Efficacy and safety of SGLT2 inhibitors in individuals with type 1 diabetes under continuous subcutaneous insulin infusion: a real-world study.

Objective. Adjuvant therapy with sodium-glucose cotransport 2 inhibitors (SGLT2i) in type 1 diabetes (T1D) is associated with an improvement in glycemic control, but increases the risk of diabetic ketoacidosis (DKA). However, real-life studies in individuals with T1D under continuous subcutaneous insulin infusion (CSII) are still scarce. We present the first real-life study performed in patients with T1D exclusively treated with CSII. The aim of the present study was to assess the metabolic impact and safety of SGLT2i in T1D individuals under CSII. Methods. Retrospective study includes 34 T1D adult individuals under CSII, who started SGLT2i until 30th June 2021. Data regarding the glycemic control and acute diabetes complications at the moment of introduction of SGLT2i and after 3, 6, and 12 months of use were collected. Results. Twenty-three individuals were included. Comparing with the moment of SGLT2i introduction after 3, 6, and 12 months of use, there was a statistically significant increase of time in range (TIR) (∆T3M=12.8%; ∆T6M=11.5%; ∆T12M=11.1%), and a decrease in time above range (∆T3M=13.6%; ∆T6M=11.9%; ∆T12M=10.5%). There were no significant differences in time below the range. Mean glucose and mean glucose management indicator significantly reduced in the 3 evaluated moments. A significant reduction in median weight was also observed (∆T6M=2 kg; ∆T12M=4.5 kg). Two patients (8.7%) developed mild euglycemic DKA during SGLT2i treatment, both were women and had body mass index (BMI) <27 kg/m2. One of them had a total daily insulin dose (TDDI) reduction of 26.9% after 3 months of use. Conclusions. The use of SGLT2i, as an adjuvant treatment in T1D individuals under CSII, was associated with a significant increase of TIR without increasing time in hypoglycemia. It also had a weight benefit. Careful use in selected participants is necessary to reduce the occurrence of DKA.

Maturity-onset diabetes of the young in a large Portuguese cohort.

AIMS: Monogenic forms of diabetes that develop with autosomal dominant inheritance are classically aggregated in the Maturity-Onset Diabetes of the Young (MODY) categories. Despite increasing awareness, its true prevalence remains largely underestimated. We describe a Portuguese cohort of individuals with suspected monogenic diabetes who were genetically evaluated for MODY-causing genes. METHODS: This single-center retrospective cohort study enrolled patients with positive genetic testing for MODY between 2015 and 2021. Automatic sequencing and, in case of initial negative results, next-generation sequencing were performed. Their clinical and molecular characteristics were described. RESULTS: Eighty individuals were included, 55 with likely pathogenic/pathogenic variants in one of the MODY genes and 25 MODY-positive family members, identified by cascade genetic testing. The median age at diabetes diagnosis was 23 years, with a median HbA1c of 6.5%. The most frequently mutated genes were identified in HNF1A (40%), GCK (34%) and HNF4A (13%), followed by PDX1, HNF1B, INS, KCNJ11 and APPL1. Thirty-six unique variants were found (29 missense and 7 frameshift variants), of which ten (28%) were novel. CONCLUSIONS: Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of its subtypes, leading to more personalized treatment and follow-up strategies.

Non-thyroidal second primary malignancy in papillary thyroid cancer patients.

Introduction: The occurrence of non-thyroidal second primary malignancy (NTSPM) in patients with papillary thyroid cancer (PTC) is well documented, but epidemiological data are conflicting. Objective: The aim of this study was to evaluate the incidence of NTSPM in a large series of patients with PTC and to assess its potential risk factors. Methods: Single-center cohort study with retrospective data collection conducted on consecutive PTC patients diagnosed from 1988 to 2018 with a minimum follow-up time of 2 years. NTSPM was defined as any primary malignancy with histological confirmation occurring in an anatomical site other than the thyroid. According to the timing of occurrence, NTSPM were subdivided into anachronous, synchronous or metachronous (diagnosed >6 months before, within 6 months and >6 months after PTC diagnosis, respectively). Results: We included 773 individuals (83.3% females), median age at PTC diagnosis was 47.0 (IQR: 37.0-58.0) years and median follow-up time was 9.9 (6.2-16.3) years. Incidence of NTSPM was 15.5% (n = 120) and its standard incidence ratio (SIR) was higher when compared to the general population (SIR: 2.70). Family history of malignancy and younger age at diagnosis were associated respectively with 206 and 4% increased risk of developing metachronous neoplasia (HR: 2.06 (95% CI: 1.10-3.86) and 1.04 (95% CI: 1.02-1.05), respectively). Conclusion: In our series, the occurrence of NTSPM was not uncommon and its incidence was higher compared to the general population. First-degree family history of malignancy was a strong risk factor for multiple primary malignancies.

Continuous Teriparatide Treatment in Chronic Hypoparathyroidism: A Case Report.

BACKGROUND Hypoparathyroidism remains the only hormone deficiency-related disorder with a standard treatment that is not based on replacing a missing hormone. Growing evidence supports the use of recombinant human parathyroid hormone (PTH), mostly with subcutaneous injections. More recently, some clinicians have administered teriparatide, a pharmaceutical form of PTH, through continuous delivery systems. CASE REPORT A 31-year-old woman was referred to our department for further evaluation of chronic severe hypocalcemia due to iatrogenic postsurgical hypoparathyroidism. Despite being chronically medicated with high doses of calcium, vitamin D, and subcutaneous teriparatide injections, she still reported symptoms of hypocalcemia on a daily basis and frequently needed treatment with intravenous calcium perfusions. During hospitalization, we ruled out treatment noncompliance and documented 6 episodes of severe hypocalcemia. Our team then decided to implement a continuous subcutaneous perfusion of teriparatide through an insulin pump. After optimizing the infusion rate, no more severe hypocalcemia episodes occurred. Four months after hospital discharge, it was possible to fully suspend oral supplementation therapy, and the patient's serum calcium level consistently remained within normal range. No other episodes of hypocalcemia occurred. CONCLUSIONS The only way to effectively restore long-term calcium homeostasis in our patient was to start a continuous subcutaneous infusion of teriparatide. There was no need to maintain calcium or vitamin D supplementation and we were able to halve the required daily dose of teriparatide. To our knowledge, this case represents one of the very few reports of successful treatment of hypoparathyroidism with a continuous perfusion of PTH.