U500 Regular Insulin use in Insulin-Resistant type 2 Diabetic Veteran Patients

ObjectiveTo evaluate the use of U500 regular insulin therapy in insulin-resistant patients with type 2 diabetes mellitus who were previously treated with high-dosage U100 insulin regimens.Methods:At a large Veterans Affairs medical center, a retrospective chart review was performed of all patients whose U100 insulin regimens were converted to U500 regular insulin regimens using a protocol to ensure patient safety. Patients were followed up for longer than 6 months. Data reviewed included total daily dosage of insulin before and after regimen conversion and changes in hemoglobin A1c, body weight, lipids, and episodes of severe hypoglycemia.ResultsFifty-three patients met inclusion criteria. Average hemoglobin A1c level on U100 insulin regimens was 9.1 ± 1.7%, which decreased to 8.1 ± 1.3% (P < .001) after an average of 20 months (range, 6-52 months) on U500 insulin. The total daily insulin dosage at study end was not significantly greater on U500 (415 ± 166 units/day) than on U100 insulin (391 ± 120 units/day) (P = .34). Body weight did not change significantly (134 ± 29 kg vs 136 ± 30 kg, P = .18). There was a 20-mg/dL decrease in total cholesterol (P = .014). Triglyceride values decreased by 97 mg/dL (P = .005). Eight episodes of severe hypoglycemia were documented in patients treated with U500 insulin, but this was similar to the incidence in these same patients while treated with U100 insulin.ConclusionWe conclude that U500 insulin can be safely and effectively used in insulin-resistant patients with type 2 diabetes followed up at a large Veterans Affairs medical center using a protocol that ensures patients are thoroughly educated and carefully monitored. (Endocr Pract. 2012;18:34-38)     

A 24-Week,Prospective, Randomized,Open-Label,Treat-To-Target Pilot Study of Obese Type 2 Diabetes Patients with Severe Insulin Resistance to Assess the Addition of Exenatide on the Efficacy of U-500 Regular Insulin Plus Metformin

ObjectiveTo compare the efficacy of 500 U/mL (U-500) regular insulin + metformin with U-500 regular insulin + metformin + exenatide in improving glycemic control in patients with severely insulin-resistant type 2 diabetes mellitus (T2DM).MethodsThirty patients with T2DM and severe insulin resistance were screened, and 28 were randomized to regular insulin U-500 + metformin or the GLP-1 analog exenatide, U-500, and metformin. Glycated hemoglobin (HbA_1c) levels, body weight, and insulin doses were documented at baseline and at 3 and 6 months. The number and severity hypoglycemic episodes were noted.ResultsThere were 7 males and 7 females in each group (U-500 + metformin and U-500 + metformin + exenatide). Overall, U-500 insulin + metformin, either alone or with the addition of exenatide, resulted in a significant improvement in HbA_1c in both groups, with no significant difference between the 2 groups. There was no meaningful weight change in those utilizing exenatide. Those on U-500 insulin and metformin alone had a tendency toward some weight gain. No severe hypoglycemia occurred during the study period. Symptomatic hypoglycemia was more common in the group on exenatide, but this occurred in only 5 patients, and the clinical significance of this is uncertain. Insulin dosage changes on U-500 regular insulin were variable but tended to be lower in those subjects on exenatide.ConclusionsU-500 regular insulin + metformin is effective for the treatment of T2DM patients with severe insulin resistance. The addition of exenatide may ameliorate potential weight gain but provides no additional improvement in glycemia. (Endocr Pract. 2014;20:1143-1150)     

The Effect of Long-Term Use of U-500 Insulin Via Continuous Subcutaneous Infusion on Durability of Glycemic Control and Weight in Obese,Insulin-Resistant Patients with Type 2 Diabetes

