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)     

Rapid-Acting Insulin Analogues in Basal-Bolus Regimens in Type 1 Diabetes Mellitus

ObjectiveTo compare rapid-acting insulin analogues with regular human insulin in terms of hemoglobin A_1c, hypoglycemia, and insulin dose when used in a basal-bolus regimen in patients with type 1 diabetes mellitus.MethodsMEDLINE and congress proceedings were searched for randomized controlled trials comparing pran- dial insulins in a basal-bolus regimen in adults or children/ adolescents with type 1 diabetes. Studies in pregnancy, ob- servational studies, studies that compared premixed insulin or continuous subcutaneous insulin infusion/insulin pumps, and studies where the basal insulin was also changed were excluded. Only studies reporting baseline-endpoint change in insulin dose, or baseline and/or endpoint values, were included.ResultsTwenty-eight studies were identified (insulin glulisine, 4; insulin aspart, 7; insulin lispro, 17). Twenty- five studies compared a rapid-acting insulin analogue with regular human insulin, and 3 trials compared 2 rapid-acting insulin analogues. Overall, rapid-acting insulin analogues in a basal-bolus regimen provided similar or greater im- provements in glycemic control than regular human insulin at similar insulin doses, as well as a lower incidence of hypoglycemia.ConclusionsResults of the studies identified in this literature review indicate that a basal-bolus regimen with prandial rapid-acting insulin analogue provides advan- tages over basal-bolus regimens using prandial regular hu- man insulin, providing improvements in glycemic control comparable to those obtained with regular human insulin, as well as a lower incidence of hypoglycemia. (Endocr Pract. 2010;16:486-505)     

Real-World Insulin Treatment Persistence among Patients with Type 2 Diabetes

ObjectiveTo evaluate real-world treatment persistence among patients with type 2 diabetes mellitus (T2DM) initiating treatment with insulin.MethodsPatient-level data were pooled from 3 previously published observational retrospective studies evaluating patients with T2DM who were previously on oral antidiabetic drugs (OADs) and initiated with a basal analog insulin (insulin glargine or insulin detemir). Treatment persistence was defined as remaining on the study drug during the 1-year follow-up period without discontinuation or switching after study drug initiation. Analyses were conducted to identify baseline factors associated with persistence with insulin therapy and to estimate the association between insulin treatment persistence and patients’ clinical and economic outcomes during the follow-up period.ResultsA total of 4,804 patients with T2DM (insulin glargine: n = 4,172, insulin detemir: n = 632) were included. The average insulin persistence rate over the 1-year follow-up period was 65.0%. A significantly higher persistence rate was associated with older age, initiation with insulin glargine using either disposable pens or vial-and-syringe, and with baseline exenatide or sitagliptin use. Higher insulin treatment persistence was also associated with lower hemoglobin A_1c (A1C) at follow-up, a greater reduction in A1C from baseline, and lower health care utilization.ConclusionIn real-world settings, treatment persistence among patients with T2DM initiating basal insulin is influenced by the type of insulin and patient factors. Greater insulin treatment persistence is linked to improved clinical outcomes and reduced health care utilization. (Endocr Pract. 2014;20:52-61)     

