Search

Despite evidence that pregnancy planning improves outcomes, in Italy, as in many other countries worldwide,50% of women with diabetes prepare their pregnancy. The aim of this study was to document training and knowledge on diabetes and pregnancy (DP) among diabetes professionals.We administered an anonymous online questionnaire, focused on diabetes and pregnancy planning, to diabetes team members. Between Nov-2017 and Jul-2018, n = 395 professionals (60% diabetes/endocrinology/internal medicine specialists, 28% fellows) completed the survey. Fifty-nine percent of the specialists, mainly (78%) those completing their fellowship after 2006, reported having received training on DP during fellowship. Considering specialists reporting training, 43% correctly identified fetal risks of inadequate preconceptional glucose control and 55% maternal risks, 38% identified risks associated with overweight/obesity, and 39% would prescribe hormonal contraception to women with diabetes only if glucose control is good.The results of our survey suggest the need to improve training and awareness of professionals in the area of diabetes and pregnancy.

To evaluate efficacy, renal safety and tolerability of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in a cohort of patients with type 2 diabetes (T2DM) aged ≥65 years.We retrospectively evaluated 364 elderly individuals with T2DM starting SGLT2i from June 2015 to June 2018. Patients were divided into 2 subgroups based on median age (70 years). Linear mixed effect models were used to estimate changes in glycated hemoglobin (HbA1c), body mass index (BMI), and glomerular filtration rate (eGFR). SGLT2i discontinuation rate and causes of treatment interruption were also recorded.A significantly higher percentage of patients achieved HbA1c7.5% (46.7% vs. 31.6%, p0.01) and8.0% (68.9% vs. 47.2%, p0.01) compared to baseline. Each year of therapy was associated with an average HbA1c decrease of 0.34% (p0.01) and BMI loss of 0.71 kg/mEfficacy, renal safety and tolerability of SGLT2i were similar in people70 compared to 65-70 years of age, suggesting that a wider use should not be worried even in the elderly. However, some caution must be paid to the occurrence of persistent eGFR decline and orthostatic hypotension, especially in patients70 years old.

Molecular variant interpretation lacks disease gene-specific cohorts for determining variant enrichment in disease versus healthy populations. To address the molecular etiology of retinal degeneration, specifically the PRPH2-related retinopathies, we reviewed genotype and phenotype information obtained from 187 eyeGENE® participants from 161 families. Clinical details were provided by referring clinicians participating in the eyeGENE® Network. The cohort was sequenced for variants in PRPH2. Variant complementary DNA clusters and cohort frequency were compared to variants in public databases to help us to determine pathogenicity by current American College of Medical Genetics and Genomics/Association for Molecular Pathology interpretation criteria. The most frequent variant was c.828+3A>T, which affected 28 families (17.4%), and 25 of 79 (31.64%) variants were novel. The majority of missense variants clustered in the D2 intracellular loop of the peripherin-2 protein, constituting a hotspot. Disease enrichment was noted for 23 (29.1%) of the variants. Hotspot and disease-enrichment evidence modified variant classification for 16.5% of variants. The missense allele p.Arg172Trp was associated with a younger age of onset. To the best of our knowledge, this is the largest patient cohort review of PRPH2-related retinopathy. Large disease gene-specific cohorts permit gene modeling for hotspot and disease-enrichment analysis, providing novel variant classification evidence, including for novel missense variants.

Introduction: In persons with type 1 diabetes (T1D) insulin dosing can be adjusted based on trend arrows derived from continuous glucose monitoring (CGM). We propose a slide rule with narrower blood glucose intervals and more classes of insulin sensitivity than are available in current models. Methods: The slide rule was tested in silico, in which a meal was simulated in 100 virtual subjects and the insulin bolus was calculated either in the standard way based on the insulin-to-carbohydrate ratio and the correction factor or according to the slide rule, following which the percentage time spent in range (70–180 mg/dl; %TIR), hypoglycemia (< 70 mg/dl; %THYPO), and hyperglycemia (> 180 mg/dl; %THYPER) was compared between the methods during the 4 h after the meal. Slide rule performance was also tested in real life by analyzing the same variables at during the 4 h postprandial period in 27 individuals with T1D. Only meals starting while the rate of change was at least 1 mg/dl per minute (increasing or decreasing) were considered for analysis. Results: In silico, when the preprandial trend arrow was increasing, our slide rule reduced %THYPER and increased %TIR (p < 0.05), whereas when the preprandial trend arrow was decreasing, it reduced %THYPO and slightly increased %THYPER (p < 0.05). In real life, our slide rule kept subjects on target for 70.8 and 91.6% of postprandial time when preprandial trend arrows were increasing or decreasing, respectively. Conclusion: The proposed slide rule performed well both in silico and in real life, suggesting that it could be safely adopted by individuals with T1D to improve glucose control.

