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Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

Objective Obesity is a growing emergency also in type 1 diabetes (T1D). Sex-differences in obesity prevalence and its clinical consequences in adult T1D subjects have been poorly investigated. The aim of this study was to investigate the prevalence of obesity and severe obesity, clinical correlates and potential sex-differences in a large cohort of T1D subjects, participating to the AMD Annals Initiative in Italy. Research design and methods The prevalence of obesity (BMI ≥30 kg/m2) and severe obesity (BMI ≥ 35 kg/m2) according to sex and age, as well as obesity-associated clinical variables, long-term diabetes complications, pharmacological treatment, process indicators and outcomes, and overall quality of care (score Q) were evaluated in 37,436 T1D subjects (45.3% women) attending 282 Italian diabetes clinics during 2019. Results Overall, the prevalence of obesity was similar in the two gender (13.0% in men and 13.9% in women; mean age 50 years), and it increased with age, affecting 1 out of 6 subjects aged >65 years. Only severe obesity (BMI >35 Kg/m2) was more prevalent among women, who showed a 45% higher risk of severe obesity, compared with men at multivariate analysis. CVD risk factors (lipid profile, glucose and blood pressure control), and the overall quality of diabetes care were worse in obese subjects, with no major sex-related differences. Also, micro- and macrovascular complications were more frequent among obese than non-obese T1D men and women. Conclusions Obesity is a frequent finding in T1D adult subjects, and it is associated with a higher burden of CVD risk factors, micro- and macrovascular complications, and a lower quality of care, with no major sex-differences. T1D women are at higher risk of severe obesity.

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.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.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.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.

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.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.survey.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.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.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 (p0.05) and a broader use of unhealthy food preparation (e.g., frying; p0.05). Primary maternal and neonatal outcomes (preterm birth, caesarean section, macrosomia) showed no statistical differences among GDM and NGT cohorts.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.

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.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.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.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.

Diabetic foot ulceration (DFU) is a severe complication of diabetes mellitus associated with a high morbidity and mortality rate, whose treatment requires considerable financial costs. This paper describes a test of the efficacy of proactive screening – autonomously managed by nurses in a community setting – in detecting patients at high risk of DFU, as an integrated part of a chronic care model strategy.

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.

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). 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. 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. 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.

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.

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.

Hypoglycemia is a major factor preventing patients with both type 1 and type 2 diabetes from achieving near-normal glycemia. The risk of hypoglycemia in diabetic patients is due to both the imperfect pharmacokinetics of current therapy that produces inappropriately high insulin concentrations and a failure in the physiological protective mechanism that limits the decrease in blood glucose concentrations. A single threshold value for plasma glucose concentration that defines hypoglycemia in diabetes cannot be assigned. The insufficient contribution of glucose to the brain with an associated cerebral reduction of oxygen causes neuroglycopenic symptoms. Glucose, in physiological conditions, provides 90% of the energy necessary for brain functioning, and the cerebral functions are totally dependent on the level of the circulating glucose. In pregnant women with intensively treated type 1 diabetes, consistent lower epinephrine and glucagon responses were found with respect to nondiabetic nonpregnant women.

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 Societa Italiana di Diabetologia (SID), and it took just a few months for the Istituto Superiore di Sanita, 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. 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. 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. In order to improve the current Italian GDM guidelines, some practical solutions have been suggested.

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

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 >15 yr, 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-75 g-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.