门冬胰岛素、地特胰岛素、甘精胰岛素分别联合二甲双胍对糖尿病孕妇妊娠结局的影响

摘要 目的：探究门冬胰岛素、地特胰岛素、甘精胰岛素分别联合二甲双胍对糖尿病孕妇妊娠结局的影响。方法：随机抽取本院400例妊娠期糖尿病产妇为研究对象，按照简单随机法分为对照组（n=100例）、试验A组（n=100例）、试验B组（n=100例）和试验C组（n=100例）。对照组采用口服二甲双胍治疗，试验A、B、C组，分别采用门冬胰岛素、地特胰岛素、甘精胰岛素联合二甲双胍治疗。对比四组产妇的分娩方式，各产程时间，体重指数（BMI）、随机血糖、内脂素、脂联素的水平，妊娠并发症发生率，新生儿结局。结果：试验A、B、C组的自然分娩率均高于对照组（P<0.05），且试验A组的自然分娩率均高于试验B组、试验C组（P<0.05），试验B组、试验C组的自然分娩率对比无差异（P>0.05）；对照组、试验A、B、C组自然分娩产妇的第一产程、第二产程、第三产程时间对比无差异（P>0.05）；试验A、B、C组的BMI指数、随机血糖、内脂素、脂联素的水平均低于对照组（P<0.05），且试验A组的BMI指数、随机血糖、内脂素、脂联素的水平均低于试验B组、试验C组（P<0.05），试验B组、试验C组的BMI指数、随机血糖、内脂素、脂联素的水平对比无差异（P>0.05）；试验A、B、C组的妊娠并发症发生率均低于对照组（P<0.05），且试验A组的妊娠并发症发生率低于试验B组、试验C组（P<0.05），试验B组、试验C组的妊娠并发症发生率对比无差异（P>0.05）；试验A、B、C组的新生儿不良结局发生率均低于对照组（P<0.05），且试验A组的新生儿不良结局发生率低于试验B组、试验C组（P<0.05），试验B组、试验C组的新生儿不良结局发生率对比无差异（P>0.05）。结论：门冬胰岛素、地特胰岛素、甘精胰岛素分别联合二甲双胍均能够提高糖尿病孕妇妊娠的自然分娩率，降低BMI指数、随机血糖、内脂素、脂联素的水平，降低妊娠并发症发生率，改良新生儿不良结局，其中门冬胰岛素的疗效最好，具有较强的临床推广价值。     

Impact of Prandial Plus Basal vs Basal Insulin on Glycemic Variability in Type 2 Diabetic Patients

ObjectiveTo determine whether metformin-treated patients with type 2 diabetes given an analogue mixture of basal and rapid-acting insulins (insulin lispro protamine suspension plus insulin lispro) would have less glycemic variability than patients given basal insulin glargine.MethodsTwo post hoc analyses were used to compare 7-point blood glucose profiles from 3 published studies comparing basal plus prandial premixed insulin lispro mixtures with insulin glargine in metformin-treated patients with type 2 diabetes. Glycemic variability indices used included standard deviation of mean daily blood glucose, coefficient of variation, M-value, mean amplitude of glycemic excursion, and J-index.ResultsPatients on the twice-daily insulin lispro mix 75/25 (75% insulin lispro protamine suspension/25% insulin lispro) plus metformin regimen had significantly lower standard deviation, M-value, and J-index than patients on the insulin glargine plus metformin regimen, but not lower coefficient of variation or mean amplitude of glycemic excursion. Patients on the 3 times daily insulin lispro mix 50/50 (50% insulin lispro protamine suspension/50% insulin lispro) plus metformin regimen had significantly lower values for all 5 indices than patients on the insulin glargine plus metformin regimen.ConclusionUse of basal plus prandial insulin lispro mixtures at 2 or 3 meals was associated with lower glycemic variability in metformin-treated patients with type 2 diabetes. (Endocr Pract. 2009;15:343-348)     

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)     

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)     

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)     

Basal Insulin Degludec and Glycemic Control Compared to Aspart Via Insulin Pump in Type 1 Diabetes (BIGLEAP): A Single-Center,Open-Label,Randomized, Crossover Trial

