Rassegna, Vol. 35 n. 3 ottobre 2023L’eterogeneità del diabete autoimmune

Autoimmune diabetes is a heterogeneous disease, encompassing both type 1 diabetes, characterized by fast progression towards an insulin-dependent state, and latent autoimmune diabetes in adults (LADA), considered a less severe form of autoimmune diabetes with a mild metabolic decompensation. An extensive genetic, phenotypic, and humoral heterogeneity is recognized even within the group of people with LADA. In this review, we discuss the pathological and clinical heterogeneity of autoimmune diabetes, highlighting the current understanding and gaps in knowledge.

Rassegna, Vol. 35 n. 3 ottobre 2023Epidemiologia e fattori di rischio del diabete di tipo 1

Type 1 diabetes (T1D) is a globally rising autoimmune condition. Genetics, viral infections, and environmental factors contribute to T1D. Comprehending these factors, along with the underlying pathophysiological mechanisms, gives rise to the concept of distinct “endotypes” within the disease, paving the way for enhanced strategies in prevention and early intervention. This review highlights the importance of understanding these multifaceted characteristics in the context of T1D, providing a comprehensive analysis of its epidemiology and risk factors, synthesizing information from relevant literature.

Rassegna, Vol. 35 n. 3 ottobre 2023Il diabete monogenico. Una condizione clinica frequentemente trascurata

Monogenic diabetes (MD) includes several forms of hyperglycemia caused by mutations in genes capable of controlling glucose homeostasis. Although MD explains 0.5-5.0% of non-autoimmune diabetes, it remains mostly overlooked. This is unfortunate, given that most of the genes involved in MD influence the monitoring and/or therapy of carrier patients, thus representing an excellent example of “precision medicine” implemented in real-life clinical practice. This review provides a practical update to help identify patients who merit genetic testing for MD and how to best clinically manage carrier patients.

Editoriale, Vol. 35 n. 3 ottobre 2023Ulcere ischemiche del piede diabetico: terapia cellulare autologa come possibile trattamento adiuvante

Risultati di uno studio prospettico non controllato sul trattamento cellulare con cellule mononucleate da sangue periferico in pazienti affetti da piede diabetico ulcerato e malattia dei piccoli vasi: efficacia, sicurezza e valutazione economica

 

Results from a prospective uncontrolled study on autologous peripheral blood mononuclear cells in patients with small artery disease and diabetic foot ulcers: efficacy, safety, and economic evaluation

 

Background/aim: this editorial is aimed at providing some insights on cell therapy in patients with diabetic foot ulcers and no-option critical limb-threatening ischemia (CLTI).
Methods and results: the present paper revised the available evidence on cell therapy in patients affected by diabetes and peripheral artery disease and reported the main results of a recently published uncontrolled study on the effects of peripheral blood mononuclear cells (PBMNC) therapy in patients with diabetic foot ulcers, no-option CLTI, and small artery disease. All patients included in that study were allocated in a surgery waiting-list for major amputations. Patients treated with autologous PBMNC experienced a significant reduction of pain levels, an increase of oxygen tissue levels, a high rate of healing without the need of a major amputation.
Conclusions: the present paper illustrates the possible favorable effects of PBMNC cell therapy in patients with diabetes and peripheral artery disease even in presence of microangiopathy.

Medicina Traslazionale, Vol. 35 n. 3 ottobre 2023Il ruolo dei progenitori delle cellule endoteliali nel diabete mellito

Diabetes is associated with increased risk of cardiovascular morbidity and mortality. Endothelial progenitor cells (EPCs) are bone marrow-derived cells involved in endothelial health, vasculogenesis and damage repair. Both subjects with type 1 and type 2 diabetes showed a lower number of EPCs and impaired EPC function, suggesting a potential pathogenic role of these cells in both micro and macrovascular complications, as well as in sexual dysfunctions in diabetes. Several glucose-lowering drugs have been reported to potentially improve EPCs levels and bioreactivity. However, larger and longer studies are needed to better explain the mechanisms involved.