Il diabete gestazionale (GDM) complica il 7–8% di tutte le gravidanze; se non diagnosticato e adeguatamente trattato, si associa a un’elevata morbilita materno-fetale riconducibile in primo luogo all’alterazione della crescita fetale. Nonostante la sua elevata incidenza e l’importante impatto clinico che lo contraddistingue, le modalita di diagnosi del GDM risultano ancora oggi oggetto di controversia. Non e ancora ben definito se per la sua individuazione debbano essere sottoposte a screening tutte le donne (screening universale) o solo quelle con determinati fattori di rischio (screening selettivo), ne tantomeno se la procedura di screening debba essere in fase unica o in due fasi, quale test di carico glucidico utilizzare (75 o 100 g?), quali i valori glicemici soglia. Per rispondere a questi interrogativi e stato disegnato un importante studio osservazionale a livello internazionale, lo studio HAPO (Hyperglycemia and Adverse Pregnancy Outcome Study), che ha coinvolto 25.000 donne con normale tolleranza glucidica in diversi paesi del mondo. I risultati dello studio hanno dimostrato in maniera inequivocabile che all’aumentare dei valori glicemici registrati, sia a digiuno che una e due ore dopo il carico glucidico, aumentava l’incidenza di tutti gli end-point primari dello studio (peso alla nascita oltre il 90° percentile, taglio cesareo, ipoglicemia neonatale, C-peptide neonatale elevato). Tuttavia, poiche l’associazione tra la glicemia e gli end-point dello studio ha mostrato un andamento lineare, lo studio non ha potuto stabilire valori glicemici soglia. Successivamente un panel di esperti a livello internazionale, partendo dai risultati dello studio HAPO ha elaborato nuove raccomandazioni per lo screening e la diagnosi del GDM. Come test diagnostico e stato scelto l’OGTT con 75 g. La nuova procedura ha avuto certamente il merito di semplificare quelle precedenti indicando in un solo test, l’OGTT a 75 g quello da utilizzare per la diagnosi. Allo stesso tempo, pero, la sua applicazione ha comportato importanti problematiche, in primo luogo legate al sensibile aumento dei casi di GDM. Pertanto le nuove raccomandazioni tardano a trovare l’approvazione da parte di importanti organismi scientifici internazionali e in Italia, dopo una prima fase di accettazione, si e proceduto ad una loro parziale riproposizione.

In September 2011 the Italian Public Health Authority established selective screening for GDM to be performed based on the presence of risk factors. In a cohort of 2552 Caucasian pregnant women we evaluated to which extent the new national guidelines (NGL) are correctly applied; moreover we estimated the prevalence of GDM assessed by NGL. Our data show that the NGL are still properly implemented since the screening test was performed in nearly the totality of the women at 24th and 28th week of gestation. GDM prevalence is 10.9%, 25% greater as compared to the one determined with the old criteria 10 years ago.

It is well known that good metabolic control maintained throughout pregnancy reduces maternal and fetal complications in diabetes. Before conception and throughout pregnancy, insulin therapy needs to be optimized and, in this context, the insulin analogs currently available in the market may help to achieve good metabolic control. We therefore review here what is known about the potential benefits and risks related to the use of these new insulins in pregnancy. Clinical and experimental data on insulin aspart and lispro strongly suggest that they have no adverse maternal or fetal effects during pregnancy in women with pregestational and gestational diabetes, and that their use results in improved glycemic control, fewer hypoglycemic episodes, and improved patient satisfaction. At present there are no published data on the use of glulisine in pregnancy. Insulin glargine during pregnancy is not recommended but, in the last years, larger surveys (retrospective and case-control studies) have been published on this field and, to date, results of about 335 pregnancies with type 1 diabetes are available showing an incidence of congenital malformation similar to that obtained with human insulin. There are no published data concerning the use of detemir in pregnancy but the results of a prospective study are expected in 2010.

As a further elaboration of our systematic definition of nutritional therapy in diabetic patients, this booklet looks at the delicate but very important question of the diabetic woman’s diet during pregnancy. The recommendations were drafted by diabetologists and nutritionists who have specifically studied the problems of nutrition in pregnancy, and are backed by the Italian Association for Clinical Dietetics and Nutrition (ADI), the Association of Medical Diabetologists (AMD), and the Italian Society for Diabetology (SID). The synergism of this joint effort has produced a document that we sincerely hope will help all members of teams who tackle this vital issue in diabetes in their daily work.

OBJECTIVE— The aim of this article was to define the metabolic phenotype of pregnant women with one abnormal value (OAV) during an oral glucose tolerance test (OGTT) and to test whether OAV could be considered metabolically comparable to gestational diabetes mellitus (GDM) or a specific entity between GDM and normal pregnancy. RESEARCH DESIGN AND METHODS— After 100-g 3-h OGTTs, 4,053 pregnant women were classified as having GDM, OAV, or normal glucose tolerance (NGT). Those with OAV were subdivided into three subgroups: fasting hyperglycemia (one abnormal value at fasting during an OGTT), 1-h hyperglycemia (one abnormal value at 1 h during an OGTT [1h-OAV]), or 2- or 3-h hyperglycemia (one abnormal value at 2 or 3 h during an OGTT). As derived from the OGTT, we measured insulin sensitivity (insulin sensitivity index [ISI] Matsuda) and insulin secretion (homeostasis model assessment for the estimation of β-cell secretion [HOMA-B], first- and second-phase insulin secretion). The product of the first-phase index and the ISI was calculated to obtain the insulin secretion–sensitivity index (ISSI). RESULTS— GDM was diagnosed in 17.9% and OAV in 18.7% of pregnant women; women with GDM and OAV were older and had higher BMI and serum triglyceride levels than those with NGT (all P < 0.05). Women with NGT had the highest ISI followed by those with OAV (−21.7%) and GDM (−32.1%). HOMA-B results were comparable with those for OAV and GDM but significantly (P < 0.01) lower than those for NGT; first- and second-phase insulin secretion appeared progressively reduced from that in women with NGT to that in women with OAV and GDM (P < 0.01). ISSI was higher in women with NGT than in women with either OAV (−34%) or GDM (−51.7%) (P < 0.001). Among OAV subgroups, the 1h-OAV subgroup showed the lowest ISSI (P < 0.05). CONCLUSIONS— OAV and GDM are clinically indistinguishable, and both groups are different from women with NGT. Women with GDM and OAV showed impaired insulin secretion and insulin sensitivity, although these defects are more pronounced in women with GDM. Compared with other OAV subgroups, 1h-OAV could be considered a more severe condition.

