Association of Glycemic Control Parameters with Clinical Outcomes in Chronic Critical Illness

ObjectiveChronic critical illness (CCI) is a term used to designate patients requiring prolonged mechanical ventilation and tracheostomy with associated poor outcomes. The present study assessed the impact of glycemic parameters on outcomes in a CCI population.MethodsA retrospective case series was performed including 148 patients in The Mount Sinai Hospital Respiratory Care Unit (2009-2010). Utilizing a semi-parametric mixture model, trajectories for the daily mean blood glucose (BG), BG range, and hypoglycemia rate over time identified low- (n = 87) and high-risk (n = 61) hyperglycemia groups and low- (n = 90) and high-risk (n = 58) hypoglycemia groups. The cohort was also classified into diabetes (DM, n = 48), stress hyperglycemia (SH, n = 85), and normal glucose (n = 15) groups.ResultsHospital- (28% vs. 13%, P = .0199) and 1-year mortality (66% vs. 46%, P = .0185) rates were significantly greater in the high- versus low-risk hyperglycemia groups, respectively. The hypoglycemia rate (< 70 mg/dL) was lower among ventilator-liberated patients compared to those who failed to liberate (0.092 vs. 0.130, P < .0001). In the SH group, both hospital mortality (high-risk hyperglycemia 48% and low-risk hyperglycemia 15%, P = .0013) and 1-year mortality (high-risk 74% and low-risk 50%, P = .0482) remained significantly different, while no significant difference in the diabetes group was observed. There were lower hypoglycemia rates with SH compared to diabetes (< 70 mg/dL: 0.086 vs. 0.182, P < .0001; < 40 mg/dL: 0.012 vs. 0.022, P = .0118, respectively).ConclusionTighter glycemic control was associated with improved outcomes in CCI patients with SH but not in CCI patients with diabetes. Confirmation of these findings may lead to stratified glycemic control protocols in CCI patients based on the presence or absence of diabetes. (Endocr Pract. 2014;20:884-893)     

Daily Inpatient Glycemic Survey (DINGS): A Process to Remotely Identify and Assist in the Management of Hospitalized Patients with Diabetes and Hyperglycemia

Objective: Hyperglycemia, hypoglycemia, and glycemic variability have been associated with increased morbidity, mortality, and overall costs of care in hospitalized patients. At the Stratton VA Medical Center in Albany, New York, a process aimed to improve inpatient glycemic control by remotely assisting primary care teams in the management of hyperglycemia and diabetes was designed.Methods: An electronic query comprised of hospitalized patients with glucose values <70 mg/dL or >350 mg/dL is generated daily. Electronic medical records (EMRs) are individually reviewed by diabetes specialist providers, and management recommendations are sent to primary care teams when applicable. Glucose data was retrospectively examined before and after the establishment of the daily inpatient glycemic survey (DINGS) process, and rates of hyperglycemia and hypoglycemia were compared.Results: Patient-day mean glucose slightly but significantly decreased from 177.6 ± 64.4 to 173.2 ± 59.4 mg/dL (P<.001). The percentage of patient-days with any value >350 mg/dL also decreased from 9.69 to 7.36% (P<.001), while the percentage of patient-days with mean glucose values in the range of 90 to 180 mg/dL increased from 58.1 to 61.4% (P<.001). Glycemic variability, assessed by the SD of glucose, significantly decreased from 53.9 to 49.8 mg/dL (P<.001). Moreover, rates of hypoglycemia (<70 mg/dL) decreased significantly by 41% (P<.001).Conclusion: Quality metrics of inpatient glycemic control improved significantly after the establishment of the DINGS process within our facility. Prospective controlled studies are needed to confirm a causal association.Abbreviations: DINGS = daily inpatient glycemic survey EMR = electronic medical record HbA1c = glycated hemoglobin ICU = intensive care unit VA = Veterans Affairs     

Comparison of Basal Insulin Regimens on Glycemic Variability in Noncritically Ill Patients with Type 2 Diabetes

