Increased frequency of microalbuminuria in patients with type 3 autoimmune polyglandular syndrome (APS) compared to isolated autoimmune type 1 diabetes mellitus: A real-life study.

AIM OF THE STUDY: The primary aim of the study was to evaluate the differences in metabolic control and chronic microvascular complications in patients with type 3 autoimmune polyglandular syndrome (APS3), compared to type 1 diabetes mellitus (T1DM) alone. Secondary aims were to evaluate the age of autoimmune thyroid disease (AIT) onset and the effects of levothyroxine treatment on metabolic control in patients with APS3. MATERIAL AND METHODS: We retrospectively reviewed 276 patients with T1DM alone and 214 patients with APS3 and evaluated clinical and metabolic parameters and microvascular complications. RESULTS: Patients with T1DM showed a longer duration of diabetes (p = 0.001) and lower age of diabetes onset (p = 0.020) compared to patients with APS3. Female gender (p = 0.001) and microalbuminuria (p = 0.006) were significantly more frequent in patients with APS3 compared to T1DM. In addition, patients with APS3 showed higher AIT onset frequency in the 16-30 quartile age-range. Furthermore, APS3 patients treated with levothyroxine showed significantly better HbA1c values than non-treated patients (p = 0.001). CONCLUSIONS: We found that patients with APS3 showed positive microalbuminuria, earlier than T1DM. Patients with APS3 showed higher frequency of AIT age of onset in the 16-30 age-range and those treated with levothyroxine had better metabolic control, than untreated ones.

Evidence of greater severity of diabetic foot ulcers during COVID-19 pandemic: A real-life single-centre cohort study.

AIMS: In the Sars-Cov-2 pandemic era, patients with diabetes mellitus (DM) manifested more severe forms of Sars-Cov-2 with greater mortality than non-diabetic patients. Several studies documented more aggressive forms of diabetic foot ulcers (DFU) during the pandemic period even though the results were not unanimously confirmed. The aim of this study was to evaluate the clinical-demographic differences between a cohort of Sicilian diabetic patients hospitalised for DFU in the pre-pandemic 3 years and a cohort of patients hospitalised in the pandemic 2 years. MATERIALS AND METHODS: One hundred and eleven patients from the pre-pandemic period 2017-2019 (Group A) and 86 patients from the pandemic period 2020-2021 (Group B) with DFU, admitted to the division of Endocrinology and Metabolism of the University Hospital of Palermo, were retrospectively evaluated. The clinical assessment of the type, staging and grading of the lesion, and the infective complication from DFU was performed. RESULTS: No differences in HbA1c values were observed between the two groups. Group B showed a significantly higher prevalence of male subjects (p = 0.010), neuro-ischaemic ulcers (p < 0.001), deep ulcers with involvement of bones (p < 0.001), white blood count levels (p < 0.001), and reactive C protein (p = 0.001) compared to group A. CONCLUSIONS: Our data show that in the COVID-19 pandemic, a greater severity of ulcers requiring a significantly greater number of revascularisations and more expensive therapy, but without an increase in the amputation rate, was observed. These data provide novel information on the impact of the pandemic on diabetic foot ulcer risk and progression.

Diabetic foot ulcers: Retrospective comparative analysis from Sicily between two eras.

AIM: The aim of this study was to analyze changes in the incidence, management and mortality of DFU in Sicilian Type 2 diabetic patients hospitalized between two eras, i.e. 2008-2013 and 2014-2019. METHODS: We compared the two eras, era1: 2008-13, era2: 2014-19. In era 1, n = 149, and in era 2, n = 181 patients were retrospectively enrolled. RESULTS: In the population hospitalized for DFU in 2008-2013, 59.1% of males and 40.9% of females died, whilst in 2014-2019 65.9% of males and 34.1% of females died. Moderate chronic kidney disease (CKD) was significantly higher in patients that had died than in ones that were alive (33% vs. 43%, p < 0.001), just as CKD was severe (14.5% vs. 4%, p < 0.001). Considering all together the risk factors associated with mortality, at Cox regression multivariate analysis only moderate-severe CKD (OR 1.61, 95% CI 1.07-2.42, p 0.021), age of onset greater than 69 years (OR 2.01, 95% CI 1.37-2.95, p <0.001) and eGFR less than 92 ml/min (OR 2.84, 95% CI 1.51-5.34, p 0.001) were independently associated with risk of death. CONCLUSIONS: Patients with DFU have high mortality and reduced life expectancy. Age at onset of diabetic foot ulcer, eGFR values and CKD are the principal risk factors for mortality.

