Dose-Dependent association of cumulative tobacco consumption with the presence of carotid atherosclerosis in individuals with type 1 diabetes.

AIMS: Evaluate the association between cumulative tobacco consumption (CTC; packs-year) and atherosclerosis in type 1 diabetes (T1D), and study whether the inclusion of CTC in the Steno T1 Risk Engine (ST1RE) equation improves the identification of plaques. METHODS: Cross-sectional study in T1D patients without cardiovascular disease (CVD), with ≥ 1 of the following: ≥40 years-old, diabetic kidney disease, and/or T1D duration ≥ 10 years + cardiovascular risk factors.Preclinical atherosclerosis was evaluated by carotid ultrasonography. RESULTS: N = 584 patients were included (46.1 % women, age 48.7 ± 10.5 years, T1D duration 27.3 ± 10.8 years, 26.2 % active smokers). The overall plaque prevalence was 40.9 %. In models adjusted for age, sex, lipids, blood pressure, kidney function, statin use, microvascular complications and HbA1c, CTC was dose-dependently associated with the number of plaques (none, 1-2, ≥3) overall and in both active and former smokers (p < 0.001). This association remained after adjusting for ST1RE (OR 1.11 [1.02-1.19]). Although the inclusion of CTC in the ST1RE did not improve plaque identification overall (p = 0.180), it did so when analyzing active smokers separately (AUC 0.738 vs. 0.768; p < 0.01). CONCLUSIONS: In T1D patients, CTC is dose-dependently associated with atherosclerosis. Further prospective studies are needed to determine if CTC could identify T1D individuals more prone to accelerated atherosclerosis.

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.

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.

Midnight Cortisol is Associated with Changes in Systolic Blood Pressure and Diabetic Neuropathy in Subjects with Type 1 Diabetes Undergoing Simultaneous Kidney-Pancreas Transplantation.

INTRODUCTION: An increased midnight cortisol (MC) has been described in end-stage kidney disease (ESKD) and type 1 diabetes (T1D). Lower circulating levels of the cytokine soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) have been found in T1D and ESKD and associated with cardiovascular (CV) events in the latter. We aimed to study MC and sTWEAK in simultaneous pancreas-kidney transplant (SPKT) recipients, and the association of these markers with CV risk factors and transplant outcomes. METHODS: This was a retrospective cohort study including subjects with T1D who received a first SPKT between 2008 and 2020. MC and sTWEAK at baseline were correlated with CV risk factors and evolution 1 year after SPKT. RESULTS: We included 29 subjects (58.6% women, mean age 43.5 ± 7.5 years, diabetes duration 31.9 ± 9.4 years). Systolic blood pressure (SBP) increased directly with MC quartiles, despite similar hypertension prevalence (p < 0.05). At 1 year, antihypertensive treatment was deintensified in those in lower MC quartiles (p < 0.05). Diabetic neuropathy prevalence decreased progressively in higher cortisol quartiles (p for trend = 0.005). Low MC was associated with delayed kidney graft function (p for trend = 0.044), and high sTWEAK with kidney graft rejection (p for trend = 0.018). In multivariate analyses, MC (standardized-ß 0.505, p = 0.004) and age (standardized-ß - 0.460, p = 0.040) were independently correlated with SBP, and MC was independently associated with the presence of diabetic neuropathy (OR 0.633, 95% CI 0.425-0.944, p = 0.025), adjusted for confounders. CONCLUSIONS: In this exploratory study, lower MC was associated with a lower baseline SBP, an improvement of antihypertensive treatment 1 year after transplant, and a higher diabetic neuropathy prevalence in SPKT recipients.

Validation of the Back-table Graft Arterial Anastomosis between the Splenic Artery and Superior Mesenteric Artery: Arterial Complications after a 21-year Single-center Experience of Pancreas Transplantation.

