Medicina Traslazionale, Vol. 34 n. 4 dicembre 2022Il ripristino della funzione beta cellulare nel diabete mellito di tipo 2: aspetti traslazionali

Type 2 diabetes (T2D) has been considered a relentlessly worsening disease, due to the progressive deterioration of the pancreatic beta cell functional mass. Evidence indicates that remission of T2D may occur in variable proportions of patients after specific treatments that are associated with recovery of beta cell function. The recovery of beta cells has been shown in human islets obtained from non-diabetic organ donors that recover from “lipo-glucotoxic” conditions, and human islets isolated from T2D organ donors exposed to specific treatments or by a period of exposure to a “non-diabetic” milieu. The improvement of insulin secretion and the associated molecular traits unveil the possibility to promote T2D remission by directly targeting pancreatic beta cells.

Aggiornamento Clinico, Vol. 34 n. 4 dicembre 2022Il monitoraggio in continuo della glicemia: stato dell’arte

Continuous glucose monitoring (CGM) system is largely used in clinical practice in patients with type 1 diabetes and insulin-treated patients with type 2 diabetes. It is a needful tool for a more comprehensive assessment of glucose control. Patients can benefit from real-time information on current glucose, glucose trend, and hypo or hyperglycemia alarms. Healthcare can rapidly understand how much time patients spend in a good glucose range, hypoglycemia or hyperglycemia.
Several clinical trials have demonstrated the benefits of CGM in reducing glycated hemoglobin, as well as the time spent in hypoglycemia, and increasing the time in range. CGM reduces the rate of severe acute complications and hospital admission improving the quality of life. Patients on insulin treatment and pregnant women are the perfect candidates for CGM. However, even patients on non-intensive insulin treatment or other therapies might benefit from CGM to gain and maintain reasonable glycemic control, and again improve the quality of life.

Aggiornamento dalla letteratura, Vol. 34 n. 3 ottobre 2022Quali target glicemici nelle donne con diabete gestazionale?

For glucose-lowering drugs inducing hypoglycemia, a marginally protective effect on the risk of MACE was observed for HbA1c 48-58 mmol/mol, whereas a significant reduction of microvascular complications was observed for HbA1c<49 mmol/mol, but with higher risk of severe hypoglycaemia. Drugs not inducing hypoglycaemia were associated with a reduction of MACE, renal adverse events, and all-cause mortality, for HbA1c<7% (no data for lower targets). Conclusions: the present paper illustrates the recommendations of the Italian guidelines for the treatment of type 2 diabetes on therapeutic targets for HbA1c. In synthesis, the improvement of glycemic control with drugs not inducing hypoglycemia is associated with a reduction in the risk of long-term chronic vascular and renal complications, and all-cause mortality suggesting an HbA1c target of 53 mmol/mol. When the reduction of HbA1c is achieved with drugs inducing hypoglycemia, a progressive reduction of complications and an increase in the risk of severe hypoglycemia is observed suggesting higher HbA1c thresholds (49-58 mmol/mol).

Editoriale, Vol. 34 n. 3 ottobre 2022I target glicemici alla luce delle nuove linee guida italiane per il trattamento del diabete di tipo 2

Background/aim: different guidelines provide similar, but not identical, therapeutic targets for HbA1c in type 2 diabetes. These targets can also depend on the different pharmacological strategies adopted for intensifying glycemic control. This editorial is aimed at providing a reference for the choice of glycemic targets in patients with type 2 diabetes, as recommended by the new Italian guidelines for the treatment of type 2 diabetes. Methods and results: the present paper revised the recently published Italian guidelines for the treatment of type 2 diabetes (outpatients), either in primary care or specialist referral. The guideline has been developed following the methods described in the Manual of the National Guideline System (http://www.snlg-iss.it) by a panel nominated by the Società Italiana di Diabetologia (SID) and Associazione Medici Diabetologi (AMD).

Rassegna, Vol. 34 n. 3 ottobre 2022Gliflozine e sindrome cardio-renale

SGLT2 inhibitors are molecules able to reduce blood glucose levels and body weight, and to lower systolic blood pressure. They also exert important diuretic and modulatory effects of renal hemodynamics, as well as a series of anti-inflammatory actions, thus contributing to reduce the cardiovascular burden in subjects with and without type 2 diabetes. Such benefit mainly translates into reduced risk for hospitalization due to heart failure, and reduced decline of glomerular filtration, associated with a powerful anti-albuminuric effect. For this reason, they constitute an indispensable treatment in a modern approach to cardiorenal prevention. This review recapitulates the clinical evidence supporting the use of SGLT2 inhibitors in these patients, and the main mechanisms of cardiorenal protection.

