Weight-Based Insulin During and After Intravenous Insulin Infusion Reduces Rates of Rebound Hyperglycemia When Transitioning to Subcutaneous Insulin in the Medical Intensive Care Unit

ObjectiveHyperglycemia often occurs after the transition from intravenous insulin infusion (IVII) to subcutaneous insulin. Weight-based basal insulin initiated earlier in the course of IVII in the medical intensive care unit (MICU), and a weight-based basal-bolus regimen after IVII, can potentially improve post-IVII glycemic control by 48 hours.MethodsThis prospective study included 69 patients in MICU who were on IVII for ≥24 hours. Exclusions were end-stage renal disease, type 1 diabetes mellitus, and the active use of vasopressors. The intervention group received weight-based basal insulin (0.2-0.25 units/kg) with IVII and weight-based bolus insulin after IVII. The control group received current care. The primary end points were glucose levels at specific time intervals up to 48 hours after IVII.ResultsThere were 25 patients in the intervention group and 44 in the control group. The mean age of the patients was 59 ± 15 years, 32 (47%) were men, and 52 (78%) had prior diabetes mellitus. The 2 groups were not different (acute kidney injury/chronic kidney disease, pre-existing diabetes mellitus, illness severity, or nothing by mouth status after IVII), except for the steroid use, which was higher in the control group than in the intervention group (34% vs 12%, respectively). Glucose levels were not lower until 36 to 48 hours after IVII (166.8 ± 39.1 mg/dL vs 220.0 ± 82.9 mg/dL, P < .001). When controlling for body mass index, nutritional status, hemoglobin A1C, and steroid use, glucose level was lower starting at 12 to 24 hours out (166.87 mg/dL vs 207.50 mg/dL, P = .015). The frequency of hypoglycemia was similar between the 2 groups (5.0% vs 7.1%). The study did not reach target enrollment.ConclusionThe addition of weight-based basal insulin during, and basal-bolus insulin immediately after, IVII in MICU results in better glycemic control at 24 hours after IVII with no increased hypoglycemia.     

Management of Hyperglycemia in Diabetic Patients with Hematologic Malignancies During Dexamethasone Therapy

ObjectiveTo compare the response to different insulin regimens for management of hyperglycemia in diabetic patients with hematologic malignancies who are receiving dexamethasone.MethodsA retrospective analysis was conducted to determine whether a basal bolus insulin (BBI) regimen with detemir and aspart is superior to a sliding scale regular insulin (SSI) regimen for management of hyperglycemia in hospitalized diabetic patients receiving dexamethasone.ResultsForty patients with hematologic malignancies were treated with intravenous (8 to 12 mg/day) or oral (40 mg/day) dexamethasone for 3 days. The average blood glucose (BG) level was 301 ± 57 mg/dL in the SSI group (n = 28) and 219 ± 51 mg/dL in the BBI group (n = 12) (P <.001). The BBI regimen resulted in an average BG reduction of 52 ± 82 mg/dL throughout the course of dexa-methasone therapy, while the SSI regimen produced an increase in the mean daily BG level of 128 ± 77 mg/dL (P <.001). On the last day of dexamethasone administration, the insulin requirement was 49 ± 29 units/day in the SSI group and 122 ± 39 units/day in the BBI group (P <.001). Three patients in the SSI group developed diabetic ketoacidosis or hyperosmolar hyperglycemia during steroid therapy. No hypoglycemia was observed in either group. The length of stay and infection rates were similar between groups.ConclusionBasal and bolus insulin regimen is an effective and safe approach for managing dexamethasone-induced hyperglycemia in hospitalized patients with hematologic malignancies. (Endocr Pract. 2013;19:231-235)     

Examination of Implementation of Intravenous and Subcutaneous Insulin Protocols and Glycemic Control in Heart Transplant Patients

