Raffaella Buzzetti

Aim The study was designed to generate real‐world evidence on IDegLira in the Italian clinical practice in two groups of patients with type 2 diabetes (T2D), switching to IDegLira either from a basal only (basal group) or basal‐bolus insulin regimen (BB group). Materials and Methods This was a non‐interventional, multicentre, single‐cohort, prospective study assessing the long‐term glycaemic control in patients with T2D, who switched to IDegLira from a basal insulin ± glucose‐lowering medication regimen with or without a bolus insulin component for approximately 18 months, conducted in 28 Italian diabetes centres. The primary endpoint was the change in glycated haemoglobin (HbA1c) levels from baseline to 6 months after IDegLira initiation. Results The study included 358 patients with a mean age 67.2 years and diabetes duration of 15.7 years. HbA1c significantly decreased from IDegLira start to all …

Context Mortality in type 2 diabetes is twice that of the normoglycemic population. Unravelling biomarkers that identify high‐risk patients for referral to the most aggressive and costly prevention strategies is needed. Objective To validate in type 2 diabetes the association with all‐cause mortality of a 14‐metabolite score (14‐MS) previously reported in the general population and whether this score can be used to improve well‐established mortality prediction models. Methods This is a sub‐study consisting of 600 patients from the “Sapienza University Mortality and Morbidity Event Rate” (SUMMER) study in diabetes, a prospective multicentre investigation on all‐cause mortality in patients with type 2 diabetes. Metabolic biomarkers were quantified from serum samples using high‐throughput proton nuclear magnetic resonance metabolomics. Results In type 2 diabetes, the 14–MS showed a significant (p < 0.0001 …

PurposeContinuous Glucose Monitoring (CGM) is a key tool for insulin-treated people with diabetes (PwD). CGM devices include both real-time CGM (rtCGM) and intermittently scanned CGM (isCGM), which are associated with an improvement of glucose control and less hypoglycemia in clinical trials of people with type 1 and type 2 diabetes.MethodsThis is an expert position to update a previous algorithm on the most suitable choice of CGM for insulin-treated PwD in light of the recent evidence and clinical practice.ResultsWe identified six different clinical scenarios, including type 1 diabetes, type 2 diabetes, pregnancy on intensive insulin therapy, regular physical exercise, new onset of diabetes, and frailty. The use of rtCGM or isCGM is suggested, on the basis of the predominant clinical issue, as suboptimal glucose control or disabling hypoglycemia, regardless of baseline HbA1c or individualized HbA1c target …

The 30th anniversary of Latent Autoimmune Diabetes in Adults (LADA) is a remarkable milestone in diabetes mellitus research. Described for the first time in 1993, LADA disputes the traditional binary classification of diabetes, with autoimmune features (autoimmune‐mediated β‐cell destruction) like that of type 1 diabetes (T1D) yet with an adult‐onset pattern not requiring insulin, at least initially and, therefore, resembling type 2 diabetes (T2D). 1, 2 Thus, commenced an extensive journey of scientific exploration. Although our understanding of LADA has grown substantially over this period, many questions surrounding LADA remain unresolved. Today, LADA patients constitute a significant fraction, that is, up to 12% of T2D patients, highlighting the pressing need to address these questions. 3, 4 This commentary discusses such questions, the ongoing efforts by scientists/physicians and future directions in search for …

Aim To compare the efficacy and safety of saxagliptin/dapagliflozin and insulin glargine in people with latent autoimmune diabetes in adults (LADA). Methods In this phase 2b multicentre, open‐label, comparator‐controlled, parallel‐group, non‐inferiority study, we randomly assigned 33 people with LADA who had a fasting C‐peptide concentration ≥0.2 nmol/L (0.6 ng/mL) to receive 1‐year daily treatment with either the combination of saxagliptin (5 mg) plus dapagliflozin (10 mg) or insulin glargine (starting dose: 10 IU), both on top of metformin. The primary outcome was the 2‐h mixed meal‐stimulated C‐peptide area under the curve (AUC), measured 12 months after randomization. Secondary outcomes were glycated haemoglobin (HbA1c) levels, change in body mass index (BMI), and hypoglycaemic events. Results In the modified intention‐to‐treat analysis, the primary outcome was similar in …

