Evaluation of time in tight range and the glycaemia risk index in adults with type 1 diabetes using an advanced hybrid closed loop system: A 1-year real-world assessment.

AIM: To assess the long-term glycaemic outcomes, with additional metrics, in adults with type 1 diabetes (T1D) using the Tandem t:slim X2 with Control-IQ technology advanced hybrid closed-loop (AHCL) system. METHODS: This was a single-centre, retrospective study involving 56 T1D patients who transitioned to the Tandem t:slim X2 with Control-IQ system. The primary and secondary endpoints consisted of variations in time in tight range (TiTR; 70-140 mg/dL) and the glycaemia risk index (GRI), respectively. Additional standardized continuous glucose monitoring (CGM) metrics, mean sensor glucose, coefficient of variation, the glucose management indicator (GMI), HbA1c and insulin daily dose, were also evaluated. Variables were measured at baseline and at 15 days, 3 months, 6 months and 1 year after Tandem t:slim X2 Control-IQ initiation. Glucose outcomes are expressed as mean (standard deviation). RESULTS: Use of Tandem t:slim X2 with Control-IQ over 1 year was associated with an increase in mean TiTR, from 38.11% (17.05%) to 43.10% (13.20%) (P = .059), and with a decline in the GRI, from 41.03 (25.48) to 28.55 (16.27) (P = .008). CGM metrics, including time in range and time above range, showed consistent improvements. Mean sensor glucose, the GMI and HbA1c decreased significantly over time. After an initial increase, insulin daily dose remained stable throughout the 12 months. CONCLUSIONS: The results highlight the sustained effectiveness of Tandem t:slim X2 with Control-IQ in improving glycaemic outcomes over 1 year and support the use of this technology for the management of T1D.

Placental diabesity: placental VEGF and CD31 expression according to pregestational BMI and gestational weight gain in women with gestational diabetes.

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".

Microvascular complications identify a specific coronary atherosclerotic phenotype in patients with type 2 diabetes mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are considered as a homogeneous cohort of patients. However, the specific role of diabetic microvascular complications (DMC), in determining the features of coronary plaques is poorly known. We investigated whether the presence of DMC may identify a different phenotype of patients associated to specific clinical, angiographic, optical coherence tomography (OCT) features and different prognosis. METHODS: We prospectively enrolled consecutive T2DM patients with obstructive coronary artery disease (CAD) at their first coronary event. Patients were stratified according to the presence or absence of DMC, including diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. OCT assessment of the culprit vessel was performed in a subgroup of patients. The incidence of major adverse cardiac events (MACEs) was assessed at follow-up. RESULTS: We enrolled 320 T2DM patients (mean age 70.3 ± 8.8 years; 234 [73.1%] men, 40% acute coronary syndrome, 60% chronic coronary syndrome). Patients with DMC (172 [53.75%]) presented a different clinical and biochemical profile and, of importance, a higher prevalence of multivessel CAD (109 [63.4%] vs. 68 [45.9%], p = 0.002). At OCT analysis, DMC was associated to a higher prevalence of large calcifications and healed plaques and to a lower prevalence of lipid plaques. Finally, MACEs rate was significantly higher (25 [14.5%] vs. 12 [8.1%], p = 0.007) in DMC patients, mainly driven by a higher rate of planned revascularizations, and DMC predicted the occurrence of MACEs (mean follow-up 33.4 ± 15.6 months). CONCLUSIONS: The presence of DMC identifies a distinct diabetic population with more severe CAD but with a more stable pattern of coronary atherosclerosis.

Relation of endothelial and cardiac autonomic function with left ventricle diastolic function in patients with type 2 diabetes mellitus.

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.

Spatial Reorganization of Liquid Crystalline Domains of Red Blood Cells in Type 2 Diabetic Patients with Peripheral Artery Disease.

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 µm in DM to 0.183 ± 0.124 µm 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.

Erythrocyte membrane fluidity as a marker of diabetic retinopathy in type 1 diabetes mellitus.

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 species, lipid peroxidation).

Teleassistance for Patients With Type 1 Diabetes During the COVID-19 Pandemic: Results of a Pilot Study.

