The relationship between endothelial-dependent flow-mediated dilation and diastolic function in type 2 diabetes.

AIMS: Diastolic dysfunction represents the earliest and most common manifestation of diabetic cardiomyopathy. Nitric oxide (NO), a potent vasodilator and anti-inflammatory mediator released from the subendocardial and coronary endothelium, favors left ventricular distensibility and relaxation. In type 2 diabetes (T2D), the NO bioavailability is reduced due to the oxidative stress and inflammatory state of the endothelium, because of chronic hyperglycemia. The aim of the present research is to evaluate the relationship between endothelial function and diastolic function in subjects with T2D. METHOD: Subjects with T2D and age and sex-matched healthy controls were consecutively recruited. All participants underwent flow-mediated dilation (FMD) to assess endothelial function, and echocardiography to evaluate diastolic function. RESULTS: Thirty-five patients (6 women, 29 men) and 35 healthy controls were included in the final analysis. FMD was significantly lower in T2D than controls (4.4 ± 3.4 vs. 8.5 ± 4.3%, p = 0.001). T2D presented different abnormalities in diastolic function compared to controls: lower E/A (early to late diastolic transmitral flow velocity), lower septal and lateral e' (early diastolic myocardial tissue velocity at septum and lateral wall), and higher E/e' (surrogate of filling pressure). In subjects with T2D, we observed a significant correlation between FMD and E/e' (r = -0.63, p = 0.001), lateral e' (r = 0.44, p = 0.03), and septal e' (r = 0.39, p = 0.05). CONCLUSIONS: Our observational study demonstrated a link between FMD and diastolic dysfunction in subjects with type 2 diabetes.

T-cell immunity against Severe Acute Respiratory Syndrome Coronavirus 2 proteins in patients with type 1 diabetes.

AIMS: Individuals with type 1 diabetes (T1D) do not appear to have an elevated risk of severe Coronavirus Disease 19 (COVID-19). Pre-existing immune reactivity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in unexposed individuals may serve as a protective factor. Hence, our study was designed to evaluate the existence of T cells with reactivity against SARS-CoV-2 antigens in unexposed patients with T1D. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from SARS-CoV-2 unexposed patients with T1D and healthy control subjects. SARS-CoV-2 specific T cells were identified in PBMCs by ex-vivo interferon (IFN)γ-ELISpot and flow cytometric assays. The epitope specificity of T cells in T1D was inferred through T Cell Receptor sequencing and GLIPH2 clustering analysis. RESULTS: T1D patients unexposed to SARS-CoV-2 exhibited higher rates of virus-specific T cells than controls. The T cells primarily responded to peptides from the ORF7/8, ORF3a, and nucleocapsid proteins. Nucleocapsid peptides predominantly indicated a CD4+ response, whereas ORF3a and ORF7/8 peptides elicited both CD4+ and CD8+ responses. The GLIPH2 clustering analysis of TCRß sequences suggested that TCRß clusters, associated with the autoantigens proinsulin and Zinc transporter 8 (ZnT-8), might share specificity towards ORF7b and ORF3a viral epitopes. Notably, PBMCs from three T1D patients exhibited T cell reactivity against both ORF7b/ORF3a viral epitopes and proinsulin/ZnT-8 autoantigens. CONCLUSIONS: The increased frequency of SAR-CoV-2- reactive T cells in T1D patients might protect against severe COVID-19 and overt infections. These results emphasise the long-standing association between viral infections and T1D.

Elevated blood flow in people with type 1 and type 2 diabetes.

