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.

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.

Role of Muscle Ultrasound for the Study of Frailty in Elderly Patients with Diabetes: A Pilot Study.

BACKGROUND: Sarcopenia and diabetes contribute to the development of frailty. Therefore, accessible methods, such as muscle ultrasounds (MUSs), to screen for sarcopenia should be implemented in clinical practice. METHODS: We conducted a cross-sectional pilot study including 47 patients with diabetes (mean age: 77.72 ± 5.08 years, mean weight: 75.8 kg ± 15.89 kg, and body mass index: 31.19 ± 6.65 kg/m2) categorized as frail by the FRAIL Scale or Clinical Frailty Scale and confirmed by Fried's Frailty Phenotype or Rockwood's 36-item Frailty Index. We used the SARC-F questionnaire to identify sarcopenia. The Short Physical Performance Battery (SPPB) and the Timed Up and Go (TUG) tests were used to assess physical performance and the risk of falls, respectively. In addition, other variables were measured: fat-free mass (FFM) and Sarcopenia Risk Index (SRI) with the bioimpedance analysis (BIA); thigh muscle thickness (TMT) of the quadriceps with MUS; and hand-grip strength with dynamometry. RESULTS: We observed correlations between the SARC-F and FFM (R = -0.4; p < 0.002) and hand-grip strength (R = -0.5; p < 0.0002), as well as between the TMT and FFM of the right leg (R = 0.4; p < 0.02) and the SRI (R = 0.6; p < 0.0001). We could predict sarcopenia using a logistic regression model with a ROC curve (AUC = 0.78) including FFM, handgrip strength, and TMT. The optimal cut-off point for maximum efficiency was 1.58 cm for TMT (sensitivity = 71.4% and specificity = 51.5%). However, we did not observe differences in the TMT among groups of greater/less frailty based on the SARC-F, SPPB, and TUG (p > 0.05). CONCLUSIONS: MUSs, which correlated with the BIA (R = 0.4; p < 0.02), complemented the diagnosis, identifying regional sarcopenia of the quadriceps in frail patients with diabetes and improving the ROC curve to AUC = 0.78. In addition, a TMT cut-off point for the diagnosis of sarcopenia of 1.58 cm was obtained. Larger studies to validate the MUS technique as a screening strategy are warranted.

The Medtronic 780G advanced hybrid closed-loop system achieves and maintains good glycaemic control in type 1 diabetes adults despite previous treatment.

INTRODUCTION: Improvements in continuous glucose monitoring (CGM) in recent years have changed the treatment of type 1 diabetes (T1D) by permitting the automation of glucose control. The Minimed 780G advanced hybrid closed-loop (ACHL) system adapts basal infusion rates and delivers auto-correction boluses in order to achieve a user-decided glucose target (100, 110 or 120mg/dL). This study set out to evaluate the effectiveness of the Medtronic 780G system in real-life conditions over 6 months. MATERIALS AND METHODS: Prospective study that included T1D subjects previously treated with insulin pump without CGM (pump group) or with sensor-augmented pump with predictive low-glucose suspend (SAP-PLGS group) who started with the Minimed 780G system. Sensor and pump data from baseline, and at 1, 3 and 6 months were downloaded and HbA1c was recorded at baseline and at 6 months. RESULTS: Fifty T1D subjects were included; 25 were previous SAP-PLGS 640G users and 25 used 640G without CGM. 66% were female, 48.6 (40-57) years of age with 20 (12-31.5) years of diabetes duration. Time in range (TIR) improved in the total cohort from baseline to 6 months (69% (57.7-76) vs. 74% (70-82); p=0.01 as did HbA1c (7.6% (7.1-7.8) vs. 7.0% (6.8-7.5); p<0.001), with improvement in times <54, >180 and >250mg/dL. Outcomes at 6 months did not differ between groups, although the SAP-PLGS subjects were prone to hypoglycaemia and the pump group mainly presented suboptimal metabolic control. CONCLUSION: The AHCL Medtronic Minimed 780G system achieves and maintains good glycaemic control over 6 months in real-life conditions in different profiles of T1D subjects.

Chondroid Tumors: Review of Salient Imaging Features and Update on the WHO Classification.

