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Introduction: IDegLira was shown to maintain glycemic control while reducing risk of hypoglycemia and body weight gain. The REX study was designed to generate real-world evidence on the use of IDegLira in Italian clinical practice in two different subgroups of patients, those switching to IDegLira from a basal insulin-supported oral therapy (BOT group) and those from a basal plus bolus insulin regimen (BB group). Methods: Adult patients with T2D diagnosed for at least 12 months and having started IDegLira 2–3 months prior to enrolment, coming from a BOT or BB regimen, were enrolled in this multicenter observational prospective cohort study conducted in 28 Italian centers. This paper presents the methodological framework of the REX study and provides the interim analysis results describing the patients’ baseline characteristics and the clinical reasons for IDegLira treatment initiation. Results: Of the 360 patients enrolled in the REX study, 331 were considered eligible for this interim analysis, 76.4% in the BOT and 23.6% in the BB group. Mean (SD) HbA1c was 8.5% (1.4) in the BOT and 8.2% (1.7) in the BB group. The most common T2D complications were diabetic macroangiopathy and diabetic nephropathy in both groups. The median (interquartile range) insulin daily dose before IDegLira was 15.0 (10.0–20.0) units in the BOT group and 42 (30.0–52.0) in the BB group. Oral antidiabetics were taken by 98% and 51.3% of patients, respectively. The main reason for switching to IDegLira was the inadequate glycemic control in the BOT group (86% of patients), and the intent to simplify the treatment in the BB group (66.7%). Conclusions: IdegLira is initiated after BOT in inadequately controlled patients to improve glycemic control, whereas in BB patients it is used to simplify the therapeutic regimen. Final results of the REX study will shed light on patients’ outcomes after IdegLira treatment under routine clinical care.

Purpose: The aim of this study is to investigate the placental expression of VEGF and CD31 in pregnancies complicated by gestational diabetes (GDM) and the influence of pregestational BMI and gestational weight gain (GWG) on this expression. Methods: We prospectively enrolled pregnant women with diagnosis of GDM and healthy controls who delivered in our Center between December 2016 and May 2017. Patients were grouped according to the presence of GDM and we compared pregnancy characteristics, placental VEGF and CD31 expression between the cases and controls. Immunochemistry analysis was performed to assess biomarkers positivity. Positivity of biomarkers was assessed in a dichotomic fashion with positivity set at 5% for VEGF and 1% for CD31. Results: 39 patients matched inclusion criteria, 29 (74.3%) women with GDM and 10 (25.7%) healthy controls. Immunochemistry analysis showed that VEGF was more expressed in placentas from women with GDM compared to controls (21/29, 72.4% vs 2/10, 20%; p = 0.007), and CD31 was more expressed in placentas from women with GDM compared to controls (6/29, 20.7% vs 0/10, 0%; risk difference 0.2). VEGF positivity was associated with the presence of GDM (aOR 22.02, 95% CI 1.13–428.08, p = 0.04), pregestational BMI (aOR 1.53, 1.00–2.34, p = 0.05) and GWG (aOR 1.47, 95% CI 1.03–2.11, p = 0.03). CD31 positivity was associated with the pregestational BMI (aOR 1.47, 95% CI 1.00–2.17, p = 0.05) and with the gestational weight gain (aOR 1.32, 95% CI 1.01–1.72, p = 0.04). Conclusion: Pregnancies complicated by GDM are characterized by increased placental expression of VEGF and CD31, and the expression of these markers is also independently associated to maternal increased pregestational BMI and GWG, defining the concept of “placental diabesity”.

Aims: Common Psychiatric Disorders (CPDs) are associated with the development of overweight and obesity, the strongest risk factors for the onset and maintenance of Type 2 Diabetes mellitus (T2D). To the best of our knowledge, this is the first study to assess the prevalence of CPDs in patients with T2D in Italy. Methods: This is a monocentric cross-sectional study; n = 184 T2D patients were screened for CPDs using the Patient Health Questionnaire (PHQ). Primary outcome was to evaluate the prevalence of CPDs. To assess association between CPDs and risk factors, we have utilized univariable logistic regression models. Results: 64.1% were men, median age was 67 (59–64) and median BMI 27 (25–30) kg/m2. The 42.9% tested positive for one or more mental disorders, 25.6% for depression. Patients with higher BMI (p = 0.04) had an increased likelihood of testing positive to the PHQ. Patients who had implemented lifestyle changes (p < 0.01) and were aware that mental health is linked to body health (p = 0.07) had a reduction in the likelihood of testing positive. Conclusions: Prevalence of CPDs in T2D patients is higher than in the general population. Since CPDs favor the onset and subsistence of T2D, integrated diabetic-psychiatric therapy is required for improvement or remission of T2D in patients with comorbid CPDs.