OBJECTIVE: To determine the role of the arterial splenomesenteric anastomosis (ASMA) vascular reconstruction technique in terms of arterial vascular complications in pancreas transplant (PT) recipients. SUMMARY BACKGROUND DATA: The ASMA technique was first described in 1992 by Hospital Clínic Barcelona group. Regardless that the iliac Y-graft technique is the most frequently used worldwide, evidence of arterial complications and implications of using a different back-table reconstruction is conspicuously absent in the literature. METHODS: Descriptive review of 407 PTs performed at a single center (1999-2019) by analyzing the type of arterial reconstruction technique, focusing on ASMA. The endpoints were the management of arterial complications and long-term patient and graft survival. RESULTS: ASMA was performed in 376 cases (92.4%) and a Y-graft in 31 cases (7.6%). A total of 34 arterial complications (8.3%) were diagnosed. In the ASMA group (n=30, 7.9%) they comprised: 15 acute thrombosis; 4 stenosis; 1 pseudoaneurysm and 10 diverse chronic arterial complications while in the Y-graft group (n=4, 12.9%) 3 acute thrombosis and 1 chronic artery-duodenal fistula occurred. Graft salvage was achieved in 16 patients (53.3%) from the ASMA group and in 2 (50%) from the Y-graft. After a median follow-up of 129.2 (IQR 25-75%, 77.2 -182) months the overall graft and patient survival for the whole cohort at 1, 5, and 10 years was 86.7%, 79.5%, 70.5%, and 98.5%, 95.3%, 92.5%, respectively. CONCLUSIONS: The ASMA proves to be a safe and more easily reproducible technique and should therefore be considered for first-line back-table reconstruction in the PT 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.

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.

Diabetic Neuropathy Is Independently Associated With Worse Graft Outcomes and Incident Cardiovascular Disease After Pancreas Transplantation: A Retrospective Cohort Study in Type 1 Diabetes.

BACKGROUND: Information about the impact of diabetic neuropathy (DN) on outcomes after pancreas transplantation (PT) is scarce. We assessed the independent relationship between DN markers with both graft survival and incident cardiovascular disease (CVD) after transplantation. METHODS: A cohort study in individuals with type 1 diabetes and end-stage kidney disease who underwent PT between 1999 and 2015 was conducted. DN was assessed with vibration perception thresholds (VPTs) and orthostatic hypotension (pre-PT and 6 mo, 2-3, 5-6, and 8-10 y after transplantation). Pretransplantation and posttransplantation DN markers were related with graft failure/dysfunction and incident CVD during follow-up. RESULTS: We included 187 participants (70% men, age 39.9 ± 7.1 y, diabetes duration 27.1 y), with a median follow-up of 11.3 y. Abnormal VPTs (≥25 V) were observed in 53%. After transplantation, VPTs improved (22.4 ± 8.4 pretransplant versus 16.1 ± 6.1 V at 8-10 y post-PT; P < 0.001); additionally, the prevalence of abnormal VPTs decreased (53% pretransplant versus 24.4% at 8-10 y; P < 0.001). After adjusting for age, sex, diabetes duration, blood pressure, body mass index, and previous CVD, pretransplant VPTs ≥25 V were independently associated with pancreas graft failure/dysfunction (hazard ratio [HR], 2.01 [1.01-4.00]) and incident CVD (HR, 2.57 [1.17-5.64]). Furthermore, persistent abnormal VPTs after 6 mo posttransplantation were associated with the worst outcomes (HR, 2.80 [1.25-6.23] and HR, 3.19 [1.14-8.96], for graft failure/dysfunction and incident CVD, respectively). CONCLUSIONS: In individuals with type 1 diabetes and end-stage kidney disease, PT was associated with an improvement of VPTs. This simple and widely available DN study was independently associated with pancreas graft function and CVD posttransplantation.

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.

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.

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.

Preemptive simultaneous pancreas kidney transplantation has survival benefit to patients.

