Once-weekly insulin icodec versus once-daily insulin degludec as part of a basal-bolus regimen in individuals with type 1 diabetes (ONWARDS 6): a phase 3a, randomised, open-label, treat-to-target trial.

BACKGROUND: ONWARDS 6 compared the efficacy and safety of once-weekly subcutaneous insulin icodec (icodec) and once-daily insulin degludec (degludec) in adults with type 1 diabetes. METHODS: This 52-week (26-week main phase plus a 26-week safety extension), randomised, open-label, treat-to-target, phase 3a trial was done at 99 sites across 12 countries. Adults with type 1 diabetes (glycated haemoglobin [HbA1c] <10·0% [86 mmol/mol]) were randomly assigned (1:1) to once-weekly icodec or once-daily degludec, both in combination with insulin aspart (two or more daily injections). The primary endpoint was change in HbA1c from baseline to week 26, tested for non-inferiority (0·3 percentage point margin) in all randomly assigned participants. This trial is registered with ClinicalTrials.gov, NCT04848480, and is now complete. FINDINGS: Between April 30 and Oct 15, 2021, of 655 participants screened, 582 participants were randomly assigned to icodec (n=290) or degludec (n=292). At week 26, from baseline values of 7·59% (icodec) and 7·63% (degludec), estimated mean changes in HbA1c were -0·47 percentage points and -0·51 percentage points, respectively (estimated treatment difference 0·05 percentage points [95% CI -0·13 to 0·23]), confirming non-inferiority of icodec to degludec (p=0·0065). Overall rate of combined clinically significant or severe hypoglycaemia (baseline to week 26) was statistically significantly higher with icodec than degludec (19·9 vs 10·4 events per patient-year of exposure; estimated rate ratio 1·9 [95% CI 1·5 to 2·3]; p<0·0001). The rate was also statistically significantly higher with icodec than degludec when evaluated over 57 weeks (52 weeks plus a 5-week follow-up period). 39 serious adverse events were reported in 24 (8%) participants receiving icodec, and 25 serious adverse events were reported in 20 (7%) participants receiving degludec. One participant in the icodec group died; this was judged unlikely to be due to the trial product. INTERPRETATION: In adults with type 1 diabetes, once-weekly icodec showed non-inferiority to once-daily degludec in HbA1c reduction at week 26, with statistically significantly higher rates of combined clinically significant or severe hypoglycaemia. For icodec, time below 3·0 mmol/L (<54 mg/dL) was at the threshold of the internationally recommended target (<1%) during weeks 22-26 and below target during weeks 48-52. FUNDING: Novo Nordisk.

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.

Continuous glucose monitoring (CGM) in a non-Icu hospital setting: The patient's journey.

AIMS: Although consistent data support the outpatient use of continuous glucose monitoring (CGM) to improve glycemic control and reduce hypoglycemic burden, and clinical outcomes, there are limited data regarding its use in the hospital setting, particularly in the non-intensive care unit (non-ICU) setting. The emerging use of CGM in the non-critical care setting may be useful in increasing the efficiency of hospital care and reducing the length of stay for patients with diabetes while improving glycemic control. DATA SYNTHESIS: The purpose of this Expert Opinion paper was to evaluate the state of the art and provide a practical model of how CGM can be implemented in the hospital. SETTING: A patient's CGM journey from admission to the ward to the application of the sensor, from patient education on the device during hospitalization until discharge of the patient to maintain remote control. CONCLUSIONS: This practical approach for the implementation and management of CGM in patients with diabetes admitted to non-ICUs could guide hospitals in their diabetes management initiatives using CGM, helping to identify patients most likely to benefit and suggesting how this technology can be implemented to maximize clinical benefits.

Understanding the clinical implications of differences between glucose management indicator and glycated haemoglobin.

