Daily Endocrinology Research Analysis

BACKGROUND & AIMS: Glucagon-like peptide 1 receptor agonist (GLP-1RA) therapies deliver histological benefit in people with metabolic dysfunction-associated steatotic liver disease (MASLD). Multiple mechanisms may be important including weight loss, improved glycaemic control and putative direct tissue-specific actions. Following cessation of GLP1-RA therapy, weight regain is common. To dissect the mechanisms underpinning their benefits, we conducted a prospective, randomised, experimental medicine study in people with MASLD, comparing GLP-1RA treatment (liraglutide) to matched lifestyle-induced weight loss and assessed the impact of treatment withdrawal. METHODS: Twenty-nine participants with MASLD, without type 2 diabetes underwent metabolic phenotyping including measurement RESULTS: Matched weight loss was achieved in both arms. Body composition changes, reductions in alanine aminotransferase, liver steatosis, and disease activity were similar following both treatments. GLP-1RA treatment, but not lifestyle, improved glucose handling, fasting lipids, and significantly deceased DNL. The subcutaneous adipose transcriptome, circulating proteome profile and stool microbiome were not different between groups after treatment. However, 12 weeks after GLP1-RA (but not lifestyle) withdrawal, circulating MMP-10, IL10RB, FGF-23, and Flt3L were elevated, alongside dysregulated adipose gene expression. CONCLUSIONS: Although matched weight loss through lifestyle or GLP-1RA have comparable effects on hepatic steatosis, GLP-1RA treatment had additional metabolic benefits on glucose homeostasis, lipid profiles, and DNL. However, GLP-1RA withdrawal may adversely impact the circulating proteome, adipose tissue gene expression, and the stool microbiome, predisposing to weight regain. IMPACT AND IMPLICATIONS: Weight loss, through either lifestyle intervention or pharmacotherapy with GLP-1RA has an equally beneficial impact on the liver, and both strategies should be considered in the management of people with MASLD. GLP-1RA therapy may have additional benefits to improve glucose homeostasis even in the absence of pre-existing type 2 diabetes. Further research is needed to explore the differential impact of treatment withdrawal and the resultant metabolic consequences. CLINICAL TRIALS REGISTRATION: This study is registered at EudraCT (2016-002045-36).

UNLABELLED: Adherence to osteoporosis screening guidelines could be considerably higher if offered at the time of routine mammography using the same imaging modality. We found that forearm density measurements using a breast imaging system provides density information with excellent diagnostic capability for osteoporosis and osteopenia status determined by hip and spine DXA. PURPOSE: Adherence to osteoporosis screening guidelines via bone mineral density (BMD) measurements with dual-energy x-ray absorptiometry (DXA) is low. Since adherence to breast cancer screening is quite high, it was suggested that the rate of osteoporosis screening can be improved if wrist imaging were performed at the time of breast screening using the very same equipment. METHODS: Digital wrist tomosynthesis (DWT) imaging was performed in 150 women using a 3D mammography system and BMD was measured from both 3D tomosynthesis and synthesized 2D images. In addition, standard DXA based BMD measurements were performed at the hip, spine, and forearm sites. We examined the extent to which DWT-derived ultradistal radius BMD correlates with DXA based BMD measurements, evaluated DWT measurement precision errors, and determined the accuracy of DWT in diagnosing low bone mass and osteoporosis in vivo. RESULTS: DWT BMD strongly correlated with DXA-derived ultradistal radius BMD (R2 up to 0.814) and discriminated osteoporosis (AUC up to 0.978) and osteopenia (AUC up to 0.938) by ultradistal T-score with low in vivo precision errors (0.91-2.3%). BMD derived from 3D DWT BMD performed comparably to forearm DXA BMD in the diagnosis of osteopenia (AUC up to 0.916) and osteoporosis (AUC up to 0.946) determined by hip and spine DXA. CONCLUSIONS: DWT can be readily implemented in mammography settings with similar diagnostic accuracy to DXA, has the potential to increase adherence to osteoporosis screening recommendations, and offers a convenient means to measure bone density within the highly accessible breast screening environment.

CONTEXT: Accurate assessment of the inflammatory status in thyroid eye disease (TED) is crucial for diagnosis and treatment; however, this assessment remains challenging. OBJECTIVES: To study whether thyrotrophin receptor antibody (TRAb) can be utilized as a quantitative and objective indicator of the inflammatory status in patients with thyroid eye disease (TED). METHODS: We gathered and analyzed TRAb and clinical characteristics from 226 consecutive TED patients. Additionally, we examined 27 inflammatory cytokines in the orbital adipose tissue of 41 patients and assessed the alterations in TRAb following intravenous methylprednisolone (IVMP) therapy in 40 patients. RESULTS: The 226 TED patients included 116 females and 110 males, with a mean age of 46.4 ± 12.2 years. The correlation between TRAb and clinical activity score (CAS) was the most pronounced (r = 0.427; p < 0.001). TRAb was identified as the most influential factor for CAS. Subsequent investigation into the relationship between TRAb and pathological inflammation revealed that TRAb exhibited a significant positive correlation with 7 pro-inflammatory cytokines (IL-8, CCL-3, Serpin E1, PDGF-AB, IL-12p70, IL-21, and PDGF-BB), and a significant negative correlation with 1 anti-inflammatory cytokine (BMP-7). IL-8, CCL-3, Serpin E1, PDGF-AB, and IL-1β were significantly upregulated in the orbital adipose tissue of TRAb-positive patients compared to TRAb-negative patients. In contrast, BMP-7 demonstrated an opposite trend. Additionally, TRAb and CAS significantly decreased following IVMP therapy, with a significant correlation between the extent of reduction in TRAb and CAS. CONCLUSIONS: TRAb significantly correlated with both CAS (clinical inflammation indicator) and inflammatory cytokines (pathological inflammation marker). Consequently, we propose, for the first time, that TRAb may serve as an objective and quantitative biomarker for assessing inflammation in TED.