Effects of GLP-1 receptor agonists on myokine levels and pro-inflammatory cytokines in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: To evaluate the change in circulating serum irisin and interleukin-6 (IL-6), in patients with type 2 diabetes mellitus (T2DM) after 6 and 12 months of GLP-1 treatment. METHODS AND RESULTS: Eighty-five patients with T2DM inadequately controlled with insulin or other hypoglycaemic drugs were added to dulaglutide (N° = 44) and liraglutide (N° = 41) treatment. After 6 months of GLP-1 analogues a significant decrease in BMI (p < 0.001), waist circumference (WC) (p < 0.001), fasting blood glucose (p < 0.001), HbA1c (p < 0.001), total cholesterol (p < 0.001), LDL-cholesterol (p = 0.003), triglycerides (p = 0.017), IL-6 (p = 0.045) and a significant increase in serum irisin (p < 0.001) were observed compared to baseline. After 12 months of treatment no significant differences were found compared to the levels at 6 months. The change in irisin from baseline (Δ_irisin) was significantly related to the changes in total-cholesterol (Δ_total-cholesterol) (r = -0.293; p = 0.020), while the change in IL-6 (Δ_IL-6) was significantly related to the changes in WC (Δ_WC) (r = 0.347; p = 0.006). CONCLUSIONS: Additive treatment with GLP1-analogues results in an increase in serum circulating irisin levels and a decrease in IL-6. The post-treatment change in irisin was correlated with a decrease in total cholesterol, while the change in IL-6 was correlated with a decrease in WC.

One Year of Dapaglifozin Add-On Therapy Ameliorates Surrogate Indexes of Insulin Resistance and Adiposity in Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: This study investigates the effects of dapagliflozin on the visceral adiposity index (VAI), lipid accumulation product (LAP), product of triglycerides and glucose (TyG) and triglycerides to HDL-cholesterol ratio (TG/HDL-C) in patients with type 2 diabetes mellitus (T2D). METHODS: In this real-life study, dapaglifozin was added to metformin alone (group 1, no. 42) or insulin plus metformin (group 2, no. 58) in 100 T2D patients. RESULTS: In group 1, after 6 months of dapaglifozin addition, a significant decrease in BMI (p < 0.001), waist circumference (WC) (p < 0.001), systolic blood pressure (SBP) (p = 0.009), diastolic blood pressure (DBP) (p = 0.012), mean fasting blood glucose (FBG), post-breakfast glucose (PBG), post-lunch glucose (PLG) and post-dinner glucose (PDG) (all p < 0.001), HbA1c (p < 0.001), VAI (p = 0.020), LAP (p = 0.028), Tyg (p < 0.001), TG/HDL-C (p = 0.020) and glutamate pyruvate transaminase (GPT) (p < 0.001) was observed compared to baseline. After 12 months a significant decrease in BMI (p < 0.001), WC (p = 0.006), SBP (p = 0.023), DBP (p = 0.005), mean FPG, PBG, PLG and PDG (all p < 0.001), HbA1c (p < 0.001), total cholesterol (p = 0.038), triglycerides (p = 0.026), VAI (p = 0.013), GPT (p < 0.001), LAP index (p = 0.024), Tyg index (p < 0.001) and TG/HDL-c ratio (p = 0.016) was observed compared to baseline. In group 2, after 6 months of dapaglifozin addition, a significant decrease in BMI (p < 0.001), WC (p < 0.001), SBP (p = 0.015), DBP (p = 0.007), mean FPG, PBG, PLG and PDG (all p < 0.001), HbA1c (p < 0.001), VAI (p = 0.040), LAP (p = 0.047), Tyg (p < 0.001), TG/HDL-C (p = 0.048) and GPT (p < 0.001) was observed compared to baseline. By contrast, after 12 months a significant decrease in BMI (p < 0.001), WC (p < 0.001), SBP (p = 0.001), DBP (p = 0.002), mean FPG, PBG, PLG and PDG (all p < 0.001), HbA1c (p < 0.001), GPT (p < 0.001) and Tyg index (p = 0.003) was observed compared to baseline. CONCLUSIONS: Dapagliflozin treatment significantly reduced surrogate indexes of insulin resistance and adiposity in patients with T2D.

Are diabetes and its medications risk factors for the development of COVID-19? Data from a population-based study in Sicily.