The short-term adverse effects of anticancer drugs (AD) in patients with type 2 diabetes (T2D) are poorly studied and their management still represents an important challenge for clinicians. We carried out a retrospective single-center study in 168 patients with T2D and cancer, evaluating both the short-term effects of first-line AD on glycemic control and chronic diabetes complications. Average glycated hemoglobin significantly increased after AD compared to values before treatment (7.5 vs. 7.1%, p < 0.005). In 46.4% of patients, diabetes therapy had to be potentiated, in most cases (82.1%) by shifting to insulin. The use of alkylating agents and high-dose glucocorticoids predicted the need to potentiate diabetes therapy. After AD transaminase values significantly increased, whereas the estimated glomerular filtration rate decreased (in 12.5%

BackgroundMaternal high blood glucose during pregnancy increases the risk for both maternal and fetal adverse outcomes. The mechanisms underlying the regulator effects of hyperglycemia on placental development and growth have not been fully illustrated yet. The placenta expresses high amounts of both insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R). It has been reported that the placenta of diabetic women has structural and functional alterations and the insulin/IGF system is likely to play a role in these changes. The aim of the present study was to measure the content of IR and IGF-1R and their phosphorylation in the placenta of women with type 1 diabetes mellitus (T1D) or with gestational diabetes mellitus (GDM) compared to women with normal glucose tolerance (NGT) during pregnancy.MethodsPlacental tissues were obtained from 80 Caucasian women with a singleton pregnancy. In particular, we collected placenta samples from 20 T1D patients, 20 GDM patients and 40 NGT women during pregnancy. Clinical characteristics and anthropometric measures of all women as well as delivery and newborn characteristics were recorded. Patients were also subdivided on the basis of peripartum glycemia either ≥90 mg/dl or ResultsIn T1D patients, a higher rate of adverse outcomes was observed. Compared to the GDM women, the T1D group showed significantly higher average capillary blood glucose levels at the third trimester of pregnancy and at peripartum, and higher third-trimester HbA1c values. In both T1D and GDM women, HbA1c values during pregnancy correlated with glucose values in the peripartum period (R-squared 0.14, p=0.02). A positive correlation was observed between phosphorylation of placental IR and the glucose levels during the third trimester of GDM and T1D pregnancy (R-squared 0.21, p=0.003). In the placenta of T1D patients, IGF-1R phosphorylation and IR isoform A (IR-A) expression were significantly increased (p=0.006 and p=0.040, respectively), compared to the NGT women. Moreover, IGF-1R phosphorylation was significantly increased (p90 mg/dl, while IR-A expression was increased in those with peripartum blood glucose higher than 120 mg/dl (p=0.046).ConclusionsTo the best of our knowledge, our study represents the first one in which an increased maternal blood glucose level during pregnancy is associated with an increased IGF-1R phosphorylation and IR-A expression in the placenta. Both these mechanisms can promote an excessive fetal growth.

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

Objective Type 1 diabetes (T1D) is frequently associated with other autoimmune diseases (AIDs). Although most of T1D patients are sporadic cases (S-T1D), 10% to 15% have a familial form (F-T1D) involving 2 or more first-degree relatives. This study evaluated the effect of T1D family aggregation and age onset on AIDs occurrence. Methods In this observational, cross-sectional, case-control, single center study, we enrolled 115 F-T1D and 115 S-T1D patients matched for gender, age, T1D age onset, and duration. With respect to T1D age onset (before or after 18 years), both groups were further subdivided into young- or adult-onset F-T1D and young- or adult-onset S-T1D. The presence of organ-specific antibodies and/or overt AIDs was evaluated. Results The F-T1D group had a higher percentage of AIDs (29.8% vs 18.4%, P = .04) and a significant earlier onset of AIDs at Cox regression analysis (P = .04) than the S-T1D group. Based on multivariate analysis, the adult-onset F-T1D subgroup had the highest prevalence of both additional organ-specific antibodies (60.5%) and overt AIDs (34.9%), whereas the adult S-T1D subgroup was the least frequently involved (29.1% and 12.7%, respectively). In F-T1D patients, offsprings develop T1D and AIDs earlier than their parents do. Conclusions In T1D patients, familial aggregation and adult-onset of T1D increase the risk for coexistent AIDs. These clinical predictors could guide clinicians to address T1D patients for the screening of T1D-related AIDs.

Good glycemic control is crucial to reduce the risk of adverse pregnancy outcomes. Our aim was to evaluate the efficacy of Flash Glucose Monitoring (FGM) on glucose control in women with pregestational diabetes.Forty women with inadequately controlled type 1 (T1D, n = 34) and type 2 (T2D, n = 6) diabetes at conception were randomly assigned to two arms: the Flash Glucose group (FG, n = 21) using FGM, and the control group (CG, n = 19) using self-monitoring of blood glucose (SMBG). Glycated hemoglobin (HbA1c, %), time in (TIR), below (TBR) and above (TAR) range, glucose variability as well as the occurrence of maternal and neonatal adverse outcomes, were evaluated. HbA1c decreased significantly (p 0.01) and similarly (-0.65 ± 0.7 vs. -0.67 ± 0.8 for FG and CG, respectively; p = 0.89) in both groups during pregnancy. HbA1c reduction was positively associated with the number of daily FGM scans (p 0.01). TBR (12.1 ± 2.0% vs. 19.6 ± 3.9%, p = 0.04) and the mean of the daily serum glucose difference (MODD) index (59.1 ± 5.4 vs. 77.7 ± 4.6, p = 0.02) were significantly lower in FG at second trimester. The rates of perinatal adverse outcomes were not different in the two studied groups.In women with pregestational diabetes, FGM and SMBG had similar efficacy on glucose control during pregnancy. FGM showed additional advantages in terms of TBR and glucose variability. Achievement of good metabolic results depended on the adequate use of glucose sensor.At ClinicalTrials.gov as NCT04666818 on December 14, 2020.