Objective: To evaluate the impact of different subcutaneous basal insulin regimens on glycemic variability (GV) and hospital complications in non-intensive care unit (ICU) patients with type 2 diabetes (T2D).Methods: This study is a post hoc analysis of 279 general medicine and surgery patients treated with either a “Basal Bolus” insulin regimen using glargine once daily and glulisine before meals or a “Basal Plus” regimen using glargine once daily plus correction doses of glulisine before meals for glucose >140 mg/dL. GV was calculated as mean delta (Δ) daily glucose, mean SD, and mean amplitude of glycemic excursions (MAGE).Results: Treatment with Basal Bolus and Basal Plus regimens resulted in similar mean daily glucose, hypoglycemia, length of stay (LOS), and hospital complications (all P>.05). There were no differences in GV between treatment groups by Δ change (72.5 ± 36 vs. 69.3 ± 34 mg/dL), SD (38.5 ± 18 vs. 37.1 ± 16 mg/dL) and MAGE (67.5 ± 34 vs. 66.1 ± 39 mg/dL) (all P>.05). Surgery patients treated with Basal Bolus had higher GV compared to those treated with Basal Plus (Δ daily glucose and SD: P = .02, MAGE: P = .009), but no difference in GV was found between treatment groups for the general medicine patients (P>.05). Patients with hypoglycemia events had higher GV compared to subjects without hypoglycemia (P<.05), but no association was found between GV and hospital complications (P>.05).Conclusion: Treating hospitalized, non-ICU, diabetic patients with Basal Plus insulin regimen resulted in similar glucose control and GV compared to the standard Basal Bolus insulin regimen. Higher GV was not associated with hospital complications.Abbreviations:BG = blood glucoseCV= coefficient of variationGV= glycemic variabilityICU = intensive care unitLOS = length of stayMAGE = mean amplitude of glycemic excursionsSSI = sliding scale insulinT2D = type 2 diabetesTDD =total daily dose     

Safety And Efficacy Of Dpp-4 Inhibitors For The Management Of Hospitalized General Medicine And Surgery Patients with Type 2 Diabetes

Objective: DPP-4 inhibitors (DPP-4i) have been shown to be effective for the management of inpatient diabetes. We report pooled data from 3 prospective studies using DPP-4i in general medicine and surgery patients with type 2 diabetes (T2D).Methods: We combined data from 3 randomized studies comparing DPP-4i alone or in combination with basal insulin or a basal-bolus insulin regimen. Medicine (n = 266) and surgery (n = 319) patients admitted with a blood glucose (BG) between 140 and 400 mg/dL, treated with diet, oral agents, or low-dose insulin therapy were included. Patients received DPP-4i alone (n = 144), DPP-4i plus basal insulin (n = 158) or basal-bolus regimen (n = 283). All groups received correctional doses with rapid-acting insulin for BG >140 mg/dL. The primary endpoint was differences in mean daily BG between groups. Secondary endpoints included differences in hypoglycemia and hospital complications.Results: There were no differences in mean hospital daily BG among patients treated with DPP-4i alone (170 ± 37 mg/dL), DPP-4i plus basal (172 ± 42 mg/dL), or basalbolus (172 ± 43 mg/dL), P = .94; or in the percentage of BG readings within target of 70 to 180 mg/dL (63 ± 32%, 60 ± 31%, and 64 ± 28%, respectively; P = .42). There were no differences in length of stay or complications, but hypoglycemia was less common with DPP-4i alone (2%) compared to DPP-4i plus basal (9%) and basal-bolus (10%); P = .004.Conclusion: Treatment with DPP-4i alone or in combination with basal insulin is effective and results in a lower incidence of hypoglycemia compared to a basal-bolus insulin regimen in general medicine and surgery patients with T2D.Abbreviations: BG = blood glucose; BMI = body mass index; CI = confidence interval; DPP-4i = dipeptidyl peptidase-4 inhibitors; HbA1c = hemoglobin A1c; OR = odds ratio; T2D = type 2 diabetes     

Decreased Mortality with Tight Glycemic Control in Critically Ill Patients: A Retrospective Analysis in a Large Community Hospital System

ObjectiveTo measure the efficacy and possible adverse consequences of tight blood glucose (BG) control when compared to relaxed control.MethodsA retrospective, observational study was conducted at a community-based teaching hospital system among adult, nonmaternity hospitalized patients admitted to the intensive care unit (ICU). Tight glycemic control of BG was compared with less strict BG control, and the following outcome measurements were compared: BG, average length of stay (ALOS), severe hypoglycemia, and mortality.ResultsBetween 2008 and 2012, 18,919 patients were admitted to the ICU. The mortality rate was significantly lower (P = .0001) in patients with an average BG between 80 and 110 mg/dL (8%) and 111 and 140 mg/dL (9.4%) than in patients with average BG between 141 and 180 mg/dL (12.9%). Using tight glycemic control (80 to 110 mg/dL), the ALOS in the ICU decreased from 4 to 2.9 days (P < .0001) among all patients, and from 4.2 to 2.1 days (P < .0001) among patients who had undergone coronary artery bypass graft. Comparatively, the ALOS for the hospital decreased from 9.4 to 8 days. The incidence of severe hypoglycemia (BG < 40 mg/dL) was higher (P = .01) in the tight BG control group (4.78%) compared with the relaxed control group (3.5%). This rate was lower than in previously published studies that analyzed the use of tight control.ConclusionTight glycemic control using protocolbased insulin administration resulted in a decrease in mortality and ALOS among all patients in the ICU. The incidence of severe hypoglycemic episodes was slightly higher in the tightly controlled group but remained lower than in previously published studies. (Endocr Pract. 2014;20: 907-918)     