Laboratory measured glycated haemoglobin (HbA1c) is the gold standard for assessing glycaemic control in people with diabetes and correlates with their risk of long-term complications. The emergence of continuous glucose monitoring (CGM) has highlighted limitations of HbA1c testing. HbA1c can only be reviewed infrequently and can mask the risk of hypoglycaemia or extreme glucose fluctuations. While CGM provides insights in to the risk of hypoglycaemia as well as daily fluctuations of glucose, it can also be used to calculate an estimated HbA1c that has been used as a substitute for laboratory HbA1c. However, it is evident that estimated HbA1c and HbA1c values can differ widely. The glucose management indicator (GMI), calculated exclusively from CGM data, has been proposed. It uses the same scale (% or mmol/mol) as HbA1c, but is based on short-term average glucose values, rather than long-term glucose exposure. HbA1c and GMI values differ in up to 81% of individuals by more than ±0.1% and by more than ±0.3% in 51% of cases. Here, we review the factors that define these differences, such as the time period being assessed, the variation in glycation rates and factors such as anaemia and haemoglobinopathies. Recognizing and understanding the factors that cause differences between HbA1c and GMI is an important clinical skill. In circumstances when HbA1c is elevated above GMI, further attempts at intensification of therapy based solely on the HbA1c value may increase the risk of hypoglycaemia. The observed difference between GMI and HbA1c also informs the important question about the predictive ability of GMI regarding long-term complications.

Health care organization and use of technological devices in people with diabetes in Italy: Results from a survey of the Working Group on Diabetes and Technology.

BACKGROUND AND AIM: The use of technology offers recognized benefits to persons with diabetes. The aim of this study was to evaluate the organization of healthcare facilities, the composition of the diabetes team, and the use of Continuous Subcutaneous Insulin Infusion (CSII) and Continuous Glucose Monitoring (CGM) in Italy. METHODS AND RESULTS: Diabetes care centers were asked to complete a web survey based on information collected in 2018. Sixty-one pediatric and 243 adult centers participated in the survey, accounting for 507,386 patients, mostly with type 2 diabetes (86.4%). Fifty-three percent of pediatric centers and 11% of adult centers reported a team composed of diabetologists, nurses, and psychologists. Overall, 13,204 patients (2.6%) were using CSII (95% with type 1 diabetes), and 28,936 (5.7%), were using CGM (74% with type 1 diabetes). When stratifying for the type of diabetes, 24% and 40.8% of patients with type 1 were using CSII and CGM, respectively, whereas low use of technology was reported for patients with type 2 and women with gestational diabetes. The percentage of adult and pediatric patients with type 1 diabetes on CSII and CGM was respectively 21% and 32%, and 35% and 57%. CONCLUSIONS: The spread of CGM and CSII increased in Italy between 2013 and 2018. However, the percentage of users is still lower than what is expected based on clinical indications for use of technology. The inadequate number of professionals in the diabetes care team and insufficient economic resources are relevant barriers to disseminating technology for diabetes management.

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.

Characteristics, Management, and Outcomes of Elderly Patients with Diabetes in a Covid-19 Unit: Lessons Learned from a Pilot Study.

Background and objectives: Diabetes may affect in-hospital mortality of patients with Coronavirus disease 2019 (COVID-19). We have retrospectively evaluated clinical characteristics, diabetes management, and outcomes in a sample of COVID-19 patients with diabetes admitted to our hospital. Materials and Methods: All patients admitted to the Infectious Diseases Unit from 28 March 2020, to 16 June 2020, were enrolled. Clinical information and biochemical parameters were collected at the time of admission. Patients were ranked according to diabetes and death. Results: Sixty-one patients with COVID-19 were analyzed. Most of them were from a long-term health care facility. Mean age was 77 ± 16 years, and 19 had type 2 diabetes (T2D). Eighteen patients died, including 8 with T2D and 10 without T2D (p = 0.15). Patients with diabetes were significantly older, had a higher prevalence of cardiovascular diseases, and a significantly lower lymphocyte count. No significant relationship was found between diabetes and in-hospital mortality (Odds Ratio OR 2.3; Confidence Interval CI 0.73-7.38, p = 0.15). Patients with diabetes were treated with insulin titration algorithm. Severe hypoglycemic events, ketoacidosis and hyperosmolar hyperglycemias did not occur during hospitalization. Mean pre-meal capillary blood glucose was 157 ± 45 mg/dL, and the coefficient of variation of glycaemia was 29%. Conclusions: Our study, albeit limited by the small number of subjects, did not describe any significant association between T2D diabetes and mortality. Clinical characteristics of patients, and acceptable glucose control prior and during hospitalization may have influenced the result. The use of an insulin titration algorithm should be pursued during hospitalization.

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).

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.

Empagliflozin influences blood viscosity and wall shear stress in subjects with type 2 diabetes mellitus compared with incretin-based therapy.

