Multiple Daily Injection Therapy Research Articles

Combined insulin pump therapy with real-time continuous glucose monitoring significantly improves glycemic control compared to multiple daily injection therapy in pump naïve patients with type 1 diabetes; single center pilot study experience.

This study assessed the safety and clinical effectiveness of the training protocol for initiating insulin pump therapy with real-time continuous glucose monitoring (MiniMed Paradigm REAL-Time System) in a stepwise approach on pump naive subjects with type 1 diabetes compared to a control group who remained on multiple daily injection (MDI) therapy. This was a 15-week treat-to-target pilot study of 16 adult subjects (n = 50% male, age 45.9 +/- 16 years) with type 1 diabetes (duration of diabetes 21.9 +/- 11 years) on MDI therapy with hemoglobin A1c levels at or above 7.5% at baseline. Subjects were randomized to either the study arm (using a combined insulin pump and real-time continuous glucose monitoring system) or the control arm [which continued on MDI therapy with self-monitored blood glucose (SMBG) only]. All subjects dosed insulin according to results of SMBG by finger stick and uploaded data into the CareLink data management software. Significant improvements in glycemic control were observed from baseline in both study groups-study arm: pre-A1c 9.45 +/- 0.55 and post-A1c 7.4 +/- 0.66 (p = 0.00037); control arm: pre-A1c 8.58 +/- 1.30 and post-A1c 7.5 +/-1.01 (p = 0.04). Both arms had no incidence of severe hypoglycemia. In this pilot study, the Paradigm REAL-Time System was initiated safely and effectively in type 1 diabetes patients who were pump naïve using a stepwise educational protocol.

Use of rapid-acting insulin analogues in the treatment of patients with type 1 and type 2 diabetes mellitus: Insulin pump therapy versus multiple daily injections

Background: Replicating endogenous insulin production is the goal of treatment for diabetes mellitus (DM) and is necessary to minimize the risk of vascular complications. The 2 main methods of achieving this goal are continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDIs) comprising basal and prandial injections. Objective: The objective of this article was to discuss the use of a rapid-acting insulin analogue, insulin aspart, in CSII and MDI compared with other insulins in adult patients with type 1 or type 2 DM. Methods: This article was based on a presentation given by the author at a satellite symposium entitled “Realising the Value of Modern Insulins: Reaching Further with Rapid-Acting Insulin Analogues” that was convened during the XIXth World Diabetes Congress, December 3, 2006, in Cape Town, South Africa. Results: In patients with type 1 DM, CSII using the rapid-acting insulin analogue insulin aspart has been reported in clinical trials to improve glycemic control compared with MDI therapy using neutral protamine Hagedorn plus insulin aspart (for basal and mealtime coverage, respectively). In patients with type 2 DM, the CSII and MDI regimens offered similar efficacy and tolerability; CSII therapy may be less burdensome, however, with fewer social limitations than MDIs. Not all insulins are equally suited for use in CSII treatment. Although the efficacy of insulin aspart in CSII was comparable to other rapid-acting insulins, the frequency of hypoglycemia was shown to be significantly lower with insulin aspart compared with human insulin or insulin lispro in patients with type 1 DM. The compatibility of insulin aspart and insulin lispro for use in CSII pumps was compared in an 8-week, double-blind, 2-period, crossover study of patients with type 1 DM. The overall adverse-effect score was significantly lower ( P < 0.005) with insulin aspart than with insulin lispro, as were scores for pain/burning and inflammation (both, P < 0.01) and dermal redness ( P < 0.001). Furthermore, a stability study reported on the suitability of insulin aspart for use in CSII pumps. Quality-of-life scores with CSII have been reported to be higher than with MDI therapy. Conclusion: CSII with the rapid-acting insulin analogue insulin aspart is a viable choice for patients with type 1 or type 2 DM who want close-to-physiologic insulin treatment.