Chondrogenic tumors are typically well recognized on radiographs, but differentiation between benign and malignant cartilaginous lesions can be difficult both for the radiologist and for the pathologist. Diagnosis is based on a combination of clinical, radiological and histological findings. While treatment of benign lesions does not require surgery, the only curative treatment for chondrosarcoma is resection. This article (1) emphasizes the update of the WHO classification and its diagnostic and clinical effects; (2) describes the imaging features of the various types of cartilaginous tumors, highlighting findings that can help differentiate benign from malignant lesions; (3) presents differential diagnoses; and (4) provides pathologic correlation. We attempt to offer valuable clues in the approach to this vast entity.

Role of Excessive Weight Gain During Gestation in the Risk of ADHD in Offspring of Women With Gestational Diabetes.

CONTEXT: Although attention-deficit/hyperactivity disorder (ADHD) has been associated with gestational diabetes mellitus (GDM) and maternal obesity, excessive weight gain (EWG) during pregnancy has scarcely been evaluated. OBJECTIVE: This study aimed to assess the joint effect of maternal weight and EWG on the risk of ADHD in offspring of GDM pregnancies. METHODS: In this cohort study of singleton births >22 weeks of gestation of women with GDM between 1991 and 2008, gestational weight gain above the National Academy of Medicine (NAM) recommendations was classified into EWG. Cox-regression models estimated the effect of maternal pregestational weight and EWG on the risk of ADHD (identified from medical records), adjusted for pregnancy outcomes and GDM-related variables. RESULTS: Of 1036 children who were included, with a median follow-up of 17.7 years, 135 (13%) were diagnosed with ADHD. ADHD rates according to pregestational maternal weight were 1/14 (7.1%) for underweight, 62/546 (11.4%) for normal weight, 40/281 (14.2%) for overweight, and 32/195 (16.4%) for obesity. Only maternal obesity was independently associated with ADHD (HRadjusted 1.66 [95% CI, 1.07-2.60]), but not maternal overweight or EWG. On evaluating the joint contribution of maternal weight and EWG, maternal obesity with EWG was associated with the highest risk of ADHD (vs normal weight without EWG; HRadjusted 2.13 [95% CI, 1.14-4.01]). Pregestational obesity without EWG was no longer associated (HRadjusted 1.36 [95% CI, 0.78-2.36]). CONCLUSION: Among GDM pregnancies, pregestational obesity was associated with a higher risk of ADHD in offspring. Nonetheless, when gestational weight gain was taken into account, only the joint association of obesity and EWG remained significant.

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).

Usefulness of Muscle Ultrasound to Study Sarcopenic Obesity: A Pilot Case-Control Study.

Background and objectives: Sarcopenic obesity (SO) is an emerging problem, especially in candidates for bariatric surgery (BS). We hypothesized that musculoskeletal ultrasound (MUS), a simple and accessible method, could be a reliable index of SO. Materials and Methods: A cross-sectional pilot study including 122 subjects (90 cases and 32 controls, 73% female, mean age: 51.2 years) who underwent BS was conducted at University Hospital Mútua Terrassa. The lean mass (LM) was calculated by bioelectrical impedance analysis (BIA) and the thigh muscle thickness (TMT) by MUS. To identify the subjects with SO by BIA, we used skeletal muscle index (SMI). The validity of MUS was determined using the ROC curve. Results: The mean BMI in the obesity group was 44.22 kg/m2. We observed a correlation between the LM and SMI assessed by BIA and the TMT assessed by MUS (R = 0.46, p < 0.001). This correlation was maintained at significant levels in the SO group (n = 40): R = 0.79; p = 0.003). The TMT assessed by MUS was able to predict SMI using BIA (AUC 0.77; 95% CI: 0.68242 to 0.84281). The optimal cut-off point for maximum efficiency was 1.57 cm in TMT (sensitivity = 75.6% and specificity = 71.1%). Conclusions: The TMT of the quadriceps assessed by US is a useful tool for identifying subjects with SO. Larger studies to validate this simple low-cost screening strategy are warranted.

Predictors of perfusion computed tomography alterations in stroke mimics attended as stroke code.

