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Context: Poor glucose control has been associated with increased mortality in COVID-19 patients with type 1 diabetes (T1D)., Objective: This work aimed to assess the effect of prevaccination glucose control on antibody response to the SARS-CoV-2 vaccine BNT162b2 in T1D., Methods: We studied 26 patients with T1D scheduled to receive 2 doses, 21 days apart, of BNT162b2, followed prospectively for 6 months with regular evaluation of SARS-CoV-2 antibodies and glucose control. Immunoglobulin G (IgG) to spike glycoprotein were assessed by enzyme-linked immunosorbent assay, and serum neutralization by a live SARS-CoV-2 assay (Vero E6 cells system). Glycated hemoglobin A1c (HbA1c) and continuous glucose monitoring (CGM), including time in range (TIR) and above range (TAR), were collected. The primary exposure and outcome measures were prevaccination glucose control, and antibody response after vaccination, respectively., Results: Prevaccination HbA1c was unrelated to postvaccine spike IgG (r = -0.33; P = .14). Of note, the CGM profile collected during the 2 weeks preceding BNT162b2 administration correlated with postvaccine IgG response (TIR: r = 0.75; P = .02; TAR: r = -0.81; P = .008). Patients meeting the recommended prevaccination glucose targets of TIR (≥ 70%) and TAR (≤ 25%) developed stronger neutralizing antibody titers (P < .0001 and P = .008, respectively), regardless of HbA1c. Glucose control along the study time frame was also associated with IgG response during follow-up (TIR: r = 0.93; P < .0001; TAR: r = -0.84; P < .0001)., Conclusion: In T1D, glucose profile during the 2 weeks preceding vaccination is associated with stronger spike antibody binding and neutralization, highlighting a role for well-controlled blood glucose in vaccination efficacy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Tandem Control-IQ and MiniMed 780G are the main Advanced Hybrid Closed Loop (AHCL) systems currently available in pediatric and adult patients with Type 1 Diabetes (T1D). The aim of our study was to evaluate glycemic control after 1-year of follow-up extending our previous study of 1-month comparison between the two systems., Methods: We retrospectively compared clinical and continuous glucose monitoring (CGM) data from the patients included in the previous study which have completed 1-year observation period. The study population consisted of 74 patients, 42 Minimed 780G users and 32 Tandem Control-IQ users. Linear mixed models with random intercept were performed to study the variations over time and the interaction between time and system; Mann-Whitney or T-test were used to compare systems at 1-year., Results: Both systems have been shown to be effective in maintaining the glycemic improvement achieved one month after starting AHCL. Significant changes over time were observed for TIR, TAR, TAR>250mg/dl, average glucose levels and SD (p<0.001). At 1-year follow-up Minimed 780G obtained better improvement in TIR (p<0.001), TAR (p=0.002), TAR>250mg/dl (p=0.001), average glucose levels (p<0.001). The comparison of the glycemic parameters at 1-year showed a significant superiority of Minimed 780G in terms of TIR (71% vs 68%; p=0.001), TAR (p=0.001), TAR>250 (p=0.009), average glucose levels(p=0.001) and SD (p=0.031)., Conclusions: The use of AHCL systems led to a significant improvement of glycemic control at 1-month, which is maintained at 1-year follow-up. MiniMed is more effective than Tandem in reaching the International recommended glycemic targets. Continuous training and education in the use of technology is essential to get the best out of the most advanced technological tools., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bassi, Patti, Silvestrini, Strati, Ponzano, Minuto and Maggi.)

Tandem Control-IQ and Minimed 780G represent the most Advanced Hybrid Closed Loop (AHCL) systems currently available in pediatric and adult subjects with Type 1 Diabetes (T1D). We retrospectively compared clinical and continuous glucose monitoring data from 51 patients who upgraded to Minimed 780G system and have completed 1-month observation period with data from 39 patients who upgraded to Tandem Control-IQ. Inverse probability weighting was used to minimize the basal characteristics imbalances. Both AHCL systems showed a significant improvement in glycemic parameters. Minimed 780G group achieved higher TIR increase (p= 0.004) and greater reduction of blood glucose average (p= 0.001). Tandem Control-IQ system significantly reduced the occurrence of TBR (p= 0.010) and the Coefficient of Variation of glucose levels (p= 0.005). The use of ACHL systems led to a significant improvement of glycemic control substantially reaching the International recommended glycemic targets. Minimed 780G appears to be more effective in managing hyperglycemia, while Tandem Control-IQ seems to be more effective in reducing time in hypoglycemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RS declared a past collaboration with several of the authors GD and NM to the handling editor., (Copyright © 2022 Bassi, Teliti, Lezzi, Iosca, Strati, Carmisciano, d’Annunzio, Minuto and Maggi.)