Basal-Bolus Regimen With Insulin Analogues Versus Human Insulin in Medical Patients with type 2 Diabetes: A Randomized Controlled Trial in Latin America

Objective: Few randomized studies have focused on the optimal management of non–intensive care unit patients with type 2 diabetes in Latin America. We compared the safety and efficacy of a basal-bolus regimen with analogues and human insulins in general medicine patients admitted to a University Hospital in Asunción, Paraguay.Methods: In a prospective, open-label trial, we randomized 134 nonsurgical patients with blood glucose (BG) between 140 and 400 mg/dL to a basal-bolus regimen with glargine once daily and glulisine before meals (n = 66) or Neutral Protamine Hagedorn (NPH) twice daily and regular insulin before meals (n = 68). Major outcomes included differences in daily BG levels and frequency of hypoglycemic events between treatment groups.Results: There were no differences in the mean daily BG (157 ± 37 mg/dL versus 158 ± 44 mg/dL; P = .90) or in the number of BG readings within target <140 mg/dL before meals (76% versus 74%) between the glargine/glulisine and NPH/regular regimens. The mean insulin dose in the glargine/glulisine group was 0.76 ± 0.3 units/kg/day (glargine, 22 ± 9 units/day; glulisine, 31 ± 12 units/day) and was not different compared with NPH/regular group (0.75 ± 0.3 units/kg/day [NPH, 28 ± 12 units/day; regular, 23 ± 9 units/day]). The overall prevalence of hypoglycemia (<70 mg/dL) was similar between patients treated with NPH/regular and glargine/glulisine (38% versus 35%; P = .68), but more patients treated with human insulin had severe (<40 mg/dL) hypoglycemia (7.6% versus 25%; P = .08). There were no differences in length of hospital stay or mortality between groups.Conclusion: The basal-bolus regimen with insulin analogues resulted in equivalent glycemic control and frequency of hypoglycemia compared to treatment with human insulin in hospitalized patients with diabetes.Abbreviations: BG = blood glucose BMI = body mass index HbA_1c = glycated hemoglobin NPH = Neutral Protamine Hagedorn T2D = type 2 diabetes     

Hypoglycemia Rates After Restriction of High-Dose Glargine in Hospitalized Patients

Objective: Hypoglycemia remains one of the main challenges of insulin therapy. To reduce insulin-related hypoglycemia at our institution, we restricted inpatient ordering of high glargine doses (≥0.5 U/kg/day) to endocrine staff in May 2013. This retrospective cohort study assesses its effect on hypoglycemia and glycemic control within 48 hours of admission (ADM).Methods: We identified 692 adult patients hospitalized at Boston Medical Center who received glargine upon ADM from November 1, 2012 through April 30, 2013 as the pre-intervention group, and 651 adult patients admitted between November 1, 2013 and April 30, 2014 as the postintervention group. Demographics, medical history, home insulin regimen, concurrent oral diabetes medications or glucocorticoid administration, ADM serum creatinine, all blood glucose levels (BG) ≤48 hours of ADM, and hemoglobin A1c values ≤3 months were assessed. Hypoglycemia was defined as BG ≤70 mg/dL, and hyperglycemia as BG ≥200 mg/dL. Multivariable regression models assessed potential associations between covariates and incidence of hypoglycemia and average BG ≤48 hours of ADM.Results: Demographics were similar between groups. Significantly less patients received high-dose glargine in the post-intervention group (5.2% vs. 0.3%, P<.001). Incidences of hypoglycemia were significantly lower in the postintervention group (20.9% vs. 17.8%, P<.001 per ADM; 3.4% vs. 2.3%, P = .001 per BG measurements [BGM]). Mean BG levels ≤48 hours of ADM and incidence of hyperglycemia were not significantly different. The adjusted incident rate ratio of hypoglycemia was 0.63 per ADM and 0.74 per BGM in the postintervention group compared to the pre-intervention group (P = .001 and P = .063, respectively).Conclusion: We found that implementation of a restriction on high doses of glargine resulted in lower rates of hypoglycemia without worsening glycemic control.Abbreviations:ADM = admissionBG = blood glucoseBGM = blood glucose measurementsBMC = Boston Medical CenterBMI = body mass indexEMR = electronic medical recordHgbA1c = hemoglobin A1cIRR = incidence rate ratioNPH = neutral protamine HagedornTDD = total daily doseT2D = type 2 diabetes     

Safety and Efficacy of Glucostabilizer in the Management of Diabetic Ketoacidosis