Genetic testing in a multisite clinical trial network for inherited eye conditions is described in this retrospective review of data collected through eyeGENE(®), the National Ophthalmic Disease Genotyping and Phenotyping Network. Participants in eyeGENE were enrolled through a network of clinical providers throughout the United States and Canada. Blood samples and clinical data were collected to establish a phenotype:genotype database, biorepository, and patient registry. Data and samples are available for research use, and participants are provided results of clinical genetic testing. eyeGENE utilized a unique, distributed clinical trial design to enroll 6,403 participants from 5,385 families diagnosed with over 30 different inherited eye conditions. The most common diagnoses given for participants were retinitis pigmentosa (RP), Stargardt disease, and choroideremia. Pathogenic variants were most frequently reported in ABCA4 (37%), USH2A (7%), RPGR (6%), CHM (5%), and PRPH2 (3%). Among the 5,552 participants with genetic testing, at least one pathogenic or likely pathogenic variant was observed in 3,448 participants (62.1%), and variants of uncertain significance in 1,712 participants (30.8%). Ten genes represent 68% of all pathogenic and likely pathogenic variants in eyeGENE. Cross-referencing current gene therapy clinical trials, over a thousand participants may be eligible, based on pathogenic variants in genes targeted by those therapies. This article is the first summary of genetic testing from thousands of participants tested through eyeGENE, including reports from 5,552 individuals. eyeGENE provides a launching point for inherited eye research, connects researchers with potential future study participants, and provides a valuable resource to the vision community.

Obesity represents a major risk factor for metabolic disorders, but some individuals, &ldquo, metabolically healthy&rdquo, (MHO), show less clinical evidence of these complications, in contrast to &ldquo, metabolically unhealthy&rdquo, (MUO) individuals. The aim of this cross-sectional study is to assess the prevalence of the MHO phenotype in a cohort of 246 overweight/obese Italian children and adolescents, and to evaluate their characteristics and the role of insulin resistance. Homeostasis model assessment&ndash, insulin resistance (HOMA-IR), insulin sensitivity index (ISI), insulinogenic index (IGI) and disposition index (DI) were all calculated from the Oral Glucose Tolerance Test (OGTT). MHO was defined by either: (1) HOMA-IR &lt, 2.5 (MHO-IRes), or (2) absence of the criteria for metabolic syndrome (MHO-MetS). The MHO prevalence, according to MHO-MetS or MHO-IRes criteria, was 37.4% and 15.8%, respectively. ISI was the strongest predictor of the MHO phenotype, independently associated with both MHO-IRes and MHO-MetS. The MHO-MetS group was further subdivided into insulin sensitive or insulin resistant on the basis of HOMA-IR (either &lt, or &ge, 2.5). Insulin sensitive MHO-MetS patients had a better metabolic profile compared to both insulin resistant MHO-MetS and MUO-MetS individuals. These data underscore the relevance of insulin sensitivity to identifying, among young individuals with overweight/obesity, the ones who have a more favorable metabolic phenotype.

Background: Continuous subcutaneous insulin infusion (CSII) is increasing worldwide, mostly because of improved technology. The aim of this study was to evaluate the current status of CSII in Italy. Materials and Methods: Physicians from 272 diabetes centers received a questionnaire investigating clinical features, pump technology, and management of patients on CSII. Results: Two hundred seventeen centers (79.8%) joined the study and, by the end of April 2013, gave information about 10,152 patients treated with CSII: 98.2% with type 1 diabetes mellitus, 81.4% adults, 57% female, and 61% with a conventional pump versus 39% with a sensor-augmented pump. CSII advanced functions were used by 68% of patients, and glucose sensors were used 12 days per month on average. Fifty-eight percent of diabetes centers had more than 20 patients on CSII, but there were differences among centers and among regions. The main indication for CSII was poor glucose control. Dropout was mainly due to pump wearability or nonoptimal glycemic control. Twenty-four hour assistance was guaranteed in 81% of centers. A full diabetes team (physician+ nurse + dietician + psychologist) was available in 23% of adult-care diabetes centers and in 53%of pediatric diabetes units. Conclusions: CSII keeps increasing in Italy. More work is needed to ensure uniform treatment strategies throughout the country and to improve pump use.

Background and aim: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII). Methods and results: Questionnaires investigating the organisation of diabetes care centres, individuals’ clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. 18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis. Conclusions: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia. Clinical trial registration number: NCT 02620917 (ClinicalTrials.gov).

