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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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Xerostomia is a symptom frequently present in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). In the present trial, the activity of an artificial saliva (aldiamed ® spray) in comparison to a placebo spray were used to evaluate the xerostomia and the saliva antioxidant capacity (SAT). Sixty patients of both genders with T1DM or T2DM were randomized into two groups of 30 subjects each. The experiment was a double-blind study approved by the Ethics Committee of the "G. d'Annunzio University" of Chieti and Pescara. Moreover, measurements of the stimulated saliva flow rate and the ultrasonography of the submandibular and parotid glands were performed at both the study time points. The results demonstrated statistically significant differences between the treatments in terms of the xerostomia average score. Specifically, the values were at baseline and after 30 days 2.9 ± 1.31 and 3.0 ± 1.44 and 1.4 ± 1.48 and 2.4 ± 0.99 for aldiamed ® spray and the placebo, respectively. Meanwhile, no statistically significant differences were shown between the two groups for the other variables, such as the salivary flow rate, the antioxidant capacity of the saliva, and the ultrasonography of the major salivary glands.

Nutrition is a modifiable key factor that is able to interact with both the genome and epigenome to influence human health and fertility. In particular, specific genetic variants can influence the response to dietary components and nutrient requirements, and conversely, the diet itself is able to modulate gene expression. In this context and the era of precision medicine, nutrigenetic and nutrigenomic studies offer significant opportunities to improve the prevention of metabolic disturbances, such as Type 2 diabetes, gestational diabetes, hypertension, and cardiovascular diseases, even with transgenerational effects. The present review takes into account the interactions between diet, genes and human health, and provides an overview of the role of nutrigenetics, nutrigenomics and epigenetics in the prevention of non-communicable diseases. Moreover, we focus our attention on the mechanism of intergenerational or transgenerational transmission of the susceptibility to metabolic disturbances, and underline that the reversibility of epigenetic modifications through dietary intervention could counteract perturbations induced by lifestyle and environmental factors.

Aim: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of probiotics in pregnancy on the incidence of gestational diabetes (GDM) and fasting plasma glucose (FPG)., Methods: A MEDLINE, EMBASE, Scopus and Cochrane search (up to May 30th, 2019) was performed to identify RCTs of comparison of probiotics with placebo/active comparators in pregnant women. Principal endpoints were the incidence of GDM and the change of FPG. Other maternal and fetal outcomes were secondary endpoints. Mantel-Haenszel Odds Ratio with 95% CI (MH-OR) was calculated for dichotomous outcomes, whereas standardized differences in means was calculated for continuous variables. (PROSPERO registration CRD42019139889)., Findings: A total of 17 RCTs, all versus placebo, was identified. The overall quality of the trials was satisfactory. No effect of probiotics on incidence of GDM (MH-OR: 0.77[0.51,1.16], p = 0.21,I2:62%) was observed, with a small but significant reduction of FPG (mean difference -1.01 [-1.96, -0.06]mg/dl, p = 0.02, I 2 :46%). Among secondary endpoints, a significant reduction of maternal insulin (both in women with or without diabetes) was observed in the probiotics group., Interpretation: Probiotics during pregnancy do not reduce the incidence of GDM, with a very little (statistically but not clinically significant) reduction of fasting plasma glucose., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Extracellular vesicles (EVs) actively participate in inter-cellular crosstalk and have progressively emerged as key players of organized communities of cells within multicellular organisms in health and disease. For these reasons, EVs are attracting the attention of many investigators across different biomedical fields. In this scenario, the possibility to study specific placental-derived EVs in the maternal peripheral blood may open novel perspectives in the development of new early biomarkers for major obstetric pathological conditions. Here we reviewed the involvement of EVs in feto-maternal crosstalk mechanisms, both in physiological and pathological conditions (preeclampsia, fetal growth restriction, preterm labor, gestational diabetes mellitus), also underlining the usefulness of EV characterization in maternal-fetal medicine.

Objective: To identify the effects of different dietary inositol stereoisomers on insulin resistance and the development of gestational diabetes mellitus (GDM) in women at high risk for this disorder. Design: A preliminary, prospective, randomized, placebo controlled clinical trial. Participants: Nonobese singleton pregnant women with an elevated fasting glucose in the first or early second trimester were studied throughout pregnancy. Intervention: Supplementation with myo-inositol, d-chiro-inositol, combined myo- and d-chiro-inositol or placebo. Main outcome measure: Development of GDM on a 75 grams oral glucose tolerance test at 24-28 weeks' gestation. Secondary outcome measures were increase in BMI, need for maternal insulin therapy, macrosomia, polyhydramnios, neonatal birthweight and hypoglycemia. Results: The group of women allocated to receive myo-inositol alone had a lower incidence of abnormal oral glucose tolerance test (OGTT). Nine women in the control group (C), one of the myo-inositol (MI), five in d-chiro-inositol (DCI), three in the myo-inositol/D-chiro-inositol group (MI/DCI) required insulin ( p  = .134). Basal, 1-hour, and 2 hours glycemic controls were significantly lower in exposed groups ( p  < .001, .011, and .037, respectively). The relative risk reduction related to primary outcome was 0.083, 0.559, and 0.621 for MI, DCI, and MI/DCI groups. Conclusions: This study compared the different inositol stereoisomers in pregnancy to prevent GDM. Noninferiority analysis demonstrated the largest benefit in the myo-inositol group. The relevance of our findings is mainly related to the possibility of an effective approach in GDM. Our study confirmed the efficacy of inositol supplementation in pregnant women at risk for GDM.

