Nasal Glucagon Reverses Insulin-induced Hypoglycemia With Less Rebound Hyperglycemia: Pooled Analysis of Clinical Trials.

Background: Rebound hyperglycemia may occur following glucagon treatment for severe hypoglycemia. We assessed rebound hyperglycemia occurrence after nasal glucagon (NG) or injectable glucagon (IG) administration in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). Methods: This was a pooled analysis of 3 multicenter, randomized, open-label studies (NCT03339453, NCT03421379, NCT01994746) in patients ≥18 years with T1D or T2D with induced hypoglycemia. Proportions of patients achieving treatment success [blood glucose (BG) increase to ≥70 mg/dL or increase of ≥20 mg/dL from nadir within 15 and 30 minutes]; BG ≥70 mg/dL within 15 minutes; in-range BG (70-180 mg/dL) 1 to 2 and 1 to 4 hours postdose; and BG >180 mg/dL 1 to 2 and 1 to 4 hours postdose were compared. Incremental area under curve (iAUC) of BG >180 mg/dL and area under curve (AUC) of observed BG values postdose were analyzed. Safety was assessed in all studies. Results: Higher proportions of patients had in-range BG with NG vs IG (1-2 hours: P = .0047; 1-4 hours: P = .0034). Lower proportions of patients had at least 1 BG value >180 mg/dL with NG vs IG (1-2 hours: P = .0034; 1-4 hours: P = .0068). iAUC and AUC were lower with NG vs IG (P = .025 and P < .0001). As expected, similar proportions of patients receiving NG or IG achieved treatment success at 15 and 30 minutes (97-100%). Most patients had BG ≥70 mg/dL within 15 minutes (93-96%). The safety profile was consistent with previous studies. Conclusion: This study demonstrated lower rebound hyperglycemia risk after NG treatment compared with IG. Clinical Trial Registration: NCT03421379, NCT03339453, NCT01994746.

Severe hypoglycemia and hypoglycemia awareness are associated with preclinical atherosclerosis in patients with type 1 diabetes without an estimated high cardiovascular risk.

AIMS: To explore the relationship between severe hypoglycemia (SH) and hypoglycemia awareness with preclinical atherosclerosis in type 1 diabetes (T1D). MATERIALS AND METHODS: Cross-sectional study in patients with T1D without cardiovascular disease (CVD), and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of T1D duration with another risk factor. CVD risk was estimated with the Steno T1 Risk Engine (Steno-Risk). Carotid plaque was evaluated using standardised ultrasonography protocol. Logistic regression models adjusted for CVD risk factors were constructed to test the independent associations with SH or hypoglycemia awareness assessed by the Clarke questionnaire (Clarke). The inclusion of SH and Clarke in Steno-Risk was further evaluated. RESULTS: We included 634 patients (52.4% men, age 48.3 ± 10.8 years, T1D duration 27.4 ± 11.1 years, 39.9% harbouring plaque). A stepped increase in the presence of plaque according to Steno-Risk was observed (13.5%, 37.7%, and 68.7%, for low, moderate, and high risk, respectively; p < 0.001). SH history (OR 4.4 [1.3-14.6]) and Clarke score (OR 1.7 [1.2-2.2]) were associated with plaque in low-risk patients (n = 192). Clarke score was also associated with plaque burden in low-moderate-risk participants (n = 436; ≥2 plaques: OR 1.2 [1.0-1.5], p = 0.031; ≥3 plaques: OR 1.4 [1.1-2.0], p = 0.025). The inclusion of SH and Clarke scores in Steno-Risk significantly improved the identification of low-risk individuals with atherosclerosis (area under the curve: 0.658 vs. 0.576; p = 0.036). CONCLUSIONS: In patients with T1D without an estimated high CVD risk, SH and hypoglycemia awareness assessment score were independently associated with preclinical atherosclerosis and improved identification of patients who would benefit from an intensive approach.

Impact of an advanced hybrid closed-loop system on glycemic control throughout the menstrual cycle in women with type 1 diabetes prone to hypoglycemia.