ObjectiveTo evaluate the long-term efficacy and safety of U-500 insulin administered via continuous subcutaneous insulin infusion (CSII) in patients with insulin-resistant type 2 diabetes and high insulin requirements.MethodsWe retrospectively reviewed the effects of U-500 insulin administered via CSII on durability of gly-cemic control (HbAlc), body weight, total daily insulin dose, and incidence of hypoglycemia in 59 patients with insulin-resistant type 2 diabetes (duration of treatment 1 to 9.5 years; mean treatment duration 49 months). All variables were analyzed by 1-way analysis of variance (ANOVA) from pre-U-500 baseline to time points from 3 to 114 months.ResultsAfter 3 months of U-500 insulin use, hemoglobin A1c dropped significantly from a mean baseline of 8.3% to a mean value of 7.3% (P = .003), and this improvement was sustained for over 66 months of use. There was no significant overall change in body weight or total daily insulin dose over time with the use of U-500 insulin. For those subjects who did gain weight, there was a parallel increase in insulin dose that correlated with weight gain.The overall incidence of severe hypoglycemia was low over the study period, with a mean occurrence of 0.1 episodes per patient per year.ConclusionsU-500 insulin is safe and effective for extended use (up to 9.5 years) in patients with insulin-resistant type 2 diabetes who require high insulin doses, and provides sustained glycemic control without causing excessive weight gain. (Endocr Pract. 2013;19:196-201)     

Analysis of Effectiveness of Human U-500 Insulin in Patients Unresponsive to Conventional Insulin Therapy

ObjectiveTo present a retrospective analysis of the effects of human U-500 insulin in 20 patients with type 2 diabetes and insulin resistance.MethodsMedical records of 20 patients with type 2 diabetes who had received U-500 insulin for at least 6 months were reviewed to determine glycemic control before and after this therapy. Human regular U-500 insulin therapy was initiated at a unit dosage equivalent to the previous standard insulin dosage. Comparisons of hemoglobin A1c levels, insulin doses, and body mass index at baseline and 6 months after changing to U-500 insulin therapy were analyzed.ResultsIn the 10 female and 10 male study subjects, the mean (± SD) hemoglobin A1c level was 9.59 ± 1.37% initially, and it decreased to 8.53 ± 1.11% at 3 months and to 7.83 ± 1.26% at 6 months after initiation of U-500 insulin therapy. In comparison with baseline, these decreases were statistically significant. The amount of insulin used and the body mass index did not change significantly from baseline to 6 months after initiation of U-500 insulin treatment.ConclusionAnalysis of data suggests that U-500 insulin therapy yields improved glycemic control in insulin-resistant patients who have poor control of blood glucose with use of standard insulin regimens. There is no proof, however, that improved glycemic control by this method decreases diabetes-related complications or improves survival. Further studies must be performed before U-500 insulin can be recommended as a standard therapy for patients with insulin resistance. (Endocr Pract. 2005;11:305-307)     

A Prospective Trial of U500 Insulin Delivered by Omnipod in Patients With Type 2 Diabetes Mellitus and Severe Insulin Resistance