Aims To estimate the prevalence of chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) in Finnish primary healthcare, and to evaluate the screening for CKD and the proportions of patients receiving antihyperglycemic and cardiovascular preventive medication. Material and methods T2D patients treated at the Rovaniemi Health Center, Finland during the years 2015–2019. Data included patient characteristics, blood pressure, HbA1c, lipid levels, kidney function and albuminuria, and medications prescribed. CKD was defined as estimated glomerular filtration rate (eGFR) Results The study population comprised of 5112 T2D patients with a mean (SD) age of 66.7 (13.0) years. Of these, 60.2% were screened for CKD with both eGFR and albuminuria, and 30.1% of these patients had CKD. The prevalence of moderately increased and severely increased albuminuria was 19.6% and 3.2%, respectively. A total of 57.0% of the study population received angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). Conclusions Screening for CKD with both recommended measures (eGFR and albuminuria) was insufficiently performed among this T2D population. Additionally, just over half of the study population had been prescribed ACE inhibitors or ARB. These results suggest an incongruity between the gold standard of diabetes care and real-world clinical practice.

Quality assurance and quality control (QA/QC) procedures are vital to good biorepository management. The National Eye Institute (NEI) core CLIA-certified laboratory of the eyeGENE(®) Network receives blood from individuals with inherited eye conditions and isolates DNA for clinical genetic diagnostic testing and research. Clinical genetic test results are returned to the affected individuals, making it imperative that sample integrity is preserved throughout laboratory processing. A clinically validated, short tandem repeat (STR)-based approach, termed Sample Confirmation Testing (SCT), was developed to ensure that no significant laboratory errors occurred during processing. SCT uses modified protocols from commercial kits to create and compare STR profiles for each participant's original blood and derived DNA. This QA/QC procedure has been performed on 47% of the more than 6000 participants in the eyeGENE Biorepository and has identified significant laboratory errors in 0.4% of samples tested. SCT improves the quality of the data returned to affected individuals and the data distributed to researchers using eyeGENE samples by ensuring the integrity of the samples and aiding in curation of the biorepository. This approach serves as a model for other repositories to improve sample quality and management procedures.

Insulin degludec is an extra‐long‐acting insulin analog that allows for enhanced efficacy and flexibility in the injection time. However, it is not approved for use during pregnancy. We report the pregnancy outcome and newborn conditions in two women with type 1 diabetes who continued preconception degludec treatment during embryogenesis. No pregnancy complication or congenital neonatal malformation was observed. Both babies presented with hypoglycemia and required neonatal intensive care unit admission. Degludec treatment did not cause adverse effects in the mothers or malformations in the newborns. The observed neonatal complications were probably independent of early pregnancy degludec treatment.

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.

eyeGENE® is a genomic medicine initiative created to facilitate research into the causes and mechanisms of inherited eye diseases and accelerate pathways to treatments. Through collaborations with clinics across the United States and Canada, eyeGENE® recruited approximately 6400 participants. To date, eyeGENE® has returned more than 5800 clinical genetic test results to participants and has granted 22 research studies controlled access to clinical and genetic data, DNA samples, and/or individuals consented to participate in research and clinical trials. These studies have identified new genes, improved our understanding of inherited eye disease, and validated new molecular diagnostic technology. eyeGENE® can serve as a model for creating a research resource to advance the study of rare, inherited diseases.

The aim of this randomized study was to examine the efficacy of two high intensity educational programs: the conversation maps-based (CM™) education and the individual education (IE), compared to usual care (UC) in a cohort of type 2 diabetic (T2DM) patients. Ninety T2DM outpatients (30 per group) were randomized and 79 finished the study and were analyzed. The CM™ and IE groups received four educational sessions at 0, 4, 8 and 12 weeks, while the UC group received two brief individual sessions at 0 and 12 weeks. We evaluated glycemic control (HbA1c), diabetes treatment, body mass index (BMI) and carried out a questionnaire survey at three time points (before intervention, at 12 and at 32 weeks) to assess patients’ satisfaction, attitudes toward diabetes and dietary knowledge. All the three groups showed a significant and comparable reduction of both HbA1c and BMI. Diabetes therapy needed to be reinforced in a higher percentage of cases (39.3%) among UC patients compared to the IE (14.8%; p = 0.04) and the CM™ (8.3%; p = 0.01) groups. At 32 weeks Diabetes Treatment Satisfaction (DTSQ Q1 + Q4–8) significantly improved in the CM™ group (25.8 ± 4.5 vs. 22.4 ± 6.0; p

The aim of this review is to provide general suggestions on physical activity (PA) in pre-gestational and gestational diabetes mellitus (GDM) and encourage women to take part in safe and effective activities throughout pregnancy, in the absence of other contraindications. PA before and during pregnancy and in postpartum has many positive effects on the mother, as it could reduce the risk of GDM, excessive weight gain and lower back pain and also prevents, in the postpartum, diabetes mellitus. It may also reduce the duration of labour and complications at childbirth, fatigue, stress, anxiety and depression, thereby leading to an improved sense of wellbeing. Clinically, it is thought to help prevent preeclampsia and premature birth even though RCTs provide conflicting evidence with regard to the prevention of GDM. The main reason for this rests on the fact that the majority of clinical trials have not been able to replicate the preventive effect of PA on the onset of GDM, such as the different adherence of the patient to PA. Herein, we survey the literature regarding exercise and PA on GDM prevention and treatment as well as on clinical outcomes in pre-GDM in pregnancy. On the basis of the current literature, we also present a series of general recommendations and suggestions on PA and exercise training in pregnancy among both diabetic patients and those at risk for GDM.