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 using the traditional meter (n=11; baseline TIR=55%, SD 17% and follow-up TIR=66%, SD 13%; P=.01) than among those using CGM, and in those with a baseline GMI of ≥7.5% (n=46; baseline TIR=45%, SD 15% and follow-up TIR=53%, SD 18%; P<.001) than in those with a GMI of <7.5% (n=120; baseline TIR=68%, SD 15% and follow-up TIR=69%, SD 15%; P=.98). The only variable independently associated with TIR was the change of ongoing therapy. The unstandardized beta coefficient (B) and 95% CI were 5 (95% CI 0.7-8.0) (P=.02). The type of glucose monitoring device and insulin delivery systems did not influence glucometric parameters. CONCLUSIONS: These findings indicate that the structured virtual visits help maintain and improve glycemic control in situations where in-person visits are not feasible.

Clinical use of a 180-day implantable glucose sensor improves glycated haemoglobin and time in range in patients with type 1 diabetes.

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).

Hypothalamitis: a diagnostic and therapeutic challenge.

To report an unusual case of biopsy-proven autoimmune hypophysitis with predominant hypothalamic involvement associated with empty sella, panhypopituitarism, visual disturbances and antipituitary antibodies positivity. We present the history, physical findings, hormonal assay results, imaging, surgical findings and pathology at presentation, together with a 2-year follow-up. A literature review on the hypothalamic involvement of autoimmune hypophysitis with empty sella was performed. A 48-year-old woman presented with polyuria, polydipsia, asthenia, diarrhea and vomiting. The magnetic resonance imaging (MRI) revealed a clear suprasellar (hypothalamic) mass, while the pituitary gland appeared atrophic. Hormonal testing showed panhypopituitarism and hyperprolactinemia; visual field examination was normal. Pituitary serum antibodies were positive. Two months later an MRI documented a mild increase of the lesion. The patient underwent biopsy of the lesion via a transsphenoidal approach. Histological diagnosis was lymphocytic "hypothalamitis". Despite 6 months of corticosteroid therapy, the patient developed bitemporal hemianopia and blurred vision, without radiological evidence of chiasm compression, suggesting autoimmune optic neuritis with uveitis. Immunosuppressive treatment with azathioprine was then instituted. Two months later, an MRI documented a striking reduction of the hypothalamic lesion and visual field examination showed a significant improvement. The lesion is stable at the 2-year follow-up. For the first time we demonstrated that "hypothalamitis" might be the possible evolution of an autoimmune hypophysitis, resulting in pituitary atrophy, secondary empty sella and panhypopituitarism. Although steroid treatment is advisable as a first line therapy, immunosuppressive therapy with azathioprine might be necessary to achieve disease control.

Radically resected pituitary adenomas: prognostic role of Ki 67 labeling index in a monocentric retrospective series and literature review.

Ki-67 Labeling Index is an immunocytochemical marker of cell proliferation. The correlation of Ki-67 expression with pituitary adenomas recurrence has been investigated and is highly debated. Aim of this study was to evaluate whether Ki-67 correlates with recurrence even in patients with an apparently completely removed pituitary adenoma. We retrospectively reviewed the database of the Hypothalamic-Pituitary Disease Unit at the Catholic University of Rome, collected between 2003 and 2011. Inclusion criteria were: patients who underwent surgery at the Department of Neurosurgery with an apparently complete removal of a pituitary adenoma; Ki-67 histological evaluation by the same operator and values of <3%. All patients underwent endocrine evaluation of the hypothalamic-pituitary function, ophthalmologic and neuro-radiological examinations, during the preoperative period and follow-up. Out of 490 patients recorded on the database of the Hypothalamic-Pituitary Disease Unit at the Catholic University of Rome, 191 cases met the inclusion criteria. Recurrence was observed in 49 cases (25.7% of the patients who had undergone radical excision). Optional cut-off value was identified at Ki-67 values of 1.50%. This was associated with worse disease-free survival time, even after correction for age at treatment, gender, positivity to p53, functional classification and Knosp grading. Ki-67 labeling index may be useful in postoperative management, even in patients who underwent radical PA removal. We suggest a Ki-67 cut-off value of 1.5% to plan an adequate clinical follow-up.

Von Willebrand factor hyperactivity affects the outcome of lower limb revascularization in subjects with type 2 diabetes mellitus complicated by diabetic foot vasculopathy: An observational pilot study.