ObjectivePerioperative glycemic management is particularly challenging in heart transplant (HT) patients who are on high-dose steroids and subject to surgical stress. The objective of the study was to examine the efficacy and safety of perioperative insulin administration in HT patients with and without diabetes.MethodsMedical records of 71 HT patients from June 1, 2005 to July 31, 2009 whose hyperglycemia was managed by our Glucose Management Service (GMS) were analyzed for up to 1 year after HT. Their daily blood glucose (BG) averages on intravenous (IV) insulin drips and subcutaneous (SQ) insulin, hypoglycemia rates, reasons for hypoglycemia, and deviations from insulin protocols were analyzed.ResultsDaily BG averages between diabetic (DM) and nondiabetic (nonDM) patients were not significantly different while on the drip but were significantly different for first 5 days on SQ (P < .05). The daily insulin glargine doses were similar. No patients developed severe hypoglycemia (BG ≤ 40 mg/dL) while on drip, and only 2.8% experienced hypoglycemia on SQ. Among 40 episodes of moderate hypoglycemia while on drip, 15 had nurse deviations from protocol prior to the episode. Posttransition day fasting glucose was at goal (mean 124.7 ± 35.4 mg/dL); however 39.4% (28/71) of patients received a transition insulin glargine dose that was different from the amount indicated by protocol. The likelihood of developing moderate hypoglycemia on SQ was associated with the glargine dose used at the time of transition (odds ratio [OR] 1.03, P = .034).ConclusionInpatient insulin protocols implemented by a GMS are successful in obtaining glycemic control with minimal side effects in patients with and without diabetes, even when they are on a high-dose steroid regimen. (Endocr Pract. 2014;20:527-535)     

Once-Daily Insulin Glargine Versus 6-Hour Sliding Scale Regular Insulin for Control of Hyperglycemia after a Bariatric Surgical Procedure: A Randomized Clinical Trial

ObjectiveTo determine whether once-daily insulin glargine could provide better glycemic control after an abdominal surgical procedure than the traditional use of sliding scale regular insulin (SSRI).MethodsBecause 20% to 30% of patients undergoing gastric bypass have a history of overt diabetes and another 5% to 10% are estimated to have impaired glucose tolerance, we chose to study these patients. We treated 81 patients with postoperative blood glucose levels of more than 144 mg/dL after a Roux-en-Y gastric bypass surgical procedure. They were randomized to receive either SSRI or insulin glargine either directly or after initial intravenous insulin infusion in the intensive care unit (ICU).ResultsOverall, the mean blood glucose level after SSRI therapy was 154 ± 33 mg/dL, and the mean blood glucose value after insulin glargine treatment was 134 ± 30 mg/dL (P < 0.01). The mean blood glucose level for patients first treated with intravenous insulin infusion in the ICU was 125 mg/dL, in comparison with 145 mg/dL in the non-ICU patients whose treatment began directly with 0.3 U/kg of insulin glargine. Of 926 blood glucose measurements, only 3 were less than 60 mg/dL.ConclusionIn this study, control of postoperative hyperglycemia was significantly better with use of insulin glargine in comparison with SSRI therapy, and hypo-glycemia was very infrequent. (Endocr Pract. 2007;13: 225-231)     

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     

A Retrospective Study Comparing Neutral Protamine Hagedorn Insulin With Glargine As Basal Therapy In Prednisone-Associated Diabetes Mellitus In Hospitalized Patients