Recent evidence indicates that people with normal glucose tolerance (NGT) but 1-h post-load plasma glucose (1-h OGTT) ≥ 155 mg/dl have an increased risk for developing Type 2 diabetes mellitus (T2DM), determining a new risk category with deeper metabolic impairment. The aim of this study was to identify, among women with gestational diabetes (GDM), which alterations at OGTT during pregnancy are more frequently associated with 1-h OGTT ≥ 155 mg/dl at post-partum examination. Among 297 women affected by GDM, we retrospectively evaluated 244 resulted NGT after delivery. Based on post-partum glucose levels at 1-h OGTT, these people were divided into 188 cases (77.0%) with 1-h OGTT

To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59–3.87), large for gestational age (OR 3.99, 95% CI 2.40–6.63), fetal malformation (OR 2.66, 95% CI 1.00–7.18), and respiratory distress (OR 4.33, 95% CI 1.33–14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00–2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04–3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02–2.27) and obesity (OR 1.62, 95% CI 1.04–2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21–2.33 for obese; OR 1.38 95% CI 1.03–1.87 for overweight). A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity.

Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is one of the most devastating of adverse drug reactions (ADRs) and was, until recently, essentially unpredictable. With the discovery of several risk alleles for drug-induced SJS/TEN and the demonstration of effectiveness of screening in reducing incidence, the stage is set for implementation of preventive strategies in populations at risk. Yet much remains to be learned about this potentially fatal complication of commonly used drugs.

The present research assessed how engaging in bilateral eye movements influences brain activity. Participants had their resting-state brain activity recorded with electroencephalography (EEG) before and after they performed 30 s of bilateral eye movements or a center-control manipulation. We assessed differences in change scores for absolute power and coherence between the eye-movement and center-control conditions. A main effect for handedness was present for EEG power in the theta and beta frequency bands, with inconsistent-handed participants displaying a greater increase than consistent-handed participants in both frequency bands. For theta, the increase in power for inconsistent handers was specific to participants in the bilateral eye-movement condition, whose increase in theta power exceeded the increase in theta power for consistent-handed participants regardless of condition. In contrast, for coherence, a main effect for condition was present for the delta frequency band, with participants in the control condition exhibiting a significant drop in posterior delta coherence pre to post. We suggest that the maintenance of posterior delta coherence over time may be an important factor in sustaining attention. Further, the malleability of EEG power for inconsistent-handed participants reveals the importance of individual-differences variables in the potential for behavioral manipulations to change brain activity.

Molecular genetics and genomics are revolutionizing the study and treatment of inherited eye diseases. In recognition of the impact of molecular genetics on vision and ophthalmology, the National Eye Institute established the National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE®) as a multidirectional research initiative whereby a clinical component for patients diagnosed with inherited eye disease fosters research into the causes and mechanisms of these ophthalmic diseases. This is accomplished by broadening access to genetic diagnostic testing and maintaining a repository of DNA samples from clinically characterized individuals and their families to allow investigations of the causes, interventions, and management of genetic eye disorders. The eyeGENE® Network currently includes Clinical Laboratory Improvement Amendments (CLIA)-certified diagnostic laboratory partners, over 270 registered clinical organizations with 500 registered users from around the United States and Canada, and is now testing approximately 100 genes representing 35 inherited eye diseases. To date, the Network has received 4400 samples from individuals with rare inherited eye diseases, which are available for access by the vision research community. eyeGENE® is a model partnership between the U.S. federal government, eye health care providers, CLIA-approved molecular diagnostic laboratories, private industry, and scientists who represent a broad research constituency.

Molecular genetics is revolutionizing the diagnosis and treatment of inherited eye diseases. The National Eye Institute of the National Institutes of Health (NIH), in an effort to facilitate future basic and clinical research in inherited eye disease, created The National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE). This review describes the process and utility of the eyeGENE program as it relates to ophthalmic clinical practice.Over the last few years, genetic testing of specific genes associated with inherited eye conditions is becoming the standard practice. Vision research and human clinical trials relying on molecular genetic testing of individuals with inherited eye conditions are becoming more common. Eye healthcare professionals must consider the options to assist patients in obtaining genetic testing results and locating trials or studies that may have benefit.eyeGENE is a DNA repository and patient registry for inherited eye diseases coupled to phenotypic descriptors and molecular genetic information. Through eyeGENE, healthcare professionals throughout the United States and Canada can obtain Clinical Laboratory Improvement Amendments-certified clinical molecular genetic results on their patients. Researchers may request access to a de-identified database of phenotype and genotype information about eyeGENE participants and DNA aliquots for their research studies. eyeGENE also offers participants the option of being included in a patient registry, whereby they may be re-contacted if an approved clinical study for which they might qualify is offered.