Background: Impaired glucose tolerance (IGT) is associated with increased cardiovascular morbidity and mortality. Enhanced thromboxane (TX)-dependent platelet activation plays a pivotal role in atherothrombosis and characterizes type 2 diabetes mellitus (DM). Whether this also pertains to IGT is currently unknown. We investigated whether TXA 2 -dependent platelet activation, as reflected by 11-dehydro-TXB 2 (TXM) urinary excretion, is comparably abnormal in IGT as in DM, is persistent over long-term follow-up, changes as a function of metabolic disease progression, and is influenced by food intake., Methods: We prospectively investigated subjects with IGT (n = 48) and two control groups with DM diagnosed either less than 12 months (n = 60) or 12 months or more (n = 58)., Results: Baseline TXM excretion was comparable between subjects with IGT and DM, with no evidence of a circadian variation. During a 36-month follow-up, urinary TXM excretion was stable over time in the DM groups, while tended to increase in subjects with IGT. Increasing urinary TXM excretion over time was observed in the subjects who progressed to diabetes vs nonprogressors., Conclusions: We conclude that TXA 2 -dependent platelet activation was at least as high in IGT as in patients with DM and further increased over time, especially in those who progressed to overt diabetes., (© 2019 John Wiley & Sons, Ltd.)

Mobile health (mHealth) applications (apps) have been recently introduced as an easily accessible tool for providing information to pregnant women with diabetes. Despite the growing number of apps on the topic "diabetes & pregnancy", a smartphone app offering comprehensive and individualized information to both women (before and during gestation) and their healthcare professionals was still missing. To overcome this lack, the Italian Diabetes and Pregnancy Study Group conceived and realized in 2016 a novel mobile app called "MySweetGestation". It is designed to be an interactive educational tool for both patients and physicians not expert in the field. Through an interactive way of learning, it provides validated information to the user, focusing on different area of interest: from prevention and risk factors for developing diabetes during pregnancy to treatment and follow-up strategies after gestation. Three years since its publication, MySweetGestation has been downloaded in different western and eastern countries worldwide, suggesting a widespread social impact. Easily accessible personalized information made available via mHealth technology may be of great importance to spread controlled information among the pregnant population. MySweetGestation, being an interactive educational device for both patients and healthcare professionals, may contribute to improve the management of pregnant women with diabetes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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

Epigenetic regulation of gene expression plays a key role in affecting human health and diseases with particular regard to human reproduction. The major concern in this field is represented by the epigenetic modifications in the embryo and the increased risk of long-life disorders induced by the use of assisted reproduction techniques, able to affect the epigenetic assessment in the first steps of embryo development. In this review, we analyze the correlation between epigenetic modifications and human reproduction, suggesting that the reversibility of the epigenetic processes could represent a novel resource for the treatment of the couple's infertility and that parental lifestyle in periconceptional period could be considered as an important issue of primary prevention.

Gestational Diabetes Mellitus (GDM) is the most common metabolic condition during pregnancy and may result in short- and long-term complications for both mother and offspring. The complexity of phenotypic outcomes seems influenced by genetic susceptibility, nutrient-gene interactions and lifestyle interacting with clinical factors. There is strong evidence that not only the adverse genetic background but also the epigenetic modifications in response to nutritional and environmental factors could influence the maternal hyperglycemia in pregnancy and the foetal metabolic programming. In this view, the correlation between epigenetic modifications and their transgenerational effects represents a very interesting field of study. The present review gives insight into the role of gene variants and their interactions with nutrients in GDM. In addition, we provide an overview of the epigenetic changes and their role in the maternal-foetal transmission of chronic diseases. Overall, the knowledge of epigenetic modifications induced by an adverse intrauterine and perinatal environment could shed light on the potential pathophysiological mechanisms of long-term disease development in the offspring and provide useful tools for their prevention.

Background and Objective: Gestational Diabetes Mellitus (GDM) is a complex and wide spread problem and is considered one of the most frequent chronic metabolic conditions during pregnancy. According to a recent consensus conference held in Italy, new technologies can play a role in the so-called process of fertilization of the individual's ecosystem engagement, representing support for systemic collaboration among the main actors. The current systematic review aimed at providing an update of the literature about telemedicine for GDM, considering the role of psychological dimensions such as empowerment/self-efficacy, engagement and satisfaction. Methods: The review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. The data sources were PubMed, ScienceDirect, Cochrane, and Scopus databases. Results: Thirteen articles were identified as eligible and relevant for the final qualitative synthesis, but none was specific for the topic of engagement. The quality or research bias of the studies presents methodological limits. Most studies had clinical outcomes as a primary object. Concerning empowerment and self-efficacy, there were only preliminary findings reporting any improvements derived from using telemedicine approaches. Conversely, there were more consistent and positive results concerning the satisfaction of patients and clinicians. Conclusions: These results are not sufficient to state a conclusive evaluation of positive effects of telemedicine use for GDM care. A more in-depth investigation of engagement and empowerment dimensions is necessary, as some benefits for the management of chronic conditions were already detected. Further investigations will also be necessary concerning the acceptability and feasibility of telemedicine systems by clinicians.

Gestational diabetes mellitus (GDM) can be considered a silent risk for out-of-pregnancy diabetes mellitus (DM) and cardiovascular disease (CVD) later in life. We aimed to assess the predictive role of 3 rd trimester lipid profile during pregnancy for the susceptibility to markers of subclinical atherosclerosis (CVD susceptibility) at 3 years in a cohort of women with history of GDM. A secondary aim is to evaluate the usefulness of novel nutrigenetic markers, in addition to traditional parameters, for predicting early subclinical atherosclerosis in such women in order to plan adequate early prevention interventions. We assessed 28 consecutive GDM women in whom we collected socio-demographic characteristics and clinical and anthropometric parameters at the 3 rd trimester of pregnancy. In a single blood sample, from each patient, we assessed 9 single nucleotide polymorphisms (SNPs) from 9 genes related to nutrients and metabolism, which were genotyped by High Resolution Melting analysis. All women then attended a 3-year-postpartum follow-up and on that occasion performed an oral glucose tolerance test (OGTT, with 75 g oral glucose), the measurement of carotid artery intima-media thickness (cIMT), and analyses of metabolic parameters. In addition, we evaluated the physical activity level and the adherence to Mediterranean diet (MedDiet) using the International Physical Activity Questionnaire (IPAQ- short version ) and PREDIMED questionnaires. We found an association between 3 rd trimester triglycerides and cIMT ( p = 0.014). We also found significant associations between the APOA5 CC genotype and cIMT after adjustments for age and body mass index ( p = 0.045) and between the interaction CC APOA5/CC LDLR and cIMT ( p = 0.010). At the follow-up, the cohort also featured a mean BMI in the overweight range and a high mean waist circumference. We found no difference in the MedDiet adherence, physical activity, and smoking but an inverse correlation between the PREDIMED and the IPAQ scores with the IMT. In conclusion, this preliminary study provides insight into the predictive role of lipid profile during pregnancy and of some genetic variants on cIMT taken as a parameter of subclinical CVD susceptibility in GDM.

