Daily Endocrinology Research Analysis

INTRODUCTION: Intra-pancreatic fat deposition (IPFD) is associated with pancreatic diseases, but its systemic implications remain unclear. MATERIALS AND METHODS: We analyzed 25,547 UK Biobank participants (median follow-up 6.27 years) with MRI-derived pancreatic proton density fat fraction. Multi-variable Cox models, causal mediation, restricted cubic splines, and subgroup analyses assessed IPFD-disease associations. Significant associations were examined through bidirectional Mendelian randomization (MR) using the UK Biobank and FinnGen data. Receiver operating characteristic curves and the Youden index were used to identify a clinically relevant and statistically optimal IPFD threshold. RESULTS: Higher IPFD independently increased the risk of 12 multi-systemic diseases: non-insulin-dependent diabetes, primary hypertension, heart failure, cerebral infarction, cholelithiasis, gastritis and duodenitis, diaphragmatic hernia, chronic renal failure, gonarthrosis, disorders of refraction and accommodation, senile cataract, and sleep disorders. Causal mediation by non-insulin-dependent diabetes was negligible. Nonlinear dose-response patterns and effect modifications by sex, race, smoking, and obesity emerged. MR analysis supported the potential causal effects of IPFD on refractive/accommodation disorders and gonarthrosis. An IPFD cutoff of 7.35% (95% CI: 5.68-9.23%) optimally stratified the risk. CONCLUSION: IPFD is an independent risk factor for diverse conditions, including metabolic, cardiovascular, digestive, musculoskeletal, ophthalmologic, urinary, and mental/behavioral disorders. A pancreatic fat threshold of 7.35% may guide clinical screening and preventive strategies. CRITICAL RELEVANCE STATEMENT: This study critically establishes intra-pancreatic fat as a novel, causal multi-system disease risk factor and provides a 7.35% quantitative threshold to advance radiological screening and prevention protocols. KEY POINTS: Limited research exists on the systemic effects of IPFD. Pancreatic fat deposition independently raises risk for 12 multi-system diseases. A 7.35% pancreatic fat threshold can guide clinical screening and prevention.

BACKGROUND: Total contact cast (TCC) is the 'reference-standard' for off-loading plantar diabetic foot ulcers (DFU). Practical limitations, associated complications, and lack of patient acceptability, limits its widespread use. Posterior slab cast (PSC) may provide an alternate way of off-loading the foot that might be more acceptable, and better tolerated, by people with DFU. AIM: To compare wound healing and foot related outcomes in people with plantar DFU using TCC or PSC for off-loading the foot. METHOD: This was a parallel-group, open-label, single-centre randomized controlled trial. Ninety-nine adults with Type 2 diabetes (T2D) with a single neuropathic Wagner grade 2 or 3 plantar DFU were randomly assigned to receive either a PSC (n = 48) or a TCC (n = 51) for off-loading the foot. The primary endpoint was wound healing rate at 6 months. Secondary endpoints included reduction in ulcer surface area at 4 weeks, wound healing rate at 3 months, and patient satisfaction with either off-loading strategy. RESULTS: The wound healing rate of DFU at 6 months among subjects using PSC (72.9%) was significantly greater than that seen among those using TCC (49%) [HR: 1.3 (1.03-1.73) (P = 0.024)]. Similarly, the wound healing rate at 3 months was also greater among subjects using PSC (50%) as compared to those on TCC (25.5%) (P = 0.011). The percentage reduction of ulcer surface area at 4 weeks from baseline was significantly higher among subjects using PSC (63.2 ± 15.5%) as compared to those using TCC (55.6 ± 18.9%) (P = 0.040). Patient satisfaction, assessed using the Likert scale, was significantly better among subjects using PSC when compared to those using TCC (4.0 ± 1.2 vs 2.5 ± 1.1 respectively, P < 0.001) CONCLUSION: Compared to TCC, PSC was more effective in healing neuropathic plantar DFUs, likely due to its less cumbersome application technique and providing easier access for wound monitoring and intervention when required. Further studies are needed to validate these results.

CONTEXT: Glucagon-like peptide-1 receptor agonists (GLP-1RA) benefit patients with diabetes mellitus (DM) and obesity. While contraindicated in medullary thyroid cancer, their effect in well-differentiated thyroid cancer (DTC) remains poorly understood. OBJECTIVE: To determine the impact of GLP-1RA on risk of DTC recurrence/progression. DESIGN AND SETTING: Retrospective observational cohort study at a tertiary care center in New York. PARTICIPANTS, INTERVENTION, MAIN OUTCOME: 536 patients with DTC exposed to GLP-1RA were matched 1:1 to 536 patients with DTC never exposed to GLP-1RA by age, date of DTC diagnosis, TNM stage, body mass index (BMI), and DM. A multi-state model enabled us to assess the impact of GLP-1RA as a time-dependent variable on the transition of patients with DTC from a "no/stable disease" state to a "recurrence/progression" state. RESULTS: A total of 1072 patients, median age 49, 71% females, 54% with DM, mean BMI±SD 35±7 kg/m², 84% with AJCC Stage I disease, 58% with American Thyroid Association (ATA) intermediate or high risk of recurrence, with median GLP-1RA exposure of 16 months were followed for a median of 69 months. GLP-1RA use was not significantly associated with recurrence or progression of disease in the survival cohort (HR = 0.87, 95% CI: 0.62-1.21, p=0.39) or the entire cohort (HR= 0.75, 95%CI:0.54-1.03, p=0.07) on a multivariable model adjusted for age, ATA risk, radioactive iodine therapy, and DM. CONCLUSION: we did not find GLP-1RA to be significantly associated with recurrent/progressive DTC. Eligible patients with DTC should not be denied the cardiometabolic benefits of GLP-1RA when clinically indicated.