Multiple-dose Insulin Therapy Research Articles

An Exploratory Study of Itolizumab on the Preservation of Beta Cell Function in Adults with Recent-Onset Type 1 Diabetes.

We conducted a phase I-IIa, randomized, monocentric, double-blind, placebo-controlled clinical trial to evaluate the safety and impact of the combination treatment of Itolizumab and insulin on preserving beta cell function in adults with recent-onset type 1 diabetes. Twelve patients were randomly assigned to three treatment groups, each receiving a different Itolizumab dose (0.4/0.8/1.6 mg/kg body weight, respectively) and a placebo group. All patients received concomitant intensive multiple-dose insulin therapy. Endogenous insulin secretion was assessed by the measurement of C-peptide during the mixed-meal tolerance test. No serious adverse events were reported. No changes in the total daily insulin doses, glycated hemoglobin levels, and stimulated C-peptide were observed between the Itolizumab and placebo groups at 52 weeks. A significant decrease in stimulated C-peptide was observed during the follow-up period (p = 0.012). One subject treated with 1.6 mg of Itolizumab showed a marked increase in the levels of stimulated C-peptide three years after completion of the trial. Taken together, this is the first study to demonstrate that combination treatment with Itolizumab and insulin is safe in humans and does not affect the residual function of beta cells up to 52 weeks. The findings from our study show preliminary evidence that high doses of Itolizumab could potentially arrest the loss of beta cell function in the long term. Further studies with a longer follow-up and larger numbers of patients are envisaged to assess the effect with high dose Itolizumab.

Comparison of effectiveness of continuous subcutaneous insulin infusion with daily insulin injection in a Chinese population of Type I diabetic patients

Purpose: To compare the clinical effectiveness of continuous subcutaneous insulin infusion therapy with that of multiple-dose insulin therapy in type 1 diabetic patients.
 Methods: A total of 1000 type 1 diabetic patients were assigned to two groups, with 500 patients per group. Patients in group I were treated with continuous subcutaneous infusion of insulin (CSII), while those in group II received multiple daily doses of insulin injection. Body mass index (BMI), insulin dose, HbA1c levels, and frequencies of hypoglycemia and diabetic-ketoacidosis (DKA) were determined in each patient at baseline, and at 4-week intervals for 4 years.
 Results: The HbA1c levels at baseline and at the end of 4th year in group I were 8.9 ± 1.1 and 8.2 ± 1.5 %, respectively, relative to corresponding values of 8.6 ± 1.2 and 9.1 ± 1.1 %, respectively in group II. The results revealed significant difference in HbA1c between the two groups (p < 0.05). After 4 years of therapy, insulin requirement was markedly higher in group II than at baseline (0.8 ± 0.1 vs 0.9 ± 0.2, p < 0.05) IU/kg/day. However, insulin requirement in group I decreased after 4 years, relative to that at baseline (0.65 ± 0.2 vs 0.8 ± 0.1 IU/kg/day; p < 0.05).
 Conclusion: CSII therapy seems to be an effective and safe gold standard method for managing type I diabetes mellitus patients.

Boluses in Insulin Therapy.

Giving a bolus is one major part in multiple dose insulin therapy (MDI) along with basal insulin substitution. To adjust the bolus optimally, different factors like carbohydrate content and composition of the meal, correction factors, and timing have to be considered. Advances in technologies like bolus advisors can assist the patients but still there a several open questions and technical challenges regarding boluses. This commentary provides an opportunity to address several of the above-mentioned factors influencing the result of bolusing. It shall draw attention to those factors and address the current opportunities, for example, continuous subcutaneous insulin infusion (CSII), as well as the need for further studies which can help to improve diabetes insulin therapy by means of the correct use of boluses.

