64 and Exchange and Continuous Subcutaneous Insulin Infusion
Introduction
Intensive insulin treatment with the goal of maintaining tight glycemic control reduces the risk of chronic complications in type 1 diabetes mellitus (T1D) patients.1 Continuous subcutaneous insulin infusion (CSII) is an effective intensive tool to improve glycemic control in patients with T1D.2,3 In fact, an additional HbA1c reduction of 5 mmol/mol (0.4%) together with a reduction of nocturnal hypoglycemia are obtained with CSII use in T1D patients compared with multiple daily injections (MDI) treatment.4
Available knowledge about CSII effects beyond randomized controlled trials was derived from monocenter or a few centres series.5–9 Most of those studies were descriptive questionnaire-based analyses from geographic areas or countries. Precise CSII use information from whole greater areas through national registries has become a current topic in T1D knowledge.10–14 Previously, the wider perspective was shown by the T1D Exchange Registry where patients using insulin pumps achieved better glycemic outcomes compared with patients using MDI.10
Moreover, observational data from the Swedish National Diabetes Register and the Canadian LMC Diabetes Registry confirmed these findings.11,12 However, information about CSII use in Mediterranean populations is scarce. We previously described that CSII was associated with a sustained improvement in glycemic control and a reduction in severe hypoglycemia through the SPAnish Insulin Pump (SPAIP) registry.13 In fact, CSII treatment was associated with a sustained improvement in glycemic control in a whole public health system in Castilla-La Mancha (south-central Spanish region).14
This study aims at presenting an updated wider snapshot of the characteristics of CSII-treated T1D patients and their glycemic outcomes from a Mediterranean scenario.
Materials and Methods
Design and ethics
A retrospective multicenter observational study was designed to assess the situation of CSII-treated T1D patients in Spain in terms of indications, improvements in glycemic control, hypoglycemia frequency, the incidence of acute complications, the way CSII and associated continuous glucose monitoring (CGM), with or without automatic functions, was used. The database was designed according to previously published data.13 The protocol for this study was approved by the Reference Ethics Committee and conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. All participants provided written informed consent.
Data were typed through the web-based SPAIP registry designed by the Diabetes Technology Working Group of the Spanish Diabetes Society. The registry was accessible to all the members of the Spanish Diabetes Association willing to participate in this study by using a personal username and password. A data manager supervised the data introduced to avoid errors and to solve potential technical issues. The database complied with the European Union data protection regulations.
The inclusion criteria were a diagnosis of T1D and treatment with CSII. There were no exclusions for age, pregnancy, planning pregnancy, or breastfeeding.
Variables and outcomes
The registry included variables related to the patients' clinical status before starting CSII and at the last follow-up visit. The recorded variables included: gender, age, diabetes duration, main CSII indication, chronic diabetes complications, CSII treatment duration, HbA1c levels (measured at Hospital Analysis Departments with the use of methods certified by the National Glycohemoglobin Standardization Program), ambulatory glucose profile (AGP) related glycemic index (time above range [TAR] >10.0 mmol/L [180 mg/dL], time in range [TIR] 3.0–10 mmol/L [70–180 mg/day], time below range [TBR] <3.9 mmol/L [70 mg/dL], TBR <3 mmol/L [54 mg/dL] and coefficient of variation percentage [CV] of interstitial glucose), frequent hypoglycemia (defined as >10% of TBR <3.9 mmol/L [70 mg/dL]), severe hypoglycemia episodes (defined as hypoglycemia requiring third-party assistance), hypoglycemia unawareness (Clarke test score >4), diabetic ketoacidosis (DKA), self-blood glucose monitoring (SBGM) use, body weight, insulin doses and distribution, intermittently scanned CGM (isCGM) use, CSII settings (basal and pattern number) use of advanced CSII functions (insulin bolus advisor use), and CGM and advanced hybrid closed-loop (AHCL) use (CGM adherence, AHCL time of use). All the data were collected from electronic records and from pump downloads.
Primary efficacy outcome was the change in HbA1c from baseline to the last visit. Secondary efficacy outcomes included evaluation of the following variables: insulin pump indication, rates of acute diabetes complications, insulin and pump use, and CGM and AHCL use.
Statistical analysis
Cross-sectional and longitudinal/retrospective analyses for patients meeting inclusion criteria were performed. An assessment of the normality of data was initially performed through the Kolmogorov–Smirnov test. A paired Student's t-test or a Wilcoxon signed-rank test was used for the analysis of differences during the follow-up. The Kruskal Wallis test with Scheffé's multiple-comparison was used to compare quantitative variables with polytomous variables. Comparisons between proportions were analyzed using a chi-squared test. Mann–Whitney U and non-paired Student's t-test tests were used to analyze statistical differences between groups.
Analysis of variance (ANOVA) or Kruskal Wallis tests were performed to analyze statistical differences between different options of CSII treatment according to goodness-of-fit to the normal distribution. Correlations between variables were examined using the Spearman correlation test for metric variables. Multivariable linear regression models were used to assess the association between HbA1c and participant characteristics, insulin and pump use, or type of CSII treatment. Significance was taken at P < 0.05. Analyses were performed with IBM SPSS software version 28.0 for Windows (SPSS, Inc., Chicago, IL, USA).