Aim: To evaluate predisposition to eating disorders (ED) or body dissatisfaction in adults with type 1 diabetes mellitus (T1DM); to further investigate any differences in ED predisposition between subjects with T1DM on multiple daily injections (MDI) or insulin pumps (CSII) and in respect to control healthy subjects.Methods: We conducted a monocentric, cross-sectional, observational study. We enrolled subjects with T1DM, aged >= 18 years, and healthy subjects (HS) as control group. All participants completed two questionnaires to detect possible predisposition to ED: 34-items Body Shape Questionnaire (BSQ) and Eating Disorder Inventory-3 (EDI-3). HS only filled BSQ. For subjects with T1DM data about glycated hemoglobin and duration of disease were also collected.Results: 162 subjects with T1DM (age 41 +/- 12 years, 77 [47%] males) and 50 HS (age 38 +/- 13 years, 18 (36%) males) were enrolled. 87 subjects with T1DM (54%) were on MDI and 75 (46%) were on CSII. No significant difference in the distribution of BSQ scores between subjects with T1DM and HS was observed (p = 0.551), although 16% of subjects with T1DM scored BSQ class 1 points while 8% of HS scored a BSQ class 1 points. No significant difference in BSQ scores was observed between subjects with T1DM on MDI or CSII. Between these two groups, no differences in EDI-3 scores were observed except for perfectionism score: subjects on MDI present more frequently a predisposition for perfectionism (p < 0.05) and, at a trend level, for bulimia.Conclusion: A non -significant higher percentage of BSQ class 1 was detected in subjects T1DM compared to healthy controls. Among subjects with T1DM, no differences between MDI and CSII were observed in ED predisposition. A more perfectionist personality has been detected among subjects on MDI.

Background: During COVID-19 pandemic, several studies have demonstrated a strong link between SARS-CoV-2 infection and diabetes mellitus. Hyperglycaemia is a frequent event during the infection, also in patients without a history of diabetes. Furthermore, several cases of diabetic ketoacidosis during COVID-19 disease have been described. No data are available about the effects of SARS-CoV-2 infection on glycaemic control in pancreas transplant patients. Case presentation: A 45-year-old woman affected by type 1 diabetes mellitus was treated with kidney-pancreas transplantation in 2015, 6 years before COVID-19 infection. After transplantation, insulin therapy was stopped with a good glycaemic control during the following years.After SARS-CoV-2 infection, she developed severe hyperglycaemia requiring insulin therapy again. During the acute phase of the infection, the detection of antibodies against islet cells (ICA) and against glutamic acid decarboxylase (GAD) was found positive. Conclusions: The onset of hyperglycaemia after SARS-CoV-2 infection might be the result of a direct virus-induced toxicity or the effect of a virus-mediated activation of autoimmunity.

Objective Through a hospital-based SARS-CoV-2 molecular and serological screening, we evaluated the effectiveness of two months of lockdown and two of surveillance, in Milan, Lombardy, the first to be overwhelmed by COVID-19 pandemics during March-April 2020. Methods All subjects presenting at the major hospital of Milan from May-11 to July-5, 2020, underwent a serological screening by chemiluminescent assays. Those admitted were further tested by RT-PCR. Results The cumulative anti-N IgG seroprevalence in the 2753 subjects analyzed was of 5.1% (95%CI = 4.3%-6.0%), with a peak of 8.4% (6.1%-11.4%) 60–63 days since the peak of diagnoses (March-20). 31/106 (29.2%) anti-N reactive subjects had anti-S1/S2 titers >80 AU/mL. Being tested from May-18 to June-5, or residing in the provinces with higher SARS-CoV-2 circulation, were positively and independently associated with anti-N IgG reactivity (OR [95%CI]: 2.179[1.455–3.264] and 3.127[1.18–8.29], respectively). In the 18 RT-PCR positive, symptomatic subjects, anti-N seroprevalence was 33.3% (95% CI: 14.8%-56.3%). Conclusion SARS-CoV-2 seroprevalence in Milan is low, and in a downward trend after only 60–63 days since the peak of diagnoses. Italian confinement measures were effective, but the risk of contagion remains concrete. In hospital-settings, the performance of molecular and serological screenings upon admission remains highly advisable.