Rassegna, Vol. 34 n. 3 ottobre 2022Uno scompenso per due, col terzo incomodo

The importance of differentiating between primary cardiovascular prevention and secondary prevention in diabetes will be discussed in light of the results obtained by the cardiovascular outcome trials (CVOTs). In patients with diabetes, the distinction between primary and secondary cardiovascular prevention could be artificial. The main criteria for enrollment in cardiovascular outcome trials that define the so-called patient in secondary prevention are, typically: i) the history of heart attack or unstable angina; ii) the history of ischemic or hemorrhagic stroke, iii) subclinical conditions, i.e., multivessel coronary artery disease, occlusive peripheral vascular disease with stenosis greater than 50%, or with a Winsor index less than 0.9. However, in patients with diabetes, a significant coronary atherosclerotic disease can be asymptomatic: this has important clinical implications, i.e., i. patients with diabetes are frequently undertreated, ii: it is unclear whether all asymptomatic patients should be screened for coronary artery disease for implementing optimal medical therapy. The conclusion is that placing the outpatient in the so-called primary or secondary prevention without a clinical event is impossible.

Rassegna, Vol. 34 n. 3 ottobre 2022Terapie innovative per il diabete: effetti sul rischio di scompenso cardiovascolare nel paziente non diabetico

Most of the glucose is reabsorbed in the kidney by the sodium-glucose cotransporters 2 (SGLT2): SGLT2i inhibitors significantly reduce the renal glucose threshold in the patient with and in the patient without diabetes. This effect explains the consistent drop in blood sugar in the patient with diabetes and a decrease (5-10 mg/dl) in the non-diabetic person. Notably, SGLT2i inhibit sodium reabsorption leading to a reduction in the expansion of plasma volume and blood pressure. At the cardiovascular level, SGLT2i reduce preload and post-load, improves cardiac metabolism and bioenergetics, inhibits the sodium hydrogen antiport, and reduce the adrenergic system’s activation. Glucagon-like peptide 1 receptor agonists (GLP-1RA) enhance endothelial function, stabilize atherosclerotic plaque and increase angiogenesis. Similar to SGLT2i, GLP-1RAs reduce arterial stiffness and low-grade inflammation. A peculiar action of GLP-1 is the inhibition of platelet aggregation, most likely linked to the ability of these drugs to stimulate nitric oxide synthesis in platelets. They also increase sodium excretion with a consequent drop in blood pressure and significantly reduce fatty liver disease, an important cardiovascular risk factor. The clinical characteristics of these two classes of drugs are described, and their benefits on the cardiovascular system in patients without diabetes are discussed.

Medicina Traslazionale, Vol. 34 n. 3 ottobre 2022Terapia cellulare e molecolare sperimentale del diabete mellito di tipo 1 con cellule staminali: stato attuale

Advances in cell and molecular technology have fostered development of innovative approaches to manage type 1 diabetes mellitus. The main focus is to replace destroyed β cells by induced pluripotent-(hiPSC) and/or mesenchymal stem cells (hMSC) thanks to multi-step differentiation protocols. The aim is to obtain β-like cells invisible to the host’s immune system by their physical envelopment within recombinant, last generation biopolymers that prevent contact between embodied cells and host’s immune system, thereby avoiding recipient’s general immunosuppression with its global side effects.

Aggiornamento Clinico, Vol. 34 n. 3 ottobre 2022Neuropatia diabetica e depressione: uovo o gallina?

Background: Painful diabetic neuropathy has been identified as the major determinant of depressive symptoms in people with diabetes. It is also known that the manifestations of diabetic neuropathy can be heterogeneous and sometimes insidious to recognize and treat.
Clinical case: We present the diagnostic-therapeutic course of a case in which diabetic neuropathy was strongly influenced by a significant psychopathological component.
Discussion/Conclusions: The boundary between depression and neuropathy can be blurred, and determining which pathology came first is controversial.

