Comparison of breakfast and bedtime administration of insulin glargine in children and adolescents with Type 1 diabetes

OBJECTIVE: The purpose of this study was to evaluate the effect of administration time of insulin glargine (IG) on glycemic control in children and adolescents with Type 1 diabetes. MATERIALS AND METHODS: A total of 31 children and adolescents (15 F and 16 M) with Type 1 diabetes on intensive therapy (bedtime NPH and premeal insulin aspart) were randomized to receive once-daily IG either at breakfast (breakfast group, n=15) or bedtime (bedtime group, n=16) while continuing insulin aspart premeals for 6 months. Blood glucose levels were measured fasting, preprandially and bedtime. Total daily insulin dose (TDD), body mass index (BMI), glycosylated hemoglobin (HbA(1c)), and frequency of hypoglycemia in the preceding 3 months were assessed at recruitment, third month and sixth month. RESULTS: The dose of IG, TDD, and fasting blood glucose levels were similar in both groups during the study period. The only significant difference in blood glucose levels between breakfast and bedtime groups was found for dinnertime at 6 months (135+/-26mg/dl versus 161+/-33mg/dl, respectively, p=0.035). In the breakfast group, the mean HbA(1c) level was significantly lower than that of baseline at month 6 (9.4+/-2.5% versus 8.0+/-0.9%, respectively, p=0.022), whereas there was no significant change in the bedtime group (9.2+/-2.1% versus 8.9+/-2.2%, respectively). The frequency of hypoglycemia was lower with IG than NPH (2.7+/-2.8/6 months versus 6.4+/-6.7/6 months, respectively, p=0.008). CONCLUSIONS: Once-daily IG at breakfast in children and adolescents with Type 1 diabetes on intensive therapy is more efficacious than bedtime administration to improve metabolic control. Also, the number of hypoglycaemic events decreased with both breakfast and bedtime administrations of IG.     

Evaluation of the superiority of insulin glargine as basal insulin replacement by continuous glucose monitoring system

To evaluate the superiority of insulin glargine as basal insulin replacement by continuous glucose monitoring system (CGMS). Twenty-four patients with type 2 diabetes mellitus (T2DM) whose blood glucose was not well controlled with sulphanylureas were enrolled. At first, they were treated with extended-release glipizide (glucotrol XL) 5mg/d before breakfast for 2 weeks, then randomized to combination treatment with glargine (16 patients) or NPH (8 patients) and treated for 12 weeks. CGMS were carried in the second week after treatment with glucotrol XL, and in the 12th week after combination treatment. The data of CGMS showed: (1) When FPG were well controlled in both groups (glargine group versus NPH group: 6.0+/-1.0 mmol/L versus 5.8+/-1.3 mmol/L), the blood glucose level at 3:00 a.m. (5.1+/-0.9 mmol/L versus 4.2+/-0.8 mmol/L) were higher (P<0.05), TPG< or =3.0 mmol/L at night were lower (2.56+/-1.79 versus 5.88+/-1.96), and the rate of nocturnal hypoglycemia (1/16 versus 4/8) were less (P=0.028) in glargine group than those in NPH group. (2) CGMS showed that the daily blood glucose profile excursion were more smoother in glargine group than those in NPH group. In conclusion, it was confirmed with CGMS that compared with traditionally basal insulin replacement with NPH, the combination treatment with glargine injection at bedtime may be predominant for stabilizing the daily blood glucose profile excursion and decreasing the nocturnal hypoglycemia events incidence. So glargine may be a more ideal basal insulin replacement than NPH.     

Omitting breakfast and lunch after injection of different long-acting insulin preparations at bedtime: a prospective study in patients with type 2 diabetes