BACKGROUND AND PURPOSE: Stroke mimics (SMs) account for a significant number of patients attended as stroke code (SC) with an increasing number over the years. Recent studies show perfusion computed tomography (PCT) alterations in some SMs, especially in seizures. The objective of our study was to evaluate the clinical characteristics and PCT alterations in SMs attended as SC in order to identify potential predictors of PCT alterations in SMs. METHODS: A retrospective study was performed including all SC activations undergoing a multimodal CT study including non-enhanced computed tomography (CT), CT angiography and PCT, as part of our SC protocol, over 39 months. Patients with a final diagnosis of SM after complete diagnosis work-up were therefore selected. Clinical variables, diagnosis, PCT alteration patterns and type of map affected (Tmax or time to peak, cerebral blood flow and cerebral blood volume) were registered. RESULTS: Stroke mimics represent up to 16% (284/1761) of SCs with a complete multimodal study according to our series. Amongst SMs, 26% (74/284) showed PCT alterations. PCT abnormalities are more prevalent in seizures and status epilepticus and the main pattern is alteration of the time to peak map, of unilateral hemispheric distribution or of non-vascular territory. In our series, the independent predictors of alteration in PCT in SMs are aphasia, female sex and older age. CONCLUSIONS: Perfusion computed tomography alterations can be found amongst almost a third of SMs attended as SC, especially older women presenting with aphasia with a final diagnosis of epileptic seizures and status epilepticus.

Nuclear magnetic resonance lipoproteins are associated with carotid atherosclerosis in type 1 diabetes and pre-eclampsia.

AIMS: Persistence of lipoprotein abnormalities in type 1 diabetes (T1D) and/or pre-eclampsia could be associated with cardiovascular disease (CVD). We assessed differences in the advanced lipoprotein profiles according to the presence of both conditions and their differential association with atherosclerosis. MATERIAL AND METHODS: We recruited 112 women without CVD and last pregnancy ≥5 years previously, divided into four groups (n = 28 per group): (a) T1D and previous pre-eclampsia; (b) T1D without pre-eclampsia; (c) pre-eclampsia without T1D; and (d) controls (without T1D/pre-eclampsia). Groups were matched by several risk factors, and diabetes duration and retinopathy in T1D. Carotid intima-media thickness (IMT) and the presence of plaque (IMT ≥1.5 mm) were assessed by ultrasonography. The lipoprotein profile was evaluated by nuclear magnetic resonance (NMR) spectroscopy. RESULTS: The participants were 44.9 ± 7.8 years old. Carotid plaque presence was 20.5%, with a higher prevalence in T1D and/or pre-eclampsia vs controls (P < .05). High-density lipoprotein (HDL)-related variables differed among groups, mainly driven by an increase in T1D (P < .05), whereas triglyceride-related variables were increased in pre-eclampsia [medium very low-density lipoprotein (VLDL) particles and triglyceride enrichment in HDL and low-density lipoprotein (LDL)]. Overall, in multivariate-adjusted models, LDL-related variables were the most strongly associated with atherosclerosis (P < .05). In age- and statin-adjusted models, previous pre-eclampsia showed an independent association with triglyceride-related variables (plaque: medium-VLDL-particles, OR 1.550 [1.013-2.374]; HDL-cholesterol/HDL-triglycerides ratio, OR 0.411 [0.175-0.967]). Regarding T1D, HDL-parameters were also differentially associated (maximum-IMT: HDL-cholesterol/HDL-particles ratio, ß = -.258, P = .036). CONCLUSIONS: NMR lipoproteins were differentially and independently associated with atherosclerosis in T1D/pre-eclampsia. Further studies are needed to ascertain the role of NMR parameters as CVD biomarkers in this high-risk population.

Preeclampsia Is Associated With Increased Preclinical Carotid Atherosclerosis in Women With Type 1 Diabetes.

PURPOSE: Although preeclampsia (PE) is a well-established cardiovascular risk factor (CVRF) in the general population, its role in type 1 diabetes (T1D) has been scarcely studied. We assessed the association between PE and preclinical atherosclerosis in T1D. METHODS: We recruited 112 women without cardiovascular disease and last pregnancy ≥5 years before: (1) T1D and previous PE (T1D+/PE+; n = 28); (2) T1D without preeclampsia (T1D+/PE-; n = 28); (3) previous PE without T1D (T1D-/PE+; n = 28); and (4) controls (without T1D or PE; T1D-/PE-; n = 28). Groups were matched by age, several CVRFs, and diabetes duration and retinopathy (in T1D participants). Carotid intima-media thickness (IMT) and the presence of plaque (IMT ≥ 1.5 mm) were assessed by standardized ultrasonography protocol. RESULTS: Mean age of the participants was 44.9 ± 7.8 years (14.3% hypertension and 21.4% active smokers). Groups including T1D (T1D+/PE+ and T1D+/PE-) more frequently presented hypertension and statin treatment (23.2% vs 5.4% and 37.5% vs 8.9%; respectively; P < 0.01), without differences in other CVRFs. Carotid plaques were observed in 20.5%. In multivariate models adjusted for age, CVRF, and statins, both T1D and PE showed a similar impact on the presence of plaque, with odds ratios (95% confidence interval), 5.45 (1.36-21.9) and 4.24 (1.04-17.3), respectively. Both entities showed an additive effect when combined, both in common carotid-IMT (T1D+/PE- or T1D-/PE+, ß = 0.198; T1D+/PE+, ß = 0.297) and in the presence of plaque (8.53 [1.07-68.2] and 28.1 [2.67-296.4], respectively). CONCLUSIONS: Previous PE was independently associated with preclinical atherosclerosis in T1D. Further studies are needed to ascertain its usefulness for stratifying risk in T1D women.