This study aimed to evaluate the impact of advanced hybrid closed-loop (AHCL) on glycemic control throughout the menstrual cycle (MC) in women with type 1 diabetes (T1D). We included 39 pairs of spontaneous MC from 13 participants, before and after switching from sensor-augmented pump to AHCL. Baseline time below range <70 mg/dL (TBR<70) was significantly higher during the mid-follicular phase than during late luteal phase (5.7±5.0% vs. 4.1±3.0%), but similar time in range 70-180 mg/dL (TIR) was observed throughout the MC. After switching to AHCL, a reduction in TBR<70 and an increase in TIR were observed in all phases. Phase-dependent changes in insulin infusion were detected and pre-existing differences in TBR<70 were eradicated (3.5±3.2% vs. 3.0±3.0%). However, TIR became significantly higher during the early follicular than during the late luteal phase (79.1±9.3% vs. 74.5±10.0%). In conclusion, AHCL improved glycemic control throughout the MC, but performance differed according to phase.

Adherence to an energy-restricted Mediterranean diet is associated with the presence and burden of carotid atherosclerosis in people with type 1 diabetes.

AIMS: People with type 1 diabetes (T1D) have an increased risk of cardiovascular disease (CVD). The Mediterranean diet is associated with reduced CVD; however, the evidence in T1D is scarce. We aimed to analyse the relationships between adherence to the energy-restricted Mediterranean diet (erMEDd) and carotid atherosclerosis. MATERIALS AND METHODS: We included children with T1D without CVD, with ≥1 of the following: age ≥40 years, diabetic kidney disease, or ≥10 years of disease duration with another risk factor. Plaque presence (intima-media thickness ≥1.5 mm) was determined by ultrasonography. The PREDIMED-Plus 17-item questionnaire (PP-17) was used to assess adherence to the erMEDd. RESULTS: Four hundred one individuals were included (48% males, age 48.3 ± 11 years, diabetes duration 26.8 ± 11.4 years). Those harbouring plaques (42%) showed lower adherence to the erMEDd (PP-17: 8.9 ± 2.3 of a maximum of 17 vs. 9.8 ± 2.5, p < 0.001). Greater adherence to the erMEDd was correlated with an overall better metabolic profile. After adjusting for multiple confounders, adherence to the erMEDd was independently associated with carotid atherosclerosis (OR 0.86 [0.77-0.95] for plaque presence and OR 0.85 [0.75-0.97] for ≥2 plaques). The consumption of fruit and nuts and preference of white over red meat was higher in individuals without atherosclerosis (p < 0.05). Fruit and nut consumption was associated with lower plaque prevalence in the fully adjusted models (OR 0.38 [0.19-0.73] and 0.51 [0.29-0.93]). CONCLUSIONS: Greater adherence to the erMEDd is associated with less carotid atherosclerosis in children with T1D at high risk of CVD. Strategies to improve and implement healthy dietary patterns in this population should be encouraged.

Neutrophil-to-lymphocyte ratio is independently associated with carotid atherosclerosis burden in individuals with type 1 diabetes.

BACKGROUND AND AIMS: Recent studies have identified a relationship between innate versus. Adaptative immunity and cardiovascular disease (CVD) in the general population, but information on type 1 diabetes (T1D) is lacking. We aimed to study the relationship between inflammatory biomarkers and preclinical atherosclerosis in this population. METHODS AND RESULTS: Cross-sectional study in T1D individuals without CVD and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of diabetes duration with classical CVD risk factors. Carotid plaques were evaluated by ultrasonography. C-reactive protein, total leukocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and systemic immune-inflammation index were assessed as inflammatory markers. Multivariate-adjusted models including age, sex, and other CVD risk factors were constructed to test their independent associations with atherosclerosis burden. We included 602 subjects (52.8% men, 48.7 ± 10.2 years old and 27.0 ± 10.5 years of diabetes duration). Carotid plaques were found in 41.2% of the individuals (12.8%, ≥3 plaques). The number of carotid plaques (none, 1-2, ≥3 plaques), was directly associated with the leukocyte count (6570 [5445-8050], 6640 [5450-8470] and 7310 [5715-8935] per mm3, respectively; p for trend = 0.021) and the NLR (1.63 [1.28-2.13], 1.78 [1.38-2.25] and 2.14 [1.58-2.92], respectively; p for trend <0.001), but only the NLR remained directly associated in fully-adjusted models (presence of plaques; OR 1.285 [1.040-1.587]; ≥3 plaques, OR 1.377 [1.036-1.829]). CONCLUSIONS: The NLR was independently and directly associated with carotid plaque burden in T1D individuals. Our data support the role of innate versus. Adaptative immunity in atherosclerosis also among the T1D population.

Impact of preeclampsia and parity on sex-based discrepancies in subclinical carotid atherosclerosis in type 1 diabetes.