ObjectiveTo compare glycemic outcomes in hospitalized patients with or without type 2 diabetes mellitus receiving neutral protamine Hagedorn insulin (NPH) vs glargine as basal insulin for management of glucocorticoid-associated hyperglycemia.MethodsWe conducted a retrospective review of electronic medical records in prednisone-treated adult patients with hyperglycemia in a university hospital. Consecutive patients were selected in both the NPH and glargine cohorts using inclusion and exclusion criteria. Baseline characteristics were assessed in each cohort. Glycemic outcomes were analyzed by comparing fasting blood glucose, mean daily blood glucose concentration, median daily blood glucose concentration, and the number of hypoglycemic episodes on a prespecified index day.ResultsOne hundred twenty patients were included: 60 patients in the NPH cohort and 60 patients in the glargine cohort. The weight-based insulin requirement was lower in the NPH cohort than in the glargine cohort (0.27 ± 0.2 units/kg vs 0.34 ± 0.2 units/kg [P = .04] for basal insulin and 0.26 ± 0.2 units/kg vs 0.36 ± 0.2 units/kg [P = .03] for bolus insulin). NPH and glargine cohorts were similar regarding age, sex, race, body mass index, hemoglobin A_1c, serum creatinine, and prednisone dosage. Glycemic outcomes in the NPH cohort compared with outcomes in the glargine cohort were similar regarding mean fasting blood glucose concentration (134 ± 49 mg/dL vs 139 ± 54 mg/dL [P = .63]), mean daily blood glucose (167 ± 46 mg/dL vs 165 ± 52 mg/dL [P = .79]), median blood glucose (160 ± 49 mg/dL vs 159 ± 57 mg/dL [P = .90]), and number of hypoglycemic episodes per day (0.12 ± 0.3 vs 0.10 ± 0.3 [P = .77]).ConclusionsNPH and glargine appear to be equally effective as basal insulin in the management of hyperglycemia in hospitalized patients receiving prednisone. However, the total daily insulin doses used were lower in the NPH cohort. (Endocr Pract. 2012;18:712-719)     

Insulin Requirements in Patients With Type 2 Diabetes Undergoing Bariatric Surgery in the Inpatient Setting and Upon Discharge: A Single-Center Retrospective Analysis of Insulin Management Strategies

ObjectiveRapid improvement in blood glucose (BG) after weight-loss surgery (WLS) can make postoperative glucose management challenging in patients with type 2 diabetes mellitus (T2DM). Our study examined the safety and efficacy of insulin management strategies during hospitalization and after discharge following WLS.MethodsThis single-center retrospective cohort study included 160 adult patients with type 2 diabetes mellitus undergoing WLS. Patients with glycated hemoglobin A1C (HbA1C) level <7% (53 mmol/mol) and not on antihyperglycemic medications or metformin monotherapy were excluded. BG and insulin dosing during hospitalization and at 2-week follow-up, and impact of preoperative HbA1C level were analyzed.ResultsMean age was 46.3 years. Median preoperative HbA1C level was 8% (64 mmol/mol). Postoperatively, most patients received basal insulin plus sliding-scale insulin (SSI; 79/160, 49%) or SSI alone (77/160, 48%). The initial postoperative basal dose was 0.23 units/kg/day. The median basal insulin dose at discharge was 61% lower than preoperative dose. At 2-week follow-up, 34 of 44 patients (77%) had BG levels between 70-200 mg/dL and 1 of 44 (2.2%) had BG levels >200 mg/dL, with no hypoglycemia. Patients with HbA1C level >9% (75 mmol/mol) had higher BG on admission and during hospitalization, required higher insulin doses while hospitalized, and were more frequently discharged on insulin.ConclusionSSI is effective in managing BG in some patients immediately after WLS. However, about half of the patients may require basal insulin at doses similar to those required by other inpatients. Preoperative hyperglycemia may affect inpatient insulin needs and BG. Low-dose basal insulin appears safe and effective upon discharge for select patients.     

Comparison of the Effect of Insulin Glulisine to Insulin Aspart on Breakfast Postprandial Blood Glucose Levels in Children with Type 1 Diabetes Mellitus on Multiple Daily Injections