ObjectiveWe compared the efficacy of the second-generation basal insulin degludec (IDeg) to that of insulin aspart via pump using continuous glucose monitoring in patients with well-controlled type 1 diabetes.MethodsIn this 40-week, single-center, randomized, crossover-controlled trial, adults with well-controlled type 1 diabetes (hemoglobin A1C of <7.5% [<58 mmol/mol]) (N = 52) who were using an insulin pump and continuous glucose monitoring were randomized to 1 of 2 treatments for a 20-week period: a single daily injection of IDeg with bolus aspart via pump or a continuous subcutaneous insulin infusion (CSII) with aspart, followed by crossover to the other treatment. The primary endpoint was time in range (70-180 mg/dL) during the final 2 weeks of each treatment period.ResultsFifty-two patients were randomized and completed both treatment periods. The time in range for IDeg and CSII was 71.5% and 70.9%, respectively (P = .553). The time in level 1 hypoglycemia for the 24-hour period with IDeg and CSII was 2.19% and 1.75%, respectively (P = .065). The time in level 2 hypoglycemia for the 24-hour period with IDeg and CSII was 0.355% and 0.271%, respectively (P = .212), and the nocturnal period was 0.330% and 0.381%, respectively (P = .639). The mean standard deviation of blood glucose levels for the 24-hour period for IDeg and CSII was 52.4 mg/dL and 51.0 mg/dL, respectively (P = .294). The final hemoglobin A1C level for each treatment was 7.04% (53 mmol/mol) with IDeg, and 6.95% (52 mmol/mol) with CSII (P = .288). Adverse events were similar between treatments.ConclusionWe observed similar glycemic control between IDeg and insulin aspart via CSII for basal insulin coverage in patients with well-controlled type 1 diabetes.     

Impact of Race/Ethnicity on the Efficacy and Safety of Commonly used Insulin Regimens: A Post HOC Analysis of Clinical Trials in Type 2 Diabetes Mellitus

ObjectiveTo explore the impact of race/ethnicity on the efficacy and safety of commonly used insulin regimens in patients with type 2 diabetes mellitus.MethodsIn this post hoc analysis, pooled data from 11 multinational clinical trials involving 1455 patients with type 2 diabetes were used to compare specific insulin treatments in Latino/Hispanic, Asian, African-descent, and Caucasian patients. Insulin treatments included once daily insulin glargine or neutral protamine Hagedorn (BASAL), insulin lispro mix 75/25 twice daily (LMBID), or insulin lispro mix 50/50 three times daily (LMTID).ResultsRace/ethnicity was associated with significant outcome differences for each of the insulin regimens. BASAL therapy was associated with greater improvement in several measures of glycemic control among Latino/Hispanic patients compared with Caucasian patients (lower end point hemoglobin A1c, greater reduction in hemoglobin A1c from baseline, and a larger proportion of patients achieving hemoglobin A1c level < 7%). In contrast, LMBID therapy was associated with higher end point hemoglobin A_1c and a smaller decrease in hemoglobin A_1c from baseline in Latino/Hispanic and Asian patients than in Caucasian patients. Furthermore, fewer Asian patients attained a hemoglobin A_1c level < 7% than did Caucasians patients. For LMTID therapy, hemoglobin A_1c outcomes were comparable across patient groups. Fasting blood glucose and glycemic excursions varied among racial/ethnic groups for the 3 insulin regimens. Weight change was comparable among racial/ethnic groups in each insulin regimen. During treatment with LMTID, Asian patients experienced higher incidence and rate of severe hypoglycemia than Caucasian patients.ConclusionsLatino/Hispanic, Asian, and African-descent patients with type 2 diabetes show different metabolic responses to insulin therapy, dependent in part on insulin type and regimen intensity. (Endocr Pract. 2010: 818-828:pp)     

Fasting Versus Postprandial Hyperglycemia as a Treatment Target to Lower Elevated Hemoglobin A1C