ObjectiveTo test the effectiveness and safety of U500 regular insulin delivered by continuous subcutaneous insulin infusion (CSII) via the Omnipod insulin delivery system in patients with uncontrolled type 2 diabetes mellitus and severe insulin resistance.MethodsIn this prospective, 1-year, proof-of-concept trial, patients with insulin-requiring type 2 diabetes who had a hemoglobin A1c level of 7.0% or higher and severe insulin resistance (average insulin requirement, 1.74 units of insulin per kilogram each day; range, 1.4 to 2.64 units of insulin per kilogram [average insulin dose, 196.4 units daily]) were identified at routine office visits at Mountain Diabetes and Endocrine Center in Asheville, North Carolina, between December 2007 and August 2008. All patients had been on intensive insulin therapy with or without oral agents for more than 3 months. All patients were switched from baseline failed therapy to U500 regular insulin by continuous subcutaneous insulin infusion via Omnipod. Effectiveness was assessed by hemoglobin A1c measurement and 72-hour continuous glucose monitoring at baseline and at weeks 13, 26, and, 52 and by treatment satisfaction assessed by the Insulin Delivery Rating System Questionnaire at baseline and at week 52 while on U500 via Omnipod.ResultsTwenty-one adults were enrolled (mean age, 54 years; mean duration of diabetes, 4 years; mean body mass index, 39.4 kg/m2; mean insulin requirement, 1.7 U/ kg per day; and mean hemoglobin A1c, 8.6%) whose previous treatment with U100 insulin regimens had failed. Twenty patients completed the study. Treatment with U500 insulin via Omnipod significantly reduced hemoglobin A1c by 1.23% (P < .001) and significantly increased the percentage of time spent in the blood glucose target range (70- 180 mg/dL) by 70.75% as assessed by continuous glucose monitoring (P < .001) without a significant increase in hypoglycemia. Patients were satisfied with treatment with U500 insulin via Omnipod, and 14 patients elected to remain on treatment at study completion.ConclusionsU500 insulin delivered subcutaneously continuously via Omnipod is a safe and effective method of insulin delivery in the very insulin-resistant type 2 diabetic population. (Endocr Pract. 2010;16:778-784)     

Clinical Efficacy and Patient Satisfaction with U-500 Insulin Pump Therapy in Patients with Type 2 Diabetes

ObjectiveTo determine the safety and efficacy of U-500 regular insulin in pump therapy and to assess satisfaction with U-500 insulin pump therapy in patients with type 2 diabetes and severe insulin resistance.MethodsWe performed a retrospective review of medical records of 6 patients with type 2 diabetes and insulin resistance who had been using U-500 insulin pump therapy for at least 6 months. In addition, we conducted a telephone follow-up patient satisfaction survey.ResultsThe mean age of the patients was 57 ± 6 years. Of the 6 patients (3 men and 3 women), 4 were white, 1 was black, and 1 was Asian. The mean hemoglobin A1c value before continuous subcutaneous insulin infusion therapy with U-500 regular insulin was 9.1% ± 1.8%, and the mean U-100 insulin dose required was 391 ± 91 U/day. In comparison, the mean U-500 insulin dose required at 6 months was 59.2 ± 13.6 U/day, which is equivalent to 296 ± 68 U/day of U-100 insulin (P = 0.04), and the mean hemoglobin A1c value at 6 months after treatment with the insulin pump using U-500 regular insulin was 6.9% ± 0.9% (P = 0.03). In addition, our study patients lost a mean of 6.1 lb during the 6-month period, and no patient had clinically significant episodes of hypoglycemia. The majority of the patients reported a higher satisfaction with the U-500 insulin pump therapy in comparison with conventional insulin treatment.ConclusionU-500 insulin pump therapy is a novel alternative for patients with type 2 diabetes and severe insulin resistance who have not met glycemic control goals with use of standard intensive insulin regimens. (Endocr Pract. 2007;13:721-725)     