ObjectiveRapid-acting insulins, including insulin aspart (NovoLog) and lispro (Humalog), do not seem to effectively control postprandial glycemic excursions in children with type 1 diabetes mellitus (T1DM). The objective of this study was to determine if insulin glulisine (Apidra), another rapid-acting insulin analog, would be superior in controlling postprandial hyperglycemia in children with T1DM.MethodsThirteen prepubertal children ages 4 to 11 years completed this study. Inclusion criteria included T1DM ≥6 months, glycosylated hemoglobin (HbAlC) 6.9 to 10%, blood glucose (BG) levels in adequate control for 1 week prior to study start, multiple daily injections (MDI) with insulin glargine or determir once daily and aspart or lispro premeal. If fasting BG was 70 to 180 mg/dL, subjects received insulin glulisine alternating with aspart prior to a prescribed breakfast with a fixed amount of carbohydrate (45, 60, or 75 g) for 20 days. Postprandial BG values were obtained at 2 and 4 hours.ResultsMean baseline BG values for insulin glulisine (136.4 ± 15.7 mg/dL; mean ± SD) and aspart (133.4 ± 14.7 mg/dL) were similar (P = .34). Mean increase in 2-hour postprandial BG was higher in glulisine (+113.5 ± 65.2 mg/dL) than aspart (+98.6 ± 66.9 mg/dL), (P = .01). BG remained higher at 4 hours (glulisine: 141.9 ± 36.5 mg/ dL, aspart: 129.0 ± 37.0 mg/dL) (P = .04). Although statistically insignificant, more hypoglycemic events occurred at 2-and 4-hours postprandial with insulin aspart.ConclusionInsulin aspart appears to be more effective than insulin glulisine in controlling 2-and 4-hour postprandial BG excursions in prepubertal children with T1DM. (Endocr Pract. 2013;19:614-619)     

Long-Acting Subcutaneously Administered Insulin for Glycemic Control Immediately After Cardiac Surgery

ObjectiveTo test the hypothesis that subcutaneous administration of basal insulin begun immediately after cardiac surgery can decrease the need for insulin infusion in patients without diabetes and save nursing time.MethodsAfter cardiac surgery, 36 adult patients without diabetes were randomly assigned to receive either standard treatment (control group) or insulin glargine once daily in addition to standard treatment (basal insulin group). Standard treatment included blood glucose measurements every 1 to 4 hours and intermittent insulin infusion to maintain blood glucose levels between 100 and 150 mg/dL. The study period lasted up to 72 hours.ResultsThere were no differences in demographics or baseline laboratory characteristics of the 2 study groups. Mean daily blood glucose levels were lower in the basal insulin group in comparison with the control group, but the difference was not statistically significant (129.3 ± 9.4 mg/ dL versus 132.6 ± 7.3 mg/dL; P = .25). The mean duration of insulin infusion was significantly shorter in the basal insulin group than in the control group (16.3 ± 10.7 hours versus 26.6 ± 17.3 hours; P = .04). Nurses tested blood glucose a mean of 8.3 ± 3.5 times per patient per day in the basal insulin group and 12.0 ± 4.7 times per patient per day in the control group (P = .01). There was no occurrence of hypoglycemia (blood glucose level < 60 mg/dL) in either group.ConclusionOnce-daily insulin glargine is safe and may decrease the duration of insulin infusion and reduce nursing time in patients without diabetes who have hyperglycemia after cardiac surgery. (Endocr Pract. 2011;17: 558-562)     

A Comparison of Twice-Daily Biphasic Insulin Aspart 70/30 and Once-Daily Insulin Glargine in Persons With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Therapy: A Randomized,Open-Label Study

ObjectiveTo compare efficacy and safety of biphasic insulin aspart 70/30 (BIAsp 30) with insulin (glargine) in type 2 diabetic patients who were not maintaining glycemic control on basal insulin and oral antidiabetic drugs.MethodsIn a 24-week, open-label, parallel-group trial, type 2 diabetic patients who were not maintaining glycemic control on basal insulin (glargine or neutral protamine Hagedorn) + oral antidiabetic drugs were randomly assigned to twice-daily BIAsp 30 + metformin or oncedaily glargine + metformin + secretagogues (secretagogues were discontinued in the BIAsp 30 arm).ResultsOne hundred thirty-seven patients were randomly assigned to the BIAsp 30 group and 143 patients were randomly assigned to the glargine group. Of 280 patients randomized, 229 (81.8%) completed the study. End-of-trial hemoglobin A_1c reductions were − 1.3% (BIAsp 30) vs − 1.2% (glargine) (treatment difference: 95% confidence interval, − 0.06 [− 0.32 to 0.20]; P = .657). Of patients taking BIAsp 30, 27.3% reached a hemoglobin A_1c level < 7.0% compared with 22.0% of patients taking glargine (treatment difference: P = .388). Glucose increment averaged over 3 meals was lower in the BIAsp 30 arm (treatment difference: − 17.8 mg/dL, P = .001). Fasting plasma glucose reductions from baseline were − 13.8 mg/ dL (BIAsp 30) vs − 42.5 mg/dL (glargine) (P = .0002). Final minor hypoglycemia rate, insulin dose, and weight change were higher in the BIAsp 30 arm (6.5 vs 3.4 events/patient per year, P <.05; 1.19 vs 0.63 U/kg; and 3.1 vs 1.4 kg, P = .0004, respectively).ConclusionsDespite not receiving secretagogues, patients taking BIAsp 30 + metformin achieved similar hemoglobin A_1c levels and lower postprandial plasma glucose compared with those receiving glargine + metformin + secretagogues. The large improvement in the glargine group suggests the patients were not true basal failures at randomization. While switching to BIAsp 30 improves glycemic control in this patient population, remaining on basal insulin and optimizing the dose may be equally effective in the short term. (Endocr Pract. 2011;17:41-50)     