Rassegna, Vol. 34 n. 2 luglio 2022Epatite C cronica e diabete: una relazione bidirezionale complessa

Chronic hepatitis C (CHC) and diabetes have a complex relationship. CHC increases the risk of developing diabetes, independently from the degree of liver fibrosis. This is due to both impairment in beta cell func¬tion and induction of insulin resistance. Conversely, diabetes worsens the liver-related prognosis of patients with CHC. Sustained virologic response, obtained by either interferon-based or interferon-free regimens, leads to a lower incidence of diabetes, to improved diabetes control in patients with known diabetes and to a lower incidence of micro- and macrovascular diabetic complications.

Rassegna, Vol. 34 n. 2 luglio 2022Effetti pleiotropici della metformina: hanno rilevanza clinica?

Sixty years after its introduction in the therapeutic arsenal of type 2 diabetes, metformin remains the first-line treatment of type 2 diabetes according to national and international guidelines. Numerous observational studies have suggested that metformin may exert beneficial therapeutic effects on diabetes – and nondiabetes – related comorbidities, including cardiovascular, hepatic, neoplastic, and infectious diseases. However, direct evidence of the pleiotropic effects of metformin from specific randomized controlled trials is still lacking.

Rassegna, Vol. 34 n. 2 luglio 2022Le reali contro-indicazioni all’utilizzo della metformina

Metformin, a molecule belonging to the biguanide family, is one of the best known and most widely used drug for the management of diabetes mellitus therapy in the world.
During sixty years of its use, countless benefits have been described, not only for the treatment of diabetes mellitus. However, due to sim-ilarity with other members of the drug family, concern remains high about the risk of developing lactic acidosis. This article attempts to take stock of the real risks associated with the use of metformin, trying to shed light on the real risks and the possible onset of lactic acidosis or renal damage. Metformin-induced lactic acidosis exists but is rare. Appropriate use of the drug, under safe conditions, induces benefits in the absence of risks.

Rassegna, Vol. 34 n. 2 luglio 2022Metformina farmaco anti-aging? Tra promesse ed evidenze

Biological aging results from molecular and cellular damage over time. This process determines a progressive decrease in physical and functional capacity, an increased risk of disease and death. Therefore, the identification of the molecular mechanisms of aging has led to research for senotherapeutic strategies. Metformin is an oral hypoglycaemic drug. It is the first choice for the treatment of type 2 diabetes mellitus (T2DM). However, clinical and preclinical evidence has shown the beneficial effects of metformin also in cardiovascular diseases, neurodegenerative diseases, and aging. This editorial explores the recent evidence on metformin as an anti-aging drug.

Editoriale, Vol. 34 n. 2 luglio 2022La disfunzione sessuale negli uomini e nelle donne con diabete: una riflessione sulle complicazioni?

Diabetes Mellitus (DM) is associated with a plethora of micro- and macro-vascular complications which should be carefully investigated and treated in order to improve quality of life and reduce the risk of premature mortality. Female and male sexual dysfunction often occurs in diabetes; while cardiovascular complications are clearly involved, psychosexological factors, endocrine complications, and endothelial dysfunction all contribute to the pathogenesis of sexual dysfunctions. Sexual dysfunctions can also act as early biomarkers of cardiovascular disease.

Medicina traslazionale: Applicazioni cliniche della ricerca di base, Vol. 34 n. 2 luglio 2022Fallimento β-cellulare nel diabete mellito di tipo 1 e di tipo 2: esistono meccanismi comuni?

Type 1 diabetes (T1D) and type 2 diabetes (T2D) are two distinct diseases, with different etiology and pathogenesis, but with a common outcome (hyperglycemia), caused by almost complete or reduced loss of β-cell functional mass, respectively. Although the causes that lead to β-cell failure are different (typically immune-mediated for T1D, while related to metabolic stress for T2D), the underlying molecular pathways are almost similar in both forms of diabetes. In this review we try to highlight common molecular mechanisms of β-cells damage in T1D and T2D, which could suggest new promising common therapeutic targets.

Aggiornamento in tema di tecnologie, Vol. 34 n. 2 luglio 2022Verso una nuova fonte di β-cellule per la cura del diabete mellito di tipo 1

Pluripotent stem cells are the best candidates for a renewable and infinite source of β-cells suitable for a future application in cell ther-apy for type 1 diabetes. Obtaining a cellular product that is safe and functional is becoming urgent, as the first clinical trials using stem cell-derived β cells are ongoing. This review summarizes the current strategies applied in the field of stem cell derived-β cells to improve in vitro differentiation and to solve the problems of tumorigenicity and immune rejection for a future stem cell based cell therapy.