Introduction. Despite the improvements of insulin therapy, people with type 1 diabetes (T1D) still suffer from a decreased quality of life and life expectancy. The search toward a cure for T1D is therefore still a scorching open field of research.Areas coveredTackling the immune checkpoint signaling pathways has gained importance in the field of cancer immunotherapy. The same pathways can be targeted in autoimmunity with an opposite principle: to dampen the exaggerated immune response. In this review, we report a comprehensive excursus on the cellular and molecular mechanisms that lead to loss of immunological tolerance, and recent evidence on the role of immune checkpoint molecules in the development of T1D and their potential application for the mitigation of autoimmune diabetes.Expert opinionContrasting results about the efficacy of immune checkpoint modulators for T1D have been published, with …

Correction: An updated algorithm for an effective choice of continuous glucose monitoring for people with insulin-treated diabetes Correction: An updated algorithm for an effective choice of continuous glucose monitoring for people with insulin-treated diabetes Endocrine. 2024 Jan 31. doi: 10.1007/s12020-023-03635-w. Online ahead of print. Authors Maria Ida Maiorino 1 2 , Raffaella Buzzetti 3 , Concetta Irace 4 , Luigi Laviola 5 , Nicola Napoli 6 , Dario Pitocco 7 , Katherine Esposito 8 9 ; LIVE CGM working group Affiliations 1 Unit of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Piazza Miraglia 2, 80138, Naples, Italy. mariaida.maiorino@unicampania.it. 2 Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia 2, 80138, Naples, Italy. mariaida.maiorino@unicampania.it. 3 Department of Experimental Medicine, "Sapienza" …

BackgroundDespite the overall improvement in care, people with type 2 diabetes (T2D) experience an excess risk of end-stage kidney disease. We evaluated the long-term effectiveness of dapagliflozin on kidney function and albuminuria in patients with T2D.MethodsWe included patients with T2D who initiated dapagliflozin or comparators from 2015 to 2020. Propensity score matching (PSM) was performed to balance the two groups. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) from baseline to the end of observation. Secondary endpoints included changes in albuminuria and loss of kidney function.FindingsWe analysed two matched groups of 6197 patients each. The comparator group included DPP-4 inhibitors (40%), GLP-1RA (22.3%), sulphonylureas (16.1%), pioglitazone (8%), metformin (5.8%), or acarbose (4%). Only 6.4% had baseline eGFR <60 ml/min/1.73 m2 and …

AimWe examined whether metabolic dysfunction-associated steatotic liver disease (MASLD) with or without significant fibrosis (assessed by validated non-invasive biomarkers) was associated with an increased risk of prevalent chronic kidney disease (CKD) or diabetic retinopathy in people with type 1 diabetes mellitus (T1DM).MethodsWe performed a retrospective multicenter cross-sectional study involving 1,409 adult outpatients with T1DM, in whom hepatic steatosis index (HSI) and fibrosis (FIB)-4 index were calculated for non-invasively detecting hepatic steatosis (defined by HSI > 36), with or without coexisting significant fibrosis (FIB-4 index ≥ 1.3 or < 1.3). CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urine albumin/creatinine ratio ≥ 3.0 mg/mmol. The presence of diabetic retinopathy was also recorded in all participants.ResultsPatients with MASLD and significant …

Background and aimsIntensive glycemic control minimizes the risk of micro- and macrovascular complications in patients with type 1 diabetes (T1D). We report glycemic control in Italian participants (age groups: 26–44, 45–64, and ≥65 years) of the global SAGE study.Methods and resultsThe primary endpoint was proportion of participants who achieved an HbA1c <7% in predefined age groups. In the 523 patients with T1D, mean age was 44.6 years and mean body mass index (BMI) was 25 kg/m2. Mean HbA1c was 7.5% and 29.4% had HbA1c <7.0%, with the highest percentage in those 26–45 years (31.7%) and the lowest in those ≥65 years (20%). Altogether, 22.9% of patients achieved their physician-established individualized HbA1c target. Most patients had ≥1 symptomatic hypoglycemic episode in the previous 3 months (≤70 mg/dL 82.5%; ≤54 mg/dL 61%). Severe hypo- and hyperglycemia were …

Nonostante l’impegno profuso dai ricercatori negli ultimi 30 anni, ad oggi nessuno studio di immuno-intervento è riuscito a indurre la remissione del diabete tipo 1 (DM1) dopo l’insorgenza clinica. Una possibile causa risiede nell’ampia eterogeneità della patologia, che non riguarda solo aspetti metabolici e clinici, ma anche patogenetici e immunologici. Questa osservazione trova conferma nella recente introduzione del concetto di “endotipo”, ovvero nell’esistenza di specifici sottotipi di diabete autoimmune, definiti da meccanismi funzionali e fisiopatologici distinti. Questo nuovo concetto implica che percorsi fisiopatologici diversi possano esitare nella stessa malattia, ma anche che studi di immuno-intervento che mirano a intercettare uno di quei percorsi, possano avere un successo limitato perché applicati indistintamente a tutta la popolazione con DM1. L’implementazione di immuno-terapia in endotipi specifici …

