Antonio Jesús Amor

Objective: To clarify whether the glucose management indicator (GMI)/glycated haemoglobin (HbA1c) ratio (GMI/HbA1c ratio) is an independent predictor of microvascular complications in Type 1 diabetes (T1D). Design and Methods: Multicentre, cross‐sectional, observational study including subjects with T1D with at least 5 years of evolution, users of continuous glucose monitoring (CGM) with a coverage ≥ 80% 56 days prior to HbA1c. Logistic regression models were used to identify the factors independently associated with grouped microvascular complications and ocular disease. Results: As per data, 1315 participants were included. Patients were classified into tertiles based on the GMI/HbA1c ratio. High glycators were older than intermediate and low glycators (55.4 vs. 53.4 vs. 50.8 years; p < 0.001), respectively. Differences were also observed among the three groups with regard to average glucose (156.3 vs. 161.8 vs. 166.1 mg/dL; p < 0.001), time in range (66.3% vs. 62.9% vs. 59.9%; p < 0.001), time in tight range (42.9% vs. 39.9% vs. 37.1%; p < 0.001), coefficient of variation (34.5% vs. 34.9% vs. 35.6%; p = 0.023), GMI (7% vs. 7.2% vs. 7.3%; p < 0.001) and HbA1c (8.1% vs. 7.3% vs. 6.6%; p < 0.001). In the high glycators group, the prevalence of microvascular complications was higher than in the intermediate and low glycators (38.9% vs. 28.2% vs. 23.7%; p < 0.001), respectively. Also, the prevalence of ocular disease (31% vs. 20.2% vs. 19.7%; p < 0.001), nephropathy (14.9% vs. 8.3% vs. 6.2%; p < 0.001) and polyneuropathy (10.6% vs. 6.8% vs. 3.4%; p < 0.001) was higher in high glycators, The GMI/HbA1c ratio was significantly associated with the presence of grouped microvascular complications (OR 0.71; 95% CI: 0.61–0.81; p < 0.001) and ocular disease (OR 0.71; 95% CI: 0.61–0.82; p < 0.001) after adjusting for clinical ad glucometric variables. Conclusions: The GMI/HbA1c ratio is associated with microvascular complications in this study. These results highlight the potential of this parameter in routine clinical practice for stratifying the risk of complications and for establishing individualized control goals and screening strategies.

OBJECTIVE: To evaluate whether the efficacy and safety of finerenone varied by baseline hemoglobin A1c (HbA1c) level, a proxy of glycemic control, and diabetes duration in people with type 1 diabetes and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: Adults with type 1 diabetes, urinary albumin-to-creatinine ratio (UACR) 200 to <5,000 mg/g, and estimated glomerular filtration rate (eGFR) 25 to <90 mL/min/1.73 m2 were randomly assigned (one to one) to finerenone or placebo. UACR change from baseline over 6 months by baseline HbA1c and diabetes duration was analyzed. RESULTS: Baseline HbA1c was available for 240 of 242 participants; mean (SD) HbA1c, diabetes duration, and eGFR were 7.6% (1.1%; 60 [12] mmol/mol), 32.0 (14.2) years, and 58.9 (19.2) mL/min/1.73 m2, respectively. At 6 months, HbA1c (95% CI) remained unchanged (finerenone +0.03% [−0.14%, 0.20%]; placebo 0.00% [−0.12%, 0.11%]; between-group difference +0.04% [−0.17%, 0.24%]; P = 0.74). Over 6 months, median UACR decreased from 574.6 to 373.5 mg/g with finerenone and from 506.4 to 475.6 mg/g with placebo, corresponding to a −25% placebo-corrected change (95% CI –35%, –13%; P = 0.0001). Treatment effects were consistent across HbA1c tertiles (8.1%), with placebo-corrected UACR changes (95% CIs) of −17% (−40%, 13%), −18% (−39%, 10%), and −37% (−55%, −13%), respectively (P interaction = 0.41). Effects were similarly consistent across diabetes duration tertiles (P interaction = 0.70). Overall safety and incidence of hyperkalemia were similar across HbA1c tertiles. CONCLUSIONS: In adults with type 1 diabetes and CKD, finerenone reduced UACR and was well tolerated irrespective of HbA1c level or diabetes duration.