Aims: 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., Methods: 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., Results: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m 2 ), 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)., Conclusions: 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.

Aims: Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy. The aim of the study is to compare the effect of different dosages of inositol stereoisomers supplementation on insulin resistance levels and several maternal-fetal outcomes in GDM women., Methods: Participants were randomly allocated to receive daily: 400 mcg folic acid (control treatment), 4000 mg myo-inositol plus 400 mcg folic acid (MI treatment), 500 mg D-chiro-inositol plus 400 mcg folic acid (DCI treatment) or 1100/27.6 mg myo/D-chiro-inositol plus 400 mcg folic acid (MI plus DCI treatment). The homeostasis model assessment of insulin resistance (HOMA-IR) was measured at the diagnosis of GDM and after 8 weeks of treatment. Secondary outcomes, obstetric outcomes and any maternal or fetal complication at delivery were also collected., Results: Eighty GDM women were assigned to one of the four arms of study (20 per arm). A significant delta decrease in HOMA-IR index was found in subjects of MI group without insulin therapy compared to control group (p < 0.001). A lower variation in average weight gain (at delivery vs pre-pregnancy and OGTT period) was detected in MI group vs control group (p = 0.001 and p = 0.019, respectively). Moreover, women exposed to MI and MI plus DCI required a significantly lower necessity of an intensified insulin treatment. Women of the control group had newborns with higher birth weight compared with women treated with inositol (p = 0.032)., Conclusions: Our study provides interesting but preliminary results about the potential role of inositol stereoisomers supplementation in the treatment of GDM on insulin resistance levels and several maternal-fetal outcomes. Further studies are required to examine the optimal and effective dosages of different inositol supplements. CLINICAL TRIAL REG. NO.: NCT02097069, ClinicalTrial.gov.

Gastroesophageal reflux disease (GERD), a clinical condition characterized by reflux of gastroduodenal contents in the oesophagus, has proved to demonstrate a strong link between oxidative stress and the development of GERD. Proton pump inhibitors (PPIs) have been universally accepted as first-line therapy for management of GERD. The potential benefits of electrolysed reduced water (ERW), rich in molecular hydrogen, in improving symptoms and systemic oxidative stress associated with GERD was assessed. The study was performed on 84 GERD patients undergoing control treatment (PPI + tap water) or experimental treatment (PPI + ERW) for 3 months. These patients were subjected to the GERD-Health Related Quality of Life Questionnaire as well as derivatives reactive oxigen metabolites (d-ROMs) test, biological antioxidant potential (BAP) test, superoxide anion, nitric oxide and malondialdehyde assays, which were all performed as a proxy for the oxidative/nitrosative stress and the antioxidant potential status. Spearman's correlation coefficient was used to evaluate the correlation between scores and laboratory parameters. Overall results demonstrated that an optimal oxidative balance can be restored and GERD symptoms can be reduced rapidly via the integration of ERW in GERD patients. The relative variation of heartburn and regurgitation score was significantly correlated with laboratory parameters. Thus, in the selected patients, combination treatment with PPI and ERW improves the cellular redox state leading to the improvement of the quality of life as demonstrated by the correlation analysis between laboratory parameters and GERD symptoms., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Aim: Gestational diabetes mellitus (GDM) is the most frequent metabolic disorder in pregnancy and it can be considered a silent risk associated to T2DM and CVD later in life. The aim of this study was to investigate the association of clinical parameters with nine single nucleotide polymorphisms (SNPs) involved with nutrients and metabolism in women with or without GDM in order to identify potential routine clinical markers for early prevention., Methods: Nine gene variants associated with nutrients and metabolism, namely PPARG2 rs1801282 (C > G); PPARGC1A rs8192678 (C > T); TCF7L2 rs7903146 (C > T); LDLR rs2228671 (C > T); MTHFR rs1801133 (C > T); APOA5 rs662799 (T > C); GCKR rs1260326 (C > T); FTO rs9939609 (T > A); MC4R rs17782313 (T > C) were genotyped in 104 GDM cases and 124 controls using High Resolution Melting (HRM) analysis., Results: The genetic variant rs7903146 (C > T) in TCF7L2 gene showed a strong association with GDM risk (OR: 2.56; 95% CI: [1.24-5.29]). Moreover, a significant correlation was observed between lipid parameters and polymorphisms in other genes, namely PPARG2 [p = 0,03], APOA5 [p = 0,02], MC4R [p = 0,03], LDLR [p = 0,04] and FTO [p = 0,03]. In addition, rs17782313 variant, mapped close to MC4R gene, was associated to BMI in pre-pregnancy [p = 0,02] and at the end of pregnancy [p = 0,03] in GDM group., Conclusion: In our study, we found significant associations between routine clinical parameters and some gene variants connected with nutrients and metabolism in women with GDM. These results can provide useful information to develop effective tools and possible personalized intervention strategies in a timely manner., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: It is essential to consider the clinical assessment of psychological aspects in patients with Diabetes Mellitus (DM), in order to prevent potentially adverse self-management care behaviors leading to diabetes-related complications, including declining levels of Quality of Life (QoL) and negative metabolic control. Purpose : In the framework of Structural Equation Modeling (SEM), the specific aim of this study is to evaluate the influence of distressed personality factors as Negative Affectivity (NA) and Social Inhibition (SI) on diabetes-related clinical variables (i.e., QoL and glycemic control). Methods: The total sample consists of a clinical sample, including 159 outpatients with Type 2 Diabetes Mellitus (T2DM), and a control group composed of 102 healthy respondents. All participants completed the following self- rating scales: The Type D Scale (DS14) and the World Health Organization QoL Scale (WHOQOLBREF). Furthermore, the participants of the clinical group were assessed for HbA1c, disease duration, and BMI. The observed covariates were BMI, gender, and disease duration, while HbA1c was considered an observed variable. Results: SEM analysis revealed significant differences between groups in regards to the latent construct of NA and the Environmental dimension of QoL. For the clinical sample, SEM showed that NA had a negative impact on both QoL dimensions and metabolic control. Conclusions: Clinical interventions aiming to improve medication adherence in patients with T2DM should include the psychological evaluation of Type D Personality traits, by focusing especially on its component of NA as a significant risk factor leading to negative health outcomes.

