Aims/hypothesis
The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type ...1 diabetes.
Methods
Children and adults (
n
= 153) on CSII with HbA
1c
7.5–9.5% (58.5–80.3 mmol/mol) were randomised to (CGM) a Sensor On or Sensor Off arm for 6 months. After 4 months’ washout, participants crossed over to the other arm for 6 months. Paediatric and adult participants were separately electronically randomised through the case report form according to a predefined randomisation sequence in eight secondary and tertiary centres. The primary outcome was the difference in HbA
1c
levels between arms after 6 months.
Results
Seventy-seven participants were randomised to the On/Off sequence and 76 to the Off/On sequence; all were included in the primary analysis. The mean difference in HbA
1c
was –0.43% (–4.74 mmol/mol) in favour of the Sensor On arm (8.04% 64.34 mmol/mol vs 8.47% 69.08 mmol/mol; 95% CI −0.32%, −0.55% −3.50, −6.01 mmol/mol;
p
< 0.001). Following cessation of glucose sensing, HbA
1c
reverted to baseline levels. Less time was spent with sensor glucose <3.9 mmol/l during the Sensor On arm than in the Sensor Off arm (19 vs 31 min/day;
p
= 0.009). The mean number of daily boluses increased in the Sensor On arm (6.8 ± 2.5 vs 5.8 ± 1.9,
p
< 0.0001), together with the frequency of use of the temporary basal rate (0.75 ± 1.11 vs 0.26 ± 0.47,
p
< 0.0001) and manual insulin suspend (0.91 ± 1.25 vs 0.70 ± 0.75,
p
< 0.018) functions. Four vs two events of severe hypoglycaemia occurred in the Sensor On and Sensor Off arm, respectively (
p
= 0.40).
Conclusions/interpretation
Continuous glucose monitoring was associated with decreased HbA
1c
levels and time spent in hypoglycaemia in individuals with type 1 diabetes using CSII. More frequent self-adjustments of insulin therapy may have contributed to these effects.
Trial registration
ClinicalTrials.gov registration no. NCT00598663.
Funding
The study was funded by Medtronic International Trading Sarl Switzerland.
Objectif Évaluation de l’effet de la MGC (Mesure du Glucose en Continu) couplée à la pompe à insuline sur le contrôle métabolique et sur la qualité de vie des patients diabétiques de type 1. Patients ...et méthodes 81 adultes et 72 enfants (HbA1c 7,5 à 9,5 %) participant à cette étude multicentrique, contrôlée, croisée, ont été randomisés pour les séquences capteur On/ Off ou l’inverse, d’une durée de 6 mois chacune avec un Wash out de 4 mois. La comparaison en fin de période On vs. Off a porté sur l’HbA1c, les doses d’insuline, la Satisfaction du Traitement (ST) chez les adultes, la qualité de vie chez les enfants. Résultats La réduction d’HbA1c était de – 0,43 % (IC 95 %, – 0,32 à – 0,55, P < 0,001) pour la population totale ; – 0,41 % (IC 95 %, – 0,28 à – 0,53, P < 0,001) chez les adultes, – 0,46 % (IC 95 %, – 0,26 à – 0,66, p < 0,001) chez les enfants (Battelino et al Diabetologia 2012). L’utilisation du capteur a réduit le temps passé < 70 mg/dl (On vs. Off ; 19 vs.31 min/ jour, p = 0,009). Chez les adultes sous MGC, la ST s’est significativement améliorée (p = 0,012), mais aucune différence de qualité de vie chez les enfants (p > 0,5). La fréquence des absences scolaires était significativement plus faible avec un port de capteur supérieur à 70 % du temps (p < 0,05). Des différences significatives du nombre d’arrêts temporaires, de bolus, d’assistant bolus, des contrôles capillaires ont été observées lors de la séquence On vs. Off. Conclusion La MGC couplée à la pompe à insuline a permis une diminution de l’HbA1c chez des patients ayant un contrôle métabolique sous-optimal. La satisfaction du traitement chez les adultes s’est améliorée. La qualité de vie des enfants n’a pas changé, toutefois ils étaient moins absents à l’école.