Since SARS-CoV-2-based disease (COVID-19) spreads as a pandemic, the necessity of a highly sensitive molecular diagnosis that can drastically reduce false negatives reverse transcription PCR (rtPCR) results, raises as a major clinical need. Here we evaluated the performance of a ddPCR-based assay to quantify SARS-CoV-2 titer in 55 suspected COVID-19 cases with negative rtPCR results thanks to in-house ddPCR assay (targeting RdRp and host RNaseP). Samples were collected at ASST-GOM Niguarda between February and May 2020 at hospital admission. Clinical and imaging data were obtained for clinical staging and definition of disease severity. Patients were mainly female (45.5%) with a median age of 73 (57–84) years. ddPCR-based assay detected SARS-CoV-2 genome in nasopharyngeal samples of 19 (34.5%) patients (median viral-load: 128 copies/mL, IQR: 72–345). In 15 of them (78.9%), chest CT showed a classical COVID-19 bilateral interstitial pneumonia; 14 patients (73.7%) showed severe COVID-19 manifestations. ddPCR did not identify any trace of SARS-CoV-2 genome in the respiratory samples of the remaining 36 patients. The serological assay performed in a subgroup of 34 patients at the later stage of illness (from 3 days to 90 days after) confirmed the presence of SARS-CoV-2 antibodies in all patients tested positive for SARS-CoV-2 in ddPCR (100%). Contrariwise, negative tests were observed in 95.0% ddPCR negative patients (P<0.001). Thanks to a ddPCR-based assay, we achieved a rapid and accurate SARS-CoV-2 diagnosis in rtPCR-negative respiratory samples of individuals with COVID-19 suspect, allowing the rapid taking care and correct management of these patients.

We report the case of a 38 year-old Caucasian man enrolled in a study aimed at investigating the physical properties of red blood cells (RBCs) using advanced microscopy techniques, including Atomic Force Microscopy (AFM). At the time of his first enrolment in the study, he had normal Fasting Plasma Glucose (FPG) values, a BMI of 24.1, and no other symptoms of diabetes, including fatigue, high triglycerides, low HDL cholesterol, and altered inflammatory and corpuscular RBC indices. The subject reported no family history of diabetes, obesity, and cardiovascular diseases. Despite his apparently healthy conditions, the biomechanics of his RBCs was altered, showing increased values of stiffness and viscosity. More than 1 year after the mechanical measurements, the subject was admitted to the Operational Unit of Diabetology of the Policlinico Gemelli Hospital with high blood glucose and glycosylated hemoglobin (HbA1c) levels and diagnosed with type 1 diabetes (T1DM). Here, we show these data, and we discuss the hypothesis that RBC mechanical properties could be sensitive to changes occurring during the pre-diabetic phase of T1DM.

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In this work, we will investigate if red blood cell (RBC) membrane fluidity, influenced by several hyperglycemia-induced pathways, could provide a complementary index of HbA1c to monitor the development of type 2 diabetes mellitus (T2DM)-related macroangiopathic complications such as Peripheral Artery Disease (PAD). The contextual liquid crystalline (LC) domain spatial organization in the membrane was analysed to investigate the phase dynamics of the transition. Twenty-seven patients with long-duration T2DM were recruited and classified in DM, including 12 non-PAD patients, and DM + PAD, including 15 patients in any stage of PAD. Mean values of RBC generalized polarization (GP), representative of membrane fluidity, together with spatial organization of LC domains were compared between the two groups; p-values < 0.05 were considered statistically significant. Although comparable for anthropometric characteristics, duration of diabetes, and HbA1c, RBC membranes of PAD patients were found to be significantly more fluid (GP: 0.501 +/- 0.026) than non-PAD patients (GP: 0.519 +/- 0.007). These alterations were shown to be triggered by changes in both LC microdomain composition and distribution. We found a decrease in Feret diameter from 0.245 +/- 0.281 mu m in DM to 0.183 +/- 0.124 mu m in DM + PAD, and an increase in circularity. Altered RBC membrane fluidity is correlated to a spatial reconfiguration of LC domains, which, by possibly altering metabolic function, are associated with the development of T2DM-related macroangiopathic complications.

The aim of this paper is to describe the direction of the link between stress, depression, increased inflammation and brain-derived neurotrophic factor (BDNF) reduction. We hypothesize that severe stress or prolonged stress can be the driving factor that promote the onset of depression. Both stress and depression, if not resolved over time, activate the production of transcription factors that will switch on pro-inflammatory genes and translate them into cytokines. This cascade fosters systemic chronic inflammation and reduced plasma BDNF levels. Since people with depression have a 60% increased risk of developing type 2 diabetes (T2D) and show high levels of inflammation and low levels of BDNF, we hypothesize possible reasons that might explain why T2D, depression and dementia are often associated in the same patient.