We recently reported that a high BMI and high waist circumference prevalence is present in Sicilian children and that the male gender is associated with a significant risk of obesity. Early-life and parent-related risk factors were investigated 1521 Sicilian children (752 females and 769 males, aged 9.0–14.0 years) to identify biological and environmental factors that can contribute to obesity onset. Anthropometric measurements of children, their urban vs rural area provenience, birth weight and neonatal feeding were collected. In addition, the BMI and educational level of their parents and the perception of their child weight status were investigated. In the study cohort, the prevalence of overweight and obesity was 27.2 and 14.1 %, respectively, significantly (p

Cataract is the world's leading cause of blindness and a disease for which no efficacious medical therapy is available. To screen potential anti-cataract agents, a lens organ culture model system was used. Opacification of lenses maintained in culture was induced by specific insults including H2O2 or the cataractogenic sugar xylose. Potential anti-cataract agents were added to the culture medium and their ability to inhibit opacification and certain biochemical changes associated with the opacification were assessed. Among the compounds tested, Tempol-H, the hydroxylamine of the nitroxide Tempol, gave the most promising results. It significantly inhibited opacification of rat lenses in an H2O2-induced cataract system as well as opacification of rhesus monkey lenses induced by xylose. Tempol-H inhibited the loss of glutathione, the leakage of protein, and decreases in the ability of cultured lenses to accumulate 3H-choline from the medium, all of which were associated with the development of lens opacification. The antioxidative activity of Tempol-H and its ability to re-dox cycle make it an attractive candidate as a therapeutic agent for the prevention of aging-related cataract.

Background and aims: Due to the worldwide increasing prevalence of diabetes (DM), patients with both diabetes and Graves' disease (GD) have become more frequent. Sporadic reports indicate that Graves' orbitopathy (GO), a GD complication that affects orbital soft tissues, can be severe in DM patients. The relationship between these diseases is not well understood. This study aims at evaluating the association of GD and GO with autoimmune and non- autoimmune diabetes (DM) and to assess diabetic features that influence GD and GO prevalence and severity. Methods and results: This retrospective study evaluated GD, GO and DM association in 1211 consecutive GD patients (447 with GO and 77 with DM). A case-control study was carried out to evaluate DM relationship with GO severity by comparing at 1:2 ratio GO patients with or without DM. A strong association was found between GD and T1DM (p Z 0.01) but not T2DM. Instead, the presence of GO was strongly associated with T2DM (p Z 0.01). Moreover, GO was more frequently severe in GD patients with T2DM (11/30 or 36.6%) than in those without T2DM (1/60 or 1.7%, p Z 0.05). T2DM was the strongest risk factor for severe GO (OR Z 34.1 vs. 4.4 p < 0.049 in cigarette smokers). DM duration, obesity and vascular complications, but not metabolic control were significant determinants of GO severity. Conclusions: GD is associated with T1DM but not with T2DM, probably because of the common autoimmune background. GO, in contrast, is more frequent and severe in T2DM, significantly associated with obesity, diabetes duration and diabetic vasculopathy but not metabolic control.

Purpose To analyze the genetic test results of probands referred to eyeGENE with a diagnosis of hereditary maculopathy. Methods Patients with Best macular dystrophy (BMD), Doyne honeycomb retinal dystrophy (DHRD), Sorsby fundus dystrophy (SFD), or late-onset retinal degeneration (LORD) were screened for mutations in BEST1, EFEMP1, TIMP3, and CTRP5, respectively. Patients with pattern dystrophy (PD) were screened for mutations in PRPH2, BEST1, ELOVL4, CTRP5, and ABCA4; patients with cone-rod dystrophy (CRD) were screened for mutations in CRX, ABCA4, PRPH2, ELOVL4, and the c.2513G>A p.Arg838His variant in GUCY2D. Mutation analysis was performed by dideoxy sequencing. Impact of novel variants was evaluated using the computational tool PolyPhen. Results Among the 213 unrelated patients, 38 had BMD, 26 DHRD, 74 PD, 8 SFD, 6 LORD, and 54 CRD; six had both PD and BMD, and one had no specific clinical diagnosis. BEST1 variants were identified in 25 BMD patients, five with novel variants of unknown significance (VUS). Among the five patients with VUS, one was diagnosed with both BMD and PD. A novel EFEMP1 variant was identified in one DHRD patient. TIMP3 novel variants were found in two SFD patients, PRPH2 variants in 14 PD patients, ABCA4 variants in four PD patients, and p.Arg838His GUCY2D mutation in six patients diagnosed with dominant CRD; one patient additionally had a CRX VUS. ABCA4 mutations were identified in 15 patients with recessive CRD. Conclusions Of the 213 samples, 55 patients (26%) had known causative mutations, and 13 (6%) patients had a VUS that was possibly pathogenic. Overall, selective screening for mutations in BEST1, PRPH2, and ABCA4 would likely yield the highest success rate in identifying the genetic basis for macular dystrophy phenotypes. Because of the overlap in phenotypes between BMD and PD, it would be beneficial to screen genes associated with both diseases.