Objectif Évaluer le rôle de la MGC (Mesure du Glucose en Continu) et des spécialistes en éducation pour améliorer le contrôle métabolique chez les patients diabétiques de type 1 traités par pompe à ...insuline Patients et méthodes 153 patients (81 adultes, 72 enfants) ont participé à une étude multicentrique, contrôlée croisée pendant 17 mois, et ont été randomisés soit dans la séquence avec capteur de glucose puis sans capteur (Sensor On : Sensor Off) ou l’inverse (Sensor Off : sensor On), chacune a duré 6 mois avec une période de 4 mois de Wash out. Des évaluations sur la connaissance du diabète ont été faites au début de l’étude, sur la formation et l’utilisation du dispositif en début du traitement. Résultats L’utilisation du capteur de glucose a significativement amélioré le contrôle glycémique avec une réduction de l’HbA1c de 0,43 %. La séquence OFF / ON a permis une amélioration plus rapide de l’HbA1c (– 0,4 % vs. – 0,3% après 3 mois On/Off). Les adultes ont eu nettement moins de consultations téléphoniques que les enfants au cours de la période capteur ON. Toutefois les enfants, lors de la séquence ON / OFF, ont téléphoné nettement plus souvent pendant la période capteur ON (avec une moyenne de durée de 3 minutes de plus) que les enfants lors de la séquence OFF / ON. Ceci a été attribué au temps d’apprentissage nécessaire aux équipes assurant la formation pour devenir plus expert afin d’aider le patient avec son nouveau traitement Conclusion L’expérience acquise par le personnel soignant lors de la première période de l’étude a permis un transfert plus efficace des compétences au cours de la deuxième période et ainsi obtenir une baisse d’HbA1c. SWITCH a permis de mettre ce point en évidence, avantage supplémentaire pour la conduite de projets de recherche en milieu hospitalier.
Aims To assess the efficacy in pre‐ and postprandial glycaemic control and the impact on treatment satisfaction of a bolus calculator (Bolus Wizard) incorporated into the insulin pump in Type 1 ...diabetic (T1D) paediatric patients using continuous subcutaneous insulin infusion (CSII) treatment at various stages of pubertal development.
Methods Thirty‐six T1D patients on CSII treatment (19 males; mean age 13.9 ± 3.5 years; range 4.9–17.8 years), were prospectively enrolled into this two‐period crossover study. Eighteen patients were randomized to begin phase A using the Bolus Wizard, followed by phase B, using their current conventional insulin dosing method to determine pre‐meal boluses. The remaining subjects were randomized to begin with phase B followed by phase A. Each study period lasted 2 weeks. A questionnaire assessing treatment satisfaction with the Bolus Wizard was compiled.
Results There was a significant reduction in blood glucose levels before and 2 h after meals and in the number of correction boluses during phase A with respect to phase B of the study. The lower frequency of hypoglycaemic events during phase A did not reach statistical significance. There were no differences between the two phases: insulin requirement, daily bolus rate (%) and meal bolus quantity.
Conclusions When paediatric patients used CSII, the bolus insulin dose calculated using the Bolus Wizard was more effective in improving pre‐ and postprandial glycaemic control with fewer correction boluses, without differences in the prandial insulin requirements and without restriction in the carbohydrate content of meals. The use of the Bolus Wizard was easy and was associated with a high level of satisfaction in these patients.
To investigate the impact of continuous glucose monitoring (CGM) on health-related quality of life (HRQOL), treatment satisfaction (TS) medical resource use, and indirect costs in the SWITCH study. ...SWITCH was a multicentre, randomized, crossover study. Patients with type 1 diabetes (
n
= 153) using continuous subcutaneous insulin infusion (CSII) were randomized to a 12 month sensor-On/Off or sensor-Off/On sequence (6 months each treatment), with a 4-month washout between periods. HRQOL in children and TS in adults were measured using validated questionnaires. Medical resource utilization data were collected. In adults, TS was significantly higher in the sensor-On arm, and there were significant improvements in ratings for treatment convenience and flexibility. There were no clinically significant differences in children’s HRQOL or parents’ proxy ratings. The incidence of severe hypoglycaemia, unscheduled visits, or diabetes-related hospitalizations did not differ significantly between the two arms. Adult patients made fewer telephone consultations during the sensor-On arm; children’s caregivers made similar numbers of telephone consultations during both arms, and calls were on average only 3 min longer during the sensor-On arm. Regarding indirect costs, children with >70 % sensor usage missed fewer school days, compared with the sensor-Off arm (
P
= 0.0046) but there was no significant difference in the adults days of work off. The addition of CGM to CSII resulted in better metabolic control without imposing an additional burden on the patient or increased medical resource use, and offered the potential for cost offsets.
Aims To determine the safety and effectiveness of continuous subcutaneous insulin infusion (CSII) in attaining long‐term glycaemic control in paediatric patients with Type 1 diabetes and to compare ...the results with those previously recorded in the same patients taking multiple daily injections (MDI) (four injections a day).