Rassegna, Vol. 34 n. 1 maggio 202223 gennaio 2022: 100 anni fa il miracolo della terapia insulinica che continua oggi

It was January 23, 1922, when the first successful subcutaneous injection of a pancreatic extract, prepared by Banting and purified by Collip, was administered to Leonard Thompson, a young boy in diabetic ketoacidosis, at the Toronto General Hospital. That day is the birth of insulin therapy which over the years has saved tens of millions of lives of people. Animal extracted insulin has been continuously purified until human insulin and the insulin analogs have been obtained with the rDNA technique to substitute insulin according to physiology. Today basal-bolus insulin therapy in type 1 diabetes, and basal insulin in type 2 (possibly in combination with GLP-1 RA) remain the consolidated gold standards of insulin therapy in diabetes.

Rassegna, Vol. 34 n. 1 maggio 2022La terapia insulinica nel diabete mellito di tipo 2

Type 2 diabetes is a very common metabolic disorder worldwide. The main defects of this disease are insulin resistance and a β cell dysfunction, leading to a reduction of insulin secretion over time. Insulin secretion is a complex mechanism that involves interactions among all the cells of the pancreatic insula. In addition, glucolipotoxicity may affect reversibly insulin secretion in type 2 diabetes. In recent years, several novel treatments have been becoming available for type 2 diabetes, nevertheless insulin still maintains an important role overall in specific situations including severe metabolic decompensation or pregnancy. The aim of the present narrative review is to discuss the main indications of insulin in the treatment of type 2 diabetes.

Rassegna, Vol. 34 n. 1 maggio 2022100 anni dopo l’insulina: cosa ancora non sappiamo della sua secrezione nel diabete di tipo 2

β-cell dysfunction is a well-known feature of type 2 diabetes mellitus. In particular, it has been shown that defects in 1st phase insulin secretion play a fundamental role in the natural history of the disease. In this review, we highlight the clinical relevance of 1st phase impairment, focusing on its connection with post meal hyperglycemia and diabetic complications; we further evaluate possible therapeutic strategies aimed at improving β-cell secretory machinery and providing a durable control of the disease. In conclusion, we discuss the clinical relevance of C-Peptide sampling in detecting secretory defects.

Editoriali, Vol. 34 n. 1 maggio 2022L’insulina alla luce delle nuove linee guida italiane per il trattamento del diabete di tipo 2: quando, in chi e perché?

Aim: this editorial is aimed at providing a reference for the insulin treatment of type 2 diabetes in adults. Methods and results: the present paper revised the recently published Italian guidelines for the treatment of type 2 diabetes (outpatients), either in primary care or specialist referral. The guideline has been developed following the methods described in the Manual of the National Guideline System (http://www.snlg-iss.it) by a panel nominated by the Società Italiana di Diabetologia (SID) and Associazione Medici Diabetologi (AMD). Prior cardiovascular events, heart failure, hypoglycemic risk, and other conditions have been considered as factors capable of modifying treatment strategies. The following areas have been assessed: 1) position of the insulin therapy in the new algorithms; 2) type of formulations (insulin analogues or human insulin); 3) use of insulin infusion pumps. Conclusions: insulin should be used only as a second/thirdline therapy due to its lower efficacy on long-term HbA1c, higher risk of hypoglycemia, and neutral effects on cardiorenal outcomes. Human insulin formulations should be avoided for safety concerns (higher hypoglycemic risk) with no preference among different insulin analogues. Insulin pumps are not recommended for the treatment of type 2 diabetes.

Medicina traslazionale: Applicazioni cliniche della ricerca di base, Vol. 34 n. 1 maggio 2022Insuline oltre l’insulina

Insulin pumps, or systems for Continuous Subcutaneous Insulin In-fusion (CSII), have changed from rudimentary devices with limited dosing flexibility to “smart” systems able to modulate insulin administration with greater flexibility and accuracy. The combination of insulin pump, continuous glucose monitoring and control algorithm now allows the automatic administration of insulin with an efficacy in glucose control never achieved previously. We review here the evolution in technology that has made possible this big advance in the care of diabetes.