Results
Patients and CSII indications
At the end of 2021, 2979 T1D patients treated with CSII were registered in the SPAIP registry. Information was gathered by diabetologists from 14 Spanish regions. The distribution of patients in each of the regions, the names of the centers, and the number of patients included per center are detailed in the Supplementary Data. Patients were followed during a median of 7.0 years (interquartile range [IQR] 3–10 years). The last follow-up visit was performed during 2021 in 1081 (36.3%) of the registered patients.
The patients (65% women) had showed a median age of 44 years (IQR 34–52 years) and a T1D duration of 27 years (IQR 18–35 years). One hundred eighty-four patients (6.2%) were younger than 18 years. Rapid-acting and basal insulin analogues were the most frequent (93%) treatment options before CSII initiation. The median duration of CSII therapy was 6 years (IQR 3–10 years). Sixty percent of the patients were treated with insulin pumps for 5 years or more. The rest of the demographics and baseline characteristics are shown in Table 1.
| Baseline characteristics | Total |
|---|---|
| n, number | 2979 |
| Sex (female/male) (%) | 65/35 |
| Age (years), median (IQR) | 44 (34–52) |
| Educational level (%) | |
| Primary education | 20.3 |
| Secondary education | 11.7 |
| General certificate of education | 29.7 |
| University | 38.3 |
| Diabetes duration (years), median (IQR) | 27 (18–35) |
| Body mass index (kg/m2), mean ± SD | 24.1 ± 4.5 |
| HbA1c (mmol/mol, %), mean ± SD | 62 ± 12 mmol/mol, 7.8 ± 1.1% |
| Daily insulin dose (units/[kg·day]), mean ± SD | 0.7 ± 0.3 |
| Basal/bolus insulin, % | 55.1/44.9 |
The most frequent indications in the whole group of patients for CSII therapy were suboptimal glycemic control, defined as HbA1c >53 mmol/mol (7%) on multiple daily insulin injections, in 33.8% of patients; problematic hypoglycemia, defined as severe hypoglycemia, nocturnal hypoglycemia, or impaired awareness of hypoglycemia, in 22.1% of patients; increased glycemic variability, defined by physician judgment, in 18.8% of patients; and ongoing or planning pregnancy, in 13.8% of the patients. Other frequent indications for the initiation of CSII therapy included a need for lifestyle flexibility (3.4%), experiencing the dawn phenomenon (2.4%), and having a low insulin requirement (1.5%).
Primary endpoint
HbA1c decreased at the end of follow-up by 6 mmol/mol (95% CI, −5 to −6 mmol/mol, P < 0.001) [−0.5%, 95% CI, −0.4 to −0.5, P < 0.001]. In fact, the final mean HbA1c was lower compared with mean HbA1c levels before CSII initiation (62 ± 12 mmol/mol vs. 56 ± 11 mmol/mol; 7.8 ± 1.1% vs. 7.3 ± 1.0%; P < 0.001). This reduction was greater in the group of patients with HbA1c >53 mmol/mol (7%) and in those with low insulin requirements as indications for CSII in which the reduction in HbA1c was of 8 mmol/mol (0.7%) (67 ± 12 mmol/mol vs. 60 ± 11 mmol/mol; 8.3% ± 1.1% vs. 7.6% ± 1.0%; P < 0.001) and 8 mmol/mol (0.7%) (60 ± 17 mmol/mol vs. 54 ± 8 mmol/mol; 7.6% ± 1.6% vs. 7.1% ± 0.7%; P < 0.001), respectively.
Table 2 shows the reduction in HbA1c for each indication for CSII. The proportion of patients achieving a significant clinical reduction in HbA1c ≥6 mmol/mol (0.5%) at the end of the follow-up was 46.7%. The HbA1c goal of <53 mmol/mol (7%) was attained by 49.2% of the youth (<18 years) and 36.4% of adult T1D patients, respectively.
| CSII indication (no. of patients) | HbA1c reduction, MDC mmol/mol (%) | 95% CI, mmol/mol (%) | P |
|---|---|---|---|
| Suboptimal glycemic control (957) | −8 (−0.7) | −9 to −7 (−0.8 to −0.6) | <0.001 |
| Problematic hypoglycemia (626) | −5 (−0.4) | −6 to −4 (−0.5 to −0.3) | <0.001 |
| Increased glycemic variability (534) | −5 (−0.4) | −6 to −4 (−0.5 to −0.3) | <0.001 |
| On-going or planning pregnancy (390) | −4 (−0.3) | −5 to −3 (−0.4 to 0.2) | <0.001 |
| Lifestyle flexibility (97) | −3 (−0.2) | −4 to 0 (−0.3 to 0.0) | 0.191 |
| Dawn phenomenon (69) | −5 (−0.4) | −8 to −3 (−0.7 to −0.2) | <0.001 |
| Low insulin requirement (43) | −8 (−0.7) | −13 to −3 (−1.2 to −0.2) | 0.004 |
| Others (281) | −2 (−0.1) | −6 to 4 (−0.5 to 0.3) | 0.780 |
| Total (2997) | −6 (−0.5) | −6 to −4 (−0.5 to −0.4) | <0.001 |
In multivariate analysis, final HbA1c was not associated with sex, age, educational level, body mass index, presence of diabetes complications, diabetes or CSII treatment duration, proportion of basal/bolus insulin, or daily bolus frequency.