Objective: To evaluate the safety and efficacy of GlucoStabilizer software intravenous insulin (IV) dosing in comparison to American Diabetes Association protocol-directed provider-guided insulin dose adjustment (PGIA).Methods: GlucoStabilizer calculates the dose of IV insulin required to reach a prescribed target glucose range. GlucoStabilizer has not been fully studied in DKA. This retrospective study compared outcomes in patients with DKA before and after the implementation of GlucoStabilizer. Insulin doses were administered based on GlucoStabilizer calculations or PGIA. The analysis evaluated before-after changes in the amount of insulin used, time to target, hypoglycemia or hypokalemia events, and the time to DKA resolution.Results: We studied 77 patients with insulin doses calculated by GlucoStabilizer and 69 patients with PGIA dosing. GlucoStabilizer was superior to PGIA. Patients treated with GlucoStabilizer-calculated doses did not experience hypoglycemia (N = 0 versus N = 10; P<.001). The 10 unique PGIA patients had a total of 18 episodes with 17 between 55 to 69 mg/dL; 1 <54 mg/dL, and no episodes <40 mg/dL. The GlucoStabilizer group required less insulin to reach DKA resolution (59.2 versus 101.2 units; P<.001). Time to glycemic target and DKA resolution were similar (6.7 versus 4.6 hours; P = .132) and (9.8 versus 9.9 hours; P = .803), respectively. No difference in the incidence of hypokalemia was seen (N = 9 versus N = 11; P = .48).Conclusion: This study demonstrates the Gluco Stabilizer settings that can be successfully used in the management of DKA with the avoidance of hypoglycemia. Patients treated with GlucoStabilizer-calculated doses experienced no hypoglycemia and required less insulin as compared to those managed with PGIA.Abbreviations: ADA = American Diabetes Association; DKA = diabetic ketoacidosis; ED = emergency department; eGMS = electronic glycemic management systems; ICU = intensive care unit; IV = intravenous; PGIA = protocol-directed provider-guided insulin dose adjustment     

Inpatient Hypoglycemic Events in a Comparative Effectiveness Trial for Glycemic Control in a High-Risk Population

Objective: Inpatient hypoglycemia (glucose ≤70 mg/dL) is a limitation of intensive control with insulin. Causes of hypoglycemia were evaluated in a randomized controlled trial examining intensive glycemic control (IG, target 140 mg/dL) versus moderate glycemic control (MG, target 180 mg/dL) on post–liver transplant outcomes.Methods: Hypoglycemic episodes were reviewed by a multidisciplinary team to calculate and identify contributing pathophysiologic and operational factors. A subsequent subgroup case control (1:1) analysis (with/without) hypoglycemia was completed to further delineate factors. A total of 164 participants were enrolled, and 155 patients were examined in depth.Results: Overall, insulin-related hypoglycemia was experienced in 24 of 82 patients in IG (episodes: 20 drip, 36 subcutaneous [SQ]) and 4 of 82 in MG (episodes: 2 drip, 2 SQ). Most episodes occurred at night (41 of 60), with high insulin amounts (44 of 60), and during a protocol deviation (51 of 60). Compared to those without hypoglycemia (n = 127 vs. n = 28), hypoglycemic patients had significantly longer hospital stays (13.6 ± 12.6 days vs. 7.4 ± 6.1 days; P = .002), higher peak insulin drip rates (17.4 ± 10.3 U/h vs. 13.1 ± 9.9 U/h; P = .044), and higher peak insulin glargine doses (36.8 ± 21.4 U vs. 26.2 ± 24.3 U; P = .035). In the case-matched analysis (24 cases, 24 controls), those with insulin-related hypoglycemia had higher median peak insulin drip rates (17 U/h vs. 11 U/h; P = .04) and protocol deviations (92% vs. 50%; P = .004).Conclusion: Peak insulin requirements and protocol deviations were correlated with hypoglycemia.Abbreviations:DM = diabetes mellitusICU = intensive care unitIG = intensive glycemic controlMELD = Model for End-stage Liver DiseaseMG = moderate glycemic controlSQ = subcutaneous     

Proactive Protocol-Based Management of Hyperglycemia and Diabetes in Colorectal Surgery Patients