Aims/hypothesis  The aim of this prospective trial was to compare the effect of different long-acting insulin preparations injected at bedtime on glucose concentrations in patients with type 2 diabetes omitting breakfast and lunch the next day. Methods  Twenty patients (ten women) with type 2 diabetes who were on an intensified insulin therapy participated. Mean (±SD) age was 63 ± 10 years, diabetes duration 18 ± 9 years, BMI 32.5 ± 5 kg/m², and HbA_1c 7.3 ± 0.7%. Patients received neutral protamine Hagedorn (NPH) insulin, insulin detemir or insulin glargine for at least 2 months; doses were adjusted to achieve morning blood glucose levels of <7 mmol/l. At the end of the respective treatment period, the long-acting insulin was injected at bedtime (at 22:45 hours) as usual but patients refrained from breakfast and lunch the next day; glucose was measured by a continuous glucose monitoring system (CGMS). Results   Comparable glucose target ranges were reached at midnight (5.8 to 6.1 mmol/l) and at 07:00 hours (6.7 to 6.9 mmol/l) with all three insulin preparations, using mean doses of 29 ± 10 U (NPH insulin), 33 ± 13 U (insulin detemir), and 32 ± 12 U (insulin glargine). Glucose levels between midnight and 07:00 hours were not significantly different for the three insulin preparations. Symptomatic hypoglycaemia did not occur from 08:00 to 16:00 hours; glucose concentrations during this time were slightly lower with NPH insulin than with insulin detemir (p = 0.012) and insulin glargine (p = 0.049). Conclusions/interpretation  Following bedtime injection of NPH insulin or of the analogues insulin detemir or insulin glargine, fasting glucose <7 mmol/l was achieved in the morning, without subsequent hypoglycaemia when participants continued to fast during the day.     

70岁以上糖尿病患者应用甘精胰岛素的疗效和安全性观察

目的比较甘精胰岛素和预混胰岛素两种方案的治疗效果和低血糖发生情况。以便寻找出更加适合老年糖尿病患者的方便有效的治疗方案。方法选取曾在我科住院患者50例,年龄大于70岁,男性26例,女性24例,甘精组（25例）根据患者的生活习惯按每天早上7点或晚上9点皮下注射一次甘精胰岛素,预混组（25例）根据血糖值进行调整胰岛素用量,早餐及晚餐前30分钟皮下注射诺和灵30R,根据两组患者餐后血糖的情况,加用阿卡波糖和/或二甲双胍,出院后随访3个月观察血糖控制和低血糖情况。结果两组患者应用胰岛素治疗后,低血糖发生次数,甘精组明显低于预混组（P〈0.05）差异具有统计学意义。甘精组的胰岛素用量明显少于预混组（P〈0.001）差异具有统计学意义。结论单用口服降糖药不能使血糖达标时,加用甘精胰岛素或预混胰岛素治疗,均能明显降低血糖,甘精胰岛素与预混胰岛素相比用量少且低血糖的发生率低,更适合老年患者。     

Basal–Prandial Insulin Delivery in Type 2 Diabetes Mellitus via the V-Go?: A Novel Continuous Subcutaneous Infusion Device

Background

The V-Go™ is a once-daily disposable device that allows coverage of basal and prandial insulin requirements over a period of 24 hours. The aim of this proof-of-concept study was to evaluate the clinical functionality, safety, and pharmacodynamics of the V-Go delivering insulin aspart and redistributing a single basal dose of insulin glargine as a constant basal infusion supplemented with prandial insulin in subjects with type 2 diabetes mellitus.

Methods

In six subjects receiving once-daily subcutaneous (SC) injections of insulin glargine (≥15 U/day) with or without concomitant oral antidiabetic drugs, glargine was discontinued following a 3-day baseline phase. The V-Go was then applied to the lower abdomen of the subjects once daily for 7 days (days 1–3 inpatient, days 4–7 outpatient). Each V-Go provided a continuous 24-hour preset basal infusion rate of insulin aspart (0.6 U/h) and up to three daily prandial doses at mealtimes. Capillary blood glucose concentrations were measured at 11 time points per day during the baseline and inpatient phases and at 4 time points per day during the outpatient phase. Additionally, glucose profiles were measured continuously on all days.

Results

The V-Go was well tolerated and operated as anticipated. The mean ± SEM prestudy daily dose of SC insulin glargine was 33.3 ± 13.8 U; the mean daily total insulin aspart dose infused with the V-Go was 31.5 ± 7.5 and 32.3 ± 7.8 U for the inpatient and outpatient periods, respectively. Fasting blood glucose values were similar to those observed at baseline throughout the study, with nonsignificant (NS) reductions in readings collected during the outpatient phase before lunch (-35 ± 27 mg/dl) and before dinner (-38 ± 25 mg/dl). The 2-hour postprandial glucose trended lower from 231 to 195 mg/dl (NS) at breakfast, 234 to 166 mg/dl (NS) at lunch, and 222 to 171 mg/dl (NS) at dinner. Bedtime blood glucose decreased (mean change from baseline -52 ± 21 mg/dl; P = 0.0313), as did nighttime (3:00 AM) measurements (-20 ± 9 mg/dl; P = 0.0313). Overall glycemic control tended to improve, as shown by continuous glucose monitoring changing from 173 to 157 mg/dl (P = 0.063, NS) and 156 mg/dl (P = 0.219) during inpatient and outpatient periods, respectively. Glycemic variability assessed by the M value similarly tended to decrease from 33 ± 9 to 25 ± 4 (NS) and 21 ± 4 (NS) for inpatient and outpatient periods, respectively.

