Acute and Chronic Glucose Control in Critically Ill Patients With Diabetes: The Impact of Prior Insulin Treatment

Abstract

Background: Emerging data highlight the interactions of preadmission glycemia, reflected by admission HbA1c levels, glycemic control during critical illness, and mortality. The association of preadmission insulin treatment with outcomes is unknown. Methods: This observational cohort study includes 5245 patients admitted to the medical-surgical intensive care unit of a university-affiliated teaching hospital. Three groups were analyzed: patients with diabetes with prior insulin treatment (DM-INS, n = 538); patients with diabetes with no prior insulin treatment (DM-No-INS, n = 986); no history of diabetes (NO-DM, n = 3721). Groups were stratified by HbA1c level: <6.5%; 6.5%-7.9% and >8.0%. Results: Among the three strata of HbA1c, mean blood glucose (BG), coefficient of variation (CV), and hypoglycemia increased with increasing HbA1c, and were higher for DM-INS than for DM-No-INS. Among patients with HbA1c < 6.5%, mean BG ≥ 180 mg/dL and CV > 30% were associated with lower severity-adjusted mortality in DM-INS compared to patients with mean BG 80-140 mg/dL and CV < 15%, ( P = .0058 and < .0001, respectively), but higher severity-adjusted mortality among DM-No-INS ( P = .0001 and < .0001, respectively) and NON-DM ( P < .0001 and < .0001, respectively). Among patients with HbA1c ≥ 8.0%, mean BG ≥ 180 mg/dL was associated with lower severity-adjusted mortality for both DM-INS and DM-No-INS than was mean BG 80-140 mg/dL ( p < 0.0001 for both comparisons). Conclusions: Significant differences in mortality were found among patients with diabetes based on insulin treatment and HbA1c at home and post-admission glycemic control. Prospective studies need to confirm an individualized approach to glycemic control in the critically ill.

Relative Hypoglycemia and Lower Hemoglobin A1c-Adjusted Time in Band Are Strongly Associated With Increased Mortality in Critically Ill Patients

“…We excluded cardiovascular surgery patients (due to their very low mortality), those admitted for diabetic ketoacidosis, and those with a new diagnosis of diabetes (patients without prior history of patients with diabetes mellitus [DM] but with A1c ≥ 6.5%). Previously published investigations have included some or all of the current cohort (16, 17, 23).…”

“…In addition, although unintentional protocol violations or changes in nutrition may have played a role, DM-INS with high HbA1c likely have greater insulin deficiency, resulting in high glucose variability before and during ICU admission, contributing to the increased occurrence of hypoglycemia seen in this group. The basis for the biologic plausibility of these findings is beyond the focus of this investigation but has been discussed in recently published literature (16,17,(33)(34)(35).…”

“…Observational studies have used hemoglobin A1c (HbA1c) measured at or near ICU admission as a reflection of baseline glycemia and have demonstrated that for patients with normal or near-normal baseline glycemia, mortality rates are higher with higher mean glycemia during ICU treatment, but for patients with high HbA1c at admission, higher mean glycemia during ICU treatment is associated with lower mortality (13)(14)(15)(16). However, for patients with diabetes, treatment with insulin prior to admission confounds these observations, for example, patients with HbA1c less than 6.5% had higher mortality with lower mean ICU glycemia (17).…”

Update on glucose control during and after critical illness

“…Observational data consistently report that the association between death and hyperglycemia is markedly affected by preexisting glucose control [23][24][25][26]. Moreover, the risk of treatment-induced hypoglycemia, a strong predictor of increased mortality, is greatest in those with preexisting hyperglycemia [27,28].…”

Nutritional therapy in critically ill patients with diabetes

“…When patients with diabetes are critically ill and admitted in an intensive care environment, the management of blood glucose might differ from non-diabetic patients. Several cohort studies [4 ▪ ] consistently found that the association between blood glucose values and outcomes differed according to the admission A1c level. Likewise, a post hoc analysis of the Leuven studies found that patients with diabetes did not benefit from tight glycaemic control by intensive insulin therapy, unlike the other patients [5].…”