Objective: The management of diabetic patients undergoing elective abdominal surgery continues to be unsystematic, despite evidence that standardized perioperative glycemic control is associated with fewer postoperative surgical complications. We examined the efficacy of a pre-operative diabetes optimization protocol implemented at a single institution in improving perioperative glycemic control with a target blood glucose of 80 to 180 mg/dL.Methods: Patients with established and newly diagnosed diabetes who underwent elective colorectal surgery were included. The control group comprised 103 patients from January 1, 2011, through December 31, 2013, before protocol implementation. The glycemic-optimized group included 96 patients following protocol implementation from January 1, 2014, through July 31, 2016. Data included demographic information, blood glucose levels, insulin doses, hypoglycemic events, and clinical outcomes (length of stay, re-admissions, complications, and mortality).Results: Patients enrolled in the glycemic optimization protocol had significantly lower glucose levels intra-operatively (145.0 mg/dL vs. 158.1 mg/dL; P = .03) and postoperatively (135.6 mg/dL vs. 145.2 mg/dL; P = .005). A higher proportion of patients enrolled in the protocol received insulin than patients in the control group (0.63 vs. 0.48; P = .01), but the insulin was administered less frequently (median [interquartile range] number of times, 6.0 [2.0 to 11.0] vs. 7.0 [5.0 to 11.0]; P = .04). Two episodes of symptomatic hypoglycemia occurred in the control group. There was no difference in clinical outcomes.Conclusion: Improved peri-operative glycemic control was observed following implementation of a standardized institutional protocol for managing diabetic patients undergoing elective colorectal surgery.Abbreviations: HbA1c = glycated hemoglobin A1c; IQR = interquartile range     

Reduced Hypoglycemia and Comparable Efficacy with Insulin Glargine 300 U/ML Versus Insulin Glargine 100 U/ML in Patients with Type 2 Diabetes Achieving Different Levels of Prebreakfast Self-Monitored Plasma Glucose

Objective: To evaluate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) and insulin glargine 100 U/mL (Gla-100) in patients with type 2 diabetes (T2D) who reached prebreakfast self-monitored plasma glucose (SMPG) levels <100 and <130 mg/dL.Methods: This was a post hoc analysis of insulin-naïve (EDITION 3, NCT01676220) and experienced (EDITION 2, NCT01499095) patients with uncontrolled T2D, randomized to 6 months of Gla-300 versus Gla-100 treatment. Endpoints included glycated hemoglobin A1c change, hypoglycemia incidence, and event rates. Separate comparisons were done for patients achieving prebreak-fast fasting glucose of <100 versus ≥100 mg/dL and <130 versus ≥130 mg/dL.Results: Efficacy did not differ significantly between treatments in either study. Overall, basal insulin doses were ~10% higher with Gla-300 versus Gla-100. EDITION 2: overall and documented (≤70 mg/dL) hypoglycemia rates were significantly lower with Gla-300 versus Gla-100 in all SMPG groups except <100 mg/dL; nocturnal hypoglycemia rates were significantly lower with Gla-300 in all SMPG groups. EDITION 3: overall hypoglycemia rates were significantly lower with Gla-300 in patients with SMPG ≥100 mg/dL and those with SMPG <130 mg/dL; documented hypoglycemia rates were significantly lower in all SMPG groups except ≥130 mg/dL. Nocturnal and nocturnal documented hypoglycemia rates did not differ by treatment group. Hypoglycemia incidence did not differ by treatment in any SMPG group.Conclusion: In patients with T2D initiating basal insulin or previously treated for ≥6 months with basal insulin, Gla-300 provides similar efficacy to Gla-100 and reduces risk of hypoglycemia for many patients, despite a ~10% higher insulin dose.Abbreviations: A1C = glycated hemoglobin A1c; ADA = American Diabetes Association; Gla-100 = insulin glargine 100 U/mL; Gla-300 = insulin glargine 100 U/mL; OAD = oral antidiabetes drug; SMPG = self-monitored plasma glucose; T2D = type 2 diabetes     

Identifying Risk Factors for Severe Hypoglycemia in Hospitalized Patients with Diabetes

ObjectiveSome of the deleterious effects of hypoglycemia in hospitalized patients include increased rates of mortality and longer length of stay. Our primary objective was to identify the risk factors associated with severe hypoglycemia to identify those patients at highest risk.MethodsThe medical records of 5,026 patients with diabetes mellitus (DM) admitted in 2010 were reviewed to identify those patients that developed severe hypoglycemia (blood glucose [BG] < 40 mg/dL). We performed c2 tests to assess statistical significance. Adjusted logical regression was used to determine the risk factors for hypoglycemia in the hospital.ResultsOut of 5,026 DM patients included in our review, 81 experienced severe hypoglycemia (1.6%). Statistically higher proportions of chronic kidney disease (CKD; 69.1% vs. 46.9%, P < .001), congestive heart failure (CHF; 48.1% vs. 28.5%, P < .001), sepsis (49.4% vs. 12.5%, P < .001), insulin use (45.7% vs. 26.04%, P = .000), type 1 DM (21% vs. 5.1%, P = .000), and cirrhosis (14.8% vs. 7.2%, P = .009) were seen in the severe hypoglycemic group compared to the nonsevere hypoglycemic group. Overall, 84% of patients who experienced an episode of severe hypoglycemia in the hospital (BG < 40 mg/dL) had a previous episode of hypoglycemia (BG < 70 mg/dL). The odds ratios (ORs) for type 1 DM, sepsis, previous hypoglycemia, and insulin use were 3.43 (95% confidence interval [CI] 1.81, 6.49), 2.64 (95% CI 1.6, 4.35), 46.1 (95% CI 24.76, 85.74), and 1.66 (95% CI 1.02, 2.69), respectively.ConclusionPrior episodes of hypoglycemia in the hospital, the presence of type 1 DM, insulin use, and sepsis were identified as independent risk factors for the development of severe hypoglycemia in the hospital. (Endocr Pract. 2014;20:1051-1056)     