Contribution of the Dawn Phenomenon to the Fasting and Postbreakfast Hyperglycemia In Type 1 Diabetes Treated With Once-Nightly Insulin Glargine

ObjectiveTo observe the effect of the dawn phenomenon on basal glucose and postbreakfast hyperglycemia in patients with type 1 diabetes treated with once-nightly insulin glargine and premeal insulin lispro.MethodsIn 49 study subjects consuming a fixed isocaloric (50% carbohydrate) diet of usual food, the insulin glargine dose was titrated from daily continuous glucose monitoring downloads to achieve a basal glucose goal of < 130 mg/dL 4 hours after meals and during serial meal omissions but with fewer than 10% of readings at < 70 mg/ dL during 24 hours. Patients also performed self-monitoring of plasma glucose 7 times a day (before and 2 hours after each meal or omitted meal and at bedtime).ResultsThe target mean basal glucose level was achieved only during the non-dawn phenomenon period (1400 hours to 0400 hours). During the dawn phenomenon, the mean (standard deviation) basal glucose level increased from 118 (57) mg/dL at 0400 hours to 156 (67) mg/dL before the breakfast meal, a 32% increase (P = .00149). The mean self-monitored plasma glucose level with meal omission was 63.8% of that increase with a breakfast meal.ConclusionThe fasting morning glucose concentration is considerably elevated because of the dawn phenomenon. Targeting insulin titration to this glucose level may result in excessive basal insulin dosing for the non-dawn phenomenon periods of the day. The dawn phenomenon is a large component of the postbreakfast hyperglycemia. Rather than increasing the morning premeal insulin bolus, consideration should be given to pretreating the earlier dawn phenomenon with an insulin pump with use of a variable basal insulin rate. (Endocr Pract. 2012;18:558-562)     

Comparison of 3 Algorithms for Basal Insulin in Transitioning from Intravenous to Subcutaneous Insulin in Stable Patients after Cardiothoracic Surgery

ObjectiveTo determine the effectiveness of an algorithm containing 1 of 3 initial subcutaneous doses of insulin detemir and flexible prandial and supplemental insulin aspart in stable patients who have undergone cardiac surgery and are being transitioned off intravenous insulin infusion.MethodsPatients were extubated, were not taking vasopressors, and were otherwise stable, requiring at least 1 unit per hour of intravenous insulin at least 48 hours after surgery. Patients were randomly assigned to once-daily insulin detemir at 50%, 65%, or 80% of intravenous basal insulin requirements and received insulin aspart according to carbohydrate intake. The dose of insulin detemir was adjusted daily over 72 hours.ResultsEighty-two patients were included. The percentages of patients with an initial morning glucose concentration of 80 to 130 mg/dL were 36%, 63%, and 56% of patients at the 50%, 65%, and 80% doses, respectively (P = .12). However, the mean overall glucose value at 24 and 72 hours was similar between groups, and 86%, 93%, and 92% of patients in each group, respectively, achieved a mean glucose concentration of 80 to 180 mg/dL at 72 hours (P = .60). Hypoglycemia (glucose < 65 mg/dL) only occurred in the 65% group (21%) and the 80% group (12%) over the first 72 hours (P = .02 in the 50% group compared with the 65% and 80% groups combined) with 1 event of a glucose concentration less than 40 mg/dL in the 80% group. There was no loss of glycemic control by the end of the once-daily dosing interval.ConclusionsGlycemic targets can be achieved without hypoglycemia by 72 hours in most patients who have undergone cardiac surgery and require intravenous insulin with a regimen consisting of an initial insulin detemir dose of 50% of basal intravenous insulin requirements and prandial and supplemental insulin. (Endocr Pract. 2011; 17:753-758)     

