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)     

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)     

How Much do I Give? Dose Estimation Formulas for Once-Nightly Insulin Glargine and Premeal Insulin Lispro in type 1 Diabetes Mellitus

ObjectiveTo evaluate the mathematical relationships between dosing factors in type 1 diabetic patients using multiple daily injections.MethodsIn this single-center, prospective study in type 1 diabetic patients, the basal continuous glucose monitoring glucose target was less than 130 mg/dL with fewer than 10% of 24-hour readings at less than 70 mg/dL. Basal glucose for the 4-hour meal periods was obtained from once-daily serial meal omissions. On an isocaloric, 50% carbohydrate, fixed diet, the insulin to carbohydrate ratio was adjusted to achieve a 2-to 4-hour postbolus glucose value within ± 20% of premeal glucose. For determining dosing formulas, the slope of the linear regression line comparing the variables of weight, total daily dose (TDD), total basal dose (TBD), insulin-to-carbohydrate ratio (ICR), and correction factor (CF) was determined.ResultsForty-nine patients were included. Titrating insulin glargine to the morning glucose led to hypoglycemia during the rest of the day (2 PM to 4 AM). Therefore the basal glucose target was the nondawn phenomenon portion of the day. The resulting estimation formulas could be rounded to the following:

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ConclusionsSmaller insulin glargine doses to achieve control are in contrast to those much larger doses reported in clinical trials in multiple daily injection-treated type 1 diabetes in which the morning fasting glucose is the basal insulin target. (Endocr Pract. 2012;18:382-386)     

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)     

Safety and Efficacy of an Insulin Infusion Protocol Designed for the Non-Intensive Care Setting

ObjectiveTo determine whether glycemic control can be safely achieved with use of a simplified insulin infusion protocol in hospitalized patients who are not in the intensive care unit (ICU).MethodsWe developed a novel intravenous insulin protocol specifically designed for use in the non-ICU setting. We then collected clinical data on the first 30 patients treated with use of this protocol. Our study focused on safety and glycemic control.ResultsThe insulin infusion protocol was used in 30 patients for a total of 634 hours. A single hypoglycemic episode (glucose level < 60 mg/dL) occurred in 3 patients. The target mean glucose level of < 150 mg/dL was achieved in 9 hours. Once the glucose target had been achieved, the mean and median glucose concentrations were 156 mg/dL and 140 mg/dL, respectively.ConclusionUse of a simple intravenous insulin protocol can safely and effectively control the blood glucose level in patients in a non-ICU setting. (Endocr Pract. 2009;15:682-688)     

Safe and Simple Emergency Department Discharge Therapy for Patients with Type 2 Diabetes Mellitus and Severe Hyperglycemia

ObjectiveTo investigate the safety and effectiveness of 2 simple discharge regimens for use in patients with type 2 diabetes mellitus (DM2) and severe hyperglycemia, who present to the emergency department (ED) and do not need to be admitted.MethodsWe conducted an 8-week, open-label, randomized controlled trial in 77 adult patients with DM2 and blood glucose levels of 300 to 700 mg/dL seen in a public hospital ED. Patients were randomly assigned to receive glipizide XL, 10 mg orally daily (G group), versus glipizide XL, 10 mg orally daily, plus insulin glargine, 10 U daily (G + G group). The primary outcome was to maintain safe fasting glucose and random glucose levels of < 350 and < 500 mg/dL up to 4 weeks and < 300 and < 400 mg/ dL, respectively, thereafter and to have no return ED visits (responders).ResultsBaseline characteristics were similar between the 2 treatment groups. The primary outcome was achieved in 87% of patients in both treatment groups. The enrollment mean blood glucose values of 440 and 467 mg/dL in the G and G + G groups, respectively, declined by the end of week 1 to 298 and 289 mg/dL and by week 8 to 140 and 135 mg/dL, respectively. Homeostasis model assessment of b-cell function and early insulin response improved 7-fold and 4-fold, respectively, in responders at the end of the 8-week study.ConclusionSulfonylurea with and without use of a small dose of insulin glargine rapidly improved blood glucose levels and b-cell function in patients with DM2. Use of sulfonylurea alone once daily can be considered a safe discharge regimen for such patients and an effective bridge between ED intervention and subsequent follow-up. (Endocr Pract. 2009;15:696-704)     

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)     

Inpatient Management of Diabets Mellitus Among Noncritically Ill Patients at the University Hospital of Puerto Rico