Impact of a Hypoglycemia Reduction Bundle and a Systems Approach to Inpatient Glycemic Management

Objective: Uncontrolled hyperglycemia and iatrogenic hypoglycemia represent common and frequently preventable quality and safety issues. We sought to demonstrate the effectiveness of a hypoglycemia reduction bundle, proactive surveillance of glycemic outliers, and an interdisciplinary data-driven approach to glycemic management.Methods: Population: all hospitalized adult non–intensive care unit (non-ICU) patients with hyperglycemia and/or a diagnosis of diabetes admitted to our 550-bed academic center across 5 calendar years (CYs). Interventions: hypoglycemia reduction bundle targeting most common remediable contributors to iatrogenic hypoglycemia; clinical decision support in standardized order sets and glucose management pages; measure-vention (daily measurement of glycemic outliers with concurrent intervention by the inpatient diabetes team); educational programs. Measures and analysis: Pearson chi-square value with relative risks (RRs) and 95% confidence intervals (CIs) were calculated to compare glycemic control, hypoglycemia, and hypoglycemia management parameters across the baseline time period (TP1, CY 2009–2010), transitional (TP2, CY 2011–2012), and mature postintervention phase (TP3, CY 2013). Hypoglycemia defined as blood glucose <70 mg/dL, severe hypoglycemia as <40 mg/dL, and severe hyperglycemia >299 mg/dL.Results: A total of 22,990 non-ICU patients, representing 94,900 patient-days of observation were included over the 5-year study. The RR TP3:TP1 for glycemic excursions was reduced significantly: hypoglycemic stay, 0.71 (95% CI, 0.65 to 0.79); severe hypoglycemic stay, 0.44 (95% CI, 0.34 to 0.58); recurrent hypoglycemic day during stay, 0.78 (95% CI, 0.64 to 0.94); severe hypoglycemic day, 0.48 (95% CI, 0.37 to 0.62); severe hyperglycemic day (>299 mg/dL), 0.76 (95% CI, 0.73 to 0.80).Conclusion: Hyperglycemia and hypoglycemia event rates were both improved, with the most marked effect on severe hypoglycemic events. Most of these interventions should be portable to other hospitals.Abbreviations: BG = blood glucose CDS = clinical decision support CI = confidence interval CY = calendar year DIG = diabetes initiative group EHR = electronic health record ICU = intensive care unit RR = relative risk SHM = Society of Hospital Medicine TP = time period     

Impaired Awareness of Hypoglycemia Continues to be a Risk Factor for Severe Hypoglycemia Despite the Use of Continuous Glucose Monitoring System in Type 1 Diabetes

Objective: Impaired awareness of hypoglycemia (IAH) is a risk factor for severe hypoglycemia in patients with type 1 diabetes (T1D) not using a continuous glucose monitoring (CGM) system. The current study investigated the prevalence of IAH and its relationship with severe hypoglycemia in T1D patients using CGM systems.Methods: This cross-sectional observational study enrolled 135 patients with T1D and ongoing real-time CGM use. A survey was conducted to assess hypoglycemia awareness with the Gold, Clarke, and Pedersen-Bjergaard questionnaires and the 6-month history of severe hypoglycemia. Other diabetes histories and the CGM glucose data were collected.Results: The Gold, Clarke, and Pedersen-Bjergaard questionnaires demonstrated the overall prevalence of IAH/abnormal awareness to be 33.3%, 43.7%, and 77.0%, respectively. Participant age and duration of T1D were consistently related to IAH or hypoglycemia unawareness with all three questionnaires (P<.05). Amongst the patients using CGM for >6 months, 24.5% were found to have at least one episode of severe hypoglycemia in the preceding 6 months. IAH identified by the Gold and Clarke questionnaires and hypoglycemia unawareness identified by the Pedersen-Bjergaard questionnaire were related to 6-, 4.63-, and 5.83-fold increased risk of severe hypoglycemia (P = .001, .004, and .013), respectively. IAH identified by the Gold/Clarke questionnaires was associated with a longer duration of CGM glucose <54 mg/dL and higher glucose coefficients of variation (P<.05).Conclusion: IAH is highly prevalent and related to a higher risk for severe hypoglycemia in T1D patients using CGM.Abbreviations: CGM = continuous glucose monitoring; CI = confidence interval; HAAF = hypoglycemia-associated autonomic failure; HbA1c = hemoglobin A1C; IAH = impaired awareness of hypoglycemia; T1D = type 1 diabetes     