Background: Diabetes mellitus (DM) is a chronic illness with impaired health-related quality of life and a high risk of psychiatric disorders. We carried out a systematic review analyzing the relationship between DM and suicide by providing a qualitative data synthesis of the studies., Methods: We conducted, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search of the literature in PubMed, Scopus, ISI Web of Science, PsycINFO, Google Scholar, and ScienceDirect. Search terms were "suicid*" combined with the Boolean "AND" operator with "diabetes.", Results: The initial search identified 568 citations. A total of 17 research reports met the predefined inclusion criteria and were analyzed. DM was found to be significantly associated with a marked increase in suicidal behaviors and suicidal ideation (SI), especially in patients with depressive symptoms. Insulin therapy, DM of long duration, and unsatisfactory glycemic control were identified as risk factors for SI in Type 1 (T1DM) and Type 2 (T2DM)., Conclusion: Health-care professionals need to be aware of the higher suicidal risk in patient subgroups based on the clinical characteristics of DM; thus, patients with these characteristics warrant special attention. In this regard, clinical management should include efforts to manage emotional distress in DM care.

Gestational diabetes mellitus (GDM) is the most frequent metabolic disorder in pregnancy. Women with a GDM history are at increased risk of developing diabetes and cardiovascular diseases. Studies have demonstrated a significant correlation between several genes involved in the metabolic pathway of insulin and environmental factors. The aim of this study was to investigate the relationship between clinical parameters in GDM and variants in genes involved with nutrients and metabolism. Several variants PPARG2 rs1801282 ( C>G ); PPARGC1A rs8192678 ( C>T ); TCF7L2 rs7903146 ( C>T ); LDLR rs2228671 ( C>T ); MTHFR rs1801133 ( C>T ); APOA5 rs662799 ( T>C ); GCKR rs1260326 ( C>T ); FTO rs9939609 ( T>A ); MC4R rs17782313 ( T>C ) were genotyped in 168 pregnant Caucasian women with or without GDM by High Resolution Melting (HRM) analysis. A significant correlation was observed between TT genotype of TCF7L2 gene and increased risk of GDM (OR 5.4 [95% CI 1.5-19.3]). Moreover, a significant correlation was observed between lipid parameters and genetic variations in additional genes, namely, PPARG2 [ p = 0,02], APOA5 [ p = 0,02], MC4R [ p = 0,03], LDLR [ p = 0,01], and FTO [ p = 0,02]. Our findings support the association between TCF7L2 rs7903146 variant and an increased GDM risk. Results about the investigated genetic variants provide important information about cardiometabolic risk in GDM and help to plan future prevention studies., Competing Interests: The authors declare that there is no conflict of interests associated with this manuscript.

Background and Objective . Diagnosis of Gestational Diabetes Mellitus (GDM) could significantly increase the likelihood of health problems concerning both potential risks for the mother, fetus, and child's development and negative effects on maternal mental health above all in terms of a diminished Quality of Life (QoL). The current systematic review study is aimed at further contributing to an advancement of knowledge about the clinical link between GDM and QoL. Methods . According to PRISMA guidelines, PubMed, Web of Science, Scopus, and Cochrane databases were searched for studies aimed at evaluating and/or improving levels of QoL in women diagnosed with GDM. Results . Fifteen research studies were identified and qualitatively analyzed by summarizing results according to the following two topics: GDM and QoL and interventions on QoL in patients with GDM. Studies showed that, in women with GDM, QoL is significantly worse in both the short term and long term. However, improvements on QoL can be achieved through different intervention programs by enhancing positive diabetes-related self-management behaviors. Conclusion . Future studies are strongly recommended to further examine the impact of integrative programs, including telemedicine and educational interventions, on QoL of GDM patients by promoting their illness acceptance and healthy lifestyle behaviors., Competing Interests: The authors declare that they have no competing interests to disclose.

Introduction: Type D personality consists of a mixture of high levels of negative affectivity and social inhibition, resulting in a stable tendency to experience negative emotions, by inhibiting the expression of these emotions. We have reanalyzed the clinically relevant studies examining the role of this personality profile in diabetes, by providing a qualitative synthesis of the data. In this regard, the aim of this study is to provide a systematic review by evaluating the clinical link between Type D personality and diabetes., Method: When focusing on PRISMA guidelines, we have performed a comprehensive research of the literature on PubMed, Scopus, ScienceDirect, ISI Web of Science, PsycINFO, and Google Scholar by using search terms as "distressed personality" OR (i.e., Boolean operator) "Type D personality" combined with the Boolean "AND" operator with "diabetes.", Results: A total of seven research studies were identified and included in the review. Type D was found to be more prevalent in diabetes patients than controls. As regards the specific association with diabetes variables, Type D personality is a significant predictor of both poor medication adherence and unhealthy behaviors, by predicting negative mental health consequences also (i.e., depressed mood, anhedonia, and anxiety)., Conclusion: Our review emphasized for the first time that Type D personality affects clinical factors in patients with diabetes by provoking adverse outcomes. The core implication of the study comprises the clinical relevance to detect, from a clinimetric point of view, Type D personality in diabetes in order to prevent potentially negative clinical outcomes.

