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.

Use of ancient grains for the management of diabetes mellitus: A systematic review and meta-analysis.

AIMS: A systematic review and meta-analysis of published randomized controlled trials was conducted to collate evidence from studies implementing ancient grains and investigate the impact of ancient grain consumption on health outcomes of patients with Diabetes Mellitus (DM). DATA SYNTHESIS: Twenty-nine randomized controlled trials were included, and 13 were meta-analyzed. Interventions ranged from 1 day to 24 weeks; most samples were affected by DM type 2 (n = 28 studies) and the ancient grains used were oats (n = 10 studies), brown rice (n = 6 studies), buckwheat (n = 4 studies), chia (n = 3 studies), Job's Tears (n = 2 studies), and barley, Khorasan and millet (n = 1 study). Thirteen studies that used oats, brown rice, and chia provided data for a quantitative synthesis. Four studies using oats showed a small to moderate beneficial effect on health outcomes including LDL-c (n = 717, MD: 0.30 mmol/l, 95% CI: 0.42 to -0.17, Z = 4.61, p < 0.05, I2 = 0%), and TC (n = 717, MD: 0.44 mmol/l, 95% CI: 0.63 to -0.24, Z = 4.40, p < 0.05, I2 = 0%). Pooled analyses of studies using chia and millet did not show significant effects on selected outcomes. CONCLUSIONS: For adults affected by DM type 2, the use of oats may improve lipidic profile. Further experimental designs are needed in interventional research to better understand the effects of ancient grains on diabetes health outcomes. PROSPERO REGISTRATION: CRD42023422386.

Predictors of efficacy of Sodium-GLucose Transporter-2 inhibitors and Glucagon-Like Peptide 1 receptor agonists: A retrospective cohort study.

AIMS: The aim of the present study was to verify predictors of HbA1c reduction with Sodium-GLucose Transporter-2 (SGLT2) inhibitors and Glucagon-Like Peptide 1 (GLP1) receptor agonists in routine clinical practice. MATERIALS AND METHODS: A retrospective cohort study was performed, enrolling patients with type 2 diabetes aged ≥18 years who received a prescription of an SGLT2 inhibitor or a long-acting GLP1 receptor agonist with at least 6 months of persistence in therapy. Therapeutic success was defined as HbA1c reduction >10 mmol/mol or attainment of the recommended HbA1c target. RESULTS: Out of 236 patients receiving SGLT2 inhibitors, 148 were categorised as successes: successes had a mean lower age and higher estimated Glomerular Filtration Rate than failures, but only age retained statistical significance at multivariate analysis (Odds Ratio with 95% confidence interval: 0.94 [0.91-0.98], p = 0.006). In the GLP1 receptor agonists cohort (N = 214) there were 146 successes, showing a significantly shorter duration of diabetes even after adjusting for age, and baseline HbA1c (HR 0.96 [0.91-0.99], p = 0.02). CONCLUSIONS: The present study is a preliminary exploration of factors associated with HbA1c response to SGLT2 inhibitors and GLP1 receptor agonists. Differences in predictors of HbA1c changes across different classes of drugs could be useful in identifying the most suitable drug in individual patients. SGLT2 inhibitors seem to be associated with a greater reduction of HbA1c in younger subjects, and GLP1 agonists in those with a shorter duration of diabetes.

Efficacy and effectiveness of Herpes zoster vaccination in adults with diabetes mellitus: a systematic review and meta-analysis of clinical trials and observational studies.