BACKGROUND AND AIMS: Diabetes mellitus (DM) has been associated with higher incidence of severe cases of COVID-19 in hospitalized patients, but it is unknown whether DM is a risk factor for the overall COVID-19 incidence. The aim of present study was to investigate whether there is an association of DM with COVID-19 prevalence and case fatality, and between different DM medications and risk for COVID-19 infection and death. METHODS AND RESULTS: retrospective observational study on all SARS-CoV-2 positive (SARS-CoV-2+) cases and deaths in Sicily up to 2020, May 14th. No difference in COVID-19 prevalence was found between people with and without DM (RR 0.92 [0.79-1.09]). Case fatality was significantly higher in SARS-CoV-2+ with DM (RR 4.5 [3.55-5.71]). No diabetes medication was associated with differences in risk for SARS-Cov2 infection. CONCLUSIONS: in Sicily, DM was not a risk factor for COVID-19 infection, whereas it was associated with a higher case fatality.

Higher cardiometabolic risk in idiopathic versus autoimmune type 1 diabetes: a retrospective analysis.

BACKGROUND: Idiopathic type 1 diabetes mellitus (IDM) is characterized by an onset with insulinopenia and ketoacidosis with negative ß-cell autoimmunity markers and lack of association with HLA. The aim of the study is to compare the clinical and metabolic parameters, the macro and microvascular complications, the adipose tissue dysfunction and the insulin secretion and sensitivity indexes in patients with IDM and autoimmune type 1 diabetes mellitus (ADM) at clinical onset. METHODS: Thirty patients with IDM and 30 with ADM, matched for age and gender, were retrospectively analyzed. BMI, waist circumference, lipids, glycemia, HbA1c, insulin requirement, glutamic oxaloacetic and glutamic pyruvic transaminases (GOT and GPT), glucagon stimulated c-peptide (GSC-pep) test levels, M value during hyperinsulinemic euglycemic clamp and Visceral Adiposity Index (VAI) were obtained from our database. RESULTS: Patients with IDM showed a significantly higher BMI (p 0.012), WC (p 0.07), VAI (p 0.004), LDL-cholesterol (p 0.027), GOT (p 0.005), GPT (p 0.001), M value (p 0.006) and GSC-pep peak (p 0.036), with concomitant lower HDL-cholesterol (p < 0.001), than patients with ADM. In addition, patients with IDM showed a more marked familial history for diabetes (p 0.005) and a higher percentage of hepatic steatosis (p 0.001), visceral obesity (p 0.032) and hypercholesterolemia (p 0.007) compared to patients with ADM. CONCLUSIONS: Patients with IDM show many metabolic complications at onset, such as visceral obesity, hepatic steatosis and hypercholesterolemia and a higher cardiometabolic risk, than patients with ADM, similarly to patients with type 2 diabetes at onset.

Author Correction: Liraglutide Improves Cardiovascular Risk as an Add-on to Metformin and Not to Insulin Secretagogues in Type 2 Diabetic Patients: A Real-life 48-Month Retrospective Study.

Author Correction to: Diabetes Ther (2018) 9:363-371.

Liraglutide Improves Cardiovascular Risk as an Add-on to Metformin and Not to Insulin Secretagogues in Type 2 Diabetic Patients: A Real-life 48-Month Retrospective Study.

INTRODUCTION: Although liraglutide is widely recognized to have glycemic and extra-glycemic effects, few studies have compared these effects in relation to hypoglycemic treatment starting from the diagnosis of diabetes. We evaluated the effectiveness of liraglutide in reducing the Framingham risk score (FRS) and visceral adiposity index (VAI) in relation to first-line hypoglycemic treatment from diagnosis of type 2 diabetes, continued without any changes. METHODS: We selected 105 diabetic outpatients who were treated with liraglutide for at least 48 months as an add-on therapy to metformin alone (group A, n = 52) or insulin secretagogues (group B, n = 53) from diagnosis time. RESULTS: Although both groups showed a reduction in BMI, waist circumference, blood pressure, HbA1c and triglycerides, only group A showed a significant reduction in FRS (p < 0.001) and VAI (p = 0.012) after 48 months. No significant intergroup difference was found for any parameters at either baseline or 48 months, with the exception of FRS at 48 months, lower in group A (p = 0.002), regardless of duration of disease, improvement in glycemic control and VAI. CONCLUSION: Our data show that during a 48-month follow-up liraglutide was more efficacious in reducing cardiovascular risk than when it was used as add-on therapy to the first-line therapy from diagnosis with metformin and not with insulin secretagogues.