Improved Glycemic Control with Insulin Glargine Versus Pioglitazone as Add-On Therapy to Sulfonylurea or Metformin in Patients with Uncontrolled Type 2 Diabetes Mellitus

ObjectiveTo compare glycemic control with add-on insulin glargine versus pioglitazone treatment in patients with type 2 diabetes.MethodsThis 48-week, multicenter, parallel-group, open-label study randomized 389 adults with poorly controlled type 2 diabetes (glycated hemoglobin A1c [A1C], 8.0% to 12.0%), despite ≥ 3 months of sulfonylurea or metformin monotherapy, to receive add-on therapy with insulin glargine or pioglitazone. Outcomes included A1C change from baseline to end point (primary), percentage of patients achieving A1C levels ≤ 7.0%, and changes from baseline in fasting plasma glucose, body mass index, weight, and serum lipids. The safety analysis included incidence of adverse events and rates of hypoglycemia.ResultsAt end point, insulin glargine yielded a significantly greater reduction in A1C in comparison with pioglitazone (-2.48% versus -1.86%, respectively; 95% confidence interval, -0.93 to -0.31; P = .0001, 48-week modified intent-to-treat population). Insulin glargine also yielded significantly greater reductions in fasting plasma glucose at all time points (end point difference, -34.9 mg/ dL; 95% confidence interval, -47.6 to -22.2; P < .0001). In comparison with pioglitazone, insulin glargine resulted in a lower overall incidence of possibly related treatmentemergent adverse events (12.0% versus 20.7%) and fewer study discontinuations (2.2% versus 9.1%), but a higher rate (per patient-year) of confirmed clinically relevant hypoglycemic episodes (blood glucose < 70 mg/dL and all severe hypoglycemia) (4.97 versus 1.04; P <.0001) and severe hypoglycemia (0.07 versus 0.01; P = .0309). Weight and body mass index changes were similar between the 2 treatment groups.ConclusionThe addition of insulin glargine early in the diabetes treatment paradigm in patients for whom sulfonylurea or metformin monotherapy had failed resulted in significantly greater improvements in glycemic control in comparison with the addition of pioglitazone. Although severe hypoglycemia was more frequent in patients with insulin glargine therapy, hypoglycemic events occurred in < 5% of patients in the insulin glargine treatment group. (Endocr Pract. 2010;16:588-599)     

Diabetes Duration and the Efficacy and Safety of Insulin Glargine Versus Comparator Treatment in Patients with Type 2 Diabetes Mellitus

ObjectiveTo evaluate the effect of diabetes duration on efficacy and safety in patients with type 2 diabetes mellitus (T2DM) using insulin glargine versus comparator (oral antidiabetic drugs [OADs], dietary changes, or other insulins).MethodsData were pooled from randomized controlled clinical trials conducted in adults with T2DM with at least 24-week treatment with insulin glargine or a comparator, where predefined insulin titration algorithms were utilized to achieve fasting plasma glucose (FPG) concentrations of ≤ 100 mg/dL. Glycated hemoglobin A1C (A1C), FPG, and insulin dose and safety (hypoglycemia) outcomes were analyzed.ResultsNine studies were included in the analysis of 2,930 patients. Patients with shorter duration of diabetes were more likely to have greater reductions in A1C compared with those who had longer-duration disease (P < .0001). Disease duration did not affect change in FPG concentrations (P = .9017), but lower weight-adjusted insulin dose was correlated with longer-duration disease (P < .0001). Patients with longer-duration diabetes had increased risks of symptomatic hypoglycemia, confirmed hypoglycemia (self-monitored blood glucose < 50 mg/dL and < 70 mg/dL), and nocturnal hypoglycemia (all P < .001). No significant relationship was found between severe hypoglycemia and duration of diabetes. However, treatment with insulin glargine lowered A1C values more effectively than comparator treatments with fewer hypoglycemic episodes.ConclusionPatients with shorter-duration T2DM better achieved target A1C levels and had less hypoglycemia than those with longer disease duration. Insulin glargine was associated with reduced A1C and fewer hypoglycemic events than comparators, regardless of disease duration. (Endocr Pract. 2014;20:120-128)     