Fetal intima-media thickness (IMT) has been suggested as a marker of pre-clinical atherosclerosis, and maternal IMT could be altered through dynamic circumstances related to pregnancy. We investigated the feasi- bility of measurement of IMT at four pre-defined fetal and four pre-defined maternal arterial locations to deter- mine vascular changes that could be associated with impaired vascular function. IMTwas measured from the first to third trimester (12-34 wk), in 38 low-risk pregnancies. We imaged a 10-mm region of interest using a Mindray (Shenzhen, China)high-resolution ultrasoundmachine withautomated IMTmeasurementsoftware.Fetal abdom- inal aorta IMTwas measurable during the second trimester in 71% and during the third trimester in 100% of the case, and umbilical artery IMTwas measurable in 50% and 82% of cases during the second and third trimesters, respectively. Fetal IMT measurements were not possible during the first trimester. It was not often feasible to mea- sure the IMT of the fetal common carotid artery, fetal renal artery and maternal iliac artery (maximal 20% of cases). Maternal common carotid artery, abdominal aorta and uterine artery IMTs were measurable throughout pregnancy. There was a significant relation between gestational age and IMTin the umbilical artery (p 50.03) and a significant relation between body mass index and IMT in the maternal common carotid artery (p 5 0.01). IMT measurements are feasible in some maternal and fetal vessels of interest. Further studies are underway to obtain more insight into vascular development during normal and pathologic pregnancies. (E-mail: roland.devlieger@ uzleuven.be) 2014 World Federation for Ultrasound in Medicine & Biology.

In this double-masked study, we compared the effects of 2 sulfonylureas—gliquidone (Gd) and glibenclamide (Gl)—on metabolic control and on the interaction of insulin with its receptor. After a 3-week run-in period, 43 untreated patients with type 2 diabetes mellitus, aged 47 to 60 years, were randomly allocated to receive treatment with Gd (n = 22) or Gl (n = 21) for 4 months. Fasting plasma glucose levels decreased similarly in both treatment groups after 4 days and 4 months of treatment. After 4 months of treatment, a superimposable decrease in glycosylated hemoglobin A 1c concentrations was seen compared with baseline values (Gd, 7.9 ± 1.4% vs 6.5 ± 0.6%; Gl, 7.6 ± 1.5% vs 6.4 ± 0.9%). No significant changes were noted between treatment groups in body weight or in lipid or leptin levels. Total cell-associated insulin (TCAI) to monocytes increased significantly in the Gd group after 4 days and after 4 months compared with baseline (baseline, 2.13 ± 0.9%; 4 days, 3.14 ± 1.1%; 4 months, 4.33 ± 0.8%; P P P P P

Background Gestational diabetes mellitus (GDM) is an increasing problem world-wide. Lifestyle interventions and/or vitamin D supplementation might help prevent GDM in some women. Methods/design Pregnant women at risk of GDM (BMI≥29 (kg/m2)) from 9 European countries will be invited to participate and consent obtained before 19+6 weeks of gestation. After giving informed consent, women without GDM will be included (based on IADPSG criteria: fasting glucose Discussion DALI is a unique Europe-wide randomised controlled trial, which will gain insight into preventive measures against the development of GDM in overweight and obese women. Trial registration ISRCTN70595832