Aim of this study is to evaluate any differences in VWF antigen, VWF activity and ADAMTS-13 activity before and after successful and non-successful Percutaneous Transluminal Angioplasty (PTA) in subjects with type 2 diabetes (T2DM) complicated by Chronic limb-threatening ischemia (CLTI) in diabetic foot vasculopathy. METHODS: In this prospective observational pilot study, we enrolled 35 T2DM subjects who underwent lower limb PTA. Transcutaneous oximetry was performed in all patients before and 6 weeks after PTA. The change in oxygen partial pressure (TcpO2) before and after PTA was expressed as TcpO2-delta (ΔTcpO2). VWF antigen, VWF activity and ADAMTS-13 activity were measured before and 6 weeks after PTA; changes were expressed as delta and ratio from baseline. RESULTS: Subjects with ∆TcpO2 < 15 mmHg presented higher ΔVWF activity (p = 0.050) and lower ADAMTS-13 activity ratio (p = 0.080). Subjects with ∆TcpO2 < 30 mmHg showed lower ADAMTS-13 activity Δ and ratio (p = 0.028). CONCLUSIONS: VWF antigen levels and VWF activity may potentially affect PTA outcome. Higher levels of VWF could derive from VWF release as consequence of PTA-induced mechanical endothelial damage and/or oxidative stress-induced modifications of VWF structure with impairment of VWF-ADAMTS13 interactions.

Reconsidering the role of depression and common psychiatric disorders as partners in the type 2 diabetes epidemic.

Common psychiatric disorders (CPDs) and depression contribute significantly to the global epidemic of type 2 diabetes (T2D). We postulated a possible pathophysiological mechanism that through Bridge-Symptoms present in depression and CPDs, promotes the establishment of emotional eating, activation of the reward system, onset of overweight and obesity and, ultimately the increased risk of developing T2D. The plausibility of the proposed pathophysiological mechanism is supported by the mechanism of action of drugs such as naltrexone-bupropion currently approved for the treatment of both obesity/overweight with T2D and as separate active pharmaceutical ingredients in drug addiction, but also from initial evidence that is emerging regarding glucagon-like peptide 1 receptor agonists that appear to be effective in the treatment of drug addiction. We hope that our hypothesis may be useful in interpreting the higher prevalence of CPDs and depression in patients with T2D compared with the general population and may help refine the integrated psychiatric-diabetic therapy approach to improve the treatment and or remission of T2D.

Insulin pump treatment vs. multiple daily insulin injections in patients with poorly controlled Type 2 diabetes mellitus: a comparison of cardiovascular effects.

AIMS: Both hyperglycaemia and large glycaemic variability are associated with worse outcomes in patients with Type 2 diabetes mellitus (T2DM), possibly causing sympatho-vagal imbalance and endothelial dysfunction. Continuous subcutaneous insulin injection (CSII) improves glycemic control compared to multiple daily insulin injections (MDI). We aimed to assess whether CSII may improve cardiac autonomic and vascular dilation function compared to MDI. METHODS: We enrolled T2DM patients without cardiovascular disease with poor glycaemic control, despite optimized MDI therapy. Patients were randomized to continue MDI (with multiple daily peripheral glucose measurements) or CSII; insulin dose was adjusted to achieve optimal target ranges of blood glucose levels. Patients were studied at baseline and after 6 months by: 1) flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the brachial artery; 2) heart rate variability (HRV) by 24-hour ECG Holter monitoring (HM). 7-day continuous glucose monitoring (CGM) was performed in 9 and 8 patients of Group 1 and 2, respectively. RESULTS: Overall, 21 patients were enrolled, 12 randomized to CSII (Group 1) and 9 to MDI (Group 2). The daily dose of insulin and Hb1AC did not differ significantly between the 2 groups, both at baseline and at follow-up. Glucose variability showed some significant improvement at follow-up in the whole population, but no differences were observed between the 2 groups. Both FMD and NMD, as well as HRV parameters, showed no significant differences between the 2 groups at 6-month follow-up. CONCLUSIONS: In this randomized small study we show that, in T2DM patients, CSII achieves a similar medium-term glycemic control compared to MDI, without any adverse effect on the cardiovascular system.

Type 1 diabetes recurrence after SARS-CoV-2 infection in a subject with pancreas transplantation.

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.

The development and evolution of insulin pumps: from early beginnings to future prospects.