Aggiornamento Clinico, Vol. 35 n. 3 ottobre 2023Diabete mellito dopo trattamento con ocrelizumab per sclerosi multipla primariamente progressiva

Objectives: immune reconstitution therapies, which include antibody-based cell-depleting therapies targeting CD20+ (ocrelizumab, ofatumumab) or CD52+ (alemtuzumab) leukocytes, are approved for the treatment of multiple sclerosis. Autoimmune thyroid disease is the most common adverse effect of treatment with alemtuzumab, but some cases of autoimmune diabetes have been reported. To date, diabetes mellitus has not been reported after CD20-targeting monoclonal antibodies therapy.
Case Report: a 41-year-old man with primary progressive multiple sclerosis was diagnosed with diabetes mellitus six months following the first ocrelizumab infusion. He experienced polyuria and polydipsia, but not other symptoms as visual loss or weight loss. We started a basal-bolus insulin therapy, with progressive and relatively rapid improvement of glycemic control. To note, C-peptide resulted indicative of a preserved beta-cell activity and autoantibodies were negative. To present date, the patient reached an excellent control with metformin.
Conclusions: this is the first case of diabetes mellitus reported after ocrelizumab administration. The timing of onset and course are similar to alemtuzumab-induced autoimmune diseases, usually interpreted as an “immune reconstitution syndrome”; however, ocrelizumab cell count depletion appears inferior in duration and cell population affected. This case suggests the need for screening and follow-up of glycemic status in patients treated with ocrelizumab.
As a novel therapeutic antibody, further investigation is required to elucidate the correlation between hyperglycemia and ocrelizumab.

 

Rassegna, Vol. 35 n. 2 luglio 2023Le citochine organo-specifiche nel diabete: aggiornamenti e prospettive future

The adipose organ is composed by two types of tissue: the white adipose tissue and the brown adipose tissue. Recently, it has been classified as a real endocrine organ whose dysfunction is involved in different diseases, mainly obesity and type 2 diabetes. The adipose tissues produce specific citokines named adipokines (the one from white adipose tissue) and batokines (the one from brown adipose tissue). They have opposite roles but mice and human data have demonstrated their capacity to convert to each other in response to the physio or pathophysiologic condition. This process is called transdifferentiation.
We here aim to retrace the adipose organ history from physiology to physiopathology, to provide therapeutic perspectives for the prevention and treatment of its two main related diseases: obesity and type 2 diabetes.

Rassegna, Vol. 35 n. 2 luglio 2023Irisina: un singolo ormone, molti cross-talk

Type 2 diabetes (T2D) is a multifactorial disease with multiple etiology, characterized by chronically elevated blood glucose levels. Although the reduction of pancreatic β-cell functional mass, associated or not with peripheral insulin resistance, is recognized as the main etiopathogenetic factor leading to the onset of T2D, the dysregulation of glucose metabolism is actually the result of multi-organs alterations, including skeletal muscle and adipose tissue dysfunction, hepatic insulin resistance, and incretin axis defects. Furthermore, the chronic elevation of blood glucose levels leads to the onset of systemic complications affecting many organs and tissues. Therefore, T2D is a multi-organ disease and future anti-diabetic drugs can no longer be considered simple hypoglycemic drugs: they should at least be able to restore β-cell functional mass, reduce peripheral insulin resistance, ensure adequate weight loss (when necessary), and exert cardio- and nephro-protective effects. In light of this, irisin, a hormone secreted by skeletal muscle in response to physical activity, should be remarked as a new promising anti-diabetes molecule, being able to exert beneficial effects on the various organs involved in the pathogenesis of T2D, in particular on pancreatic β-cells, liver, skeletal muscle, adipose tissue, and many of the organs affected by diabetes complications.