Aggiornamento in tema di tecnologie, Vol. 34 n. 1 maggio 2022La terapia con microinfusore: stato dell’arte

Insulin pumps, or systems for Continuous Subcutaneous Insulin In-fusion (CSII), have changed from rudimentary devices with limited dosing flexibility to “smart” systems able to modulate insulin administration with greater flexibility and accuracy. The combination of insulin pump, continuous glucose monitoring and control algorithm now allows the automatic administration of insulin with an efficacy in glucose control never achieved previously. We review here the evolution in technology that has made possible this big advance in the care of diabetes.

Aggiornamento in tema di tecnologie, Vol. 34 n. 1 maggio 2022Il ruolo della tecnologia nella gestione del bambino e dell’adolescente con diabete di tipo 1

In Italy, it is estimated there are about 25,000 children and adolescents with type 1 diabetes between 0 and 18 years, most of whom using electronic devices for blood glucose control. Among these many have chosen a sensor for measuring blood glucose, often integrated, or combined with an insulin pump, preferably included in (advanced) hybrid closed-loop systems, that increasingly resemble artificial pancreases. This technology has seen an enormous progress in the last two decades, making these tools fundamental for improving glycemic control and the quality of life of patients with diabetes and their families. However, major challenges remain, including cybersecurity vulnerability, cost, and accessibility, with a substantial geographical variation in access to diabetes technologies. The hope is that the very recent guidelines of SID, AMD and SIEDP will help to rationalize and improve access to available technologies.

Allegato100 anni dalla scoperta dell’insulina: innovazione e real world evidence , allegato al Vol. 33, N.3, novembre 2021

Introduzione

Luigi Laviola

Qual è la terapia “migliore” per la persona con diabete di tipo 2? Questa domanda risuona costantemente nella mente di chi si dedica alla gestione delle persone con diabete, e che affronta, ogni giorno, la realtà dei nostri ambulatori con troppe richieste, con risorse troppo scarse, con amministrazioni troppo lontane. È un interrogativo che include e comprende i nostri “desideri insoddisfatti”: strategie di intervento che permettano di mantenere stabile nel tempo l’HbA1c, di preservare la funzione beta-cellulare, di agire con efficacia senza incrementare il peso corporeo, di prevenire le complicanze, di modulare il profilo di rischio cardiovascolare. La stagione esaltante che abbiamo la fortuna di vivere è stata caratterizzata negli ultimi 15 anni dalla immissione sul mercato di nuove classi di farmaci, sostenuti da solide evidenze scientifiche derivanti da trial di intervento e di outcome cardiovascolare e da studi di real world. Tuttavia, gli aggiornamenti progressivi delle linee guida, mai così rapidi e numerosi, hanno forse generato la sensazione che la terapia insulinica sia “passata di moda”, e che nella faretra di opzioni terapeutiche a disposizione del diabetologo del XXI secolo stia diventando sempre meno utile. Con questo numero monotematico, vorremmo condividere invece la convinzione che, nonostante i suoi anni, la terapia insulinica è ancora giovane, e rappresenta una risorsa importante per il trattamento della persona con diabete di tipo 2 in ogni fase della malattia. Una tragica conferma del ruolo centrale della terapia insulinica nel paziente instabile è arrivata nelle corsie dei centri COVID di tutto il mondo, in cui l’insulina ha rappresentato la prima scelta per la gestione efficace dell’iperglicemia. Ma prima e oltre le necessità dei pazienti ospedalizzati, la terapia insulinica si rivela oggi ancor più efficace e sicura grazie ai progressi tecnologici e biotecnologici che hanno messo a disposizione del diabetologo insuline con cinetiche di assorbimento sempre più vicine alla fisiologia della secrezione beta-cellulare, insieme a strumenti sempre più sofisticati e pratici per la somministrazione del farmaco ed il monitoraggio della glicemia. Tutto ciò consente un impiego versatile e adattabile, con la possibilità di intensificare, de-intensificare o interrompere la terapia seguendo l’evoluzione del quadro clinico. La disponibilità di nuovi analoghi consente inoltre il raggiungimento dei target con rischio ridotto di ipoglicemia, e l’associazione con altri antidiabetici permette di modulare e personalizzare il trattamento secondo le esigenze del paziente. In particolare, la combinazione dell’insulina con farmaci della classe degli agonisti del recettore del GLP-1 rappresenta l’opzione più moderna ed efficace nel panorama della terapia iniettiva del diabete di tipo 2, offrendo la massima potenza ipoglicemizzante, una notevole riduzione degli effetti collaterali, e la possibilità di modificare la storia naturale della malattia grazie alla documentata protezione cardio-renale. I diversi capitoli di questa monografia affronteranno tutte queste tematiche, con l’auspicio che, a 100 anni dalla sua scoperta, l’insulina possa rappresentare un’ulteriore opportunità per una diabetologia moderna, attenta all’ottimizzazione dei risultati, ma anche alla personalizzazione della terapia e al miglioramento della qualità di vita del paziente diabetico, per il presente e per il futuro.