Introduction: IDegLira was shown to maintain glycemic control while reducing risk of hypoglycemia and body weight gain. The REX study was designed to generate real-world evidence on the use of IDegLira in Italian clinical practice in two different subgroups of patients, those switching to IDegLira from a basal insulin-supported oral therapy (BOT group) and those from a basal plus bolus insulin regimen (BB group). Methods: Adult patients with T2D diagnosed for at least 12 months and having started IDegLira 2–3 months prior to enrolment, coming from a BOT or BB regimen, were enrolled in this multicenter observational prospective cohort study conducted in 28 Italian centers. This paper presents the methodological framework of the REX study and provides the interim analysis results describing the patients’ baseline characteristics and the clinical reasons for IDegLira treatment initiation. Results: Of the 360 patients enrolled in the REX study, 331 were considered eligible for this interim analysis, 76.4% in the BOT and 23.6% in the BB group. Mean (SD) HbA1c was 8.5% (1.4) in the BOT and 8.2% (1.7) in the BB group. The most common T2D complications were diabetic macroangiopathy and diabetic nephropathy in both groups. The median (interquartile range) insulin daily dose before IDegLira was 15.0 (10.0–20.0) units in the BOT group and 42 (30.0–52.0) in the BB group. Oral antidiabetics were taken by 98% and 51.3% of patients, respectively. The main reason for switching to IDegLira was the inadequate glycemic control in the BOT group (86% of patients), and the intent to simplify the treatment in the BB group (66.7%). Conclusions: IdegLira is initiated after BOT in inadequately controlled patients to improve glycemic control, whereas in BB patients it is used to simplify the therapeutic regimen. Final results of the REX study will shed light on patients’ outcomes after IdegLira treatment under routine clinical care.

Background and aims: Diabetes mellitus (DM) is a risk factor for left ventricle (LV) diastolic dysfunction. Aim of this study was to investigate whether endothelial and/or autonomic dysfunction are associated with LV diastolic dysfunction in DM patients. Methods: We studied 84 non-insulin-dependent type 2 DM (T2DM) patients with no heart disease by assessing: 1) LV diastolic function by echocardiography; 2) peripheral vasodilator function, by measuring flow-mediated dilation (FMD) and nitrate-mediate dilation (NMD); 3) heart rate variability (HRV) on 24-h Holter electrocardiographic monitoring. Results: Twenty-five patients (29.8%) had normal LV diastolic function, while 47 (55.9%) and 12 (14.3%) showed a mild and moderate/severe diastolic dysfunction, respectively. FMD in these 3 groups was 5.25 ± 2.0, 4.95 ± 1.6 and 4.43 ± 1.8% (p = 0.42), whereas NMD was 10.8 ± 2.3, 8.98 ± 3.0 and 8.82 ± 3.2%, respectively (p = 0.02). HRV variables did not differ among groups. However, the triangular index tended to be lower in patients with moderate/severe diastolic dysfunction (p = 0.09) and a significant correlation was found between the E/e’ ratio and both the triangular index (r = −0.26; p = 0.022) and LF amplitude (r = −0.29; p = 0.011). Conclusions: In T2DM patients an impairment of endothelium-independent, but not endothelium-dependent, dilatation seems associated with LV diastolic dysfunction. The possible role of cardiac autonomic dysfunction in diastolic dysfunction deserves investigation in larger populations of patients.

Maturity-onset diabetes of the young (MODY) is a rare form of non-autoimmune diabetes with an autosomal dominant inheritance. To date, 14 genes have been reported as genetic basis of MODY. GCK gene, encoding the glucokinase enzyme, was the first MODY gene to be identified. GCK heterozygous inactivating variants cause the GCK-MODY or MODY2 subtype. However, partial or whole gene deletions have been rarely identified, showing it to be a rare cause of GCK-MODY. We reported the molecular evaluation of a Ukrainian patient with clinical diagnosis of MODY2. We performed the Next generation sequencing of the clinical exome using the Clinical Exome Solution® kit (SOPHiA Genetics), followed by the design of a 14 genes virtual panel related to the suggestive diagnosis of MODY. Bioinformatics analysis was performed using the SOPHiA DDM platform (SOPHiA Genetics). The SALSA MLPA kit for MODY (MRC-Holland) was used for relative quantification of GCK exons. From the molecular evaluation, no pathogenic sequence variants were detected in the investigated genes. Copy Number Variation analysis was able to identify a large deletion involving the last three exons of the GCK gene. This result was confirmed by MLPA. To the best of our knowledge, the identified rearrangement has never been reported in the literature.