ObjectiveTo describe the state of glycemic control in noncritically ill diabetic patients admitted to the Puerto Rico University Hospital and adherence to current standard of care guidelines for the treatment of diabetes.MethodsThis was a retrospective study of patients admitted to a general medicine ward with diabetes mellitus as a secondary diagnosis. Clinical data for the first 5 days and the last 24 hours of hospitalization were analyzed.ResultsA total of 147 noncritically ill diabetic patients were evaluated. The rates of hyperglycemia (blood glucose ≥ 180 mg/dL) and hypoglycemia (blood glucose < 70 mg/dL) were 56.7 and 2.8%, respectively. Nearly 60% of patients were hyperglycemic during the first 24 hours of hospitalization (mean random blood glucose, 226.5 mg/dL), and 54.2% were hyperglycemic during the last 24 hours of hospitalization (mean random blood glucose, 196.51 mg/dL). The mean random last glucose value before discharge was 189.6 mg/dL. Most patients were treated with subcutaneous insulin, with basal insulin alone (60%) used as the most common regimen. The proportion of patients classified as uncontrolled receiving basal-bolus therapy increased from 54.3% on day 1 to 60% on day 5, with 40% continuing to receive only basal insulin. Most of the uncontrolled patients had their insulin dose increased (70.1%); however, a substantial proportion had no change (23.7%) or even a decrease (6.2%) in their insulin dose.ConclusionThe management of hospitalized diabetic patients is suboptimal, probably due to clinical inertia, manifested by absence of appropriate modification of insulin regimen and intensification of dose in uncontrolled diabetic patients. A comprehensive educational diabetes management program, along with standardized insulin orders, should be implemented to improve the care of these patients. (Endocr Pract. 2014;20:452-460)     

Glycemic Variation and Hypoglycemia in Patients with well-Controlled Type 1 Diabetes on a Multiple Daily Insulin Injection Program with use of Glargine and Ultralente as Basal Insulin

ObjectiveTo evaluate glycemic variation and hypo-glycemia in patients with well-controlled type 1 diabetes receiving multiple daily insulin injections during glargine and Ultralente use as basal insulin in a clinical trial.MethodsTwenty-two patients (12 men and 10 women, median age, 43 years), with a hemoglobin A1c level < 7.8%, were randomized in a crossover design to receive either insulin glargine or Ultralente insulin as basal insulin for 4 months each, with insulin aspart as prandial insulin. Continuous glucose monitoring and the Fear of Hypoglycemia questionnaire were used at baseline and at the end of each treatment period.ResultsWhereas the mean amplitude of glycemic excursions showed a correlation with the area under the curve of blood glucose < 3.89 mmol/L per day, the number of periods during the day with hypoglycemia was significantly correlated with the M value. Measures of glycemic variation did not differ significantly between glargine and Ultralente treatment. With use of glargine therapy, the SD of blood glucose levels showed a tendency to be lower and the SD of nocturnal blood glucose concentrations was significantly lower. Glucose concentrations were significantly lower during the 1 hour before and the 3 hours after lunch with use of Ultralente. The “Worry” scale on the Fear of Hypoglycemia questionnaire was less during Ultralente therapy and correlated with the number of times blood glucose concentrations were < 3.89 mmol/L daily.ConclusionMeasures of glycemic variability and hypoglycemia need to be studied more in clinical trials of glycemic control in patients with type 1 diabetes. Glycemic variability is less, particularly at night, with glargine as basal insulin. (Endocr Pract. 2007;13:244-250)     

Adapting to the new consensus guidelines for managing hyperglycemia during critical illness: the updated Yale insulin infusion protocol

ObjectiveTo report our preliminary experience with the revised, more conservative Yale insulin infusion protocol (IIP) that targets blood glucose concentrations of 120 to 160 mg/dL.MethodsWe prospectively tracked clinical responses to the new IIP in our medical intensive care unit (ICU) by recording data on the first 115 consecutive insulin infusions that were initiated. All blood glucose values; insulin doses; nutritional support including intravenous dextrose infusions; caloric values for enteral and parenteral nutrition; and use of vasopressors, corticosteroids, and hemodialysis or continuous venovenous hemodialysis were collected from the hospital record.ResultsThe IIP was used 115 times in 90 patients (mean age, 62 [± 14 years]; 51% male; 35% ethnic minorities; 66.1% with history of diabetes). The mean admission Acute Physiology and Chronic Health Evaluation II score was 24.4 (± 7.5). The median duration of insulin infusion was 59 hours. The mean baseline blood glucose concentration was 306.1 (± 89.8) mg/dL, with the blood glucose target achieved after a median of 7 hours. Once the target was reached, the mean IIP blood glucose concentration was 155.9 (± 22.9) mg/dL (median, 150 mg/dL). The median insulin infusion rate required to reach and maintain the target range was 3.5 units/h. Hypoglycemia was rare, with 0.3% of blood glucose values recorded being less than 70 mg/dL and only 0.02% being less than 40 mg/dL. In all cases, hypoglycemia was rapidly corrected using intravenous dextrose with no evident untoward outcomes.ConclusionsThe updated Yale IIP provides effective and safe targeted blood glucose control in critically ill patients, in compliance with recent national guidelines. It can be easily implemented by hospitals now using the original Yale IIP. (Endocr Pract. 2012;18:363-370)     