The geochemical evolution of brines from phosphogypsum deposits in Huelva (SW Spain) and its environmental implications.

The present study focuses on the geochemistry of large phosphogypsum deposits in Huelva (SW Spain). Phosphogypsum slurry waste from fertiliser production was disposed in large ponds containing aqueous waste (i.e. brines) and exposed to weathering. These evaporation ponds were found to be dynamic environments far from attaining steady state conditions where a number of trace pollutants are subjected to temporal variations in response to changing environmental conditions. Chemical, mineralogical and morphological data were used to improve our understanding on the dynamics of a large number of elements in the phosphogypsum-brine-evaporation deposits system. Weekly sampling of brines over the course of 1 yr indicated a substantial enrichment in potentially harmful elements (e.g. As, Cr, Cu, F, Ni, U, V, Zn) present in time-dependent concentrations. The evaporation deposits formed multi-layered precipitates of chlorides, sulphates, phosphates and fluorides containing a large number of pollutants in readily soluble forms. The precipitation sequence revealed a time-dependent composition reflecting alternating precipitation and re-dissolution processes associated with seasonal changes in the local weather conditions. Concatenation of precipitation/re-dissolution stages was found to progressively enrich the brines in pollutants. These findings were supported by the observations from a tank experiment simulating the phosphogypsum-brine-evaporation deposits system under laboratory conditions. Given the substantially high concentrations of pollutants present in mobile forms in the brine-salt system, actions to abate these compounds should be implemented.

Evaluación de la efectividad de la terapia ISCI a largo plazo mediante el objetivo combinado de descenso de HbA1c y ausencia de hipoglucemia grave / Assessment of the effectiveness of long-term insulin pump therapy using a combined goal of HbA1c decrease and absence of severe hypoglycemia

Objetivo: Menos de un tercio de los pacientes con diabetes tipo 1 (DT1) consiguen el objetivo de punto de corte establecido como control metabólico óptimo (HbA1c < 7%). Sin embargo, reducciones porcentuales de HbA1c y la prevención de hipoglucemias graves (HG) han demostrado beneficios clínicamente relevantes. Por ello, el objetivo de este estudio ha sido evaluar la efectividad de la terapia con infusión subcutánea continua de insulina (ISCI) a los 5 años de seguimiento en una cohorte de pacientes de una unidad especializada mediante objetivos combinados de descenso de HbA1c y ausencia de HG. Material y métodos: Estudio observacional retrospectivo que incluye a 178 pacientes que iniciaron terapia ISCI de manera consecutiva entre los años 2003 y 2008. Se han analizado las características basales de los individuos, la HbA1c inicial y a los 5 años de tratamiento con ISCI y la presencia o no de HG. Se calcularon las variables combinadas: a) descenso de al menos 0,5 puntos de HbA1c y ausencia de HG en los últimos 2 años; b) HbA1c a los 5 años < 7,5% sin HG en los últimos 2 años; c) HbA1c < 8,5% sin HG en los últimos 2 años, y d) descenso ≥ 0,5 puntos y/o HbA1c < 7,5% a los 5 años sin presencia de HG en los 2 últimos años de seguimiento. Resultados: Veintisiete de los 178 pacientes fueron excluidos debido a pérdida del seguimiento o abandono de la terapia ISCI. Se analizó a 151 pacientes (edad 37,4 ± 10,5 años, 64% mujeres, 19,2 ± 10,7 años de evolución de la DT1). Las 2 indicaciones principales para el inicio de ISCI fueron: control metabólico subóptimo (60,9%) e HG o hipoglucemia desapercibida (28,5%). Las HbA1c de la cohorte total y de control metabólico subóptimo fueron de 8,0 ± 1,2 y 8,4 ± 1,1% al inicio de la terapia ISCI y de 7,8 ± 1,2 y 8,0 ± 1,3% a los 5 años (p = 0,104 y p = 0,016), respectivamente. En la cohorte global un 55,5% de los pacientes alcanzaron a los 5 años el objetivo combinado HbA1c < 7,5% y/o un descenso ≥ 0,5% sin HG. Conclusiones: Tras 5 años de terapia ISCI más de la mitad de nuestros pacientes consiguen el objetivo combinado de reducción significativa de HbA1c y ausencia de HG. La utilización de objetivos combinados nos ofrece la posibilidad de evaluar la efectividad de las terapias en la DT1 desde un punto de vista más cercano a su significado clínico