A 64-year-old woman has undergone in February 2019 total spleen-preserving pancreatectomy for cystic pancreatic neoplasia. In her medical history, in 2010 she also underwent total thyroidectomy because of thyroid cancer. She is a former smoker who quitted smoking in 2014. From February 2019, she assumes pancrelipase 10.000 UI daily as pancreatic replacement therapy and from 2010 levotiroxine for thyroid replacement. At the discharge, insulin therapy with multiple daily injections, supported by advanced educational therapeutic plan about carbohydrates counting, was started, but, after a severe hypoglycemic event, she developed an important fear of hypoglycemia with a consequent wrong approach to the insulin therapy, preferring to maintain glycemic values higher than 200 mg/dL in order to avoid hypoglycemia. Insulin therapy with continuous subcutaneous insulin infusion (CSII) was suggested, but she refused mainly because of discomfort. Yearly mean glycated hemoglobin (HbA1c) was 74 mmol/mol (8.9%). In December 2019, she was admitted to emergency room because of another severe hypoglycemia with loss of consciousness due to inappropriate insulin administration. After this event, patient started real-time continuous glucose monitoring (CGM—Medtronic Guardian Connect, Northridge California).

Respiratory viruses are associated with more severe symptoms and complications in diabetic subjects. We hypothesize that the diabetic neuropathy could provide a signifcant contribution to risk of disease severity. The diabetic neuropathy and the autonomic dysfunction might determine the loss of immune response regulation and contribute to reduction of pulmonary function, in particular gas exchange.

Background: Telemedicine use in chronic disease management has markedly increased during health emergencies due to COVID-19. Diabetes and technologies supporting diabetes care, including glucose monitoring devices, software analyzing glucose data, and insulin delivering systems, would facilitate remote and structured disease management. Indeed, most of the currently available technologies to store and transfer web-based data to be shared with health care providers. Objective: During the COVID-19 pandemic, we provided our patients the opportunity to manage their diabetes remotely by implementing technology. Therefore, this study aimed to evaluate the effectiveness of 2 virtual visits on glycemic control parameters among patients with type 1 diabetes (T1D) during the lockdown period. Methods: This prospective observational study included T1D patients who completed 2 virtual visits during the lockdown period. The glucose outcomes that reflected the benefits of the virtual consultation were time in range (TIR), time above range, time below range, mean daily glucose, glucose management indicator (GMI), and glycemic variability. This metric was generated using specific computer programs that automatically upload data from the devices used to monitor blood or interstitial glucose levels. If needed, we changed the ongoing treatment at the first virtual visit. Results: Among 209 eligible patients with T1D, 166 completed 2 virtual visits, 35 failed to download glucose data, and 8 declined the visit. Among the patients not included in the study, we observed a significantly lower proportion of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) users (n=7/43, 16% vs n=155/166, 93.4% and n=9/43, 21% vs n=128/166, 77.1%, respectively; P<.001) compared to patients who completed the study. TIR significantly increased from the first (62%, SD 18%) to the second (65%, SD 16%) virtual visit (P=.02); this increase was more marked among patients usi

Continuous glucose monitoring (CGM) might be an effective tool to improve glycemic control in gestational diabetes mellitus (GDM). Few data are available about its utilization as a diagnostic tool to find potential alterations of glycemia in subjects with normal oral glucose tolerance test (OGTT). In this preliminary prospective real-life observational study, we aimed to analyze the glycemic pattern in normal and gestational diabetes mellitus (GDM) women by continuous glucose monitoring (CGM) in order to detect potential differences between the two groups and glycemic alterations despite a normal OGTT. After the screening for GDM, subjects were connected to a CGM system for seven consecutive days. The areas under the curve of the first 60 minutes after each meal and 60 minutes before breakfast were analyzed. Women with normal OGTT that during CGM showed impaired glycemic values (more than 95 fasting or more than 140 one hour after meals or more than 120 two hours after meals) performed one week of self-monitoring of blood glucose (SMBG). After OGTT, 53 women considered normal and 46 affected by GDM were included. CGM parameters did not show any differences between the two groups with impaired glycemic excursions found in both groups. After CGM period, 33 women with normal OGTT showed abnormal glycemic patterns. These 33 women then performed one week of SMBG. After evaluation of one week of SMBG, 21 required diet therapy and 12 required insulin treatment and were followed until the delivery. An increase in gestational weight gain was observed in normal women with normal OGTT but this was not significant. No significant data were found regarding neonatal outcomes in the two groups of women. In conclusion, CGM use in pregnancy might help to detect glycemic fluctuations in women with normal OGTT, improving their treatment and outcomes.