Conclusions

These first data suggest that use of the V-Go is an attractive alternative to SC insulin injection therapy because metabolic control appears to be maintained or even improved without increasing daily insulin doses.     

Adding insulin glargine vs. NPH insulin to metformin results in a more efficient postprandial β‐cell protection in individuals with type 2 diabetes

Aim: Postprandial release of intact proinsulin (IP) is an independent marker for β‐cell dysfunction in patients with type 2 diabetes. This open‐label, parallel‐group, two‐arm, pilot study compared the β‐cell protective effect of adding insulin glargine (GLA) vs. NPH insulin to ongoing metformin. Material and methods: Overall, 28 insulin‐naive type 2 diabetes subjects (mean ± SD age, 61.5 ± 6.7 years; diabetes duration, 9.8 ± 6.5 years; HbA1c, 7.1 ± 0.5%; BMI, 30.7 ± 4.3 kg/m²) treated with metformin and sulfonylurea were randomized to add once‐daily GLA or NPH at bedtime. At baseline and after 3 months, subjects received a standardized breakfast, lunch and dinner, with pre‐ and postprandial blood sampling to measure plasma IP, total insulin and blood glucose (BG). Results: Insulin dose after 3 months was comparable in both groups (GLA vs. NPH: 23.6 ± 13.4 vs. 23.3 ± 12.7; p = NS ). Both treatments significantly reduced fasting BG levels (GLA: 158 ± 19 to 121 ± 23 mg/dl; NPH: 156 ± 34 to 119 ± 29 mg/dl; both p < 0.01 vs. baseline). Fasting and postprandial BG levels did not differ between groups. IP levels decreased in both groups (p < 0.05 at all timepoints). Although IP release after breakfast did not differ between treatments, GLA induced a greater reduction in IP release after lunch (p = 0.08) and dinner (p = 0.04). Total plasma insulin levels did not differ between groups. Conclusions: Adding basal insulin to metformin reduces postprandial β‐cell load. While GLA and NPH had comparable effects at breakfast, GLA reduces β‐cell stress more effectively at dinner, and with a trend at lunch, most probably because of its longer lasting pharmacodynamic profile.     

甘精胰岛素与瑞格列奈联用治疗2型糖尿病的临床研究

目的 观察甘精胰岛素联合瑞格列奈治疗2型糖尿病临床疗效.方法 常规治疗糖尿病基础上,对照组早晚餐前30min注射诺和灵30R 0.3～1.0U·kg-1·d-1;观察组每餐前15min口服瑞格列奈1mg,3次/d,根据餐后2h血糖每3d调整瑞格列奈量,最大量为4mg,3次/d;每晚睡前注射甘精胰岛素,起始剂量为0.1U·kg-1·d-1,剂量均根据患者的病情进行个体化调整.治疗前后测定两组患者空腹血糖、早餐后2h血糖及糖化血红蛋白(HbA1c)水平;观察胰岛素用量、体质量和BMI、低血糖事件发生率及安全性指标.结果 观察组患者空腹血糖、早餐后2h血糖、胰岛素用量、体质量和BMI、低血糖事件发生明显改善,优于对照组,未见明显不良反应.两组总有效率比较,差异有统计学意义(P＜0.05).结论 甘精胰岛素联合瑞格列奈治疗2型糖尿病临床疗效良好,值得推广.     

Temporal and Geographic Patterns of Hypoglycemia among Hospitalized Patients with Diabetes Mellitus

Background

Hypoglycemia is often cited as a barrier to achieving inpatient glycemic targets. We sought to characterize hypoglycemic events in our institution by work-shift cycle and by specific treatment area.

Methods

Capillary (bedside) and blood (laboratory) glucose values of <70 mg/dl for patients with either a known diagnosis of diabetes or with evidence of hyperglycemia were abstracted from our laboratory database for hospitalizations between October 1, 2007, and February 3, 2008. Hypoglycemic events were analyzed by 12 h nursing work-shift cycles (day shift, 07:00 to 18:59; night shift, 19:00 to 06:59) and by the six medical, surgical, and intensive care areas in the hospital (designated areas 1 to 6).