Objective: Less than one third of patients with type 1 diabetes mellitus (T1DM) achieve the cut-off value proposed as good metabolic control by most guidelines, HbA1c < 7%. However, HbA1c reductions and prevention of severe hypoglycemia (SH) have shown clinically relevant benefits. The study objective therefore was to assess the effectiveness of continuous subcutaneous insulin infusion (CSII) therapy at 5 years of follow-up in a cohort of patients attending a specialized unit using HbA1c reduction and abscence of SH as combined goals. Methods: A retrospective, observational study on 178 patients with T1DM who started CSII treatment at Hospital Clinic of Barcelona between 2003 and 2008. HbA1c levels at baseline and after 5 years of treatment with CSII and presence or absence of SH were recorded. The combined variables calculated included: a) HbA1c reduction by ≥ 0.5 points and absence of SH in the last 2 years; b) HbA1c at 5 years < 7.5% and no SH in the last 2 years; c) HbA1c < 8.5% and no HG in the last 2 years, and d) HbA1c reduction by ≥ 0.5 points and/or HbA1c < 7.5% at 5 years with no SH in the last 2 years of follow-up. Results: Twenty-seven of the 178 patients were excluded due to loss to follow-up or CSII discontinuation. A total of 151 patients (aged 37.4 ± 10.5 years, 64% women, diabetes duration of 19.2 ± 10.7 years) were therefore analyzed. The 2 main reasons for starting CSII were suboptimal metabolic control (60.9%) and severe hypoglycemia/hypoglycemia unawareness (28.5%). HbA1c levels in the total cohort and in patients with suboptimal metabolic control were 8.0 ± 1.2 and 8.4 ± 1.1% at CSII start and 7.8 ± 1.2 and 8.0 ± 1.3% at 5 years of treatment (P = .104 and P = .016) respectively. In the overall cohort, 55.5% of patients achieved at 5 years the combined goal of HbA1c < 7.5% and/or HbA1c reductions ≥ 0.5% without SH. Conclusions: After 5 years of CSII therapy, more than half of the patients achieved the combined goal of significant HbA1c reduction and absence of SH. The use of combined goals offers the opportunity to assess the effectiveness of T1DM treatment from a clinically more meaningful point of view

Minimizing postprandial hypoglycemia in Type 1 diabetes patients using multiple insulin injections and capillary blood glucose self-monitoring with machine learning techniques.

BACKGROUND: Diabetic patients treated with intensive insulin therapies require a tight glycemic control and may benefit from advanced tools to predict blood glucose (BG) concentration levels and hypo/hyperglycemia events. Prediction systems using machine learning techniques have mainly focused on applications for sensor augmented pump (SAP) therapy. In contrast, insulin bolus calculators that rely on BG prediction for multiple daily insulin (MDI) injections for patients under self-monitoring blood glucose (SMBG) are scarce because of insufficient data sources and limited prediction capability of forecasting models. METHODS: We trained individualized models that can predict postprandial hypoglycemia via different machine learning algorithms using retrospective data from 10 real patients. In addition, we designed and tested a hypoglycemia reduction strategy for a similar in silico population. The system generates a bolus reduction suggestion as the scaled weighted sum of the predictions. We evaluated the general and postprandial glycemic outcomes of the in silico population to assess the systems capability of avoiding hypoglycemias. RESULTS: The median [IQR] sensitivity and specificity for hypoglycemia cases where the BG level was below 70 mg/dL were 0.49 [0.2-0.5] and 0.74 [0.7-0.9], respectively. For hypoglycemia cases where the BG level was below 54 mg/dL, the median [IQR] sensitivity and specificity were 0.51 [0.4-0.6] and 0.74 [0.7-0.8], respectively. CONCLUSIONS: The results indicated a decrease of 37% in the median number of postprandial hypoglycemias median decrease of 44% for hypoglycemias of 70 mg/dL and 54 mg/dL, respectively. This dramatic reduction makes this method a good candidate to be integrated into any Decision Support System for diabetes management.