Comparison between multiple daily insulin injection therapy (MDI) and continuous subcutaneous insulin infusion therapy (CSII), results of the five nations study

Continuous subcutaneous insulin infusion (CSII) is an alternative to multiple daily insulin injections (MDII) as intensive insulin therapy for optimising glycaemic control in type 1 diabetes. The Diabetes Control and Complications Trial (DCCT) showed the benefits of intensive insulin therapy in reducing the risk of microvascular complications. CSII was an option in the intensive control arm of the study. However, the value and place of CSII in the management of type 1 diabetes remains controversial. In this article we will present what we until recently do know about the benefits of CSII therapy and shall especially give some information about the recently published 5-Nations Study. In our view CSII usage offers significant benefits over NPH-based MDI for individuals with type 1 diabetes with improvement in all significant metabolic parameters as well as in patients' quality of life.

Intradiscal pressures in rat tail discs measured using a miniaturized fiber-optic sensor

Sensor-augmented pump (SAP) technology, which combines continuous subcutaneous insulin infusion (CSII) and real-time continuous glucose monitoring (RT-CGM), has been available for several years in China. In this study, the time required to reach predefined glycaemic targets with SAP vs multiple daily injection (MDI) therapy was compared in hospitalized patients with type 2 diabetes mellitus (T2DM).Adults (aged 18–65 years) with T2DM treated with insulin and admitted to hospital for glucose management were randomized to either SAP (Medtronic MiniMed™ Paradigm™ 722 system) or MDI with blinded CGM (Medtronic MiniMed CGMS System Gold™) for a 2-week period. Glycaemic targets were defined as three preprandial measurements between 80 and 130 mg/dL (4.4 and 7.2 mmol/L) and three 2-h postprandial measurements between 80 and 180 mg/dL (4.4 and 10.0 mmol/L) within the same day.When data from 81 patients (40 SAP, 41 MDI) were analysed, 21 patients using SAP therapy, compared with six using MDI therapy, achieved their glycaemic targets within 3 days, and their time to reach their glucose targets was significantly shorter (3.7 ± 1.1 vs 6.3 ± 3.1 days for MDI; P < 0.001), while three MDI patients failed to reach glycaemic targets within 14 days. SAP vs MDI patients experienced significantly less hypoglycaemia [sensor glucose < 50 mg/dL (2.8 mmol/L): 0.04% vs 0.32%, respectively; P < 0.05] and significantly less hyperglycaemia [sensor glucose > 180 mg/dL (10 mmol/L): 21.56% vs 35.03%, respectively; P < 0.05].SAP vs MDI therapy in hospitalized patients with T2DM significantly reduced the time required to achieve glycaemic targets, and such systems may be a cost-effective way to improve glucose control and reduce hospital stays in T2DM patients.

Age and A1C Are Important Clinical Predictors of Continuous Subcutaneous Insulin Infusion Efficacy in Type 1 Diabetic Patients

Only a few studies have reported a long-term follow-up in a significant number of patients using continuous subcutaneous insulin infusion (CSII) (1). Who stands to benefit more from this costly insulin therapy is still unclear. The aim of our observational, retrospective study was to evaluate the possible predictors of the degree of improvement of metabolic control with CSII in 82 consecutive type 1 diabetic patients (age 37.9 ± 13.4 years, 42 men and 40 women, duration of diabetes 19.7 ± 9.9 years) who started CSII in the Diabetes Unit of Bergamo Hospital between June 1999 and March 2004. The patients had been treated with multiple daily injection (MDI) therapy (regular [ n = 22] or rapid-acting analog insulin [ n = 60] before meals plus NPH [ n = 72] or glargine [ n = 10] as basal insulin) for at least 1 year. During CSII treatment, lispro or aspart analogs were used. All patients were evaluated …

Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections

With either continuous subcutaneous insulin infusion (CSII) or multiple daily insulin injection (MDII) therapy, the optimal meal insulin is a rapid-acting analog (lispro or aspart). To date, the efficacy of CSII versus MDII therapy has been evaluated in a limited number of randomized controlled trials in which rapid-acting analogs were used for both regimens. In this context, we recently conducted a pooled analysis (1) using raw trial data from three such studies undertaken in adults with type 1 diabetes (2–4). This analysis suggested that CSII is associated with better glycemic control, particularly in those patients with poor initial control. Indeed, the relative benefit of CSII over …

