Real-world evidence of off-label use of commercially automated insulin delivery systems compared to multiple daily insulin injections in pregnancies complicated by type 1 diabetes.

AIMS: To compare glycemic control and maternal-fetal outcomes of women with type 1 diabetes (T1D) using hybrid closed loop (HCL) vs. multiple daily insulin injections (MDI) plus continuous glucose monitoring (CGM). METHODS: Multicenter prospective cohort study of pregnant women with T1D in Spain. We evaluated HbA1c and time spent within (TIR), below (TBR) and above (TAR) the pregnancy-specific glucose range 3.5-7.8 mmol/L. Adjusted models were performed for adverse pregnancy outcomes including baseline maternal characteristics and center. RESULTS: 112 women were included (HCL n=59). Women in the HCL group had a longer duration of diabetes and higher rates of prepregnancy care. There were no between-group differences in HbA1c in any trimester. However, in the second trimester, MDI users had a greater decrease in HbA1c (-6.12±9.06 vs. -2.16 ±7.42 mmol/mol, p=0.031). No differences in TIR (3.5-7.8 mmol/L) and TAR were observed between HCL and MDI users, but with a higher total insulin dose in the second trimester (+0.13 IU/Kg/d). HCL therapy was associated with increased maternal weight gain during pregnancy (ßadjusted 3.20 kg, 95%CI 0.90-5.50). Regarding neonatal outcomes, newborns of HCL users were more likely to have higher birthweight (ßadjusted 279.0 g, 95% CI 39.5-518.5) and macrosomia (ORadjusted 3.18, 95% CI 1.05-9.67) compared to MDI users. These associations disappeared when maternal weight gain or third trimester HbA1c were included in the models. CONCLUSIONS: In a real-world setting, HCL users gained more weight during pregnancy and had larger newborns than MDI users, while achieving similar glycemic control in terms of HbA1c and TIR.

Impact of Flash Glucose Monitoring on the Fear of Hypoglycemia Phenomenon in Adults with Type 1 Diabetes.

Objective: To assess the clinical impact of flash glucose monitoring (FGM) systems on fear of hypoglycemia (FoH) and quality of life in adults with type 1 diabetes mellitus (T1DM). Methods: Prospective quasi-experimental study with a 12-month follow-up. People with T1DM (18-80 years old) and self-monitoring by blood capillary glycemia controls were included. The FH15 questionnaire, a survey validated in Spanish in a comparable study population, was used to diagnose FoH with a cutoff point of 28 points. Results: A total of 181 participants were included, with a FoH prevalence of 69% (n = 123). A mean reduction in FH15 score of -4 points (95% confidence interval [-5.5 to -3]; P < 0.001) was observed, along with an improvement in quality of life (EsDQOL-test (Diabetes Quality of Life, Spanish version), -7 points [-10; -4], P < 0.001) and satisfaction with treatment (Diabetes Treatment Satisfaction questionnaire, self-reported version [DTSQ-s] test, +4.5 points [4; 5.5], P < 0.001). At the end of the follow-up, 64.2% of the participants saw an improved FoH intensity, compared to 35.8% who scored the same or higher. This improvement in FoH status was associated with a higher time-in-range at the end of the follow-up (P = 0.003), as well as a lower time spent in hyperglycemia (P = 0.005). In addition, it was linked to participants with a high baseline FoH levels (P < 0.001) and those who were university degree holders (P = 0.07). Conclusions: FGM is associated with an overall reduction of FoH in adults with T1DM and with an increase in their quality of life. Nevertheless, a significant percentage of patients may experience an increase of this phenomenon leading to clinical repercussions and a profound impact on quality of life.

A Multicenter Prospective Evaluation of the Benefits of Two Advanced Hybrid Closed-Loop Systems in Glucose Control and Patient-Reported Outcomes in a Real-world Setting.