Objective: Postprandial hyperglycemia (PPHG) may need addressing when glycemic control cannot be maintained in patients with type 2 diabetes mellitus. We investigated whether glycated hemoglobin A_1c (A_1c) levels ≥7.0% can indicate postprandial defects warranting prandial therapy after optimized basal insulin therapy.Methods: From 6 clinical trials of insulin glargine treatment, data were pooled from 496 patients with A_1c ≥7.0% after 24 weeks. Patient characteristics and clinical outcomes were summarized according to fasting plasma glucose (FPG) target achievement (<130 mg/dL), postprandial blood glucose (PPBG) levels, and PPBG increments (ΔPPBG). Basal and postprandial contributions to hyperglycemia were determined.Results: After 24 weeks of insulin glargine titration, A_1c change from baseline was greater in patients with FPG <130 mg/dL versus ≥130 mg/dL (-1.35% versus -1.11%, respectively; P = .0275), but with increased confirmed hypoglycemia rates (blood glucose <70 mg/dL; 4.06 events/patient-year versus 3.31 events/patient-year; P = .0170). However, increased severe hypoglycemia rates were observed in patients with FPG ≥130 mg/dL. At week 24, postprandial contributions to hyperglycemia increased (>60% regardless of PPBG). Patients with high FPG had lower, but substantial, relative postprandial contributions versus patients achieving FPG target. A similar pattern was observed according to whether patients had a ΔPPBG ≥50 mg/dL after any meal.Conclusion: After optimized basal insulin therapy, elevated A_1c is the most effective indicator of residual PPHG, regardless of existent FPG or PPBG. When confronted with an uncontrolled A_1c after reasonable titration of basal insulin, clinicians should be aware of probable postprandial contributions to hyperglycemia and consider prandial therapy.Abbreviations:A_1c = glycated hemoglobin A_1cAUC = area under the curveAUC_B = area under the curve (basal hyperglycemia)AUC_G = total area under the curve (total glucose)AUC_N = area under the curve (normal glycemic exposure)AUC_P = area under the curve (postprandial hyperglycemia)BHG = basal hyperglycemiaFBG = fasting blood glucoseFPG = fasting plasma glucoseGLP-1 = glucagon-like peptide 1HE = hyperglycemic exposureOADs = oral antidiabetes drugsPPBG = postprandial blood glucoseΔPPBG = change in postprandial blood glucosePPHG = postprandial hyperglycemiaSMBG = self-monitored blood glucoseT2DM = type 2 diabetes mellitus     

Patients Achieving Good Glycemic Control (HBA1c <7%) Experience A Lower Rate of Hypoglycemia With Insulin Degludec Than with Insulin Glargine: A Meta-Analysis of Phase 3A Trials

Objective: Meta-analysis to compare hypoglycemia rates of basal insulin degludec (IDeg) with insulin glargine (IGlar) in patients with diabetes achieving good glycemic control (hemoglobin A_1c [HbA_1c] <7% at end of trial).Methods: In a preplanned meta-analysis, patient data from 7 randomized, treat-to-target, 26- or 52-week trials in patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) who administered IDeg (n = 2,899) or IGlar (n = 1,431) once daily were analyzed. Using a negative binomial regression model, this meta-analysis compared hypoglycemia rates in patients achieving HbA_1c <7% at end of trial with IDeg (n = 1,347) and IGlar (n = 697).Results: In all trials, IDeg was noninferior to IGlar in HbA_1c reduction from baseline. At end of trial, 2,044 patients (T2DM, n = 1,661; T1DM, n = 383) achieved HbA_1c <7%. The overall confirmed hypoglycemia rate, defined as plasma glucose <56 mg/dL or severe hypoglycemia if requiring assistance, was significantly lower with IDeg versus IGlar (estimated rate ratio [ERR] IDeg:IGlar, 0.86; 95% confidence interval [CI], 0.76 to 0.98). The nocturnal confirmed hypoglycemia rate, defined as occurring between midnight and 6:00 am, was significantly lower with IDeg (ERR, 0.63; 95% CI, 0.52 to 0.77). In the maintenance period (16 weeks onward when average insulin dose and glycemic levels stabilized), the overall confirmed hypoglycemia rate was significantly lower (ERR, 0.79; 95% CI, 0.68 to 0.92) and the nocturnal confirmed hypoglycemia rate was significantly lower (ERR, 0.57; 95% CI, 0.45 to 0.72) with IDeg versus IGlar.Conclusion: Patients with T1DM and T2DM achieved HbA_1c <7% with significantly lower rates of overall and nocturnal confirmed hypoglycemia with IDeg versus IGlar. The lower hypoglycemia rate with IDeg was more pronounced in the maintenance period.Abbreviations: ERR = estimated rate ratio; HbA_1c = hemoglobin A_1c; IDeg = insulin degludec; IGlar = insulin glargine; NPH = Neutral Protamine Hagedorn; PG = plasma glucose; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus     