Secondary endpoints
The percentage of patients with at least one episode of severe hypoglycemia in the year before starting insulin pump use decreased from 14.9% (n = 445) to 0.9% (n = 28) in the year before the final follow-up visit (P < 0.001). Only those patients using AHCL systems benefited from severe hypoglycemia reduction (P = 0.001), although patients treated with a sensor-augmented pump (SAP) presented a change approaching statistical significance (P = 0.058).
Patients suffering from hypoglycemia unawareness decreased from 12.1% (n = 361) before CSII to 8.5% (n = 252) at the end of the follow-up (P < 0.001). Finally, the percentage of patients with at least one episode of DKA during the last year remained stable from the beginning of the study to the end of the follow-up (4.5% vs. 4.0%, P = 0.332).
The daily insulin dose was reduced from the period before CSII to the end of the follow-up (0.7 ± 0.3 UI/[kg·day] vs. 0.6 ± 0.2 UI/[kg·day], P < 0.001). The proportion of bolus insulin was increased (44.8% ± 13.6% vs. 48.2% ± 13.1%, P < 0.001), whereas the proportion of basal insulin was decreased (55.2% ± 13.6% vs. 51.8% ± 13.1%, P < 0.001). We also detected a higher frequency of daily meal insulin boluses throughout the study, from 2.3 ± 0.2 to 3.0 ± 0.2 bolus/day (P < 0.001). Eighty-six percent of patients used the bolus advisor for most of their boluses, and 24% used different types of boluses. Patients used a mean of 6.4 ± 2.7 basal rates per day and 1.4 ± 1.1 basal patterns.
The CGM was already used before CSII initiation in 15.0% (448) of the registered patients, with real-time CGM being the most frequent option (50.9%), followed by isCGM (49.1%), whereas CGM was combined with CSII in 40.1% (1194) of the registered patients at the last follow-up visit. Among these patients, an insulin pump combined with isCGM was the most frequent treatment option (n = 560, 46.9%), followed by AHCL (n = 427, 35.8%) and SAP therapy with automatic low glucose suspend functions (n = 207, 17.3%).
The detected reduction in HbA1c was of −6 mmol/mol (95% CI, −5 to −7, P < 0.001) [−0.5%, 95% CI, −0.4 to −0.6, P < 0.001)], −5 mmol/mol (95% CI, −3 to −6 mmol/mol, P < 0.001) [−0.4%, 95% CI, −0.2 to −0.5, P < 0.001] and −8 mmol/mol (95% CI, −7 to −9 mmol/mol, P < 0.001) [−0.7%, 95% CI −0.6 to −0.8, P < 0.001] for CSII plus isCGM, SAP, and AHCL users, respectively. Patients treated with AHCL showed the greatest HbA1c reduction compared with other CSII options. Even those patients using CSII exclusively combined with SBGM attained a significant—5 mmol/mol (95% CI, −4 to −6, P < 0.001) (−0.4%, 95% CI, −0.3 to −0.5, P < 0.001) HbA1 reduction at the end of the study (Fig. 1).
FIG. 1. Boxplot showing HbA1c change from baseline levels from patients treated with CSII+SBGM (n = 932), CSII+isCGM (n = 383), SAP (n = 146), and AHCL (n = 319). AHCL, advanced hybrid closed-loop; CGM, continuous glucose monitoring; CSII, continuous subcutaneous insulin infusion; HbA1c, glycated hemoglobin A1c; isCGM, intermittently scanned CGM; SAP, sensor-augmented pump; SBGM, self-blood glucose monitoring.
We observed an inverse correlation between HbA1c levels at the end of the follow-up and CGM adherence (R =−0.24, P < 0.001). Even after excluding patients with a CGM adherence lower than 70% or 80%, we observed this correlation (R =−0.15, P < 0.001 and R =−0.1, P = 0.01, respectively) (Fig. 2A). However, this correlation was not found in patients with a CGM adherence greater than 90% (R = 0.02, P = 0.53).
FIG. 2. Correlation between HbA1c levels at the end of the follow-up and CGM adherence (A) and the percentage of time with active AHCL functions (B). CGM, continuous glucose monitoring; AHCL, advanced hybrid closed-loop.
We also detected an inversely correlation between final HbA1c and the percentage of time with active AHCL functions (R =−0.25, P < 0.001). Moreover, this correlation was maintained after excluding those patients with AHCL adherence <80% (R =−0.26, P < 0.001) (Fig. 2B). Finally, we detected an inverse correlation between the daily frequency of isCGM scanning and final HbA1c levels among insulin pump combined with isCGM users (R =−0.19, P = 0.001).
Complementary AGP profile data at the end of follow-up from 31.8% (n = 946) of the patients showed TAR >10 mmol/L (180 mg/dL), TIR 3.9–10 mmol/L (70–180 mg/dL), and TBR <3.9 mmol/L (70 mg/dL) percentages of 28.4%, 67.4%, and 4.2%, respectively. However, no differences were detected in these glycemic indexes between different options of CSII treatment (P > 0.05). A direct and an inverse correlation between TIR 3.9–10 mmol/L (70–180 mg/dL) (R = 0.276, P < 0.001) and TBR <3.9 mmol/L (70 mg/dL) (R =−0.264, P < 0.001) with the percentage of time with active AHCL functions were observed.