Results

We identified 206 individual patients with either diabetes or hyperglycemia (mean age, 67 years; 56% men; 83% white) who had 423 hypoglycemic events. There were 78% more hypoglycemic events during the night shift (n = 271 events in 128 individual patients) than during the day shift (n = 152 events in 96 individual patients). Most of the night-shift hypoglycemic measurements were detected between 04:00 and 04:59 or 06:00 and 06:59. The mean hypoglycemic level was comparable between shifts (p = .79) and across the six inpatient areas. The number of hypoglycemic events per person increased with lengths of hospital stay >5 days. The prevalence of hypoglycemia varied across patient care areas within the hospital, with most (28%) detected in one area of the hospital.

Conclusion

There are temporal and geographic patterns in the occurrence of hypoglycemia among patients with diabetes or hyperglycemia in our hospital. Further study should focus on the reasons underlying these variations so that specific interventions can address the risk of hypoglycemia during peak times and places.     

Cleveland Clinic Cardiovascular Intensive Care Unit Insulin Conversion Protocol

Background

The importance of near-normal blood glucose in the immediate postoperative period is generally accepted and is best achieved in the perioperative period with a constant intravenous (IV) infusion of insulin. This requires intensive nursing only achievable in an intensive care unit (ICU) setting. Glucose management after transfer to a regular nursing floor (RNF) has not been studied systematically. In August 2006, the Cleveland Clinic began using long-acting insulin glargine as the insulin infusion was terminated in the ICU.

Methods

This prospective analysis examined all patients receiving IV insulin infusion after cardiothoracic surgery in a 1 month period. The analyses evaluated the safety and efficacy of a protocol using a transition to subcutaneous insulin glargine of 50% of the calculated 24 h requirement at the end of the ICU insulin infusion protocol in preparation for transfer to the RNF.

Results

Only 1 patient in 99 developed hypoglycemia, and no patient suffered severe hypoglycemia (glucose < 40 mg/dl), while the majority (70%) had euglycemia (glucose between 70 and 150 mg/dl).

Conclusions

This approach was both safe—as there was very little hypoglycemia (1 patient in 99)—and effective, as blood sugar was well controlled in most subjects. Efficacy for achieving euglycemia was 70%. Efficacy was likely reduced because of the upper limit of insulin glargine dosage imposed by some providers as a safety consideration. Although there was a physician option to override, the maximum protocol dose of 30 U was rarely exceeded, leading to inadequate dosing in some subjects who required high insulin infusion rates in the ICU.     

甘精胰岛素联合瑞格列奈治疗老年2型糖尿病患者的疗效与安全性

目的 观察甘精胰岛素注射液联合口服降糖药物瑞格列奈对老年2型糖尿病患者的血糖控制情况和低血糖的风险. 方法 选择口服降糖药物血糖控制不良的老年2型糖尿病患者64例,随机分为甘精胰岛素组(简称甘精组)和预混胰岛素组(诺和灵30R,简称预混组),每组各32例.甘精组在每天3餐前口服瑞格列奈的基础上,每晚22时注射甘精胰岛素1次;预混组每天早、晚餐前分别注射诺和灵30R预混胰岛素;根据空腹血糖及餐后血糖的水平,每3天调整瑞格列奈及胰岛素剂量,以空腹血糖<7.2 mmol/L,餐后血糖<10.0 mmol/L为治疗目标,共治疗16周,观察血糖控制和低血糖发生情况. 结果 治疗16周后两组的全天血糖谱和糖化血红蛋白(HbAlc)有明显下降(P<0.05),甘精组全天各时点血糖均值低于预混组,其中午餐后、晚餐后2 h血糖与预混组比较,差异有统计学意义(均为P<0.05),甘精组HbAlc值明显低于预混组(P<0.05);体质指数(BMI)甘精组无明显增加(P>0.05),预混组BMI较治疗前明显增加(P相似文献   

A comparison of bedtime insulin glargine with bedtime neutral protamine hagedorn insulin in patients with type 2 diabetes: subgroup analysis of patients taking once-daily insulin in a multicenter, randomized, parallel group study