A Stepwise Approach to Insulin Therapy in Patients with Type 2 Diabetes Mellitus and Basal Insulin Treatment Failure

ObjectiveTo determine whether 1 or 2 preprandial injections before the meals of greatest glycemic impact can be as effective as 3 preprandial injections in patients with type 2 diabetes mellitus and basal insulin treatment failure.MethodsThis was an open-label, parallel-group, 1:1:1 randomized study of adults with type 2 diabetes mellitus on oral antidiabetic drugs with glycated hemoglobin (A1C) levels of 8.0% or greater. After a 14week run-in with insulin glargine, patients with an A1C level greater than 7.0% were randomly assigned to 1, 2, or 3 time(s) daily insulin glulisine for 24 weeks. Changes in A1C from randomization to study end; percentage of patients achieving an A1C level less than 7.0%; changes in A1C, fasting glucose concentrations, and weight at individual study points; and safety (adverse events and hypoglycemia) were assessed throughout the study.ResultsThree hundred forty-three of 631 patients (54%) completing the run-in phase with insulin glargine were randomly assigned to treatment arms. During the randomization phase, A1C reductions with insulin glulisine once or twice daily were noninferior to insulin glulisine 3 times daily (confidence intervals: -0.39 to 0.36 and -0.30 to 0.43; P > .5 for both). However, more patients met the target A1C with 3 preprandial injections (46 [46%]) than with 2 injections (34 [33%]) or 1 injection (30 [30%]). Severe hypoglycemia occurred in twice as many patients receiving 3 preprandial injections (16%) compared with those receiving 2 injections (8%) and 1 injection (7%), but these differences did not reach significance.ConclusionThis study provides evidence that initiation of prandial insulin in a simplified stepwise approach is an effective alternative to the current routine 3 preprandial injection basal-bolus approach. (Endocr Pract. 2011;17:395-403)     

Outcomes Associated With Insulin Therapy Disruption After Hospital Discharge Among Patients with Type 2 Diabetes Mellitus who Had Used Insulin Before and During Hospitalization

ObjectiveTo evaluate outcomes associated with insulin therapy disruption after hospital discharge in patients with type 2 diabetes mellitus who had used insulin before and during hospitalization.MethodsIn this observational, retrospective analysis of medical records obtained from a coordinated health system in the United States, patients with type 2 diabetes mellitus who had used insulin 30 days before and during hospitalization were included. Clinical and cost outcomes were compared between patients who continued insulin therapy and those who had disrupted insulin therapy after hospital discharge.ResultsIn total, 2160 records were analyzed (851 patients with continued insulin therapy and 1309 patients with disrupted insulin therapy). Mean baseline glycated hemoglobin A_1c levels were 8.56% and 7.73% in patients who continued insulin therapy and patients who disrupted insulin therapy, respectively (P <.001), suggesting that patients who discontinued insulin therapy had better glycemic control at baseline. Continued insulin therapy was associated with an expected greater reduction in glycated hemoglobin A_1c (P <.001); similar hypoglycemia rates; lower risks of all-cause hospital readmission, diabetesrelated readmission, and all-cause emergency department visits; and improved survival. Continued insulin therapy was associated with $3432 lower total medical service costs than disrupted therapy over the 6-month postdischarge period.ConclusionEnsuring adherence to insulin therapy in patients who require insulin therapy after hospitalization should be a priority for postdischarge patient care programs. However, the clinical implications of this study are limited by the fact that it could not be determined whether all patients required insulin therapy after hospital discharge. (Endocr Pract. 2012;18:651-659)     