Continuous Subcutaneous Insulin Infusion (CSII) of Insulin Aspart Versus Multiple Daily Injection of Insulin Aspart/Insulin Glargine in Type 1 Diabetic Patients Previously Treated With CSII

Multiple daily injection (MDI) therapy of bolus insulin aspart and basal insulin glargine was compared with continuous subcutaneous insulin infusion (CSII) with aspart in type 1 diabetic patients previously treated with CSII. One hundred patients were enrolled in a randomized, multicenter, open-label, crossover study. After a 1-week run-in period with aspart by CSII, 50 subjects were randomly assigned to MDI therapy (aspart immediately before each meal and glargine at bedtime) and 50 subjects continued CSII. After 5 weeks of the first treatment, subjects crossed over to the alternate treatment for 5 weeks. During the last week of each treatment period, subjects wore a continuous glucose monitoring system for 48-72 h. Mean serum fructosamine levels were significantly lower after CSII therapy than after MDI therapy (343 +/- 47 vs. 355 +/- 50 micromol/l, respectively; P = 0.0001). Continuous glucose monitoring profiles over a 24-h time period showed that glucose exposure was 24 and 40% lower for CSII than MDI as measured by area under the curve (AUC) glucose >/=80 mg/dl (1,270 +/- 742 vs. 1,664 +/- 1,039 mg . h . dl(-1); P < 0.001) and AUC glucose >/=140 mg/dl (464 +/- 452 vs. 777 +/- 746 mg . h . dl(-1), CSII vs. MDI, respectively; P < 0.001). Similar percentages of subjects reported hypoglycemic episodes (CSII: 92%, MDI: 94%) and nocturnal (12:00 a.m. to 8:00 a.m.) hypoglycemic episodes (CSII: 73%, MDI: 72%). Major hypoglycemia was infrequent (CSII: two episodes, MDI: five episodes). In a trial of short duration, CSII therapy with insulin aspart resulted in lower glycemic exposure without increased risk of hypoglycemia, as compared with MDI with insulin aspart and glargine.

Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections: The Impact of Baseline A1c

We agree with Blumer’s (1) contention that patients with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) therapy represent a well-motivated patient population. In this context, he asks whether differences in patient motivation (as reflected in adherence to frequent self-monitoring of blood glucose and regular contact with diabetes educators) may underlie the finding of improved glycemic control with CSII as compared with multiple daily insulin injection (MDII) therapy in our recent pooled analysis …

Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections

Rapid-acting insulin analogs (insulin lispro and insulin aspart) have emerged as the meal insulin of choice in both multiple daily insulin injection (MDII) therapy and continuous subcutaneous insulin infusion (CSII) for type 1 diabetes. Thus, a comparison of efficacy between CSII and MDII should be undertaken only in studies that used rapid-acting analogs for both intensive regimens. We performed a pooled analysis of the randomized controlled trials that compared CSII and optimized MDII therapy using rapid-acting analogs in adults with type 1 diabetes. The three studies that met inclusion criteria provided data on 139 patients, representing 596 patient-months for CSII and 529 patient-months for MDII. Mean age was 38.5 years, with duration of diabetes of 18.0 years. The studies differed significantly in mean baseline A1c (7.95, 8.20, and 9.27%). The pooled estimate of treatment effect comparing the percentage reduction in A1c by CSII with that by MDII (CSII - MDII) was 0.35% (95% CI -0.10 to 0.80, P = 0.08) using a random effect to account for heterogeneity between studies. Importantly, the interaction between baseline A1c and treatment modality emerged as an independent predictor of treatment effect (CSII - MDII) (P = 0.002). The relative benefit of CSII over MDII was found to increase with higher baseline A1c. A model derived from these data predicts that in a patient with a baseline A1c of 10%, CSII would reduce the A1c by an additional 0.65% compared with MDII. Conversely, there would be no A1c benefit of CSII compared with MDII if baseline A1c were 6.5%. There was no significant difference between CSII and MDII in the rate of hypoglycemic events. When using rapid-acting insulin analogs in CSII and MDII regimens in adult patients with type 1 diabetes, insulin pump therapy is associated with better glycemic control, particularly in those individuals with higher baseline A1c. Thus, CSII emerges as an important modality for implementing intensive therapy and may be uniquely advantageous in patients with poor glycemic control.