Diabetes technology has proliferated extensively over the past few decades with vast ameliorations in glucose monitoring and in insulin delivery systems. From a treatment based on daily insulin injections, we have moved to increasingly advanced technologies. Despite such advancements which have allowed better glycemic control, decreased diabetes-related complications, and improved the quality of life among diabetic patients, it has left many individuals unsatisfied with the current rate of commercial artificial pancreas development, stemming the need for further research into novel technologies. Accordingly, the Juvenile Diabetes Research Foundation has marked three generations for the development of an artificial pancreas comprising historical landmarks and future prospects which aim to produce an advanced technological system that attempts to mimic the endogenous pancreas, eliminating the need for user input. This review presents a synopsis of the development and evolution of insulin pumps, starting with the earliest technologies available such as continuous subcutaneous insulin infusion and continuous glucose monitoring as separate components, to currently available integrated advanced closed-loop hybrid systems and possible future technologies. The aim of the review is to provide insight of the advantages and limitations of past and currently available insulin pumps with the hope of driving research into novel technologies that attempt to mimic endogenous pancreatic function as closely as possible.

Lights and shadows on the use of metformin in pregnancy: from the preconception phase to breastfeeding and beyond.

During pregnancy, the complex hormonal changes lead to a progressive decrease of insulin sensitivity that can drive the onset of gestational diabetes (GDM) or worsen an already-known condition of insulin resistance like type 2 diabetes, polycystic ovarian syndrome (PCOS), and obesity, with complications for the mother and the fetus. Metformin during pregnancy is proving to be safe in a growing number of studies, although it freely crosses the placenta, leading to a fetal level similar to maternal concentration. The aim of this literature review is to analyze the main available evidence on the use of metformin during, throughout, and beyond pregnancy, including fertilization, lactation, and medium-term effects on offspring. Analyzed studies support the safety and efficacy of metformin during pregnancy. In pregnant women with GDM and type 2 diabetes, metformin improves obstetric and perinatal outcomes. There is no evidence that it prevents GDM in women with pregestational insulin resistance or improves lipid profile and risk of GDM in pregnant women with PCOS or obesity. Metformin could have a role in reducing the risk of preeclampsia in pregnant women with severe obesity, the risk of late miscarriages and preterm delivery in women with PCOS, and the risk of ovarian hyperstimulation syndrome, increasing the clinical pregnancy rate in women with PCOS undergoing in vitro fertilization (IVF/FIVET). Offspring of mothers with GDM exposed to metformin have no significant differences in body composition compared with insulin treatment, while it appears to be protective for metabolic and cardiovascular risk.

Microvascular Complications Are Associated With Coronary Collateralization in Type 2 Diabetes and Chronic Occlusion.

CONTEXT: Coronary collateral (CC) vessel development appears to be protective with regard to adverse cardiovascular events and survival in patients with coronary chronic total occlusion (CTO). The influence of type 2 diabetes mellitus (T2DM) on CC growth has been controversial. In particular, the role of diabetic microvascular complications (DMC) in determining coronary collateralization has not been elucidated. OBJECTIVE: To investigate whether patients with DMC presented differences in CC vessel presence and grading as compared with patients without DMC. METHODS: We conducted a single-center observational study, including consecutive T2DM patients, without previous cardiovascular history, undergoing a clinically indicated coronary angiography for chronic coronary syndrome (CCS) and angiographic evidence of at least one CTO. Patients were subdivided into 2 study groups according to the presence/absence of at least one DMC (neuropathy, nephropathy, or retinopathy). The presence and grading of angiographically visible CC development from the patent vessels to the occluded artery were assessed using the Rentrop classification. RESULTS: We enrolled 157 patients (mean age 68.6 ± 9.8 years; 120 [76.4%] men). Patients with DMC (75 [47.8%]) had a higher prevalence of CC (69 [92.0%] vs 62 [75.6%], P = .006) and high-grade CC (55 [73.3%] vs 39 [47.6%], P = .001) compared with those without, and we found a positive association between the number of DMC in each patient and the prevalence of high-grade CC. CONCLUSION: Among T2DM patients with coronary CTO, the presence of DMC was associated with a high CC development.

Evaluation of the prevalence of the most common psychiatric disorders in patients with type 2 diabetes mellitus using the patient health questionnaire: results of the cross-sectional "DIA2PSI" study.

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.

Predisposition to eating disorders in adults with type 1 diabetes: Comparison between multiple daily injections and continuous subcutaneous insulin infusion.

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.

A Novel GCK Large Genomic Rearrangement in a Patient with MODY-2 Detected by Clinical Exome Sequencing.

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.