BACKGROUND: Basal insulin is frequently administered once daily. This subgroup analysis of a multicenter, randomized, parallel study compared insulin glargine (Lantus Aventis Pharmaceuticals, Bridgewater, NJ) with neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes, evaluating only patients treated previously with once-daily NPH insulin. METHODS: Patients received bedtime insulin glargine or NPH insulin, with preprandial regular insulin. One hundred patients (mean age, 57.9 years; mean glycohemoglobin, 8.4%; mean fasting blood glucose, 167 mg/dL) were treated for up to 28 weeks. RESULTS: Patients treated with insulin glargine (n = 52) and NPH insulin (n = 48) achieved similar reductions from baseline in glycohemoglobin (-0.41% versus -0.46%) and fasting blood glucose (-22 mg/dL versus -22 mg/dL) at week 28. The proportion of patients reaching target fasting blood glucose (<120 mg/dL) at 28 weeks was 34.2% with insulin glargine and 24.4% with NPH insulin. Similar proportions of patients achieved glycohemoglobin less than 7% and less than 8% in both groups. Baseline and week-28 mean daily doses of insulin glargine (27.3 IU versus 36.4 IU) were similar to NPH insulin doses (25.5 IU versus 30.2 IU). However, significantly fewer patients reported one or more episodes of hypoglycemia with insulin glargine (46.2%) versus NPH insulin (60.4%; P < 0.05). Significantly fewer patients also reported one or more symptomatic episodes confirmed by blood glucose less than 50 mg/dL with insulin glargine (17.3%) versus NPH insulin (31.3%; P < 0.005). CONCLUSION: Bedtime insulin glargine is as effective as bedtime NPH insulin in improving glycemic control, with significantly less hypoglycemia.     

Artificial Pancreas Systems: Overnight Closed-Loop Insulin Delivery with Model Predictive Control: Assessment of Hypoglycemia and Hyperglycemia Risk Using Simulation Studies

Background

Hypoglycemia and hyperglycemia during closed-loop insulin delivery based on subcutaneous (SC) glucose sensing may arise due to (1) overdosing and underdosing of insulin by control algorithm and (2) difference between plasma glucose (PG) and sensor glucose, which may be transient (kinetics origin and sensor artifacts) or persistent (calibration error [CE]). Using in silico testing, we assessed hypoglycemia and hyperglycemia incidence during over-night closed loop. Additionally, a comparison was made against incidence observed experimentally during open-loop single-night in-clinic studies in young people with type 1 diabetes mellitus (T1DM) treated by continuous SC insulin infusion.

Methods

Simulation environment comprising 18 virtual subjects with T1DM was used to simulate overnight closed-loop study with a model predictive control (MPC) algorithm. A 15 h experiment started at 17:00 and ended at 08:00 the next day. Closed loop commenced at 21:00 and continued for 11 h. At 18:00, protocol included meal (50 g carbo-hydrates) accompanied by prandial insulin. The MPC algorithm advised on insulin infusion every 15 min. Sensor glucose was obtained by combining model-calculated noise-free interstitial glucose with experimentally derived tran-sient and persistent sensor artifacts associated with FreeStyle Navigator® (FSN). Transient artifacts were obtained from FSN sensor pairs worn by 58 subjects with T1DM over 194 nighttime periods. Persistent difference due to FSN CE was quantified from 585 FSN sensor insertions, yielding 1421 calibration sessions from 248 subjects with diabetes.

Results

Episodes of severe (PG ≤ 36 mg/dl) and significant (PG ≤ 45 mg/dl) hypoglycemia and significant hy-perglycemia (PG ≥ 300 mg/dl) were extracted from 18,000 simulated closed-loop nights. Severe hypoglycemia was not observed when FSN CE was less than 45%. Hypoglycemia and hyperglycemia incidence during open loop was assessed from 21 overnight studies in 17 young subjects with T1DM (8 males; 13.5 ± 3.6 years of age; body mass index 21.0 ± 4.0 kg/m2; duration diabetes 6.4 ± 4.1 years; hemoglobin A1c 8.5% ± 1.8%; mean ± standard deviation) participating in the Artificial Pancreas Project at Cambridge. Severe and significant hypoglycemia during simulated closed loop occurred 0.75 and 17.11 times per 100 person years compared to 1739 and 3479 times per 100 person years during experimental open loop, respectively. Signifi-cant hyperglycemia during closed loop and open loop occurred 75 and 15,654 times per 100 person years, respec-tively.

Conclusions

The incidence of severe and significant hypoglycemia reduced 2300- and 200-fold, respectively, during simu-lated overnight closed loop with MPC compared to that observed during open-loop overnight clinical studies in young subjects with T1DM. Hyperglycemia was 200 times less likely. Overnight closed loop with the FSN and the MPC algorithm is expected to reduce substantially the risk of hypoglycemia and hyperglycemia.     