The composite endpoint of TAR >10 mmol/L (180 mg/dL) <25%, TIR 3.9–10 mmol/L (70–180 mg/dL) >70%, TBR <3.9 mmol/L (70 mg/dL) <4% and CV of interstitial glucose ≤36% was achieved by 23.6% (n = 223) of these patients.
Additional AGP metrics from 4.2% (n = 124) of the patients were analyzed from the beginning of the study until the end of the follow-up. We observed an increment in the TIR 3.9–10 mmol/L (70–180 mg/dL) of 14.7% (95% CI, 11.7–17.7, P < 0.001) and a TBR <3.9 mmol/L (70 mg/dL) reduction of −5.8% (95% CI, −4.1 to −7.5, P < 0.001) during the follow-up. Glycemic variability expressed as CV was lower at the end of the follow-up (44.2% vs. 33.4%, P = 0.001). The rest of these glycemic metrics are shown in Table 3.
| Baseline | End of follow-up | MDC (95% CI) | P | |
|---|---|---|---|---|
| GMI, % | 7.0 ± 0.7 | 6.7 ± 0.5 | −0.2 (−0.1 to −0.4) | 0.001 |
| mmol/mol | 53 ± 8 | 49.7 ± 6 | −3 (−2 to −5) | |
| Mean interstitial glucose, mg/dL | 153 | 144 | −9 (−4 to −14) | 0.001 |
| mmol/L | 8.5 | 8.0 | − 0.5 (−0.2 to −0.8) | |
| Mean blood glucose, mg/dL | 165 | 153 | −11 (−1 to −23) | 0.044 |
| mmol/L | 9.2 | 8.5 | −0.6 (−0.1 to −1.3) | |
| CV (%) | 44.2 | 33.4 | −10.8 (−4.8 to −16.8) | 0.001 |
| TAR >180 mg/dL (>10 mmol/L) | 31.2 | 22.5 | −8.7% (−5.7 to −11.8) | <0.001 |
| TIR 70–180 mg/dL (3.9–10 mmol/L) | 57.5 | 72.2 | 14.7 (11.7 to 17.7) | <0.001 |
| TBR <70 mg/dL (<3.9 mmol/L) | 10.9 | 5.0 | −5.8 (−4.1 to −7.5) | <0.001 |
| TBR <54 mg/dL (<3 mmol/L) | 0.8 | 0.5 | −0.3 (−0.9 to 0.3) | 0.352 |
Discussion
The novelty of the present results lies in the updated description of CSII-treated T1D patients in Spain. Overall, we found a reduction in HbA1c of −6 mmol/mol (95% CI, −5 to −6 mmol/mol, P < 0.001) (−0.5%, 95% CI, −0.4 to −0.5, P < 0.001) during the 7-year follow-up period. To date, this is the most comprehensive description of insulin pump benefits over glycemic control in a Mediterranean scenario.
The CSII is an effective intensive tool for improving glycemic control in patients with T1D.2,3,15–17 An additional HbA1c reduction of 5 mmol/mol (0.4%) is achieved with CSII use in T1D patients compared with MDI treatment.4 Despite this advantage and the increasing use of technology to treat T1D patients, only a small percentage (21%) of adult T1D patients achieved the HbA1c target <53 mmol/mol (7%) in the T1D Exchange registry.10 In fact, the average HbA1c observed in adult patients on CSII was close to 58 mmol/mol (7.5%).18
Data from the Canadian LMC Diabetes Registry confirmed similar mean HbA1c values (61.7 mmol/mol, 7.8%) in CSII-treated T1D patients.12 European registries showed non-clinically different HbA1c results in Sweden (63 mmol/mol, 7.9%) and Denmark (59.6 mmol/mol, 7.6%).19,20 Here, we describe a slightly lower HbA1c value (56.3 mmol/mol, 7.3%) compared with other registries, and a sustained benefit in terms of glycemic control compared with our previously published data (58 mmol/mol, 7.5%).13
This improved outcome may be due to the recent introduction of more advanced intensive insulin options such as AHCL in routine clinical practice. In fact, real-world hybrid closed-loop system use allowed successful achievement of glycemic control within recommended targets and overall glycemic control that trended similarly with the system pivotal trial outcomes and previous real-world system use analyses.21,22 Admittedly, AHCL use seemed to be best for HbA1c reduction and was considered the primary driver for significant HbA1c reductions, among integrated insulin delivery systems, in a recent meta-analysis focused on diabetes technology for T1D treatment.23
However, the many barriers to the adoption and use of CSII and combined CGM technology in Spain are well known: therapeutic inertia, logistical and organizational failures, and a lack of leadership, to name but a few.24
We demonstrate a greater HbA1c reduction with AHCL compared with other CSII treatment options. Notably, an inverse correlation was observed between final HbA1c levels and the percentage of time with active AHCL functions (R =−0.25, P < 0.001). In addition, in the subgroup of patients for whom AGP glycometrics were available, a direct and an inverse correlation between TIR (R = 0.276, P < 0.001) and TBR (R =−0.264, P < 0.001) with the percentage of time with active AHCL functions were found. To the best of our knowledge, this is the first time that AGP glycometrics have been described from a national diabetes registry.