Breastfeeding and the Basal Insulin Requirement in Type 1 Diabetic Women

ObjectiveTo evaluate whether breastfeeding in women with type 1 diabetes mellitus is associated with a decreased insulin requirement.MethodsIn this prospective study conducted between September 2006 and August 2008, type 1 diabetic pregnant women were recruited before the third trimester of pregnancy. Eligible women had no evidence of diabetes-related complications and were treated with continuous subcutaneous insulin infusion pump therapy. During pregnancy and in the first 8 weeks of the postpartum period, participants performed daily fingerstick blood glucose monitoring with at least 12 measurements per day; insulin dosages were adjusted to maintain normoglycemia. Participant characteristics, diabetic parameters, and neonatal growth were compared between women who breastfed exclusively and women who did not breastfeed.ResultsOf 18 women, 12 breastfed and 6 did not. Compared with nonbreastfeeding mothers, breastfeeding mothers showed a decreased need for total daily basal insulin (0.21 ± 0.05 units/kg per day vs 0.33 ± 0.02 units/kg per day). The mean value of total daily basal insulin was significantly lower in the breastfeeding group than in the nonbreastfeeding group. The mean number of hyperglycemic episodes in the first 2 weeks post partum and during the third to eighth weeks was not different between the groups.However, the mean number of hypoglycemic episodes in the first 2 weeks post partum in the breastfeeding group was significantly higher than in the nonbreastfeeding group (11.9 ± 2.6 episodes vs 5.5 ± 1.6 episodes, P < .001). No differences were observed between the groups in neonatal birth weight or infant weight after 8 weeks of age.ConclusionsDecreased need in total daily basal insulin is caused by increased glucose use during lactation. We recommend that the starting total daily basal insulin dosage for type 1 diabetic women who breastfeed be calculated as 0.21 units times the weight in kg per day. This regimen results in normoglycemia and minimizes the risk of severe hypoglycemia associated with lactation. (Endocr Pract. 2009;15:187-193)     

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)     

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)     

Use of Insulin Pump Therapy in Patients with Type 2 Diabetes After Failure of Multiple Daily Injections

ObjectiveTo determine the effectiveness of insulin pump use (continuous subcutaneous insulin infusion; CSII) in patients with type 2 diabetes (DM2) who have failed multiple daily injection (MDI) therapy.MethodsIn this retrospective study, charts of patients with DM2 who were started on CSII after failure of MDI were reviewed. Patients were categorized as primarily manual (fixed) bolus users or calculated (using pump software) bolus users. The change in hemoglobin A1c (HbA1c), weight, and basal insulin dose from baseline to 6 months was determined.ResultsFifty-seven patients (20 men and 37 women) ranging in age from 13 to 71 were identified in the study. A significant reduction in HbA1c was observed from 8.75 to 7.69% (P<.001). There was an increase in body mass index (BMI) from a mean of 36.53 to a mean of 37.21. A decrease in basal insulin requirement per kilogram of weight (−0.10 U/kg) was noted (P = .03). Seven patients using U-500 insulin in the pump also had a significant decrease in HbA1C of 1.1 % (P<.001), along with a 0.071 U/kg drop in basal insulin requirements (P<.001). When comparing calculated bolus users to manual bolus users, there was no difference in HbA1C improvement (P = .58).ConclusionWe found that CSII improves glucose control in patients with DM2 who have failed MDI despite a decrease in overall insulin requirements. This includes patients with severe insulin resistance using U-500 insulin. Use of frequent bolus adjustment incorporating carbohydrate counting and current glucose level does not appear to be required for this benefit. (Endocr Pract. 2013;19: 9-13)     

Insulin Glargine or Neutral Protamine Hagedorn in Patients with Severe Insulin Resistance: is There A Benefit?

ObjectiveTo determine the benefit of neutral protamine Hagedorn (NPH) insulin compared with insulin glargine in a patient with type 2 diabetes mellitus and severe insulin resistance.MethodsWe describe the patient’s clinical findings and treatment course.ResultsA 52-year-old man with a 3-year history of type 2 diabetes mellitus did not achieve adequate glucose control despite escalation of his treatment regimen to insulin glargine, 80 units twice daily; insulin lispro, 60 units before each meal; and metformin. Dietary and lifestyle changes were emphasized and implemented while medication adherence with appropriate insulin technique was reviewed at each visit. Insulin glargine was replaced with the same dosage of NPH insulin. After 3 months, a significant drop in hemoglobin A_1c was noted, from 9.5% to 6.1%, consistent with the improved capillary glucose measurements. The effect was maintained over the following year, without any major hypoglycemic events.ConclusionNPH insulin might be superior to the long-acting analogue insulin glargine in cases of severe insulin resistance, but randomized studies are needed to confirm our finding and clarify the involved mechanisms. (Endocr Pract. 2012;18:e49-e51)     