Diurnal Glucose Profiles Using Continuous Glucose Monitoring to Identify the Glucose-Lowering Characteristics of Colesevelam HCL (WELCHOL)

ObjectiveThe study's purpose was to identify the antihyperglycemic affects of colesevelam-HCl (C-HCl) by characterizing the diurnal and postprandial glucose patterns in type 2 diabetic subjects treated concomitantly with metformin, sulfonylurea, or a combination of metformin/ sulfonylurea. A secondary aim was to determine whether C-HCl significantly increased the risk of hypoglycemia.MethodsA prospective, randomized, double-blind, placebo-controlled, crossover study employing continuous glucose monitoring (CGM) with ambulatory glucose profile (AGP) analysis was undertaken. Fifteen males and 6 females, age 60 ± 8 years, treated with metformin (n = 8), sulfonylurea (n = 2), or combination (n = 11) participated.ResultsTreatment with C-HCl led to reductions in glycated hemoglobin (HbAlc) (7.5 ± 0.3 to 7.0 ± 0.4% P<.0001), LDL (90.9 ± 18.6 to 68.9 ± 15.2 mg/dL, P<.0007) and total cholesterol (169.2 ± 24.4 to 147.8 ± 21.5 mg/dL, P<.001). Significantly lower normalized diurnal (21 mg/dL/hour, P = .0006), nocturnal (19 mg/dL/hour, P = .0005), and daytime (22 mg/dL/hour, P = .0008) glucose exposure was detected immediately upon C-HCl administration. Additionally, there was a significant (P<.004) decline in postprandial glucose excursions (averaging 15% or -36 mg/dL/hour) pronounced at dinner following C-HCl administration. There was a nonsignificant increase in the incidence of hypoglycemia (0.4-1%), with no difference due to antihyperglycemic medications.ConclusionsAGP analysis of CGM visually and quantitatively showed immediate and midterm impacts of C-HCl on basal and postprandial glucose patterns. This suggests a multifactorial glucose-lowering mechanism for C-HCl affecting both meal-related and basal glucose levels. (Endocr Pract. 2013;19:275-283)     

Effectiveness of Inpatient Insulin Order Sets Using Human Insulins in Noncritically Ill Patients in A Rural Hospital

Objective: Recent guidelines recommend a physiologic approach to non–intensive care unit (ICU) inpatient glucose management utilizing basal-bolus with correctional (BBC) insulin over traditional sliding-scale insulin monotherapy. Unfortunately, few studies exist using a BBC approach restricted to human insulins (regular and neutral protamine Hagedorn [NPH]). This study evaluated changes in provider prescribing patterns, effects on blood glucose, and safety with implementation of hospital order sets for BBC using human insulins.Methods: Order sets were developed for non-ICU inpatients, consisting of basal, prandial, and correctional insulin using NPH and regular human insulins. Evaluation compared a 4-month period before (admissions, n = 274) with a 4-month period after order set availability (n = 302). Primary outcome was change in insulin prescribing patterns. Secondary outcomes included use of nonpreferred diabetes treatments, hemoglobin A_1c testing, mean daily blood glucose, and incidence of hypoglycemia.Results: Use of BBC insulin regimen increased from 10.6 to 27.5% after order set implementation (P<.001). Use of oral antihyperglycemic agents decreased from 24.1 to 14.9% after implementation (P = .006). Hemoglobin A_1c testing rose from 50.0 to 62.3% after (P = .003). Mean daily blood glucose improved, with an estimated mean difference of 14.4 mg/dL (95% confidence interval, 2.2 to 26.5 mg/dL) over hospital days 3 through 9 (P = .02). There was no significant change in the incidence of moderate or severe hypoglycemia.Conclusion: Implementation of hospital-wide human insulin order sets led to improvements in prescribing practices and blood glucose control, without increasing the incidence of hypoglycemia. These order sets may be useful for facilities limited by formulary and cost considerations to the use of older human insulins.Abbreviations: BBC = basal-bolus with correctional insulin ICU = intensive care unit NPH = neutral protamine Hagedorn NPO = nil per os     

Effect of Total Daily Dose on Efficacy,Dosing, and Safety of 2 Dose Titration Regimens of Human Regular U-500 Insulin in Severely Insulin-Resistant Patients with Type 2 Diabetes