AIMS: The study aimed to evaluate blood flow (BF) and microvascular function in the forearm of people with type 1 and type 2 diabetes at rest and after ischemia. Microvascular function plays a crucial role in regulating BF in peripheral tissues based on metabolic demand. METHODS: People with diabetes and sex-matched healthy controls were recruited. Brachial artery diameter and blood velocity were continuously measured at rest and after ischemia by an automatic tracking system. BF and vascular conductance were then calculated. RESULTS: Forty-nine people with diabetes and 49 controls were enrolled. BF at rest and after ischemia was significantly higher in people with diabetes than controls: Type 1, 243 ± 116 and 631 ± 233 ml/min; controls, 180 ± 106 and 486 ± 227 ml/min; Type 2, 332 ± 149 and 875 ± 293 ml/min; controls 222 ± 106 and 514 ± 224 ml/min. Vascular conductance was significantly higher in Type 2 than in controls at rest and after ischemia. CONCLUSIONS: People with diabetes exhibited significantly increased BF, with Type 2 also showing heightened vascular conductance. Activating metabolic pathways triggered by hyperglycemia may lead to distinct vascular redistribution, potentially impairing blood flow over time. These findings of the study underscore the importance of understanding overall vascular dynamics in diabetes and its implications for vascular health.

Digital technology and healthcare delivery in insulin-treated adults with diabetes: a proposal for analysis of self-monitoring blood glucose patterns using a dedicated platform.

PURPOSE: A remote platform for diabetes care (Roche Diabetes® Care Platform, RDCP) has been developed that allows combined face-to-face consultations and remote patient monitoring (RPM). METHODS: A dedicated flowchart is proposed as a clinical approach to help healthcare professionals in the appropriate interpretation of structured self-monitoring blood glucose data, as visualized on the RDCP during the visits, and in the optimal management of patients using the integrated RDCP-RPM tools. RESULTS: The platform organizes patterns in different blocks: (i) hypoglycemia; (ii) hyperglycemia; (iii) blood glucose variability; (iv) treatment adherence, which identifies a possible individual pattern according to glycemic control challenges, potential causal factors, and behavioral type patterns. The flowchart proposed for use of the RDCP-RPM is self-explanatory and entails 3 steps: (1) evaluation of quality and quantity of self-monitoring blood glucose data; (2) pattern analysis; (3) personalized suggestions and therapy changes. CONCLUSION: The main aim of the remote treatment flowchart proposed is to support healthcare professionals in the identification of hypoglycemic and hyperglycemic patterns using the RDCP regardless of the HbA1c value and ongoing treatment, which however, become crucial in combination with pattern analysis in the therapeutical choice.

Continuous Glucose Monitoring-Derived Metrics and Capillary Vessel Density in Subjects with Type 1 Diabetes without Diabetic Retinopathy.

Optical coherence tomography angiography (OCTA) is an innovative and reliable technique detecting the early preclinical retinal vascular change in patients with diabetes. We have designed our study to evaluate whether an independent relationship exists between continuous glucose monitoring (CGM)-derived glucose metrics and OCTA parameters in young adult patients with type 1 diabetes without diabetic retinopathy (DR). Inclusion criteria were age ≥ 18 years, diagnosis of type 1 diabetes from ≥ 1 year, stable insulin treatment in the last three months, use of real-time CGM, and CGM wear time ≥ 70%. Each patient underwent dilated slit lamp fundus biomicroscopy to exclude the presence of DR. A skilled operator performed OCTA scans in the morning to avoid possible diurnal variation. CGM-derived glucose metrics from the last 2 weeks were collected through the dedicated software during OCTA. Forty-nine patients with type 1 diabetes (age 29 [18; 39] years, HbA1c 7.7 ± 1.0%) and 34 control subjects participated in the study. Vessel density (VD) of the whole image and parafoveal retina in the superficial (SCP) and deep capillary plexus (DCP) was significantly lower in patients with type 1 diabetes compared to controls. The coefficient of variation of average daily glucose, evaluated by CGM, significantly correlated with foveal and parafoveal VD in SCP and with foveal VD in DCP. High glucose variability might be responsible for the early increase of VD in these areas. Prospective studies may help understand if this pattern precedes DR. The difference we detected between patients with and without diabetes confirms that OCTA is a reliable tool for detecting early retinal abnormalities.

A Head-to-Head Comparison of Two Algorithms for Adjusting Mealtime Insulin Doses Based on CGM Trend Arrows in Adult Patients with Type 1 Diabetes: Results from an Exploratory Study.