Advanced Insulin Management program reduces A1C levels and regimen-related distress without weight gain in patients with type 1 diabetes mellitus

Background: Despite the availability of effective treatments, many patients with diabetes have suboptimal glycemic control.Objective: This study was designed to determine whether the Advanced Insulin Management (AIM) program could help patients with type 1 diabetes mellitus (DM) reduce their A1C levels to ≤7.5% without weight gain, increased incidence of hypoglycemia, or increased diabetes-related distress.Methods: The AIM program, developed to intensify glycemic control in patients with type 1 DM, consisted of a screening visit and 3 to 6 interactive group sessions, depending on whether the patient elects multiple daily injections (MDIs) or an insulin pump. Patients who wanted to learn additional diabetes management skills were referred by their endocrinologist, and those with competent carbohydrate-counting skills and record-keeping practices were eligible to enroll. A nurse, dietitian, psychologist, and physician provided group instruction and supported individual goal setting. The program included depression screening, regimen adjustments, and problem-solving activities. Outcome measures, including blood glucose, A1C, weight, and diabetes-related distress, were tracked for 12 months.Results: The study included 113 adult patients with type 1 DM (59% female; mean age, 39 years). Twenty patients already had insulin pumps, 46 patients initiated pump therapy during the study, and 47 patients elected MDIs. Mean A1C declined by 0.5% (to 7.3%) after 12 months, without weight gain or increased hypoglycemia. A significant decrease in diabetes-related distress was observed.Conclusion: The AIM program was associated with important improvements in glycemic control in patients with type 1 DM, without weight gain or increased hypoglycemic episodes.     

Analysis of Guidelines for Basal-Bolus Insulin Dosing: Basal Insulin,Correction Factor,and Carbohydrate-To-Insulin Ratio

ObjectiveTo analyze and compare the underlying mathematical models for basal-bolus insulin-dosing guidelines in patients with type 1 diabetes in a retrospective controlled study.MethodsAlgebraic model-development yielded several systems of models with unknown constants, including 3 systems currently in use. These systems were compared for logic and consistency. One of these systems was the accurate insulin management (AIM) system, which we developed in the setting of our large endocrine practice. Our database consisted of retrospective clinical records for a 7-month period. During this time, correction factor (CF), carbohydrate-to-insulin ratio (CIR), and basal insulin were being adjusted incrementally by titration. The variables studied were height, body weight in pounds (BWlb), CF, CIR, hemoglobin A1c (A1C), basal insulin, and 6-day mean total daily dose of insulin (TDD). The values of the variables used in the study were those determined on arrival of the patients at the office. The last 6 TDDs were entered into the database, and the mean was calculated by formulas within the database. We sorted our database into 2 groups, a well-controlled test group (n = 167; A1C ≤ 7%, time on pump > 180 days, no severe hypoglycemic events since the last office visit, and C-peptide level ≤ 0.5 ng/mL) and a control group with poor control (n = 209; A1C > 7% or time on pump < 180 days). We obtained one office visit per patient, as follows: from the test group, we chose the visit with the lowest A1C value; from the control group, we chose one visit by use of a computer’s random number generator. A significant difference was demonstrated between the correlation constants of the test group versus the control group by performing T tests between the means and F tests between the standard deviations. The least squares estimates of the correlation constants from the test group were recommended in the guidelines, in place of the means, to gain accuracy. By these methods, the guidelines used by the patients with good glycemic control are made available for all patients.ResultsWith use of the AIM system, the TDD for continuous subcutaneous insulin infusion = 0.24 * BWlb; basal insulin = 0.47 * TDD; CF = 1,700/TDD; and CIR = 2.8 * BWlb/TDD.ConclusionThree mathematical models for CIR are presented, with a rationale for supporting one of them (the AIM model). This model, together with 3 related AIM models, when provided with statistically correlated constants, constitutes the AIM system of guidelines, a consistent and convenient means of estimating insulin-dosing variables for patients with type 1 diabetes. (Endocr Pract. 2008;14:1095-1101)     

