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.

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.

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.

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.

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.

Fournier's gangrene and sodium-glucose co-transporter-2 inhibitors: A meta-analysis of randomized controlled trials.

Fournier's gangrene (FG) is a rare, life-threatening necrotizing fasciitis of the perineum. The US Food and Drug Administration (FDA) released a Drug Safety Communication regarding the risk of FG associated with sodium-glucose co-transporter-2 inhibitors (SGLT2i), relying on the FDA Adverse Event Reporting System. To verify this association, we performed a meta-analysis of all randomized controlled trials enrolling patients with type 2 diabetes, comparing SGLT2i with placebo or different therapies, collecting cases of FG reported as a serious adverse event. Risk of abscess, cellulitis and erysipela were secondary outcomes. We retrieved 84 trials enrolling 42 415 patients in the SGLT2i group and 27 158 patients in comparator groups. No difference was observed between SGLT2i and comparators in the risk of FG (Mantel-Haenzel odds ratio [MH-OR] 0.41 [0.09, 1.82]), abscess (MH-OR 0.94 [0.54, 1.65]), cellulitis (MH-OR 0.90 [0.71, 1.13] or erysipela (MH-OR 0.89 [0.45, 1.77]). The number of events was small, leading to a wide confidence interval that does not allow ruling out an increase in FG or skin and subcutaneous tissue infections.

Glucagon-like peptide-1 receptor agonists and cardiovascular outcomes in patients with and without prior cardiovascular events: An updated meta-analysis and subgroup analysis of randomized controlled trials.

AIM: To conduct a meta-analysis of cardiovascular outcome trials on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major adverse cardiovascular events (MACE). METHODS: A search of MEDLINE, EMBASE, Cochrane database and clinicaltrials.gov was performed to identify controlled trials (up to 15 June 2019) of GLP-1RAs with a cardiovascular endpoint. The principal endpoint of the present meta-analysis was MACE; secondary endpoints included myocardial infarction, stroke, cardiovascular and all-cause mortality, and hospitalization for heart failure. Mantel-Haenszel odds ratios (MH-ORs) with 95% confidence intervals (CIs) were calculated for all outcomes. RESULTS: In the seven trials included, all placebo-controlled, GLP-1RA treatment was associated with a reduction in MACE (MH-OR 0.87 [95% CI 0.81, 0.93]). Cardiovascular and all-cause mortality, myocardial infarction and stroke were also reduced (MH-OR 0.88 [95% CI 0.80, 0.96], MH-OR 0.90 [95% CI 0.82, 0.98], MH-OR 0.91 [95% CI 0.84, 0.98] and MH-OR 0.86 [95% CI 0.77, 0.97], respectively). Results for hospitalization for heart failure were not statistically significant (MH-OR 0.93 [95% CI 0.83, 1.04]). The meta-analyses of patient subgroups showed a significant reduction in MACE with GLP-1RAs, irrespective of gender, advanced age and obesity. CONCLUSIONS: GLP-1RAs are associated with a reduction in cardiovascular morbidity and mortality in high-risk patients with diabetes. This effect does not appear to be moderated by gender or body mass index. The possibility of different effects of GLP-1RAs between patients in primary and secondary prevention merits further investigation.

Combined continuous glucose monitoring and subcutaneous insulin infusion versus self-monitoring of blood glucose with optimized multiple injections in people with type 1 diabetes: A randomized crossover trial.