BACKGROUND: Continuous glucose monitoring (CGM) users are encouraged to consider trend arrows before injecting a meal bolus. We evaluated the efficacy and safety of two different algorithms for trend-informed bolus adjustments, the Diabetes Research in Children Network/Juvenile Diabetes Research Foundation (DirectNet/JDRF) and the Ziegler algorithm, in type 1 diabetes. METHODS: We conducted a cross-over study of type 1 diabetes patients using Dexcom G6. Participants were randomly assigned to either the DirectNet/JDRF or the Ziegler algorithm for two weeks. After a 7-day wash-out period with no trend-informed bolus adjustments, they crossed to the alternative algorithm. RESULTS: Twenty patients, with an average age of 36 ± 10 years, completed this study. Compared to the baseline and the DirectNet/JDRF algorithm, the Ziegler algorithm was associated with a significantly higher time in range (TIR) and lower time above range and mean glucose. A separate analysis of patients on CSII and MDI revealed that the Ziegler algorithm provides better glucose control and variability than DirectNet/JDRF in CSII-treated patients. The two algorithms were equally effective in increasing TIR in MDI-treated patients. No severe hypoglycemic or hyperglycemic episode occurred during the study. CONCLUSIONS: The Ziegler algorithm is safe and may provide better glucose control and variability than the DirectNet/JDRF over a two-week period, especially in patients treated with CSII.

The Effect of Two Different Insulin Formulations on Postprandial Hyperglycemia after High and Low Glycemic-Index Meal in Type 1 Diabetes.

Despite multiple pharmacological options, including rapid-acting insulin analogs, postprandial hyperglycemia is still highly prevalent in patients with type 1 and type 2 diabetes. We hypothesize that the new rapid-acting insulin formulation, the so-called faster-acting Aspart, may have a different effect in controlling postprandial hyperglycemic burden according to the quality of the meal compared to the traditional Aspart. Twenty-five patients with type 1 diabetes were consecutively recruited at the diabetes care center of the University Hospital affiliate of the Magna Græcia University of Catanzaro. Each patient performed four meal tests one week apart, two with a predefined high glycemic index (HGI) food and two with a low glycemic index (LGI) food using insulin Aspart once and Faster Aspart the other time. The 0-30 min, 0-60 min, and 0-120 min glucose Area Under the Curve (AUC) of postprandial glycemic excursion, calculated from continuous glucose monitoring data, were significantly lower with Faster Aspart administered before the HGI test meal as compared to Aspart. A significant difference in favor of Faster Aspart was also found when comparing the 0-60 min and 0-120 min AUC after the LGI meal. Faster Aspart may provide better postprandial glucose control than Aspart regardless of the glycemic index of the meal.

Autoimmune thyroiditis and celiac disease do not worsen endothelial function in subjects with type 1 diabetes: an observational study.

BACKGROUND: Type 1 diabetes (T1D) is frequently associated with autoimmune thyroiditis (AT) and coeliac disease (CD). Whether the coexistence of multiple autoimmune diseases increases cardiovascular risk is uncertain. We evaluated the effects of AT and CD on arterial wall thickening and endothelial function in patients with T1D. METHODS: This observational study analyzed data from T1D patients regularly followed by the Diabetes Care Centre. Clinical and biochemical characteristics and micro and macrovascular complications were collected from the electronic medical records. All subjects performed Echo-Doppler to evaluate Intima-Media Thickness (IMT) of the common carotid artery (CCA) and endothelial function by the flow-mediated dilation (FMD) technique. The statistical analyses were performed by SPSS for Macintosh. Comparison between means was performed using the t-test for unpaired data and the Mann-Whitney U test. The ANalysis Of VAriance and the Tukey posthoc test were applied to compare patients with and without other autoimmune diseases, and control subjects. The p-value for statistical significance was set at p < 0.05. RESULTS: A total of 110 patients were enrolled. Among these, 69 had T1D and 41 T1D and AT and or CD, of whom 33 AT, 7 CD, and 1 both AT and CD. The mean age was 35 years, mean HbA1c was 7.6%, and mean diabetes duration 18 years. The IMT of the CCA was not significantly different between T1D patients with and without concomitant autoimmune diseases (with AT and CD: right CCA 603 ± 186 µ, left 635 ± 175 µ; without AT and CD: right CCA 611 ± 176 µ, left CCA 631 ± 200 µ). FMD was also comparable between T1D groups, with AT and CD 7.9 ± 4.2%; without AT and CD 8.8 ± 4.4%. CONCLUSION: Patients with T1D and concomitant AT and or CD show no worse morphological or functional vascular damage, evaluated by CCA IMT and brachial artery flow-mediated dilation, than patients with T1D alone.