A Bridge to Insulin Pump Therapy: Twice-Daily Regimen with NPH and Detemir Insulins During Initial Treatment of Youth with Type 1 Diabetes Mellitus

ObjectiveTo describe clinical outcomes in youth with new-onset type 1 diabetes mellitus (TlDM) treated with a modified, twice-daily regimen of a mixture of NPH insulin and rapid-acting insulin analogue at breakfast and separate injections of rapid-acting insulin analogue and insulin detemir at dinner.MethodsOur clinic database was used to describe changes in insulin doses, hemoglobin A_1c (A1C) levels, and frequency of severe hypoglycemia during the first year of therapy in young patients with T1DM diagnosed between September 2006 and April 2009. Data are presented as median values (25%, 75%).ResultsOverall, 108 patients (62 girls; mean age, 10.0 ± 0.4 years) were eligible for inclusion. Total daily insulin doses at 3, 6, and 12 months were 0.6 (0.4, 0.8), 0.7 (0.4, 0.9), and 0.8 (0.6, 0.9) U/kg, respectively. A1C levels were 9.8% (8.5%, 10.8%) at 2 weeks (baseline). Of the 108 patients, 19 had switched to insulin pump therapy by 3 months and 49 had switched by 12 months after initial diagnosis of T1DM. The 49 pump-treated patients had an A1C of 6.9% (6.6%, 7.3%), whereas the 59 injection- treated patients had an A1C of 7.2% (6.7%, 7.7%) by 12 months. There were only 6 severe hypoglycemic events in 5 patients; none occurred during the first 3 months, none occurred during the night, and all occurred in patients receiving insulin injection treatment.ConclusionA twice-daily insulin regimen that uses insulin detemir for overnight basal replacement and morning NPH insulin to avoid lunch and afternoon snack doses is an effective initial treatment for young patients with new-onset T1DM that can provide a smooth transition to intensive basal/bolus insulin pump therapy. (Endocr Pract. 2011;17:862-866)     

Clinical Use of Liraglutide in Type 2 Diabetes and its Effects on Cardiovascular Risk Factors

ObjectiveTo assess whether liraglutide, a glucagonlike peptide-1 receptor agonist, has cardioprotective properties in addition to its glycemic effects.MethodsWe performed a retrospective analysis of medical records of 110 obese patients with type 2 diabetes mellitus treated with liraglutide for at least 6 months between March 2010 and April 2011 at our tertiary care referral center. The variables analyzed were body mass index, hemoglobin A_1c (A1C), systolic blood pressure (SBP), plasma C-reactive protein (CRP) concentrations, and serum lipids.ResultsIn our overall study cohort, we noted a reduction in mean weight from 120 ± 5 kg to 115 ± 3 kg and a decrease in mean A1C from 7.8% ± 0.6% to 7.2% ± 0.2%. The mean triglyceride concentration decreased from 173 ± 19 mg/dL to 151 ± 15 mg/dL, the mean SBP was reduced from 132 ± 6 mm Hg to 125 ± 4 mm Hg, and the mean CRP concentration declined from 4.7 ± 0.8 mg/L to 3.2 ± 0.4 mg/L after treatment with liraglutide for a minimal duration of 6 months and a mean duration of 7.5 months (for all the foregoing changes, P < .05).These variables decreased whether these patients were previously treated with orally administered hypoglycemic agents alone or in combination with insulin or exenatide.ConclusionOur findings in a clinical practice show that liraglutide is a potent antidiabetes drug, whether given in combination with orally administered agents or insulin or as a substitution for exenatide. It lowers body weight, A1C levels, SBP, and CRP and triglyceride concentrations. (Endocr Pract. 2012;18:140-145)     