CONTEXT: The excess risk of fatal and non-fatal cardiovascular events is roughly twice as high in women than in men with type 1 diabetes (T1D). OBJECTIVE: To evaluate the impact of preeclampsia and parity on sex-based discrepancies in preclinical atherosclerosis and on the diagnostic performance of a cardiovascular risk scale. DESIGN: Cross-sectional study. SETTING: Single tertiary hospital. PATIENTS: 728 T1D (48.5% women) without cardiovascular disease and age ≥40 years, nephropathy, and/or ≥10 years of diabetes duration with another risk factor. INTERVENTION: Standardized carotid ultrasonography. MAIN OUTCOME MEASURES: Carotid plaque determined by ultrasonography and cardiovascular risk estimated according to the Steno T1 Risk Engine (Steno-Risk). RESULTS: Nulliparous women and parous women without previous preeclampsia had a lower risk for carotid plaque than men (adjusted odds ratio [OR]: 0.48, 95% confidence interval [0.28-0.82]; adjusted OR: 0.51 [0.33-0.79], respectively), without differences in the preeclampsia group. The prevalence of carotid plaque increased as the estimated cardiovascular risk increased in all subgroups except for preeclampsia group. The area under the curve (AUC) of the Steno-Risk for identifying ≥2 carotid plaques was lower in the preeclampsia group (men: 0.7886, nulliparous women: 0.9026, women without preeclampsia: 0.8230, preeclampsia group: 0.7841; p between groups=0.042). Neither the addition of parity nor preeclampsia in the Steno-Risk led to a statistically significant increase in the AUC. CONCLUSIONS: The risk for carotid plaque in women compared to men decreased as exposure to obstetric factors diminished. However, the addition of these factors did not improve the prediction of the Steno-Risk.

Safety and performance of a hybrid closed-loop insulin delivery system with carbohydrate suggestion in adults with type 1 diabetes prone to hypoglycemia.

AIMS: To evaluate the safety and performance of a hybrid closed-loop (HCL) system with automatic carbohydrate suggestion in adults with type 1 diabetes (T1D) prone to hypoglycemia. METHODS: A 32-hour in-hospital pilot study, including a night period, 4 meals and 2 vigorous unannounced 45-minute aerobic sessions, was conducted in 11 adults with T1D prone to hypoglycemia. The primary outcome was the percentage of time in range 70-180 mg/dL (TIR). Main secondary outcomes were time below range < 70 mg/dL (TBR < 70) and < 54 (TBR < 54). Data are presented as median (10th-90th percentile ranges). RESULTS: The participants, 6 (54.5%) men, were 24 (22-48) years old, and had 22 (9-32) years of T1D duration. All of them regularly used an insulin pump and a continuous glucose monitoring system. The median TIR was 78.7% (75.6-91.2): 92.7% (68.2-100.0) during exercise and recovery period, 79.3% (34.9-100.0) during postprandial period, and 95.4% (66.4-100.0) during overnight period. The TBR < 70 and TBR < 54 were 0.0% (0.0-6.6) and 0.0% (0.0-1.2), respectively. A total of 4 (3-9) 15-g carbohydrate suggestions were administered per person. No severe acute complications occurred during the study. CONCLUSIONS: The HCL system with automatic carbohydrate suggestion performed well and was safe in this population during challenging conditions in a hospital setting.

Systematic Literature Review and Indirect Treatment Comparison of Three Ready-to-Use Glucagon Treatments for Severe Hypoglycemia.