BACKGROUND: Cardiovascular protection following empagliflozin therapy is not entirely attributable to the glucose lowering effect. Increased hematocrit might influence the shear stress that is the main force acting on the endothelium, regulating its anti-atherogenic function. OBJECTIVE: We designed the study with the aim of investigating the effect of empagliflozin on blood viscosity and shear stress in the carotid arteries. A secondary endpoint was the effect of empagliflozin on carotid artery wall thickness. METHODS: The study was a non-randomized, open, prospective cohort study including 35 type 2 diabetic outpatients who were offered empagliflozin or incretin-based therapy (7 liraglutide, 8 sitagliptin) in combination with insulin and metformin. Blood viscosity, shear stress and carotid wall thickness were measured at baseline and at 1 and 3 months of treatment. Blood viscosity was measured with a viscometer, and shear stress was calculated using a validated formula. Intima-media thickness (IMT) of the carotid artery was detected by ultrasound and was measured with dedicated software. RESULTS: Blood viscosity (4.87 ± 0.57 vs 5.32 ± 0.66 cP, p < 0.02) and shear stress significantly increased in the Empagliflozin group while no change was detected in the Control group (4.66 ± 0.56 vs 4.98 ± 0.73 cP, p = NS). IMT significantly decreased in the Empagliflozin group after 1 and 3 months (baseline: 831 ± 156, 1-month 793 ± 150, 3-month 766 ± 127 µm; p < 0.0001), while in the liraglutide group, IMT significantly decreased only after 3 months (baseline 879 ± 120; 1-month 861 ± 163; 3-month 802 ± 114 µm; p < 0.001). In the sitagliptin group, IMT remained almost unchanged (baseline 901 ± 135; 1-month 902 ± 129; 3-month 880 ± 140 µm; p = NS). CONCLUSIONS: This study is the first to describe a direct effect of empagliflozin on blood viscosity and wall shear stress. Furthermore, IMT was markedly reduced early on in the Empagliflozin group.

Blood viscosity but not shear stress associates with delayed flow-mediated dilation.

PURPOSE: Flow-mediated dilation (FMD) is a complex mechanism involving several mediators, and different hemodynamic forces. Temporally distinct FMD patterns can be elicited by ischemic stimulus. Some subjects dilate early after cuff release, while others dilate later or do not dilate at all. Aim of the present research was to verify if hemorheological and hemodynamic factors might influence different FMD pattern. METHODS: 148 free-living subjects were studied. FMD was measured at 50 s, 2 min and 3 min. Blood viscosity was measured and shear stress calculated. Shear stress stimulus was quantified as the area under the curve after ischemia (SSAUC) over the first 40-s post-occlusion. RESULTS: Based on the timing or absence of arterial dilation, 82 subjects were classified as Early dilators, 37 as Late dilators and 29 as No dilators. Peak FMD was 7.9 ± 4.3 % in Early dilators, and 9.1 ± 5.7 in Late dilators (p = NS). SSAUC was not significantly different among three groups, while blood viscosity was significantly higher in Late FMD subjects. Regression analyses showed the independent predictive role of age and blood viscosity on FMD patterns, and the lack of any association between FMD pattern and the magnitude of SS. CONCLUSIONS: The present study demonstrates that age and blood viscosity but not the magnitude of SS explain the different timing of the dilatory response to ischemia.

Delayed vasodilation is associated with cardiovascular risk.

BACKGROUND: Flow-mediated dilation (FMD) of the brachial artery is widely used to assess cardiovascular risk. In recent years, much attention has been paid to the kinetics of vasodilation in an attempt to better characterize the endothelial function. Here, we investigated whether FMD magnitude and/or latency are most related to individual cardiovascular risk. MATERIALS AND METHODS: Four hundred subjects were recruited. Individual risk prediction was estimated by Framingham cardiovascular risk score and CUORE project calculator. Subjects were divided into Early dilators (peak FMD at 50 s), Late dilators (peak FMD over 50 s) and No dilators. RESULTS: Cardiovascular risk was highest in No dilators and significantly higher in Late than Early dilators despite comparable peak FMD. When divided according to peak FMD quintiles, Early and Late dilators showed decreased cardiovascular risk with increasing magnitude of vasodilation. However, subjects in the first three quintiles of Late dilators had a markedly higher risk score despite a peak vasodilation similar to that of Early dilators. CONCLUSION: These results suggest that the magnitude of the FMD and its latency are both important for identifying patients at risk of cardiovascular disease. Subjects with a delayed though significant vasodilation associated with a blunted early response exhibit the highest cardiovascular risk.

