Saxagliptin/dapagliflozin is non-inferior to insulin glargine in terms of ß-cell function in subjects with latent autoimmune diabetes in adults: A 12-month, randomized, comparator-controlled pilot study.

AIM: To compare the efficacy and safety of saxagliptin/dapagliflozin and insulin glargine in people with latent autoimmune diabetes in adults (LADA). METHODS: In this phase 2b multicentre, open-label, comparator-controlled, parallel-group, non-inferiority study, we randomly assigned 33 people with LADA who had a fasting C-peptide concentration ≥0.2 nmol/L (0.6 ng/mL) to receive 1-year daily treatment with either the combination of saxagliptin (5 mg) plus dapagliflozin (10 mg) or insulin glargine (starting dose: 10 IU), both on top of metformin. The primary outcome was the 2-h mixed meal-stimulated C-peptide area under the curve (AUC), measured 12 months after randomization. Secondary outcomes were glycated haemoglobin (HbA1c) levels, change in body mass index (BMI), and hypoglycaemic events. RESULTS: In the modified intention-to-treat analysis, the primary outcome was similar in participants assigned to saxagliptin/dapagliflozin or to insulin glargine (median C-peptide AUC: 152.0 ng*min/mL [95% confidence interval {CI} 68.2; 357.4] vs. 122.2 ng*min/mL [95% CI 84.3; 255.8]; p for noninferiority = 0.0087). Participants randomized to saxagliptin/dapagliflozin lost more weight than those randomized to insulin glargine (median BMI change at the end of the study: -0.4 kg/m2 [95% CI -1.6; -0.3] vs. +0.4 kg/m2 [95% CI -0.3; +1.1]; p = 0.0076). No differences in HbA1c or in the number of participants experiencing hypoglycaemic events were found. CONCLUSIONS: Saxagliptin/dapagliflozin was non-inferior to glargine in terms of ß-cell function in this 12-month, small, phase 2b study, enrolling people with LADA with still viable endogenous insulin production. Weight loss was greater with saxagliptin/dapagliflozin, with no differences in glycaemic control or hypoglycaemic risk.

Short- and long-term effects of very low- and low-calorie ketogenic diets on metabolism and cardiometabolic risk factors: a narrative review.

Worldwide obesity and cardiovascular diseases have encouraged the adoption of new and efficient dietary strategies. Among various proposed diets, ketogenic diets, both the very-low-calorie ketogenic diet (VLCKD) and the low-calorie ketogenic diet (LCKD), have been suggested in recent years as an effective nutritional approach for obesity management. The VLCKD and the LCKD are characterized by a low carbohydrate content (<50 g/day), 1-1.5 g of protein/kg of ideal body weight, less than 20-30 g of lipids, and a daily intake of about 800 calories for VLCKD and about 1200-1400 calories for LCKD. The purpose of our narrative review is to offer an overview of the most impactful studies in the scientific literature regarding VLCKD and LCKD to discuss their short- and long-term effects (less than 12 months and more than 12 months respectively) on weight loss, metabolic and cardiovascular aspects. Articles we focused on were cohort studies, case-control studies, cross-sectional studies, randomized controlled trials, and meta-analyses. Results indicate that VLCKD and LCKD could be helpful to ameliorate metabolic and cardiovascular risk factors such as weight loss, glucose, and cholesterol levels, both in the short and long term. Further research in this area may include more randomized controlled trials to gather more data.

Efficacy of radiofrequency and laser thermal ablation in solving thyroid nodule-related symptoms and cosmetic concerns. A systematic review and meta-analysis.

