Interaction of Glycemia With Mortality in Diabetes
Interaction of Glycemia With Mortality in Diabetes
Objectives: The relationship between hyperglycemia and mortality is altered by the presence of diabetes mellitus. Biological adjustment to preexisting hyperglycemia might explain this phenomenon. We tested whether the degree of preexisting hyperglycemia would modulate the association between glycemia and outcome during critical illness in patients with diabetes mellitus.
Design: Retrospective observational study.
Setting: Two tertiary intensive care units.
Patients: Four hundred fifteen critically ill diabetic patients with HbA1c levels measured within 3 months of intensive care unit admission.
Interventions: None.
Measurements and Main Results: There were 9,946 blood glucose measurements in this study cohort (glucose measured 6.7 times per day; every 3.6 hrs on average). The median preadmission HbA1c level was 7.0%. There was no significant difference in HbA1c levels (p = .17) or time-weighted average of blood glucose concentrations (p = .49) between survivors and nonsurvivors. The time-weighted average of blood glucose concentrations during intensive care unit stay for nonsurvivors was lower than that of survivors when the HbA1c was >6.8%. In multivariate analysis, we found that there was a significant interaction between HbA1c and the time-weighted glucose level, indicating that the relationship between HbA1c and mortality changed according to the levels of time-weighted average of blood glucose concentrations (p = .008). As a consequence, in patients with higher (>7%) preadmission levels of HbA1c, the higher the time-weighted acute glucose concentration during intensive care unit stay (>10 mmol/L), the lower the hospital mortality compared with the lower HbA1c cohort (<7%).
Conclusions: In patients with diabetes mellitus admitted to intensive care units, there was a significant interaction between preexisting hyperglycemia and the association between acute glycemia and mortality. These observations generate the hypothesis that glucose levels that are considered safe and desirable in other patients might be undesirable in diabetic patients with chronic hyperglycemia. Further studies are required to confirm or refute our findings.
Acute hyperglycemia is associated with increased mortality. After reports that intensive insulin therapy reduced mortality in selected critically ill patients, targeted blood glucose control was recommended in international consensus guidelines and applied irrespective of the presence of diabetes mellitus (DM).
Recently, we reported that the relationship between hyperglycemia and outcomes was altered by the presence of DM. We showed that patients with DM had lower odds ratios of death at all levels of hyperglycemia compared with those without DM. This observation is consistent with other studies and can be interpreted to suggest that optimal blood glucose concentration might be higher in these patients.
One possible explanation for these findings might relate to biological adjustment to preexisting hyperglycemia in DM patients. Such adjustment would make rapid decreases in glycemia potentially dangerous. If this notion were true, the risk associated with lowering blood glucose during critical illness in patients with diabetes should increase with and be proportional to the degree of pre-intensive care unit (pre-ICU) admission hyperglycemia.
Accordingly, we hypothesized that preexisting glycemic control may have altered the association between acute glycemia and outcome in critically ill patients with DM. We tested this hypothesis in critically ill patients with DM by studying the interaction between pre-ICU admission HbA1c levels, ICU glucose levels, and outcome in these patients.
Abstract and Introduction
Abstract
Objectives: The relationship between hyperglycemia and mortality is altered by the presence of diabetes mellitus. Biological adjustment to preexisting hyperglycemia might explain this phenomenon. We tested whether the degree of preexisting hyperglycemia would modulate the association between glycemia and outcome during critical illness in patients with diabetes mellitus.
Design: Retrospective observational study.
Setting: Two tertiary intensive care units.
Patients: Four hundred fifteen critically ill diabetic patients with HbA1c levels measured within 3 months of intensive care unit admission.
Interventions: None.
Measurements and Main Results: There were 9,946 blood glucose measurements in this study cohort (glucose measured 6.7 times per day; every 3.6 hrs on average). The median preadmission HbA1c level was 7.0%. There was no significant difference in HbA1c levels (p = .17) or time-weighted average of blood glucose concentrations (p = .49) between survivors and nonsurvivors. The time-weighted average of blood glucose concentrations during intensive care unit stay for nonsurvivors was lower than that of survivors when the HbA1c was >6.8%. In multivariate analysis, we found that there was a significant interaction between HbA1c and the time-weighted glucose level, indicating that the relationship between HbA1c and mortality changed according to the levels of time-weighted average of blood glucose concentrations (p = .008). As a consequence, in patients with higher (>7%) preadmission levels of HbA1c, the higher the time-weighted acute glucose concentration during intensive care unit stay (>10 mmol/L), the lower the hospital mortality compared with the lower HbA1c cohort (<7%).
Conclusions: In patients with diabetes mellitus admitted to intensive care units, there was a significant interaction between preexisting hyperglycemia and the association between acute glycemia and mortality. These observations generate the hypothesis that glucose levels that are considered safe and desirable in other patients might be undesirable in diabetic patients with chronic hyperglycemia. Further studies are required to confirm or refute our findings.
Introduction
Acute hyperglycemia is associated with increased mortality. After reports that intensive insulin therapy reduced mortality in selected critically ill patients, targeted blood glucose control was recommended in international consensus guidelines and applied irrespective of the presence of diabetes mellitus (DM).
Recently, we reported that the relationship between hyperglycemia and outcomes was altered by the presence of DM. We showed that patients with DM had lower odds ratios of death at all levels of hyperglycemia compared with those without DM. This observation is consistent with other studies and can be interpreted to suggest that optimal blood glucose concentration might be higher in these patients.
One possible explanation for these findings might relate to biological adjustment to preexisting hyperglycemia in DM patients. Such adjustment would make rapid decreases in glycemia potentially dangerous. If this notion were true, the risk associated with lowering blood glucose during critical illness in patients with diabetes should increase with and be proportional to the degree of pre-intensive care unit (pre-ICU) admission hyperglycemia.
Accordingly, we hypothesized that preexisting glycemic control may have altered the association between acute glycemia and outcome in critically ill patients with DM. We tested this hypothesis in critically ill patients with DM by studying the interaction between pre-ICU admission HbA1c levels, ICU glucose levels, and outcome in these patients.
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