Rassegna, Vol. 35 n. 2 luglio 2023Il Counselor nel team diabetologico

The present review will depict the role and the boundaries of a relatively new profession, entering the world of diabetes and surroundings, the Counselor. Originally, only large companies were hiring Counselors to improve inter-personal relationships, and approach and resolve human resources problems. More recently, the Counselor was introduced in the Health environment with the scope of reinforcing relationship among patients and physicians, improve physician to patient communication but also improving physician to physician relationships and in general communication among health workers. Specific examples of fields of action of Counselors will be presented, with a specific focus on the interaction between Counselor and patients with type 1 and type 2 diabetes. In conclusion, the wide array of potential applications of Counselors will make this new profession particularly appealing for the Diabetes Team World-wide.

Editoriali, Vol. 35 n. 2 luglio 2023Trent’anni fa i risultati del DCCT: cosa significarono allora e cosa rappresentano oggi

The DCCT (Diabetes Control Complication Trials) has conclusively demonstrated in 1993 that good glycaemic control prevents the micro-angiopathy caused by chronic hyperglycaemia in T1DM. The subsequent follow-up study EDIC (Epidemiology of Diabetes Interventions and Complications) has demonstrated similar results for macro-angiopathy. Taken together, DCCT and EDIC strongly indicate the need for aggressive treatment of T1DM with intensive therapy to target near-normoglycaemia since clinical onset of T1DM to prevent long-term micro- and macro-vascular complications. Today and in the years to come, this message remains and will remain as fundamental as it was 30 years ago.

Editoriali, Vol. 35 n. 2 luglio 2023Screening e diagnosi del diabete gestazionale

The aim of this editorial is to comment two recent papers published in the New England Journal of Medicine that investigated the screening and diagnostic methods for gestational diabetes mellitus (GDM). There is still worldwide controversy concerning which screening and which diagnostic criteria are more appropriated. The main findings of these articles are discussed and its implications for the management of pregnant women.

Medicina Traslazionale, Vol. 35 n. 2 luglio 2023Ruolo dell’insulina e del recettore insulinico nel tessuto adiposo

Insulin regulates whole-body energy and lipid metabolism by activating the insulin receptor (INSR) consisting in two isoforms: INSR-A expressed in less-differentiated cells with prominent mitogenic effect; INSR-B mostly expressed in adult tissues with pronounced metabolic properties. It is well known that tissue-specific variation in INSR-A/INSR-B ratio may favour the development of metabolic abnormalities. Herein, we examine the role of insulin/INSR signalling in the regulation of several aspects of adipose tissue physiology and the effects of insulin mimetics on adiposity.

Aggiornamento in tema di tecnologie, Vol. 35 n. 2 luglio 2023Sistemi di somministrazione insulinica automatizzata open source: a che punto siamo?

The artificial pancreas or automated insulin delivery (AID) system is an important step forward in the treatment of diabetes. Besides commercial AID systems, open-source automated insulin delivery systems (opensource-AID), known more colloquially as “Do-it-Yourself Artificial Pancreas Systems” (DIY APS) have become available. They couple algorithms developed by patients with diabetes, with commercially available and regulatory-approved insulin pumps and continuous glucose monitoring (CGM) sensors. These closed loop systems, are categorized by the technology and algorithm they incorporate (OpenAPS, Android APS or Loop). Until now only one open-source algorithm has been approved by Food and Drug Administration.
Different studies, observational, real time and randomized-controlled have shown that AID open-source systems can improve metabolic control and quality of life in patients with diabetes, while decreasing the burden of diabetes management.
Aim of this paper is to summarize data from the literature and to reason about the implications that the arrival of this new technique will have for patients and caregivers.

Vita della Sid, Vol. 35 n. 2 luglio 2023LA VITA DELLA SID

Congresso Regionale AMD-SID Toscana, Pisa, 10 giugno 2023. L’impatto e i rischi delle complicanze del diabete: dalle complicanze tradizionali alle complicanze emergenti

È nato EUDF Italia, network indipendente di discussione e proposta, a livello nazionale nell’ambito dell’European Diabetes Forum

SID: la prima società scientifica di diabetologia nella World Obesity Federation

Firmato protocollo d’intesa tra il CONI, l’Intergruppo parlamentare Obesità e Diabete, FeSDI, SID e AMD per la tutela della pratica sportiva degli atleti con diabete e per la promozione di corretti stili di vita attraverso lo sport

Aumenta il diabete nelle città: firmato il Protocollo d’intesa tra FeSDI, Intergruppi Parlamentari ‘Obesità e Diabete’ – ‘Qualità di Vita nelle Città’ e Sport e Salute per la promozione dell’attività fisica e sportiva come strumento di prevenzione

Rassegna, Vol. 35 n. 1 maggio 2023Possiamo ottenere un cambiamento dello stile di vita significativo e stabile nel tempo?