Aims: To improve insulin sensitivity, insulin-sensitizing drugs such as metformin are commonly used in overweight and obese T1D patients. Similarly to metformin, D-chiro-inositol (DCI), as putative mediator of intracellular insulin action, can act as insulin sensitizer. The aim of this pilot study was to evaluate the hypothesis that DCI plus folic acid may improve glucose control reducing insulin resistance in overweight or obese T1D patients., Methods: A 24-week randomized control trial was carried out in 26 overweight or obese T1D patients, undergoing intensive insulin therapy. Patients were randomized to 1 g DCI plus 400 mcg folic acid once daily (treated group) or to 400 mcg folic acid only once daily (control group). The primary end point was to evaluate the efficacy of DCI on metabolic control as assessed by HbA1c. As secondary endpoints, BMI and insulin requirement (IR) were evaluated. Paired t test (two tailed) and analysis of variance were used to evaluate differences in HbA1c, BMI and IR at different time points., Results: A significant reduction in HbA1c levels in treated group versus control group (7.5% ± 0.9 vs. 7.9% ± 1.7, respectively, p < 0.05) was observed. However, no significant reduction in BMI and IR was observed [(BMI 25.7 ± 2.8 vs. 26.7 ± 1.0, respectively, p NS); (IR 0.52 ± 0.26 vs. 0.52 ± 0.19, respectively, p NS)]., Conclusions: This trial demonstrated for the first time that DCI plus folic acid oral supplementation can improve metabolic control in overweight T1D patients. CLINICALTRIAL., Gov Id: NCT02730949.

Background: Vitamin D supplementation in childhood improves the achievement of peak bone mass. We investigated the effect of supplementation with calcitriol on bone turnover in recent-onset type 1 diabetes (T1D). Moreover, the association between osteocalcin and parameters of β-cell function and metabolic control was examined., Methodology/principal Findings: We conducted a post-hoc analysis of a double-blind, placebo-controlled study of calcitriol supplementation to preserve β-cell function. 27 recent-onset T1D subjects, mean age 22 years, were randomized to 0.25 µg calcitriol per day or placebo (1:1) and followed up for one year. Changes in bone formation (osteoclacin) and resorption (beta-CrossLaps) markers, and differences between placebo and calcitriol-treated group were evaluated. At baseline, osteocalcin levels were significantly lower in female than in male patients (P<0.01) while no other metabolic parameters as HbA1c and C-peptide differed between gender. No significant correlations were found in relation to HbA1c, insulin requirement and C-peptide. At 1 year follow-up, no significant differences were observed between calcitriol and placebo groups for osteocalcin and β-CrossLaps. In the placebo group osteocalcin levels were unrelated with parameters of metabolic control, such as C-peptide, insulin requirement or HbA1c. Changes of C-peptide, insulin requirement and HbA1c were not related to osteocalcin levels., Conclusions: Supplementation with 0.25 µg calcitriol per day to patients with new-onset T1D does not affect circulating markers of bone turnover. OC levels were unrelated to β-cell function and other metabolic parameters suggesting that OC is ineffective to control pancreatic function in presence of aggressive autoimmune destruction.

Background: A high frequency of blue eyes and fair skin are reported in northern European Caucasians with type 1 diabetes (T1D). Also there is an inverse relationship between latitude and T1D incidence. We determined whether iris colour and skin pigmentation are risk factors in a Caucasian population living in two Mediterranean regions located at the same latitude with higher ultraviolet B irradiance, but with different T1D incidence., Methods: We studied iris colour in 281 consecutive subjects with T1D and 298 controls. Skin type was evaluated by melanin quantification., Results: In Lazio, blue eyes and fair skin type are significantly more common in T1D subjects than in controls (21 versus 9%, p = 0.002; 50 versus 35%, p < 0.001, respectively). In Sardinia, the frequency of blue eyes in T1D subjects is twice that in controls (5.8 versus 2.6% and significantly higher when compared to the expected calculated frequency in the entire population). By logistic regression analysis, only blue eyes are independent and significant predictors of T1D [odds ratio for blue eyes = 2.2; 95% confidence interval (1.1-4.4), p = 0.019]., Conclusions: As previously shown in a Caucasian population from northern Europe, blue eyes and a trend for fair skin increase the risk for T1D also in a Caucasian population born and residing in a Mediterranean region (Continental Italy). This finding may be relevant for explaining different T1D incidence as prevalence of blue eyes differ substantially between northern and southern European Caucasians., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: Intensive insulin therapy is the gold standard therapy for type 1 diabetes (T1D) patients. To achieve optimal glycemic control, adjustments of insulin dose at mealtimes must be made taking into account several parameters: blood glucose levels, insulin/carbohydrate ratio, carbohydrate intake, and physical activity. Calsulin (Thorpe Products Ltd., Cambridge, UK) is a new tool for the administration of insulin dose before each meal. The aim of this study was to evaluate the efficacy of Calsulin on metabolic control in T1D patients undergoing intensive insulin therapy., Subjects and Methods: Forty consecutive patients affected by T1D, 18-65 years old, with disease duration of >1 year, were randomized to Calsulin or to the control group. Hemoglobin A1c (HbA1c) was evaluated at entry into the study and at 3- and 6-month follow-ups. Paired t test (two tailed) and analysis of variance were used to evaluate differences in HbA1c at 3 and 6 months in the two groups., Results: HbA1c at entry was 7.9 ± 1.0% (SD) in the Calsulin-treated group and 7.8 ± 1.6% (SD) in control patients (P not significant). Data showed a slight improvement in HbA1c levels at 3 months in the Calsulin-treated group (-0.61% vs. -0.14% difference, respectively; P not significant). At the 6-month follow-up, a significant reduction in HbA1c levels was observed in the Calsulin-treated group versus the control group (-0.85% vs. -0.07% difference, respectively; P < 0.05)., Conclusions: Calsulin is an acceptable and practical tool that makes the process of calculating insulin doses easy to use, and, most importantly, it improves metabolic control as shown by a significant reduction of HbA1c levels.