Time in Range Does Not Associate With Carotid Artery Wall Thickness and Endothelial Function in Type 1 Diabetes.

BACKGROUND: Patients with Type 1 diabetes (T1D) have an increased risk of developing atherosclerosis and complications as myocardial infarction and peripheral artery disease. The thickening of the carotid wall and the brachial artery dysfunction are early and preclinical manifestations of atherosclerosis. The standard marker of care for assessment of glycemic control, glycated hemoglobin, does not associate with early atherosclerosis. We have hypothesized that the emerging metric of glycemic control, as the time spent in the target range (TIR), might be associated with carotid thickening and endothelial dysfunction. According to the hypothesis, we have designed the present research with the aim to evaluate the association between TIR collected in the short and long term and the measures of arterial morphology and function in patients with T1D. METHODS: In our study, 70 patients and 35 healthy controls underwent ultrasound vascular study to measure carotid artery intima-media thickness (IMT) and brachial artery endothelial function by the flow-mediated dilation (FMD) technique. TIR was collected by a continuous glucose monitoring system for 2 weeks, 3 months, and 6 months before the vascular study. RESULTS: Patients with T1D showed a significantly higher carotid IMT (mean±SE, 644±19 vs. 568±29 µ; p= 0.04) and a significantly lower FMD (mean±SE, 7.6±0.4 vs. 9.8±0.6%; p=0.01) compared with control subjects. No significant relationship between IMT, FMD, and TIR collected in the short and long term emerged. CONCLUSIONS: Young patients with T1D have early vascular abnormalities. The percent of TIR does not correlate with preclinical atherosclerosis. This finding underlines the complexity of the interplay between diabetes and atherosclerosis.

Effect of Extra Virgin Olive Oil and Butter on Endothelial Function in Type 1 Diabetes.

Post-prandial hyperglycemia can be relevant in developing early manifestations of atherosclerosis. EVOO (Extra Virgin Olive Oil), rich in saturated fatty acids and commonly used in the Mediterranean diet, seems to control post-prandial hyperglycemia better than butter. Subjects with type 1 diabetes are at higher risk of developing cardiovascular disease and show endothelial dysfunction, an early manifestation of atherosclerosis in the first years of the disease. Our study aims to evaluate whether EVOO and butter influence endothelial function in subjects with type 1 diabetes when added to a single high glycemic index (HGI) meal. In this exploratory cross-over study, 10 subjects with type 1 diabetes and 6 healthy subjects were scheduled to receive two types of HGI meals: one enriched with EVOO and one with butter. Before and after each test meal at different time points, all subjects underwent the evaluation of endothelial function by flow-mediated dilation technique, glucose and lipids measurements, and gastric emptying assessment by ultrasound. Flow-mediated dilation significantly increased after EVOO-enriched meal compared with butter in subjects with type 1 diabetes (two-way-repeated measurements ANOVA, p = 0.007). In patients with type 1 diabetes, the add-on of EVOO to HGI meal improves vascular function compared to butter, which has detrimental effects.

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.

Time spent in target range assessed by self-monitoring blood glucose associates with glycated hemoglobin in insulin treated patients with diabetes.