INTRODUCTION: Ready-to-use glucagon represents a significant advancement in the management of severe hypoglycemia for people with diabetes and their caregivers. This indirect treatment comparison (ITC) evaluated the efficacy and safety differences among the three ready-to-use glucagon treatments, Baqsimi® (nasal glucagon), Gvoke® (glucagon injection) and Zegalogue® (dasiglucagon injection), in adults and children with type 1 diabetes (T1D) or type 2 diabetes (T2D). METHODS: A systematic literature review was conducted to identify randomized clinical trials assessing the efficacy and safety of Baqsimi, Gvoke or Zegalogue versus reconstituted, injectable glucagon (IG) in reversing insulin-induced hypoglycemia. Bayesian fixed-effect network meta-analysis was used to perform the ITC. Study endpoints included proportion of participants achieving treatment success, maximum blood glucose achieved, time to achieve treatment success and maximum blood glucose and treatment-emergent adverse events (TEAE). RESULTS: Ten clinical trials were included in the ITC (four for Baqsimi, three for Gvoke, and three for Zegalogue). All three treatments achieved high proportions of treatment success (> 98%). In adults, the efficacy results from combined T1D and T2D analysis were consistent with the T1D analysis, except statistically significantly faster in achieving treatment success for Baqsimi vs Gvoke in the combined analysis (13.96 vs 14.66 min). The mean maximum blood glucose values were also statistically significantly lower for Baqsimi (168 mg/dl) vs Gvoke (220 mg/dl) and Zegalogue (190 mg/dl). There was a trend towards a lower number of adults experiencing ≥ 1 TEAE with Baqsimi compared to Gvoke or Zegalogue, but no statistical significance was reached. CONCLUSION: Baqsimi, Gvoke and Zegalogue had comparable high proportions of treatment success in reversing insulin-induced hypoglycemia. Baqsimi achieved a lower mean maximum blood glucose value, which may have implications for the re-establishment of euglycemia. These findings may help support patients, caregivers and health care providers in their decision-making process when discussing various ready-to-use glucagon treatment options.

Effectiveness of flash glucose monitoring in patients with type 1 diabetes and recurrent hypoglycemia between early and late stages after flash glucose monitoring initiation.

AIMS: Evaluate the effectiveness of reimbursed flash glucose monitoring with optional alarms (FGM) in preventing severe hypoglycemia (SH) and reducing hypoglycemia exposure in T1D patients prone to hypoglycemia. METHODS: Ambispective study in T1D patients treated with multiple daily injections (MDI) and prone to hypoglycemia, initiating reimbursed FGM (FreeStyle Libre 2). The primary outcome was the number of SH events (requiring third party assistance) and main secondary outcomes were time below range < 70 (TBR < 70) and < 54 mg/dL (TBR < 54), impaired awareness of hypoglycemia (IAH) and quality of life (QoL). Logistic regression models were constructed to explore variables associated with success of the intervention. RESULTS: We included 110 patients (52.7 % women, mean age 47.8 ± 17.0 years). SH events at 1-year follow-up decreased from 0.3 ± 0.6 to 0.03 ± 0.2 (p < 0.001). Significant reductions in patients presenting an SH (26.4 % vs. 2.9 %, p < 0.001) and IAH (47.1 % vs. 25.9 %, p = 0.002) were observed, as well as improvements in QoL. TBR < 70 and TBR < 54 were not significantly reduced. Baseline GMI was inversely associated with a decrease in TBR < 70 [OR 0.37 (0.15-0.93)] and directly with an increase in time in range 70-180 mg/dL [OR 2.10 (1.03-4.28)]. CONCLUSIONS: FGM decreased SH and improved hypoglycemia awareness and QoL. Initial tight glycemic control was associated with a decrease in hypoglycemia, while patients with suboptimal control reduced hyperglycemia.

Impaired hypoglycaemia awareness in early pregnancy increases risk of severe hypoglycaemia in the mid-long term postpartum irrespective of breastfeeding status in women with type 1 diabetes.

INTRODUCTION: Information regarding the postpartum period in women with type 1 diabetes (T1D) is scarce. We aim to evaluate the relation of impaired hypoglycaemia awareness (IAH) in early pregnancy and breastfeeding status (its presence and duration) with severe postpartum hypoglycaemia (SH). MATERIALS AND METHODS: Retrospective cohort study of women with T1D followed during pregnancy between 2012 and 2019. Data on SH were recorded before and during pregnancy. IAH was evaluated at the first antenatal visit. Data on breastfeeding and the long-term postpartum period were collected by questionnaire and from medical records. RESULTS: A total of 89 women with T1D were included with a median follow-up after pregnancy of 19.2 [8.7-30.5] months. Twenty-eight (32%) women had IAH at the first antenatal visit. At discharge, 74 (83%) started breastfeeding during a median of 8 [4.4-15] months. A total of 18 (22%) women experienced ≥1 SH during postpartum. The incidence of SH significantly increased from pregestational to the gestational and post-partum period (0.09, 0.15 and 0.25 episodes/patient-year, respectively). Postpartum SH rates were comparable in breastfeeding and non-breastfeeding women (21.4% vs. 25%, respectively, p>0.05). Clarke test score at the first antenatal visit was associated with postpartum SH (for each 1-point increase: OR 1.53; 95% CI, 1.06-2.21) adjusted for confounders. No other diabetes and pregnancy-related variables were identified as predictors of SH in this period. CONCLUSIONS: SH are common in the long-term postpartum period independently of breastfeeding. Assessing IAH in early pregnancy could identify those at an increased risk of SH in the postpartum period.