AIM: The risk for Herpes zoster (HZ) and its complications is higher in people with diabetes mellitus (DM). Our aim is to assess efficacy and effectiveness of the currently available live-attenuated zoster vaccine (LZV) and recombinant zoster vaccine (RZV) in adults with DM. METHODS: A Systematic Review and Meta-analysis of clinical trials and observational studies comparing incidence of HZ and its complications in vaccinated and unvaccinated people with DM was performed, on PubMed, Cochrane, Clinical Trials.gov and Embase databases, up to January 15th, 2023. Risk of bias was assessed through the Cochrane Collaboration tool and the Newcastle-Ottawa Scale. The protocol was registered on the PROSPERO website (CRD42022370705). RESULTS: Only three observational studies reported LZV efficacy and effectiveness in people with DM. A lower risk for HZ infection (MH-OH Ratio 95% CI = 0.52 [0.49, 0.56] was observed, for unadjusted analysis, and 0.51 [0.46, 0.56] for adjusted analysis, both with P < 0.00001 and no heterogeneity). No data on LZV safety were reported. A pooled analysis of two trials comparing RZV and placebo, showed a reduced risk for HZ incidence: (95% CI Odds Ratio: 0.09 [0.04-0.19]), with no difference in severe adverse events and mortality. CONCLUSIONS: In our meta-analysis of three observational studies LZV showed a 48% effectiveness in reducing HZ incidence in adults with diabetes whereas in a pooled analysis of two RCTs, RZV showed a 91% efficacy. No data are available on the effects of vaccination on the incidence and severity of HZ-related complications among subjects with diabetes.

Influenza: Diabetes as a risk factor for severe related-outcomes and the effectiveness of vaccination in diabetic population. A meta-analysis of observational studies.

AIMS: In order to better define the need for influenza vaccination in people with diabetes (DM), we collected all available evidence on the effect of DM as a risk factor for complications of both seasonal and pandemic influenza, and on the specific effectiveness of vaccines in patients with DM. DATA SYNTHESIS: Two distinct systematic searches on MEDLINE, Cochrane, ClinicalTrials.gov and Embase databases were performed, one for each metanalysis, collecting all observational studies and randomized clinical trials performed on humans up to May 31st, 2022. We retrieved 34 observational studies comparing risk for influenza complications in people with or without diabetes, and 13 observational studies assessing vaccine effectiveness on preventing such complications. Mortality for influenza and hospitalization for influenza and pneumonia resulted significantly higher in individuals with versus without DM, both when unadjusted and adjusted data are analyzed. In diabetic individuals vaccinated for influenza overall hospitalization, hospitalization for influenza or pneumonia and overall mortality are significantly lower in comparison with not vaccinated DM subjects, both when unadjusted and adjusted data were analyzed. CONCLUSION: This systematic review and meta-analysis shows that: 1) influenza is associated with more severe complications in diabetic versus not diabetic individuals and 2) influenza vaccination is effective in preventing clinically relevant outcomes in adults with DM with a NNT (number needed to treat) of 60, 319, and 250 for all-cause hospitalization, specific hospitalization, and all-cause mortality, respectively. The identification of diabetic patients as the target of vaccination campaigns for influenza appears to be justified by available clinical evidence.

Orthorexia nervosa and type 1 diabetes: results of a cross-sectional study.

AIM: Orthorexia nervosa (ON) is a condition characterized by an excessive importance attributed to the intake of healthy foods. This study was aimed at investigating the prevalence of ON in subjects with type 1 diabetes (T1D) compared to control subjects. METHODS: Patient with T1D using either flash glucose monitoring or continuous glucose monitoring were enrolled. For the selection of control group, each patient was asked to indicate one non-diabetic subject of their same sex and approximate age among colleagues at work and school. Patients and controls completed the following questionnaires: ORTO-15, Dusseldorf Orthorexie Scale (DOS), Eating Disorder Examination Questionnaire (EDE-Q) and Brief Symptom Inventory (BSI). The principal outcome was the prevalence of ON among T1D and control subjects. RESULTS: We enrolled 44 patients with T1D aged 39.7 ± 15.7 years, with BMI 24.3 ± 4.3 kg/m2, and mean HbA1c 53.5 [49-57] mmol/mol. Control subjects were similar to T1D with respect to sex, age and BMI. Thirty-two [72%] and 29 [65%] subjects among patients and controls, respectively, had ORTO15 < 40 (between-group p = 0.48). Two (4.5%) and zero subjects among patients and controls, respectively, had DOS ≥ 30 (p = 0.29). Median scores of DOS, but not of ORTO-15, were significantly higher in patients than in controls. None of the metabolic variables showed a correlation with psychometric tests in T1D. CONCLUSION: Although the prevalence of ON was not significantly higher in T1D than in controls, patients with T1D showed higher scores of some, but not all, tests assessing orthorexia, without any significant correlation with metabolic parameters.