AIM: To investigate the efficacy of a combination of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) versus an optimized degludec-based multiple daily injections (MDI) regimen + self-monitoring of blood glucose (SMBG) in people with type 1 diabetes with regard to optimizing glucose control. MATERIAL AND METHODS: The trial included 28 individuals who underwent a 4-week run-in phase, and were then randomized 1:1 to: (a) CSII + CGM followed by MDI + SMBG or (b) an MDI basal-bolus regimen followed by CSII + CGM. RESULTS: In patients randomized to the CSII + CGM → MDI + SMBG arm, a significant reduction in glycated haemoglobin (HbA1c) versus baseline was found at the end of the first phase (CSII + CGM) without significant variation in the following MDI + SMBG phase. In the arm randomized to the MDI + SMBG → CSII + CGM sequence, a significant improvement in HbA1c was observed in the first phase (MDI + SMBG), together with a further decrease in the following CSII + CGM phase. In the comparison of the two treatments using a mixed linear model, CSII + CGM was superior to MDI + SMBG with respect to change in HbA1c (P = 0.001). CONCLUSIONS: This study suggests that CSII + CGM improves glycaemic control without relevant safety issues in type 1 diabetes, in comparison with MDI + SMBG.

Exploring the heterogeneity of the effects of SGLT-2 inhibitors in cardiovascular outcome trials.

BACKGROUND AND AIM: The interpretation of discrepancies across cardiovascular safety trials (CVOT) with SGLT-2 inhibitors in the incidence of major cardiovascular events (MACE) and mortality is complex, because of heterogeneity in trial protocols and baseline characteristics of patients enrolled. Aim of this analysis is the exploration of possible determinants of heterogeneity of relative risk reduction for major cardiovascular events (MACE) and all-cause mortality. METHODS AND RESULTS: Incidence of events (MACE and mortality) in intervention and control groups and baseline characteristics of patients were extracted for each trial (EMPAREG, CANVAS, and DECLARE). For studies including both primary and secondary prevention cohorts, those two subgroups were considered separately. Metaregression analysis was used to assess the association of relative risk reduction with baseline characteristics of patients, including observed incidence of events with placebo. The estimated reduction in the incidence of MACE associated with SGLT-2 inhibitors showed a significant association with the incidence of MACE in the control group, suggesting that a greater effect was observed in trials enrolling patients at higher risk (Slope -0.008 [-0.023; 0.007], p = 0.31). A higher proportion of patients treated with statins, ß-blockers and insulin at baseline was associated with a greater reduction of MACE, but not of mortality. CONCLUSIONS: In CVOT trials, the magnitude of the effect of SGLT-2 inhibitors on MACE is driven by absolute risk of enrolled patients; as a consequence, the estimated risk reduction is lower in primary prevention cohorts, which have a lower risk. This result supports the hypothesis of a class effect of SGLT-2 inhibitors on MACE.

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.

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors and cancer: A meta-analysis of randomized controlled trials.

AIM: The aim of this meta-analysis of randomized trials was to assess the effects of SGLT-2i on the overall incidence of malignancies and on different types of cancer, summerizing the results of trials with a duration of at least 1 year. This was done in light of the effect of SGLT-2 inhibitors (SGLT-2is) that has been highlighted by some studies, showing an increased incidence of bladder cancer, particularly with use of empagliflozin. MATERIALS AND METHODS: A Medline and Embase search for "Canaglifozin", "Dapaglifozin", "Empaglifozin", "Ertuglifozin", "Ipraglifozin", Tofoglifozin" or "Luseoglifozin" was performed, identifying randomized trials with a duration of more than 52 weeks up to 1 December 2018 that compared SGLT-2is with placebo or active comparators. The outcomes considered were all types of cancer and several site-specific cancers (ie, breast, pulmonary, gastrointestinal, hepatic, pancreatic, skin, prostate and bladder). Mantel-Haenszel odds ratios with 95% Confidence Intervals (MH-OR, 95% CI) were calculated for all outcomes. RESULTS: A total of 27 trials fulfilled the inclusion criteria. Retrieved trials had enrolled 27 744 and 20 441 patients in SGLT-2 inhibitor and comparator groups, respectively. No difference was observed in the incidence of all malignancies between patients allocated to SGLT-2i and comparators (MH-OR 0.98[0.77-1.24]). The incidence of bladder cancer, and of any other type of cancer, was not significantly increased by treatment with any SGLT-2i. CONCLUSIONS: Available data from randomized trials do not suggest a detrimental effect of SGLT-2is on the incidence of malignancies in general, or in bladder cancer in particular.