Changes in physical activity habits in subjects with type 1 diabetes: A comparative study 10 years apart.

INTRODUCTION: Physical activity (PA) is highly recommended in type 1 diabetes (T1D). Few studies have reported the amount of PA performed by individuals with T1D in their daily life, and there is no information about changes over time. MATERIAL AND METHODS: Cross-sectional study in patients with T1D from a referral hospital recruited in two different periods: data from the Biobank registers from 2009 and data from patients attending visits at the hospital in 2019, on a consecutive basis. Data included clinical characteristics and the PA assessment through the International Physical Activity Questionnaire-short form (IPAQ-SF). RESULTS: In 2019, participants with T1D (n=135) reported a lower sedentary lifestyle and greater levels of high PA compared to subjects with T1D (n=355) from 10 years earlier (6.7% vs. 14.1% sedentariness, p=0.015; and 52.6% vs. 25.4% of high PA, p<0.001, respectively). Similar results were identified when the groups were divided according to sex. Both groups presented similar distribution by sex (women, 54% vs. 55%), age (40 vs. 39 years old), years with diabetes (20 vs. 18 years), BMI (25 vs. 24kg/m2) and glycated haemoglobin (7.5% vs. 7.5%, respectively; p>0.05 for all comparisons). Sex and age groups were not determinant for sedentary lifestyle in the different years studied. Analysing all the 490 participants, there was an inverse correlation of age with sitting hours (p=0.024, r=-0.102), total METs (p<0.001, r=-0.146) and HbA1c (p=0.038, r=-0.097). No correlations were found between PA and HbA1c or BMI. CONCLUSIONS: The findings indicate that PA has significantly increased in subjects with T1D over the last 10 years. Future studies are needed to assess whether these healthier habits translate into better outcomes in this high-risk population.

Advanced lipoprotein profile identifies atherosclerosis better than conventional lipids in type 1 diabetes at high cardiovascular risk.

BACKGROUND AND AIMS: People with type 1 diabetes (T1D) present lipoprotein disturbances that could contribute to their increased cardiovascular disease (CVD) risk. We evaluated the relationship between lipoprotein alterations and atherosclerosis in patients with T1D. METHODS AND RESULTS: Cross-sectional study in subjects with T1D, without previous CVD, but high-risk (≥40 years, nephropathy, or ≥10 years of evolution of diabetes with another risk factor). The presence of plaque (intima-media thickness ≥1.5 mm) in the different carotid segments was determined by ultrasound. The advanced lipoprotein profile was analysed by magnetic resonance imaging (1H NMR). We included 189 patients (42% women, 47.8 ± 10.7 years, duration of diabetes 27.3 ± 10.1 years, HbA1c 7.5% [7-8]). Those with carotid plaques (35%) were older, with longer diabetes duration, had a higher prevalence of hypertension, and showed lower and smaller LDL particles (LDL-P) and HDL particles (HDL-P), but higher VLDL particles (VLDL-P). Some LDL, HDL and VLDL-related parameters were associated with atherosclerosis in sex, age and statin use adjusted models (p < 0.05), but after adjusting for multiple confounders, including conventional lipid parameters, only HDL-P (OR 0.440 [0.204-0.951]; p = 0.037), medium HDL-P (OR 0.754 [0.590-0.963]; p = 0.024), HDL-P cholesterol content (OR 0.692 [0.495-0.968]; p = 0.032), 1H NMR LDL-P number/conventional LDL-cholesterol (OR 1.144 [1.026-1.275]; p = 0.015), and 1H NMR non-HDL particle number/conventional non-HDL-cholesterol ratios (OR 1.178 [1.019-1.361], p = 0.026) remained associated with atherosclerosis. CONCLUSIONS: In adults with T1D at high-risk, variables related to HDL, LDL and total atherogenic particle number are independently associated with preclinical atherosclerosis. Advanced lipoprotein profiling could be used to identify those at the highest risk of CVD.

