Diabetes mellitus is one of the most pressing health problems worldwide due to the enormous personal, social and economic costs that it incurs. Type 1 diabetes mellitus (T1DM), though less prevalent than type 2 diabetes, is a growing health problem1 that primarily affects a young sector of the population, in which blood glucose control and prevention of short- and long-term complications are keys to treatment.2 Therapeutic management of patients with T1DM is under continuous development, and since the publication in 1993 of the Diabetes Control and Complication Trial (DCCT) study3 and, after that, the results of the observational Epidemiology of Diabetes Intervention and Complication Trial (EDICT) study,4 it has been clear that achieving and maintaining blood glucose levels as close as possible to normal causes significant reduction in the microvascular and macrovascular complications associated with the disease. To achieve this end, in the past decade, there have been major changes in the tools for treating T1DM. Advanced treatment education programmes and newly developed insulins have improved current insulin therapy regimens and brought them closer to physiologically normal patterns.5 With new automated continuous subcutaneous insulin infusion (CSII) systems6,7 and simplification of continuous glucose monitoring (CGM) devices,8 technology has engendered great hopes for improving blood glucose control outcomes. However, this technification of treatment for T1DM has increased the complexity of treatments, and the need for greater specialisation and training of endocrinology and nutrition specialists, who must dedicate more time in their practice to optimising these therapies and making the most of their potential.9

In 2010, the DIACAM1 (DIAbetes tipo 1 en CAstilla la Mancha) study backed by the Sociedad Castellano Manchega de Endocrinología, Nutrición y Diabetes (SCAMEND) was designed in an attempt to determine the situation of patients with T1DM with regard to control and complications in the Autonomous Community of Castilla-La Mancha. DIACAM1 documented the glycaemic control status, treatment regimens used and factors related to better glycaemic control in a representative cohort of patients with DM1 in this autonomous community.10 After 10 years, the results of this cohort were reviewed to analyse whether there were changes in the degree of metabolic control and treatment patterns and to assess, where possible, the factors related to achieving metabolic control targets and how technology may be influencing this.

The DIACAM1 study was an observational, cross-sectional, multicentre study of patients with T1DM in regular follow-up in endocrinology outpatient clinics in the eight health areas of Castilla-La Mancha (Albacete, Ciudad Real, Cuenca, Guadalajara, La Mancha Centro, Puertollano, Talavera de la Reina and Toledo). The selection criteria for the patients included in the study were previously reported.10 The initial cohort (2009–2010) included 1,465 patients with T1DM 16 years of age or older, with more than five years since onset at the time of inclusion in the study.

This sample represented a third of the estimated population with T1DM over 14 years of age in the Autonomous Community. The sample size was calculated based on the diabetic population registry of Castilla-La Mancha primary care teams (Turriano, 2008 Castilla-La Mancha Health Department activity report), considering 5% of the population with T1DM and a prevalence of 0.31% in people over 14 years of age. A representative number of patients was established for each of the eight health areas, based on the registered resident population.

The study was approved by the Complejo Hospitalario de Toledo [Toledo Hospital Complex] Research Ethics Committee as the investigator-coordinating centre and patients gave their written informed consent to be included in the study.

The results analysed in this study corresponded to 1,121 patients in active follow-up and are presented jointly for the eight Castilla-La Mancha health areas.

The prevalence of T1DM in Castilla-La Mancha is high,12 and recently published data show that, in our Autonomous Community, T1DM accounts for 10% of visits made to outpatient clinics.13 To determine the situation with regard to blood glucose control in this group of patients, 10 years ago, the DIACAM1 study was designed.10 In 2010, the results obtained showed that a quarter of the people with T1DM included had good metabolic control, defined as a HbA1c under 7, and two thirds had acceptable control, defined as a HbA1c under 8%. The 2020 DIACAM1 study was designed to determine the degree of metabolic control and treatment regimens of the DIACAM1 cohort, after 10 years of follow-up under regular clinical practice conditions. After this period, the overall degree of blood glucose control improved in this cohort, but the proportion of patients who achieved the objective of a HbA1c below 7% remained stable.

These results show that, despite the advances achieved in the therapeutic management of patients with T1DM, clinical practice lies far from achieving the recommended objectives. Several recent cross-sectional Spanish national studies14–16 have yielded outcomes similar to the DIACAM1 cohort, with just 25%–35% of the patients included in these studies achieving the overall objective of HbA1c <7%.

The DIACAM1 study was the first Spanish national multicentre study having prospectively analysed an extensive cohort of patients with T1DM, from the Spanish public health system, 10 years after their inclusion. Our results showed that even in patients with long-standing diabetes, it is possible to improve metabolic control outcomes. In a study by Carral et al.15 after 10 years of follow-up of HbA1c, it was significantly reduced. The same happened in a study in Catalonia by Amor et al.,14 but both studies analysed results in the context of a single-specialisation clinic with a programme aimed at comprehensive follow-up of patients with T1DM. Our results for improvement in blood glucose control over time contrasted with the findings published for the North American Exchange study,17 which prospectively analysed an extensive cohort of patients with T1DM between 2010 and 2018 in the United States. The data from the latest analysis demonstrated little variation in HbA1c between the 2010-2012 cohort and the 2016-2018 cohort, with a worsening of control in the group of adolescents.17 On a national level, with the objective of examining the degree of blood glucose control in the child/juvenile population with T1DM at a specialised referral practice, outcomes in nearly 300 patients were analysed,18 a mean HbA1c of 6.7% was achieved, with ADA objectives attained in more than 90% of the children and youth included, far from the 17% published in the Exchange study.17 In the SED1 study,16 while it was not designed to analyse a population under 18 years of age, this subgroup achieved a HbA1c of 7.6%, with 29% of youths achieving the target of a HbA1c under 7%; the results were similar in adults.

