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1.
J Clin Med ; 13(11)2024 May 23.
Article in English | MEDLINE | ID: mdl-38892765

ABSTRACT

Background/Objectives: Semaglutide is the unique once-daily oral glucagon-like receptor agonist presently available. Aims of this study were to describe clinical characteristics of patients with type 2 diabetes (T2D) initiating oral semaglutide, to assess its effects on glycemic control, body weight (BW) and its tolerability in routine clinical practice. Methods: Electronic medical records from two Italian diabetes clinics were evaluated. Mean glycated hemoglobin (HbA1c) and BW were assessed in adults with T2D before and 6 months after oral semaglutide prescription. Treatment discontinuation and safety data were reported. Results: A total of 192 patients initiating oral semaglutide (44% female) presented a mean age of 66 years, a diabetes duration of 10 years, HbA1c of 7.9% and a BW of 82.6 kg. Almost 50% of patients were obese. Mean HbA1c and BW changes from baseline to follow up were -0.7% and -2.6 kg, respectively. Greater HbA1c reduction was observed in patients with baseline HbA1c ≥ 8% and with diabetes duration <5 years. The composite endpoint of HbA1c ≤7% and a weight loss ≥5% was achieved in 22.5% of the participants. A total of 40 patients (20.8%) discontinued treatment: 26 because of gastrointestinal adverse events, and 10 due to limited effectiveness in lowering HbA1c and/or BW. Conclusions: In a real clinical setting, patients initiating oral semaglutide showed suboptimal metabolic control, short diabetes duration and obesity; a significant improvement in HbA1c and BW was achieved mainly in patients with a more recent diabetes diagnosis, supporting the use of oral semaglutide in the early phase of the disease.

2.
Nutr Metab Cardiovasc Dis ; 33(11): 2102-2106, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37684171

ABSTRACT

The current board of the interassociative Italian association of medical diabetologists (AMD)/Italian society of diabetology (SID) Diabetes and Pregnancy Italian Study Group commented about two recent papers published in the New England Journal of Medicine that investigated the screening and diagnostic methods for gestational diabetes mellitus (GDM). It is well recognized that effective screening and accurate, early diagnosis of GDM contributes to better management of these women in order to reduce adverse maternal and fetal/neonatal outcomes. However, there is worldwide controversy concerning which screening (selective or universal; one step or two steps) and which diagnostic criteria (glucose thresholds) are appropriate. The main findings of these papers are discussed along with their implications for the management of pregnant women.

3.
Acta Diabetol ; 60(10): 1421-1437, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37401946

ABSTRACT

OBJECTIVE: This document purpose is to create an evidence-based position statement on the role of metformin therapy in pregnancy complicated by obesity, gestational diabetes (GDM), type 2 diabetes mellitus (T2DM), polycystic ovary syndrome (PCOS) and in women undergoing assisted reproductive technology (ART). METHODS: A comprehensive review of international diabetes guidelines and a search of medical literature was performed to identify studies presenting data on the use of metformin in pregnancy. The document was approved by the councils of the two scientific societies. RESULTS: In condition affecting the fertility, as PCOS, metformin use in pre-conception or early in pregnancy may be beneficial for clinical pregnancy, even in ART treatment, and in obese-PCOS women may reduce preterm delivery. In obese women, even in the presence of GDM or T2DM, metformin use in pregnancy is associated with a lower gestational weight gain. In pregnancy complicated by diabetes (GDM or T2DM), metformin improves maternal glycemic control and may reduce insulin dose. Neonatal and infant outcomes related to metformin exposure in utero are lacking. Metformin use in women with GDM or T2DM is associated with lower birth weight. However, an increased tendency to overweight-obesity has been observed in children, later in life. CONCLUSIONS: Metformin may represent a therapeutic option in selected women with obesity, PCOS, GDM, T2DM, and in women undergoing ART. However, more research is required specifically on the long-term effects of in utero exposition to metformin.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetes, Gestational , Metformin , Polycystic Ovary Syndrome , Pregnancy , Infant, Newborn , Child , Female , Humans , Metformin/therapeutic use , Metformin/pharmacology , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/pharmacology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes, Gestational/drug therapy , Diabetes, Gestational/epidemiology , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/drug therapy , Obesity/complications , Obesity/drug therapy , Obesity/epidemiology
4.
Acta Diabetol ; 60(5): 705-710, 2023 May.
Article in English | MEDLINE | ID: mdl-36828942

ABSTRACT

AIMS: Several insulin delivery systems are available to control glycemia in patients with diabetes. Recently introduced devices feature connectivity enabling data transfer to smartphone applications to provide decision support and reduce errors in dosing and timing, while reducing the cognitive burden. METHODS: We conducted an online survey in Italian patients with a self-reported diagnosis of diabetes to assess patient perceptions of insulin therapy management, and their impressions of connection-enabled insulin pens compared to standard insulin pens. The Morisky Medication Adherence Scale-8 was used to assess adherence to insulin therapy. RESULTS: Among 223 respondents (108 with type 1 diabetes; 115 with type 2 diabetes), the most prominent unmet need was the necessity to overcome the cognitive burden of care associated with measuring, calculating, timing, and recording therapy. Only 25% of respondents had high adherence; 28% had low adherence. CONCLUSIONS: When asked to compare the attributes of a non-connected insulin pen with those of a new connected device, 71% of patients rated the new proposal "very useful". The cognitive burden associated with self-management of diabetes therapy may influence preferences for advanced insulin delivery systems.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Self-Management , Humans , Insulin/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Diabetes Mellitus, Type 1/drug therapy
5.
Cells ; 12(3)2023 01 28.
Article in English | MEDLINE | ID: mdl-36766773

ABSTRACT

Diabetes has been shown to accelerate vascular senescence, which is associated with chronic inflammation and oxidative stress, both implicated in the development of endothelial dysfunction. This condition represents the initial alteration linking diabetes to related cardiovascular (CV) complications. Recently, it has been hypothesised that the acetyltransferase, p300, may contribute to establishing an early vascular senescent phenotype, playing a relevant role in diabetes-associated inflammation and oxidative stress, which drive endothelial dysfunction. Specifically, p300 can modulate vascular inflammation through epigenetic mechanisms and transcription factors acetylation. Indeed, it regulates the inflammatory pathway by interacting with nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit (NF-κB p65) or by inducing its acetylation, suggesting a crucial role of p300 as a bridge between NF-κB p65 and the transcriptional machinery. Additionally, p300-mediated epigenetic modifications could be upstream of the activation of inflammatory cytokines, and they may induce oxidative stress by affecting the production of reactive oxygen species (ROS). Because several in vitro and in vivo studies shed light on the potential use of acetyltransferase inhibitors, a better understanding of the mechanisms underlying the role of p300 in diabetic vascular dysfunction could help in finding new strategies for the clinical management of CV diseases related to diabetes.


Subject(s)
Cardiovascular System , Diabetes Mellitus , Humans , Acetyltransferases , Cardiovascular System/metabolism , Inflammation , NF-kappa B/metabolism
6.
Acta Diabetol ; 59(12): 1597-1607, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36053391

ABSTRACT

AIMS: As recommended by the Institute of Medicine (IOM), health practitioners should encourage a healthy nutrition and adequate weight gain during pregnancy in order to ensure favorable pregnancy and fetal outcomes, and to prevent diseases later in life for both mother and child. The purpose of this online survey was to determine the knowledge, attitude, and practice of the 2009 IOM recommendations among healthcare professionals managing nutritional therapy in pregnancies complicated by diabetes in Italy. METHODS: A cross-sectional survey was conducted by using an online self-administered questionnaire undertaken between October and December 2021. RESULTS: Of the 220 participants 89% were diabetologists/endocrinologists/internal medicine specialists and 11% dietitians/nutritionists. The survey found that the 53% of respondents provide a personalized diet to pregnant women with diabetes, while 32% a standard diet plan and only 15% healthy dietary advice. The 69% of the participants investigated for appropriate gestational weight gain, mainly based on pre-pregnancy BMI (96%), gestational weight gain (GWG) at first prenatal visit (80%) and presence of twin pregnancy (58%). Maternal weight gain was evaluated at each regularly scheduled prenatal visit and compared with IOM recommendations for the 87% of healthcare professionals. Diet plan was periodically re-evaluated and/or modified (90% of participants), based on inadequate maternal weight gain and/or fetal growth abnormalities (78%), trimester transition (53%), changes in physical activity and/or a "feel hungry" (50%). CONCLUSIONS: This survey reported the knowledge and attitude of IOM guidelines and the nutritional knowledge and practice of Italian professionals on the nutritional management of diabetes in pregnancy. The application of these recommendations seemed more feasible in clinics/team dedicated to "Diabetes in Pregnancy".


Subject(s)
Diabetes Mellitus , Gestational Weight Gain , Pregnancy Complications , Female , Humans , Pregnancy , Body Mass Index , Cross-Sectional Studies , Diabetes Mellitus/therapy , Health Knowledge, Attitudes, Practice , National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division , Pregnancy Outcome , United States/epidemiology , Weight Gain
7.
Front Endocrinol (Lausanne) ; 13: 892702, 2022.
Article in English | MEDLINE | ID: mdl-35909534

ABSTRACT

Aims: This study aims to evaluate the effectiveness and tolerability of once-weekly glucagon-like peptide receptor agonists (OW GLP-1RAs) and to assess the clinical benefits of switching from one GLP-1RA to another (switchers) in a routine clinical setting. Materials and Methods: This is a retrospective, real-world cohort study, based on electronic medical records utilized in one Italian diabetes clinic. Estimated mean changes in HbA1c and body weight after 6 and 12 months from the first prescription of a long-acting GLP1-RA were evaluated using longitudinal linear mixed models for repeated measures. The effectiveness of the three long-acting GLP1-RAs was compared separately in the GLP1-RA naive and switchers cohorts, after propensity score adjustment. Results: Initiating a long-acting GLP1-RA was associated with statistically significant improvements in HbA1c (-1%) and body weight (-2.6 kg) after 6 months, and benefits were maintained after 12 months. In GLP1-RA naive cohort, semaglutide showed the largest effect on HbA1c (-1.55%; 95%CI, -1.77;-1.34) and body weight (-3.76 kg; 95%CI, -5.05;-2.47) at 6 months, maintained at 12 months (-1.55%; 95%CI, -1.82;-1.28 and -6.29 kg; 95%CI, -7.94;-4.63). In the switchers' cohort, statistically significant reductions at 6 months in HbA1c and body weight were documented with semaglutide and dulaglutide only, with semaglutide associated with the most marked reduction (-0.84%; 95%CI, -1.03;-0.65 and -3.43 kg; 95%, -4.67;-2.19). Dropout rates were 9.2%, 28.5%, and 41.7% in semaglutide, dulaglutide, and exenatide groups, respectively. Conclusions: The effectiveness and tolerability of the OW GLP-1RAs in the real world were documented. Semaglutide was associated with the highest response without impact on safety. Clinical improvements were obtained even in switchers, especially in those switching to semaglutide.


Subject(s)
Diabetes Mellitus, Type 2 , Body Weight , Cohort Studies , Diabetes Mellitus, Type 2/drug therapy , Drug Administration Schedule , Glucagon-Like Peptide-1 Receptor/agonists , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/therapeutic use , Retrospective Studies
8.
Front Endocrinol (Lausanne) ; 13: 768363, 2022.
Article in English | MEDLINE | ID: mdl-35721757

ABSTRACT

The regulation of the female reproductive system is one of the most relevant actions of thyroid hormones. Adequate thyroid hormones production is essential for normal menstrual function and fertility as well as for the successful maintenance of pregnancy. The relationship between reproductive failure and thyroid disorders is particularly relevant and attracts attention worldwide. Thyroid autoimmunity (TAI), defined by the presence of circulating antithyroid antibodies targeting thyroid peroxidase (TPOAb) and thyroglobulin (TgAb), is prevalent among women of reproductive age and is the most frequent cause of thyroid dysfunction. Several studies addressed the association between TAI, thyroid function, and fertility as well as pregnancy outcome after spontaneous or assisted conception. Infertility, miscarriages, and fetal-maternal complications are described in overt autoimmune hypothyroidism. More debatable is the role of mild thyroid dysfunction, mainly subclinical hypothyroidism (SCH), and TAI in the absence of thyroid dysfunction in infertility and reproductive outcome. Assisted reproductive technology (ART) has become an integral element of care for infertility. Women with TAI undergoing ART are of particular interest since they carry a higher risk of developing hypothyroidism after the ovarian stimulation but whether TAI, in absence of thyroid dysfunction, adversely affects ART outcome is still controversial. Likewise, the role of levothyroxine (LT4) in improving fertility and the success of ART in euthyroid women with TAI is unclear. This review discusses the role of TAI, in the absence of thyroid dysfunction, in infertility and in ART outcome.


Subject(s)
Hypothyroidism , Infertility, Female , Thyroid Diseases , Autoimmunity , Female , Humans , Hypothyroidism/complications , Infertility, Female/complications , Infertility, Female/therapy , Pregnancy , Reproductive Techniques, Assisted/adverse effects , Thyroid Diseases/complications , Thyroxine
9.
Nutr Metab Cardiovasc Dis ; 31(12): 3257-3270, 2021 11 29.
Article in English | MEDLINE | ID: mdl-34627692

ABSTRACT

Patients with type 2 diabetes mellitus (T2DM) show an increased risk of cardiovascular diseases (CVD) and mortality. Many factors are implicated in the pathogenesis of CVD in patients with T2DM. Among the factors involved, chronic hyperglycemia and the cluster of CVD risk factors, such as dyslipidemia, hypertension, and obesity, play a major role. For many years, the control of hyperglycemia has been complicated by the fact that the use of many available drugs was associated with an increased risk of hypoglycemia. Paradoxically, hypoglycemia per se represents a risk factor for CVD. Recently, new drugs for the control of hyperglycemia have become available: many of them can determine a good control of hyperglycemia with minor risks of hypoglycemia. Among these new classes of drugs, glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer many advantages. In addition to a strong anti-hyperglycemic action, they possess the ability to act on body weight and other relevant risk factors for CVD. Consistently, some of the GLP-1RAs have demonstrated, in RCT designed to assess their safety, to reduce the risk of major adverse cardiovascular events. Furthermore, GLP-1RAs possess properties useful to treat additional conditions, as the capability of improving liver damage in patients with NAFLD or NASH, highly prevalent conditions in people with T2DM. In this document, written by experts of the Italian diabetes society (SID), we will focus our attention on the therapy with GLP-1RAs in patients with T2DM, particularly on the effects on hyperglycemia, cardiovascular disease risk factors, NAFLD/NASH and CVD prevention.


Subject(s)
Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Expert Testimony , Glucagon-Like Peptide-1 Receptor/antagonists & inhibitors , Glucagon-Like Peptide-1 Receptor/therapeutic use , Glycemic Control , Heart Disease Risk Factors , Humans , Italy/epidemiology , Non-alcoholic Fatty Liver Disease/epidemiology , Societies, Medical , Treatment Outcome
10.
Nutrients ; 13(7)2021 Jun 27.
Article in English | MEDLINE | ID: mdl-34199095

ABSTRACT

Myo-inositol (Myo) improves insulin resistance, glucose metabolism, and helps gestational diabetes (GDM) management. GDM is associated with a pro-inflammatory state and increased oxidative stress, which are both involved in vascular damage in diabetes. Our aim was to study Myo anti-inflammatory/antioxidant potential effects on an in vitro model of human umbilical vein endothelial cells (HUVECs). To this end, monocyte cell adhesion to HUVECs, adhesion molecule membrane exposure, and oxidative stress levels were determined in cells from control (C-) and GDM women treated during pregnancy either with diet only (GD-) or with diet plus Myo (GD+Myo). To deeply study the vascular effects of Myo, the same evaluations were performed in C- and GD-HUVECs following 48 h in vitro stimulation with Myo. Notably, we first observed that GD-HUVECs obtained from women assuming Myo supplementation exhibited a significantly decreased number of monocytes that adhered to endothelial cells, less adhesion molecule exposure, and lower intracellular reactive oxygen species (ROS) levels in the basal state as compared to GD-HUVECs obtained from women treated by diet only. This Myo anti-inflammatory/antioxidant effect was confirmed by 48 h in vitro stimulation of GD-HUVECs as compared to controls. Altogether, these results strongly suggest that Myo may exert protective actions against chronic inflammation induced by endothelial dysfunction in diabetes.


Subject(s)
Hyperglycemia/metabolism , Inflammation/drug therapy , Inositol/therapeutic use , Oxidative Stress/drug effects , Adult , Antioxidants/pharmacology , Cell Adhesion/drug effects , Cell Adhesion Molecules/metabolism , Diabetes, Gestational/metabolism , Female , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Monocytes/metabolism , Pregnancy , Reactive Oxygen Species/metabolism , U937 Cells
12.
FASEB J ; 35(6): e21662, 2021 06.
Article in English | MEDLINE | ID: mdl-34046935

ABSTRACT

Human umbilical cord endothelial cells (HUVECs) obtained from women affected by gestational diabetes (GD-HUVECs) display durable pro-atherogenic modifications and might be considered a valid in vitro model for studying chronic hyperglycemia effects on early endothelial senescence. Here, we demonstrated that GD- compared to C-HUVECs (controls) exhibited oxidative stress, altered both mitochondrial membrane potential and antioxidant response, significant increase of senescent cells characterized by a reduced NAD-dependent deacetylase sirtuin-1 (SIRT1) activity together with an increase in cyclin-dependent kinase inhibitor-2A (P16), cyclin-dependent kinase inhibitor-1 (P21), and tumor protein p53 (P53) acetylation. This was associated with the p300 activation, and its silencing significantly reduced the GD-HUVECs increased protein levels of P300 and Ac-P53 thus indicating a persistent endothelial senescence via SIRT1/P300/P53/P21 pathway. Overall, our data suggest that GD-HUVECs can represent an "endothelial hyperglycemic memory" model to investigate in vitro the early endothelium senescence in cells chronically exposed to hyperglycemia in vivo.


Subject(s)
Antioxidants/metabolism , Cellular Senescence , Diabetes, Gestational/physiopathology , Gene Expression Regulation , Human Umbilical Vein Endothelial Cells/pathology , Models, Biological , Oxidative Stress , Cells, Cultured , Cyclin-Dependent Kinase Inhibitor p21/genetics , Cyclin-Dependent Kinase Inhibitor p21/metabolism , E1A-Associated p300 Protein/genetics , E1A-Associated p300 Protein/metabolism , Female , Human Umbilical Vein Endothelial Cells/metabolism , Humans , In Vitro Techniques , Pregnancy , Sirtuin 1/genetics , Sirtuin 1/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
13.
Nutr Metab Cardiovasc Dis ; 31(7): 2151-2155, 2021 06 30.
Article in English | MEDLINE | ID: mdl-34039507

ABSTRACT

AIM: To discuss available information on the opportunity for pregnant women affected by diabetes/obesity to receive COVID-19 vaccine. DATA SYNTHESIS: Pregnant women with SARS-CoV-2 (COVID-19) infection are at high risk for severe acute respiratory syndrome and adverse outcomes. Pregnant women with severe COVID-19 present increased rates of preterm delivery (<37 gestational weeks), cesarean delivery and neonatal admissions to the intensive care unit. Comorbidity such as diabetes (pregestational or gestational) or obesity further increased maternal and fetal complications. It is known that diabetic or obese patients with COVID-19 present an unfavorable course and a worse prognosis, with a direct association between worse outcome and suboptimal glycol-metabolic control or body mass index (BMI) levels. Critical COVID-19 infection prevention is important for both mother and fetus. Vaccination during pregnancy is a common practice. Vaccines against COVID-19 are distributed across the world with some population considered to have a priority. Since pregnant women are excluded from clinical trials very little information are available on safety and efficacy of COVD-19 vaccines during pregnancy. However, it is well known the concept of passive immunization of the newborn obtained with transplacental passage of protective antibodies into the fetal/neonatal circulation after maternal infection or vaccination. Moreover, it has been reported that COVID-19 vaccine-induced IgG pass to the neonates through breastmilk. Therefore, maternal vaccination can protect mother, fetus and baby. CONCLUSIONS: After an individual risk/benefit evaluation pregnant and lactating women should be counselled to receive COVID-19 vaccines.


Subject(s)
Blood Glucose/metabolism , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Diabetes, Gestational/blood , Lactation , Pregnancy Complications, Infectious/prevention & control , Pregnancy in Diabetics/blood , SARS-CoV-2/pathogenicity , Vaccination , Antibodies, Viral/blood , Biomarkers/blood , Body Mass Index , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/adverse effects , Clinical Decision-Making , Diabetes, Gestational/diagnosis , Diabetes, Gestational/therapy , Female , Glycemic Control , Humans , Immunity, Maternally-Acquired , Maternal-Fetal Exchange , Milk, Human/immunology , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , Pregnancy in Diabetics/diagnosis , Pregnancy in Diabetics/therapy , Prenatal Care , Risk Assessment , Risk Factors , SARS-CoV-2/immunology , Vaccination/adverse effects
14.
Acta Diabetol ; 58(9): 1187-1197, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33842997

ABSTRACT

AIMS: To assess the proportion of women with gestational diabetes (GDM) by performing postpartum Oral Glucose Tolerance Test (OGTT) and to identify GDM phenotypes at high-risk of postpartum dysglycemia (PPD). METHODS: Observational, retrospective, multicenter study involving consecutive GDM women. Recursive partitioning (RECPAM) analysis was used to identify distinct and homogeneous subgroups of women at different PPD risk. RESULTS: From a sample of 2,736 women, OGTT was performed in 941 (34.4%) women, of whom 217 (23.0%) developed PPD. Insulin-treated women having family history of diabetes represented the subgroup with the highest PPD risk (OR 5.57, 95% CI 3.60-8.63) compared to the reference class (women on diet with pre-pregnancy BMI < = 28.1 kg/m2). Insulin-treated women without family diabetes history and women on diet with pre-pregnancy BMI > 28.1 kg/m2 showed a two-fold PPD risk. Previous GDM and socioeconomic status represent additional predictors. Fasting more than post-prandial glycemia plays a predictive role, with values of 81-87 mg/dl (4.5-4.8 mmol/l) (lower than the current diagnostic GDM threshold) being associated with PPD risk. CONCLUSIONS: Increasing compliance to postpartum OGTT to prevent/delay PPD is a priority. Easily available characteristics identify subgroups of women more likely to benefit from preventive strategies. Fasting BG values during pregnancy lower than those usually considered deserve attention.


Subject(s)
Diabetes, Gestational , Adult , Blood Glucose , Diabetes, Gestational/diagnosis , Diabetes, Gestational/epidemiology , Female , Glucose Tolerance Test , Humans , Postpartum Period , Pregnancy , Retrospective Studies , Risk Factors
15.
Oxid Med Cell Longev ; 2021: 7887426, 2021.
Article in English | MEDLINE | ID: mdl-34987703

ABSTRACT

Chronic hyperglycemia and vascular damage are strictly related. Biomarkers of vascular damage have been intensively studied in the recent years in the quest of reliable cardiovascular risk assessment tools able to facilitate risk stratification and early detection of vascular impairment. The present study is a narrative review with the aim of revising the available evidence on current and novel markers of hyperglycemia-induced vascular damage. After a discussion of classic tools used to investigate endothelial dysfunction, we provide an in-depth description of novel circulating biomarkers (chemokines, extracellular vesicles, and epigenetic and metabolomic biomarkers). Appropriate use of a single as well as a cluster of the discussed biomarkers might enable in a near future (a) the prompt identification of targeted and customized treatment strategies and (b) the follow-up of cardiovascular treatment efficacy over time in clinical research and/or in clinical practice.


Subject(s)
Biomarkers/metabolism , Endothelium, Vascular/physiopathology , Hyperglycemia/physiopathology , Humans
17.
Oxid Med Cell Longev ; 2020: 6381380, 2020.
Article in English | MEDLINE | ID: mdl-33133348

ABSTRACT

Nowadays, the dramatically increased prevalence of metabolic diseases, such as obesity and diabetes mellitus and their related complications, including endothelial dysfunction and cardiovascular disease, represents one of the leading causes of death worldwide. Dietary nutrients together with healthy lifestyles have a crucial role in the endothelium health-promoting effects. From a growing body of evidence, active natural compounds from food, including polyphenols and carotenoids, have attracted particular attention as a complementary therapy on atherosclerosis and cardiovascular disease, as well as preventive approaches through the attenuation of inflammation and oxidative stress. They mainly act as radical scavengers by promoting a variety of biological mechanisms, such as improvements in endothelial function, blood pressure, platelet activity, and insulin sensitivity, and by modulating various known biomarkers. The present review highlights the role of polyphenols and carotenoids in early endothelial dysfunction with attention to their beneficial effect in modulating both classical and recent technologically generated emerging biomarkers. These, alone or in combination, can play an important role in the prediction, diagnosis, and evolution of cardiovascular disease. However, a main challenge is to speed up early and prompt new interventions in order to prevent or slow down disease progression, even with an adequate intake of bioactive compounds. Hence, there is an urgent need of new more validated, appropriate, and reliable diagnostic and therapeutic biomarkers useful to diagnose endothelial dysfunction at an earlier stage.


Subject(s)
Biomarkers/metabolism , Carotenoids/pharmacology , Endothelium, Vascular/physiopathology , Polyphenols/pharmacology , Animals , Diet , Endothelium, Vascular/drug effects , Humans , Models, Biological
18.
Nutr Metab Cardiovasc Dis ; 30(11): 1926-1936, 2020 10 30.
Article in English | MEDLINE | ID: mdl-32928628

ABSTRACT

AIMS: Type 2 diabetes mellitus is characterized by an increased risk of developing long-term cardiovascular complications. Several underlying mechanisms have been proposed for the diabetes-related increase in cardiovascular risk, i.e. chronic hyperglycemia, duration of the disease, drug-induced hypoglycemia, coexistence of multiple cardiovascular risk factors, etc. In the last few years, new pharmacological approaches capable of treating chronic hyperglycemia without increasing the risk of hypoglycemia have emerged for the treatment of diabetes. DATA SYNTHESIS: With data mainly obtained from randomized controlled trials recruiting patients with type 2 diabetes in secondary prevention of cardiovascular disease, some of these newer antihyperglycemic drugs have shown to significantly reduce the risk of cardiovascular disease. In addition, the combined control of traditional cardiovascular risk factors, e.g. dyslipidemia, hypertension, etc., has demonstrated to be effective in reducing the burden of cardiovascular diseases in patients with type 2 diabetes. CONCLUSIONS: In this document written by some experts of the Italian diabetes society (SID), we will focus our attention on oral antihyperglycemic agents for people with type 2 diabetes in primary or secondary prevention of cardiovascular disease, excluding for brevity the injection therapies for diabetes, such as insulin and glucagon-like peptide-1 receptor agonists.


Subject(s)
Blood Glucose/drug effects , Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 2/drug therapy , Glycemic Control , Hypoglycemic Agents/administration & dosage , Administration, Oral , Biomarkers/blood , Blood Glucose/metabolism , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Heart Disease Risk Factors , Humans , Primary Prevention , Protective Factors , Risk Assessment , Secondary Prevention , Treatment Outcome
19.
Clin Ther ; 42(9): 1738-1749.e1, 2020 09.
Article in English | MEDLINE | ID: mdl-32753164

ABSTRACT

PURPOSE: The goal of this study was to evaluate the effectiveness and safety of exenatide once weekly (EOW) and to determine predictors of treatment response and drug discontinuation in patients with type 2 diabetes mellitus (T2DM) followed up for 18 months in a real-world setting. METHODS: This retrospective cohort study included patients with T2DM who initiated EOW 2 mg between 2014 and 2019 in an outpatient diabetes clinic in Italy. Data were collected at baseline and at follow-up visits (6, 12, and 18 months after EOW). We estimated glycosylated hemoglobin (HbA1c) and body weight mean changes from baseline to follow-up visits and assessed the proportion of patients reaching HbA1c target ≤7% and a 5% weight loss after 12 months of treatment. We then attempted to establish predictors of glycemic and weight response, and compared patient characteristics between subjects who persisted on treatment versus those who discontinued EOW. FINDINGS: One-hundred eighty-six patients (46.2% male) were included in the study. The mean (SD) age and diabetes duration were 63.2 (8.9) years and 10.7 years (18.3), respectively. Significant reductions in HbA1c values (-0.9%; 95% CI, -1.1 to -0.8) and body weight (-2.8 kg; 95% CI, -3.4 to -2.2) were observed after 6 months. Sixty-one percent of patients (87 of 143) achieved target HbA1c values ≤ 7% after 12 months, and 34% (45 of 134) exhibited a weight loss of at least 5% of baseline body weight. Blood glucose and weight reductions were maintained after an 18-month follow-up. Predictors of adequate glycemic and weight response were shorter diabetes duration and nonuse of a different GLP-1RA, respectively. Patients on sulfonylureas failed to reach metabolic and body weight targets. The most common adverse events were gastrointestinal side effects (7.5%) and injection site reactions (6.4%), followed by headache (1.1%) and allergic reactions (1.1%). Forty-three percent of patients (79 of 186) discontinued EOW. The main reasons for discontinuation were insufficient HbA1c improvement and/or limited weight reduction (19.9%), side effects (16.1%), or patient decision (6.5%). Predictors of discontinuation were higher HbA1c levels at baseline and use of basal insulin therapy before EOW treatment. IMPLICATIONS: EOW treatment, in a real-world setting, offers sustained and effective glycemic control and weight loss over 18 months in patients with T2DM. Diabetes duration and basal insulin therapy, however, may affect the outcome of EOW treatment, suggesting that early initiation of EOW could improve glycemic control and reduce the risk of treatment discontinuation.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Exenatide/therapeutic use , Hypoglycemic Agents/therapeutic use , Aged , Blood Glucose/drug effects , Body Weight/drug effects , Cohort Studies , Female , Glycated Hemoglobin/analysis , Humans , Insulin/therapeutic use , Italy , Male , Middle Aged , Retrospective Studies , Sulfonylurea Compounds/therapeutic use , Time Factors
20.
Diabetes Res Clin Pract ; 166: 108345, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32710999

ABSTRACT

Many specialists use the remote management of people with chronic disease as diabetes, but structured management protocols have not been developed yet. The COVID-19 pandemic has given a big boost to the use of telemedicine, as it allows to maintain the physical distance, essential to the containment of contagion having regular health contact. Encouraging results related to the use of telemedicine in women with hyperglycaemia in pregnancy, have been recently published. It is well known that hyperglycaemia alters the immune response to infections, that inflammation, in turn, worsens glycaemic control and that any form of hyperglycaemia in pregnancy (HIP) has effects not only on the mother but also on development of the foetus. Therefore, the Italian Diabetes and Pregnancy Study Group, together with a group of experts, developed these recommendations in order to guide physicians in the management of HIP, providing specific diagnostic, therapeutic and assistance pathways (PDTAs) for the COVID-19 emergency. Three detailed PDTAs were developed, for type 1, type 2 and gestational diabetes.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/prevention & control , Diabetes, Gestational/drug therapy , Hyperglycemia/prevention & control , Insulin/therapeutic use , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Practice Guidelines as Topic/standards , Pregnancy Complications, Infectious/prevention & control , Blood Glucose/analysis , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Diabetes, Gestational/physiopathology , Diabetes, Gestational/virology , Disease Management , Female , Humans , Hyperglycemia/epidemiology , Hyperglycemia/virology , Hypoglycemic Agents/therapeutic use , Italy/epidemiology , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , SARS-CoV-2 , Telemedicine/methods
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