During pregnancy, complex changes occur in lipid profiles. From the 12th week of gestation, phospholipids, cholesterol (total, LDL, HDL), and triglycerides (TG) increase in response to estrogen stimulation and insulin resistance. Transition to a catabolic state favors maternal tissue lipid use as energy sources, thus sparing glucose and amino acids for the fetus. In addition, maternal lipids, that is, cholesterol, are available for fetal use in building cell membranes and as precursor of bile acids and steroid hormones. It is also required for cell proliferation and development of the growing body. Free-fatty acids (FFA), oxidized in the maternal liver as ketone-bodies, represent an alternative fuel for the fetus. Maternal hypertriglyceridemia (vs. other lipids) has many positive effects such as contributing to fetal growth and development and serving as an energy depot for maternal dietary fatty acids. However, increased TG during pregnancy appears to increase risk of preeclampsia and preterm birth. Some have suggested that maternal hypertriglyceridemia has a role in increasing cardiovascular risk later in life. This chapter reviews lipid metabolism during pregnancy to elucidate its effect on fetal growth and its potential role in pregnancy-associated complications and future cardiovascular risk.

Gestational diabetes (GD) results from insufficient endogenous insulin supply. No information is available on features of islet cells in human GD. Herein, we describe several properties of islets from a woman with GD. Immunohistochemical stainings and EM analyses were performed on pancreatic samples. Islet isolation was achieved by enzymatic dissociation and density gradient centrifugation. Ex vivo insulin secretion was studied in response to fuel secretagogues. Control islets were obtained from matched non-pregnant, non-diabetic women. Total insulin positive area was lower in GD, mainly due to the presence of smaller islets. β-cell apoptosis and the presence of Ki67 positive islet cells were similar in GD and controls, whereas the amount of insulin positive cells in or close to the ducts was decreased in GD. Ex vivo insulin secretion did not differ between GD and non-pregnant, non-diabetic islets. These findings suggest that in this case of human GD there might mainly be a defect of β-cell amount, not due to increased apoptosis, but possibly to insufficient regeneration.

Fetal overgrowth is the most important complication of gestational (GDM) and pregestational diabetes mellitus.We correlated maternal glucose profiles, as detected by continuous glucose monitoring (CGM), with fetal growth parameters for 80 pregnant women (32 with type 1 diabetes, 31 with GDM, and 17 healthy controls). Glucose profiles were monitored in the first, second, and third trimesters of pregnancy for type 1 diabetes women and in the second and third trimesters for GDM women and controls. To analyze glycemic variability, we considered the mean amplitude of glycemic excursion, mean glycemia, the continuous overlapping net glycemic action (CONGA), the SD, the High Blood Glucose Index (HBGI), the Low Blood Glucose Index, and the interquartile range (IQR).Mean age was the same for the three groups. Prepregnancy body mass index was higher for the women with diabetes (GDM and type 1) than for controls. The newborn's mean birth weight and ponderal index were higher, although not significantly so, for the women with diabetes than for controls. For the type 1 diabetes patients, ponderal index correlated with the HBGI in the first trimester, CONGA1 and IQR in the second, and mean glycemia and SD in the third. For GDM patients, ponderal index correlated with mean glycemia and the HBGI in the second trimester.Fetal exposure to glycemic variability and hyperglycemia seems to be important in determining fetal overgrowth in pregnant women with diabetes. Optimal glucose control and less glucose variability are needed as early as possible in both type 1 diabetes and GDM patients to ensure normal fetal growth.

Endothelial progenitor cells (EPCs) play a role in angiogenesis during pregnancy. The aim of this study was to evaluate circulating EPCs in pregnant women with gestational alterations of glucose tolerance. Glucose tolerance, insulin sensitivity and β-cell function were derived from oral glucose tolerance tests in 23 women with normal glucose tolerance (NGT), 18 with gestational impaired glucose tolerance (GIGT) and 24 with gestational diabetes mellitus (GDM). Circulating cells expressing CD34 in combination with CD133, kinase insert domain receptor (KDR) or both were quantified by flow cytometry. Women with GIGT and GDM had lower CD34+KDR+ and CD34+CD133 +KDR+ cells at 27±3.2 weeks’ gestation compared with NGT (ANOVA p+KDR+ and CD34+CD133+KDR+ cells were inversely correlated with the area-under-the-glucose-curve ( p

This study was planned to evaluate whether increased nuchal translucency (NT) thickness in the first trimester of gestation can be related to onset of gestational diabetes mellitus (GDM) during pregnancy.From January 2006 to August 2008, a group of 678 singleton pregnancies who had developed GDM has been selected as a study group among a total of 3966 pregnant women who had undergone first trimester screening for aneuploidies at 11-14 weeks of gestation. A group of 420 single pregnant women with physiological pregnancy were enrolled as control group. Both fetal structural and karyotype's anomalies were excluded in the two groups. NT was mesured by a Fetal Medicine Foundation certificated operator; GDM was diagnosed at 24-28 weeks of gestation following Carpenter and Coustan criteria. In the analyses of continuos variables, study and control group were compared by Student's t-test and Anova test.There was no significative difference (p = 0.585) between NT values in the study (mean = 1.56) and control group (mean = 1.54).NT thickness does not show a significative increase in those women who subsequently develop GDM. Therefore, NT assessment does not prove to be an useful ultrasound parameter for predicting GDM onset during pregnancy.