SOMMARIO

Senza categoriaProspettive future ed innovazione nell’ambito della terapia insulinica: respiro al presente e solidità al passato

Abstract

A 100 anni dall’isolamento dell’insulina e dalla dimostrazione della sua capacità di ridurre la glicemia, la terapia insulinica rappresenta ancora oggi una risorsa importante per la gestione del diabete mellito di tipo 2 (DMT2), in tutte le sue fasi. La sintesi dei nuovi analoghi dell’insulina ha consentito di ottenere vantaggi aggiuntivi quali la riduzione del rischio di ipoglicemie, la flessibilità terapeutica, la possibilità di intensificare il trattamento in sicurezza, la personalizzazione della terapia. Per il prossimo futuro la ricerca mira a migliorare ulteriormente la tollerabilità e a facilitare la gestione della terapia e la qualità di vita. Gli analoghi a lunga emivita, con somministrazione settimanale e l’insulina orale aprono scenari interessanti nella gestione del diabete.

 

Senza categoriaL’emergenza COVID-19 e i cambiamenti nella gestione del paziente in terapia insulinica

Abstract

I diabetologi hanno spesso in cura soggetti complessi,fragili, con numerose comorbilità, anziani e politrattati che non possono essere gestiti secondo le linee guida che sono disegnate su studi clinici randomizzati (RCT) i quali escludono questa tipologia di pazienti. Per tale motivo, si è reso necessario integrare i risultati ottenuti dai RCT con quelli ottenuti dalla pratica clinica, ovvero dalla real life. Gli studi della Real World Evidence, insieme all’uso di nuove tecnologie per il monitoraggio della glicemia, hanno consentito di definire le modalità per intensificare, deintensificare o interrompere la terapia ipoglicemizzante seguendo l’evoluzione del quadro clinico.

 

Senza categoriaLa terapia insulinica nell’era delle Real World Evidence

Abstract

L’impatto della pandemia da COVID-19 è stato particolarmente gravoso per le persone affette da diabete mellito che, presentando un rischio elevato di esiti negativi legati all’infezione virale (e alle sue complicanze) sono stati particolarmente attenti al mantenimento del corretto distanziamento sociale, affrontando un lungo periodo nel quale la continuità e la qualità dell’assistenza sanitaria sono state ostacolate. L’implementazione di tecnologie avanzate per la teleassistenza e la telemedicina ha permesso solo in parte di ovviare alle necessità del controllo periodico, pur se alcune esperienze hanno permesso il raggiungimento di soddisfacenti obiettivi clinici e terapeutici. Vengono citati, ad esempio, le proposte di monitoraggio continuo della glicemia interstiziale con controllo in remoto, l’esperienza di telemedicina svolta dalla Diabetologia della AOU di Careggi, il percorso di supporto a distanza del paziente e, infine, la proposta di autotitolazione dell’insulina basale effettuate dal Centro Regionale Diabete Mellito della ASST di Bergamo Ovest.

Senza categoriaIl place in therapy della terapia insulinica nel trattamento dei pazienti con diabete di tipo 2

Abstract

Alla luce dello sviluppo di nuovi farmaci antidiabete e di nuove formulazioni insuliniche le linee guida ADA/EASD (Davies MJ 2018) raccomandano un’attenta valutazione del rapporto rischio/beneficio nella scelta della terapia ipoglicemizzante, che deve essere centrata sull’inquadramento del profilo di rischio cardiovascolare e renale e sulle esigenze specifiche del paziente. Questo articolo discute alcuni argomenti dibattuti sull’uso dell’insulina in questo contesto: quando cominciare il trattamento insulinico? Qual è il trattamento iniziale (basale o prandiale)? Qual è il ruolo delle possibili combinazioni con altri farmaci antidiabete orali e iniettivi? Quanto pesano, nella scelta del diabetologo, i potenziali effetti collaterali, tra cui soprattutto il rischio di ipoglicemia?