Despite the introduction of better insulin analogues and isCGM in T1D treatment, reaching the goal of an HbA1c < 53 mmol/mol (7%) has remained distant for most people with T1D.25–29 Recently, the Sociedad Española de Diabetes (SED1) study showed that 70% of patients in Spain did not achieve this HbA1c level.30 Therefore, it is not surprising that having suboptimal glycemic control is the most common (33.8%) indication for CSII treatment in our country. Our main indications of CSII treatment are consistent with other published series.31,32
The use of insulin pump therapy previously demonstrated an effect on nocturnal hypoglycemia, reducing this without increasing HbA1c values. The most recent literature-summary meta-analysis of the literature found no difference in severe or mild hypoglycemia with CSII therapy compared with MDI treatment.4 However, the ratio of severe hypoglycemia in randomized controlled trials of MDI versus CSII in T1D patients is 2.0 (1.08–3.69; P = 0.027) for decision-making meta-analysis.33
During follow-up, we observed a reduction in the percentage of CSII-treated patients with at least one severe hypoglycemic episode in the previous year and hypoglycemia unawareness. This benefit was only detected among AHCL technology users (P = 0.001) and almost detected in SAP-treated patients (P = 0.058). Recent studies have shown that the integration of CGM with CSII therapy significantly reduces the occurrence of these conditions by providing real-time glucose readings/trends and automatically suspending insulin infusion when glucose is too low or even before glucose is too low but is predicted to drop soon.34
Indeed, these results confirmed the long-term benefits of this treatment in control over severe hypoglycemia and impaired the perception of hypoglycemia published in our previous studies.13,14 In addition, a decrease in TBR <3.9 mmol/L (70 mg/dL) was observed in patients in whom glycometric AGP information was available during the study.
Nowadays, the risk of DKA with CSII treatment is considered to be as low as the risk for patients on MDI therapy.35 Insulin pump therapy can lead to different outcomes, especially in relation to DKA depending on receiving access to appropriate diabetes educational programs. Specific diabetes training focused on insulin pumps contains extensive information, including how to detect and correct early ketosis situations. In fact, we described a similar percentage of patients suffering from at least one episode of DKA during the year before the introduction of CSII compared with the same period before the last visit.
The current study has several strengths. No other national registry has ever described the clinical effect of insulin pump use in people with T1D in a Mediterranean setting. Previous geographically limited studies describing the distribution, clinical impact, and safety of pumps have only used questionnaires or cohort data. In addition, our data provide a relatively long follow-up (7 years), with 60% of patients treated with CSII for 5 years or more. Finally, the typical glycemic endpoints (HbA1c, severe hypoglycemia, DKA, etc.) in T1D patients were supplemented with AGP information where possible.
Nevertheless, there are some limitations to this study. Firstly, in the absence of comparable data on patients treated with other MDI regimens, we are unable to present data from a control group and therefore can only build upon data from patients before the onset of the CSII treatment. Second, due to the characteristics of an observational study, we could not establish a direct cause-and-effect relationship between the use of insulin pumps and the clinical benefits.
There are other factors that may also have contributed to the benefits described, such as the time health care professionals spent with patients in relation to the initiation of therapy, education about carbohydrate counting, more intensive monitoring of blood glucose, and avoidance of hypoglycemia. Health care professionals may even have had better access to patient data during clinical review through device uploads, which may have been particularly important during the COVID-19 pandemic when remote health care was practiced.
Unfortunately, we did not collect this information, so these confounding factors should be considered. Finally, there are specific subgroups of patients with T1D who have different glycemic targets. As described, this study was essentially a survey of adults (6.2% of participants were younger than 18 years), and pregnant women or women planning to become pregnant represented 13% of the total cohort. Therefore, our results should be interpreted with caution in other groups of CSII-treated patients.
Conclusions
Nonetheless, the magnitude of the improvements and the long-term results sufficiently demonstrate the benefit of CSII treatment, particularly the visible improvement of patients who were treated with intensified MDI insulin regimens with inadequate results until the commencement of CSII treatment.
In conclusion, treatment with CSII was associated with a relevant and sustained improvement in glycemic control in Spain.
Authors' Contributions
J.M.-F. and P.I.B.-V. designed the study. J.M.F. wrote the study protocol and published this in a public registry. J.M.F. and P.I.B.V. helped gather the data. J.M.F. and J.R.M.-R. contributed to the interpretation of the results. J.R.M.-R. supervised the statistical analysis. J.M.F. took the lead in writing the article. All authors provided critical feedback and helped shape the final article.