Impact of technology on glycaemic control in type 2 diabetes: A meta-analysis of randomized trials on continuous glucose monitoring and continuous subcutaneous insulin infusion.

AIM: To conduct a meta-analysis to assess the effect of continuous subcutaneous insulin infusion (CSII), continuous glucose monitoring (CGM), and the combination of the two, on glycaemic control in type 2 diabetes. MATERIALS AND METHODS: The analysis included randomized clinical trials comparing CSII with multiple daily injections (MDI) in people with type 2 diabetes, as well as studies comparing CGM or flash glucose monitoring (FGM) with self-monitoring of blood glucose (SMBG), with a duration of at least 12 weeks, identified in Medline or clinicaltrials.gov. The principal endpoint was glycated haemoglobin (HbA1c) at the end of the trial. Mean and 95% confidence intervals (CIs) for HbA1c and Mantel-Haenzel odds ratios for severe hypoglycaemia were calculated, using random-effect models. RESULTS: The retrieved trials showed a significant heterogeneity (I2 = 90%). The difference in HbA1c between CSII and MDI was not statistically significant (-0.26% [95% CI -0.74;0.22]; P = .29). The difference in endpoint HbA1c between CGM and SMBG was marginally significant (-0.24 [95% CI -0.49;0.00]; P = .05), and CGM was possibly associated with a lower hypoglycaemic risk. Only one trial explored the effect of FGM, as compared with SMBG, on HbA1c in type 2 diabetes, finding no difference across groups (at study end: 8.4% ± 0.8% vs 8.3% ± 1.1% with FGM and SMBG, respectively). Conversely, FGM was associated with an improvement in quality of life and with a lower incidence of hypoglycaemic events. The small number of retrieved trials indicates that the results should be interpreted with caution. CONCLUSIONS: The analysis showed that CSII, CGM and FGM provide only small benefits compared with MDI (on either HbA1c, hypoglycaemic risk or quality of life) in insulin-treated people with type 2 diabetes.

Drugs for type 2 diabetes: role in the regulation of bone metabolism.

Until a few years ago, the possibility that glucose-lowering drugs affect glucose metabolism and fracture risk was not even considered. The increased incidence of fractures with thiazolidinediones in women was a causal finding. This phenomenon, which has been demonstrated by large-scale clinical trials, is associated with a reduction in bone density. Thiazolidinediones stimulate adipocyte differentiation, and inhibit osteoblast differentiation, from bone marrow stromal cells; other mechanisms could also be involved in the thiazolidinedione-induced reduction of bone density. Insulin has an anabolic effect on the bone, but it is nonetheless associated with an increased incidence of fractures in observational studies. Although this finding could be partly due to unaccounted confounders, it is likely that insulin-induced hypoglycemia, and consequent falls, produce a higher risk for fractures, at least in the elderly. Among older drugs, metformin and sulfonylureas do not appear to produce any beneficial or detrimental effects on the bone. Of newer agents, DPP4 inhibitors have been associated with a possible protective effect in earlier trials, but this result has not been confirmed in larger scale studies on patients with a higher level of comorbidities. Considering that the increase in active incretin levels determined by DPP4 inhibitors could theoretically improve bone density, further clinical studies are needed to assess more clearly the effect of this class of drugs. GLP-1 receptor agonists also increase bone density in experimental models, but human data are still insufficient to draw any conclusion.

Achieving HbA1c targets in clinical trials and in the real world: a systematic review and meta-analysis.

