A total of 25,400 were included in the study analysis. Mean age of the patients was 69.9 ± 18.0 and 12,524 were males (49.3%). Number of patients defined as having SCIC was 5,639 (22.2%), and 62.2% of the cases had day of SCIC equal to 0. and 92.7% of patients had day of SCIC lower than 7 days. Table 1 describes patients’ demographic characteristics, comorbidities and baseline laboratory data by SCIC status. Patients with SCIC were older, had longer hospitalization, and more co-morbidities. They had more acute infection as reason for admission. Regarding laboratory tests, patients with SCIC had higher CRP and white blood cells levels, and lower albumin level.
Association between SCIC status and hypoglycemia.
Number of patients with hypoglycemia was 1,548 (6.1% of patient population). Patients with SCIC had higher incidence of hypoglycemia compared to patients without. This was true for patients with DM (14.9% vs 5.8%, respectively, p< 0.001) and without DM (11.8% vs 3.4%, respectively, p< 0.001). Patients with SCIC had also higher incidence of hypoglycemia documented in chemistry panel among patients with DM (9.9% vs 3.0%, respectively, p< 0.001) and without DM (10.7% vs 3.1%, respectively, p< 0.001).
Logistic regression models showed that SCIC (yes/no) was associated with an increased risk of hypoglycemia (OR 1.853, 95% CI 1.586-2.166, p<0.001). Other covariates associated with increased risk included DM (OR 2.495, 95% CI 2.150-2.895, p<0.001) and length of hospital stay (OR 1.036, 95% CI 1.031-1.042, p<0.001). Factors associated with decreased incidence of hypoglycemia were admission levels of albumin (OR 0.360, 95% CI 0.320-0.406, p<0.001), hemoglobin (OR 0.951, 95% CI 0.923-0.978, p=0.001), and eGFR (OR 0.993, 95% CI 0.990-0.997, p<0.001). Age (OR 0.983, 95% CI 0.979-0.987, p<0.001) and average glucose level (OR 0.990, 95% CI 0.988-0.991, p<0.001) were also associated with decreased risk. Similar results were obtained when analysing only hypoglycemia events documented in the chemistry panel. Results were similar after omitting the patients that had "improved" SCIC.
Among patients with at least one hypoglycemia event, the average number of events recorded during the hospitalization was higher among patients with SCIC (2.5±3.0 vs 1.8±1.6, p<0.001). To control for longer length of stay and hospital mortality, a linear regression analysis was performed, with the number of events as the dependent variable. The independent covariates were the same as the logistic regression model, but also including death during hospitalization (yes/no). The model showed that SCIC was associated with an increased risk for multiple events (HR 0.102, 95% CI 0.076-0.128, p<0.001). additional parameters associated with increased number of hypoglycemic events included length of hospital stay (HR 0.015, 95% CI 0.014-0.015, p<0.001), diabetes mellitus status (HR 0.144, 95% CI 0.118-0.169, p<0.001) and death during the hospitalization (HR 0.243, 95% CI 0.192-0.293, p<0.001). Parameters associated with reduced number of events were older age (HR -0.002, 95% CI -0.003 - -0.001, p<0.001), higher admission hemoglobin level (HR -0.009, 95% CI -0.014 - -0.004, p=0.001), higher admission serum albumin (HR -0.125, 95% CI -0.146 - -0.103, p<0.001), higher average glucose during hospitalization (HR -0.002, 95% CI -0.002 - -0.001, p<0.001) and acute infection as reason for admission (HR -0.033, 95% CI -0.057 - -0.009, p=0.009). Similar results were obtained when using only events recorded in the chemistry panel. Figure 1 shows the estimated marginal means of the number of hypoglycemic events according to SCIC status and DM status.
Association between SCIC magnitude and hypoglycemia.
Among patients with SCIC, magnitude of creatinine change was significantly associated with hypoglycemia (OR 1.316, 95% CI 1.197-1.447, p<0.001). The model also showed that LOS (OR 1.025, 95% CI 1.020-1.031, p<0.001), and diabetes mellitus status (OR 2.236, 95% CI 1.826-2.737, p<0.001) were associate with increased incidence of hypoglycemia. Older age (OR 0.991, 95% CI 0.985-0.996, p=0.001), higher admission hemoglobin (OR 0.949, 95% CI 0.913-0.987, p=0.008), higher admission serum albumin (OR 0.418, 95% CI 0.359-0.487, p<0.001), and higher average glucose during the hospitalization (OR 0.992, 95% CI 0.990-0.994, p<0.001) were all associated with reduced incidence of hypoglycemia. Rate of hypoglycemia incidence across quintiles of creatinine change among patients with SCIC is described in Figure 2.
