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Background: International guidelines for diabetes care emphasize the urgency of promptly achieving and sustaining adequate glycemic control to reduce the occurrence of micro/macrovascular complications in patients with type 2 diabetes mellitus (T2DM). However, data from the Italian Association of Medical Diabetologists (AMD) Annals reveal that only 47% of T2DM patients reach appropriate glycemic targets, with approximately 30% relying on insulin therapy, either solely or in combination. This artificial intelligence analysis seeks to assess the potential impact of timely insulin initiation in all eligible patients via a “what-if” scenario simulation, leveraging real-world data. Methods: This retrospective cohort study utilized the AMD Annals database, comprising 1,186,247 T2DM patients from 2005 to 2019. Employing the Logic Learning Machine (LLM), we simulated timely insulin use for all eligible patients, estimating its effect on glycemic control after 12 months within a cohort of 85,239 patients. Of these, 20,015 were employed for the machine learning phase and 65,224 for simulation. Results: Within the simulated scenario, the introduction of appropriate insulin therapy led to a noteworthy projected 17% increase in patients meeting the metabolic target after 12 months from therapy initiation within the cohort of 65,224 individuals. The LLM’s projection envisages 32,851 potential patients achieving the target (hemoglobin glycated < 7.5%) after 12 months, compared to 21,453 patients observed in real-world cases. The receiver operating characteristic (ROC) curve analysis for this model demonstrated modest performance, with an area under the curve (AUC) value of 70.4%. Conclusions: This study reaffirms the significance of combatting therapeutic inertia in managing T2DM patients. Early insulinization, when clinically appropriate, markedly enhances patients’ metabolic goals at the 12-month follow-up.

Summary: Background: A delay in reaching HbA1c targets in patients with newly-diagnosed type 2 diabetes (T2D) is associated with an increased long-term risk of developing cardiovascular diseases (CVD), a phenomenon referred to as legacy effect. Whether an early introduction of glucose-lowering drugs with proven benefit on CVD can attenuate this phenomenon is unknown. Methods: Using data derived from a large Italian clinical registry, i.e. the AMD Annals, we identified 251,339 subjects with newly-diagnosed T2D and without CVD at baseline. Through Cox regressions adjusted for multiple risk factors, we examined the association between having a mean HbA1c between 7.1 and 8% or >8%, compared with ≤7%, for various periods of early exposure (0–1, 0–2, 0–3 years) and the development of later (mean subsequent follow-up 4.6 ± 2.9 years) CVD, evaluated as a composite of myocardial infarction, stroke, coronary or peripheral revascularization, and coronary or peripheral bypass. We performed this analysis in the overall cohort and then splitting the population in two groups of patients: those that introduced sodium-glucose transport protein 2 inhibitors (SGLT-2i) during the exposure phase and those not treated with these drugs. Findings: Considering the whole cohort, subjects with both a mean HbA1c between 7.1 and 8% and >8%, compared with patients attaining a mean HbA1c ≤ 7%, showed an increased risk of developing the outcome in all the three early exposure periods assessed, with the highest risk observed in patients with mean HbA1c > 8% in the 3 years exposure period (hazard ratio [HR]1.33; 95% confidence interval [CI] 1.063–1.365). The introduction of SGLT-2i during the exposure periods of 0–1 and 0–2 years eliminated the association between poor glycemic control and the outcome (p for interaction 0.006 and 0.003, respectively, vs. patients with the same degree of glycemic control but not treated with these drugs). Interpretation: Among patients with newly diagnosed T2D and free of CVD at baseline, a poor glycemic control in the first three years after diagnosis is associated with an increased subsequent risk of CVD. This association is no longer evident when SGLT-2i are introduced in the first two years, suggesting that these drugs attenuate the phenomenon of legacy effect. An early treatment with these drugs might thus promote a long-lasting benefit in patients not attaining proper glycemic control after T2D diagnosis. Funding: This work was supported, in part, by the Italian Ministry of Health (Ricerca Corrente) to IRCCS MultiMedica.