Acknowledgments
The authors are very grateful to Spanish Diabetes Association (SED) for their support in promoting the SPAIP registry and this study. Collaborating researchers of the SPAIP study (listed by surname alphabetical order): Ainhoa Abad López, Hospital Universitario Puerta del Hierro, Madrid; Eva Aguilera Hurtado, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona; Mercé Albareda Riera, Hospital Moises Broggi, Barcelona; Francisco Javier Ampudia Blasco, Hospital Clínico Universitario de Valencia, Valencia; Víctor Manuel Andía Melero, Hospital Universitario Gregorio Marañón, Madrid; Ramiro Antuña de Alaiz, Clínica Diabetológica, Asturias; Teresa Armenta Joya, Hospital Universitario La Princesa, Madrid; J. Alfonso Arranz Martín, Hospital Universitario La Princesa, Madrid; Sharona Azriel Mira, Hospital Infanta Sofía, San Sebastian de los Reyes, Madrid; María Pilar Bahillo Curieses, Hospital Clínico Universitario de Valladolid, Valladolid; Antonio Ballesteros Martín-Portugués, Hospital Universitario de Jeréz de la Frontera, Cádiz; Virginia Bellido Castañeda, Hospital Universitario Virgen del Rocío, Sevilla; Benito Blanco Samper, Hospital Virgen del Prado, Talavera de la Reina, Toledo; Raquel Barrios Castellanos, Centro Médico D-Medical, Madrid; Martín Cuesta Hernández, Hospital Clínico San Carlos, Madrid; Cristina del Castillo Villaescusa, Hospital Universitario Dr. Peset, Valencia; Gonzalo Díaz Soto, Hospital Clínico Universitario de Valladolid, Valladolid; Beatriz García Cuartero, Hospital Universitario Ramón y Cajal, Madrid; José Manuel García López, Hospital Universitario de Santiago de Compostela, La Coruña; Marta García Mouriz, Hospital Universitario de Navarra, Pamplona; Marga Giménez Álvarez, Hospital Clinic, Barcelona; Estela Gil Poch, Complejo Hospitalario de Badajoz, Badajoz; Francisco Javier Gómez Alfonso, Hospital La Mancha-Centro, Alcázar de San Juan, Ciudad Real; Cintia González Blanco, Hospital de la Santa Creu i Sant Pau, Barcelona; Javier González López, Hospital Virgen de la Luz, Cuenca; María José Goñi Iriarte, Hospital Universitario de Navarra, Pamplona; Noelia Gros Herguido, Hospital Universitario Virgen del Rocío, Sevilla; Sandra Herranz Antolín, Hospital Universitario de Guadalajara, Guadalajara; Belén Huidobro Fernández, Hospital de Cabueñes-Gijón, Asturias; Luz María López Jiménez, Hospital Universitario de Albacete, Albacete; Gracia María Lou Francés, Hospital Universitario Miguel Servet, Zaragoza; Beatriz Mantiñan Gil, Hospital Universitario de Santiago de Compostela, La Coruña; Pilar Martín Vaquero, Centro Médico D-Medical, Madrid; Elena Mena Ribas, Hospital Universitario Son Espases, Palma, Islas Baleares; Juan Francisco Merino Torres, Hospital Universitario La Fe, Valencia; Marta Murillo Vallés, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona; Víctor Navas Moreno, Hospital Universitario La Princesa, Madrid; Lía Nattero Chávez; Hospital Universitario Ramón y Cajal, Madrid; Nerea Petrirena Gorosterrazu, Complejo Hospitalario de Navarra, Pamplona; María Picallo Pérez, Hospital Universitario de Áraba, Álava; María José Picón César, Hospital Universitario Virgen de la Victoria, Málaga; Pedro José Pinés Corrales, Hospital Universitario de Albacete, Albacete; Ángel Rebollo Román, Hospital Universitario Reina Sofía, Córdoba; Mercedes Rigla Cros, Hospital Parc Taulí, Sabadell, Barcelona; Carlos Roa Llamazares, Hospital General Universitario de Ciudad Real, Ciudad Real; Rosa Márquez Pardo, Hospital Universitario de Jerez de la Frontera, Cádiz; Elena Parreño Caparrós, Hospital de la Vega Lorenzo Guirao, Murcia; Belén Roldán Martín, Hospital Ramón y Cajal, Madrid; Yolanda Salgado Frutos, Hospital de Cruces, Barakaldo, Biskaia; Amaya Sainz de los Terreros Errea, Hospital Universitario de Navarra, Pamplona; Paula Sánchez Sobrino, Hospital Universitario de Pontevedra, Pontevedra; Francisco Javier Sanz Gallur, Hospital Lluís Alcanyís, Xátiva, Alicante; Olga Simo Servat, Hospital Vall d´Hebron, Barcelona; Patricia Sierra Gutiérrez, Hospital El Ángel y Clínica Rincón, Málaga; Inmaculada Simón Muelas, Hospital Universitario Joan XXIII, Tarragona; Eva Solá Izquierdo, Hospital Universitario Dr. Peset, Valencia; Estíbaliz Ugarte Albasolo, Hospital Universitario de Basurto, Bilbao; Federico Vázquez San Miguel, Hospital de Cruces, Barakaldo, Biskaia.