Lifestyle is universally considered a fundamental issue in the prevention and therapy of both type 2 diabetes and metabolic syndrome. However, implementation at a general population level of recommendations resulting from available evidence is largely insufficient. In particular, only a limited fraction of the general population meets the recommended levels of aerobic physical activity, and individuals meeting the recommended levels of resistance physical activity are even less. Interestingly, there is further reduction in these proportions in subjects with prediabetes and especially in those with type 2 diabetes. It is noteworthy that people with or at risk for diabetes represent a significant proportion of the general population, show objective evidence of impaired exercise capacity, for different mechanisms, and frequently have long-standing sedentary habits, difficult to be changed. All these aspects should be taken into account, when designing in-tervention programs aimed at improving the current situation. As regards the possibility of a stable increase in physical exercise levels and reduction in sedentary habits of individuals with diabetes, available data are limited. However, they indicate that it is possible to improve these aspects in a significant proportion of subjects. Behavioral changes reported in studies are generally smaller than the prefixed improvements, but sufficient to obtain favorable and clinically significant effects. Interventions applied in these programs show several shortcomings, indicating the need for a continuous revision of strategies.

Rassegna, Vol. 35 n. 1 maggio 2023Il cambiamento che possiamo ottenere produce effetti clinicamente rilevanti?

Adopting and maintaining a physically active lifestyle provides significant health benefits to people with diabetes and prediabetes by increasing energy expenditure, insulin sensitivity, and physical fitness and decreasing chronic low-grade inflammation. Physical activity (PA)/exercise favors control of hyperglycemia and other risk factors for cardiovascular disease (CVD) and, therefore, it is recommended for diabetes prevention and treatment and for improving overall health. According to current guidelines, people with type 2 diabetes are re-commended to perform at least 150 min/week of moderate-to-vigorous intensity aerobic exercise plus 2-3 sessions/week of resistance exercise on non-consecutive days. Unfortunately, these individuals are usually well below the recommended level of PA and, hence, it is difficult for them to put into action guideline recommendations for a number of external and internal barriers, thus suggesting the need for effective strategies to promote a sustained behavior change. Several randomized clinical trials have shown that supervised exercise programs are effective in improving surrogate endpoints such as blood glucose and other CVD risk factors, physical fitness, and well-being. However, such programs are not suitable for long-term implementation in routine clinical practice and adherence to PA/exercise is usually strictly dependent on participation to supervised sessions and falls once the intervention ends. In this regard, counseling interventions appear to be more feasible and adequate to promote a true, long-lasting behavior change. A limited number of studies have tested the efficacy of counseling interventions designed to promote walking through the provision of pedometers. These interventions resulted in modest and transient increases in moderate-to-vigorous PA (MVPA) and, accordingly, failed to significantly improve CVD risk factors and other surrogate outcomes or to produce sustained increases in cardiorespiratory fitness. These results are in contrast with those of several epidemiological surveys, showing that, in physically inactive and sedentary or unfit individuals, even modest amounts of (MV)PA, corresponding to one-third to one-half of those recommended by guidelines, exert a beneficial impact on morbidity and mortality. This discrepancy might be explained by the fact that walking-based interventions are focused only on leisure-time MPVA. Conversely, current guidelines consider also other domains, such as sedentary behavior and light-intensity PA (LPA), and other settings, such as home, work and commuting, as they recommend also to decrease the amount of sedentary (SED)-time and to interrupt prolonged sitting with bouts of LPA every 30 min. In fact, in the Italian Diabetes and Exercise Study 2 (IDES_2), a counseling intervention targeting both MVPA and sedentary behavior was effective in promoting increases in MVPA, which were modest but sustained over a three-year follow-up and associated with larger decreases in SED-time and corresponding increases in LPA. This resulted in clinically meaningful improvements in physical fitness and, to a lesser extent, in CVD risk factors and scores over a three-year follow-up. Conversely, no clinically meaningful effects were observed in counseling intervention targeting only SED-time. In conclusion, counseling interventions are effective in producing clinically meaningful effects, even when resulting in only modest increments in leisure-time MVPA, provided that they also target the other domains and settings of PA/sedentary behavior.