BACKGROUND AND AIMS: Self-monitoring blood glucose (SMBG) remains a widespread tool to monitor blood glucose. The development of diabetes management systems (DMS) allows SMBG to provide additional information as time spent in target range (TIR). This study evaluates the association between HbA1c and TIR, evaluated through DMS, over 2 months, and 2 weeks. METHODS AND RESULTS: Type 1 (T1D) and Type 2 (T2D) insulin-treated patients with diabetes were enrolled. We used the term PIR (Points in Range) instead of TIR, since SMBG provides point-in-time glucose values rather than a continuous trend over time. PIR was calculated in 2-month and 2-week time ranges before available HbA1c measurement. One-hundred ninety-seven patients with T1D and 36 with T2D were recruited. HbA1c and PIR were inversely associated (2 months: R -0.72, 2 weeks R -0.70; p < 0.0001) in all subjects. The relationship did not change when T1D and T2D patients were analyzed separately. For every 10% change of PIR, there was a change of HbA1c by 0.4%. CONCLUSIONS: Our study, for the first time, demonstrates a significant correlation between HbA1c and PIR calculated by DMS. DMS offers additional information useful in disease management of patients with T1D and T2D performing SMBG.

Effect of empagliflozin on brachial artery shear stress and endothelial function in subjects with type 2 diabetes: Results from an exploratory study.

Empagliflozin reduces the risk of cardiovascular mortality in subjects with type 2 diabetes. We demonstrated that empagliflozin increases blood viscosity and carotid shear stress and decreases carotid wall thickness. Shear stress is the force acting on the endothelial surface and modulates arterial function. The current study evaluates the influence of empagliflozin on brachial artery shear stress and endothelial function compared to incretin-based therapy. The study is a nonrandomized, open, prospective cohort study including 35 subjects with type 2 diabetes administered empagliflozin or incretin-based therapy. Shear stress was calculated with a validated formula, and endothelial function was evaluated using the flow-mediated dilation technique. Both treatments resulted in comparable reductions in blood glucose and glycated haemoglobin. Brachial artery shear stress significantly increased exclusively in the empagliflozin group (61 ± 20 vs 68 ± 25 dynes/cm2, p = 0.04), whereas no significant difference was detected in the incretin-based therapy group (60 ± 20 vs 55 ± 12 dynes/cm2, p = not significant). Flow-mediated dilation significantly increased in the empagliflozin group (4.8 ± 4.5% vs 8.5 ± 5.6%, p = 0.03). Again, no change was detected in the incretin-based therapy group (5.1 ± 4.5% vs 4.7 ± 4.7%, p = not significant). The present findings demonstrate the beneficial effect of empagliflozin on shear stress and endothelial function in subjects with type 2 diabetes independent of the hypoglycaemic effect.

Hepatic Steatosis Index Is Associated with Type 1 Diabetes Complications.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of complications in type 1 diabetes (T1DM) patients. To date, several biochemical indexes of NAFLD have been developed. Among these, hepatic steatosis index (HSI) strongly relates with the results of magnetic resonance. AIM: The aim of the present study was to evaluate the possible association between HSI and complications in T1DM. METHODS: Medical records of patients with T1DM were evaluated. Macro- and micro-vascular complications were evaluated by a combination of instrumental (ECG, carotid artery echo-Doppler, fundus examination, vibration threshold at biothesiometry) and laboratory examination. HSI was calculated based on gender, body mass index and transaminases level. RESULTS: Of the 124 patients evaluated, 71 were free of complications and 53 had at least one complication. The prevalence of diabetes complications was: 27% for retinopathy, 15% for carotid atherosclerosis, 16% for neuropathy. HSI was directly correlated with age, disease duration, triglycerides, total daily insulin and inversely with HDL and eGFR. In logistic regression analysis, HSI was independently associated with diabetic complications. CONCLUSION: These findings show that HSI is independently associated with the presence of complications in subjects with T1DM. This can be of clinical utility, allowing a better diagnostic classification of the patient and possibly guiding the therapeutic choice.