Objectives: To determine the relationship between preadmission glycemia, reflected by hemoglobin A1c level, glucose metrics, and mortality in critically ill patients. Design: Retrospective cohort investigation. Setting: University affiliated adult medical-surgical ICU. Patients: The investigation included 5,567 critically ill patients with four or more blood glucose tests and hemoglobin A1c level admitted between October 11, 2011 and November 30, 2019. The target blood glucose level was 90–120 mg/dL for patients admitted before September 14, 2014 (n = 1,614) and 80–140 mg/dL or 110–160 mg/dL for patients with hemoglobin A1c less than 7% or greater than or equal to 7% (n = 3,953), respectively, subsequently. Interventions: None. Measurements and Main Results: Patients were stratified by hemoglobin A1c: less than 6.5.(n = 4,406), 6.5–7.9% (n = 711), and greater than or equal to 8.0% (n = 450). Increasing hemoglobin A1c levels were associated with significant increases in mean glycemia, glucose variability, as measured by coefficient of variation, and hypoglycemia (p for trend < 0.0001, < 0.0001, and 0.0010, respectively). Among patients with hemoglobin A1c less than 6.5%, mortality increased as mean glycemia increased; however, among patients with hemoglobin A1c greater than or equal to 8.0%, the opposite relationship was observed (p for trend < 0.0001 and 0.0027, respectively). Increasing glucose variability was independently associated with increasing mortality only among patients with hemoglobin A1c less than 6.5%. Hypoglycemia was independently associated with higher mortality among patients with hemoglobin A1c less than 6.5% and 6.5–7.9% but not among those with hemoglobin A1c greater than or equal to 8.0%. Mean blood glucose 140–180 and greater than or equal to 180 mg/dL were independently associated with higher mortality among patients with hemoglobin A1c less than 6.5% (p < 0.0001 for each). Among patients with hemoglobin A1c greater than or equal to 8.0% treated in the second era, mean blood glucose greater than or equal to 180 mg/dL was independently associated with decreased risk of mortality (p = 0.0358). Conclusions: Preadmission glycemia, reflected by hemoglobin A1c obtained at the onset of ICU admission, has a significant effect on the relationship of ICU glycemia to mortality. The different responses to increasing mean glycemia support a personalized approach to glucose control practices in the ICU.

To determine the associations of relative hypoglycemia and hemoglobin A1c-adjusted time in blood glucose (BG) band (HA-TIB) with mortality in critically ill patients. DESIGN: Retrospective cohort investigation.SETTING: University-affiliated adult medical-surgical ICU. PATIENTS:Three thousand six hundred fifty-five patients with at least four BG tests and hemoglobin A1c (HbA1c) level admitted between September 14, 2014, and November 30, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:Patients were stratified for HbA1c bands of <6.5%; 6.5-7.9%; greater than or equal to 8.0% with optimal affiliated glucose target ranges of 70-140, 140-180, and 180-250 mg/dL, respectively. HA-TIB, a new glycemic metric, defined the HbA1c-adjusted time in band. Relative hypoglycemia was defined as BG 70-110 mg/dL for patients with HbA1c ≥ 8.0%. Further stratification included diabetes status-no diabetes (NO-DM, n = 2,616) and preadmission treatment with or without insulin (DM-INS, n = 352; DM-No-INS, n = 687, respectively). Severity-adjusted mortality was calculated as the observed:expected mortality ratio (O:EMR), using the Acute Physiology and Chronic Health Evaluation IV prediction of mortality. Among NO-DM, mortality and O:EMR, decreased with higher TIB 70-140 mg/dL (p < 0.0001) and were lowest with TIB 90-100%. O:EMR was lower for HA-TIB greater than or equal to 50% than less than 50% and among all DM-No-INS but for DM-INS only those with HbA1 greater than or equal to 8.0%.Among all patients with hba1c greater than or equal to 8.0% And no bg less than 70 mg/dl, mortality was 18.0% For patients with relative hypoglycemia (bg, 70-110 mg/dl) (p < 0.0001) And was 0.0%, 12.9%, 13.0%, And 34.8% For patients with 0, 0.1-2.9, 3.0-11.9, And greater than or equal to 12.0 Hours of relative hypoglycemia (p < 0.0001). CONCLUSIONS:These findings have considerable bearing on interpretation of previous trials of intensive insulin therapy in the critically ill. Moreover, they suggest that BG values in the 70-110 range may be deleterious for patients with HbA1c greater than or equal to 8.0% and that the appropriate target for BG should be individualized to HbA1c levels. These conclusions need to be tested in randomized trials.