Assessment of the effectiveness of long-term insulin pump therapy using a combined goal of HbA1c decrease and absence of severe hypoglycemia. / Evaluación de la efectividad de la terapia ISCI a largo plazo mediante el objetivo combinado de descenso de HbA1c y ausencia de hipoglucemia grave.

OBJECTIVE: Less than one third of patients with type 1 diabetes mellitus (T1DM) achieve the cut-off value proposed as good metabolic control by most guidelines, HbA1c<7%. However, HbA1c reductions and prevention of severe hypoglycemia (SH) have shown clinically relevant benefits. The study objective therefore was to assess the effectiveness of continuous subcutaneous insulin infusion (CSII) therapy at 5 years of follow-up in a cohort of patients attending a specialized unit using HbA1c reduction and abscence of SH as combined goals. METHODS: A retrospective, observational study on 178 patients with T1DM who started CSII treatment at Hospital Clinic of Barcelona between 2003 and 2008. HbA1c levels at baseline and after 5 years of treatment with CSII and presence or absence of SH were recorded. The combined variables calculated included: a) HbA1c reduction by≥0.5 points and absence of SH in the last 2 years; b) HbA1c at 5 years<7.5% and no SH in the last 2 years; c) HbA1c<8.5% and no HG in the last 2 years, and d) HbA1c reduction by≥0.5 points and/or HbA1c<7.5% at 5 years with no SH in the last 2 years of follow-up. RESULTS: Twenty-seven of the 178 patients were excluded due to loss to follow-up or CSII discontinuation. A total of 151 patients (aged 37.4±10.5 years, 64% women, diabetes duration of 19.2±10.7 years) were therefore analyzed. The 2 main reasons for starting CSII were suboptimal metabolic control (60.9%) and severe hypoglycemia/hypoglycemia unawareness (28.5%). HbA1c levels in the total cohort and in patients with suboptimal metabolic control were 8.0±1.2 and 8.4±1.1% at CSII start and 7.8±1.2 and 8.0±1.3% at 5 years of treatment (P=.104 and P=.016) respectively. In the overall cohort, 55.5% of patients achieved at 5 years the combined goal of HbA1c<7.5% and/or HbA1c reductions≥0.5% without SH. CONCLUSIONS: After 5 years of CSII therapy, more than half of the patients achieved the combined goal of significant HbA1c reduction and absence of SH. The use of combined goals offers the opportunity to assess the effectiveness of T1DM treatment from a clinically more meaningful point of view.

Risk-based postprandial hypoglycemia forecasting using supervised learning.

BACKGROUND: Predicting insulin-induced postprandial hypoglycemic events is critical for the safety of type 1 diabetes patients because an early warning of hypoglycemia facilitates correction of the insulin bolus before its administration. The postprandial hypoglycemic event counts can be lowered by reducing the size of the bolus based on a reliable prediction but at the cost of increasing the average blood glucose. METHODS: We developed a method for predicting postprandial hypoglycemia using machine learning techniques personalized to each patient. The proposed system enables on-line therapeutic decision making for patients using a sensor augmented pump therapy. Two risk-based approaches were developed for a window of 240 min after the meal/bolus, and they were tested based on real retrospective data from 10 patients using 70 mg/dL and 54 mg/dL as thresholds according to the consensus for Level 1 and Level 2 hypoglycemia, respectively. Due to the small size of the patient cohort, we trained personalized models for each patient. RESULTS: The median specificity and sensitivity were 79% and 71% for Level 1 hypoglycemia, respectively, and 81% and 77% for Level 2. CONCLUSIONS: The results demonstrated that it is feasible to anticipate hypoglycemic events with a reasonable false-positive rate. The accuracy of the results and the trade-off between performance metrics allow its use in decision support systems for patients who wear insulin pumps.

Real-Life Management and Effectiveness of Insulin Pump with or Without Continuous Glucose Monitoring in Adults with Type 1 Diabetes.