Effect of Gluten-FREE Diet on Metabolic Control and Anthropometric Parameters in Type 1 Diabetes with Subclinical Celiac Disease: A Randomized Controlled Trial

Objective: It is unclear whether the institution of gluten-free diet (GFD) is beneficial in patients with type 1 diabetes (T1DM) and subclinical celiac disease (CD). Our primary objective was to evaluate the effect of GFD on the frequency of hypoglycemia, in patients with T1DM and subclinical CD. Our secondary objective was to investigate the effect of GFD on height, weight, glycosylated hemoglobin (HbA1c), insulin dose requirement, and bone mineral homeostasis.Methods: We carried out a prospective open label randomized controlled trial (RCT). Patients with T1DM and subclinical CD were randomized to receive GFD or a normal diet for 1 year. The primary outcome was the frequency of hypoglycemic episodes (blood glucose <70 mg/dL) measured by self-monitoring of blood glucose (SMBG) at the sixth month of the study in the 2 groups.Results: Screening for CD was carried out in 320 T1DM patients. Thirty eligible patients were randomized to receive GFD (n = 15) or a normal diet (n = 15). The mean number of hypoglycemic episodes/month recorded by SMBG and the mean time spent in hypoglycemia measured by CGM (minutes) in the GFD group versus the non-GFD group at six months was 2.3 minutes versus 3.4 minutes (P = .5) and 124.1 minutes versus 356.9 minutes (P = .1), respectively. The mean number of hypoglycemic episodes/month significantly declined in the GFD group (3.5 episodes at baseline versus 2.3 episodes at the sixth month; P = .03). The mean HbA1c declined by 0.73% in the GFD group and rose by 0.99% in non-GFD group at study completion.Conclusion: This is the first RCT to assess the effect of GFD in T1DM and subclinical CD. A trend towards a decrease in hypoglycemic episodes and better glycemic control was seen in patients receiving GFD.Abbreviations: BMC = bone mineral content; BMI = body mass index; CD = celiac disease; CGM = continuous glucose monitoring; GFD = gluten-free diet; Hb = hemoglobin; HbA1c = glycosylated hemoglobin; iPTH = intact parathyroid hormone; RCT = randomized controlled trial; SMBG = self-monitoring of blood glucose; T1DM = type 1 diabetes mellitus; tTG-IgA = tissue transglutaminase immunoglobulin A     

Evaluation,Medical Therapy,and Course of Adult Persistent Hyperinsulinemic Hypoglycemia After Roux-En-Y Gastric Bypass Surgery: A Case Series

ObjectiveTo describe the evaluation and treatment of hyperinsulinemic hypoglycemia in adults who had undergone gastric bypass surgery. A small number of patients who undergo Roux-en-Y bypass surgery develop postprandial hypoglycemia in the absence of dumping. In some cases, such patients have been treated with pancreatectomy.MethodsWe report the demographics, diagnostic results, response to medical therapy, and subsequent course of 6 referral patients with post–Roux-en-Y gastric bypass hypoglycemia.ResultsCharacteristic clinical and metabolic parameters consistent with hyperinsulinemic hypoglycemia were identified. Parameters were similar for both spontaneous and glucose-challenge-induced hypoglycemia. In the context of exclusively postprandial symptoms, simultaneous glucose ≤ 55 mg/dL, insulin ≥ 17 μU/mL, C peptide ≥ 3.0 ng/mL, and insulin to glucose ratio > 0.3 were associated with Roux-en-Y gastric bypass hyperinsulinemic hypoglycemia. Five of 6 patients improved on therapy consisting of dietary modification plus either calcium channel blockade, acarbose, or both. Two patients have remained on therapy for 12 to 15 months. The nonresponder was atypical and had had hypoglycemic events for several decades. Three treated patients were subsequently observed to have undergone partial or complete remission from hypoglycemic episodes after 2 to 37 months of therapy. None of the 6 have undergone pancreatectomy, and none have evidence of insulinoma. Invasive diagnostic procedures were of limited utility.ConclusionIn a subset of patients with post–Roux-en-Y gastric bypass hyperinsulinemic hypoglycemia, medical management can be efficacious and an alternative to partial pancreatectomy. In some cases, the disorder remits spontaneously. (Endocr Pract. 2015;21:237-246)     