BackgroundWe assessed whether hepatic steatosis with or without significant fibrosis (determined by validated non-invasive biomarkers) is associated with an increased 10-year estimated risk for cardiovascular disease (CVD) in people with type 1 diabetes mellitus (T1DM).MethodsWe conducted a retrospective, multicenter, cross-sectional study involving 1,254 adults with established T1DM without pre-existing CVD. We used the hepatic steatosis index (HSI) and fibrosis (FIB)-4 index for non-invasively detecting hepatic steatosis (defined as HSI > 36), with or without coexisting significant fibrosis (defined as FIB-4 index ≥ 1.3 or < 1.3). We calculated the Steno type 1 risk engine and the atherosclerotic CVD (ASCVD) risk score to estimate the 10-year risk of developing a first fatal or nonfatal CVD event.ResultsUsing the Steno type 1 risk engine, a significantly greater proportion of patients with hepatic steatosis …

Glycated haemoglobin in the first year after diagnosis of type 1 diabetes is an independent risk factor for diabetic retinopathy: The IMDIAB 25 years follow-up study Glycated haemoglobin in the first year after diagnosis of type 1 diabetes is an independent risk factor for diabetic retinopathy: The IMDIAB 25 years follow-up study Diabetes Obes Metab. 2023 Nov;25(11):3415-3419. doi: 10.1111/dom.15213. Epub 2023 Jul 14. Authors Ernesto Maddaloni 1 , Angela Carlone 1 , Dario Pitocco 2 , Giulia Leanza 3 , Concetta Suraci 4 , Maria Altomare 4 , Maria G Cavallo 1 , Ilaria Barchetta 1 , Susanna Morano 1 , Chiara Moretti 1 , Lucia Coraggio 1 , Natalia Visalli 5 , Flavia Tramontana 3 , Riccardo Schiaffini 6 , Antonino Crinò 6 , Raffaella Buzzetti 1 , Paolo Pozzilli 3 ; IMDIAB study group Collaborators IMDIAB study group: Marco G Baroni, Carla Bizzarri, Sara Bodini, Raffaella Buzzetti, Marco Cappa, Maria Cassone Faldetta, …

OBIETTIVI La rivoluzione nell’approccio terapeutico al diabete di tipo 2 (T2D) impone un ripensamento del posizionamento della terapia insulinica. Dato il numero considerevole di domande aperte, è stato riunito un gruppo di esperti, con l’obiettivo di fornire, tramite il metodo Delphi, una guida pratica per i medici.METODI Uno gruppo di 6 esperti (Delphi board) ha sviluppato una serie di 29 statement su: ruolo del controllo metabolico alla luce delle linee guida più recenti; strategie di intensificazione dell’insulina basale (BI): 1) add-on vs switch; 2) inerzia nell’iniziare e nel titolare; 3) combinazione libera vs. rapporto fisso; strategie di intensificazione e de-intensificazione da basal-bolus; analoghi di seconda generazione della BI (2BI). È stato quindi individuato un panel di 31 diabetologi che, tramite accesso al sito web dedicato, hanno assegnato a ciascuno statement un punteggio di rilevanza su una scala a 9 punti. È stato adottato il RAND/UCLA Appropriateness Method per valutare l’esistenza di disaccordo tra i partecipanti.

Aim To determine whether the magnitude of the cardiorenal benefits of sodium‐glucose co‐transporter‐2 inhibitors (SGLT2is) varies with baseline kidney function. Methods We searched randomized, placebo‐controlled trials testing the effects of SGLT2is on renal and cardiovascular outcomes. Efficacy outcomes, stratified by baseline estimated glomerular filtration rate (eGFR) categories, included renal disease progression, a composite heart failure (HF) outcome and mortality. Results Thirteen trials testing SGLT2is in 90 402 participants with available eGFR data were included. The risk of bias was judged as low for all trials. SGLT2is reduced the relative risks of renal disease progression by 27% to 57% and of HF outcomes by 13% to 32% across different eGFR categories, with an overall low heterogeneity. Meta‐regression analyses showed a significant direct relationship between baseline eGFR and the …