A randomized multicentre trial of insulin glargine compared with NPH insulin in people with type 1 diabetes

BACKGROUND: To compare insulin glargine with NPH human insulin for basal insulin supply in adults with type 1 diabetes. METHODS: People with type 1 diabetes (n = 585), aged 17-77 years, were randomized to insulin glargine once daily at bedtime or NPH insulin either once- (at bedtime) or twice-daily (in the morning and at bedtime) according to their prior treatment regimen and followed for 28 weeks in an open-label, multicentre study. Both groups continued with pre-meal unmodified human insulin. RESULTS: There was no significant difference between the two insulins in change in glycated haemoglobin from baseline to endpoint (insulin glargine 0.21 +/- 0.05% (mean +/- standard error), NPH insulin 0.10 +/- 0.05%). At endpoint, self-monitored fasting blood glucose (FBG) had decreased similarly in each group (insulin glargine -1.17 +/- 0.12 mmol/L, NPH insulin -0.89 +/- 0.12 mmol/L; p = 0.07). However, people on >1 basal insulin injection per day prior to the study had a clinically relevant decrease in FBG on insulin glargine versus NPH insulin (insulin glargine -1.38 +/- 0.15 mmol/L, NPH insulin -0.72 +/- 0.15 mmol/L; p < 0.01). No significant differences in the number of people reporting >or=1 hypoglycaemic episode were found between the two groups, including severe and nocturnal hypoglycaemia. Insulin glargine was well tolerated, with a similar rate of local injection and systemic adverse events versus NPH insulin. CONCLUSIONS: A single, bedtime, subcutaneous dose of insulin glargine provided a level of glycaemic control at least as effective as NPH insulin, without an increased risk of hypoglycaemia.     

A 16-week open-label, multicenter pilot study assessing insulin pump therapy in patients with type 2 diabetes suboptimally controlled with multiple daily injections

Background

We assessed the efficacy, safety, and patient-reported outcomes (PROs) of insulin pump therapy in patients with type 2 diabetes mellitus (T2DM) who were suboptimally controlled with a multiple daily injection (MDI) regimen.

Methods

In this subanalysis of a 16-week multicenter study, 21 insulin-pump-naïve patients [age 57 ± 13 years, hemoglobin A1c (A1C) 8.4 ± 1.0%, body weight 98 ± 20 kg, total daily insulin dose 99 ± 65 U, mean ± standard deviation] treated at baseline with MDI therapy with or without oral antidiabetic agents discontinued all diabetes medications except metformin and initiated insulin pump therapy. Insulin was titrated to achieve the best possible glycemic control with the simplest possible dosing regimen. Outcome measures included A1C, fasting and postprandial glucose, body weight, incidence of hypoglycemia, and PROs.

Results

Glycemic control improved significantly after 16 weeks: A1C 7.3 ± 1.0% (−1.1 ± 1.2%, p < .001), fasting glucose 133 ± 33mg/dl (−32 ± 74 mg/dl, p < .005), and postprandial glucose 153 ± 35 mg/dl (−38 ± 46 mg/dl, p < .001). At week 16, the mean daily basal, bolus, and total insulin doses were 66 ± 36, 56 ± 40, and 122 ± 72 U (1.2 U/kg), respectively, and 90% of patients were treated with two or fewer daily basal rates. Body weight increased by 2.8 ± 2.6 kg (p < .001). Mild hypoglycemia was experienced by 81% of patients at least once during the course of the study with no episodes of severe hypoglycemia. There were significant improvements in PRO measures.

Conclusions

Insulin pump therapy using a relatively simple dosing regimen safely improved glucose control and PROs in patients with T2DM who were unable to achieve glycemic targets with MDI therapy. Controlled trials are needed to further assess the clinical benefits and cost-effectiveness of insulin pumps in this patient population.     

Efficacy of conversion from bedtime NPH insulin to morning insulin glargine in type 2 diabetic patients on basal-prandial insulin therapy

In normal subjects, approximately half of the daily insulin requirement constitutes basal insulin. We investigated whether increasing the dose of insulin glargine up to half of the total insulin requirement could lead to better glycemic control in type 2 diabetic patients who were treated on basal-prandial insulin therapy. A total of 62 patients with type 2 diabetes on mealtime rapid-acting insulin analogue and bedtime NPH were randomized to either continuation of bedtime NPH (n=31) or morning glargine (n=31) for 6 months while continuing the aspart/lispro at each meal. The two groups were matched for age, sex, diabetes duration, BMI, HbA(1C), endogenous insulin secretion, and proportion of numbers using aspart/lispro and using oral hypoglycemic agents. The dose of insulin glargine was increased by 2-4 units to meet the target fasting blood glucose, whereas the dose of NPH was principally unchanged as a control group. Mean HbA(1C) at baseline was similar between patients with glargine and NPH (7.2% versus 6.9%). The percentage of glargine dose increased significantly (31% at baseline to 48% at 6 months) without any significant changes in total insulin dose. Mean HbA(1C) at 3 months was 6.6% with glargine and 7.0% with NPH (P<0.0001, adjusted mean change between-treatment difference 0.6% [95% CI 0.3-0.9]), and the values at 6 months were 6.6% and 6.9%, respectively (P=0.007). Frequency of hypoglycemia did not differ between the groups. Increasing the dose of glargine without changing the total daily insulin dose resulted in significantly better glycemic control in type 2 diabetic patients on basal-prandial insulin therapy. Conversion from bedtime NPH to morning glargine appears efficacious with no increase in frequency of hypoglycemia.     