Author Disclosure Statement
The authors declare that they have not received research support or compensation from Medtronic, Tandem, Roche, or Ypsomed. J.M.-F. reports consultant fees from and speaker honoraria from Medtronic, Tandem, Dexcom, Abbott, Roche, and Ypsomed. M.P. reports consultant fees from and speaker honoraria from Novo Nordisk, Lilly, Boehringer-Lilly, Esteve, Sanofi, MSD, Sanofi, and Pfizer. P.I.B.V. has received speaking/consulting honoraria from Medtronic Diabetes, Roche Diabetes, Abbot, Novalab, and Lilly. The rest of the authors declare that they have no conflicts of interest concerning this article.
Funding Information
Research reported in this study was in part supported by Instituto de Salud Carlos III (Project PI17/01674) and co-supported by the European Union (ERDF/ESF, "Investing in your future").
Supplementary Material
Supplementary Data
References
- 1. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329(14):977–986; doi:
10.1056/NEJM199309303291401 . Crossref, Medline, Google Scholar - 2. In type 1 diabetic patients with good glycaemic control, blood glucose variability is lower during continuous subcutaneous insulin infusion than during multiple daily injections with insulin glargine. Diabet Med J Br Diabet Assoc 2008;25(3):326–332; doi:
10.1111/j.1464–5491.2007.02365.x . Crossref, Medline, Google Scholar - 3. A randomized, prospective trial comparing the efficacy of continuous subcutaneous insulin infusion with multiple daily injections using insulin glargine. Diabetes Care 2004;27(7):1554–1558; doi:
10.2337/diacare.27.7.1554 . Crossref, Medline, Google Scholar - 4. Continuous subcutaneous insulin infusion versus multiple daily injections in individuals with type 1 diabetes: A systematic review and meta-analysis. Endocrine 2017;55(1):77–84; doi:
10.1007/s12020-016-1039-x . Crossref, Medline, Google Scholar - 5. Continuous subcutaneous insulin infusion (CSII) in the Veneto Region: Efficacy, acceptability and quality of life. Diabet Med J Br Diabet Assoc 2002;19(8):628–634; doi:
10.1046/j.1464-5491.2002.00750.x . Crossref, Medline, Google Scholar - 6. Long-term outcome of insulin pump therapy: Reduction of hypoglycaemia and impact on glycaemic control. Diabet Med J Br Diabet Assoc 2016;33(10):1422–1426; doi:
10.1111/dme.13094 . Crossref, Medline, Google Scholar - 7. Comparison between a multiple daily insulin injection regimen (basal once-daily Glargine plus Mealtime Lispro) and continuous subcutaneous insulin infusion (Lispro) using continuous glucose monitoring in metabolically optimized type 1 diabetes patients: A randomized open-labelled parallel study. Med Clin (Barc) 2016;146(6):239–246; doi:
10.1016/j.medcli.2015.09.020 . Crossref, Medline, Google Scholar - 8. Type 1 diabetes and long-term continuous subcutaneous insulin infusion therapy: A 10-year experience from Macedonia. Diabetes Technol Ther 2017;19(12):739–743; doi:
10.1089/dia.2017.0227 . Link, Google Scholar - 9. Insulin-pump use in everyday practice: Data from an Exhaustive Regional Registry in France. Diabetes Metab 2008;34(2):132–139; doi:
10.1016/j.diabet.2007.10.010 . Crossref, Medline, Google Scholar - 10. State of type 1 diabetes management and outcomes from the T1D Exchange in 2016–2018. Diabetes Technol Ther 2019;21(2):66–72; doi:
10.1089/dia.2018.0384 . Link, Google Scholar - 11. Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18,168 people with type 1 diabetes: Observational study. BMJ 2015;350:h3234; https://www.bmj.com/content/350/bmj.h3234.long; doi:
10.1136/bmj.h3234 . Crossref, Google Scholar - 12. The Canadian LMC Diabetes Registry: A profile of the demographics, management, and outcomes of individuals with type 1 diabetes. Diabetes Technol Ther 2021;23(1):31–40; doi:
10.1089/dia.2020.0204 . Link, Google Scholar - 13. A National Survey on the efficacy and safety of continuous subcutaneous insulin infusion in patients with type 1 diabetes in Spain. Diabetes Res Clin Pract 2018;137:56–63; https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(17)31425-0/fullte; doi: 10.1016/j.diabres.2017.12.009. Crossref, Medline, Google Scholar
- 14. Continuous subcutaneous insulin infusion in adult type 1 diabetes mellitus patients: Results from a Public Health System. Diabetes Technol Ther 2019;21(8):440–447; doi:
10.1089/dia.2019.0097 . Link, Google Scholar - 15. Continuous subcutaneous insulin infusion is more effective than multiple daily insulin injections in preventing albumin excretion rate increase in type 1 diabetic patients. Diabet Med J Br Diabet Assoc 2009;26(6):602–608; doi:
10.1111/j.1464-5491.2009.02736.x . Crossref, Medline, Google Scholar - 16. . Long-acting insulin analogs versus insulin pump therapy for the treatment of type 1 and type 2 diabetes. Diabetes Care 2008;31 Suppl 2:S140–S145; doi: 10.2337/dc08-s235. Crossref, Medline, Google Scholar