INTRODUCTION: To describe and compare the routine use of continuous subcutaneous insulin infusion (CSII) in type 1 diabetes (T1D) patients with and without continuous glucose monitoring (CGM) in routine clinical practice and its relationship with glycemic outcomes. METHODS: Retrospective observational case-control study collecting routine use of CSII and CGM in T1D patients between January 2016 and December 2016. Patients with T1D using sensor augmented pump (SAP) were matched by sex and disease duration in a 1:3 ratio with those treated only with CSII. Patients used a Paradigm Veo or 640G Medtronic-Minimed® insulin pump with or without a glucose sensor (Enlite, Medtronic-Minimed®) for at least 12 months. RESULTS: A total of 160 subjects with T1D were included, 40 using SAP and 120 on CSII (age 47 ± 12 years, 88 women, diabetes duration 29 ± 9.0 years, 10 ± 4.7 years on CSII, HbA1C 7.6 ± 0.8%). Those in SAP therapy used the sensor 63% of time, performed less self-monitored blood glucose (SMBG)/day (3.3 ± 1.9 vs. 4.5 ± 2.0; p < 0.01), more bolus/day (6.2 ± 3.6 vs. 4.8 ± 1.6; p < 0.05), more basal insulin segment/day (6.5 ± 2.1 vs. 5.9 ± 1.5; p < 0.05), and more suspension time of the pump (97 ± 93 vs. 9.6 ± 20 min/day; p < 0.0001). Regarding metabolic control, SAP therapy patients had lower HbA1c (7.4 ± 0.7 vs. 7.7 ± 0.9%; p = 0.068), lower average SMBG value (151 ± 32 vs. 163 ± 30 mg/dL; p < 0.05), a lower percentage of SMBG values greater than 180 mg/dL (30 ± 19 vs. 37 ± 16%; p < 0.05) with no differences in SMBG values less than 70 mg/dL (12 ± 8.0 vs. 9.8 ± 9.8%; p = 0.33) compared with patients on CSII. There were no differences in bolus wizard targets or in insulin/carbohydrate ratios per day. CONCLUSION: In a real-world setting, SAP therapy is associated with more self-adjustments of insulin therapy when compared to CSII alone. This could result in an improvement in glucose control.

Experiences and real life management of insulin pump therapy in adults with type 1 diabetes / Experiencias y gestión en la vida real del tratamiento con bomba de insulina de adultos con diabetes tipo 1

Objective: There is scarce information regarding the performance of a specific, structured education program addressed to patients with type 1 diabetes (T1D) using continuous subcutaneous insulin infusion (CSII) including both routine use of the therapy and patient experience evaluation. We aimed to assess the routine use of CSII and patient's experience and satisfaction regarding a specific structured patient self-management education and care program. Methods: A retrospective, observational, cross-sectional study collecting CSII routine use downloaded data. Patient experience and satisfaction were evaluated using an anonymous online survey covering different aspects of CSII self-management education and care program. Results: 380 T1D subjects were included (aged 45.3±12.17 years, 62.1% women, diabetes duration 27.8±10.3 years, 9.7±4.7 years on CSII, HbA1c 7.7+1.0%; 61.0±7.9mmol/mol). Participants with HbA1c≤7.5% (58mmol/mol, n=178) did more SMBGs per day (4.4±2.1 vs. 3.9±1.9); used more boluses (5.0±1.8 vs. 4.5±2.0); the percentage of insulin given as bolus was higher (50.1±12.8 vs. 44.9±13.2%); the night bolus wizard (BW) high glucose target was lower (125.9±4.4 vs. 130.5±12.8mg/dl) and time on CSII therapy was shorter (8.9±4.6 vs. 10.3±4.6 years. p<0.05 all comparisons). More SMBG/day, shorter duration of CSII treatment, a lower BW low glucose target at night, a lower BW high glucose target at night, total insulin dose per day and total number of carbohydrates per day were related with better HbA1c levels. 60% of 373 patients answered the questionnaire. The response to the different aspects of the educational program was homogeneously highly satisfactory. Seventy-seven percent of patients scored the program as very useful. Ninety-three percent of CSII users would not return to their previous insulin treatment. Conclusions: The analysis of routine clinical use of CSII by T1D patients demonstrates that glucose control may be associated with some pump usage and adherence parameters. The overall user experience and satisfaction with our CSII self-management education and care program was remarkably favorable

