Antonio Nicolucci

Purpose: Characteristics defining “early” type 2 diabetes (T2D) are unclear, and type and timing of treatment intensification with glucose-lowering drugs (GLD) in these patients are understudied. Methods: Within the AMD Annals Initiative, we evaluated the prevalence and clinical characteristics of early T2D subjects, evaluated by diabetologists and defined according to a recent Delphi Consensus. Patient characteristics of early T2D subjects were compared to those of non-early patients. We also explored the time and mode of first intensification in a longitudinal cohort from 2010 to 2023. Results: Overall, 127,456 people were seen in 2023, of whom 10,700 (8.39%) showed an early phenotype. Early patients were younger, more often females, had lower HbA1c, used less cardiovascular-related drugs, and had a lower prevalence of cardiovascular disease. Conclusion: In real life, T2D could be considered as early in only ~ 8% of people. Among them, less than 10% received treatment intensification during the first year of observation, although the timing of the introduction of add-on GLD improved during time and drugs with cardiovascular benefit were often chosen as second-line GLD. In longitudinal analysis, of 42,786 early patients initially treated with metformin, 9.37% were prescribed an add-on treatment during 12 months, more frequently represented by SGLT2i, followed by GLP1-RAs and DPP4i. Mean level of HbA1c at treatment intensification improved over time, suggesting an encouraging trend through a proactive approach.

Aims: To investigate the independent association of albuminuria within the normoalbuminuric range with all‐cause mortality in normoalbuminuric people with type 2 diabetes with and without chronic kidney disease (CKD). Materials and Methods: This observational, prospective, multicentre, cohort study enroled 15,773 individuals with type 2 diabetes in 2006–2008. At baseline, albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR) were assessed together with cardiometabolic risk profile, treatments, complications, and comorbidities. All‐cause mortality was verified on 31 October 2015. Results: Of the 15,656 participants (99.3%) with valid information on vital status, 11,460 (71.2%) were normoalbuminuric, 9984 (87.1%) without and 1476 (12.9%) with CKD. Normoalbuminuric individuals were stratified into three (< 5, 5–15, and > 15 mg·day ⁻¹ ) or two (< 10 and 10–29 mg·day ⁻¹ ) AER subcategories. When adjusting for age, sex, eGFR, prior cardiovascular disease, cardiovascular risk factors, and treatments, mortality risk was higher in participants with AER 10–29 versus < 10 mg·day ⁻¹ (hazard ratio, 1.120 [95% confidence interval, 1.028–1.221], p = 0.009) and 15–29 versus < 5 mg·day ⁻¹ (1.243 [1.099–1.406], p < 0.0001). When stratifying by CKD status, the adjusted risk remained significantly increased only for AER 15–29 versus < 5 mg/24 h in individuals with (1.404 [1.111–1.774], p = 0.005) and, to a lesser extent, without (1.167 [1.009–1.350], p = 0.038) CKD. A non‐linear association was observed between AER as Log2 transformed continuous variable and mortality. Conclusions: For the same level of kidney function, higher AER within the normoalbuminuric range was independently associated with all‐cause mortality, thus supporting to the use of albuminuria‐lowering drugs in people with type 2 diabetes and mildly elevated albuminuria. Trial Registration: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.

The real-world PatiEnt satisfactiON studY (PEONY) involves postmenopausal women already treated or starting local estrogen therapy (LET) or ospemifene. The aim of the present analysis was to assess treatment satisfaction and persistence, effectiveness and patient-reported outcomes (PROs) in sexual function and quality of life after 6 months of therapy with LET or ospemifene to treat vulvovaginal atrophy (VVA). PEONY is an ongoing prospective, observational study conducted in 17 gynecology centers. Participants complete questionnaires at baseline (T0) and after 3 months (T3) and 6 months (T6). The main outcome measures were treatment satisfaction, severity of symptoms, Day-to-Day Impact of Vaginal Aging (DIVA), Female Sexual Function Index (FSFI), Female Sexual Distress Scale - Revised (FSDS-R) and SF-12 Health Survey. Overall, 385 women were included, of whom 145 started (87.6%) or continued (12.4%) ospemifene and 240 started (66.7%) or continued (33.3%) LET at T0. The likelihood of moderate/severe VVA symptoms decreased by 70-90% and the mean treatment satisfaction score increased overall from 7.3 (95% confidence interval [CI]: 7.0; 7.5) at T3 to 7.7 (95% CI: 7.4; 7.9) at T6 (p = 0.003). DIVA and FSDS-R scores significantly improved in both groups. PEONY underlines the importance of proactively treating VVA with LET or ospemifene to alleviate the burden associated with the disease.