Effects of multiple daily injection therapy with humalog mixtures versus separately injected insulin lispro and NPH insulin in adults with type I diabetes mellitus

Background: Injection of insulin lispro (LP) before meals provides a more physiologic insulin activity profile than regular human insulin, but the relatively short duration of action of LP may allow the blood glucose (BG) level to increase during the late postprandial period (4–7 hours after meals) unless basal insulin is optimally replaced. One approach to basal insulin optimization has been to combine small doses of NPH with LP before meals. When used in a similar fashion, premixed, fixed-ratio insulin preparations containing LP and NPL (an LP-based intermediate-acting insulin) may provide the basis for an optimized basal-bolus insulin regimen. Objective: This study assessed mean late postprandial glycemic control during treatment with a premixed formulation consisting of a high proportion of LP (75% LP/25% NPL; H) and a premixed formulation consisting of a medium proportion of LP (50% LP/50% NPL; M). The H/M formulation was given before meals and was compared with treatment with preprandial LP + NPH (LP + N) in patients with type 1 diabetes mellitus (DM). Methods: This multicenter, randomized, open-label, 2-period crossover study was conducted at 4 centers in Italy and 1 center in France. Patients eligible for the study had type 1 DM, were ≥ 18 years of age, and had a glycosylated hemoglobin (HbA 1c) <150% of the upper limit of normal. Patients were randomly assigned to 1 of 2 treatment sequences: LP self-mixed with NPH before meals plus NPH alone at bedtime for 8 weeks (LP + N) followed by preprandial H or M, plus NPH alone at bedtime for 8 weeks (H/M), or the opposite sequence. Assessments included 8-point self-monitored BG profiles, HbA 1c, and hypoglycemia (any sign or symptom of hypoglycemia or BG < 3.0 mmol/L [<54.0 mg/dL]). The primary outcome measure was the late postprandial BG value, calculated as the mean of the combined prelunch (late postbreakfast), predinner (late postlunch), and bedtime (late postdinner) values. Results: A total of 89 patients with type 1 DM were enrolled (44 men, 45 women; mean [SD] age, 38.3 [12.8] years; mean [SD] body weight, 70.8 [11.6] kg; mean [SD] body mass index, 24.6 [3.0] kg/m 2; mean [SD] duration of diabetes, 17.8 [10.5] years; mean HbA 1c, 7.9% [0.88%]). The mean (SD) late postprandial BG values were similar between treatments (8.9 [2.1] mmol/L [160.3 (37.8) mg/dL] for H/M vs 9.0 [1.8] mmol/L [162.1 (32.4) mg/dL] for LP + N), as were the end point HbA 1c values (7.8% [0.9%] for H/M vs 7.9% [0.8%] for LP + N). The rate of hypoglycemia was significantly higher during treatment with H/M, primarily because of episodes occurring between 12 PM and 6 PM, but was relatively low in both groups (mean/median rate per patient per 30 days: 2.87/2.14 for H/M and 2.11/1.07 for LP + N; P < 0.05). Conclusions: In this population of patients with type 1 DM, preprandial H/M provided an effective alternative regimen for prandial and basal insulin replacement. Late postprandial BG control, an indicator of basal insulin sufficiency, was similar to that achieved with an intensified regimen of LP + N injected separately before meals, and the end point HbA 1c was similar between the 2 treatments.