PURPOSE: To review the proportion of diabetic patients reaching recommended therapeutic goals, as reported in intervention trials and observational studies, and to analyse the factors associated with success or failure in achieving these targets. METHODS: A systematic review and meta-analysis through a Medline and Embase search for "diabetes" and "HbA1c" has been performed between 1 January 1995 and 1 March 2012 on randomised clinical trials and observational studies on type 1 (T1DM) or type 2 diabetes (T2DM) enrolling at least 200 patient*year. RESULTS: Out of 169 patient groups in RCTs with results available for analysis, the overall proportion of patients reaching HbA1c ≤ 7 % was 36.6 (34.1-39.1) %. Of these, 8 groups included T1DM subjects [proportion at target (PAT) 27.2 (22.7-32.3) %] and 161 T2DM patients [PAT 37.1 (34.5-39.7) %]. In patients with T2DM on oral agents, at multivariate analysis, higher success rate was associated with higher age and body mass index (BMI), lower duration of diabetes, lower proportion of Caucasians and more recent publication year. Among the insulin treated, only duration of diabetes retained a significant association with success rate. Among 41 groups from cross-sectional studies, 6 and 22 were composed of patients with T1DM and T2DM, respectively, and the remaining 13 included both types. Patients at target for HbA1c were 19.8 (12.4-30.1), 36.1 (31.5-41.0), and 39.0 (32.9-45.3) %, respectively. Higher age, lower BMI, shorter duration of diabetes and a higher proportion of males and Caucasians were associated with a higher success rate. CONCLUSIONS: Available data show that a wide distance remains between recommended targets and actual achievements in routine clinical practice.

The therapy of insulin resistance in other diseases besides type 2 diabetes.

Insulin resistance is a clinical condition shared by many diseases besides type 2 diabetes (T2DM) such as obesity, polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD). Experimental evidence, produced over the years, suggests that metformin has many benefits in the treatment of these diseases. Metformin is a first-line drug in the treatment of overweight and obese type 2 diabetic patients, offering a selective pathophysiological approach by its effect on insulin resistance. Moreover, a number of studies have established the favorable effect of metformin on body weight, not only when evaluating BMI, but also if body mass composition is considered, through the reduction of fat mass. In addition, it reduces insulin resistance, hyperinsulinemia, lipid parameters, arterial hypertension and endothelial dysfunction. In particular, a new formulation of metformin extended-release (ER) is now available with different formulation in different countries. Metformin ER delivers the active drug through hydrated polymers which expand safe uptake of fluid, prolonging gastric transit and delaying drug absorption in the upper gastrointestinal tract. In addition, Metformin ER causes a small, but statistically significant decrease in BMI, when added to a lifestyle intervention program in obese adolescents. Because of the suggested benefits for the treatment of insulin resistance in many clinical conditions, besides type 2 diabetes, the prospective exists that more indications for metformin treatment are becoming a reality.

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.

Psychopathology and continuous subcutaneous insulin infusion in type 1 diabetes.

AIM: Continuous subcutaneous insulin infusion (CSII) is used as an option in patients with diabetes failing to multiple daily injections (MDI). Psychological factors may play a relevant role in the failure to attain therapeutic goals in patients on MDI. This could lead to an overrepresentation of psychopathology in patients treated with CSII. METHODS: A consecutive series of 100 patients with type 1 diabetes was studied, collecting main clinical parameters and assessing psychopathology with the self-reported questionnaire Symptom Checklist 90-revised. Patients on CSII were then compared with those on MDI. RESULTS: Of the 100 enrolled patients, 44 and 56 were on CSII and MDI, respectively. Among men, those on CSII were younger than those on MDI; conversely, no difference in age was observed in women. Women on CSII showed higher scores on most Symptom Checklist 90 subscales than those on MDI, whereas no differences were observed in men. CONCLUSION: Women with type 1 diabetes treated with CSII display higher levels of psychopathology than those on MDI. This is probably the consequence of the fact that patients selected for CSII are those failing to MDI. Higher levels of psychopathology could represent a limit for the attainment and maintenance of therapeutic goals with CSII.

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.

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.

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.