Several organ allocation protocols give priority to wait-listed simultaneous kidney-pancreas (SPK) transplant recipients to mitigate the higher cardiovascular risk of patients with diabetes mellitus on dialysis. The available information regarding the impact of preemptive simultaneous kidney-pancreas transplantation on recipient and graft outcomes is nonetheless controversial. To help resolve this, we explored the influence of preemptive simultaneous kidney-pancreas transplants on patient and graft survival through a retrospective analysis of the OPTN/UNOS database, encompassing 9690 simultaneous transplant recipients between 2000 and 2017. Statistical analysis was performed applying a propensity score analysis to minimize bias. Of these patients, 1796 (19%) were transplanted preemptively. At ten years, recipient survival was significantly superior in the preemptive group when compared to the non-preemptive group (78.9% vs 71.8%). Dialysis at simultaneous kidney-pancreas transplantation was an independent significant risk for patient survival (hazard ratio 1.66 [95% confidence interval 1.32-2.09]), especially if the dialysis duration was 12 months or longer. Preemptive transplantation was also associated with significant superior kidney graft survival compared to those on dialysis (death-censored: 84.3% vs 75.4%, respectively; estimated half-life of 38.57 [38.33 -38.81] vs 22.35 [22.17 - 22.53] years, respectively). No differences were observed between both groups neither for pancreas graft survival nor for post-transplant surgical complications. Thus, our results sustain the relevance of early referral for pancreas transplantation and the importance of pancreas allocation priority in reducing patient mortality after simultaneous kidney-pancreas transplantation.

Patient Experience in Pancreas-Kidney Transplantation-A Methodological Approach Towards Innovation in an Established Program.

Simultaneous pancreas-kidney transplantation (SPKT) leads to increased survival and quality of life, and is an alternative treatment for insulin-dependent diabetes mellitus and end-stage kidney disease. Due to the particularities of this population (often with multiple comorbidities) and of the surgery (only performed in a few centers), a comprehensive analysis of patients' experience along the SPKT process is crucial to improve patient care and add value to this procedure. Therefore, we applied a systematic and iterative methodology with the participation of both patients and professional teams working together to explore and identify unmet needs and value-adding steps along the transplant patient journey at an established pancreas transplant program. Four main steps (to comprehend, to explore, to experiment and to assess) led to several interventions around three major areas: Administration and logistics, information and communication, and perceived quality of assistance. As a result, both displacements to the hospital for diagnostic purposes and the time delay involved in joining the patient waiting list for transplantation were reduced in parallel to the administrative procedures. In conclusion, the methodological implementation of key organizational changes has great impact on overall patient experience. Further quantitative analysis from the patient's perspective will consolidate our program and may add new prototype service design components.

Current Trends in Organ Preservation Solutions for Pancreas Transplantation: A Single-Center Retrospective Study.

Due to the high vulnerability of the pancreas to ischemia-reperfusion injury, choices regarding preservation solution markedly affect pancreas transplant success. A retrospective single-center analysis of 380 pancreas transplants (2000-2019) was performed to correlate current preservation solutions with transplant outcomes. Early graft failure requiring transplantectomy within 30 days post-transplant occurred in 7.5% for University of Wisconsin (UW) group (n = 267), 10.8% of Celsior (CS) group (n = 83), 28.5% of Histidine-Tryptophan-Ketoglutarate (HTK) group (n = 7), and none for Institut Georges Lopez-1 (IGL-1) group (n = 23). The most common causes of technical failures in this cohort included abdominal hemorrhage (8.4%); graft pancreatitis (3.7%); fluid collections (2.6%); intestinal complications (6.6%); and vascular thrombosis (20.5%). Although IGL-1 solution provided lower surgical complication rates, no significant differences were found between studied groups. Nevertheless, HTK solution was associated with elevated pancreatitis rates. The best graft survival was achieved at 1 year using UW and IGL-1, and at 3 and 5 years using IGL-1 (p = 0.017). There were no significant differences in patient survival after a median follow-up of 118.4 months. In this setting therefore, IGL-1 solution appears promising for perfusion and organ preservation in clinical pancreas transplantation, compared to other commonly used solutions.

Impact of Simultaneous Pancreas-kidney Transplantation on Cardiovascular Risk in Patients With Diabetes.