Background: A high level of glycosylated haemoglobin (HbA1c), which is a nonenzymatic glycosylation product, is correlated with an increased risk of developing microangiopathic complications in Diabetes Mellitus (DM). Erythrocyte membrane fluidity could provide a complementary index to monitor the development of complications since it is influenced by several hyperglycaemia-induced pathways and other independent risk factors. Materials and methods: 15 healthy controls and 33 patients with long-duration (≥20 years) type 1 Diabetes Mellitus (T1DM) were recruited. Diabetic subjects were classified into two groups: T1DM, constituted by 14 nonretinopathic patients, and T1DM + RD, constituted by 19 patients in any stage of diabetic retinopathy. Red blood cells (RBC) were incubated with the fluorescent Laurdan probe and median values of Generalized Polarization (GP), representative of membrane fluidity, were compared between the two groups. Baseline characteristics among groups have been compared with Student's t test or ANOVA. Values of P <.05 were considered statistically significant. Results: All the participants were comparable for age, Body Mass Index (BMI), creatinine and lipid profile. The duration of diabetes was similar for T1DM (34.4 ± 7.8 years) and T1DM + RD (32.8 ± 7.5 years) subjects as well as values of HbA1c: (55.6 ± 8.1) mmol/mol for T1DM and (61.2 ± 11.0) mmol/mol for T1DM + RD, respectively. Erythrocyte plasmatic membranes of RD patients were found to be more fluid (GP: 0.40 ± 0.04) than non-RD patients (GP: 0.43 ± 0.03) with a statistically significant difference (P =.035). Conclusions: Altered erythrocyte membrane fluidity may therefore represent a marker of retinopathy in T1DM patients as a result of post-translational modifications of multifactorial aetiology (nonenzymatic glycosylation of proteins, generation of reactive oxygen speci

In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID19.

Miller et al investigate the risk factors involved in First Manifestation of Cardiovascular Disease in Type1 Diabetes. Surprisingly in this paper no evaluation was performed about the presence of diabetic retinopathy (DR) and neuropa- thy (DN) in the population included in the study. It is well known that in type 1 diabetes microvascular complications burden might be associated with all cause mortality and cardiovascular events, and regarding DR this significant correlation remained after adjusting for traditional CV risk factors. Otherwise DN, in particular autonomic DN, regulates inflammation, one of the main mechanisms involved in pathogenesis of macrovascular complications. The modula- tion and the improvement of Sympatho-vagal balance produce a significant reduction of the markers of inflammation. For example calcium score, measure of atherosclerotic burden, is associated with both DR and DN [4,5] and vascular calcification is linked to DN. Previously we showed, although in type 2 diabetes, that diabetic subjects have a predominantly calcific plaque phenotype at the level of Minimum Lumen Area of culprit segment with less lipid quadrants and a smaller lipid arc. It should support the potential involvement of other mechanisms in the pathogenesis of macrovascular complications in diabetes. Furthermore diabetic subjects exhibit at the time of first acute coronary event, a better collateral development towards the culprit vessel despite more severe coronary atherosclerosis than non-diabetic subjects. Therefore I hypothesize that in diabetes, and in particular in type 1 diabetes with microvascular complications, there is an early development of cardiovascular atherosclerosis with the formation of collateral vessels, as mechanism of adaptation, that can resemble what happens in the DR with retinal neovascularization, and the occurrence of first cardiovacular event might be the consequence of a breakdown of this equilibrium. It could be the consequence of the progress

Aims: This real-world study evaluated the changes in glycated haemoglobin (HbA1c) and continuous glucose monitoring (CGM) metrics associated with use of the implantable 180-day Eversense CGM System (Eversense) in patients with type 1 diabetes. Materials and methods: This was a prospective, multicentre, observational study among adult participants aged ≥18 years with type 1 diabetes across seven diabetes-care centres in Italy who had Eversense inserted for the first time. HbA1c was measured at baseline and at 180 days. Changes in time in range [TIR (glucose 70–180 mg/dL)], time above range [TAR (glucose >180 mg/dL)], time below range [TBR (glucose <70 mg/dL)] and glycaemic variability were also assessed. Data were also analysed by previous CGM use and by mode of insulin delivery. Results: One-hundred patients were enrolled (mean age 36 ± 12 years, mean baseline HbA1c 7.4 ± 0.92% [57 ± 10 mmol/mol]). Fifty-six per cent of patients were users of the continuous subcutaneous insulin infusion pump and 45% were previous users of CGM. HbA1c significantly decreased in patients after 180 days of sensor wear (−0.43% ± 0.69%, 5 ± 8 mmol/mol, P < 0.0001). As expected, CGM-naïve patients achieved the greatest reduction in HbA1c (−0.74% ± 0.48%, 8 ± 5 mmol/mol). TIR significantly increased and TAR and mean daily sensor glucose significantly decreased while TBR did not change after 180 days of sensor wear. Conclusions: Real-world clinical use of the Eversense CGM System for 180 days was associated with significant improvements in HbA1c and CGM metrics among adults with type 1 diabetes. The study is registered on clinicaltrials.gov (NCT04160156).