Gestational diabetes mellitus (GDM) is a common complication characterized by increased insulin resistance, and by increased risk for adverse pregnancy outcomes affecting both the mother and the fetus. International guidelines describe optimal ways to recognize it, and the recommended treatment of patients affected to reduce adverse outcomes. Improving insulin resistance could reduce incidence of GDM and its complications. Recently, a few trials have been published on the possible prevention of GDM. Inositol has been proposed as a food supplement that might reduce gestational diabetes incidence in high-risk pregnant women.

Introduction: Healthy lifestyle promotion programs are essential to prevent metabolic diseases such as obesity and diabetes. Adolescents could represent the ideal target population especially using serious web games., Objective: To test the improvement of knowledge about healthy nutrition in adolescents and to analyze participants' enjoyment in playing the web game "Gustavo in Gnam's Planet" in comparison with a leisure web game., Subjects and Methods: Sixty-five adolescents were engaged in three supervised group sessions. Measures about healthy food knowledge and games' enjoyment were collected during the three stages of assessment., Results: After playing Gustavo in Gnam's Planet, participants significantly improved their knowledge on a healthy diet, compared to the recreational web games; whereas the level of fun experienced while playing the recreational and the educational games was not significantly different., Conclusions: Gustavo in Gnam's Planet is an important promising tool, with entertainment property, to promote a healthy lifestyle in Italian adolescents.

Objective: The goal of this study was to design, develop, and evaluate a game for health, "Gustavo in Gnam's Planet" ("Gustavo"), aimed to improve knowledge on healthy foods and to increase consumption of healthy foods., Subjects and Methods: Eighty-three high school students were enrolled in the study. The game was designed and developed by a multidisciplinary team. Behavioral change theories were adopted to guide the design of the health messages. Participants were assessed about food frequency, healthy food knowledge, and the game's interest., Results: Forty-seven subjects (mean age, 14.9±1.0 years; 72.3 percent males) completed the study. At posttest, participants showed significant higher scores (i.e., increased knowledge) in the questionnaire on knowledge of healthy foods (70.0±9.2 versus 71.3±10.0 for pretest and posttest, respectively; P<0.05). Improvements in healthy eating habits were also detected: higher frequency of consumption during a week of white meat (1 [1-2] versus 2 [1-2]; P=0.01), eggs (1 [1-1] versus 1 [1-2]; P=0.01], and legumes (1 [0-1] versus 1 [1-2]; P=0.03) and lower frequency of consumption of sugar-containing packaged snacks (1 [0-1] versus 0 [0-1]; P=0.009). Most of the participants found the game easy to use and clear in its content. Half of the participants found the game interesting., Conclusions: Our study shows that "Gustavo" is a promising tool for health education, in schools or in other environments. Limitations of the study and future directions are discussed.

Objective: To test the hypothesis that dietary myo-inositol may improve insulin resistance and the development of gestational diabetes mellitus (GDM) in women at high risk of this disorder., Design: A prospective, randomized, double-blind, placebo controlled clinical trial, pilot study., Participants: Non-obese singleton pregnant women with an elevated fasting glucose in the first or early second trimester were studied throughout pregnancy., Intervention: Supplementation with myo-inositol or placebo during pregnancy., Main Outcome Measure: Development of GDM on a 75 g oral glucose tolerance test at 24-28 weeks' gestation. Secondary outcome measures were increased in BMI, need for maternal insulin therapy, macrosomia, polyhydramnios, neonatal birthweight and hypoglycemia., Results: Thirty-six women were allocated to receive myo-inositol and 39 placebo. The incidence of GDM in mid-pregnancy was significantly reduced (p = 0.001) in women randomized to receive myo-inositol compared to placebo (relative risk 0.127). Women randomized to receive myo-inositol also required less insulin therapy, delivered at a later gestational age, had significantly smaller babies with fewer episodes of neonatal hypoglycemia., Conclusions: Myo-inositol supplementation in pregnancy reduced the incidence of GDM in women at high risk of this disorder. The reduction in incidence of GDM in the treatment arm was accompanied by improved outcomes.

Circulating endothelial cells (CEC) and endothelial microparticles (EMP) are emerging as markers of endothelial repair and activation/apoptosis. Although significant changes in the number of CEC and EMP in pathological conditions have been reported, their reliable identification and quantification still remain a technical challenge. Here, we present a novel methodology for the identification and quantitation of CEC and EMP based on multicolor flow cytometry. Using a lyse/no wash protocol, we observed that in 50 μl of peripheral blood, the large majority of events expressing an endothelial phenotype (CD45-/CD146+/CD34+) are due to non-nucleated particles (DRAQ5-) carrying mitochondrial activity (MitoTracker+) and, therefore, classified as EMP. We enumerated circulating EMP by single platform absolute count in a lyse/no wash four-color flow-cytometric procedure, which allowed the distinction, within the whole endothelial compartment, of EMP derived from endothelial progenitors (CD45-/CD146+/CD34+/CD117+) and from mature endothelial cells (CD45-/CD146+/CD34+/CD117-). A significant increase in both subsets was observed in patients with diabetes mellitus. Thus, this simple and highly reproducible method may be useful for monitoring endothelial dysfunction in clinical settings., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background. About 10% of pregnancies are complicated by previously unknown impairment of glucose metabolism, which is defined as gestational diabetes. There are little data available on prevalence of thyroid disorders in patients affected by gestational diabetes, and about their postgestational thyroid function and autoimmunity. We therefore investigated pancreatic and thyroid autoimmunity in gestational diabetic patients and in women who had had a previous gestational diabetic pregnancy. Methods. We investigated 126 pregnant women at the time of a 100-g oral glucose tolerance test: 91 were classified as gestational diabetics, and 35 were negative (controls). We also studied 69 women who had delivered a baby 18-120 months prior to this investigation and who were classified at that time gestational diabetics (38 women) or normally pregnant (31 women; controls). Results. Our data show no differences for both thyroid function and prevalence of autoimmune disorders during pregnancy; however, a significant increase in thyroid autoimmunity was seen in women previously affected by gestational diabetes. This increased prevalence of thyroid autoimmunity was not associated with the development of impaired glucose metabolism after pregnancy. Conclusions. Our data suggest that maternal hyperglycemia is a risk factor for the development of thyroid autoimmunity, a conclusion that should now be confirmed in a larger cohort of patients.