Background The aim of this study was to determine the efficacy of real-time continuous glucose monitoring in T1D patients treated with insulin pump therapy or multiple daily insulin therapy. Methods Twenty adult patients (ten insulin pump therapy and ten multiple daily insulin) with poor glycaemic control (HbA1c > 8.0%) were randomized into two groups for 6 months: the continuous glucose monitoring arm (using real-time continuous glucose monitoring) and the SMBG arm. After 2 months of wash-out, the participants crossed over. The primary outcome was HbA1c reduction. The secondary outcomes were hypoglycaemia and hyperglycaemia risk assessment (area under the curve 200 mg/dL/day, respectively) and glucose variability. Results Fourteen patients (eight multiple daily insulin, six insulin pump therapy) used continuous glucose monitoring appropriately (at least 40% of the time). In these patients, the improvement in glycaemic control was more evident during the real-time continuous glucose monitoring period (7.76% ± 0.4 vs 8.54% ± 0.4, p

Background Typhoid fever is a systemic infection caused by the bacterium Salmonella enterica subspecies enterica serotype typhi, which is acquired by ingestion of contaminated food and water. Each year the disease affects at least 16 million persons world-wide, most of whom reside in the developing countries of Southeast Asia and Africa. In Italy the disease is uncommon with a greater number of cases in Southern regions than in Northern ones. Case presentation We report on a 57-year-old Sri-Lankan male affected by typhoid fever, the onset of which was accompanied by oropharyngeal candidiasis. This clinical sign was due to a transient cell-mediated immunity depression (CD4+ cell count was 130 cells/mm3) probably caused by Salmonella typhi infection. Human immunodeficiency virus infection was ruled out. Diagnosis of typhoid fever was made by the isolation of Salmonella typhi from two consecutive blood cultures. The patient recovered after a ten days therapy with ciprofloxacin and his CD4+ cell count improved gradually until normalization within 3 weeks. Conclusion Our patient is the first reported case of typhoid fever associated with oropharyngeal candidiasis. This finding suggests a close correlation between Salmonella typhi infection and transitory immunodepression.

The care of a spinal cord injury (SCI) person constitutes a great challenge for the provider: SCI persons are mobility impaired, and they are prone to develop multiple comorbidities such as diabetes mellitus, hypertension, obesity, bladder infections, wounds, and depression. Furthermore, disease manifestations can be misleading depending on the level of injury. The utilization of telemedicine to monitor patients and deliver care has opened a new horizon for SCI persons. Several telehealth programs are now in use to monitor pressure ulcers and postdischarge rehabilitation in SCI persons. To answer the need for a more comprehensive approach to the multifaceted manifestation of SCI at the James J. Peters VAMC, we have started a customized telerehabilitation program. The program monitors the most common comorbidities of SCI, it is instrumental in the reintegration of the SCI person in the community, it offers individualized in-home rehabilitation programs, it addresses safety issues, and it offers counseling, weight reduction, and maintenance plans. A team of SCI specialists-including an internist, a registered nurse, a physical therapist, a nutritionist, a psychologist, and a recreational therapist-are available for weekly meetings with the patients. The programs are tailored to the patients' needs and agreed upon by both parties. Both messaging devices and video monitors are utilized. An interdisciplinary template is used to record assessments and plans. Preliminary results are encouraging; coordination of the team and relative poor technology are some of the obstacles we have identified. Further evaluation is necessary to determine cost effectiveness.

Purpose. To investigate possible causes and implications of the decrease in glutathione concentration in rat lenses during organ culture.Methods. Freshly excised lenses were incubated in modified TC-199 medium. Ellman's Reagent or the GSH-400 assay were used to assay glutathione levels in lenses cultured for different times and under a variety of altered culture conditions.Results. In lenses from young rats the glutathione decrease was not ameliorated by reduction of oxygen tension in the incubator, nor by supplementation of the culture medium with various antioxidants or sulfhydryl compounds, nor with the amino acid precursors of glutathione. Addition of 2-mercaptoethanol stimulated cysteine transport into the lens but had only a modest effect in maintaining the level of glutathione. The decrease in glutathione concentration was less in cultured lenses from older rats. Lenses from rhesus monkeys exhibited no decrease in glutathione levels when maintained in organ culture for up to 48 h.Conclusions. The b...