OBJECTIVE: Advanced hybrid closed-loop systems (AHCL) have been shown to improve glycemic control and patient-reported outcomes in type 1 diabetes. The aim was to analyze the outcomes of two commercially available AHCL in real life. RESEARCH DESIGN AND METHODS: A prospective study was performed, including adolescents and adults with type 1 diabetes, AHCL naïve, from 14 centers, who initiated the use of MM780G with SmartGuard or Tandem t:slimX2 with Control-IQ. Baseline and 3-month evaluations were performed, assessing HbA1c, time in different glycemic ranges, and patient-reported outcomes. The primary outcome was the between-group time in range 70-180 mg/dL difference from beginning to end of follow-up. RESULTS: One hundred fifty participants were included, with 75 initiating each system (age: 39.9 ± 11.4 years [16-72]; 64% female; diabetes duration: 21.6 ± 11.9 years). Time in range increased from 61.53 ± 14.01% to 76.17 ± 9.48% (P < 0.001), with no between-group differences (P = 0.591). HbA1c decreased by 0.56% (95% CI 0.44%, 0.68%) (6 mmol/mol, 95% CI 5, 7) (P < 0.001), from 7.43 ± 1.07% to 6.88 ± 0.60% (58 ± 12 to 52 ± 7 mmol/mol) in the MM780G group, and from 7.14 ± 0.70% to 6.56 ± 0.53% (55 ± 8 to 48 ± 6 mmol/mol) in the Control-IQ group (both P < 0.001 to baseline, P = 0.819 between groups). No superiority of one AHCL over the other regarding fear of hypoglycemia or quality of life was found. Improvement in diabetes-related distress was higher in Control-IQ users (P = 0.012). Sleep quality was improved (PSQI: from 6.94 ± 4.06 to 6.06 ± 4.05, P = 0.004), without differences between systems. Experience with AHCL, evaluated by the INSPIRE measures, exceeded the expectations. CONCLUSIONS: The two AHCL provide significant improvement in glucose control and satisfaction, with no superiority of one AHCL over the other.

A prospective observational concordance study to evaluate computational model-driven clinical practice guidelines for Type 2 diabetes mellitus.

BACKGROUND: Clinical Practice Guidelines (CPGs) provide healthcare professionals with performance and decision-making support during the treatment of patients. Sometimes, however, they are poorly implemented. The IDE4ICDS platform was developed and validated with CPGs for type 2 diabetes mellitus (T2DM). OBJECTIVE: The main objective of this paper is to present the results of the clinical validation of the IDE4ICDS platform in a real clinical environment at two health clinics in the Andalusian Public Health System (SSPA) in the southern Spanish region of Andalusia. METHODS: National and international knowledge sources on T2DM were selected and reviewed and used to define a diabetes CPG model on the IDE4ICDS platform. Once the diabetes CPG was configured and deployed, it was validated. A total of 506 patients were identified as meeting the inclusion criteria, of whom 130 could be recruited and 89 attended the appointment. RESULTS: A concordance analysis was performed with the kappa value. Overall agreement between the recommendations provided by the system and those recorded in each patient's EHR was good (0.61 - 0.80) with a total kappa index of 0.701, leading to the conclusion that the system provided appropriate recommendations for each patient and was therefore well-functioning. CONCLUSIONS: A series of possible improvements were identified based on the limitations for the recovery of variables related to the quality of these recolected variables, the detection of duplicate recommendations based on different input variables for the same patient, and clinical usability, such as the capacity to generate reports based on the recommendations generated. Nevertheless, the project resulted in the IDE4ICDS platform: a Clinical Decision Support System (CDSS) capable of providing appropriate recommendations for improving the management and quality of patient care and optimizing health outcomes. The result of this validation is a safe and effective pathway for developing and adopting digital transformation at the regional scale of the use of biomedical knowledge in real healthcare.

Effectiveness of a flash glucose monitoring systems implementation program through a group and telematic educational intervention in adults with type 1 diabetes.