The aim of this study was to evaluate the hepatoprotective and anti-inflammatory effects of silybin-phospholipids and vitamin E complex (SPV complex), by determining cytokine patterns and various markers of liver disease. Forty Caucasian patients with chronic HCV infection were recruited and divided into two groups: 30 were treated with SPV complex for 3 months, while the other 10 did not receive any treatment. Ten other subjects without HCV infection but with staeatosic diagnosis were recruited and treated with SPV complex. Biochemical and hepatic principal parameters were investigated at 0 (T0) and 3 months (T3). The group of HCV patients treated showed an improvement trend of hepatic indecises and viral load, and had a significant and persistent reduction of ALT (P = 0.02) and AST serum level (P = 0.01). In this group cytokines showed a statistically significant increase of IL-2 (P = 0.03) and IL-6 were significantly reduced (P = 0.02) at T0 and T3. After the treatment the group of hepatic steatosics showed a significant decrease in ALT (P = 0.02), AST (0.008), gammaGT (0.004) alkaline phosphatase (0.05), total cholesterol (P = 0.03), fasting glucose (P = 0.008), insulinemia (0.0006), HOMA value (0.002) and C-reactive protein (CRP; 0.04). There was a significant reduction of IFN-gamma, TNF-alpha, and IL-6 (P = 0.02, 0.05 and 0.04, respectively). The data suggest that the SPV complex exerts hepatoprotective, anti-inflammatory and antifibrotic effects. This new compound may therefore be useful in clinical practice in patients with chronic hepatitis C who cannot undergo conventional antiviral therapy., (2008 Wiley-Liss, Inc.)

Aim: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels., Methods: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated., Results: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids. Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test., Conclusion: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.

Evaluation of liver function is crucial in the overall management of patients with liver disease. In particular, patients with end-stage liver disease need accurate prognostic indicators to plan liver transplantation, and in this case, to manage their presence in the waiting list. Availability of predictors of clinical outcome is further essential after liver transplant, mainly to correctly diagnose and adequately treat complications, such as acute rejection, drug toxicity, liver dysfunction. Breath tests using labelled substrates selectively metabolized within the liver may represent an accurate diagnostic and prognostic tool in these clinical conditions, possibly with an adjuntive role to the most commonly used prognostic models (Child-Pugh and MELD scores). Promising results have been in fact recently obtained by the use of different substrates (aminopyrine, methacetin, erythromycin, methionine) which explore different metabolic function of the hepatocyte. The usefulness of breath tests has been documented in liver disease patients both before and after liver transplantation, in the early as well as in the late phase.

Background: Transforming growth factor-beta1 (TGF-beta1) has been demonstrated to be overexpressed in hypertension. Leptin, an adipocyte product, has been shown to play a role in obesity-related hypertension and in vitro studies demonstrated a biologic interaction between leptin and TGF-beta1. Thus, we evaluate a possible in vivo association between TGF-beta1, body mass index (BMI), and leptin circulating levels in hypertensive subjects., Methods: Blood samples for fasting leptin and TGF-beta1, were evaluated in 29 overweight, 46 obese, and 29 nonobese hypertensive patients before and after a 12-week calorie-restricted diet. Monocyte cultures were used for in vitro experiments., Results: Transforming growth factor-beta1 was significantly elevated in hypertensive obese patients (n = 46) as compared with TGF-beta1 levels of hypertensive patients with normal BMI (n = 29) (8. 9 +/- 3 ng/mL v 4.4 +/- 2; P < .001). The circulating levels of TGF-beta1 were associated with BMI and leptin levels in an univariate analysis (r = 0.59, P < .0001; r = 0.62, P < .0001, respectively) and these associations were still present after stepwise multivariate analysis. Weight loss of 10% produced a parallel decrease in TGF-beta1 (from 8.9 +/- 3 ng/mL to 5.3 +/- 2.8 ng/mL; P < .01) and leptin levels (from 30 +/- 24 ng/mL to 17 +/- 14; P < .05). In vitro experiments showed that leptin is able to induce a dose-dependent increase in TGF-beta1 production and mRNA expression in human monocyte cultures., Conclusions: Our data indicate that TGF-beta1 levels are positively associated with BMI and leptin levels in hypertensive patients and suggest that adipose tissue may be an important determinant of TGF-beta1 levels possibly by a leptin-dependent pathway.