During pregnancy, complex changes occur in lipid profiles. From the 12th week of gestation, phospholipids, cholesterol (total, LDL, HDL), and triglycerides (TG) increase in response to estrogen stimulation and insulin resistance. Transition to a catabolic state favors maternal tissue lipid use as energy sources, thus sparing glucose and amino acids for the fetus. In addition, maternal lipids, that is, cholesterol, are available for fetal use in building cell membranes and as precursor of bile acids and steroid hormones. It is also required for cell proliferation and development of the growing body. Free-fatty acids (FFA), oxidized in the maternal liver as ketone-bodies, represent an alternative fuel for the fetus. Maternal hypertriglyceridemia (vs. other lipids) has many positive effects such as contributing to fetal growth and development and serving as an energy depot for maternal dietary fatty acids. However, increased TG during pregnancy appears to increase risk of preeclampsia and preterm birth. Some have suggested that maternal hypertriglyceridemia has a role in increasing cardiovascular risk later in life. This chapter reviews lipid metabolism during pregnancy to elucidate its effect on fetal growth and its potential role in pregnancy-associated complications and future cardiovascular risk.

We designed this study to assess the potential effects of physical activity and dietary habits on glucose tolerance during pregnancy.This is an observational study involving 268 women who underwent a 50-g oral glucose challenge test (GCT) at 27±6.9 week of gestation. Plasma glucose level at 1-h GCT ≥ 140 mg/dl was used to define abnormal glucose tolerance (AGT). Physical activity was evaluated using the short form of the International Physical Activity Questionnaire (IPAQ), while for dietary habits we used a food frequency questionnaire linked to a computerised program.One hundred five women had AGT (AGT+) and 163 had normal glucose tolerance (AGT−). There was no difference between the two groups in demographic and clinical data, with the exception of pre-pregnancy BMI and weight gain both higher in AGT+ women. Also, all parameters referring to physical activity energy and diet (Kcal and diet components) were not statistically different between the two groups. After a multivariate analysis, only pre-pregnancy BMI (F-value 9.264, p=0.002) remained an independent predictor of 1-h plasma glucose.Our study suggests that high pre-pregnancy BMI confers a substantially high risk of AGT, independently of lifestyle during pregnancy.

In women with previous gestational diabetes (pGDM), the risk of developing Type 2 diabetes is greatly increased, to the point that GDM represents an early stage in the natural history of Type 2 diabetes. In addition, in the years following the index pregnancy, women with pGDM exhibit an increased cardiovascular risk profile and an increased incidence of cardiovascular disease. This paper will review current knowledge on the metabolic modifications that occur in normal pregnancy, underlining the mechanism responsible for GDM, the link between these alterations and the associated long-term maternal complications. In women with pGDM, accurate follow-up and prevention strategies (e.g., weight control and regular physical exercise) are needed to reduce the subsequent development of overt diabetes and other metabolic abnormalities related to cardiovascular disease. Therefore, our paper will provide arguments in favor of performing follow-up programs aimed at modifying risk factors involved in the pathogenesis of Type 2 diabetes and cardiovascular disease.

The aim of this study was to evaluate the effects of continuous subcutaneous insulin infusion (CSII) on glycemic control and pregnancy outcomes in Type 1 diabetic pregnant women. We retrospectively evaluated 42 subjects, 20 treated with CSII and 22 with multiple dose insulin injections (MDI). The two groups were comparable for age, pre-pregnancy BMI, and primiparous rate, whereas women in the CSII group showed a tendency toward a longer diabetes duration (p = 0.06). Pre-pregnancy diabetic retinopathy and/or nephropathy were present in nine women of CSII and three of MDI. In all women metabolic control improved during pregnancy, without differences between the two groups and at the end of gestation HbA1c was 6.3 +/- 0.6 in CSII and 6.1 +/- 1.1% in MDI. Moreover, there were no differences in weight gain, whereas insulin requirement resulted significantly (p = 0.009) lower in CSII than in MDI. We recorded only one severe hypoglycaemic episode in both groups. No cases of deteriorations of the chronic diabetic complications were observed. The delivery occurred at 36.4 +/- 2.2 weeks; birth weight, the rate of large for gestational age, and the parameters of foetal morbidity were similar in both groups. In conclusions, CSII and MDI are both effective in improving maternal glucose control and have both similar pregnancy outcomes.