Presentamos el caso de una paciente de 70 años, con el único antecedente médico de interés de anafilaxia por Anisakis, que presenta un fracaso renal agudo con biopsia compatible con nefritis tubulointersticial de etiología alérgica tras la ingesta de pescado. A pesar de que no se ha publicado ningún caso previo de nefritis por hipersensibilidad a Anisakis, la clínica, evolución y biopsia fueron compatibles con esta sospecha, sin poderse encontrar otra posible etiología del fracaso renal agudo.

We evaluated gender-differences in quality of type 1 diabetes (T1DM) care. Starting from electronic medical records of 300 centers, 5 process indicators, 3 favorable and 6 unfavorable intermediate outcomes, 6 treatment intensity/appropriateness measures and an overall quality score were measured. The likelihood of women vs. men (reference class) to be monitored, to reach outcomes, or to be treated has been investigated through multilevel logistic regression analyses; results are expressed as Odd Ratios (ORs) and 95% confidence intervals (95%CIs). The inter-center variability in the achievement of the unfavorable outcomes was also investigated. Overall, 28,802 subjects were analyzed (45.5% women). Women and men had similar age (44.5±16.0 vs. 45.0±17.0 years) and diabetes duration (18.3±13.0 vs. 18.8±13.0 years). No between-gender differences were found in process indicators. As for intermediate outcomes, women showed 33% higher likelihood of having HbA1c ≥8.0% (OR = 1.33; 95%CI: 1.25-1.43), 29% lower risk of blood pressure ≥140/90 mmHg (OR = 0.71; 95%CI: 0.65-0.77) and 27% lower risk of micro/macroalbuminuria (OR = 0.73; 95%CI: 0.65-0.81) than men, while BMI, LDL-c and GFR did not significantly differ; treatment intensity/appropriateness was not systematically different between genders; overall quality score was similar in men and women. Consistently across centers a larger proportion of women than men had HbA1c ≥8.0%, while a smaller proportion had BP ≥140/90 mmHg. No gender-disparities were found in process measures and improvements are required in both genders. The systematic worse metabolic control in women and worse blood pressure in men suggest that pathophysiologic differences rather than the care provided might explain these differences.

AIMS: Beta-cell dysfunction is an early event in the natural history of type 2 diabetes. However, its progression is variable and potentially influenced by several clinical factors. We report the baseline data of the BetaDecline study, an Italian prospective multicenter study on clinical predictors of beta-cell dysfunction in type 2 diabetes. MATERIALS AND METHODS: Clinical, lifestyle, and laboratory data, including circulating levels of inflammatory markers and non-esterified fatty acids, were collected in 507 type 2 diabetic outpatients on stable treatment with oral hypoglycemic drugs or diet for more than 1 year. Beta-cell dysfunction was evaluated by calculating the proinsulin/insulin ratio (P/I). RESULTS: At baseline, the subjects in the upper PI/I ratio quartile were more likely to be men and receiving secretagogue drugs; they also showed a borderline longer diabetes duration (P = 0.06) and higher serum levels of glycated hemoglobin (HbA1c), fasting blood glucose, and triglycerides. An inverse trend across all PI/I quartiles was noted for BMI and serum levels of total cholesterol (T-C), LDL-C, HDL-C and C reactive protein (CRP), and with homeostatic model assessment (HOMA-B) and HOMA of insulin resistance (HOMA-IR) values (P

Background: International guidelines for diabetes care emphasize the urgency of promptly achieving and sustaining adequate glycemic control to reduce the occurrence of micro/macrovascular complications in patients with type 2 diabetes mellitus (T2DM). However, data from the Italian Association of Medical Diabetologists (AMD) Annals reveal that only 47% of T2DM patients reach appropriate glycemic targets, with approximately 30% relying on insulin therapy, either solely or in combination. This artificial intelligence analysis seeks to assess the potential impact of timely insulin initiation in all eligible patients via a "what-if" scenario simulation, leveraging real-world data. Methods: This retrospective cohort study utilized the AMD Annals database, comprising 1,186,247 T2DM patients from 2005 to 2019. Employing the Logic Learning Machine (LLM), we simulated timely insulin use for all eligible patients, estimating its effect on glycemic control after 12 months within a cohort of 85,239 patients. Of these, 20,015 were employed for the machine learning phase and 65,224 for simulation. Results: Within the simulated scenario, the introduction of appropriate insulin therapy led to a noteworthy projected 17% increase in patients meeting the metabolic target after 12 months from therapy initiation within the cohort of 65,224 individuals. The LLM's projection envisages 32,851 potential patients achieving the target (hemoglobin glycated < 7.5%) after 12 months, compared to 21,453 patients observed in real-world cases. The receiver operating characteristic (ROC) curve analysis for this model demonstrated modest performance, with an area under the curve (AUC) value of 70.4%. Conclusions: This study reaffirms the significance of combatting therapeutic inertia in managing T2DM patients. Early insulinization, when clinically appropriate, markedly enhances patients' metabolic goals at the 12-month follow-up. [ABSTRACT FROM AUTHOR]