Utilization of an abbreviated diabetes impact management scale to assess change in subjective disability during a trial of pulsatile insulin delivery demonstrates benefit

A prospective interventional study of pulsatile intravenous insulin infusion therapy has demonstrated reduction of left ventricular mass and blunting of progression of diabetic nephropathy. We anticipated that improvements in objective parameters would be associated with similar improvement measurable by the self-administered Diabetes Impact Management Scale (DIMS). The DIMS was administered at baseline and 12 months for 19 participants randomized to receive either standard insulin treatment of 3 to 4 injections of insulin daily or insulin treatment plus an additional day per week of 3 intravenous pulses over an 8-hour period. For standard vs pulsed intravenous insulin therapy, mean baseline scores were similar for the 12 total questions as well as the groups of 7 questions with emotional content and 5 with physical (neurologic) content. Mean study group scores at 1 year and changes over 1 year were not significantly different for the 7 questions with emotional content ( P = .3143, .7574). Score results for the 5 questions related to neurologic status at 1 year and changes over 1 year were significantly different between patients with standard and with pulsed insulin therapy ( P = .0144, 0.0004). Pulsatile intravenous insulin, when added to standard multiple-dose insulin therapy, was demonstrated to improve subjective perception of neurologic disability on repeated use of an abbreviated form of the DIMS.

Benefits, risks, costs, and patient satisfaction associated with insulin pump therapy for the pregnancy complicated by type 1 diabetes mellitus

Objective: Glycemic control, perinatal outcome, and health care costs were evaluated among women with type 1 diabetes mellitus who began insulin pump therapy during pregnancy (group 1, n = 24), were treated with multiple insulin injections (group 2, n = 24), or were already using an insulin pump before pregnancy (group 3, n = 12). Patient satisfaction and continuation of pump therapy post partum were assessed. Study Design: A retrospective review of maternal and neonatal medical records was performed, and a questionnaire was sent to patients after delivery. Patients in groups 1 and 2 were matched for age, age at onset and duration of diabetes mellitus, White class, and date of delivery. Results: No differences in glycosylated hemoglobin A levels were observed among groups 1, 2 or 3 in the first, second, or third trimester. Patients in group 1 started pump therapy at a mean of 16.8 weeks' gestation, and 17 (70.8%) began therapy as outpatients. No deterioration in glycemic control was noted during the 2- to 4-week period after the start of pump treatment. Among the women in group 1 eight had at least one episode of severe hypoglycemia before starting pump therapy, but only one had such an episode after this treatment was begun. Two episodes of ketoacidosis occurred in group 1, and no episodes occurred in groups 2 and 3. No significant differences in perinatal outcomes or health care costs were observed among groups 1, 2, and 3. After delivery 94.7% of the women in group 1 continued to use the pump because it provided better glycemic control and a more flexible lifestyle. Postpartum glycosylated hemoglobin A values were 7.2% in group 1 and 9.1% in group 2, a significant difference. Conclusions: Insulin pump therapy was initiated during pregnancy without a deterioration of glycemic control and was associated with maternal and perinatal outcomes and health care costs comparable to those among women who were already using the pump before pregnancy or who received multiple-dose insulin therapy. Women who began pump therapy in pregnancy were highly likely to continue pump use after delivery and preferred the flexible lifestyle that this treatment allowed. (Am J Obstet Gynecol 2000;182:1283-91.)

Severe hypoglycaemia in children and adolescents during multiple-dose insulin therapy.

Episodes of severe hypoglycaemia, resulting in coma and/or convulsions, were documented in an unselected, population-based group of 376 children and adolescents with Type 1 diabetes mellitus (Type 1 DM) treated at the Aurora Hospital, City of Helsinki. A prospective study in 1994-95 yielded 493 patient-years and a retrospective study in 1990-93, 904 patient-years of data. Of these patients, 77-85% received insulin in three or more daily doses. During 1990-95, 43 patients had a total of 48 severe hypoglycaemic episodes. For each episode (n = 48), one control Type 1 DM patient who had never experienced any severe hypoglycaemia, matched by age, diabetes duration and puberty, was sought from the study population. Incidence of severe hypoglycaemia was 3.1/100 patients years prospectively and 3.6/100 retrospectively. At the time of the episode, median age was 13.3 (range 2.2-21) years, and median diabetes duration 6.1 (0.5-14.6) years. Rates were similar in different age groups (< 6, 6-12.9 and > or = 13 years). A potential explanation for the hypoglycaemia was found in 79% of the episodes. Insulin dose was higher (p = 0.04) and HbA1c lower (p = 0.005) in patients with severe hypoglycaemia than in controls. In conclusion, multiple-dose insulin therapy in young patients with Type 1 DM can be associated with a low rate of severe hypoglycaemia. The majority of such episodes seem to be preventable.

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.