Pancreatitis and pancreatic cancer in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonists: an updated meta-analysis of randomized controlled trials.

INTRODUCTION: An association between glucagon-like peptide-1 receptor agonists (GLP1-RA) and risk of pancreatitis and pancreatic cancer has been suggested. Since its first description, several new trials (including three cardiovascular outcome trials) have been published, substantially increasing the available data set. This suggests the need for an update of the previous meta-analysis. EVIDENCE ACQUISITION: A Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials, with duration ≥52 weeks, enrolling patients with type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug. The endpoints were pancreatitis, pancreatic cancer reported as serious adverse events. Mantel-Haenszel Odds Ratio (MH-OR) with 95% confidence interval (95% CI) was calculated for all outcomes defined above, on an intention-to-treat basis. EVIDENCE SYNTHESIS: A total of 43 trials fulfilling inclusion criteria (all reporting data on pancreatitis and pancreatic cancer) was identified. GLP-1 RA showed no association with pancreatitis (MH-OR 1.24 [0.94, 1.64]; P=0.13) and pancreatic cancer (MH-OR 1.28 [0.87, 1.89]; P=0.20). CONCLUSIONS: No clear evidence of risk for pancreatitis was observed, whereas data on pancreatic cancer are too scarce to draw any conclusion.

Periodontitis predicts HbA1c levels and glucose variability in type 1 diabetic patients: the PARODIA Florence Project study.

OBJECTIVE: The aim of the present study was to assess the extent and severity of periodontal disease among type 1 diabetic patients (T1DM) and to investigate the possible association with systemic markers of glucose control and variability. MATERIAL AND METHODS: Patients were consecutively enrolled in a Diabetic Unit. A full-mouth periodontal evaluation was performed, and data on systemic markers of diabetes were collected. Descriptive statistics and logistic and linear models were performed. RESULTS: A total of 136 T1DM patients (mean age: 45.5 ± 14.6 years) were examined. Periodontitis was detected in 62% of cases (mean CAL: 3.0 ± 0.9 mm): stage III periodontitis was diagnosed in 32% of patients while stage IV in 8%. Mean level of glycated hemoglobin (HbA1c) was 7.5% ± 1.4. Among the investigated factors, mean CAL (p=0.040) was associated with HbA1c ≥ 7%; 93% of patients with mean CAL > 6 mm showed HbA1c ≥ 7%. Mean CAL (p=0.004), mean PPD (p=0.005), mean FMPS (p=0.030), and stage III/IV periodontitis (p=0.018) predict glucose coefficient of variation (CV). CONCLUSIONS: Periodontitis showed a relevant prevalence in the present, well-controlled T1DM population and predicts poor glycemic control (HbA1c ≥7%) and higher glucose variability. The present findings suggest that periodontal infection may have systemic effects also in T1DM patients. CLINICAL RELEVANCE: The extent and severity of periodontitis and its possible systemic effects in T1DM patients could be underestimated.

Glucose-lowering therapy in patients undergoing percutaneous coronary intervention.

The number of individuals with diabetes and pre-diabetes is constantly increasing. These conditions are overrepresented in patients undergoing percutaneous coronary intervention and are associated with adverse prognosis. Optimal glycaemic control during an acute coronary syndrome is a relevant factor for the improvement of longer-term outcomes. In addition, the implementation of newer glucose-lowering drugs with proven cardiovascular benefits has a remarkable impact on recurrence of events, hospitalisations for heart failure and mortality. In this narrative review, we outline the current state-of-the art recommendations for glucose-lowering therapy in patients with diabetes undergoing coronary intervention. In addition, we discuss the most recent evidence-based indications for revascularisation in patients with diabetes as well as the targets for glycaemic control post revascularisation. Current treatment goals for concomitant risk factor control are also addressed. Lastly, we acknowledge the presence of knowledge gaps in need of future research.