Optimizing Hospital Use of Intravenous Insulin Therapy: Improved Management of Hyperglycemia and Error Reduction With a New Nomogram

ObjectiveTo assess the efficacy and safety of intravenous (IV) insulin administration with use of our institution’s old protocol (pre-nomogram phase) as compared with our new insulin nomogram (post-nomogram phase), which titrates insulin dose based on the rate of change of plasma glucose values and uses multipliers to determine the new insulin infusion rate.MethodsHospitalized adults receiving an IV insulin infusion in our tertiary care medical center were enrolled in this study after informed consent was obtained. The study was an observational analysis conducted before and after implementation of the new insulin infusion nomo-gram. Measurements included episodes of hypoglycemia and incidence of the following errors in the insulin infusion process: (1) episodes of documented failure to increase insulin infusion rate despite persistent hyper-glycemia and (2) number of times the IV infusion was stopped without subcutaneous administration of insulin.ResultsOverall, 66 patients were analyzed (38 in the pre-nomogram phase and 28 in the post-nomogram phase). The new nomogram reduced by nearly 3-fold (from 0.89 ± 0.68 to 0.36 ± 0.49 occurrence per patient per 24 hours; P < 0.001) the mean incidence of failure to give insulin subcutaneously before discontinuation of IV insulin infusion. Moreover, the nomogram nearly eliminated the error of caregiver nonresponsiveness to persistent hyperglycemia: mean incidence 0.39 ± 0.65 occurrence per patient per 24 hours before implementation of the new nomogram versus 0.02 ± 0.09 afterward (P < 0.002). There was no statistically significant difference in episodes of hypoglycemia between the 2 study groups.ConclusionSafe IV administration of insulin through error prevention is essential. Implementation of a new IV insulin infusion nomogram, which adjusts insulin infusion using multipliers, reduces errors and improves glycemic control without increasing hypoglycemic episodes. (Endocr Pract. 2005;11:240-253)     

Efficacy and Safety of Analog Insulin in Comparison With Human Insulin for Hyperglycemia in Hospitalized Patients With Acute Stroke: A Randomized,Open-Label,Single-Center Trial

ObjectiveTo assess the efficacy and safety of analog insulins in comparison with human insulins for hyperglycemia in hospitalized patients with acute stroke.MethodsIn this single-center, open-label, randomized trial, 102 patients (age 59.4 ± 11.7 years, 54 women) admitted with acute stroke (52 ischemic, 50 hemorrhagic) and hyperglycemia were assigned to analog insulin (n = 52) or human insulin (n = 50) group during February to June 2021. Insulin was initiated and titrated according to the predefined standard protocol. The capillary blood glucose (BG) level was monitored by standardized glucometers. The primary outcomes were mean daily BG and the number of hypoglycemic events.ResultsBetween the 2 treatment groups, there was no significant difference in the mean daily BG (P >.05 for all days) or in the frequency of hypoglycemic episodes (P =.727). Four participants experienced severe hypoglycemia; all were receiving human insulin (P =.054). In the analog insulin group, there was a tendency toward lower daily total requirement for insulin (P =.053). The difference in bolus insulin dose was significantly lower in the analog insulin group (P =.029), but the difference in basal insulin dose was similar (P =.167). Between the 2 groups, there were no significant differences in the hospital mortality rate, modified Rankin Scale score on outcome, or length of hospital stay (P =.729,.658, and.918, respectively).ConclusionHospitalized patients acute stroke and hyperglycemia exhibited similar mean BG but a trend of lower incidence of severe hypoglycemia when treated with analog insulins in comparison with human insulin.