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     

Evaluating the Impact of Inadequate Meal Consumption on Insulin-Related Hypoglycemia in Hospitalized Patients

ObjectiveMeal intake is sometimes reduced in hospitalized patients. Meal-time insulin administration can cause hypoglycemia when a meal is not consumed. Inpatient providers may avoid ordering meal-time insulin due to hypoglycemia concerns, which can result in hyperglycemia. The frequency of reduced meal intake in hospitalized patients remains inadequately determined. This quality improvement project evaluates the percentage of meals consumed by hospitalized patients with insulin orders and the resulting risk of postmeal hypoglycemia (blood glucose [BG] <70 mg/dL, <3.9 mmol/L).MethodsThis was a retrospective quality improvement project evaluating patients with any subcutaneous insulin orders hospitalized at a regional academic medical center between 2015 and 2017. BG, laboratory values, point of care, insulin administration, diet orders, and percentage of meal consumed documented by registered nurses were abstracted from electronic health records.ResultsMeal consumption ≥50% was observed for 85% of meals with insulin orders, and bedside registered nurses were accurate at estimating this percentage. Age ≥65 years was a risk factor for reduced meal consumption (21% of meals 0%-49% consumed, P < .05 vs age < 65 years [12%]). Receiving meal-time insulin and then consuming only 0% to 49% of a meal (defined here as a mismatch) was not rare (6% of meals) and increased postmeal hypoglycemia risk. However, the attributable risk of postmeal hypoglycemia due to this mismatch was low (4 events per 1000) in patients with premeal BG between 70 and 180 mg/dL.ConclusionThis project demonstrates that hospitalized patients treated with subcutaneous insulin have a low attributable risk of postmeal hypoglycemia related to inadequate meal intake.     

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)     

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     

Chromium Infusion In Hospitalized Patients with Severe Insulin Resistance: A Retrospective Analysis

ObjectiveTo investigate the effects of intravenous chromium on serum glucose and insulin infusion rates in hospitalized patients with severe insulin resistance.MethodsIn this retrospective study, we reviewed hospital records from January 1, 2008, to December 1, 2008, to identify patients for whom intravenous chromium was ordered at our academic medical center. To be included, patients were required to demonstrate profound insulin resistance and uncontrolled hyperglycemia (defined as the inability to achieve a blood glucose value less than 200 mg/ dL during the 12 hours before chromium was given despite administration of continuous insulin infusion at a rate of 20 or more units/h) and to have received a continuous infusion of chromium chloride at 20 mcg/h for 10 to 15 hours for a total dose of 200 to 240 mcg.ResultsFourteen patients met our inclusion criteria. Over the hour preceding intravenous chromium infusion, the mean ± standard deviation rate of insulin infusion was 31 ± 15 units/h, and blood glucose was 326 ± 86 mg/dL. Twelve hours after the initiation of chromium, these values were 16 ± 16 units/h and 162 ± 76 mg/dL, respectively (P = .011 for difference in mean insulin rate from baseline, P <.001 for difference in mean blood glucose from baseline) and 24 hours after, these values were 12 ± 15 units/h and 144 ± 48 mg/dL, respectively (P <.001 for both).ConclusionsIntravenous chromium decreases insulin needs and improves glucose control at 12 and 24 hours compared with baseline values. Chromium appears to improve hyperglycemia and insulin resistance in acutely ill patients and represents a potential new therapy. Future prospective randomized controlled trials are needed to confirm these results. (Endocr Pract. 2012;18:394-398)     

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)