Glucose control in diabetes during home confinement for the first pandemic wave of COVID-19: a meta-analysis of observational studies.

AIM: To assess the effect on glycaemic control of confinement due to lockdown measures, during COVID-19 pandemic, in people with type 1 (T1DM) and type 2 (T2DM) diabetes. METHODS: Meta-analysis of observational studies reporting measures of glucose control and variability before and during and/or after periods of confinement caused by COVID-19 in 2020 and/or 2021. RESULTS: We included 27 studies on T1DM. No significant change in Hba1c was observed after lockdown (WMD - 1.474 [- 3.26; 0.31] mmol/mol, I2 = 93.9). TIR significantly increased during and after lockdown (WMD: 2.73 1.47; 4.23 %, I2 = 81% and 3.73 [1.13; 5.33] %, I2 = 85%, respectively).We retrieved nine studies on T2DM patients. No significant variation in HbA1c was detected (WMD - 1.257 - 3.91; 1.39 mmol/mol, I2 = 98.3%). HbA1c had a more favourable trend in studies performed in Asia than in Europe (p = 0.022 between groups). CONCLUSION: Lockdown showed no significant detrimental effect on HbA1c in either T1DM or T2DM. Conversely, home confinement led to a reduction in mean glucose and glucose variability in T1DM, although with a high heterogeneity of results.

Glucose variability and periodontal disease in type 1 diabetes: a cross-sectional study-The "PAROdontopatia e DIAbete" (PARODIA) project.

AIMS: Periodontal disease (PD) is a chronic inflammation of periodontal tissue associated with infection from specific anaerobic pathogens contained in dental plaque. Both type 1 and type 2 diabetes are associated with an increased prevalence of PDs. A two-way relationship between diabetes and periodontitis has been proposed, with diabetes increasing the risk for periodontitis, and periodontal inflammation negatively affecting glycaemic control. To date, the relationship between PD and glucose variability in type 1 diabetes has not been evaluated. To investigate the prevalence of PD in patients with type 1 diabetes and its association with glycemic control and glucose variability. METHODS: In this cross-sectional study, all enrolled patients were scheduled to attend both a diabetologic and a periodontal visit. HbA1c, glucose coefficient of variation (CV), loss of clinical attachment (CAL), and periodontal probing depth (PPD) were collected. RESULTS: 136 patients were included in the analysis. The prevalence of PD was 63%. A significant correlation was found between mean CAL and glucose CV (r = 0.31, p = 0.002), but not with HbA1c. Mean PPD was also associated with glucose CV (r = 0.27 and 0.044), but not with HbA1c. In a multiple linear regression model, with mean CAL as dependent variable, age, glucose CV, and smoking habit resulted significantly associated (r = 0.23, p = 0.013; r = 0.33, p = 0.001; r = 0.34, p < 0.001, respectively). Assuming mean PPD as dependent variable, multiple linear regression analysis showed a significant association with glucose CV and smoking habits only. CONCLUSIONS: PD is associated with glucose variability in patients with type 1 diabetes also after adjusting for the main confounders.

Efficacy and safety of glucose-lowering agents in patients with type 2 diabetes: A network meta-analysis of randomized, active comparator-controlled trials.