OBJECTIVES: Verifying the clinical effectiveness and the impact on quality-of-life parameters, fear of hypoglycaemia and satisfaction with the treatment obtained with a flash glucose monitoring (MFG) devices implantation program that includes a telematic and group educational intervention in adults with type 1 diabetes. PATIENTS AND METHODS: Prospective quasi-experimental study, carried out during the COVID-19 pandemic period with a 9-month follow-up at the Virgen Macarena University Hospital, Sevilla. RESULTS: Eighty-eight participants were included (men: 46.6%; mean age (years) 38.08, SD: 9.38); years of DM1 evolution: 18.4 (SD: 10.49); treatment with multiple doses insulin (MDI) 70.5% vs 29.5% subcutaneous insulin infusion therapy (CSII)). Baseline HbA1c was 7.74% (1.08). After the intervention, the global decrease in HbA1c was -0.45% (95% CI [-0.6, -0.25], P < 0.01), increasing to -1.08% in the group that started with HbA1c ≥ 8% (P < 0.01). A mean decrease in the Fear of Hypoglycemia 15 (FH15) test score of -6.5 points was observed (P < 0.01). In the global score of the Spanish version of Diabetes Quality Of Life (DQOL-s) test, the decrease was -8.44 points (P < 0.01). In Diabetes Treatment Satisfaction Questionnaire test (DTQ-s), global score increased in + 4 points (P < 0.01). CONCLUSIONS: The incorporation of an educational program in group and telematic format within the development of MFG devices implantation strategies is an effective option, with associated benefits in quality of life and fear of hypoglycemia in adult patients with DM1. This option can be implemented in usual clinical practice.

Flash Glucose Monitoring and Diabetes Mellitus Induced by Immune Checkpoint Inhibitors: An Approach to Clinical Practice.

Objectives: The aim of this study is to investigate in depth diabetes mellitus associated with immune checkpoint inhibitors (DM-ICIs) by analysing a case series. We also evaluated the clinical impact of flash glucose monitoring (FGM) systems in the management of this entity. Methods: We conducted an observational cohort study of DM-ICIs diagnosed in two hospitals in Seville (Spain). Patients with a new diagnosis of diabetes mellitus (DM) or with sudden worsening of preexisting DM after starting treatment with ICIs, with a random 5 hour-postprandial C-peptide value of <0.6 nmol/L and without possibility of subsequent withdrawal of insulin treatment, were included. Results: A total of 7 cases were identified, mostly males (n = 6; 85.7%), with a mean age of 64.9 years. The mean glycated hemoglobin (HbA1c) upon diagnosis was 8.1%, with diabetic ketoacidosis (DKA) observed in 6 cases (85.7%). Subcutaneous flash glucose monitoring (FGM) systems were used in six cases, with a mean follow-up period of 42.7 weeks. During the first 90 days of use, mean average glucose was 167.5 mg/dL, with a coefficient of variation (CV) of 34.6%. The mean time in the range 70-180 mg/dL (TIR) was 59.7%, with a mean time above range (TAR) 181-250 mg/dL of 27.8% and a mean TAR > 250 mg/dL of 10.2%. The mean time below range (TBR) 54-69 mg/dL was 2%, while the mean TBR < 54 mg/dL was 0.3%. The mean glucose management indicator (GMI) was 7.3%. No significant differences were observed in FGM values for the following 90 days of follow-up. A progressive improvement in all parameters of glycaemic control was observed between the first month of FGM use and the sixth month of FGM use. Of note, there was a decrease in mean CV (40.6% to 34.1%, p = 0.25), mean TAR 181-250 (30.3% to 26%, p = 0.49), mean TAR > 250 mg/dL (16.3% to 7.7%, p = 0.09), mean TBR 54-69 mg/dL (5.2% to 2%, p = 0.16), and mean TBR < 54 mg/dL (1.8% to 0.2%, p = 0.31), along with an increase in mean values of TIR 70-180 mg/dL (46.5% to 60.5%, p = 0.09). The lack of statistical significance in the differences observed in the mean FGM values over the follow-up period may be related to the small sample size. Conclusion: DM-ICI is recognised by a state of sudden-onset insulinopenia, often associated with DKA. The use of FGM systems may be a valid option for the effective management of DM-ICIs and for the prevention of severe hyperglycaemic and hypoglycaemic episodes in this condition.