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.

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.

Yoga as an alternative to cycling in type 1 diabetes: A preliminary study of acute effects on glucose levels.

We evaluated the acute effects of yoga compared to cycling on glucose change and variability, and the occurrence of hypoglycemia in adults with type 1 diabetes. Fifteen participants performed 50 min of cycling or yoga. Glucose values were collected before and after exercise. Coefficient of variation (CV) and hypoglycemic episodes were evaluated from the start up to 12 h after exercise. Cycling and yoga significantly reduced glucose values during exercise, and CV was lower after yoga. One hypoglycemic episode occurred with yoga and seven with cycling. Yoga is a safe exercise that acutely reduces glucose values, but with lower risk of hypoglycemia compared to cycling.

Diabetes as a risk factor for pneumococcal disease and severe related outcomes and efficacy/effectiveness of vaccination in diabetic population. Results from meta-analysis of observational studies.

AIMS: To collect all available evidence on the effect of diabetes mellitus (DM) as a risk factor for pneumococcal disease incidence and related complications, and on the efficacy/effectiveness of vaccines in patients with DM. METHODS: Two distinct systematic searches on MEDLINE, Cochrane, ClinicalTrials.gov and EMBASE databases were performed, one for each meta-analysis, collecting all observational (cohort and case-control) studies and randomized clinical trials performed on humans up to June 1st, 2023. RESULTS: We retrieved 36 observational studies comparing risk for pneumococcal disease and related complications in people with or without DM, and 11 studies (1 randomized clinical trial and 10 observational studies) assessing conjugated and polysaccaridic vaccines efficacy/effectiveness on preventing such outcomes. People with DM were at higher risk for Invasive Pneumococcal Disease (unadjusted OR 2.42 [2.00; 2.92]); Case-Fatality Rate (unadjusted OR 1.61 [1.25; 2.07], Pneumococcal pneumonia (unadjusted OR 2.98 [2.76; 3.22), and Intensive care unit admission for pneumococcal disease (unadjusted OR 2.09 [1.20; 3.66]). In diabetic individuals vaccinated with conjugated vaccine, incidence of pneumonia specific for vaccine type in a clinical trial (OR 0.237 [0.008; 0.704]), and hospitalization for overall pneumonia during the year following the polysaccharide vaccination in observational studies (unadjusted OR 0.63 [0.45-0.89]) were significantly lower in comparison with unvaccinated DM subjects, with no significant differences for other outcomes. CONCLUSIONS: People with diabetes mellitus are at higher risk for less favourable course of pneumococcal disease and should be therefore targeted in vaccination campaigns; more evidence needs to be collected on vaccination outcomes in people with diabetes.

Delayed flow-mediated vasodilation and carotid atherosclerosis.

BACKGROUND: In a previous study, we identified temporally distinct postischaemic flow-mediated dilation (FMD) patterns comparing the standard clinical measurement time of 50s postcuff release with measurement at 2 min. The comparison revealed a cohort with the highest FMD at 50s (Early FMD), another cohort with the highest FMD at 2 min (Late FMD) and a third cohort with no FMD (Absent FMD). The aim of this study was to examine whether these temporally distinct FMD patterns associated with different degrees of carotid atherosclerosis. MATERIALS AND METHODS: One hundred and twenty-four free-living white subjects, participating in a cardio-vascular disease prevention campaign, were enrolled. FMD was measured at 50s, 2 min and 3 min after forearm ischaemia. The intima-media thickness (IMT) of the common carotid artery was measured, and the artery was evaluated for the presence and number of carotid plaques. RESULTS: Fifty-seven subjects had Early FMD, 34 had Late FMD and 33 had Absent FMD. The three groups were comparable for age, sex and cardiovascular risk factors. The number of plaques in the carotid arteries, and IMT, increased progressively from Early, to Late, and to Absent FMD (P < 0·03), indicating that the FMD pattern is an independent predictive variable for IMT and carotid atherosclerosis. CONCLUSIONS: The present study demonstrates that temporal patterns associated with the degree of atherosclerosis of the carotid arteries. Patients with delayed vasodilation (Late FMD) had a higher degree of atherosclerosis than those with early vasodilation (Early FMD), and subjects with no postischaemic vasodilation (Absent FMD) had the most atherosclerosis.