Nuclear Magnetic Resonance-Based Lipidomics in the Assessment of Cardiometabolic Risk in Type 1 Diabetes: An Exploratory Analysis.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of mortality in type 1 diabetes (T1D). However, there is a need for daily practice tools for identifying those more prone to suffer from these events. We aimed to assess the relationships between nuclear magnetic resonance (1H NMR)-based lipidomic analysis and several CVD risk variables (including preclinical carotid atherosclerosis) in individuals with T1D at high risk. METHODS: We included patients with T1D without CVD, with at least one of the following: age ≥ 40 years, diabetic kidney disease, or ≥ 10 years of evolution with another risk factor. The presence of plaque (intima-media thickness > 1.5 mm) was determined by standardized ultrasonography protocol. Lipidomic analysis was performed by 1H NMR. Bivariate and multivariate-adjusted differences in 1H NMR lipidomics were evaluated. RESULTS: We included n = 131 participants (49.6% female, age 46.4 ± 10.3 years, diabetes duration 27.0 ± 9.5 years, 47.3% on statins). Carotid plaques were present in 28.2% of the individuals (n = 12, with ≥ 3 plaques). Glucose (HbA1c), anthropometric (body mass index and waist circumference), and insulin resistance-related (fatty liver index and estimated glucose disposal rate) variables were those most associated with 1H NMR-derived lipidomic analysis (p < 0.01 for all). Regarding preclinical atherosclerosis, sphingomyelin was independently associated with carotid plaque presence (for 0.1 mmol/L increase, OR 0.50 [0.28-0.86]; p = 0.013), even after adjusting for age, sex, hypertension, statin use, mean 5-year HbA1c and diabetes duration. Furthermore, linoleic acid and ω-6 fatty acids remained independently associated with higher plaque burden (≥ 3 plaques) in multivariate models (0.17 [0.03-0.93] and 0.27 [0.07-0.97], respectively; p < 0.05 for both). CONCLUSION: In our preliminary study of individuals with T1D at high risk, several 1H NMR-derived lipidomic parameters were independently associated with preclinical atherosclerosis. Specifically, ω-6 fatty acids and linoleic acid seem promising for identifying those with higher plaque burden.

Radiomics-Based Assessment of OCT Angiography Images for Diabetic Retinopathy Diagnosis.

Purpose: To evaluate the diagnostic accuracy of machine learning (ML) techniques applied to radiomic features extracted from OCT and OCT angiography (OCTA) images for diabetes mellitus (DM), diabetic retinopathy (DR), and referable DR (R-DR) diagnosis. Design: Cross-sectional analysis of a retinal image dataset from a previous prospective OCTA study (ClinicalTrials.govNCT03422965). Participants: Patients with type 1 DM and controls included in the progenitor study. Methods: Radiomic features were extracted from fundus retinographies, OCT, and OCTA images in each study eye. Logistic regression, linear discriminant analysis, support vector classifier (SVC)-linear, SVC-radial basis function, and random forest models were created to evaluate their diagnostic accuracy for DM, DR, and R-DR diagnosis in all image types. Main Outcome Measures: Area under the receiver operating characteristic curve (AUC) mean and standard deviation for each ML model and each individual and combined image types. Results: A dataset of 726 eyes (439 individuals) were included. For DM diagnosis, the greatest AUC was observed for OCT (0.82, 0.03). For DR detection, the greatest AUC was observed for OCTA (0.77, 0.03), especially in the 3 × 3 mm superficial capillary plexus OCTA scan (0.76, 0.04). For R-DR diagnosis, the greatest AUC was observed for OCTA (0.87, 0.12) and the deep capillary plexus OCTA scan (0.86, 0.08). The addition of clinical variables (age, sex, etc.) improved most models AUC for DM, DR and R-DR diagnosis. The performance of the models was similar in unilateral and bilateral eyes image datasets. Conclusions: Radiomics extracted from OCT and OCTA images allow identification of patients with DM, DR, and R-DR using standard ML classifiers. OCT was the best test for DM diagnosis, OCTA for DR and R-DR diagnosis and the addition of clinical variables improved most models. This pioneer study demonstrates that radiomics-based ML techniques applied to OCT and OCTA images may be an option for DR screening in patients with type 1 DM. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Use of the Steno T1 Risk Engine Identifies Preclinical Atherosclerosis Better Than Use of ESC/EASD-2019 in Adult Subjects With Type 1 Diabetes at High Risk.