Novel APOB nonsense variant related to familial hypobetalipoproteinemia and hepatic steatosis: A case report and review.

Hereditary familial hypobetalipoproteinemia (FHBL) is a syndrome caused by variants in the APOB gene, that cause a defect in the secretion and mobilization of liver lipids to peripheral tissues, associated with the synthesis of truncated ApoB100 apolipoproteins. This condition causes significant reduction in total cholesterol (TC), low-density lipoproteins (LDL), very low-density proteins (VLDL) and serum triglyceride levels, with unchanged high-density lipoprotein (HDL) cholesterol levels. Herein we present the case of a middle-aged woman diagnosed with FHBL and hepatic steatosis, heterozygous for c.4698C>A; (p.Tyr1566Ter) variant in APOB. The variant presented herein showed high expressiveness in the two generations of individuals analyzed and has not yet being described in the medical literature. Early diagnosis and screening for associated metabolic comorbidities such as metabolic fatty liver disease and its subsequent progression to fibrosis are the two main goals in the treatment of this condition, in order to prevent medium to long term potential complications.

Continuous Subcutaneous Insulin Infusion in Type 1 Diabetes Mellitus Patients: Results from the Spanish National Registry.

Aim: To analyze the clinical effect of continuous subcutaneous insulin infusion (CSII) in type 1 diabetes mellitus (T1D) patients in the Spanish real-world scenario. Methods: All T1D patients on CSII registered in the SPAnish Insulin Pump (SPAIP) registry were included. The primary efficacy outcome was change in HbA1c during follow-up. Secondary efficacy outcomes included: insulin pump indications, diabetes complication rates, insulin and pump use, and continuous glucose monitoring (CGM) glycometrics. Patient data were typed through the web-based SPAIP registry. Results: Data from 2979 T1D patients treated with CSII were analyzed. The median age was 44 years (interquartile range [IQR] 34-52 years), and T1D duration was 27 years (IQR 18-35 years). The median duration of CSII therapy was 6 years (IQR 3-10 years). The main indications for treatment were suboptimal glycemic control (33.8%), hypoglycemia (22.1%), and increased glycemic variability (18.8%). Glycated hemoglobin decreased 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] during the follow-up. The percentage of patients with severe hypoglycemia decreased from 14.9% to 0.9% (P < 0.001). We observed an inverse correlation between final HbA1c levels and CGM adherence (R = -0.24, P < 0.001) or percentage of time with active hybrid closed-loop functions (R = -0.25, P < 0.001). Conclusions: CSII treatment was associated with a sustained improvement in glycemic control in the Spanish population. This benefit was greater among patients with higher CGM or active hybrid closed-loop functions adherence. The protocol was publicly registered at ClinicalTrials.gov (NCT04761094).

Changes in the Epidemiology of Diabetic Retinopathy in Spain: A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of the present study was to determine the prevalence and incidence of diabetic retinopathy (DR) and its changes in the last 20 years in type 2 diabetes mellitus (T2DM) patients in Spain. METHODS: A systematic review with a meta-analysis was carried out on the studies published between 2001-2020 on the prevalence and incidence of DR and sight-threatening diabetic retinopathy (STDR) in Spain. The articles included were selected from four databases and publications of the Spanish Ministry of Health and Regional Health Care System (RHCS). The meta-analysis to determine heterogeneity and bias between studies was carried out with the MetaXL 4.0. RESULTS: Since 2001, we have observed an increase in the detection of patients with DM, and at the same time, screening programs for RD have been launched; thus, we can deduce that the increase in the detection of patients with DM, many of them in the initial phases, far exceeds the increased detection of patients with DR. The prevalence of DR was higher between 2001 and 2008 with values of 28.85%. These values decreased over the following period between 2009 and 2020 with a mean of 15.28%. Similarly the STDR prevalence decrease from 3.67% to 1.92% after 2008. The analysis of the longitudinal studies determined that the annual DR incidence was 3.83%, and the STDR annual incidence was 0.41%. CONCLUSION: In Spain, for T2DM, the current prevalence of DR is 15.28% and 1.92% forSTDR. The annual incidence of DR is 3.83% and is 0.41% for STDR.