In type 1 diabetes, beta cells are attacked and destroyed by auto reactive T cells causing major impairment of blood glucose metabolism and, ultimately, the development of life-threatening complications. Currently, the treatment of this chronic disease is based on the use of endogenous insulin and no curative therapies are available. Treatment approaches in this respect need to be directed toward the primary causes of the disease tackling beta cells' auto reactive T cells. The goal of any curative intervention in type 1 diabetes is the preservation of insulin-secreting cells. This may be achieved by the abrogation of the pathogenic reactivity to beta cell auto antigens while preserving full capacity to generate a normal immune response against foreign antigens. In this review, some of the most promising drugs for immune intervention in type 1 diabetes are presented and discussed including phase 3 clinical trials that involve: DiaPep277, Anti-CD3 Otelixizumab, Glutamic Acid Decarboxylase (GAD) and anti-IL1 receptor antagonist. These approaches are currently being tested in international multicenter trials and all of them have a very similar outcome in terms of a beneficial effect on beta cells.

Type 1 diabetes is an autoimmune disease where β-cells are in a constant process of death and renewal. Reg genes play a role in β-cells regeneration. Reg proteins may be target of an autoimmune response in type 1 diabetes with consequent production of autoantibodies and failure of regeneration. The objective of this work was to characterize the role of Reg1α proteins and anti-Reg1α antibodies as biomarkers of β-cell regeneration and damage. Serum levels of Reg1α protein were investigated in 87 type 1 diabetic subjects (31 newly diagnosed and 56 long standing), 63 type 2 diabetic subjects, 39 subjects with systemic lupus erythematosus (SLE), a nonpancreatic autoimmune disorder, and 64 healthy subjects. The presence of anti-Reg1α antibodies and correlation with metabolic, immune, and genetic parameters were analyzed in diabetic subjects. Increased levels of Reg1α protein were observed in newly diagnosed (p=0.002), and long standing (p=0.001) type 1 diabetes patients and type 2 diabetic subjects (p<0.001). Anti-Reg1α antibodies were found in 47% of patients with type 1 diabetes. No correlation was found with metabolic, immune, and genetic parameters. Patients with SLE showed no increase in Reg1α protein. We report here for the first time raised serum Reg1α protein in type 1 and type 2 diabetes and anti-Reg1α antibodies in type 1 diabetes. Reg1α levels appear not to be influenced by genetic or metabolic control. These findings allow considering future studies on Reg1α protein and autoantibody as new tools in the evaluation and monitoring of β-cells regeneration and autoimmunity., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: We investigated whether supplementation of the active form of vitamin D (calcitriol) in recent-onset type 1 diabetes can protect beta-cell function evaluated by C-peptide and improve glycemic control assessed by A1C and insulin requirement., Research Design and Methods: Thirty-four subjects (aged 11-35 years, median 18 years) with recent-onset type 1 diabetes and high basal C-peptide >0.25 nmol/l were randomized in a double-blind trial to 0.25 microg/day calcitriol or placebo and followed-up for 2 years., Results: At 6, 12, and 24 months follow-up, A1C and insulin requirement in the calcitriol group did not differ from the placebo group. C-peptide dropped significantly (P < 0.001) but similarly in both groups, with no significant differences at each time point., Conclusions: At the doses used, calcitriol is ineffective in protecting beta-cell function in subjects (including children) with recent-onset type 1 diabetes and high C-peptide at diagnosis.