Purpose Ciliary neurotrophic factor (CNTF) protects rod photoreceptors from retinal degenerative disease in multiple nonhuman models. Thus far, CNTF has failed to demonstrate rod protection in trials for human retinitis pigmentosa. Recently, CNTF was found to improve cone photoreceptor function in a canine CNGB3 achromatopsia model. This study explores whether this finding translates to humans with CNGB3 achromatopsia. Methods A five-subject, open-label Phase I/II study was initiated by implanting intraocular microcapsules releasing CNTF (nominally 20 ng/d) into one eye each of CNGB3 achromat participants. Fellow eyes served as untreated controls. Subjects were followed for 1 year. Results Pupil constriction in treated eyes gave evidence of intraocular CNTF release. Additionally, scotopic ERG responses were reduced, and dark-adapted psychophysical absolute thresholds were increased, attributable to diminished rod or rod pathway activity. Optical coherence tomography revealed that the cone-rich fovea underwent structural changes as the foveal hyporeflective zone (HRZ) became diminished in CNTF-treated eyes. No objectively measurable enhancement of cone function was found by assessments of visual acuity, mesopic increment sensitivity threshold, or the photopic ERG. Careful measurements of color hue discrimination showed no change. Nonetheless, subjects reported beneficial changes of visual function in the treated eyes, including reduced light sensitivity and aversion to bright light, which may trace to decreased effective ambient light from the pupillary constriction; further they noted slowed adaptation to darkness, consistent with CNTF action on rod photoreceptors. Conclusions Ciliary neurotrophic factor did not measurably enhance cone function, which reveals a species difference between human and canine CNGB3 cones in response to CNTF. (ClinicalTrials.gov number, NCT01648452.).

Background The diffuse sclerosing variant of papillary thyroid carcinoma (DSPC) is a relatively rare variant of papillary thyroid cancer. Large studies of patients with DSPC have been infrequently performed, and controversy still exists concerning some DSPC features and outcomes. The aim of the present study was to retrospectively evaluate the clinicopathologic features and outcomes in a series of 34 consecutive patients with DSPC and to compare them with a larger group of 245 consecutive patients with the classic variant of papillary thyroid carcinoma (cPTC) that were evaluated in the same period. Patients and methods Clinical and histological features (sex, age, tumor size,multifocality, bilaterality, extra thyroid extension, and local and distant metastases) were recorded in all patients, as well as any persistent or recurrent disease and the patients' disease status at last observation. Patients with cPTC were classified as either low (122) or high risk (123). DSPC and high-risk patients were all treated with the same protocol, including ¹³¹I treatment. All patients were included in a Cox regression model analysis to investigate the effect of each variable on the hazard ratio. Results As expected, multifocality, bilaterality, and extra thyroid extension were more frequently noted at presentation, and the pT1 category of TNM classification was less frequently noted in DSPC and high-risk patients with cPTC compared with low-risk patients with cPTC. No significant difference was found between patients with DSPC and those with high-risk cPTC, except that extra thyroid extension was found more frequently in the patients with DSPC. Using multivariate analysis, diffuse sclerosing variant was an independent variable for predicting a high risk of persistent and recurrent disease during initial follow-up. However, at a later time, and after further treatment, the disease status was not different between patients with DSPC and those with high-risk cPTC, and only the presence of distant metastases affected the final outcome. Conclusions DSPC is a thyroid papillary carcinoma variant characterized by high aggressiveness. In patients with DSPC, the outcome is worse than in patients with low-risk cPTC; and, at presentation, characteristics are somewhat worse than for patients with high-risk cPTC.At medium term, the outcome is similar to that observed in patients with high-risk cPTC, provided aggressive treatment is used (additional surgical intervention, when required, and/or ¹³¹I radiotherapy).

Insulin pump therapy combined with real-time continuous glucose monitoring, known as sensor-augmented pump (SAP) therapy, has been shown to improve metabolic control and to reduce the rate of hypoglycemia in adults with type 1 diabetes compared to multiple daily injections or standard continuous subcutaneous insulin infusion. Glycemic variability is also reduced in patients on SAP therapy. This approach allows patients to monitor their glucose levels being informed of glycemic concentration and trend. Trained diabetic patients, therefore, can appropriately modify insulin infusion and/or carbohydrate intake in order to prevent hypo- or hyperglycemia. For these reasons, SAP therapy is now considered the gold standard for type 1 diabetes treatment. To be clinically effective, however, devices and techniques using advanced technology should not only have the potential to theoretically ameliorate metabolic control, but also be well accepted by patients in terms of satisfaction and health-related quality of life, because these factors will improve treatment adherence and consequently overall outcome. SAP therapy is generally well tolerated by patients; however, many clinical trials have identified significant noncompliance in the use of this device, most notably in the pediatric and adolescent populations. In this review we aim to analyze the main reasons for good or poor adherence to SAP therapy and to provide useful tips in order to fully benefit from this kind of novel therapeutic approach.

That the Archives of Ophthalmology is devoting this issue to genomics in ophthalmology just over one year from its two issues on genetics in ophthalmology is a testament to that fact that the era of genomic medicine is rapidly being incorporated into ophthalmology.(1) The evolution of genetic medicine has been accelerated following the full sequencing of the human genome,(2) the HapMap Project,(3) and the identification important genetic components to complex diseases such as macular degeneration and glaucoma.(4–7) Science has moved forward at a rapid pace. Now is the time to put this knowledge into clinical practice. Approximately 71% of respondents to a recent survey wanted more information from their physicians about genetic conditions in their family.(8) Our patients are looking for us as ophthalmologists to take the lead.