Andalusian program for early detection of diabetic retinopathy: implementation and 15-year follow-up of a population-based screening program in Andalusia, Southern Spain.

INTRODUCTION: Diabetic retinopathy (DR) is a preventable cause of vision loss and blindness worldwide. We aim at analyzing the impact of a population-based screening program of DR using retinal photography with remote reading in terms of population coverage, diagnosis of asymptomatic DR and impact on visual disability, in the region of Andalusia, Spain, in the period 2005-2019. RESEARCH DESIGN AND METHODS: Descriptive study. Sociodemographic and clinical features included in the Andalusian program for early detection of diabetic retinopathy (APDR) were analyzed. Population coverage, annual incidence of DR, and DR severity gradation were analyzed. Estimated data on prevalence and incidence of legal blindness due to DR were included. RESULTS: 407 762 patients with at least one successful DR examination during the study period were included. Most of the performed retinographies (784 584, 84.3%) were 'non-pathological.' Asymptomatic DR was detected in 52 748 (5.9%) retinographies, most of them (94.2%) being classified as 'mild to moderate non-proliferative DR.' DR was detected in 44 815 patients, while sight-threatening DR (STDR) in 6256 patients; cumulative incidence of DR was 11.0% and STDR was 1.5%, as DR and STDR was detected in 44 815 and 6256 patients, respectively. Annual incidence risk per patient recruitment year progressively decreased from 22.0% by January 2005 to 3.2% by June 2019. CONCLUSIONS: Implementation of a long-term population-based screening program for early detection of DR is technically feasible and clinically viable. Thus, after 15 years of existence, the program has enabled the screening of the vast majority of the target population allowing the optimization of healthcare resources and the identification of asymptomatic DR.

Gender differences in quality of life in adults with long-standing type 1 diabetes mellitus.

BACKGROUND: To assess gender differences in Quality of life (QoL) and in sociodemographic, clinical and psychological factors associated with impaired QoL in adults with long-standing type 1 diabetes mellitus (DM1). METHODS: Cross-sectional evaluation in a random cohort of DM1 adult patients from a tertiary care hospital. QoL was evaluated using translated and validated self-administered Diabetes QoL questionnaire (Es-DQoL), and results transformed into a 0-100 scale. Psychological assessment included a planned psychological interview and self-reported questionnaires (Beck Depression Inventory II, State-Trait Anxiety Inventory Form Y, Fear of hypoglycaemia Scale, Medical Outcomes Study Social Support Survey). RESULTS: A total of 312 patients (51.6% male; 38.2 ± 12.7 years; HbA1c 7.5 ± 1.1% (58.5 ± 14.2 mmol/mol); 20.4 ± 12.0 years of DM1) were included in the analysis. Male and female subgroups showed similar sociodemographic and diabetes-related features and comparable social support. Among female patients, higher frequency of depression [31.7% (IC95% 26.2-40.8) vs. 14.9% (IC95% 10.1-20.8), p < 0.05] and anxiety [23.2% (IC95% 19.3-33.14) vs. 13.0% (IC95% 8.1-18.4), p < 0.05] and severity of depressive and anxious symptoms were also found. Compared to male patients, female patients showed lower QoL [75 (IC95% 73.6-77.5) vs. 80 (IC95% 75.7-83.1), p < 0.05] and scored significantly worse in subscale Diabetes-related worries [69 (IC95% 50.0-81.0) vs. 75 (IC95% 72.9-79.0), p < 0.05]. Fear of hypoglycemia and severity of depressive and anxious symptoms were factors independently associated to lower QoL in men and women while high frequency of glycemic excursions was a female-specific predictive one. CONCLUSIONS: Adult women with long-standing DM1 showed lower QoL probably related to higher frequency and severity of psychopathological syndromes. Depressive and anxious symptoms and, among women, exposure to glycemic excursions were identified as modifiable, QoL-related variables. Educational, technological and psychological interventions are needed in order to improve QoL in DM1 patients.