OBJECTIVE: To evaluate the concordance between the 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD (ESC/EASD-2019) and the Steno T1 Risk Engine (Steno-Risk) cardiovascular risk scales for individuals with type 1 diabetes (T1D) without cardiovascular disease (CVD) and to analyze the relationships of their use with identification of preclinical atherosclerosis. RESEARCH DESIGN AND METHODS: We consecutively selected patients with T1D, without CVD, age ≥40 years, with nephropathy, and/or with ≥10 years of T1D evolution with another risk factor. The presence of plaque at different carotid segments was determined by ultrasonography. Cardiovascular risk was estimated in accord with ESC/EASD-2019 risk groups (moderate/high/very high) and the Steno-Risk (<10%, low; 10-20%, moderate; ≥20%, high), as T1D-specific scores. In an exploratory analysis, we also evaluated the non-T1D-specific 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk (ACC/AHA-2013) pooled cohort equation for individuals between 40 and 79 years of age. RESULTS: We included 501 patients (53% men, mean age 48.8 years, median T1D duration 26.5 years, 41.3% harboring plaques). Concordance between T1D-specific scales was poor (κ = 0.19). A stepped increase in the presence of plaques according to Steno-Risk category was seen (18.4%, 38.2%, and 64.1%, for low, moderate, and high risk, respectively; P for trend <0.001), with no differences according to ESC/EASD-2019 (P = 0.130). Steno-Risk identified individuals with plaques, unlike ESC/EASD-2019 (area under the curve [AUC] 0.691, P < 0.001, vs. AUC 0.538, P = 0.149). Finally, in polynomial regression models (with adjustment for lipid parameters and cardioprotective treatment), irrespective of the ESC/EASD-2019 category, high risk by Steno-Risk was directly associated with atherosclerosis (in moderate/high-risk by ESC/EASD-2019 odds ratio 2.91 [95% CI 1.27-6.72] and 4.94 [2.35-10.40] for the presence of plaque and two or more plaques). Similar results were obtained with discordant higher Steno-Risk versus ACC/AHA-2013 (P < 0.001). CONCLUSIONS: Among T1D patients undergoing primary prevention, use of Steno-Risk seems to result in better recognition of individuals with atherosclerosis in comparison with ESC/EASD-2019. Notwithstanding, carotid ultrasound could improve the categorization of cardiovascular risk.

Carotid ultrasonography as a strategy to optimize cardiovascular risk management in type 1 diabetes: a cohort study.

BACKGROUND AND AIMS: Although cardiovascular disease (CVD) remains the leading cause of mortality in type 1 diabetes (T1D), the use of cardioprotective drugs is scarce. We aimed to evaluate the impact of carotid ultrasonography (US) on the improvement in cardiovascular risk factors (CVRFs) in T1D. METHODS AND RESULTS: T1D patients without CVD meeting criteria for lipid treatment according to guidelines (age ≥ 40 years, nephropathy and/or ≥ 10 years of diabetes duration with ≥ 1 additional CVRFs) were included. The carotid-US group (US-G) underwent a standardized US protocol and CVRF assessment; recommendations were made according to subclinical atherosclerosis status. The control group (CG) followed usual clinical practice. Changes in CVRFs, specially statin use and LDL cholesterol levels, at 1 year were analysed. A total of 318 patients were included (51.3% female, mean age of 49.1 years and 25.5 years of diabetes duration): 211 in the US-G and 107 in the CG. Participants in the US-G had a higher baseline LDL cholesterol than controls (114 vs. 102 mg/dL; p < 0.001). Lipid-lowering treatment was modified in 38.9% in the US-G and 6.5% in the CG (p < 0.001). At 1 year, the US-G was more frequently on statins, had lower LDL cholesterol and 27% had stopped smoking (p < 0.001 for all). Changes were more pronounced in those with plaques (p < 0.001). In multivariate analyses adjusted for age, sex and other CVRFs, belonging to the US-G was independently associated with the intensification of lipid-lowering treatment (OR 10.47 [4.06-27.01]). Propensity score-matching analysis yielded similar results (OR 20.09 [7.86-51.37]). CONCLUSION: Carotid-US is independently associated with an intensification of lipid-lowering therapy in a high-risk T1D population.

Hyperglycemia and hypoglycemia exposure are differentially associated with micro- and macrovascular complications in adults with Type 1 Diabetes.