Dr. Daniele: The case record presented here is that of D.S., a woman who is now 35 years. Her case report begins when she was 14 years (1987) at which time she underwent screening for diabetes because of her obesity (weight 95 kg, BMI 36 kg/m) and her family history of diabetes (mother and maternal grandmother). Based on her fasting glucose level (160 mg/dl), she was diagnosed with diabetes mellitus. At that time, her level of HbA1c was 7.8%. D.S. began treatment with a low calorie diet with which she obtained a moderate weight reduction (about 10–15 kg). During the following years, she has had several weight fluctuations until she reached 67 kg in 1995. Throughout that period, she had several medical visits, but there is no available information regarding her glucose levels. At 22 years of age (1996), she was admitted into the hospital following a hyperglycemic crisis, accompanied by polyuria and polydipsia. This hospitalization resulted in the diagnosis of insulin-dependent diabetes mellitus and subsequently, she began insulin treatment. On that occasion, diabetic retinopathy was found. The following years she saw an improvement in her glucose levels (HbA1c 6.5%) but a worsening of the retinopathy (diffuse microaneurysms, microhemorthages, and hard exudates) that required bilateral laser therapy. Concurrently, she developed a peripheral motor and sensory neuropathy, and then microalbuminuria but with preserved renal function. She continued insulin with four daily injections and maintained good metabolic control (HbA1c \ 6.5–7%), although her body weight rose continuously until she again reached 95 kg in 2000. In 2003, her HbA1c levels increased (7.8%) and she gained an additional 5 kg.

Objective This prospective study evaluated the impact of gestational diabetes on maternal and fetal outcome in a large cohort of women with gestational diabetes mellitus (GDM) followed up using standardized clinical criteria. Study design Between 1999 and 2003, we collected 3465 GDM women from 31 Italian regional obstetric or diabetes centers, recording the time and mode of delivery, gestational hypertension, pre-eclampsia, eclampsia, congenital malformations, and neonatal mortality, comparing findings with the Italian general pregnant population. Results The rate of cesarean sections was 34.9% and macrosomia 8.7% (33.2 and 7.4%, respectively, in the general population, p = ns). The stillbirth and neonatal mortality rates were no different in GDM patients and normal pregnancies (0.34% vs. 0.30%, p = 0.176 and 0.29% vs. 0.32%, p = 0.748), but the former had twice as many newborn with congenital malformations (2.05% vs. 0.89%, p

Background and aim To determine pregnancy outcome in women with type 1 and type 2 diabetes. Methods and results A prospective study was conducted in 33 centers in Italy between 1999 and 2003, mainly recording preterm delivery, stillbirths, neonatal mortality, congenital malformations and birthweight. Of the 668 women examined, 504 had type 1 diabetes and 164 had type 2. Pre-pregnancy counseling had been provided to 43.9% of the women who had type 1 diabetes and 29.1% of the women who had type 2 diabetes and correlated with a better HbA1c value throughout pregnancy. The preterm delivery rate was significantly higher in type 1 and 2 diabetics than in normal pregnant women and was related to HbA1c values higher than 8%, gestational hypertension, pre-eclampsia and the presence of retinopathy before pregnancy. The stillbirth and neonatal mortality rates were also higher in diabetic pregnant women (1.26% and 0.63%, respectively) than in Italian pregnancies in general (0.30% and 0.32%), and the same was true for major congenital malformations (4.9% for diabetic pregnancies, 0.86% for normal Italian pregnancies). Conclusions In our population, pregnancy in diabetic women was still associated with a high rate of stillbirths, neonatal mortality and congenital malformations. Unplanned pregnancies and non-optimal glycemia control may help explain the high rates of maternal and neonatal complications.

