COVID-19 vaccines and blood glucose control: Friend or foe?

PURPOSE: To overview the recent literature regarding the relationship between COVID-19 vaccines and glycemic control. METHODS: Data were extracted from text and tables of all available articles published up to September 2023 in PubMed Database describing glucose homeostasis data in subjects exposed to COVID-19 vaccines, focusing on patients with diabetes mellitus (DM). RESULTS: It is debated if the immune system impairment observed in diabetic patients makes them susceptible to lower efficacy of vaccines, but evidence suggests a possible improvement in immune response in those with good glycemic control. Despite their proven protective role lowering infection rates and disease severity, COVID-19 vaccines can result in diabetic ketoacidosis, new-onset diabetes, or episodes of hyper- or hypoglycemia. CONCLUSIONS: Evidence with COVID-19 vaccines highlights the strong relationship existing between DM and immune system function. Clinicians should strive to achieve optimal glucose control before vaccination and promptly manage possible glucose homeostasis derangement following vaccine exposure.

Real-world sex differences in type 2 diabetes patients treated with GLP-1 receptor agonists.

AIMS: To evaluate the determinants of cardiovascular (CV) protection in men and women treated with glucagon-like peptide-1 receptor agonists (GLP1-RA). METHODS: Retrospective cohort study of 550 patients (43% women), with and without established CV disease, followed at a single center after the first prescription of a GLP1-RA. We analyzed the determinants of major adverse cardiovascular events (MACE) in men and women. RESULTS: The rate of MACE was similar between sexes. In primary prevention, among men, older age (HR 1.13, 95 % C.I. 1.05-1.22; P = 0.001) and GLP-1 RA withdrawal by time (HR 2.77, 95 % C.I. 1.15-6.68; P = 0.023) increased the HR for MACE. Among women, significant predictors of MACE were diabetes duration (HR 1.05, C.I. 1.01-1.10; P = 0.020), GLP-1 withdrawal by time (HR 2.84, 95 % C.I. 1.13-7.10; P = 0.026) and BMI at GLP-1 RA withdrawal (HR 1.08, 95 % C.I. 1.01-1.15; P = 0.026). For individuals with prior CV disease, the HR for MACE was solely impacted by GLP-1 withdrawal over time in males (HR 2.18, 95 % C.I. 1.10-4.30; P = 0.025) and by older age at GLP-1 RA initiation (HR 1.17, 95 % C.I. 1.03-1.33; P = 0.015) in females. CONCLUSIONS: Although MACE rates were similar, the factors contributing to MACE differed by sex.

DXA-derived lumbar bone strain index corrected for kyphosis is associated with vertebral fractures and trabecular bone score in acromegaly.

PURPOSE: The bone strain index (BSI) is a marker of bone deformation based on a finite element analysis inferred from dual X-ray absorptiometry (DXA) scans, that has been proposed as a predictor of fractures in osteoporosis (i.e., higher BSI indicates a lower bone's resistance to loads with consequent higher risk of fractures). We aimed to investigate the association between lumbar BSI and vertebral fractures (VFs) in acromegaly. METHODS: Twenty-three patients with acromegaly (13 males, mean age 58 years; three with active disease) were evaluated for morphometric VFs, trabecular bone score (TBS), bone mineral density (BMD) and BSI at lumbar spine, the latter being corrected for the kyphosis as measured by low-dose X-ray imaging system (EOS®-2D/3D). RESULTS: Lumbar BSI was significantly higher in patients with VFs as compared to those without fractures (2.90 ± 1.46 vs. 1.78 ± 0.33, p = 0.041). BSI was inversely associated with TBS (rho -0.44; p = 0.034), without significant associations with BMD (p = 0.151), age (p = 0.500), BMI (p = 0.957), serum IGF-I (p = 0.889), duration of active disease (p = 0.434) and sex (p = 0.563). CONCLUSIONS: Lumbar BSI corrected for kyphosis could be proposed as integrated parameter of spine arthropathy and osteopathy in acromegaly helping the clinicians in identifying patients with skeletal fragility possibly predisposed to VFs.

The Novel SSTR3 Agonist ITF2984 Exerts Antimitotic and Proapoptotic Effects in Human Non-Functioning Pituitary Neuroendocrine Tumor (NF-PitNET) Cells.

Somatostatin receptor ligands (SRLs) with high affinity for somatostatin receptors 2 and 5 (SSTR2 and SSTR5) are poorly efficacious in NF-PitNETs, expressing high levels of SSTR3. ITF2984 is a pan-SSTR ligand with high affinity for SSTR3, able to induce SSTR3 activation and to exert antitumoral activity in the MENX rat model. The aim of this study was to test ITF2984's antiproliferative and proapoptotic effects in NF-PitNET primary cultured cells derived from surgically removed human tumors and to characterize their SSTR expression profile. We treated cells derived from 23 NF-PitNETs with ITF2984, and a subset of them with octreotide, pasireotide (SRLs with high affinity for SSTR2 or 5, respectively), or cabergoline (DRD2 agonist) and we measured cell proliferation and apoptosis. SSTR3, SSTR2, and SSTR5 expression in tumor tissues was analyzed by qRT-PCR and Western blot. We demonstrated that ITF2984 reduced cell proliferation (-40.8 (17.08)%, p < 0.001 vs. basal, n = 19 NF-PitNETs) and increased cell apoptosis (+41.4 (22.1)%, p < 0.001 vs. basal, n = 17 NF-PitNETs) in all tumors tested, whereas the other drugs were only effective in some tumors. In our model, SSTR3 expression levels did not correlate with ITF2984 antiproliferative nor proapoptotic effects. In conclusion, our data support a possible use of ITF2984 in the pharmacological treatment of NF-PitNET.

Prediction of adrenal insufficiency after pituitary surgery: a retrospective study using beckman access cortisol assay.

PURPOSE: Identifying patients requiring glucocorticoid replacement therapy after pituitary surgery is challenging as the tests commonly used for the diagnosis of secondary adrenal insufficiency (SAI) are not recommended in the immediate postoperative period. There are controversial data on the role of postoperative days' morning cortisol, with no specific data for each cortisol assay. The aim of this study is to investigate the reliability of 8.00 a.m. cortisol of the first and second postoperative days in predicting SAI. METHODS: Data of patients underwent pituitary surgery in Humanitas Research Hospital in Italy, from March 2017 to August 2022, were retrospectively analyzed. Definitive diagnosis of SAI was made through ACTH test 1 µg six weeks after surgery. Cortisol was measured through Beckman Access Cortisol and the diagnosis of SAI was made if cortisol peak was below 14.8 µg/dL (408 nmol/L) at 30 or 60 min after stimulus. RESULTS: Of the sixty-four patients enrolled, seven developed SAI. The ROC curves demonstrated that both first- and second-day postoperative 8.00 a.m. cortisol predict SAI (AUC 0.94 and 0.95, respectively). The optimal thresholds were 15.6 µg/dL (430.3 nmol/L; accuracy 89%) for the first day and 11.5 µg/dL (317.2 nmol/L, accuracy 81%) for the second day. Patients who developed SAI had larger tumors (p = 0.004) and lower fT4 (p = 0.038) before surgery. CONCLUSIONS: Clinicians might rely on the first- and second- postoperative days 8.00 a.m. cortisol to identify patients to discharge with glucocorticoid replacement therapy waiting for the confirmation of SAI through the ACTH test.