AimWe examined whether different insulin administration modalities, i.e., multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII by insulin pumps), are differently associated with the risk of having metabolic dysfunction-associated fatty liver disease (MAFLD), with or without coexisting significant liver fibrosis (assessed by validated non-invasive biomarkers), in adults with type 1 diabetes mellitus (T1DM).MethodsWe conducted a retrospective, multicenter, cross-sectional study involving 1,417 adult individuals with established T1DM treated with MDI or CSII. We calculated hepatic steatosis index (HSI) and fibrosis (FIB)-4 index for non-invasively detecting MAFLD (defined by HSI >36), with or without coexisting significant fibrosis (defined by FIB-4 index ≥ 1.3 or <1.3, respectively).ResultsCompared to the MDI group (n = 1,161), insulin-pump users (n = 256; 18.1%) were more likely to be …

Gli inibitori del checkpoint immunitario (ICI) sono usati per trattare un’ampia varietà di tumori solidi. Comprendono tre tipi di anticorpi monoclonali: anticorpi anti-CTLA4, anticorpi anti-PD1 e anticorpi anti-PD-L1 (Tabella 1). Essi agiscono principalmente favorendo e potenziando la risposta immunitaria T-mediata contro le cellule tumorali. La loro tossicità riflette il loro meccanismo d’azione, per cui essi possono provocare fenomeni autoimmunitari a carico di vari organi e tessuti, tra cui l’insorgenza di diabete di tipo 1 [1, 2]. Il diabete di tipo 1 secondario agli inibitori del checkpoint immunitario (ICI-T1DM) è caratterizzato da una rapida distruzione β-cellulare; esordisce spesso con chetoacidosi diabetica (DKA) e richiede un trattamento insulinico a vita [3]. Lo studio condotto da Xuan Chen e collaboratori ha analizzato un database di pazienti sottoposti a trattamento con ICI negli Stati Uniti (US) e ha valutato, in tali …

Corrigendum to Comparative effectiveness of Glargine 300 U/mL vs. Degludec 100 U/mL in patients with type 2 diabetes switching from 1 generation basal insulins> Nutr Metab Cardiovasc Dis. 2022 Sep; 32 (9): 2255-2263Corrigendum to Comparative effectiveness of Glargine 300 U/mL vs. Degludec 100 U/mL in patients with type 2 diabetes switching from 1 generation basal insulins> Nutr Metab Cardiovasc Dis. 2022 Sep; 32 (9): 2255-2263

Recent evidence suggests a role for Diabetes Mellitus in adverse outcomes from COVID‐19 infection; yet the underlying mechanisms are not clear. Moreover, attention has turned to prophylactic vaccination to protect the population from COVID‐19‐related illness and mortality. We performed a comprehensive peer‐reviewed literature search on an array of key terms concerning diabetes and COVID‐19 seeking to address the following questions: 1. What role does diabetes play as an accelerator for adverse outcomes in COVID‐19?; 2. What mechanisms underlie the differences in outcomes seen in people with diabetes?; 3. Are vaccines against COVID‐19 efficacious in people with diabetes? The current literature demonstrates that diabetes is associated with an increased risk of adverse outcomes from COVID‐19 infection, and post‐COVID sequelae. Potential mechanisms include dysregulation of Angiotensin …

Chitotriosidase (CHIT), a mammalian chitinase secreted by neutrophils and activated macrophages, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. The aim of this study is to evaluate CHIT activity as an early biomarker of arterial stiffness in people with T2D free from overt vascular complications. In this cross-sectional study, arterial stiffness as measured using standard pulse wave velocity (PWV) was evaluated in 174 people with T2D without overt vascular disease. Then, we measured CHIT serum activity with an electrochemiluminescence assay in two subgroups of participants: 35 with the highest (high-PWV) and 40 with the lowest (low-PWV) PWV values. CHIT activity was no different between the low-PVW and high-PWV groups (12.7 [9.6–17.9] vs. 11.4 [8.8–15.0] nmol/mL/h, respectively). Compared with the low-PWV group, the high-PWV participants were older (p < 0.001); had a longer duration of diabetes (p = 0.03); higher ankle–brachial index ABI (p = 0.04), systolic blood pressure (p = 0.002), diastolic blood pressure (p = 0.005), fasting blood glucose (p = 0.008), and HbA1c (p = 0.005); and lower eGFR (p = 0.03) and body mass index (BMI) (p = 0.01). No association was present with sex, duration of diabetes, age, BMI, peripheral blood pressure, laboratory parameters, and glucose-lowering medications or ongoing antihypertensive therapy. Although no association was found, this study provides novel data about the association of CHIT activity with CVD, focusing on a specific outcome (arterial stiffness) in a well-defined population of subjects …