To determine if women with previous gestational diabetes mellitus (pGDM), a population at high risk for type 2 diabetes and metabolic syndrome (1), have signs of subclinical atherosclerosis, we measured carotid intimal-medial thickness (IMT) and multiple cardiovascular risk factors in 28 women with and 24 without pGDM (control group) 2 years after delivery. A 75-g 2-h oral glucose tolerance test was performed for assessment of glucose tolerance, area under the glucose curve (AUCgluc), insulin sensitivity index, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, oxidized LDL (oxLDL), C-reactive protein (CRP), adiponectin, and fibrinogen. Family history, anthropometric parameters, and blood pressure were recorded. IMT was measured at four segments of …

Background and aims The aims of this study were to establish the prevalence of metabolic syndrome (MS), in type 2 diabetes mellitus (DM), according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, and to assess the association of MS with other cardiovascular (CV) risk factors in these patients. Methods and results A cross-sectional study was conducted in 1610 patients with type 2 DM. Glycated hemoglobin A1c (HbA1c), total cholesterol, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), uric acid, fibrinogen, creatinine, and albumin/creatinine ratios were measured. The risk of coronary heart disease (CHD) was calculated using the UKPDS Risk Engine. Seventy percent of the diabetic population met the criteria for MS; central obesity and hypertension were the most common criteria. Subjects with MS had higher levels of HbA1c, LDL-C, non-HDL-C, uric acid, and fibrinogen compared to patients without MS. Similarly, microalbuminuria and a high triglyceride (Tg)/HDL-C ratio (a marker of small LDL-C) occurred more frequently in patients with MS. When patients with no history of CHD events were considered, mean CHD risk was greater in those with, than those without, MS. Conclusions MS is highly prevalent in type 2 DM and is commonly associated with non-traditional CV risk factors. The diagnosis of MS seems to confer additional CHD risk in patients with type 2 diabetes.

The aim of this article was to define the metabolic phenotype of pregnant women with one abnormal value (OAV) during an oral glucose tolerance test (OGTT) and to test whether OAV could be considered metabolically comparable to gestational diabetes mellitus (GDM) or a specific entity between GDM and normal pregnancy.After 100-g 3-h OGTTs, 4,053 pregnant women were classified as having GDM, OAV, or normal glucose tolerance (NGT). Those with OAV were subdivided into three subgroups: fasting hyperglycemia (one abnormal value at fasting during an OGTT), 1-h hyperglycemia (one abnormal value at 1 h during an OGTT [1h-OAV]), or 2- or 3-h hyperglycemia (one abnormal value at 2 or 3 h during an OGTT). As derived from the OGTT, we measured insulin sensitivity (insulin sensitivity index [ISI] Matsuda) and insulin secretion (homeostasis model assessment for the estimation of beta-cell secretion [HOMA-B], first- and second-phase insulin secretion). The product of the first-phase index and the ISI was calculated to obtain the insulin secretion-sensitivity index (ISSI).GDM was diagnosed in 17.9% and OAV in 18.7% of pregnant women; women with GDM and OAV were older and had higher BMI and serum triglyceride levels than those with NGT (all P0.05). Women with NGT had the highest ISI followed by those with OAV (-21.7%) and GDM (-32.1%). HOMA-B results were comparable with those for OAV and GDM but significantly (P0.01) lower than those for NGT; first- and second-phase insulin secretion appeared progressively reduced from that in women with NGT to that in women with OAV and GDM (P0.01). ISSI was higher in women with NGT than in women with either OAV (-34%) or GDM (-51.7%) (P0.001). Among OAV subgroups, the 1h-OAV subgroup showed the lowest ISSI (P0.05).OAV and GDM are clinically indistinguishable, and both groups are different from women with NGT. Women with GDM and OAV showed impaired insulin secretion and insulin sensitivity, although these defects are more pronounced in women with GDM. Compared with other OAV subgroups, 1h-OAV could be considered a more severe condition.

Background: The reference intervals for hemoglobin A1c (Hb A1c) in pregnant women without diabetes are not well defined, and few examples of reference intervals established by networks of different laboratories are available.Methods: Five Italian Diabetic Care Units were involved in the study. Data were collected from 445 pregnant women without diabetes, selected on the basis of glucose challenge test results, and from 384 nonpregnant control women. The Hb A1c measurements were performed with HPLC systems aligned to the Diabetes Control and Complications Trial. Plasma glucose measurements were also performed locally. Both Hb A1c and glucose measurements were harmonized by running appropriate external quality assessment schemes. The reference intervals were calculated in terms of nonparametric 2.5th to 97.5th percentiles with 0.90 confidence intervals.Results: The Hb A1c measurements were reproducible (CV = 2.0%) and accurate [mean (SE) difference from the target values, −0.10 (0.06)%]. Glucose measurements were also reproducible (mean CV = 3.2%) and accurate [difference from the target values, −0.01 (0.04) mmol/L]. To calculate common reference intervals, we merged the data collected in the different centers. The Hb A1c reference intervals were 4.0%–5.5% for pregnant nondiabetic women and 4.8%–6.2% for nonpregnant controls.Conclusions: Healthy pregnant women have lower Hb A1c concentrations than nonpregnant women. The reference intervals for Hb A1c in pregnant women should therefore be lower than those currently in use.