Methods Forty‐two patients (mean age 12.2 ± 3.4 years; range 4.5–17 years; 24 males; mean duration of Type 1 diabetes 5.1 ± 3.0 years) were studied. The following parameters were assessed in the year before starting CSII treatment (during MDI treatment) and during the 4 years of insulin pump treatment: annual mean HbA1c, insulin requirements (U/kg per day), annual mean of body mass index (BMI) z scores, and adverse events (severe hypoglycaemia and diabetic ketoacidosis/patient per year). Two patients discontinued pump therapy (after 1‐year and 2‐year follow‐up, respectively) because of non‐compliance with CSII therapy.
Results Compared with the annual mean HbA1c observed prior to CSII therapy (8.9 ± 1.0%), the mean HbA1c levels were lower during the first (8.2 ± 0.9%; P = 0.00), second (8.6 ± 1.0%; P = 0.05), third (8.4 ± 0.9%; P = 0.01) and fourth (8.2 ± 1%; P = 0.00) year of CSII therapy. The insulin requirements (U/kg per day) decreased during CSII treatment compared with MDI treatment. Compared with the annual mean of BMI z scores prior to CSII therapy, BMI z scores were significantly lower during the third and fourth years of CSII therapy. Through the first, second, third and fourth years of follow‐up the number of episodes of severe hypoglycaemia (20.0, 20.0, 20.0 and 0 episodes/1000 patient‐years, respectively) and diabetic ketoacidosis (0.05, 0.00, 0.03 and 0.00 episodes/patient per year, respectively), events were similar to that in the year preceding CSII therapy (20.0 and 0.03, respectively).
Conclusion In this population of selected patients in our clinic, CSII appears to be a safe and effective therapeutic alternative to MDI treatment. This therapy may ensure a stable improvement in long‐term glycaemic control in paediatric patients, with no increase in diabetic ketoacidosis and severe hypoglycaemic events and, on the other hand, with a trend of reduction in BMI z scores.
This study analyzed the changes in insulin requirement in the transition from multiple daily injections (MDI) to continuous subcutaneous insulin infusion (CSII) and the differences through the CSII ...treatment in pediatric patients in different pubertal developmental stages.
We analyzed, through a longitudinal retrospective study, the insulin usage patterns and glycemic control of 40 patients with type 1 diabetes on CSII treatment for 12 months. The patients were subdivided in three groups: group A, 13 prepubertal subjects (Tanner stage I); group B, 15 pubertal subjects (Tanner stage II-IV); and group C, 12 postpubertal subjects (Tanner stage V).
During the transition from MDI to CSII, the insulin requirements decreased significantly by 21 +/- 5% (0.89 +/- 0.26 U/kg/day vs. 0.70 +/- 0.11 U/kg/day). Through the CSII treatment the percentage of total daily insulin delivered as the basal rate in groups A, B, and C was 54-60%, 52-54%, and 52-54%, respectively. The number of basal rates per day was significantly higher in groups A and B. The overall profile of basal rate differed among the groups. During the night, prepubertal patients required more insulin from 12 p.m. to 2 a.m., whereas pubertal and postpubertal patients required more insulin between 2-3 a.m. to 7 a.m. Prepubertal patients had a maximum basal rate between 9 a.m. to 12 a.m. and 2 p.m. to 4 p.m., in contrast to pubertal and postpubertal patients between 2 p.m. to 3 p.m. and 5 p.m. to 6 p.m. The number of "extra" boluses per day was significantly higher in groups B and C compared to group A.
Age-related differences exist in insulin usage patterns of pediatric patients on pump treatment. A greater knowledge of these variations may help to obtain optimum conditions in the CSII treatment in pediatric patients.
A multi-centre, observational, cross-sectional study was carried out to determine whether the health-related quality of life (HRQOL) of adolescents with type 1 diabetes is affected by different ...insulin treatment systems, and which features of HRQOL are impacted by the respective insulin treatment. The study regarded 577 adolescents, aged 10–17 years, with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) (
n
= 306) or multiple daily injections (MDI) (
n
= 271). The Insulin Delivery System Rating Questionnaire was validated in Italian and was self-completed by the subjects during a routine visit to the centres. Subjects were compared following the domains of the questionnaire. Good HRQOL was seen in subjects treated with either MDI or CSII. Significant differences were not found in the domains for general diabetes, including diabetes worries, social burden and psychological well-being. Multiple quantile regression analysis showed that CSII confers significant advantages in terms of HRQOL with improvements in treatment satisfaction, perceived clinical efficacy and reduction in treatment interference with daily activities. This favourable impact was more evident in subjects reporting lower HRQOL scores, suggesting that CSII may be especially useful for individuals perceiving a poor HRQOL. Analysis of the domains indicated that CSII was associated with a higher HRQOL than MDI. Life-course HRQOL evaluation using a standardised questionnaire can ensure better chronic disease management. This is particularly important when providing individualised care for adolescents, as they become increasingly responsible for managing their diabetes.