Intervention in emotional abilities for adolescents with type 1 diabetes mellitus in a hospital setting: a study protocol for a randomised controlled trial.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is one of the most frequent chronic endocrine diseases in the paediatric population. As a result, this disease has a strong impact on psychological well-being. In line with this, emotional factors play an important role in adaptation. The aim of the present study protocol is to design an emotional abilities programme to improve metabolic control assessed by haemoglobin A1c (HbA1c) samples. Specifically, this intervention will be focused on adaptive coping strategies to deal with unpleasant emotions associated with T1DM. The primary aim of this project is to assess whether the employment of this new psychological intervention improves the emotional abilities of adolescents with T1DM. METHODS AND ANALYSIS: Two focus groups will be carried out for the design and evaluation of the programme following the APEASE criteria (affordability, practicability, effectiveness, acceptability, side effects/safety and equity). Behavioural change will be based on the Behaviour Change Wheel. Sixty-two participants from 12 to 18 years of age will be recruited at a public hospital and randomised to either an intervention or a control group. The intervention group will receive an emotional abilities training programme. The control group will receive usual educational intervention. The primary outcomes are metabolic control and emotional abilities. The secondary outcomes include emotional distress control, positive and negative affect, healthy habits, and quality of life. Data will be collected at baseline, immediately postintervention, and at follow-up visits at 6 and 12 months. A feasibility analysis will be conducted. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of Universidad Loyola Andalucía. Results will be submitted for publication in peer-reviewed journals and disseminated across the scientific community. TRIAL REGISTRATION NUMBER: NCT03734367.

Renal function and choroidal thickness using swept-source optical coherence tomography in diabetic patients.

AIM: To assess the relationship between choroidal thickness and renal function in diabetic patients. METHODS: Cross-sectional retrospective clinical study of 42 eyes of 21 ocular treatment-naïve diabetic patients. Demographic data included: age, sex, type and course of diabetes. Ocular data included: severity of diabetic retinopathy; retinal thickness at the central macular region, as well as choroidal thickness at the central and paracentral quadrants, using automatically generated maps by swept-source optical coherence tomography; presence of cystic macular edema; and ocular axial length (AXL). Lab-test parameters included: glycated hemoglobin (HbA1c), albuminuria, albumin/creatinine ratio in urine, and glomerular filtration rate. RESULTS: A significant negative correlation was mainly observed between several choroidal thicknesses, age (P<0.020) and ocular AXL (P<0.030). On the contrary, a significant positive correlation was found between all choroidal thicknesses, HbA1c (P<0.035) and albuminuria (P<0.040). CONCLUSION: Choroidal thickness can represent an additional tool to help clinicians predicting the renal status in ocular treatment-naïve diabetic patients.

Emotional abilities and HbA1c levels in patients with type 1 diabetes.

In recent years a growing body of research is focused on the relationships between emotions and health. When it comes to diabetes, findings suggest that distress might play a key role in the acquisition and maintenance of health habits associated with diabetic management. This report describes two studies examining the roles of emotional abilities in diabetic management from two different conceptual points of view using two culturally different samples. In study 1, we examined the relationship between emotional intelligence and HbA1c levels in a sample of eighty-five patients with type 1 diabetes mellitus (DM1) in Israel. In study 2, we examined the relationship between specific emotional regulation strategies and HbA1c in sixty-seven adolescents with DM1, while examining the mediating role of distress in this association. The results showed a negative association between emotional intelligence and HbA1c levels, even after controlling for potential intervening factors. We found that the relationship between difficulties in emotion regulation and HbA1c seemed to be mediated by diabetes-related distress. These findings may aid in the design of psychological models for future research as well as interventions aimed at improving emotional abilities in people with DM1.