Women with previous gestational diabetes (pGDM) are at high risk of developing type 2 diabetes mellitus. The aim of this study was to evaluate insulin action and insulin secretion in women with pGDM.One hundred and fifty-three pGDM women and 45 with normal glucose tolerance during pregnancy (controls) were studied 1-3years after delivery. Insulin sensitivity (ISI) and beta-cell secretory capacity (beta-index) were derived from 75-g OGTT. Disposition Index was calculated as the product of beta-index and ISI. One hundred and twenty-two pGDM were normotolerant (NGT) and 31 had impaired glucose regulation (IGR) i.e. impaired glucose tolerance and/or impaired fasting glucose. NGT-pGDM, as compared to controls, had significant impairment in insulin action (ISI: 5.46+/-2.81 vs. 7.38+/-3.68, P0.01) and insulin secretion (beta-index: 4.68+/-1.01 vs. 5.24+/-0.82 pmol/min/m(2); P0.01). A further impairment was apparent in IGR-pGDM for beta-index (4.16+/-1.09; P0.05). The disposition index was reduced in NGT-pGDM as compared to controls (33.9%) and further reduced in IGR-pGDM (28.6%, vs. NGT-pGDM; ANOVA P0.001). In women of normal weight, ISI and beta-index were significantly (P0.01) impaired in NGT-pGDM compared to controls and further reduced in IGR-pGDM, although a more pronounced defect in insulin secretion was apparent in these women (beta-index: 4.02+/-0.9; P0.05).Normotolerant women with pGDM show both impairment in insulin secretion and action irrespective of body weight. A more pronounced defect in insulin secretion seems to characterize normal weight women while a more prominent defect in insulin action is found in overweight women.

Gestational diabetes mellitus (GDM) is associated with increased risk of maternal and neonatal morbidity with macrosomia being the most common neonatal complication (1). The risk of macrosomia and/or disproportionate fetal growth is closely related to 1-h postprandial glucose concentration (2). Therefore, the treatment of GDM should be aimed at normalizing maternal glycemia including the early postprandial response. Insulin therapy is needed whenever strict normoglycemia cannot be achieved by medical nutritional therapy alone (3). Because of their pharmacokinetic properties, short-acting insulin analogs (Insulin Aspart [ASP] and Insulin Lispro [LIS]) could be more effective in pregnancy than human regular insulin (HI) (4). Nevertheless, data …

In order to evaluate the prevalence of gestational diabetes mellitus (GDM) and the presence of risk factors for GDM, we conducted a retrospective study of a cohort of Italian women. In addition, we compared universal versus selective screening to validate the ADA's recommendations in our population. From June 1st, 1995 to December 31st, 2001, universal screening for GDM was performed in 3950 women. The glucose challenge test (GCT) was positive (GCT+) in 1389 cases (35.2%). The 1-h glucose level after GCT enabled us to diagnose GDM directly in 24 pregnant women. Oral glucose tolerance test (OGTT) was performed in 1221 GCT+ women (144 cases with GCT+ dropped out) and GDM was diagnosed in 284 (23.2%) of them. OGTT was also performed in 391 randomly chosen, women from the GCT negative (GCT-) group. In this last group 25 (6.3%) women had GDM. Thus, the total number of subjects with GDM was 333 out of 3806 with a prevalence of 8.74% in the entire cohort. Assuming that the rate of GDM observed in the random sample of GCT- women is applicable to the whole group of 2561 GCT- women, then 161 GCT- patients could also have GDM. This will further increase the estimated prevalence for the whole cohort up to 12.3% (i.e. 469 out of 3806 pregnant women). There were 236 (5.6%) women with a low risk for GDM (normal weight, age less than 25 years and without a family history of diabetes). In this group we found 34 cases and five cases with positive screening test and GDM, respectively. Thus, if we excluded low risk women from the screening test, as suggested by ADA recommendations, only five women with GDM would have been missed. However, about 95% of our population were at medium or high risk for GDM and, therefore, would have been screened. The rate of GDM was significantly higher in women with a positive history of diabetes, increasing age, previous pregnancies, pre-pregnancy overweight and short stature. After logistic regression analysis, GDM diagnosis was significantly correlated with age (P