Rassegna, Vol. 35 n. 1 maggio 2023L’esercizio fisico nel diabete di tipo 2: come possiamo migliorare l’aderenza?

Regular exercise is associated to several health benefits. However, only 39% of adults with type 2 diabetes reach the recommended goals for physical activity. Adherence to exercise needs removing barriers to behavioural changes by setting realistic goals. To make the change lasting, group is fundamental and automatic behaviours must be created. However, the extent of the problem clearly indicates that a patientcentred approach is not enough. National policies including programs to encourage regular exercise are needed, with intensive interventions and investments.

Editoriale, Vol. 35 n. 1 maggio 2023Le raccomandazioni nutrizionali alla luce delle nuove linee guida italiane (e degli aggiornamenti) per il trattamento del diabete di tipo 2

Background/aim: this editorial is aimed at providing a reference for the medical nutritional therapy (MNT) in patients with type 2 diabetes, as recommended by the new Italian guidelines for the treatment of type 2 diabetes and its 2023-Update. Methods and results: the present paper revised the recently published Italian guidelines for the treatment of type 2 diabetes (outpatients) and its update, 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). Available literature on nutritional therapy showed a greater efficacy of: 1) MNT vs. unstructured nutritional advices, 2) Mediterranean diet vs. other dietary approaches, and the use of low- vs. high-glycemic index nutrients in reducing HbA1c and body weight.
Conclusions: the present paper illustrates the recommendations of the Italian guidelines (and its 2023-update) for the treatment of type 2 diabetes on medical nutritional therapy. In synthesis, the panel suggests a structured medical therapy, balanced diet (Mediterranean), and the use of low-, rather than high-glycemic index nutrients due to the improvement of glycemic control and body weight.

Medicina Traslazionale, Vol. 35 n. 1 maggio 2023Lo screening nella retinopatia diabetica

Diabetic retinopathy (DR) is the main ocular complication of diabetes. Among all the causes of blindness, it is the only one whose global prevalence has increased over the past 30 years. DR prevalence is expected to increase in the upcoming years. Therefore, it is essential to establish cost-effective screening programs for early diagnosis of DR, which using new imaging systems, telemedicine and artificial intelligence prevent its evolution to advanced sight-threatening stages.

Aggiornamento Clinico, Vol. 35 n. 1 maggio 2023Sindrome progeroide atipica con lipodistrofia parziale familiare, dovuta alla mutazione missenso c.1045 C > T (p.Arg349Trp) in eterozigosi del gene LMNA, e diabete mellito di tipo 2