Several studies have showed good/excellent results of thermal-ablation (TA) to reduce volume of benign thyroid nodule (TN). Nevertheless, no systematic review has reported information about clinical achievements with TA. Being the latter of high interest, this systematic review was undertaken to achieve high evidence about the efficacy of TA in reducing TN-related symptoms and cosmetic concerns. Radiofrequency (RFA) and laser (LA) therapies were considered. A comprehensive literature search of online databases was performed on January 2022 looking for studies reporting clinical results obtained by RFA or LA in terms of VAS (namely, Visual Analogic Scale) and cosmetic concerns. Initially, 318 records were found and 14 were finally included in the meta-analysis. VAS data were available in all RFA studies and the pooled mean reduction was of 3.09 points with significant heterogeneity. Cosmetic score data were available in 11 RFA studies and the pooled mean reduction was of 1.45 with significant heterogeneity. Regarding LA studies, 4 series reported VAS data and the pooled mean reduction was of 2.61 points with significant heterogeneity. The analysis of LA data about cosmetic concerns was not performed due to data paucity. Importantly, heterogeneities were not explained by meta-regression analyses using several covariates (i.e., baseline TN volume, follow-up duration, volume reduction rate). This systematic review showed that clinical data about TN TA efficacy are sparse and affected by high unexplained inconsistency. International societies should give indication about how we should clinically select and evaluate patients undergoing TN TA.

DXA-Based Bone Strain Index: A New Tool to Evaluate Bone Quality in Primary Hyperparathyroidism.

CONTEXT: Primary hyperparathyroidism (PHPT) is associated with impaired bone quality and increased fracture risk. Reliable tools for the evaluation of bone quality parameters are not yet clinically available. Bone Strain Index (BSI) is a new metric for bone strength based on Finite Element Analysis from lumbar spine and femoral neck dual-energy x-ray absorptiometry (DXA) images. OBJECTIVE: To assess the lumbar spine (LS), femoral neck (FN), and total hip (TH) BSI in PHPT patients compared with controls and to investigate the association of BSI with vertebral fractures (VFs) in PHPT. METHODS: This case-control study enrolled 50 PHPT patients and 100 age- and sex-matched control subjects from an outpatient clinic. The main outcome measures were LS-BSI, FN-BSI, and TH-BSI. RESULTS: FN bone mineral density (BMD) and one-third distal radius BMD were lower in the PHPT group than in controls (FN 0.633 ± 0.112 vs 0.666 ± 0.081, P = 0.042; radius 0.566 ± 0.07 vs 0.625 ± 0.06, P < 0.001). PHPT group has significant lower TBS score compared with controls (1.24 ± 0.09 vs 1.30 ± 0.10, P < 0.001). BSI was significantly higher at LS (2.28 ± 0.59 vs 2.02 ± 0.43, P = 0.009), FN (1.72 ± 0.41 vs 1.49 ± 0.35, P = 0.001), and TH (1.51 ± 0.33 vs 1.36 ± 0.25, P = 0.002) in PHPT. LS-BSI showed moderate accuracy for discriminating VFs (AUC 0.667; 95% CI, 0.513-0.820). LS-BSI ≥ 2.2 and was a statistically significant independent predictor of VFs, with an adjusted odds ratio ranging from 5.7 to 15.1. CONCLUSION: BSI, a DXA-derived bone quality index, is impaired in PHPT and may help to identify PHPT subjects at high risk of fractures.

Irisin as a regulator of bone and glucose metabolism.

In humans, irisin is produced mainly by skeletal muscle in response to physical activity. It has been demonstrated that irisin plays a pivotal role in inducing fat browning and regulating energy expenditure. New findings from various studies conducted in both animals and humans suggest that irisin can affect bone and glucose metabolism. In particular, irisin is able to increase bone cortical mass by stimulating the osteoblast pathways, and irisin levels are inversely correlated with the incidence of fragility fractures among postmenopausal women affected by osteoporosis. Most available evidence shows that irisin significantly influences glucose and energy homeostasis. Indeed, higher irisin concentrations are inversely correlated with type 2 diabetes. Unfortunately, contradictory findings exist concerning the role of irisin in humans, and most of the human studies that have analyzed interactions between bone health, glucose metabolism, and irisin have several limitations; therefore, their results must be interpreted with caution. The purpose of this narrative review is mainly to describe the effects of irisin on glucose and bone metabolism.