AIMS: Evaluate the relationship between high and low exposure continuous glucose monitoring (CGM)-derived glucometrics and micro- and macrovascular complications in type 1 diabetes (T1D). METHODS: Cross-sectional study in T1D without cardiovascular disease (CVD) and with ≥ 1 of the following: ≥40 years, diabetic nephropathy, or ≥ 10 years of diabetes duration with CVD risk factors. Glucometrics were obtained over 14 consecutive days: glucose management indicator (GMI) and proportion of time < 54 (TBR < 54), <70, 70-180 (TIR), >180 (TAR). Carotid plaque was evaluated by ultrasonography. Logistic regression models adjusted for age, sex, and other risk factors were constructed to test the independent associations with chronic complications. RESULTS: We included 152 patients (54.6% men, 48.7 ± 10.0 years-old). Sixty-seven patients had plaque and n = 71 microvascular complications. TAR (OR 1.28 [1.09-1.51]) and GMI (OR 3.05 [1.46-6.36]) were directly associated with the presence of microvascular complications, while TIR had an inverse relationship (OR 0.79 [0.66-0.93]). TBR < 54 was directly associated with the presence of plaque, even after adjusting for 5-year mean HbA1c (OR 1.51 [1.07-2.13]). CONCLUSIONS: High-glucose glucometrics were independently associated with microvascular complications. Only low-glucose exposure glucometrics was significantly associated with preclinical atherosclerosis. Our data support the role of hypoglycemia in the development of CVD in this population.

Cost of Severe Hypoglycemia and Budget Impact with Nasal Glucagon in Patients with Diabetes in Spain.

INTRODUCTION: Severe hypoglycemic events (SHE) represent a clinical and economic burden in patients with diabetes. Nasal glucagon (NG) is a novel treatment for SHEs with similar efficacy, but with a usability advantage over injectable glucagon (IG) that may translate to improved economic outcomes. The economic implications of this usability advantage on SHE-related spending in Spain were explored in this analysis. METHODS: A cost-offset and budget impact analysis (BIA) was conducted using a decision tree model, adapted for the Spanish setting. The model calculated average costs per SHE over the SHE treatment pathway following a treatment attempt with IG or NG. Analyses were performed separately in three populations with insulin-treated diabetes: children and adolescents (4-17 years) with type 1 diabetes (T1D), adults with T1D and adults with type 2 diabetes (T2D), with respective population estimates applied in BIA. Treatment probabilities were assumed to be equal for IG and NG, except for treatment success following glucagon administration. Epidemiologic and cost data were obtained from Spanish-specific sources. BIA results were presented at a 3-year time horizon. RESULTS: On a per SHE level, NG was associated with lower costs compared to IG (children and adolescents with T1D, EUR 820; adults with T1D, EUR 804; adults with T2D, EUR 725). Lower costs were attributed to reduced costs of professional medical assistance in patients treated with NG. After 3 years, BIA showed that relative to IG, the introduction of NG was projected to reduce SHE-related spending by EUR 1,158,969, EUR 142,162,371, and EUR 6,542,585 in children and adolescents with T1D, adults with T1D, and adults with insulin-treated T2D, respectively. CONCLUSIONS: In Spain, the usability advantage of NG over IG translates to potential cost savings per SHE in three populations with insulin-treated diabetes, and the introduction of NG was associated with a lower budget impact versus IG in each group.

A Machine Learning Approach to Minimize Nocturnal Hypoglycemic Events in Type 1 Diabetic Patients under Multiple Doses of Insulin.

Nocturnal hypoglycemia (NH) is one of the most challenging events for multiple dose insulin therapy (MDI) in people with type 1 diabetes (T1D). The goal of this study is to design a method to reduce the incidence of NH in people with T1D under MDI therapy, providing a decision-support system and improving confidence toward self-management of the disease considering the dataset used by Bertachi et al. Different machine learning (ML) algorithms, data sources, optimization metrics and mitigation measures to predict and avoid NH events have been studied. In addition, we have designed population and personalized models and studied the generalizability of the models and the influence of physical activity (PA) on them. Obtaining 30 g of rescue carbohydrates (CHO) is the optimal value for preventing NH, so it can be asserted that this is the value with which the time under 70 mg/dL decreases the most, with almost a 35% reduction, while increasing the time in the target range by 1.3%. This study supports the feasibility of using ML techniques to address the prediction of NH in patients with T1D under MDI therapy, using continuous glucose monitoring (CGM) and a PA tracker. The results obtained prove that BG predictions can not only be critical in achieving safer diabetes management, but also assist physicians and patients to make better and safer decisions regarding insulin therapy and their day-to-day lives.