2 TABLE Raw incidence rates (IR) of type 1 diabetes in Piedmont (Italy) by 100 000 residents and rate ratios (RR), comparison between before and during the COVID pandemic years. Nevertheless, over the 3 years of the COVID-19 pandemic, the overall incidence of DM1 has remained ~17% higher than before the pandemic, suggesting further work to understand the link between coronaviruses and diabetes is a priority. Keywords: database research; observational; population study; study; type 1 diabetes EN database research observational population study study type 1 diabetes 3068 3070 3 09/06/23 20231001 NES 231001 BACKGROUND There have now been several reports that the incidence of type 1 diabetes (DM1) increased during the COVID-19 pandemic, particularly in young children,[[1], [3]] although some data are conflicting.[4] Overall, however, there is emerging evidence from diabetes registries that this observed increase is real. [Extracted from the article]

Incidence rate ratios (RRs) were calculated as the ratio between the incidence of each year with the appropriate incidences in 2017 (reference year). Increased incidence of type 1 diabetes in 2 years of COVID-19 pandemic Comparisons of pooled incidence between three non-COVID years (2017-2019) and the two COVID-19 years (2020-2021) confirm the above significant increase in the total population. [Extracted from the article]

Purpose: A multicentre, randomized, double-blind, placebo-controlled, parallel-group study aimed to define the potential positive effect of dipeptidyl peptidase-4 inhibition on left ventricular systolic function (LVSF) beyond glycemic control in type 2 diabetes mellitus (T2DM) (DYDA 2™ trial). Methods: Individuals with fairly controlled T2DM and asymptomatic impaired LVSF were randomized in a 1:1 ratio to receive for 48 weeks either linagliptin 5 mg daily or placebo, in addition to their stable diabetes therapy. Eligibility criteria were age ≥ 40 years, history of T2DM with a duration of at least 6 months, HbA1c ≤ 8.0% (≤ 64 mmol/mol), no history or clinical signs/symptoms of cardiac disease, evidence at baseline echocardiography of concentric LV geometry (relative wall thickness ≥ 0.42), and impaired LVSF defined as midwall fractional shortening (MFS) ≤ 15%. The primary end-point was the modification from baseline to 48 weeks of MFS. As an exploratory analysis, significant changes in LV global longitudinal strain and global circumferential strain, measured by speckle tracking echocardiography, were also considered. Secondary objectives were changes in diastolic and/or in systolic longitudinal function as measured by tissue Doppler. Results: A total of 188 patients were enrolled. They were predominantly males, mildly obese, with typical insulin-resistance co-morbidities such as hypertension and dyslipidemia. Mean relative wall thickness was 0.51 ± 0.09 and mean MFS 13.3% ± 2.5. Conclusions: DYDA 2 is the first randomized, double-blind, placebo-controlled trial to explore the effect of a dipeptidyl peptidase-4 inhibitor on LVSF in T2DM patients in primary prevention regardless of glycemic control. The main characteristics of the enrolled population are reported. Trial registration: ClinicalTrial.gov Identifier: NCT02851745. [ABSTRACT FROM AUTHOR]