Aims: To validate a newly developed questionnaire for the measurement of patients' knowledge and practices, with particular attention to its ability in predicting HbA1c levels., Research Design and Methods: The Knowledge and Practices Diabetes Questionnaire (KPDQ) is a questionnaire composed of two scales, investigating patient knowledge and practices. Twenty-two questions, 12 dealing with patients' knowledge and 10 relative to patients' practices, were initially identified. Factor analysis and reliability analysis were used to validate the questionnaire. The ability of the two scales in predicting metabolic control was then evaluated. The questionnaire was administered to a population of Type 1 diabetic subjects intensively treated and regularly attending the diabetes outpatient clinic of Pescara General Hospital. The mean of all HbA1c measurements performed after patients were taken in charge by the clinic was used as an indicator of metabolic control., Results: Out of 133 Type 1 patients identified, 77 (58 %) filled in the questionnaire. Respondents had a mean age (+/- SD) of 37 +/- 13 years and a mean diabetes duration of 13 +/- 9 years. The application of factor and reliability analyses led to the definition of two final scales composed of 10 (Knowledge Score, KS) and 5 items (Practice Score, PS), respectively. Item-scale correlation was > or = 0.40 for all the items investigated. Cronbach's alpha coefficient exceeded the value of 0.70 for both scales. The mean number of HbA1c determinations during a median period of observation of 4 years was of 11 +/- 5. The mean HbA1c value for the whole population was of 7.0% +/- 1.4, while the proportion of patients with values < or = 7.0% was of 57%. After adjusting for clinical and patient-related characteristics, the KS was the only independent predictor of metabolic control. Patients in the lowest quartile of the KS showed a more than 20-fold increased risk of having mean HbA1c values > or = 7.0% as opposed to those in the highest quartile (odds ratio, OR=23.3;p=0.009). No association emerged between metabolic control and PS., Conclusions: The KPDQ presents excellent psychometric properties. The KS also shows a very impressive association with the mean HbA1c values over a period of 4 years. These findings are particularly remarkable in that many studies have failed in documenting such a relationship. The KS can thus be considered as a quick and efficient screening tool to be used in an ambulatory setting to monitor the level of practice-oriented knowledge of patients with Type 1 diabetes as well as to identify those subjects who need individualized educational interventions.

Background: Diabetes mellitus (DM) is associated with enhanced lipid peroxidation and persistent platelet activation. We tested the hypothesis that the in vivo formation of the F2-isoprostane 8-iso-prostaglandin (PG)F2alpha, a bioactive product of arachidonic acid peroxidation, is enhanced in DM and contributes to platelet activation., Methods and Results: Urine samples were obtained from 85 diabetic patients and 85 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF2alpha and 11-dehydro-thromboxane B2 (TXM), an in vivo index of platelet activation. Sixty-two had non-insulin-dependent (NID)DM, and 23 had insulin-dependent (ID) DM. Vitamin E supplementation, metabolic control, and cyclooxygenase inhibitors were used to investigate the mechanisms of formation of 8-iso-PGF2alpha in this setting. Urinary 8-iso-PGF2alpha excretion was significantly higher (P=0.0001) in NIDDM patients (419+/-208 pg/mg creatinine; range 160 to 1014) than in age-matched control subjects (208+/-92; 41 to 433). Urinary 8-iso-PGF2alpha was linearly correlated with blood glucose and urinary TXM. 8-iso-PGF2alpha excretion was also significantly (P=0. 0001) higher in IDDM patients (400+/-146; 183 to 702) than in control subjects (197+/-69; 95 to 353). Vitamin E supplementation (600 mg/d for 14 days) was associated with a statistically significant reduction in both urinary 8-iso-PGF2alpha (by 37%) and TXM (by 43%) in 10 NIDDM patients. Improved metabolic control was associated with a significant (P=0.0001) reduction in 8-iso-PGF2alpha and TXM excretion by 32% and 41%, respectively, in 21 NIDDM patients. 8-iso-PGF2alpha was unchanged after 2-week dosing with aspirin and indobufen despite profound suppression of TXM excretion., Conclusions: We conclude that DM is associated with increased formation of F2-isoprostanes, as a correlate of impaired glycemic control and enhanced lipid peroxidation. This may provide an important biochemical link between impaired glycemic control and persistent platelet activation. These results provide a rationale for dose-finding studies of antioxidant treatment in diabetes.

The aim of this work was to observe whether different types of carbohydrates might require different insulin doses. Five type 1 CSII-treated diabetic subjects (age 39 +/- 4 years), C-peptide negative and in optimal metabolic control (HbA1c 7.5 +/- 0.2) were selected for the study. They were connected to the Biostator 6 times with an interval of 4-10 days between sessions and fed a meal containing 75 g of carbohydrates of different types: bread, pasta, potatoes, apples, oranges and sucrose. The following net (above basal) insulin requirement for the 30 meals were found (IU - mean + SD): bread 9.15 +/- 1.97; pasta 6.00 +/- 1.37; potatoes 7.05 +/- 2.58; apples 4.54 +/- 1.42; oranges 6.21 +/- 2.62; sucrose 7.83 +/- 2.33. A statistically significant difference was found by ANOVA among insulin requirements for foods (p less than 0.05). Single comparisons between bread and the other foods showed a statistically significant difference only between bread and apple (p less than 0.05). Mean coefficient of variation was 33.9% for the subjects and 30.7% for the meals. A significant correlation was found between Jenkins' glycaemic index and insulin requirement (r = 0.897; p less than 0.001). In conclusion, the high intraindividual variability of insulin requirement does not advice the use of the glycaemic index during optimized insulin therapy.

Many studies have reported the predictive role of unphysiological levels of microalbuminuria for the development of diabetic nephropathy. It is known that physiological levels of 24-h microalbuminuria do not exceed 20 micrograms/min (28.8 mg/day), but a few data are available for shorter periods. Since an accurate 24-h urine collection is difficult to obtain in screening programs, it seems important to study whether a circadian oscillation exists and, if so, to find more precise reference values. Eleven healthy subjects (mean age 30.6 +/- 2.46 years) with normal glucose tolerance and no family history of diabetes mellitus or nephropathy were studied during the usual routine activity. Urines were collected 6 times at 4-h intervals. It was possible to document the existence of a statistically significant circadian rhythm with the following parameters: MESOR 6.95 +/- 0.49 micrograms/min; amplitude 1.96 +/- 0.37 micrograms/min; acrophase 15(06); 95% CL 13(01)-17(45). These data show that reference values are higher during daytime as compared with nighttime and suggest that the time of urine collection must be taken into consideration in order to define the upper physiological limits more precisely.