Ethnic disparity in hemoglobin A1c levels among normoglycemic offspring of parents with type 2 diabetes mellitus

ObjectiveTo investigate the racial/ethnic disparities in hemoglobin A_1c levels among nondiabetic persons with similar parental history of type 2 diabetes mellitus.MethodsWe studied a community-based sample of adult offspring of parents with type 2 diabetes mellitus. Measurements included anthropometry, hematology assessments, serial fasting plasma glucose, oral glucose tolerance testing, plasma insulin, hemoglobin A_1c, insulin sensitivity, and b-cell function, using a homeostasis model assessment.ResultsThe study included 302 participants (135 white, 167 black). Compared with white participants, black participants had lower fasting plasma glucose levels (91.9 ± 0.51 mg/dL vs 93.6 ± 0.50 mg/dL, P = .015), lower area under the curve of plasma glucose during oral glucose tolerance testing (P = <.001), higher body mass index (31.1 ± 0.61 kg/m² vs 28.5 ± 0.57 kg/m², P = <.001), and similar insulin sensitivity and b-cell function. Hemoglobin A_1c was higher in black participants than in white participants (5.68 ± 0.033% vs 5.45 ± 0.028%, P <.001). The absolute black-white difference in hemoglobin A_1c level of approximately 0.22% persisted after adjusting for age, hemoglobin, hematocrit, body mass index, waist circumference, fasting plasma glucose, glucose area under the curve, and other covariates.ConclusionsAmong healthy offspring of parents with type 2 diabetes mellitus in this study, African American participants had higher hemoglobin A_1c levels than white participants after adjusting for age, adiposity, blood glucose, and known variables. Thus, plasma glucose level is more valid than hemoglobin A_1c for diagnosing prediabetes or diabetes in black persons. (Endocr Pract. 2012; 18:356-362)     

Effects of Insulin Detemir and NPH Insulin on Body Weight and Appetite-Regulating Brain Regions in Human Type 1 Diabetes: A Randomized Controlled Trial

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00626080","term_id":"NCT00626080"}}NCT00626080.     

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)     

Concomitant Oral Antihyperglycemic Agent Use and Associated Treatment Outcomes After Initiation of Insulin Therapy

ObjectiveTo compare outcomes in patients with type 2 diabetes initiating insulin lispro mix 75/25 (75% insulin lispro protamine suspension and 25% lispro) or insulin glargine therapy, stratified by baseline oral antihyperglycemic agent (OHA) use.MethodsWe performed a post hoc analysis of 6-month data from the DURABLE clinical trial, which enrolled patients with hemoglobin A_1c (A1C) levels > 7.0% treated with 2 or more OHAs (metformin, sulfonylurea, and thiazolidinedione), and randomly assigned them to treatment with twice-daily insulin lispro 75/25 or oncedaily glargine.ResultsIn both insulin treatment groups, metformin/ thiazolidinedione-treated patients had significantly greater improvement in A1C levels (-2.19% to -2.36%), lower end point A1C values, and lower rates of occurrence of hypoglycemia in comparison with metformin/sulfonylurea-treated patients (all P < .05). Patients treated with sulfonylurea/thiazolidinedione or metformin/sulfonylurea/thiazolidinedione did not differ significantly from metformin/sulfonylurea-treated patients in A1C change (-1.56% to -1.84%) or rates of occurrence of hypoglycemia.ConclusionIn these post hoc analyses, patients with type 2 diabetes initiating premixed or basal insulin therapy and treated concomitantly with the OHA combination of metformin/thiazolidinedione at baseline demonstrated significantly greater A1C improvement with less hypoglycemia in comparison with patients treated with metformin/ sulfonylurea. (Endocr Pract. 2011;17:563-567)     

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)