A quality-of-life assessment of intensive insulin therapy using insulin lispro switched from short-acting insulin and measured by an ITR-QOL questionnaire: a prospective comparison of multiple daily insulin injections and continuous subcutaneous insulin infusion

We examined quality-of-life (QOL) of patients with a prospective comparison of multiple daily insulin injections therapy (16 patients in MDI group) and continuous subcutaneous insulin infusion therapy (12 patients in CSII group) using insulin lispro (LP), which was switched from short-acting insulin on the basis of a questionnaire about insulin-therapy-related QOL measure (ITR-QOL). The overall score of ITR-QOL before using LP in the CSII group was significantly higher ( P<0.01) than the MDI group. In four subscales of ITR-QOL, the scores of social and daily activities and of therapy-related feelings in the CSII group were significantly higher ( P<0.02) than those in the MDI group, respectively, while there was no significant difference in the score of physical function between the two groups. Three months after using LP, the score of daily activities in the MDI group was significantly higher ( P<0.02) than that before using LP, while there were no significant differences in other scores of the two groups. There were no significant differences in HbA1c between two groups before and after using LP. The frequency of hypoglycemic events in the MDI group before using LP was higher than that in the CSII group and decreased after using LP. These results show that QOL of patients treated by CSII is superior to that treated by MDI and demonstrate that insulin lispro has a more beneficial effect on daily activities in patients treated by MDI than short-acting insulin.

Comparison Between Continuous Subcutaneous Insulin Infusion and Multiple Insulin Injection Therapy in Type 1 Diabetes Mellitus: 18-Month Follow-Up

To compare the results with continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) of insulin in the treatment of type 1 diabetes during 18 months of follow-up. We prospectively studied 29 patients with type 1 diabetes in Brazil; 17 patients elected to change from conventional insulin therapy (2 injections daily) (N = 3) or MDI (N = 14) to CSII therapy, and the other 12 continued to receive MDI therapy. All patients were treated with insulin lispro; patients in the MDI treatment group also received NPH insulin. We compared hemoglobin A1c (HbA1c) values, determined at baseline and every 3 months, between the two treatment groups. Other variables analyzed included weight, body mass index, total daily dose of insulin, and incidence of severe hypoglycemia. Patients in the CSII group had a significant decrease (P<0.001) in mean HbA1c at 18 months in comparison with baseline (8.3% versus 6.5%). In the MDI group, no significant changes were found in mean HbA1c. After 3 months of treatment, patients in the CSII group had a significantly lower mean HbA1c level than did patients receiving MDI (P<0.05). Of the 17 patients treated with CSII, all had HbA1c values less than 7.5% at 18 months, and 13 (76%) had HbA1c levels less than 7%. Although no significant variations in weight were observed in either group, the insulin/weight ratio decreased in the CSII group from baseline to 18 months (0.8 U/kg to 0.6 U/kg; P = 0.02). No episodes of severe hypoglycemia were noted in either group. Patients with diabetes treated with insulin lispro have better glycemic control with CSII than with MDI. Most of our patients in the CSII group were able to achieve target HbA1c levels less than 7% at 18 months without an increase in hypoglycemic episodes.

Recent advances in treatment of youth with Type 1 diabetes: better care through technology.

While treatment of Type 1 diabetes mellitus (T1DM) in children and adolescents is especially difficult, recent technological advances have provided new therapeutic options to clinicians and patients. The urgency to achieve strict diabetes control and the introduction of new and improved insulin pumps have been accompanied by a marked increase in use of continuous subcutaneous insulin infusion (CSII) therapy in youth with diabetes. Results of clinical outcome studies indicate that CSII provides a safe and effective alternative to multiple daily injection (MDI) therapy, even when employed in a regular clinic setting in a large number of children. The safety and efficacy of CSII is further enhanced by the introduction of lispro and aspart insulin. The sharper peaks and shorter duration of action of these very rapid-acting insulin analogues provides a means to achieve better control of post-prandial hyperglycaemia with less late post-prandial and nocturnal hypoglycaemia. Glargine insulin, a soluble and essentially peakless long-acting insulin analogue, may provide a better basal insulin for MDI regimens, but there are limited published data with this agent in children with T1DM. A number of systems for pulmonary delivery of insulin are in development and preliminary results of Phase III studies have been promising. Like CSII, inhaled insulin allows the child to take bolus insulin doses before each meal without having to take a premeal injection. A major obstacle to effective treatment is that self-monitoring of three to four blood glucose levels a day often misses the marked glycaemic excursions that characterize T1DM in young patients. On the other hand, new continuous glucose sensing systems provide a wealth of data that can be used to optimize basal and bolus therapy, regardless of how insulin is administered. Even more important, we may finally be at the threshold of development of a practically applicable artificial pancreas.