Background/Objectives: Ischemia–reperfusion injury (IRI) contributes to graft dysfunction in solid organ transplantation, with the pancreas vulnerable due to its fragile vasculature. Endothelial glycocalyx (eGCX) disruption is central to this process. This study prospectively examined perioperative endothelial injury in pancreas transplantation. Methods: Fifty-two recipients were included, of whom 47 underwent simultaneous pancreas-kidney (SPK) transplantation and 5 pancreas retransplantation. Biomarkers of eGCX degradation (syndecan-1, heparan sulfate (HS) and hyaluronan) and endothelial injury (soluble thrombomodulin, VEGF and soluble VEGFR1) were measured in plasma preoperatively, 10 min after pancreas reperfusion, 24 h later, and at discharge. Associations with donor type and early post-transplant outcomes were explored. Results: A marker endothelial injury was evident within 10 min of pancreas reperfusion, before kidney implantation, characterized by increased syndecan-1, HS, and sVEGFR1, together with decreased VEGF. Hyaluronan peaked at 24 h, consistent with a broader systemic endothelial response. Controlled donation after circulatory death donors showed higher syndecan-1 levels at 10 min PR and higher VEGF at 24 h. Seven recipients developed pancreas graft loss, which was linked to lower VEGF at 10 min post-reperfusion and lower hyaluronan levels both before surgery and at discharge. Kidney acute tubular necrosis was related with higher preoperative HS and elevated 24 h sVEGFR1. Among recipients with functioning grafts, preoperative endothelial biomarkers were linked to postoperative complications. Conclusions: Pancreas transplantation triggers early endothelial injury and glycocalyx shedding, particularly in a predominant SPK setting. Perioperative endothelial biomarkers may have a value for early risk stratification after transplantation.

Cardiovascular disease (CVD) remains the leading cause of premature mortality in type 1 diabetes (T1D). Despite this burden, current prevention guidelines and risk stratification tools are largely extrapolated from type 2 diabetes or general populations, often failing to capture the unique pathophysiological drivers of atherosclerosis in T1D. This narrative review aims to critically evaluate current cardiovascular prevention strategies, identify the limitations of generic risk calculators, and analyse the clinical utility and discriminatory performance of population-specific risk equations. Current clinical practice guidelines provide heterogeneous and inconsistent recommendations for T1D. Generic risk calculators (e.g. SCORE2, ACC/AHA pooled cohort equations) are limited by short-term prediction horizons and a lack of validation in T1D cohorts, frequently leading to poor diagnostic performances in this population. Conversely, T1D-specific equations, such as Steno Type 1 Risk Engine (Steno-Risk) and the emerging LIFE-T1D model, incorporate disease-specific variables such as diabetes duration or albuminuria. Available evidence indicates that T1D equations as Steno-Risk demonstrate superior discriminatory performance compared to generic scores identifying those individuals with higher cardiovascular risk. However, despite improved calibration, specific tools still classify a substantial proportion of patients with established subclinical atherosclerotic disease as 'moderate risk,' creating a grey area that complicates therapeutic decision-making. Generic cardiovascular risk algorithms are inadequate for the T1D population. While specific equations represent a significant advancement toward accurate stratification, mathematical models alone may be insufficient. Moving toward precision medicine requires a combined approach that integrates validated T1D-specific risk calculators with subclinical atherosclerosis screening (e.g. carotid ultrasound, CAC scoring) and novel biomarkers. This synergistic strategy is essential to refine classification in the 'moderate risk' category and guide individualised cardioprotective interventions.

Introduction Simultaneous pancreas–kidney (SPK) transplantation normalizes glycemia in patients with diabetes and end-stage kidney disease, yet data on continuous glucose monitoring (CGM) remain scarce. Methods We retrospectively analyzed CGM metrics in SPK recipients using FreeStyle Libre 2®, comparing pre- and post-transplant profiles. Results Among n = 19 recipients, only n = 14 continued CGM use after transplantation (n = 9 continuously during the entire study period). Within 1 month, all CGM metrics improved significantly, including increased time-in-range (54.21 vs. 83.85%) and time-in-tight-range (TITR; 33.45 vs. 69.77%), and reduced glucose variability (p < 0.05 for all comparisons), with stability over 24 months. Optimal graft function was associated with superior CGM outcomes, notably higher TITR and lower mean amplitude of glycemic excursions (MAGE; p < 0.05). However, hypoglycemia-related targets were not consistently achieved despite otherwise optimal graft performance. Conclusions SPK transplantation was linked to rapid and sustained improvement in CGM profiles. These findings underscore CGM’s value for monitoring graft function and support its integration into post-transplant care to optimize metabolic outcomes.

Background/Objectives: To evaluate the long-term impact of a structured diabetic foot education program on major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs) in individuals with type 1 diabetes. Methods: Retrospective cohort study including 327 adults with type 1 diabetes who participated in a structured diabetic foot education program between 1990 and 2014. The program included 10 h of education focused on diabetes self-management and foot care. Participants were encouraged to attend annual refresher sessions. The primary outcomes were the first occurrence of MALE (major amputation or lower-limb revascularization) and MACE (non-fatal stroke, non-fatal myocardial infarction, or all-cause death). Cox proportional hazards models were used to assess associations between the number of educational programs (EPs) attended (1, 2–3, >3) and outcomes. Results: Participants attended a median of two EPs during a median follow-up of 26.3 years. Of the total number of events, 21 were MALEs (crude incidence of 1.9 per 1000 person-years) and 108 were MACEs (incidence of 12.9 per 1000 person-years). Risk of MALE was not associated with the number of EPs attended (p = 0.384). In contrast, participants who attended >3 EPs had a significantly lower risk of MACE compared with those attending only one program (HR 0.48, 95% CI 0.24–0.99, p = 0.044), although this association was attenuated after adjusting for smoking status. Conclusions: Frequent participation in a structured diabetic foot education program was associated with fewer cardiovascular events, but this benefit was diminished by smoking. Integrating tobacco cessation into education programs may enhance their long-term impact.