Significant early morning hyperglycemia (the so-called "dawn phenomenon") has been observed in insulin-dependent diabetics who were otherwise well controlled. This phenomenon, if present, could lead to errors in adapting the basal insulin infusion in CSII treated diabetic patients, because a normal glucose level in the morning could be associated with asymptomatic hypoglycemic values in the night. In order to observe the occurrence and to quantify the magnitude of this phenomenon 14 well controlled CSII-treated type I diabetics were hospitalized for 1 night and samples for the determination of blood glucose (14 patients) and serum cortisol, free insulin and NEFA (8 patients) were drawn at 24.00, 02.00, 04.00, 06.00, 08.00 h. Blood glucose values were slightly but significantly higher at 06.00 than at 02.00 (106 +/- 7.92 v.s. 88.57 +/- 7.02 mg/dl, p less than 0.025, paired Student t test) while serum free insulin values decreased from midnight to 02.00 and then they remained stable. It is concluded that the small increase of blood glucose values in the morning is not a major clinical problem in CSII treated diabetic patients.

The recent availability of human insulin raised the question of evaluating its effectiveness in comparison with traditional animal insulins in the treatment of type I diabetics. 9 long-term CSII treated type I diabetics were shifted from pork insulin to human semisynthetic insulin and followed up to 8 months. The following parameters were evaluated: basal insulin infusion allowing morning blood glucose of 100-140 mg/dl and the serum insulin binding capacity (Bio-Merieux). 5 subjects did not show any variation of basal insulin requirement whereas in 4 subjects the occurrence of hypoglycemia induced a reduction of basal insulin requirement of 15%, 16%, 27% and 15%, after 1,2,2 and 8 months respectively, from the shift to human insulin. Serum insulin binding capacity was undetectable in 3 subjects, unchanged in 4, slightly decreasing in 2. One of these two exhibited as well a decrease of basal insulin requirement (16%), while in the other the state of pregnancy prevented its precise assessment. In conclusion human insulin appears as effective as pork insulin; further studies are needed to confirm the suggestions of its lower immunogenicity.

Aim of this work is to evaluate the relative role of ingested carbohydrates and proteins in determining post-prandial insulin requirement in type I diabetic patients by means of artificial pancreas 5 male diabetics were given two times a day a diet with a high amount of carbohydrates (140g) or with a high amount of proteins (120g) while connected to the Biostator. Basal and post-prandial required insulin was evaluated. Post-prandial insulin requirement after high proteins meals did not appear greater than basal requirement, while insulin requirement after high carbohydrates meals appeared statistically greater than basal requirement. No difference could be observed between insulin requirement after morning (h. 10.00) or afternoon (h. 16.00) meals. These results could be of some help in optimizing the portable infuser-treated diabetic patients.

In our previous observations we could detect the existence of circadian rhythms of either tolbutamide-induced insulin release with the acrophase early in the morning (at 04.20) or an insulin-induced hypoglycemia with the acrophase at 10.30 a.m. Aim of our work was to extend the observation to circannual rhythms of the same parameters. Four healthy young volunteers were submitted to the study in the early months of the year and observed in a 24 hrs-period, every other month, in the course of one year. 250 mg tolbutamide were injected i.v. in each day of the experiment every four hours with starting points at a random sequence. The data were analyzed by microscopic analysis: Halberg's Cosinor method. The highest insulin release occurred in winter (Acrophase: Jan. 19 with 95% confidence limits: Oct. 31 - April 1).

In a group of seven brittle diabetic males, hospitalized, two kind of treatment has been compared: conventional insulin therapy (three daily injections) versus continuous subcutaneous insulin infusion. A strike improvement of metabolic control has been reached with the latter procedure. It is concluded that this new type of treatment seems very useful in brittle diabetics. The possible benefit on diabetic complications remains to be investigated.

Circadian and circannual variations of several endocrine activities and their biological implications in health and diseases were described in men. Aim of our work was to perform a further observation on circannual bioperiodicities of some hormone: free fractions of T3 and T4, cortisol, HGH, PTH and serum insulin. Four healthy young males volunteered to be submitted to the study from June and their blood-samples collected six times a day, every other month, in the course of one year. Our data were analysed by macroscopic (mean chronogram) and microscopic (Cosinor test) methods. First we could document a circadian phase-shift of the highest peak of secretion, occurring in the course of the year, for FT3, FT4, Cortisol, HGH and serum basal insulin. Then we could detect a circannual oscillation of the highest diurnal secretion for FT3 (October), cortisol (December) HGH (April) and serum basal insulin (February). FT4 showed the lowest secretion in October. Almost the same cyclic variations were demonstrated when Mesors and Amplitudes of the same values were examined except for slight shiftings. PTH showed no cyclic variation during the period of observation.

A multicentric study has been carried out to compare the efficacy and the safety of monocomponent human insulins of different concentration (Novo Actrapid HM U-40 and U-100) in CSII-treated Type 1 diabetics. 15 males, all of whom had been diabetic for at least 2 yr, had been treated by CSII and were skillful in the self-monitoring of diabetes were selected for observation at 3 different clinical centres (Bologna, Chieti and Torino). After a 1-week period of insulin dose optimization, the patients were asked not to modify either basal or pre-prandial insulin infusion during the following 2 weeks in which they were treated alternately by U-40 or by U-100 insulin (7 days for each treatment in random sequence). Each day or at least every other day, patients recorded at home a 9-point blood glucose profile by means of glucose-sensitive strips and photometric reading (Reflocheck System-BOEHRINGER MANNHEIM, FRG). The patients used the microinfuser Miles Microjet Bolus 2 for the U-40 infusion and the same model with appropriate modifications for the U-100 infusion. On the last day of each study period, blood samples were drawn after the pre-breakfast insulin bolus. Paired Student's t-test analyses between blood glucose values obtained with different regimens did not show a significant difference in metabolic control. Similarly no difference could be observed in insulin absorption after an identical bolus of U-40 or U-100 insulin. In conclusion human U-100 insulin seems to be as effective and safe as U-40 and is recommended in order to reduce the size of microinfusers.