When we analysed determining factors in blood glucose control in our cohort, level of education attained was a factor maintained over the course of the 10 years of follow-up;10 this determining factor was similarly reflected in the recently published SED1 study16 and could be an indirect indicator of the degree of adherence to the treatment education programme.19

An intensified insulin therapy regimen is the gold standard for achieving better blood glucose control. Since the results of the DCCT/EDIC study were published,4 the most physiologically normal insulin therapy regimens have been known to yield the best results. In the Exchange study, patients who used CSII achieved lower HbA1c levels.17 Several recent studies in Spain20 and in our Autonomous Community21 have also demonstrated better blood glucose control outcomes in patients with CSII. The percentage of patients who use CSII in Spain is rising, although it is still lower than expected and the country is far from the CSII usage figures in Europe more broadly.22 In 2010, just 9% of the patients included in the DIACAM1 cohort used CSII; the increase to 13% after 10 years was significant, but lower than that reported in other groups,16 representing an opportunity for improvement. Similar to the use of CSII, the use of CGM is associated with better blood glucose control outcomes.16,17 The development of the Flash® glucose measurement system has represented a “before” and “after” in self-management of blood glucose in patients with T1DM. Its lower costs and benefits have allowed more patients to access CGM and increased the indications for it, ultimately making funding by the public health system possible for all patients with T1DM over 4 years of age. In Castilla-La Mancha, CGM has been funded since November 2019, leading in a certain way to the results obtained in this study. The results ended in June 2020, just six months after the start of public funding, and three months after the start of the COVID-19 pandemic, which has hindered the implementation of this monitoring system due to initial lock-downs at home. Some 27% of the patients from the 2020 DIACAM1 study used CGM and achieved better blood glucose control regardless of the insulin regimen used. Recently published data indicates that, although prescription of CGM is higher in patients who use complex insulin regimens or CSII, the impact on the improvement of blood glucose control is higher even with simpler insulin regimens.23

HbA1c is a marker of chronic hyperglycaemia. Metabolic memory not only leads to lesser development of microvascular and macrovascular complications, but also was the most powerful independent factor in our cohort in achieving suitable blood glucose control. Lower blood glucose exposure 10 years earlier would contribute to maintaining suitable blood glucose control today. This must influence the need to intensify therapeutic and educational measures to achieve good blood glucose control from the beginning, which will surely yield better long-term outcomes. Studies analysing series of patients with T1DM in regular periodic follow-up since the onset of the disease, with a structured educational programme and intensified treatment, have achieved good control as of the first few years, resulting in better overall blood glucose control and a lower rate of complications.24

The impact of classic cardiovascular risk factors on blood glucose control has been extensively studied in the DCCT/EDIC cohort25 and in recent population studies of adult patients with T1DM.26 The absence of active tobacco use in the initial DIACAM1 cohort was associated with better blood glucose control.10 In the multivariate analysis of the 2020 cohort, an independent relationship was maintained between the achievement of HbA1c under 7% and the absence of hyperlipidaemia; this was consistent with the known effects of blood glucose control on lipid metabolism.25 This inter-relationship between cardiovascular risk factors and blood glucose control should help develop intervention measures for managing comorbidities and reducing cardiovascular risk in patients with T1DM.27,28

Our patients with T1DM showed a worsening in their cardiovascular risk profile after 10 years of follow-up; however, this must be qualified. First, the prevalence of tobacco use improved, although not significantly. In addition, the intensification of lipid-lowering and hypotensive treatment regimens contributed significantly to the fact that the percentage of patients with hypertension and dyslipidaemia increased (as the use of these treatments is included in the definition of these risk factors). However, this intensification was key to the fact that the achievement of lipid and blood-pressure control targets improved compared to the 2010 DIACAM1 study, especially with respect to targets for lipid (LDL-C and HDL-C) control.

Weight gain due to ageing and associated with intensified insulin therapy itself has been known to be a complication since the first data from the DCCT study was released.3 It requires a specific approach with education and exercise programmes, as well as, possibly, the use of drugs that contribute to weight loss.29 In our cohort, the use of metformin remained constant at around 8% over the course of these 10 years; rates of incretin drugs and glucosuric drugs were around 1%. Concomitant use of other antidiabetic agents in the treatment of T1DM was not collected in most of the Spanish series analysed,14,16,24 apart from a study by Carral et al.15 in which 6.5% of the patients included used other antidiabetic drugs.

Our study had several limitations, some inherent to observational, cross-sectional studies and others resulting from the COVID-19 pandemic, which surely affected some of the anthropometric and laboratory data collected in the final months of the study (March to June 2020). In addition, collecting data from medical records did not allow us to gather reliable data on the incidence of episodes of severe hypoglycaemia. We believe the great strength of the 2020 DIACAM1 study, on the other hand, was that we managed to collect and analyse data for 80.5% of the patients in the initial cohort; this rate was similar to that achieved in other European multicentre studies.30 Although it was far from the 96% rate achieved in the EDIC study, it constitutes an extensive cohort representative of the population with T1DM in Castilla-La Mancha.

The data for overall blood glucose control, estimated based on HbA1c in patients with T1DM en Castilla-La Mancha, did not differ from those documented elsewhere in Spain, and improved after 10 years of follow-up. The use of intensified insulin regimens and the implementation of the use of technology applied to diabetes care appear to be determining factors in achieving this improvement, and offer an opportunity to continue improving outcomes in blood glucose control and complications in DM1.

The authors declare that they have no conflicts of interest in relation to the results of the study.