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.

Background: Interventional studies investigating blood glucose (BG) management in intensive care units (ICU) have been inconclusive. New insights are needed. We assessed the ability of a new metric, the Glycemic Ratio (GR), to determine the relationship of ICU glucose control relative to preadmission glycemia and mortality. Methods: Retrospective cohort investigation (n = 4790) in an adult medical-surgical ICU included patients with minimum four BGs, hemoglobin (Hgb), and hemoglobin A1c (HbA1c). The GR is the quotient of mean ICU BGs (mBG) and estimated preadmission BG, derived from HbA1c. Results: Mortality displayed a J-shaped curve with GR (nadir GR 0.9), independent of background glycemia, consistent for HbA1c <6.5% vs >6.5%, and Hgb >10 g/dL vs <10 g/dL and medical versus surgical. An optimal range of GR 0.80 to 0.99 was associated with decreased mortality compared with GR above and below this range. The mBG displayed a linear relationship with mortality at lower HbA1c but diminished for HbA1c >6.5%, and dependent on preadmission glycemia. In adjusted analysis, GR remained associated with mortality (odds ratio = 2.61, 95% confidence interval = 1.48-4.62, P = .0012), but mBG did not (1.004, 1.000-1.009, .059). A single value on admission was not independently associated with mortality. Conclusions: The GR provided new insight into malglycemia that was not apparent using mBG, or an admission value. Mortality was associated with acute change from preadmission glycemia (GR). Further assessment of the impact of GR deviations from the nadir in mortality at GR 0.80 to 0.99, as both relative hypo- and hyperglycemia, and as duration of exposure and intensity, may further define the multifaceted nature of malglycemia.

Context The outcome of patients requiring intensive care can be influenced by the presence of previously undiagnosed diabetes (undiagDM). Objective – To define the clinical characteristics, glucose control metrics and outcomes of patients admitted to the ICU with undiagDM, and compare these to patients with known DM (DM). Methods This case:control investigation compared undiagDM (HbA1c ≥ 6.5%, no history of diabetes) to patients with DM. Glycemic ratio (GR) was calculated as the quotient of mean ICU BG and estimated preadmission glycemia, based on HbA1c ([28.7*HbA1c]-46.7 mg/dL). GR was analyzed by bands: &lt; 0.7, 0.7-≤0.9, 0.9-&lt;1.1,  ≥ 1.1. Risk-adjusted mortality was represented by the Observed:Expected mortality ratio (OEMR), calculated as the quotient of observed mortality and mortality predicted by the severity of illness (APACHE IV prediction of mortality). Findings - Of 5,567 patients 294 (5.3%) were undiagDM. UndiagDM had lower ICU mean blood glucose (p &lt; 0.0001), coefficient of variation (p &lt; 0.0001) but similar rates of hypoglycemia (p = 0.08). Mortality and risk-adjusted mortality were similar in patients with GR &lt;1.1 comparing undiagDM and DM. However, for patients with GR ≥ 1.1 mortality (38.5% vs. 10.3% [p = 0.0072]) and risk-adjusted mortality (OEMR 1.18 vs 0.52 [p &lt; 0.0001]) were higher in undiagDM than in DM. Conclusions These data suggest that patients with diabetes may develop tolerance to hyperglycemia that occurs during critical illness, a protective mechanism not observed in undiagDM, for whom hyperglycemia remains strongly associated with higher risk of mortality. These results may shed light on the natural history of diabetes.