Genistein and endothelial function in postmenopausal women with metabolic syndrome.

BACKGROUND: Previous data have suggested that genistein could exert beneficial effects on endothelial function and on predictors of cardiovascular risk in healthy postmenopausal women. In a randomized clinical trial, we studied the effects of genistein on endothelial function in postmenopausal women with metabolic syndrome (MS). METHODS: Twenty postmenopausal women with MS, according to modified NCEP-ATP III criteria were randomly assigned to receive placebo or genistein (54 mg/day) for 6 months, along with a Mediterranean-style diet. Postmenopausal women without MS (n = 15), served as controls. The primary goal was the assessment of endothelial function by flow-mediated vasodilation (FMD) of brachial artery; moreover, time-to-peak dilation in the FMD response has been evaluated. Secondary outcomes were fasting glucose, fasting insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, visfatin, adiponectin and homocysteine blood levels. Data on adverse events were also recorded. RESULTS: After 6 months of treatment, FMD at 50s and peak FMD significantly increased in genistein recipients compared with placebo. Moreover, genistein significantly decreased the blood levels of total cholesterol, triglycerides, homocysteine and visfatin compared with placebo, while blood adiponectin levels were increased. Genistein recipients neither experienced more side-adverse effects than placebo nor discontinued the study. CONCLUSIONS: Six months of treatment with genistein effectively improves brachial artery flow-mediated vasodilation in postmenopausal women with metabolic syndrome.

Common carotid and brachial artery hemodynamic alterations in periodontal disease.

AIM: In patients affected by periodontal disease, hypertension and systemic inflammation might cause an arterial hemodynamic derangement; this, in turn, can act as a mediator of the atherogenic process often seen in these patients. This study aimed at a comprehensive hemodynamic evaluation in periodontal patients. METHODS: Fourty-eight subjects participating to a cardiovascular prevention programme were enrolled. Periodontitis, classical risk factors for atherosclerosis, and shear and tensile forces in both carotid and brachial arteries were evaluated. Calculated periodontal indexes were plaque, gingival and pocket deep (PD) indexes. Simple and multiple regression analyses were performed. Afterwards, 30 of them with normal PD index were compared with 30 carefully - matched patients with periodontitis. RESULTS: Brachial and carotid parietal tension were significantly associated with periodontal indexes, especially PD-Sum, in both simple (r = 0.42, p < 0.001 for carotid artery and r = 0.36, p < 0.02 for brachial artery) and multiple regression analyses. Shear stress gave similar results. In case-control analysis, shear stress was lower by 15% and 30%, respectively, in carotid and brachial artery in patients with high PD; common carotid parietal tension was higher. Arterial stiffness resulted not associated with periodontitis. CONCLUSIONS: Periodontal disease is associated to a complex atherosclerotic prone hemodynamic derangement, particularly in large elastic arteries.

An updated algorithm for an effective choice of continuous glucose monitoring for people with insulin-treated diabetes.

PURPOSE: Continuous Glucose Monitoring (CGM) is a key tool for insulin-treated people with diabetes (PwD). CGM devices include both real-time CGM (rtCGM) and intermittently scanned CGM (isCGM), which are associated with an improvement of glucose control and less hypoglycemia in clinical trials of people with type 1 and type 2 diabetes. METHODS: This is an expert position to update a previous algorithm on the most suitable choice of CGM for insulin-treated PwD in light of the recent evidence and clinical practice. RESULTS: We identified six different clinical scenarios, including type 1 diabetes, type 2 diabetes, pregnancy on intensive insulin therapy, regular physical exercise, new onset of diabetes, and frailty. The use of rtCGM or isCGM is suggested, on the basis of the predominant clinical issue, as suboptimal glucose control or disabling hypoglycemia, regardless of baseline HbA1c or individualized HbA1c target. CONCLUSION: The present algorithm may help to select the best CGM device based on patients' clinical characteristics, needs and clinical context, offering a further opportunity of a "tailored" therapy for people with insulin-treated diabetes.