Optimized Basal-Bolus Insulin Regimens in Type 1 Diabetes: Insulin Glulisine Versus Regular Human Insulin in Combination with Basal Insulin Glargine

ObjectiveTo compare the efficacy and safety of insulin glulisine (GLU), a new rapid-acting insulin analogue, injected 0 to 15 minutes before or immediately after meals, with regular human insulin (RHI), injected 30 to 45 minutes before meals.MethodsPatients with type 1 diabetes (N = 860) received once-daily insulin glargine and subcutaneous injections of either GLU (premeal or postmeal) or premeal RHI in this open-label, randomized, controlled, multicenter, parallel-group, 12-week study.ResultsBaseline to endpoint changes in mean glycated hemoglobin (as A1c equivalents) (A1c) occurred in the premeal GLU, postmeal GLU, and premeal RHI groups (-0.26%, -0.11%, and -0.13%, respectively). The reduction in A1c was greater for the premeal GLU group in comparison with the RHI group (P = 0.02) and the post-meal GLU group (P = 0.006); no significant between-treatment difference was found for postmeal GLU versus RHI. Overall, blood glucose profiles were similar in all 3 treatment groups but were significantly lower for premeal GLU 2-hour postbreakfast measurements (premeal versus postmeal GLU, P = 0.0017; premeal GLU versus RHI, P = 0.0001) and 2-hour postdinner measurements (premeal GLU versus RHI, P = 0.0001; premeal versus postmeal GLU, P = 0.0137). Severe hypoglycemic episodes were comparable for premeal GLU, postmeal GLU, and pre-meal RHI groups (8.4%, 8.4%, and 10.1%, respectively). Body weight increased (+ 0.3 kg) in the RHI and premeal GLU groups; however, weight decreased in the postmeal GLU group (-0.3 kg; between-treatment difference, P = 0.03).ConclusionBetter A1c reductions were obtained with premeal GLU, but postmeal administration of GLU was as safe and effective as premeal GLU or RHI in combination with insulin glargine and was not associated with weight gain. (Endocr Pract. 2005;11:11-17)     

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)     

Reduced Risk of Hypoglycemia with Insulin Degludec Versus Insulin Glargine in Patients with Type 2 Diabetes Requiring High Doses of Basal Insulin: A Meta-Analysis of 5 Randomized Begin Trials

ObjectiveThis meta-analysis of 5 trials from the Phase 3a insulin degludec (IDeg) clinical trial program evaluated the risk of hypoglycemia in a subset of subjects with type 2 diabetes (T2D) who required high basal insulin doses at the end of the trials.MethodsThis meta-analysis compared glycated hemoglobin (HbA_1c), fasting plasma glucose (FPG), basal insulin dose, body weight, and rates of overall and nocturnal confirmed hypoglycemia in a pooled population of T2D subjects using > 60 U basal insulin at trial completion. Five Phase 3a, open-label, randomized, treat-to-target, confirmatory 26-or 52-week trials with IDeg (n = 2,262) versus insulin glargine (IGlar) (n = 1,110) administered once daily were included. Overall confirmed hypoglycemia was defined as self-measured blood glucose < 56 mg/dL or any episode requiring assistance; nocturnal confirmed hypoglycemia had an onset between 00:01 and 05:59 am.ResultsMore than one-third of IDeg-(35%) and IGlar-(34%) treated T2D subjects required > 60 U of basal insulin daily at the ends of the trial. Patients achieved similar mean HbA_1c values (estimated treatment difference [ETD] IDeg - IGlar: 0.05%, P = .44) while mean FPG values were lower with IDeg than IGlar (ETD: - 5.9 mg/ dL, P = .04) at end-of-trial. There was a 21% lower rate of overall confirmed hypoglycemic episodes for IDeg (estimated rate ratio [RR] IDeg/IGlar: 0.79, P = .02) and a 52% lower rate of nocturnal confirmed hypoglycemic episodes for IDeg (RR: 0.48, P < .01).ConclusionIn this post hoc meta-analysis, more than 30% of subjects with T2D required > 60 U/day of basal insulin at the end of the trials. In these individuals, IDeg achieves similar HbA_1c reduction with significantly less overall and nocturnal confirmed hypoglycemia compared with IGlar. (Endocr Pract. 2014;20:285-292)     