Diabetes could be a risk factor for severity and mortality in patients with coronavirus disease 2019 COVID-19. It has been hypothesized that DPP4 inhibition, a therapy currently available for type 2 diabetes, might represent a target for decreasing the risk of the acute respiratory complications of the COVID-19 infection but (1) lack of demonstration of SARS-CoV2 binding to DPP4 (2) possible protective role of sDPP4 in Middle East respiratory Syndrome (MERS-CoV) (3) demonstrated inhibition and downregulation of DPP4 by HIV1 and MERS-CoV and (4) not exclusive role of the receptor binding in tropism of the Coronavirus family, support that DPP4 inhibition at present doesn't represent a plausible approach to mitigate COVID-19.

Background: The diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. Introduction: The present review provides a concise account of the advances made over the last twenty-five years in understanding the pathogenesis and management of Charcot neuroarthropathy (CN). Methods: In this study, the widely known pathogenetic mechanisms underpinning CN are brought into focus, particularly the role of RANKL/RANK/OPG system and advanced glycation end production in the pathogenesis of CN. Furthermore, other potential triggering factors, namely nitric oxide, endothelial dysfunction, macro calcifications and body weight that influence CN have also been discussed. Results: The wide range of diagnostic tools available to clinicians for accurate staging of this pathology has been examined, particularly radiological and nuclear medicine imaging. Additionally, the difficult differential diagnosis between osteomyelitis and CN is also elucidated. Conclusion: The review concludes with the comprehensive summary of the major promising therapeutic strategies, including conservative treatment involving orthopedic devices, pharmacological approach, and the most common surgical techniques currently employed in the diagnosis and treatment of this acute disease.

Background: Diabetic Ketoacidosis (DKA) is one of the most commonly encountered diabetic complication emergencies. It typically affects people with type 1 diabetes at the onset of the disease. It can also affect people with type 2 diabetes, although this is uncommon. Methods: Research and online content related to diabetes online activity is reviewed. DKA is caused by a relative or absolute deficiency of insulin and elevated levels of counter-regulatory hormones. Results: Goals of therapy are to correct dehydration, acidosis, and to reverse ketosis, gradually restoring blood glucose concentration to near normal. Conclusion: It is essential to monitor potential complications of DKA and, if necessary, to treat them and any precipitating events.

Background: A high level of glycosylated haemoglobin (HbA1c), which is a nonenzymatic glycosylation product, is correlated with an increased risk of developing microangiopathic complications in Diabetes Mellitus (DM). Erythrocyte membrane fluidity could provide a complementary index to monitor the development of complications since it is influenced by several hyperglycaemia-induced pathways and other independent risk factors. Materials and methods: 15 healthy controls and 33 patients with long-duration (≥20 years) type 1 Diabetes Mellitus (T1DM) were recruited. Diabetic subjects were classified into two groups: T1DM, constituted by 14 nonretinopathic patients, and T1DM + RD, constituted by 19 patients in any stage of diabetic retinopathy. Red blood cells (RBC) were incubated with the fluorescent Laurdan probe and median values of Generalized Polarization (GP), representative of membrane fluidity, were compared between the two groups. Baseline characteristics among groups have been compared with Student's t test or ANOVA. Values of P <.05 were considered statistically significant. Results: All the participants were comparable for age, Body Mass Index (BMI), creatinine and lipid profile. The duration of diabetes was similar for T1DM (34.4 ± 7.8 years) and T1DM + RD (32.8 ± 7.5 years) subjects as well as values of HbA1c: (55.6 ± 8.1) mmol/mol for T1DM and (61.2 ± 11.0) mmol/mol for T1DM + RD, respectively. Erythrocyte plasmatic membranes of RD patients were found to be more fluid (GP: 0.40 ± 0.04) than non-RD patients (GP: 0.43 ± 0.03) with a statistically significant difference (P =.035). Conclusions: Altered erythrocyte membrane fluidity may therefore represent a marker of retinopathy in T1DM patients as a result of post-translational modifications of multifactorial aetiology (nonenzymatic glycosylation of proteins, generation of reactive oxygen speci

Wernicke-Korsakoff encephalopathy (WKE) is a neurologic disease due to a severe thiamine deficiency. This vitamin, an essential cofactor for cellular metabolism, is not produced by the human organism, so its total supply comes from diet, being absorbed from the duodenum. Wernicke described its acute onset in 1881; its classic form is characterized by the triad of ataxia, abnormal mental state, and ocular abnormalities (especially nystagmus). Although it is most commonly associated with chronic alcohol misuse (90% of all cases in USA), other medical conditions resulting in inadequate thiamine intake, such as gastrointestinal disease (vomiting, diarrhea), hyperemesis gravidarum, hemodialysis, sepsis, GI cancer, Crohn’s disease, psychiatric disorders, HIV infection, and malnutrition can determinate the onset of the disease. Another well-established cause of WKE is bariatric surgery. However, in most bariatric surgery-related cases, there were no specific neurological symptoms and no definitive neuroimaging markers were established. Moreover, a recent review upon the most common bariatric procedures showed that the large majority of cases develop in a range of onset between 4 and 12 weeks post-surgery (12 days up to 18 months). No significant difference in the time of onset in the different surgical procedures was observed. Roux-en-Y gastric bypass was the most related procedure (52%), followed by sleeve gastrectomy (21%); biliopancreatic diversion was associated with a small percentage of cases of WKE (3%). Biliopancreatic diversion is a single surgical procedure combining a sleeve gastrectomy and gut bypass, connecting the reduced stomach (about the 20% of the former organ) and the second tract of duodenum with the last part of the small intestine, with the aim to reduce calorie and nutrient absorption. Precipitating factors were persistent vomiting, diarrhea, rapid weight loss, anorexia, minimal food intake or glucose-containing intravenous feeding, alcohol misuse, a