Magnitude of SCIC was also associated with number of events. Every 0.1 mg/dL change in creatinine was associated with a hazard ratio of 0.054 (95% CI 0.021-0.087, p=0.001). Other parameters to significantly affect the number of events included age (HR -0.004, 95% CI -0.006 - -0.001, p=0.002), length of hospital stay (HR 0.054, 95% CI 0.021-0.087, p=0.001), admission hemoglobin (HR -0.022, 95% CI -0.040 - -0.005, p=0.012) and albumin (HR -0.213, 95% CI -0.286 - -0.139, p<0.001), average glucose during the hospitalization (HR -0.003, 95% CI -0.004 - -0.002, p<0.001), diabetes mellitus status (HR 0.254, 95% CI 0.167-0.342, p<0.001) and death during the hospitalization (HR 0.233, 95% CI 0.124-0.342, p<0.001). Again, similar results were obtained when analysing hypoglycemia events documented in the chemistry panel alone.
Ascertaining timing of SCIC and hypoglycemia
Figure 3 shows the percent of patients with hypoglycemia according to timing of first hypoglycemic event from SCIC, among patients with (right panels) and without DM (left panels). More than 60% of patients with hypoglycemia had their first event documented during days 0-6 after SCIC was observed (top panels). This was true for patients with (right panels) and without DM (left panels). 2.1 percent of the hospitalized patients without DM and 2.1% of patients with DM had their first documented hypoglycemic event on day 0 from SCIC. Similar rates were observed on day 1 from SCIC, and this rate showed a gradual decrease throughout the first 5 days from SCIC. Rate of first documented hypoglycemia was maintained relatively low and with similar rates prior to SCIC, and from day 6 onward following SCIC.
To ascertain causality between SCIC and incident hypoglycemia, a Cox regression analysis was used. The model showed that SCIC was a significant covariate to affect day of first documented hypoglycemia (OR 1.626, 95% CI 1.443-1.831, p<0.001) (Figure 4). Additional covariates to significantly affect the timing of hypoglycemia included average glucose during the hospitalization (OR 0.990, 95% CI 0.989-0.992, p<0.001), diabetes mellitus status (OR 2.420, 95% CI 2.135-2.744, p<0.001), hospital mortality status (OR 1.873, 95% CI 1.600-2.191, p<0.001), acute infection as reason for admission (OR 0.889, 95% CI 0.791-0.999, p=0.048), admission serum albumin (OR 0.499, 95% CI 0.451-0.553, p<0.001) and age (0.987, 95% CI 0.984-0.990, p<0.001). Other covariates such as sex, admission cholesterol and WBC did not affect the timing of hypoglycemia.
Association between age, incident hypoglycemia and SCIC
Results of our models showed that age was a protective parameter against hypoglycemia, both in incidence and number of events. Given this, we performed several analyses to study the association between age, hypoglycemia and SCIC in our patient population. In a regression model including incident hypoglycemia as the dependent variable and age, sex and diabetes mellitus status as the independent variables, age was positively correlated with incident hypoglycemia (OR 1.004, 95% CI 1.001-1.007, p=0.011). After controlling for SCIC status and eGFR, age was found to be protective against incident hypoglycemia (OR 0.993, 95% CI 0.990-0.997, p=0.001).
Association between age and SCIC was also investigated. In a regression model using SCIC as the dependent variable, and age as the independent variable, age was associated with increased risk of SCIC (OR 1.029, 95% CI 1.027-1.031, p<0.001). When controlling for admission eGFR, DM status, acute infection as reason for admission, and HTN and CHF as comorbidities, age was associated with lower incidence of SCIC (OR 0.974, 95% CI 0.971-0.977, p<0.001).
"Deteriorating" SCIC Vs. "Improving" SCIC
Table 2 shows the comparison of patients according to positive or negative SCIC. Patients with deteriorated SCIC (i.e. increased serum creatinine during hospitalization) had a longer length of stay, higher rates of CHF, HTN and DM, and higher rates of hypoglycemia during the hospitalization.