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)     

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)     

Insulin Injections in Relation to Meals in the Hospital Medicine Ward: Comparison of 2 Protocols

ObjectiveTo investigate whether changing the prandial regular insulin to rapid-acting insulin analogue in hospital medicine wards improves the timing of insulin delivery in relation to meals and improves patient safety and glucose control.MethodsThis open-label randomized controlled trial in type 2 diabetic patients compared insulin lispro with meals and basal insulin glargine (intervention) vs regular insulin before meals and basal neutral protamine Hagedorn insulin twice daily (control). The primary endpoint was the rate of targeted timing of insulin to meals (target time). In the intervention group, target time was defined as insulin administered from 15 minutes before to 15 minutes after the patient started a meal. For the control group, target time was defined as insulin administered from 30 minutes before to 30 minutes after the patient started a meal. Hypoglycemic, hyperglycemic, and severe hyperglycemic patient-days were compared between groups.ResultsTwenty-seven patients in the intervention group and thirty-three patients in the control group were studied. The percentage of times that the insulin was given within target time was significantly higher in the intervention group as a whole (88.9% vs 70.1%, P < .001) and was higher for lunch and the evening meal (90% vs 66.7% and 94.7% vs 70.1%, P < .001). The rate of hypoglycemia was lower in the intervention group (1.85% vs 15%, P < .001). The rate of hyperglycemia was similar in both groups (68.2% vs 59.8%, P = .224), but the intervention group had a higher rate of severe hyperglycemia (28.9% vs 12.9%, P = .003).ConclusionsThe use of prandial insulin analogues in medicine wards allows better timing with meals than regular insulin and results in better hypoglycemic outcomes. Higher rates of hyperglycemia with prandial analogues may need adjustment in insulin doses. (Endocr Pract. 2011:17:737-746)     

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     

Successful treatment of prediabetes in clinical practice: targeting insulin resistance and β-cell dysfunction

ObjectiveTo determine the effectiveness of targeted pharmacologic interventions to reverse documented pathophysiologic abnormalities in prediabetes.MethodsPatients with impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) were treated with insulin sensitizers (pioglitazone + metformin) or insulin sensitizers + exenatide on the basis of oral glucose tolerance testing-derived indices of insulin resistance and impaired b-cell function. Patients who declined pharmacologic therapy received lifestyle modification only.ResultsOne hundred five patients with IGT and/or IFG were treated with insulin sensitizers (pioglitazone + metformin) (n = 40), insulin sensitizers + exenatide (n = 47), or lifestyle modification only (n = 18). After a mean follow-up period of 8.9 months, the lifestyle modification group demonstrated no significant changes in fasting plasma glucose, plasma glucose area under the curve during oral glucose tolerance testing, insulin sensitivity, or b-cell function. In the pioglitazone + metformin group (24 hours off medication), fasting plasma glucose fell from 109 to 102 mg/dL; plasma glucose area under the curve decreased by 12.0%; insulin sensitivity and b-cell function improved by 42% and 50%, respectively (all P < .001); 14.3% converted to normal glucose tolerance; and no patient developed diabetes. In the pioglitazone + metformin + exenatide group (24 hours off medication), fasting plasma glucose fell from 109 to 98 mg/dL; plasma glucose area under the curve decreased by 21.2%; insulin sensitivity and b-cell function improved by 52% and 109%, respectively (all P < .001); 59.1% of patients with IGT reverted to normal glucose tolerance; and no patient developed diabetes.ConclusionsTargeted pathophysiologic therapy based on oral glucose tolerance test-derived measures of insulin sensitivity and b-cell function can be implemented in general internal medicine and endocrine practice and is associated with marked improvement in glucose tolerance and reversion of prediabetes to normal glucose tolerance in more than 50% of patients. (Endocr Pract. 2012;18: 342-350)     

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)     

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)