AIM: Aim of the present network meta-analysis (NMA) is the comparison across glucose-lowering drugs (GLA) concerning their effects on glucose control, body weight, hypoglycemia, gastrointestinal adverse events, and quality of life. DATA SYNTHESIS: This NMA includes randomized clinical trials comparing different head-to-head comparison trials with EMA-approved GLA in type 2 diabetes, with a duration of ≥52 weeks. All drugs have to be administered at the maximal approved dose. Primary endpoints were HbA1c at 12, 52, and 104+ weeks. Secondary endpoints were body weight, quality of life, hypoglycemia, and gastrointestinal disorders. Indirect comparisons of different GLA were performed by NMA choosing metformin as reference. The standardized difference in means (SDM) and Mantel-Haenzel Odds Ratio [MH-OR] (using random-effect models) with 95% Confidence Intervals were calculated for categorical and continuous variables, respectively. We included 68 trials fulfilling all inclusion criteria. At 12 weeks, when considering indirect comparisons, insulin secretagogues (IS) were associated with a significantly greater reduction in comparison with metformin (SDM, -0.3 [-0.4;-0.2]%); a significantly lower efficacy was observed for pioglitazone. At 52 weeks, IS were no longer associated with a greater reduction of HbA1c; whereas a significant decrease in HbA1c was observed for GLP-1 RA (SDM, -0.2 [-0.1;-0.3]%). At 104+ weeks, only SGLT-2 inhibitors showed a significantly greater HbA1c reduction (SDM, -0.2 [-0.1;-0.3]%), whereas sulfonylureas and insulin showed a significantly lower efficacy (SDM, 0.1 [0.0; 0.2]%), and 0.4 [0.3; 0.5]%, respectively). CONCLUSIONS: The results of this meta-analysis should be considered together with evidence on long-term outcomes for selecting the most appropriate drugs for individual patients.

Deprescription in elderly patients with type 2 diabetes mellitus.

AIMS: The Primary aim is to verify physicians' adherence to the 2016 Italian diabetes guidelines therapeutic targets, and their habits on deprescription in elderly persons with Type 2 Diabetes Mellitus (T2DM). Secondary aims are the assessment of the potential impact of the targets' changes in 2018 Italian guidelines, and the outcomes of deprescription in the management of T2DM. METHODS: Observational retrospective cohort study, enrolling persons with T2DM, aged > 75 years, who attended a visit throughout 2017, and a second visit 6 months later in our outpatient clinic. RESULTS: Of the 387 patients included, 336 (87, 8%) were on target, according to 2016 guidelines. Deprescription was advisable in 62% of patients on target. Among those, 22% were deprescribed. In patients undergoing deprescription, during the following 6 months, no severe hypoglycemia occurred (versus 5 cases in the prior 6 months). Glycated Hemoglobin (HbA1c) increased (p < 0.05) from 47.0 [41.7-51.0] to 53.0 [45.4-59.5] mmol/mol). Applying to the sample the 2018 Italian Guidelines targets, 57.2% would have been on target, 18.5% above, and 24.3% below (needing deprescription). CONCLUSION: In our study, a minority of suitable patients received deprescription. Deprescription led to a significant reduction in severe hypoglycemia rate, whereas HbA1c remained on target in the majority of cases.

Major cardiovascular events, heart failure, and atrial fibrillation in patients treated with glucagon-like peptide-1 receptor agonists: An updated meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Glucagon-like Peptide 1 Receptor Agonists (GLP1-RA) has been associated with a reduction of major cardiovascular events (MACE) and mortality on the basis of the results of cardiovascular outcome trials (CVOT). Several meta-analyses on this issue have been recently published; however, they were all restricted to CVOT, with the exclusion of all studies designed for other endpoints; moreover, other cardiovascular endpoints, such as atrial fibrillation and heart failure have not been fully explored. METHODS AND RESULTS: A Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration ≥52 weeks, enrolling patients with type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug. We included 43 trials, enrolling 63,134 patients. A significant reduction of MACE (MH-OR 0.87 [0.83, 0.92]), all-cause mortality (MH-OR 0.89 [0.83, 0.96]), and a nonstatistical trend toward reduction of heart failure (MH-OR 0.93 [0.85, 1.01]) was observed - GLP1-RA did not increase the risk of atrial fibrillation (MH-OR 0.94 [0.84, 1.04]). CONCLUSION: The present meta-analysis confirms the favorable effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events, cardiovascular and all-cause mortality, stroke, and possibly myocardial infarction. Conversely, the effects on heart failure remain uncertain. Available data on atrial fibrillation seems to exclude any major safety issues in this respect. REGISTRATION NUMBER (PROSPERO): CRD42018115577.