Objetivo: Hay poca información sobre la eficacia de un programa educativo estructurado específico dirigido a los pacientes con diabetes tipo 1 (DT1) que utilizan infusión subcutánea continua de insulina (ISCI) que incluye tanto el uso habitual del tratamiento como la evaluación de la experiencia de los pacientes. Nuestro objetivo era valorar el uso habitual de la ISCI, la experiencia y la satisfacción del paciente con un programa educativo y asistencial estructurado específico para autogestión de los pacientes. Métodos: Estudio transversal retrospectivo observacional en el que se recogieron datos descargados sobre el uso habitual de la ISCI. Se evaluaron la experiencia y la satisfacción de los pacientes mediante una encuesta en línea anónima que abarcaba distintos aspectos del programa educativo y asistencial para autogestión de la ISCI. Resultados: Se incluyó a 380 pacientes con DT1 (45,3±12,17 años de edad, 62,1% mujeres, duración de la diabetes 27,8±10,3 años, 9,7±4,7 años con ISCI, HbA1c 7,7+1,0%; 61,0±7,9mmol/mol). Los participantes con HbA1c<7,5% (58mmol/mol, n=178) practicaron más autocontroles al día (4,4±2,1 vs. 3,9±1,9); usaron más bolos (5,0±1,8 vs. 4,5±2,0); tuvieron un porcentaje de insulina administrada en bolo mayor (50,1±12,8 vs. 44,9±13,2%) y el objetivo de glucosa nocturna alta en el recomendador de bolo (bolus wizard, BW) era más bajo (125,9±4,4 vs. 130,5±12,8mg/dl), y su tiempo con ISCI era menor (8,9±4,6 vs. 10,3±4,6 años, p<0,05 para todas las comparaciones). Más autocontroles al día, la menor duración del tratamiento con ISCI, un objetivo de glucosa baja del BW menor por la noche, un objetivo de glucosa alta del BW por la noche menor, la dosis total diaria de insulina y el número total de hidratos de carbono diarios estaban relacionados con mejores valores de HbA1c. El 60% de 373 pacientes contestaron el cuestionario. La respuesta a los distintos aspectos del programa educativo fue muy satisfactoria en conjunto. El 77% de los pacientes valoraron el programa como muy útil. El 93% de los usuarios de ISCI no volverían el tratamiento de insulina previo. Conclusiones: El análisis del uso clínico sistemático de la ISCI por pacientes con DT1 demuestra que el control de la glucosa puede relacionarse con algunos parámetros de uso y cumplimiento de la bomba. La experiencia global del usuario y la satisfacción con nuestro programa educativo y asistencial de autogestión de la ISCI fueron notablemente favorables

Experiences and real life management of insulin pump therapy in adults with type 1 diabetes.

OBJECTIVE: There is scarce information regarding the performance of a specific, structured education program addressed to patients with type 1 diabetes (T1D) using continuous subcutaneous insulin infusion (CSII) including both routine use of the therapy and patient experience evaluation. We aimed to assess the routine use of CSII and patient's experience and satisfaction regarding a specific structured patient self-management education and care program. METHODS: A retrospective, observational, cross-sectional study collecting CSII routine use downloaded data. Patient experience and satisfaction were evaluated using an anonymous online survey covering different aspects of CSII self-management education and care program. RESULTS: 380 T1D subjects were included (aged 45.3±12.17 years, 62.1% women, diabetes duration 27.8±10.3 years, 9.7±4.7 years on CSII, HbA1c 7.7+1.0%; 61.0±7.9mmol/mol). Participants with HbA1c≤7.5% (58mmol/mol, n=178) did more SMBGs per day (4.4±2.1 vs. 3.9±1.9); used more boluses (5.0±1.8 vs. 4.5±2.0); the percentage of insulin given as bolus was higher (50.1±12.8 vs. 44.9±13.2%); the night bolus wizard (BW) high glucose target was lower (125.9±4.4 vs. 130.5±12.8mg/dl) and time on CSII therapy was shorter (8.9±4.6 vs. 10.3±4.6 years. p<0.05 all comparisons). More SMBG/day, shorter duration of CSII treatment, a lower BW low glucose target at night, a lower BW high glucose target at night, total insulin dose per day and total number of carbohydrates per day were related with better HbA1c levels. 60% of 373 patients answered the questionnaire. The response to the different aspects of the educational program was homogeneously highly satisfactory. Seventy-seven percent of patients scored the program as very useful. Ninety-three percent of CSII users would not return to their previous insulin treatment. CONCLUSIONS: The analysis of routine clinical use of CSII by T1D patients demonstrates that glucose control may be associated with some pump usage and adherence parameters. The overall user experience and satisfaction with our CSII self-management education and care program was remarkably favorable.