Objective: To examine the influence of baseline U-100 insulin total daily dose (TDD) on clinical outcomes in severely insulin-resistant patients with inadequately controlled type 2 diabetes treated with human regular U-500 insulin (U-500R) from the perspective of current dosing recommendations.Methods: Data from a recent prospective, randomized trial comparing thrice-daily (TID) and twice-daily (BID) U-500R in 325 patients transitioned from highdose/high-volume U-100 insulin were analyzed across baseline U-100 TDD units and units/kg subgroups (≤300 units [n = 224, 68.9%] and >300 units [n = 101, 31.1%]; ≤2 units/kg [n = 96, 29.5%] and >2 units/kg [n = 229, 70.5%]). Subgroup effects on treatment differences were evaluated, and outcomes between treatment-pooled subgroups were compared.Results: At 24 weeks, significant reductions in glycated hemoglobin (HbA1c) were observed for all subgroups (range: -1.01% to -1.38%, P<.05). Within-subgroup treatment effects were similar with no treatment-by-subgroup interactions; however, a greater reduction was noted in the >300-units subgroup (P = .04). No TID/BID differences within subgroups or treatment-by-subgroup interactions were observed for TDD or weight increase from baseline. Overall hypoglycemia rates were similar between treatments (within subgroups) and showed no interactions. However, rates were higher in the >300-units subgroup for severe hypoglycemia (P = .04) and in both higher-dose subgroups for documented symptomatic hypoglycemia ≤70 mg/dL (P<.001, units; P = .001, units/kg).Conclusion: Both TID and BID U-500R were efficacious and safe across TDD subgroups, though higher hypoglycemia rates were observed in higher-dose, treatment-pooled subgroups. U-500R dosing recommendations have been updated accordingly.Abbreviations:AE = adverse eventBID = twice dailyHbA1c = glycated hemoglobinQID = 4 times dailyRCT = randomized clinical trialT2D = type 2 diabetesTDD = total daily doseTID = thrice dailyU-500R = human regular U-500 insulin     

Overcoming Clinical Inertia in the Management of Postoperative Patients with Diabetes

ObjectiveTo assess the impact of an intervention designed to increase basal-bolus insulin therapy administration in postoperative patients with diabetes mellitus.MethodsEducational sessions and direct support for surgical services were provided by a nurse practitioner (NP). Outcome data from the intervention were compared to data from a historical (control) period. Changes in basalbolus insulin use were assessed according to hyperglycemia severity as defined by the percentage of glucose measurements > 180 mg/dL.ResultsPatient characteristics were comparable for the control and intervention periods (all P ≥ .15). Overall, administration of basal-bolus insulin occurred in 9% (8/93) of control and in 32% (94/293) of intervention cases (P < .01). During the control period, administration of basal-bolus insulin did not increase with more frequent hyperglycemia (P = .22). During the intervention period, administration increased from 8% (8/96) in patients with the fewest number of hyperglycemic measurements to 60% (57/95) in those with the highest frequency of hyperglycemia (P < .01). The mean glucose level was lower during the intervention period compared to the control period (149 mg/dL vs. 163 mg/dL, P < .01). The proportion of glucose values > 180 mg/dL was lower during the intervention period than in the control period (21% vs. 31% of measurements, respectively, P < .01), whereas the hypoglycemia (glucose < 70 mg/dL) frequencies were comparable (P = .21).ConclusionAn intervention to overcome clinical inertia in the management of postoperative patients with diabetes led to greater utilization of basal-bolus insulin therapy and improved glucose control without increasing hypoglycemia. These efforts are ongoing to ensure the delivery of effective inpatient diabetes care by all surgical services. (Endocr Pract. 2014;20:320-328)     

Temporal Occurrences and Recurrence Patterns of Hypoglycemia During Hospitalization

Objective: To describe the temporal distribution of hypoglycemia and its rate of recurrence during hospitalization to aid in the development of strategies to prevent hypoglycemia in hospitalized patients.Methods: Retrospective review of hypoglycemia (blood glucose <50 mg/dL) audit data in adult hospitalized patients at 2 academic hospitals. Demographics, timing, and blood glucose values were recorded. Antihyperglycemic medications, number of recurrent events, and change in basal insulin dose following the hypoglycemic event were also extracted.Results: A total of 274 index occurrences of hypoglycemia were analyzed. The mean age of the patients was 53.8 years, with roughly equal gender distributions. Twenty-eight percent of the events occurred in the absence of antihyperglycemic therapy. The incidence of hypoglycemia peaked between midnight and 6 AM. There were 36 instances of recurrent hypoglycemia associated with antihyperglycemic therapy, with 78% (n = 28) cases involving basal insulin. Patients on basal insulin who developed hypoglycemia did not have their dose changed prior to the time of the next administration in 75% of the cases.Conclusion: Hypoglycemia in hospitalized patients may occur with greater frequency overnight. Although cumbersome, routine nocturnal glycemic testing should be considered. Education regarding insulin management in the hospital and improved communication between night and day staff may aid in decreasing subsequent hypoglycemic events.Abbreviations: BG = blood glucose EHR = electronic health record ICU = intensive care unit IV = intravenous