We evaluated gender-differences in quality of type 1 diabetes (T1DM) care. Starting from electronic medical records of 300 centers, 5 process indicators, 3 favorable and 6 unfavorable intermediate outcomes, 6 treatment intensity/appropriateness measures and an overall quality score were measured. The likelihood of women vs. men (reference class) to be monitored, to reach outcomes, or to be treated has been investigated through multilevel logistic regression analyses; results are expressed as Odd Ratios (ORs) and 95% confidence intervals (95%CIs). The inter-center variability in the achievement of the unfavorable outcomes was also investigated. Overall, 28,802 subjects were analyzed (45.5% women). Women and men had similar age (44.5±16.0 vs. 45.0±17.0 years) and diabetes duration (18.3±13.0 vs. 18.8±13.0 years). No between-gender differences were found in process indicators. As for intermediate outcomes, women showed 33% higher likelihood of having HbA1c ≥8.0% (OR = 1.33; 95%CI: 1.25–1.43), 29% lower risk of blood pressure ≥140/90 mmHg (OR = 0.71; 95%CI: 0.65–0.77) and 27% lower risk of micro/macroalbuminuria (OR = 0.73; 95%CI: 0.65–0.81) than men, while BMI, LDL-c and GFR did not significantly differ; treatment intensity/appropriateness was not systematically different between genders; overall quality score was similar in men and women. Consistently across centers a larger proportion of women than men had HbA1c ≥8.0%, while a smaller proportion had BP ≥140/90 mmHg. No gender-disparities were found in process measures and improvements are required in both genders. The systematic worse metabolic control in women and worse blood pressure in men suggest that pathophysiologic differences rather than the care provided might explain these differences. [ABSTRACT FROM AUTHOR]

Aims: Beta-cell dysfunction is an early event in the natural history of type 2 diabetes. However, its progression is variable and potentially influenced by several clinical factors. We report the baseline data of the BetaDecline study, an Italian prospective multicenter study on clinical predictors of beta-cell dysfunction in type 2 diabetes. Materials and Methods: Clinical, lifestyle, and laboratory data, including circulating levels of inflammatory markers and non-esterified fatty acids, were collected in 507 type 2 diabetic outpatients on stable treatment with oral hypoglycemic drugs or diet for more than 1 year. Beta-cell dysfunction was evaluated by calculating the proinsulin/insulin ratio (P/I). Results: At baseline, the subjects in the upper PI/I ratio quartile were more likely to be men and receiving secretagogue drugs; they also showed a borderline longer diabetes duration (P = 0.06) and higher serum levels of glycated hemoglobin (HbA1c), fasting blood glucose, and triglycerides. An inverse trend across all PI/I quartiles was noted for BMI and serum levels of total cholesterol (T-C), LDL-C, HDL-C and C reactive protein (CRP), and with homeostatic model assessment (HOMA-B) and HOMA of insulin resistance (HOMA-IR) values (P<0.05 for all). At multivariate analysis, the risk of having a P/I ratio in the upper quartile was higher in the subjects on secretagogue drugs (odds ratio [OR] 4.2; 95% confidence interval [CI], 2.6–6.9) and in the males (OR 1.8; 95% CI, 1.1–2.9). Conclusions: In the BetaDecline study population, baseline higher PI/I values, a marker of beta-cell dysfunction, were more frequent in men and in patients on secretagogues drugs. Follow-up of this cohort will allow the identification of clinical predictors of beta-cell failure in type 2 diabetic outpatients. [ABSTRACT FROM AUTHOR]

The voltammetric generation of corannulene anions was investigated over a large range of experimental conditions comprising either “traditional” electrochemical solvents, such as dimethylformamide, acetonitrile, and tetrahydrofuran, or “unconventional” solvents, such as liquid ammonia, liquid methylamine, or liquid dimethylamine, and several different supporting electrolytes. Strong ion pairing effects were found to dominate the electrochemical generation of corannulene higher anions, and through the suitable choice of the solvent/electrolyte system, we observed, for the first time, the reversible electrochemical generation of up to the triply reduced corannulene. The standard potentials obtained experimentally compared rather well with the theoretical values calculated by ab initio and density functional methods, in which solvation and ion pairing effect were explicitly taken into account. In particular, the calculations considered the effect of the electrolyte cation size on ion pairing in order to rationalize the occurrence of the third reduction within the experimental potential window. [ABSTRACT FROM AUTHOR]