To evaluate blood glucose and HbA1c levels, insulin dosage, hypoglycemia rate and body mass index (BMI) at baseline, and at 3 and 6 months after initiation of continuous subcutaneous insulin infusion ...(CSII) in children and youth with type 1 diabetes mellitus (DM).
A 6-month trial of pump therapy was carried out in 40 patients with type 1 DM and one with cystic fibrosis (CF) induced DM (25 males), aged 4-25 years (mean 13.5 +/- 4.2 SD; 4-8 years, n = 6; 8-10 years, n = 8; 10-12 years, n = 4; 12-15 years, n = 11; >15 years, n = 12).
HbA1c was significantly reduced from 9.5 +/- 1.7% to 8.6 +/- 1.2% at 3 months (p < 0.03), and at 6 months 8.8 +/- 1.5% (p < 0.05). The mean daily values of blood glucose, as well as individual mean values of blood glucose at fasting and before lunch, also exhibited a significant reduction (p < 0.05) at 3 and 6 months. There was a significant reduction in the number of hypoglycemic events (level of plasma glucose <3.3 mmol/l, calculated as number of events per patient/30 days) at 3 months (6.5 +/- 5.5 vs 2.8 +/- 3.3; p = 0.02) and at 6 months (6.5 +/- 5.5 vs 3.5 +/- 3.0; p = 0.04). The insulin requirement dropped by 27.2% (1.03 +/- 0.30 U/kg/day before starting CSII; 0.75 +/- 020 U/kg/day on insulin pump therapy onset; 0.76 +/- 0.18 U/kg/day at 3 months; 0.75 +/- 0.21 U/kg/day at 6 months). During the follow-up 0.10 events of diabetic ketoacidosis/patient/year were recorded. The patients exhibited no increase in BMI during the 6 months of follow-up.
CSII was safe and effective in improving short- and medium-term metabolic control in young adults, adolescents and younger children with DM.
The aim of this study was to assess the prevalence of glucokinase gene mutations in Italian children with MODY and to investigate genotype/phenotype correlations of the mutants.
Screening for ...sequence variants in the glucokinase gene was performed by denaturing gradient gel electrophoresis and direct sequencing in 132 children with maturity onset diabetes of the young (MODY) and in 9 children with chronic fasting hyperglycaemia but without laboratory evidence for Type I (insulin-dependent) diabetes mellitus and with normoglycaemic parents ("non-classical" MODY).
Altogether 54 mutations were identified in the MODY group (54/132 or 41%) and 3 among the "non-classical" MODY individuals (3/9 or 33%). Paternity testing indicated that the latter mutations have arisen de novo. Mean fasting plasma glucose concentrations of the children with the mutant glucokinase was in the expected impaired fasting glucose range. In contrast, results of the oral glucose tolerance test showed a wide range from normal glucose tolerance (Group 1: 2-h OGTT = 6.7 +/- 1.1 mmol/l; 11 patients) to diabetes (Group 2: 2-h OGTT = 11.5 +/- 0.5 mmol/l; 9 patients), with the remaining in the impaired glucose tolerance range. Disruptive mutations (i.e. nonsense, frameshifts, splice-site) were equally represented in Groups 1 and 2 and were not clearly associated with an impaired first-phase insulin response. Surprisingly, 5 out of 11 children (or 45%) in Group 1 were found to be overweight but no children in Group 2 were overweight. Sensitivity index (SI), calculated by a recently described method, was found to be significantly lower in Group 2 than in Group 1 (SI Group 2 = 0.0013 +/- 0.0009 ml Kg(-1) min(-1)/muU/ml; SI Group 1 = 0.0068 +/- 0.0048, p < 0.0035).
Mutations in glucokinase are the first cause of MODY among Italian children selected through a low threshold limit of fasting plasma glucose (i. e. > 5.5 mmol). The lack of correlation between the molecular severity of glucokinase mutations, insulin secretion at intravenous glucose tolerance test and differences in glucose tolerance suggests that factors outside the beta cell are also involved in determining post-load glucose concentrations in these subjects. Our results seem to indicate that the differences observed in the 2-h responses at the OGTT among children with MODY 2 could be related to individual differences in insulin sensitivity.
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