MODERN INSULIN THERAPY FOR TYPE 1 DIABETES MELLITUS

Modern insulin therapy for Type 1 diabetes is part of a comprehensive treatment program designed to achieve and maintain blood glucose levels as close to normal as possible. The insulin regimens most likely to be successful approximate physiologic insulin delivery by combining basal and meal doses. Several options are available, including constant infusion by external pump and multiple daily injection therapy. Modern therapy affords major health benefits through improved blood glucose control, as well as lifestyle benefits associated with increased flexibility and spontaneity.

Documented symptomatic hypoglycaemia in children and adolescents using multiple daily insulin injection therapy.

Symptomatic episodes of documented hypoglycaemia were characterized with the aid of a 3-month diary in a single-centre, unselected group of 161 children and adolescents with Type 1 diabetes mellitus, treated mainly (81%) with multiple-dose insulin therapy. Patients and families were asked to write in the diary all the symptomatic episodes in which blood glucose concentration proved to be < or =3 mmol l(-1) before treatment. Of the patients, 83 (52%) had a total of 287 hypoglycaemic episodes (0.6 attack per month per patient). The majority of the attacks, 221 (77%), were mild (patients > or =6 years able to treat themselves). Only two attacks were severe, resulting in coma and/or convulsion. The most common dominant symptoms were weakness (29%), tremor (20%), hunger (14%), and drowsiness (12%). Of all the dominant symptoms, 39% were classified as autonomic, 20% neuroglycopenic, and 41% non-specific. In children under 6 years, autonomic symptoms were less common than in adolescents 15 years or over (34% vs 57%, p = 0.01). In conclusion, the incidence of documented symptomatic hypoglycaemia was low. The symptoms were more often neuroglycopenic or non-specific than autonomic, especially in young children.

Documented symptomatic hypoglycaemia in children and adolescents using multiple daily insulin injection therapy

Documented symptomatic hypoglycaemia in children and adolescents using multiple daily insulin injection therapy

Intensive Insulin Therapy in Insulin Dependent Diabetes and Combination Therapy

Intensive insulin therapy (IIT) and combination therapy using sulfonylurea and insulin are two insulin regimens being used more frequently to improve glycemic control. For those patients with insulin-dependent diabetes, IIT or multiple daily injection therapy mimics normal pancreatic function by its timing of insulin delivery. The improvement in glycemic control carries with it the risk of a two- to threefold increase in episodes of hypoglycemia. For those with non-insulin-dependent diabetes, combination therapy attempts to provide a bridge between maximal dose oral hypoglycemic agents and aggressive insulin therapy. Although this therapy remains controversial, it has proved useful in select patient groups. This article discusses the rationale for IIT, and its implementation. Variables that affect IIT are discussed. The combination therapy section provides guidelines for patient selection and insulin protocols for evening insulin administration. The health care provider is familiarized with these alternative therapies and their successful applications.

Diets for insulin pump and multiple daily injection therapy.

The role of diet in achieving and maintaining normalized blood glucose control in type I diabetic patients using insulin pumps or multiple daily injection (MDI) regimens is not well defined. We describe herein dietary guidelines that have proved effective in the management of such patients over 3 yr. The guidelines stress the importance of a careful dietary history, the regularity and consistency of diet during the preliminary adjustment period, the establishment of a variable insulin dosage schedule based on meal size and content as well as blood glucose, the appropriate treatment for hypoglycemia, and dietary adjustments for exercise. While insulin pump and MDI therapy may ultimately provide increased flexibility in certain aspects of dietary therapy, the diet must be carefully controlled if these innovative modes of insulin delivery are to succeed.