- 17. Diabetes Technology: Standards of Medical Care in Diabetes-2022. Diabetes Care 45(Suppl 1):S97–S112; doi:
10.2337/dc22-S007 . Crossref, Google Scholar - 18. HbA1c levels in type 1 diabetes from early childhood to older adults: A deeper dive into the influence of technology and socioeconomic status on HbA1c in the T1D Exchange Clinic Registry Findings. Diabetes Technol Ther 2020;22(9):645–650; doi:
10.1089/dia.2019.0393 . Link, Google Scholar - 19. Prevalence and geographical distribution of insulin pump therapy in the Central Denmark Region and its association with metabolic parameters. Diabetes Res Clin Pract 2018;141:148–155; https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(17)32014-4/fullte; doi: 10.1016/j.diabres.2018.04.042. Crossref, Medline, Google Scholar
- 20. Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: A Nationwide, Register-Based Cohort Study. Lancet Lond Engl 2018;392(10146):477–486; doi:
10.1016/S0140-6736(18)31506-X . Crossref, Medline, Google Scholar - 21. Glycemic outcomes during real-world hybrid closed-loop system use by individuals with type 1 diabetes in the United States. J Diabetes Sci Technol 2022;19322968221088610 (In Press); https://journals.sagepub.com/doi/10.1177/19322968221088608?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed; doi:
10.1177/19322968221088608 . Crossref, Google Scholar - 22. Six-month glycemic control with a hybrid closed-loop system in type 1 diabetes patients in a Latin American Country. Diabetes Technol Ther 2022;24(3):220–226; doi:
10.1089/dia.2021.0248 . Link, Google Scholar - 23. The efficacy of technology in type 1 diabetes: A systematic review, network meta-analysis, and narrative synthesis. Diabetes Technol Ther 2020;22(5):411–421; doi:
10.1089/dia.2019.0417 . Link, Google Scholar - 24. . Possible causes of under-use of continuous subcutaneous insulin infusion in Spain. Av En Diabetol 2013;29(1):1–3; doi:
10.1016/j.avdiab.2012.11.002 . Crossref, Google Scholar - 25. Effect of flash glucose monitoring in adults with type 1 diabetes: A nationwide, longitudinal observational study of 14,372 flash users compared with 7691 glucose sensor Naive controls. Diabetologia 2021;64(7):1595–1603; doi:
10.1007/s00125-021-05437-z . Crossref, Medline, Google Scholar - 26. Intermittently scanned continuous glucose monitoring is associated with high satisfaction but increased hba1c and weight in well-controlled youth with type 1 diabetes. Pediatr Diabetes 2020;21(8):1465–1474; doi:
10.1111/pedi.13128 . Crossref, Medline, Google Scholar - 27. Effect of flash glucose monitoring on glycemic control, hypoglycemia, diabetes-related distress, and resource utilization in the Association of British Clinical Diabetologists (ABCD) Nationwide Audit. Diabetes Care 2020;43(9):2153–2160; doi:
10.2337/dc20-0738 . Crossref, Medline, Google Scholar - 28. Important drop in rate of acute diabetes complications in people with type 1 or type 2 diabetes after initiation of flash glucose monitoring in France: The RELIEF Study. Diabetes Care 2021;44(6):1368–1376; doi:
10.2337/dc20-1690 . Crossref, Medline, Google Scholar - 29. Two-year use of Flash Glucose Monitoring Is Associated with Sustained Improvement of Glycemic Control and Quality of Life (FLARE-NL-6). BMJ Open Diabetes Res Care 2021;9(1):e002124; doi:
10.1136/bmjdrc-2021-002124 . Crossref, Google Scholar - 30. Clinical characteristics and management of type 1 diabetes in Spain. The SED1 Study. Endocrinol Diabetes Nutr 2021;68(9):642–653; doi:
10.1016/j.endien.2021.11.020 . Crossref, Google Scholar - 31. Indications for insulin pump therapy in type 1 diabetes and associations with glycemic control. J Diabetes Sci Technol 2016;10(5):1027–1033; doi:
10.1177/1932296816650209 . Crossref, Medline, Google Scholar - 32. Sustained benefit of continuous subcutaneous insulin infusion on glycaemic control and hypoglycaemia in adults with type 1 diabetes. Diabet Med J Br Diabet Assoc 2015;32(11):1453–1459; doi:
10.1111/dme.12869 . Crossref, Medline, Google Scholar - 33. . The evidence base for diabetes technology: Appropriate and inappropriate meta-analysis. J Diabetes Sci Technol 2013;7(6):1567–1574; doi:
10.1177/193229681300700617 . Crossref, Medline, Google Scholar - 34. Prevention and management of severe hypoglycemia and hypoglycemia unawareness: Incorporating sensor technology. Curr Diab Rep 2018;18(10):83; doi:
10.1007/s11892-018-1065-6 . Crossref, Google Scholar - 35. Contrasting the clinical care and outcomes of 2,622 children with type 1 diabetes less than 6 years of age in the United States T1D Exchange and German/Austrian DPV Registries. Diabetologia 2014;57(8):1578–1585; doi:
10.1007/s00125-014-3272-2 . Crossref, Medline, Google Scholar
Source: https://www.liebertpub.com/doi/10.1089/dia.2022.0207
0 Response to "64 and Exchange and Continuous Subcutaneous Insulin Infusion"
Post a Comment