Comparison of pre-dinner regular versus pre-lunch NPH of a third insulin application in adolescents with type 1 diabetes from a Public Health Service

The majority of the type 1 Diabetes (DM1) patients are seen in Public Health Services. The management of these children, by several reasons, did not meet most of the standards for good diabetes control. In the present study we compare 2 different insulin treatment strategies in 53 uncontrolled DM1 adolescents despite a twice-a-day insulin regimen. A regimen: NPH + R before breakfast, R insulin before dinner and bedtime NPH. B regimen: NPH + R before breakfast and lunch and bedtime NPH. This was a 12-month open-label, randomized, clinical trial conducted in a Public Hospital. BMI (A: 23.4+/-3.5 Kg/m2 x B: 23.5+/-0.8 Kg/m2), average daily insulin dose (A: 1.04+/-0.28 U/Kg/d x B: 1.08+/-0.22 U/Kg/d) as well as the overall frequency of severe hypoglycemia (A: 9.4% x B: 7.5%) were similar in both groups during the study. However, HbA1c values at the end of the study were significantly lower in the B (9%) as compared to the A regimen (7,5%; p = 0.05). In conclusion, we have shown that breakfast and lunchtime NPH + R insulin plus bedtime NPH insulin is superior to pre-dinner R insulin plus breakfast and bedtime NPH insulin for overall glycemic control with similar weight status and comparable frequency of hypoglycemia. Thus, three times a day NPH insulin application is a feasible option for public service patients.     

The effect of extend bar containing uncooked cornstarch on night-time glycemic excursion in subjects with type 2 diabetes

The objective of this study was to determine the effects of ingesting a snack bar containing uncooked cornstarch (Extend Bar, Clinical Products, Limited, Key Biscayne, FL) on nocturnal glycemic excursion in 28 adults (ages 22-78 years) with type 2 diabetes mellitus (mean HbAlc 8.21+/-1.28%). Thirteen subjects were treated with oral agents, eight with a combination of insulin and oral agents, and seven with insulin alone. Subjects ingested the study bar (Extend Bar, containing 30 g of total carbohydrate, including 5 g of uncooked cornstarch, 3 g protein, and 3 g fat) for three evenings followed by a placebo bar for 3 evenings (30 g of total carbohydrate, 3 g protein, and 3 g fat), or vice versa. Pre-snack before bedtime, midnight and before breakfast finger stick blood glucose levels were compared to determine the incidence of hypoglycemia (<60 mg/dl), hyperglycemia (>250 mg/dl), and to calculate any differences in the group's mean blood glucose levels when ingesting the study versus the placebo bar. There were no episodes of hypoglycemia or hyperglycemia. The mean blood glucose levels pre-snack at bedtime were nearly identical (Extend Bar value 117.5+/-45.6 mg/dl; placebo bar value 117.3+/-40.0 mg/dl; P=0.977), and lower at midnight and before breakfast on the Extend Bar nights compared to the placebo bar nights (Extend Bar, midnight value 127.9+/-31.0 mg/dl; placebo bar midnight value 148.2+/-32.1 mg/dl; P=0.0001; Extend Bar breakfast value 114.2+/-15.8 mg/dl; placebo bar breakfast value 158.49+/-30.3 mg/dl; P<0.0001). These data suggest that ingesting Extend Bar containing uncooked cornstarch as the nighttime snack may be an effective strategy to lesson the frequency of nocturnal and morning hyperglycemia in subjects with type 2 diabetes.     

