 case-control pairs of FDS1 participants in whom statin use was confirmed for pneumonia-related or closely contemporaneous non-infectionrelated admissions in cases and controls, respectively. Coding for pneumonia was confirmed by chart review in all the cases. There was no significant difference in the proportion of patients using statin therapy amongst FDS1 patients admitted with pneumonia compared to those hospitalized for indications other than infection (23.1 vs 13.5 , P = 0.27).Serious Bacterial Infections in Type 2 DiabetesTable 2. Bivariate baseline associates of hospitalization for any infection after study entry.No hospitalizationNumber ( ) Age (years) Male ( ) Age at diabetes diagnosis (years) Diabetes duration (years) Body mass index (kg/m2) Ethnic background: Anglo-Celt Southern European Other European Asian Mixed/other Aboriginal Fasting serum glucose (mmol/L) HbA1c ( ) Diabetes treatment: Diet Oral agents Insulin 6 oral agents Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) On blood pressure-lowering medication ( ) Total serum cholesterol (mmol/L) Serum HDL-cholesterol (mmol/L) Serum triglycerides (mmol/L) On lipid-lowering medication ( ) Taking statin therapy ( ) Taking 75 mg/day aspirin ( ) Urinary albumin:creatinine (mg/mmol) Estimated glomerular filtration rate ,60 mL/min/1.73 m2 ( ) Any retinopathy ( ) Peripheral neuropathy ( ) Peripheral arterial disease ( ) Cerebrovascular disease ( ) Ischemic heart disease ( ) Any exercise in past two weeks ( ) Smoking status ( ): Never Ex-smoker Current Alcohol use (average standard drinks/day) Prior hospitalization for any infection ( )* 1043 (80.6) 63.6611.4 47.6 57.7611.6 4.0 [0.9?.0] 29.465.4 61.5 17.4 8.2 3.8 7.9 1.2 8.4 [6.8?0.7] 7.4 [6.4?.7] 32.9 55.4 11.7 150624 80611 49.9 5.561.1 1.0760.32 1.9 (1.1?.2) 11.1 6.9 20.8 3.0 (0.7?2.6) 41.4 15.1 29.4 29.1 9.3 28.3 73.1 46.2 38.9 14.9 0 [0?.3] 5.Hospitalization 251 (19.4) 66.1610.6 53.8 58.9611.5 4.1 [1.5?1.0] 30.365.6 61.8 19.1 9.6 1.2 6.0 2.4 8.6 [7.1?1.3] 7.6 [6.5?.1] 28.0 58.8 13.2 155623 81611 55.8 5.561.0 1.0460.34 2.0 (1.2?.5) 8.0 6.0 25.6 3.8 (0.8?7.9) 51.8 22.1 37.0 30.2 12.7 35.1 67.5 38.4 46.0 15.6 0 [0?.8] 10.P-value0.001 0.08 0.13 0.012 0.012 0.0.16 0.07 0.,0.001 0.53 0.11 0.45 0.21 0.016 0.17 0.68 0.11 0.012 0.003 0.011 0.028 0.76 0.10 0.038 0.08 0.0.12 0.Data are , mean 6 SD, median [IQR] or geometric mean (SD range);*between January 1982 and study entry doi:10.1371/journal.pone.0060502.twas increased by 23 in Danish diabetic patients [27,28], while studies from the US [29] and UK [30] have shown a diabetesassociated relative risk for UTI of 2.1 to 2.2. There are a variety of mechanisms by which diabetic patients are at increased risk of bacterial infection. These include hyperglycemia-related impairment of immune function and the adverse effects of the vascular and neuropathic complications of diabetes on tissue structure and function [5]. The relationship between glycemic control and infection in previous studies hasbeen strongest for skin infections and periodontal disease and relatively weak in the case of respiratory tract and genitourinary infections [5].