In patients with growth hormone (GH) deficiency (GHD), low doses of recombinant human GH (rhGH) have a similar or better long-term clinical effect than higher doses. Pharmacogenetic studies suggest that GH receptor (GHR) polymorphism only influences some metabolic parameters. Nonetheless, there is no clear scientific evidence proving the effects of lower rhGH dose regimens on metabolic parameters. The aim of our prospective study was to evaluate the effects of GHR polymorphism in adult GHD patients treated with low rhGH dose during short- (6 and 12 months) and long-term (5 years) follow-up. Sixty-nine GHD adult patients were studied, before and during treatment with rhGH, using a standardised low-dose protocol calculated on the basis of body weight (0.01-0.03 mg kg-1 week-1 ) and monitored by an insulin-like growth factor (IGF)-I plasma assay, as well as anthropometric and metabolic parameters. The GHR genotype (flfl, fld3 or d3d3) was determined from the peripheral blood. d3-GHR carriers showed a more effective short- and long-term response to low rhGH dose with respect to low-density lipoprotein reduction, body composition and blood pressure (homozygous patients only); d3-GHR homozygosity is related to a significant IGF-I increase during short-term follow-up. Regression analysis demonstrated that rhGH dose, age at diagnosis and GHR genotype are the major determinants of IGF-I increase at 6 and 12 months of replacement therapy. The d3d3-GHR genotype may influence some metabolic effects during the short- and long-term follow-up of low rhGH dose and could be an independent determinant of the increase of IGF- I during short-term follow-up.

Diabetic foot ulcers (DFUs), a micro-vascular complication, are associated with a substantial increase in morbidity and mortality. DFUs are a complicated mixture of neuropathy, peripheral arterial diseases, foot deformities, and infections. Foot infections are frequent and potentially devastating complications. Infection prospers in more than half of all foot ulcers and is the factor that most often leads to lower extremity amputation. The complications of microbial flora span the spectrum from superficial cellulitis to chronic osteomyelitis and gangrenous extremity lower limb amputations. Wounds without confirmed soft tissue or bone infections do not require antibiotic therapy. Mild and moderate infections need empiric therapy covering Gram-positive cocci, while severe infections caused by drug-resistant organisms require broad-spectrum anti-microbials targeting aggressive Gram-negative aerobes and obligate anaerobes.

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OBJECTIVE: Obesity and gestational diabetes mellitus (GDM) are rising worldwide. This study retrospectively evaluated the role of excessive gestational weight gain (eGWG) in women with GDM and different pre-pregnancy body mass indices (BMIs). PATIENTS AND METHODS: Optimal glycaemic control was defined as achieving glucose target thresholds in more than 80% of measurements. 283 women with GDM were categorized as underweight, normal weight, overweight or obese based on WHO's classification scheme. eGWG was defined as >18.0 kilograms for women who were underweight, >15.8 kilograms for those who were normal weight, >11.3 kilograms for those who were overweight and >9.0 kilograms for those who were obese. For the analysis, women were divided into two groups: normal and excessive GWG. The main outcomes measured were incidences of large/small for gestational age (LGA/SGA), macrosomia, preterm delivery, hypertensive disorders and caesarean sections (CS). RESULTS: Excessive GWG was associated with higher birth weight and percentile (p<0.001), and with a higher prevalence of LGA (p<0.001), macrosomia (p=0.002) and hypertensive disorders (p=0.036). No statistical differences were found for the week of delivery, or prevalence of CS and SGA. The multivariate analysis highlighted both pre-pregnant BMI and eGWG as independent risk factors for LGA and macrosomia. Women with a pre-pregnant BMI of at least 25 and eGWG have a 5.43-fold greater risk of developing LGA (p=0.005). CONCLUSIONS: When combined with an inadequate pre-pregnant BMI, eGWG acts as a "synergic risk factor" for a poor outcome. When obesity or GDM occur, an optimal GWG can guarantee a better pregnancy outcome.