BACKGROUND: Cardiovascular disease is the major cause of death in patients with type 1 diabetes. Of the available risk predictors for this population, the Steno Type 1 Risk Engine (STENO T1) is the only one that includes kidney function as a risk factor, which is a well-described independent risk factor for cardiovascular disease. METHODS: We explore how simultaneous pancreas-kidney transplantation (SPKT) modifies the predicted cardiovascular risk by the STENO T1 through a retrospective study including recipients of a first SPKT between 2000 and 2016. RESULTS: Two hundred sixty-eight SPKT recipients with a mean age of 40 y old and a median follow-up of 10 y were included. Before transplantation, the expected incidence of cardiovascular events (CVEs) at 5 and 10 y according to STENO T1 would have been 31% and 50%, respectively, contrasting with an actual incidence of 9.3% and 16% for the same timepoints, respectively (P < 0.05). These differences were attenuated when STENO T1 was recalculated assuming 12th-mo glomerular filtration rate (at 5 and 10 y predicted CVE incidence was 10.5% and 19.4%, respectively). Early pancreas graft failure (hazard ratio [HR] 3.00, 95% confidence interval [CI], 1.14-7.88; P = 0.02) was an independent risk factor for post-SPKT CVE, alongside kidney graft failure (HR 2.90, 95% CI, 1.53-5.48; P = 0.001), and diabetes duration (HR 1.04, 95% CI, 1.00-1.09, P = 0.04). CONCLUSIONS: SPKT decreases in more than two-thirds of the predicted cardiovascular risk by the STENO T1. A functioning pancreas graft further reduces CVE risk, independently of kidney graft function.

Impact of insulin therapy before donation on graft outcomes in pancreas transplantation: An analysis of the OPTN/UNOS database.

AIMS: Information on the impact of insulin therapy before pancreas donation on pancreas outcomes is scarce. We aim to explore the influence of insulin therapy before donation on recipient and pancreas graft survival. METHODS: Registry study including 12,841 pancreas recipients from the OPTN/UNOS registry performed between 2000 and 2017. Inverse probability of treatment weighting (IPTW) was used to account for covariate imbalance between recipients from a donor with and without insulin requirements. RESULTS: A total of 7765 (60%) patients received a pancreas from a donor with insulin before donation (IBD). Pancreas graft survival (death-censored) was similar between recipients from IBD and non-IBD donors at 1, 5 and 10 years (89% vs 89%, 78% vs 79 and 69% vs 70%, respectively, P = 0.35). Recipients from IBD donors presented a similar 90-days pancreas graft survival. After IPTW weighting, IBD donors were neither associated with any post-transplant surgical complication (HR 1.11 [95% CI 0.98-1.24], P = 0.06), nor with risk for recipient death (HR 0.94 [95% CI 0.85-1.04], P = 0.26), nor pancreas graft failure (HR 1.06 [95% CI 0.98-1.16], P = 0.15). CONCLUSIONS: Insulin therapy before donation in accepted pancreas donors was not associated, per se, with an impaired pancreas graft and patient survival.

Optical Coherence Tomography Angiography in Type 1 Diabetes Mellitus. Report 4: Glycated Haemoglobin.

The purpose of this study was to evaluate specifically the relationship between glycated haemoglobin (HbA1c) levels and retinal optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in type 1 Diabetes Mellitus (DM). A total of 478 type 1 DM patients and 115 controls were included in a prospective OCTA trial (ClinicalTrials.gov NCT03422965). Subgroup analysis was performed for controls, no diabetic retinopathy (DM-no DR) and DR patients (DM-DR), and HbA1c levels. OCT and OCTA measurements were compared with HbA1c levels (current and previous 5 years). DM-no DR patients with HbA1c levels >7.5% showed lower VD than DM-DR and controls (20.16 vs. 20.22 vs. 20.71, p < 0.05), and showed a significant correlation between HbA1c levels and FAZc (p = 0.04), after adjusting for age, gender, signal strength index, axial length, and DM disease duration. DM-DR patients with HbA1c > 7.5% presented greater CRT than DM-no DR and controls (270.8 vs. 260 vs. 251.1, p < 0.05) and showed a significant correlation between HbA1c and CRT (p = 0.03). In conclusion, greater levels of HbA1c are associated with OCTA changes in DM-no DR patients, and with structural OCT changes in DM-DR patients. The combination of OCTA and OCT measurements and HbA1c levels may be helpful to identify patients at risk of progression to greater stages of the diabetic microvascular disease.