Insulin glargine versus NPH insulin therapy in Asian Type 2 diabetes patients

OBJECTIVE: This study investigated the effect of insulin glargine (LANTUS) versus NPH insulin on metabolic control and safety in Asian patients with Type 2 diabetes, inadequately controlled on oral hypoglycemic agents (OHAs). STUDY DESIGN AND METHODS: In this open-label, randomized, parallel, multinational, 24-week, non-inferiority study, 443 patients received either once-daily insulin glargine (n=220) or NPH insulin (n=223) at bedtime, plus glimepiride (Amaryl). RESULTS: Baseline characteristics were similar between the two groups. HbA(1c) levels decreased in the insulin glargine and NPH groups over the study period in the per-protocol (PP; -1.10% versus 0.92%) and full-analysis (FA; -0.99% versus -0.77%) populations. In the PP population, the difference between adjusted means (predefined equivalence region >-0.4%) was 0.19% (90% confidence interval [CI]: 0.02, 0.36), demonstrating non-inferiority between the two treatments. In a superiority analysis (FA population), the difference between adjusted mean changes in the two groups was 0.22% (95% CI: 0.02, 0.42), demonstrating the superiority of insulin glargine (p=0.0319). Moreover, the number of hypoglycemic episodes was significantly lower with insulin glargine versus NPH insulin (p<0.004), particularly severe (p<0.03) and nocturnal (p<0.001). Daily insulin dose increased from 9.6+/-1.5 to 32.1+/-17.6 U in the insulin glargine group and from 9.8+/-1.9 to 32.8+/-18.9 U in the NPH insulin group. CONCLUSION: These results confirm earlier reports that insulin glargine provides superior glycemic control with less hypoglycemia and demonstrates that these benefits are consistent between different ethnicities.     

Insulin glargine compared to NPH among insulin-naïve, U.S. inner city, ethnic minority type 2 diabetic patients

Aims

We compared basal regimens of glargine or NPH among insulin-naïve, U.S. inner city, ethnic minority type 2 diabetic patients who were sub-optimally controlled on maximally tolerated doses of combination oral agents.

Methods

Eighty-five subjects were randomized to 26 weeks of open-label, add-on therapy using single doses of bedtime NPH, bedtime glargine, or morning glargine; initially through an 8-week dose titration phase, followed by a 16-week maintenance phase during which insulin doses were adjusted only to avoid symptomatic hypoglycemia.

Results

All three groups were comparable at baseline (mean HbA_1c 9.3 ± 1.4%), and improved their HbA_1c (to 7.8 ± 1.3%), fasting, and pre-supper glucose readings, with no significant between-group differences. Weight gain was greater with either glargine regimen (+3.1 ± 4.1 kg and +1.7 ± 4.2 kg) compared to NPH (−0.2 ± 3.9 kg), despite comparable total insulin doses. Pre-supper hypoglycemia occurred more frequently with morning glargine, but nocturnal hypoglycemia and improvements in treatment satisfaction did not differ among groups.

Conclusions

Among inner city ethnic minority type 2 diabetic patients in the U.S., we found no differences in basal glycemic control or nocturnal hypoglycemia between glargine and NPH, although glargine precipitated greater weight gain.     

门冬胰岛素50治疗肝源性糖尿病患者初步疗效研究*

目的观察门冬胰岛素50治疗肝源性糖尿病（HD）患者的临床疗效。方法117例HD患者被随机分为两组,分别接受甘精胰岛素联合阿卡波糖治疗58例和门冬胰岛素50治疗59例,观察12 w。观察两组患者空腹血糖（FPG）、餐后2 h血糖（2 hPBG）、糖化血红蛋白（HbA1c）、胰岛素用量、血糖达标时间、低血糖发生情况等指标的变化,从而比较治疗效果及其安全性。结果在治疗12 w末,门冬胰岛素50治疗组FBG为（5.97±1.26） mmol/L,与甘精胰岛素治疗组的【（5.54±1.48） mmol/L】比,无显著差异（P>0.05）;门冬胰岛素50组PBG为（7.45±2.56） mmol/L,显著低于甘精胰岛素组【（8.95±2.44） mmol/L,P<0.05】, HbA1c为（6.81±0.23）%,显著低于甘精胰岛素组的【（7.56±0.31）%,P<0.05】,每日胰岛素用量为（37.2±7.0） U·d-1,与甘精胰岛素组的【（35.1±6.8） U·d-1】比,无显著统计学差异（P>0.05）,血糖达标时间为（14.2±2.8）d,与甘精胰岛素组的【（14.5±3.2） d】比,无显著统计学差异（P>0.05）,轻微低血糖发生率为3.5%,与甘精胰岛素组的5.1%比,无统计学差异（P>0.05）。结论门冬胰岛素50治疗HD患者疗效肯定,对餐后血糖的控制存在优势,且安全性良好。