Background: To assess the real‐world effectiveness of switching from first‐generation basal insulins (1BIs) to either glargine U300 (Gla‐300) or degludec U100 (Deg‐100) in children and adolescents with type 1 diabetes (T1D), using data from the Italian ISPED CARD clinical registry. Materials and Methods: This multicenter retrospective observational study included 1063 pediatric patients with T1D from 22 diabetes centers across Italy who switched from 1BI to either Gla‐300 (64.6%) or Deg‐100 (35.4%) between 2021 and 2023. Propensity score matching (PSM) was applied to create comparable groups ( n = 353 per group). Primary endpoint was the change in HbA1c at 6 months. Secondary endpoints included fasting blood glucose (FBG), standardized body mass index (BMI/SDS), and insulin doses at 6 and 12 months. Longitudinal models for repeated measures were used to assess treatment effectiveness. Results: Both groups showed significant and clinically relevant reductions in HbA1c at 6 months from ~ 8.7% to ~ 7.4% (−1.3 percentage points), maintained at 12 months, with no significant differences between groups. FBG also decreased significantly in both groups, slightly favoring Deg‐100, but without statistical significance between groups. BMI/SDS remained stable. Gla‐300 was associated with a slight increase in basal insulin dose over 12 months, while Deg‐100 showed a temporary reduction at 6 months. A significant reduction in short‐acting insulin dose (−0.03 U/kg) was observed in both groups. Conclusion: Switching from 1BI to either Gla‐300 or Deg‐100 significantly improves glycemic control in pediatric T1D patients without weight gain. Although both insulins showed comparable effectiveness, differences in titration patterns highlight the need for individualized treatment strategies and improved clinician education in insulin optimization. Safety outcomes, particularly hypoglycemia, could not be assessed.

Aim: Intraindividual body weight variability (BWV), that is, the degree of weight fluctuations over time, is associated with an increased risk of cardiovascular diseases (CVDs) in multiple settings. The impact of BWV on cardiovascular risk in type 1 diabetes (T1D) remains unclear, despite the issues relative to weight management in individuals with this condition. Materials and methods: Using data from the Swedish National Diabetes Register, we identified individuals with T1D and without CVD at baseline with at least three measurements of body weight taken over three consecutive years. We estimated BWV as quartiles of the standard deviation of weight measures and explored its longitudinal association with the incidence of CVD during a 12.7 ± 4.6 year follow‐up through adjusted Cox regression models. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke and all‐cause mortality. We modelled the function of risk in relation to the magnitude of BWV, testing also whether weight trends, that is, increasing, stable or decreasing, age, sex and glycaemic control modified the association between BWV and the outcome. Results: Among the 36 333 individuals with T1D in the register, we identified 19 373 individuals with at least three measures of body weight and without CVD at baseline. Participants with the highest BWV had a 42% increased risk of reaching the primary endpoint compared to those with the lowest BWV (hazard ratio [HR] = 1.42, 95% confidence interval [CI]: 1.24–1.62). In addition, high BWV was significantly associated with a 51% increased risk of all‐cause mortality (HR = 1.51, 95% CI: 1.28–1.78), a 37% increased risk of peripheral artery disease (HR = 1.37, 95% CI: 1.06–1.77) and a 55% increased risk of hospitalization for heart failure (HR = 1.55, 95% CI: 1.20–2.01). BWV showed a quasi‐linear association with the primary endpoint. No interaction was observed when comparing subgroups for weight trends, sex or degree of glycaemic control. In the subgroup of elderly individuals, the association of BWV with the primary endpoint was no longer significant. Conclusions: High BWV is associated with an increased risk of CVD and all‐cause mortality in individuals with T1D, independently of canonical risk factors. Weight trends, sex and glycaemic control do not modify such association while older age attenuates it.

Early, intensive glycemic control in patients with type 2 diabetes (T2D) is associated with long-term benefits in cardiovascular disease (CVD) development. Evidence on benefits of achieving HbA1c targets close to normal values is scant. Individuals with newly diagnosed T2D, without CVD at baseline, were identified in an Italian clinical registry (n = 251,339). We adopted three definitions of early exposure periods (0–1, 0–2, and 0–3 years). Mean HbA1c was categorized into HbA1c 8.0%. The outcome was the incidence of major cardiovascular events. After a mean follow-up of 4.6 ± 2.9 years, at multivariate Cox regression analysis, compared with mean HbA1c 8.0%, respectively. The same trend was documented in all exposure periods. In conclusion, our data support that an early achievement of stringent targets of HbA1c <5.7% is worthy for CVD prevention. Article Highlights: