Advances in diabetes management: have pregnancy outcomes in women with type 1 diabetes changed in the last decades?

AIMS: Over the recent years multiple therapeutic and management opportunities have been made available to treat pregnant women with Type 1 diabetes (T1DM). However, analyses assessing whether these different approaches may have any specific advantage/disadvantage in metabolic control and neonatal outcomes is still limited. The aim of this study was to compare metabolic control and neonatal outcomes in pregnant women with T1DM among different basal insulins (NPH vs. analogue), insulin administration ways [Multiple Daily Injections (MDI) vs. Continuous Subcutaneous Insulin Infusion (CSII)] and glucose monitoring systems [Self-Monitoring of Blood Glucose (SMBG) vs. real-time/intermittently scanned Continuous Glucose Monitoring (rtCGM/isCGM)]. METHODS: A retrospective analysis on metabolic data and neonatal outcomes of 136 T1DM pregnant women (76% on MDI, based on NPH (51%) or analogue (49%); 24% on CSII; 24% using rtCGM/isCGM), managed between 2008 and 2020, was performed, comparing different therapeutic approaches. RESULTS: Metabolic data and neonatal outcomes were comparable among women treated with different basal insulins. Women on CSII planned their pregnancy more frequently (82 vs. 60%; p = 0.043) and had better pregestational HbA1c (52 ± 5 vs. 60 ± 13 mmol/mol; p = 0.044) and first trimester HbA1c (48 ± 4 vs. 51 ± 8 mmol/mol; p = 0.047). Pregestational and first trimester HbA1c were also lower in women using rtCGM/isCGM (53 ± 8 vs. 58 ± 13 mmol/mol; p = 0.027 and 46 ± 5 vs. 51 ± 7 mmol/mol; p = 0.034, respectively). In the whole cohort, LGA risk was directly correlated to HbA1c at third trimester (correlation coefficient: 0.335, p = 0.001) and inversely correlated to the achievement of HbA1c target (≤6% [<42 mmol/mol]) at third trimester (correlation coefficient: - 0.367, p < 0.001). CONCLUSION: Treatment with insulin analogs didn't significantly change metabolic control and neonatal outcomes in T1DM women, while CSII and rtCGM/isCGM can optimize preconception and first trimester pregnancy glycemic control. Irrespective of the therapeutic management, third trimester HbA1c remains the strongest risk factor for LGA.

Polybrominated Diphenyl Ethers (PBDEs) and Human Health: Effects on Metabolism, Diabetes and Cancer.

There is increasing evidence of the role of endocrine disruptors (EDs) derived from commonly employed compounds for manufacturing and processing in altering hormonal signaling and function. Due to their prolonged half-life and persistence, EDs can usually be found not only in industrial products but also in households and in the environment, creating the premises for long-lasting exposure. Polybrominated diphenyl ethers (PBDEs) are common EDs used in industrial products such as flame retardants, and recent studies are increasingly showing that they may interfere with both metabolic and oncogenic pathways. In this article, a multidisciplinary panel of experts of the Italian Association of Medical Diabetologists (AMD), the Italian Society of Diabetology (SID), the Italian Association of Medical Oncology (AIOM), the Italian Society of Endocrinology (SIE) and the Italian Society of Pharmacology (SIF) provides a review on the potential role of PBDEs in human health and disease, exploring both molecular and clinical aspects and focusing on metabolic and oncogenic pathways.

Continuous glucose monitoring (CGM) in a non-Icu hospital setting: The patient's journey.

AIMS: Although consistent data support the outpatient use of continuous glucose monitoring (CGM) to improve glycemic control and reduce hypoglycemic burden, and clinical outcomes, there are limited data regarding its use in the hospital setting, particularly in the non-intensive care unit (non-ICU) setting. The emerging use of CGM in the non-critical care setting may be useful in increasing the efficiency of hospital care and reducing the length of stay for patients with diabetes while improving glycemic control. DATA SYNTHESIS: The purpose of this Expert Opinion paper was to evaluate the state of the art and provide a practical model of how CGM can be implemented in the hospital. SETTING: A patient's CGM journey from admission to the ward to the application of the sensor, from patient education on the device during hospitalization until discharge of the patient to maintain remote control. CONCLUSIONS: This practical approach for the implementation and management of CGM in patients with diabetes admitted to non-ICUs could guide hospitals in their diabetes management initiatives using CGM, helping to identify patients most likely to benefit and suggesting how this technology can be implemented to maximize clinical benefits.

The legacy effect of hyperglycemia and early use of SGLT-2 inhibitors: a cohort study with newly-diagnosed people with type 2 diabetes.

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

Pregestational exposure to hormonal combined contraceptives and risk of gestational diabetes: an observational retrospective population study.

AIMS: To investigate whether pregestational exposure to oral combined hormonal contraception (CHC) is associated with a rise in the risk of gestational diabetes (GDM). METHODS: Prevailing GDM was assessed for all pregnancies that occurred in Tuscany, Italy, from years 2010 to 2018, using administrative data coupled with information about CHC prescriptions in the year prior to pregnancy retrieved from the regional registry of drug prescription claims. The relation between exposure to CHC and risk of GDM, expressed as Odds Ratio: OR (95% Confidence Intervals, CI), was calculated separately based on citizenship of mothers using multiple logistic regression analysis models, after adjusting for confounders. RESULTS: Among 210,791 pregnancies from 170,126 mothers, GDM was present in 22,166 (10.5%) pregnancies. CHC prescription within 12 months before the index pregnancy was present in 9065 (4.3%) mothers. The risk of GDM was weakly but significantly higher in pregnancies exposed to pregestational CHC only in pregnancies of mothers of Italian citizenship: OR:1.11 (95% CI 1.02-1.21); p = 0.02, after adjusting for age, parity, calendar year and pregestational body-mass index. The CHC-mediated effect was no longer present in pregnancies of mothers at higher risk of GDM, such as pregestational obesity, migrating from countries at higher GDM risk or after adjusting for the entire panel of confounders including employment status, prior spontaneous abortions, and education degree. CONCLUSIONS: CHC had a modest effect on GDM risk, which became insignificant when added to basal prevailing risk factors for impaired glucose metabolism in pregnancy, such as pregestational obesity or originating from countries at high GDM risk.

Achieving Good Metabolic Control Without Weight Gain with the Systematic Use of GLP-1-RAs and SGLT-2 Inhibitors in Type 2 Diabetes: A Machine-learning Projection Using Data from Clinical Practice.

PURPOSE: Recently, the 2022 American Diabetes Association and European Association for the Study of Diabetes (ADA-EASD) consensus report stressed the importance of weight control in the management of patients with type 2 diabetes; weight control should be a primary target of therapy. This retrospective analysis evaluated, through an artificial-intelligence (AI) projection of data from the AMD Annals database-a huge collection of most Italian diabetology medical records covering 15 years (2005-2019)-the potential effects of the extended use of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and of glucose-like peptide 1 receptor antagonists (GLP-1-RAs) on HbA1c and weight. METHODS: Data from 4,927,548 visits in 558,097 patients were retrospectively extracted using these exclusion criteria: type 1 diabetes, pregnancy, age >75 years, dialysis, and lack of data on HbA1c or weight. The analysis revealed late prescribing of SGLT-2is and GLP-1-RAs (innovative drugs), and considering a time frame of 4 years (2014-2017), a paradoxic greater percentage of combined-goal (HbA1c <7% and weight gain <2%) achievement was found with older drugs than with innovative drugs, demonstrating aspects of therapeutic inertia. Through a machine-learning AI technique, a "what-if" analysis was performed, using query models of two outcomes: (1) achievement of the combined goal at the visit subsequent to a hypothetical initial prescribing of an SGLT-2i or a GLP-1-RA, with and without insulin, selected according to the 2018 ADA-EASD diabetes recommendations; and (2) persistence of the combined goal for 18 months. The precision values of the two models were, respectively, sensitivity, 71.1 % and 69.8%, and specificity, 67% and 76%. FINDINGS: The first query of the AI analysis showed a great improvement in achievement of the combined goal: 38.8% with prescribing in clinical practice versus 66.5% with prescribing in the "what-if" simulation. Addressing persistence at 18 months after the initial achievement of the combined goal, the simulation showed a potential better performance of SGLT-2is and GLP-1-RAs with respect to each antidiabetic pharmacologic class or combination considered. IMPLICATIONS: AI appears potentially useful in the analysis of a great amount of data, such as that derived from the AMD Annals. In the present study, an LLM analysis revealed a great potential improvement in achieving metabolic targets with SGLT-2i and GLP-1-RA utilization. These results underscore the importance of early, timely, and extended use of these new drugs.

Metrics of Gender Differences in Mortality Risk after Diabetic Foot Disease.

BACKGROUND: The aim of this study was to clarify any gender differences in the mortality risk of people with DFD since patients with diabetic foot disease (DFD) are at a high risk of mortality and, at the same time, are more likely to be men. METHODS: From regional administrative sources, the survival probability was retrospectively evaluated by the Kaplan-Meier method and using the Cox proportional-hazards model comparing people with DFD to those without DFD across the years 2011-2018 in Tuscany, Italy. Gender difference in mortality was evaluated by the ratio of hazard ratios (RHR) of men to women after initial DFD hospitalizations (n = 11,529) or in a cohort with prior history of DFD hospitalizations (n = 11,246). RESULTS: In both cohorts, the survival probability after DFD was lower among women. Compared to those without DFD, after initial DFD hospitalizations, the mortality risk was significantly (18%) higher for men compared to women. This excess risk was particularly high after major amputations but also after ulcers, infections, gangrene, or Charcot, with a lower reduction after revascularization procedures among men. In the cohort that included people with a history of prior DFD hospitalizations, except for the risk of minor amputations being higher for men, there was no gender difference in mortality risk. CONCLUSIONS: In people with DFD, the overall survival probability was lower among women. Compared to those without DFD after a first DFD hospitalization, men were at higher risk of mortality. This excess risk disappeared in groups with a history of previous DFD hospitalizations containing a greater percentage of women who were older and probably had a longer duration of diabetes and thus becoming, over time, progressively frailer than men.

Transparent machine learning suggests a key driver in the decision to start insulin therapy in individuals with type 2 diabetes.

AIMS: The objective of this study is to establish a predictive model using transparent machine learning (ML) to identify any drivers that characterize therapeutic inertia. METHODS: Data in the form of both descriptive and dynamic variables collected from electronic records of 1.5 million patients seen at clinics within the Italian Association of Medical Diabetologists between 2005-2019 were analyzed using logic learning machine (LLM), a "clear box" ML technique. Data were subjected to a first stage of modeling to allow ML to automatically select the most relevant factors related to inertia, and then four further modeling steps individuated key variables that discriminated the presence or absence of inertia. RESULTS: The LLM model revealed a key role for average glycated hemoglobin (HbA1c) threshold values correlated with the presence or absence of insulin therapeutic inertia with an accuracy of 0.79. The model indicated that a patient's dynamic rather than static glycemic profile has a greater effect on therapeutic inertia. Specifically, the difference in HbA1c between two consecutive visits, what we call the HbA1c gap, plays a crucial role. Namely, insulin therapeutic inertia is correlated with an HbA1c gap of <6.6 mmol/mol (0.6%), but not with an HbA1c gap of >11 mmol/mol (1.0%). CONCLUSIONS: The results reveal, for the first time, the interrelationship between a patient's glycemic trend defined by sequential HbA1c measurements and timely or delayed initiation of insulin therapy. The results further demonstrate that LLM can provide insight in support of evidence-based medicine using real world data.

Role of telemedicine during COVID-19 pandemic in type 2 diabetes outpatients: The AMD annals initiative.

AIMS: Telemedicine is advocated as a fundamental tool in modern clinical management. However, data on the effects of telemedicine vs face-to-face consultation on clinical outcomes in type 2 diabetes (T2DM) are still uncertain. This paper describes the use of telemedicine during the 2020 COVID-19 emergency and compares volume activity and quality indicators of diabetes care between face-to-face vs telemedicine counseling in the large cohort of T2DM patients from the AMD Annals Initiative. METHODS: Demographic and clinical characteristics, including laboratory parameters, rate of the screening of long-term complications, current therapies and the Q-score, a validated score that measures the overall quality of care, were compared between 364,898 patients attending face-to-face consultation and 46,424 on telemedicine, during the COVID-19 pandemic. RESULTS: Patients on telemedicine showed lower HbA1c levels (7.1 ± 1.2 % vs 7.3 ± 1.3 %, p < 0.0001), and they were less frequently treated with metformin, GLP1-RAs and SGLT2i and more frequently with DPP4i. The telemedicine group showed reduced monitoring of the various parameters considered as process indicators, especially, eye and foot examination. The proportion of patients with a good quality of care (Q score > 25) was higher among those receiving face-to-face consultation. Moreover, in the telemedicine group, all major clinical outcomes remained stable when further compared to those collected in the year 2019, when the same patients underwent a regular face-to-face consultation, suggesting that the care provided through telemedicine did not negatively affect the most important parameters. CONCLUSIONS: During the COVID-19 pandemic, telemedicine provided an acceptable quality of diabetes care, comparable to that of patients attending face-to-face consultation, although a less frequent screening of complications seems to have occurred in subjects consulted by telemedicine.

Dietary habits, lifestyle, and gestational diabetes in immigrant women: a survey in Northwestern Tuscany (Central Italy).

BACKGROUND: immigrant women diagnosed with gestational diabetes mellitus (GDM) have additional language and cultural obstacles in following lifestyle and dietary recommendations within a Western health care setting. OBJECTIVES: to describe: • sociodemographic characteristics and dietary and lifestyle behaviours in Italian and immigrant pregnant women who underwent a GDM screening; • any differences in these aspects among GDM Italian and immigrant women; • any differences in terms of primary maternal-neonatal outcomes among GDM and normal glucose tolerance (NGT) cohorts. DESIGN: survey. SETTING AND PARTICIPANTS: this survey was conducted in three hospitals located in Tuscany Region (Central Italy). According to a convenience sampling, an ad hoc questionnaire was administered both to Italian and immigrant women who underwent an oral glucose tolerance test. MAIN OUTCOME MEASURES: information about nutrition and lifestyle, medical and obstetric history, clinical and therapy data, maternal and neonatal primary outcomes was analysed. Eating habits have been investigated referring to the prudent diet, in order to also include those foods specifically consumed by the immigrant women, in addition to the Mediterranean Diet which is more widespread among Italians. RESULTS: a total of 117 Italian women (42 diagnosed with GDM) and 95 immigrant women (36 with GDM) were enrolled. Immigrant women showed lower adherence to the prudent diet compared to Italian women (p<0.05) and a broader use of unhealthy food preparation (e.g., frying; p<0.05). Primary maternal and neonatal outcomes (preterm birth, caesarean section, macrosomia) showed no statistical differences among GDM and NGT cohorts. CONCLUSIONS: even if immigrant and Italian women gained similar pregnancy outcomes, immigrant women showed lower adherence to the prudent diet at the time of GDM screening. An ethnic and tailored meal plan is needed to overcome cultural barriers in dietary recommendations during pregnancy in immigrant women.

The impact of fetal sex on risk factors for gestational diabetes and related adverse pregnancy outcomes.

AIMS: To investigate whether fetal sex affects the impact of classical GDM risk factors on the diagnosis of gestational diabetes (GDM) as well as on related adverse pregnancy outcomes. METHODS: This retrospective observational study concerned 206,917 singleton live births born to 170,126 women aged 15-45 over the years 2010-2018 in Tuscany, Italy. GDM was identified by administrative data-sources in 21,613 pregnancies (10.5%) by assessing, through multiple logistic models, whether fetal sex modified the risk of GDM driven by maternal risk factors, and whether it modified the risk of adverse outcomes such as prematurity (birth ≤ 37th gestational week), large for gestational age (LGA), unplanned caesarean sections, or 5-min-Apgar-index ≤ 7 in pregnancies with GDM. RESULTS: GDM was diagnosed in 21,613 pregnancies (10.5%). Male fetal sex predicted a higher adjusted risk of GDM: OR = 1.05(95% CI: 1.01-1.07); p < 0.0009. In pregnancies with female sex, pre-pregnancy obesity amplified the risk of GDM: OR = 1.09(95% CI: 1.01-1.19); p = 0.04. In pregnancies with GDM, carrying a female fetus increased the risk of LGA associated with pregestational obesity OR = 1.45(95% CI: 1.15-1.81); p = 0.001, and in primiparous pregnancies, it protected mothers from the risk of unplanned caesarean sections OR = 0.80(95%CI: 0.67-0.92); p = 0.001. CONCLUSIONS: While male fetal sex is associated with rise in the risk of GDM, giving birth to a girl amplifies the excess GDM risk driven by pregestational obesity, thus increasing the risk of LGA in pregnancies with GDM. Additionally, female fetal sex in pregnancies with GDM seems to protect from the risk of unplanned caesarean sections in primiparous pregnancies.

Pregnancy outcomes and maternal characteristics in women with pregestational and gestational diabetes: a retrospective study on 206,917 singleton live births.

AIMS: To examine risk of adverse pregnancy outcomes, mothers' characteristics and incidence rate over time of pregestational type 1 (T1D), type 2 (T2D) or gestational diabetes (GDM). METHODS: The study included all singleton live births born from women aged 15-45 year, in Tuscany, Italy from 2010 to 2018. Pregnancy outcomes were retrieved by certificates of care at delivery compiled by midwives. Pregestational diabetes and GDM were identified by regional administrative databases. Time course of pregestational diabetes and GDM across last decade was assessed by Poisson analysis. Logistic regression analysis was used to calculate adjusted odds ratios (OR; 95% CI) for maternal characteristics or neonatal outcomes. RESULTS: Among 206,917 singleton live births, GDM was diagnosed in 21,613 pregnancies (10.46%) and pregestational diabetes in 979, being T2D more prevalent than T1D (606; 0.29% vs. 373; 0.18%). Pregestational T2D incidence progressively decreased over last decade, T1D remained stable while GDM progressively rose. Pre-pregnancy obesity, preterm deliveries or cesarean sections were common characteristics of pregestational diabetes and GDM. Risk of neonatal distress and neonatal malformations was higher in pregestational T1D. Risk of prior spontaneous abortions was higher in GDM and in pregestational T2D (OR: 4.19; 3.30-5.33), mostly treated with metformin. Risk of neonatal macrosomia was increased only in pregestational diabetes. CONCLUSIONS: In our population, pregestational T2D was more prevalent than T1D. Neonatal complications were mostly associated with pregestational T1D. Increased risk of previous spontaneous abortions was the hallmark of pregestational T2D. GDM, even if sharing adverse outcomes with pregestational T2D, was unrelated to rise in risk of neonatal macrosomia.

Recommendations and management of hyperglycaemia in pregnancy during COVID-19 pandemic in Italy.

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.

Risk and adverse outcomes of gestational diabetes in migrants: A population cohort study.

AIMS: To evaluate the risk of gestational diabetes (GDM) and of neonatal/maternal complications (macrosomia, large for gestational age (LGA), cesarean sections, preterm deliveries, neonatal distress and fetal malformations) among women coming from High Migration Pressure Countries (HMPC), compared to native (Italian) mothers. METHODS: Risks of GDM and related neonatal/maternal complications were evaluated in a cohort of 581,073 Italian compared with 105,111 HMPC women of age 15-45 yr, resident in Tuscany, Italy along years 2012-2017, delivering 122,652 singleton live births (18,596 from HMPC mothers). RESULTS: HMPC women, compared to Italian ones, were at higher risk of GDM (OR: 1.586; 1.509-1.666;p < 0.0001), peaking for women originating from South Asia (OR:3.0.49; 2.618-3.553;p < 0.0001). GDM was associated with increased risk of preterm delivery and cesarean sections, while migrants, regardless of GDM, were burdened by a higher risk of all considered complications. The rise in all these risks, including macrosomia or LGA however, disappeared, after addition of interaction term GDM × HMPC ethnicity. CONCLUSION: Compared to Italian mothers, HMPC women had higher risk of GDM and of all considered adverse events. The addiction of the interaction term GDM × HMPC ethnicity in the predictive model, however reversed the rise in risk of all HMPC associated adverse outcomes.

Guidelines for the screening and diagnosis of gestational diabetes in Italy from 2010 to 2019: critical issues and the potential for improvement.

AIMS: In 2010, Italian health professionals rapidly implemented the one-step screening for gestational diabetes mellitus (GDM) based on a 75 g OGTT, to comply with the diagnostic criteria proposed by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). The change was promoted by the two main Italian scientific societies of diabetology, Associazione Medici Diabetologi (AMD) and Società Italiana di Diabetologia (SID), and it took just a few months for the Istituto Superiore di Sanità, together with several scientific societies, to revise the criteria and include them in the National Guidelines System. Over the last 9 years, the implementation of these guidelines has shown some benefits and some drawbacks. METHODS: In order to evaluate the critical issues arisen from the implementation of the current Italian guidelines for the diagnosis of GDM, the studies published on this topic have been reviewed. The search was performed using the following keywords: "gestational diabetes" AND "diagnostic criteria" OR screening AND Ital*. The study is an expert opinion paper, based on the relevant scientific literature published between 2010 and 2019. The databases screened for the literature review included PubMed, MEDLINE, and Scopus. RESULTS: The implementation of the Guidelines for Screening and Diagnosis of GDM in Italy present some strengths and some weaknesses. One of the positive aspects is that high-risk women are required to perform an OGTT early in pregnancy. By contrast, there are several aspects in need of improvement: (1) In spite of the current indications, only a minority of high-risk women perform OGTT early in pregnancy; (2) several low-risk women are screened for GDM; (3) in some low-risk women affected by GDM, the diagnosis might be missed with the application of the current guidelines; (4) there is a lack of homogeneity in the risk assessment data from different regions. CONCLUSIONS: In order to improve the current Italian GDM guidelines, some practical solutions have been suggested.

Pasta Consumption and Connected Dietary Habits: Associations with Glucose Control, Adiposity Measures, and Cardiovascular Risk Factors in People with Type 2 Diabetes-TOSCA.IT Study.

BACKGROUND: Pasta is a refined carbohydrate with a low glycemic index. Whether pasta shares the metabolic advantages of other low glycemic index foods has not really been investigated. The aim of this study is to document, in people with type-2 diabetes, the consumption of pasta, the connected dietary habits, and the association with glucose control, measures of adiposity, and major cardiovascular risk factors. METHODS: We studied 2562 participants. The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. Sex-specific quartiles of pasta consumption were created in order to explore the study aims. RESULTS: A higher pasta consumption was associated with a lower intake of proteins, total and saturated fat, cholesterol, added sugar, and fiber. Glucose control, body mass index, prevalence of obesity, and visceral obesity were not significantly different across the quartiles of pasta intake. No relation was found with LDL cholesterol and triglycerides, but there was an inverse relation with HDL-cholesterol. Systolic blood pressure increased with pasta consumption; but this relation was not confirmed after correction for confounders. CONCLUSIONS: In people with type-2 diabetes, the consumption of pasta, within the limits recommended for total carbohydrates intake, is not associated with worsening of glucose control, measures of adiposity, and major cardiovascular risk factors.

Preventing type 2 diabetes and cardiovascular disease in women with gestational diabetes - The evidence and potential strategies.

Gestational Diabetes Mellitus is a condition strongly related to the development of type 2 diabetes later in life, although the risk and the onset have not been fully identified yet. Although glucose tolerance returns to normal levels after delivery in the majority of women with GDM, this condition represents an early stage in the natural history of T2DM. In addition, women with previous GDM exhibit an increased cardiovascular risk profile and a raised incidence of cardiovascular diseases. Lifestyle changes and pharmacological interventions might be able to reduce the incidence of type 2 diabetes in pGDM women, although results are still not conclusive. Long term continuous programs specifically addressed to women with pGDM should be implemented, with the ambitious target to encourage them to regularly check glucose tolerance, lipid profile and other parameters related to cardiovascular diseases, aimed at improving women's health. In this paper, we review the relationship between type 2 diabetes, cardiovascular diseases and a history of GDM.

Long-Term Effectiveness of Liraglutide for Treatment of Type 2 Diabetes in a Real-Life Setting: A 24-Month, Multicenter, Non-interventional, Retrospective Study.

INTRODUCTION: The aim of the study was to evaluate whether the reduction in glycated hemoglobin (HbA1c) observed in clinical trials with liraglutide in type 2 diabetes (T2D) could be attained in routine clinical practice. METHODS: ReaL was a multicenter, non-interventional, observational, retrospective, longitudinal study on the effectiveness of liraglutide, a human glucagon-like peptide-1 analog, in individuals with T2D treated in daily practice in Italy. Between 26 March and 16 November 2015, data were taken from clinical records of patients aged ≥ 18 years with treatment follow-up data of up to 24 months and who received their first prescription of liraglutide in 2011. RESULTS: A total of 1723 patients were included in the analysis. At baseline, mean age was 58.9 years, duration of diabetes was 9.6 years, and HbA1c was 8.3%. At 12 months, 36.1% of patients were prescribed the maximum 1.8 mg dose; 43.5% [95% confidence interval (CI): 40.9; 46.2] of patients attained the primary outcome of a reduction in HbA1c of ≥ 1% point at 12 months. At 24 months, 40.9% (95% CI 38.1; 43.7) of patients had attained the HbA1c target of ≤ 7%. Additionally, body weight significantly decreased by 3.4 kg (95% CI - 3.6; - 3.1, p < 0.0001). CONCLUSION: In this observational study conducted in routine clinical practice for up to 2 years, treatment with liraglutide improved HbA1c and reduced body weight in a similar fashion to that observed under randomized clinical trial conditions. The data support the use of liraglutide as an effective treatment for T2D in clinical practice. FUNDING: Novo Nordisk S.p.A. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02255266.

Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial.

BACKGROUND: The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. METHODS: TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50-75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2-3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15-45 mg) or a sulfonylurea (5-15 mg glibenclamide, 2-6 mg glimepiride, or 30-120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. FINDINGS: Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 per 100 person-years) who were given sulfonylureas (hazard ratio 0·96, 95% CI 0·74-1·26, p=0·79). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p<0·0001). Moderate weight gain (less than 2 kg, on average) occurred in both groups. Rates of heart failure, bladder cancer, and fractures were not significantly different between treatment groups. INTERPRETATION: In this long-term, pragmatic trial, incidence of cardiovascular events was similar with sulfonylureas (mostly glimepiride and gliclazide) and pioglitazone as add-on treatments to metformin. Both of these widely available and affordable treatments are suitable options with respect to efficacy and adverse events, although pioglitazone was associated with fewer hypoglycaemia events. FUNDING: Italian Medicines Agency, Diabete Ricerca, and Italian Diabetes Society.

Screening for gestational diabetes in Tuscany, Italy. A population study.

AIMS: According to current Italian guidelines, only women at higher risk of gestational diabetes (GDM) are eligible for receiving a glucose tolerance test (OGTT) during pregnancy. This study evaluates the compliance to national guidelines, additionally proposing an algorithm able to identify women with GDM. METHODS: The study included 23,270 pregnant women aged >15yr, resident in Tuscany, a region in central Italy, delivering in year 2015, identified by certificates of care at delivery. Eligibility to screening was evaluated by fulfillment to regional guidelines recommending a 2-h-75g-OGTT only in presence of risk factors. Additionally, a validated algorithm is proposed to diagnose GDM from regional administrative databases. RESULTS: Glucose tolerance was tested in 79.2% of women. Eligibility criteria were fulfilled in 55.6% of OGTT performers and in 40.2% of those who didn't perform any OGTT. Performers' rate increased with age, body weight, higher education degree and in those followed by a well defined clinical setting. Housewives and students had a lower chance of receiving an OGTT. Algorithm identified GDM in 11% of women, ranging from 14% among eligible and 7% among non-eligible ones. CONCLUSION: Selective screening for GDM is not being currently applied in Tuscany. Despite the percentage of eligible women by national guidelines was 55%, the rate of those who performed the screening was about 80%, with a 40% of low risk women continuing to be screened. Moreover, GDM rate, calculated by algorithm, was relatively large (7%) among non-eligible women, suggesting the need of universal glucose screening to adequately capture all GDM cases.