Familial partial lipodystrophy (FPLD) associated with LMNA gene mutations is a rare form of lipodystrophy disorder characterized by partial absence of subcutaneous adipose tissue and predisposition to develop metabolic complications related to insulin-resistance inclu-ding type 2 diabetes mellitus (T2D). Recently, this peculiar phenotype has been associated to atypical progeroid syndrome (APS). We present a case of 31-year-old woman with progeria features, partial lipodystrophy, type 2 diabetes mellitus (T2D), hypertriglyceridemia and hepatic steatosis. The baseline insulin sensitivity and secretion assessment showed strong insulin-resistance with hyperglycemia and elevated insulin secretion. Genetic analysis revealed a missense heterozygous LMNA mutation c.1045 C > T (p. Arg349Trp) that established APS diagnosis with FPLD, so far studied and described in only 10 patients worldwide. The patient was initially treated with metformin, fenofibrate, omega-3 and low carb and low fat diet with optimal results on metabolic control related to glycemic and lipid profile; later, liraglutide (Glucagon-Like Peptide-1 analog, GLP-1) therapy was added. During the 6 month follow-up the anthropometric parameters improved, in particular a significant improvement in body composition with redistribution of fat mass and a reduction of visceral fat and liver volume were observed. The improvements obtained were consolidated and maintained in the following years. However, with disease progression, focal segmental glomerulosclerosis (FSGS) and peripheral neuropathy developed.
This case highlights the clinical and metabolic characteristics of this rare form of lipodystrophy and proposes an innovative therapeutic approach to manage the disease.

Rassegna, Vol. 34 n. 4 dicembre 2022Meccanismi comuni tra diabete e declino cognitivo

The increased prevalence of diabetes (DM) constitutes a major public health problem, primarily due to its numerous comorbidity and complications. It is widely demonstrated that DM is a significant risk factor for the development of cognitive impairment. Metabolic diseases can influence cognitive functions through multiple interconnected mechanisms. Cerebral insulin resistance, oxidative stress, neuroinflammation, and neuroendocrine dysfunctions can further the development of neurodegeneration diseases. The identification of the molecular mechanisms involved represents the target for the founding of early potential markers and new therapeutic targets of neurodegenerative diseases.

Rassegna, Vol. 34 n. 4 dicembre 2022Diabete e declino cognitivo: dall’epidemiologia ai test diagnostici

Today, 463 million people worldwide suffer from diabetes, while 374 million have prediabetes. Unfortunately, this number is expected to double by 2030. However, data about the prevalence of diabetes are influenced by the age group to which it refers. For example, in 2000, 12% of people between 65 and 70 years old as well as 15% of the over 80s were affected by diabetes. Nowadays, the percentage of over 65s with diabetes is about 20-25%, with some geographical differences. Dementia is another critical health problem which is greatly increasing especially among the elderly. While it is well known that diabetes is a significant risk factor for worsening vision, renal function, and increased risk of cardiovascular disease, a number of recent epidemiological evidence reported that diabetes can also be considered a risk factor for cognitive dysfunction. Therefore, while basic research and trials on human models are focused on understanding the pathophysiological mechanisms underlying the development of cognitive decline in individuals with diabetes, in clinical practice the prevention of cognitive decline in the individual with diabetes is critically important. In this paper, we will discuss the pathogenetic mechanisms, clinical approach, and diagnostic strategies that can be used in a clinical-ambulatory setting for early diagnosis of cognitive decline in patients with diabetes.

Rassegna, Vol. 34 n. 4 dicembre 2022Crononutrizione: una tematica emergente nella gestione del diabete di tipo 2

Evidence has been accumulated that a different timing in the consumption of meals, namely the chrononutrition, is able to influence the daily metabolic biorhythms, influencing the onset and possibly the treatment of clinical conditions as obesity and diabetes, including the possibility of independently influencing the cardiovascular risk. Behaviors originating from new social customs are able to interfere with these physiological mechanisms activating of genes and proteins that make individuals more or less flexible, capable of adaptation. So, the inability to adapt could favor a higher risk to health. Therefore, chrononutrition is a characteristic of the diet that is important to address further to the amount of energy and macronutrient intake. Once again, even in this area, the Mediterranean dietary style proves to be a healthy reference approach.

Editoriale, Vol. 34 n. 4 dicembre 2022L’elefante nella stanza

Despite its increasing prevalence, severity and mortality, the Diabetic Foot Syndrome (DFS) still remains an unaddressed critical issue in Diabetology.
The management of DFS is adequately performed only in few Centres, and clinical outcomes vary, depending on the possibility of patients to access optimal standards of care.
To rivitalize the debate upond DFS and to make concrete proposals to improve the quality of therapy and the accessibility to optimal care, we wrote this editorial.

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.