Objectives: Cardiovascular risk factor (CVRF) management and healthy lifestyles protect against cardiovascular disease (CVD), although their impact in type 1 diabetes (T1D) is underexplored. This study aimed to examine the relationship between healthy lifestyle parameters and preclinical atherosclerosis in this population.Materials and Methods: Cross‐sectional study in individuals with T1D without established CVD, meeting one of the following: ≥ 40 years‐old, diabetic kidney disease, or ≥ 10 years duration of T1D with another CVRF. We used a modification of the American Heart Association ‘Life's Simple Seven’ (AHA‐LSS) scoring system, measuring 7 variables (body mass index, smoking, physical activity, Mediterranean diet, LDL‐cholesterol, blood pressure, and HbA1c) scoring ranging 0–13 points (higher score, better CVRF profile). Presence of plaques was assessed using carotid ultrasound. Patients were categorised into low (AHA‐LSS ≤ 5), medium (AHA‐LSS 6–7) and high (AHA‐LSS ≥ 8) tertiles. Associations between AHA score and atherosclerosis were assessed using logistic regression models.Results: We included n = 518 individuals (55% women, age 48 ± 11 years, T1D duration 27 ± 11 years, HbA1c 7.49 ± 0.90%, AHA‐LLS 6 [5–8]). An inverse relationship was observed between AHA‐LSS score and different CVRFs and plaque burden (p < 0.05 for all). This inverse relationship persisted after adjusting for classical and specific‐T1D CVRFs not included in the score, both for plaque presence (OR 0.37 [0.20–0.70]) and ≥ 2 plaques (OR 0.30 [0.13–0.68]; p < 0.05).Conclusions: Holistic control of CVRFs and healthy lifestyles are associated with lower preclinical atherosclerosis prevalence in individuals with T1D. These findings highlight the need to address non‐glycaemic factors in this population to improve cardiovascular health.

Chronic kidney disease (CKD) is a common comorbidity of both type 1 diabetes (T1D) and type 2 diabetes (T2D) and is associated with increased mortality, end-stage kidney disease and cardiovascular disease risk. Despite standard-of-care treatment with renin–angiotensin system inhibitors added to blood pressure and glycaemic control, people with CKD and T1D have a residual risk of CKD progression. Advances in therapeutic management have been limited over the past 3 decades, especially compared with CKD in T2D, for which new treatment options have emerged in the last 5 years. In this review article we discuss the similarities and differences between T1D and T2D populations with CKD, including epidemiology, pathophysiology and clinical findings. Additionally, we explore the use of albuminuria as a potential bridging biomarker to extrapolate clinical evidence from one population to the other. This concept could offer a promising strategy to narrow the gap in treatment availability between these populations and address the unmet therapeutic need in people with CKD and T1D. The FINE-ONE trial is investigating the non-steroidal mineralocorticoid receptor antagonist finerenone in a population with CKD and T1D using the change in urine albumin:creatinine ratio from baseline over 6 months as its primary endpoint and bridging biomarker. Similarities between the populations from FINE-ONE trial and FIDELITY (a pooled dataset of individuals with CKD and T2D included in two large phase 3 clinical trials of finerenone) may inform the translation of clinical evidence on finerenone from people with CKD and T2D to those with CKD and T1D.

Background/objectives: Individuals with type 1 diabetes (T1DM) face an elevated risk of cardiovascular disease (CVD), yet the factors driving atherosclerosis remain unclear. This study aimed to assess factors associated with preclinical atherosclerosis development or progression in T1DM. Methods: We conducted a prospective study in T1DM individuals without established CVD, aged ≥40 years, with diabetic kidney disease and/or ≥10 years of T1DM plus another cardiovascular risk factor (CVRF). Baseline evaluation followed a standardized CV risk assessment protocol, including carotid ultrasound and cardiovascular risk estimation using the Steno Type 1 Risk Engine (ST1RE). Ultrasound was repeated after 3–5 years; progression was defined as an increase in plaque number. CVRF control was considered optimal when LDL-cholesterol was within target based on atherosclerotic burden, blood pressure p < 0.05), 40.4% experienced progression. Older age (OR 1.38 [1.1–1.8]) and active smoking (OR 3.29 [1.4–7.5]) were significant predictors of progression. Baseline cardiovascular risk measured by the ST1RE independently predicted progression (OR 1.09 [1.03–1.15]) after adjusting for other CVRFs. Persistent smoking (OR 2.52 [1.06–5.99]) and baseline ST1RE (OR 1.06 [1.02–1.11]) remained significant after accounting for baseline and follow-up CVRFs. Conclusions: Despite improved CVRF control, atherosclerosis progression is common in T1D. ST1RE may help identify individuals at highest risk for targeted preventive strategies.