Frontiers in Endocrinology

ObjectivesThere is currently insufficient evidence linking COVID-19 infection with Graves disease (GD). Following the complete lifting of COVID-19 restrictions on December 13, 2022, widespread infection in Guangzhou provides a basis for this study. This research aims to investigate the correlation between COVID-19 infection and GD onset, explore the epidemiological characteristics of newly diagnosed GD post-infection, and offer a scientific basis for treatment. MethodsThe study population included 494 GD outpatients treated in the Department of Endocrinology at the Second Affiliated Hospital of Guangzhou Medical University from January 1 to June 30 each year between 2021 and 2023. They were divided into two groups: 2023 (N=219) and 2021-2022 (N=275), based on the time node of widespread COVID-19 infection in 2023. The new diagnosis rate, general clinical characteristics, and serological test results of GD patients were analyzed before and after the outbreak of COVID-19. ResultsCompared with the 2021-2022 group, the new diagnosis rate of GD patients in 2023 showed a significant increase (12.8% vs. 8.4%, P<0.001). Furthermore, there was a significant decrease in pre-treatment thyrotropin receptor antibody levels (P=0.01), white blood cell count (P=0.02), and neutrophil proportion (P=0.04), while there was a significant increase in the proportion of patients with a family history (P=0.047). Follow-up until June 30 of that year revealed that the proportion of newly diagnosed GD patients developing hypothyroidism during treatment in 2023 significantly increased compared to the 2021-2022 group (P<0.001). ConclusionsAfter widespread infection of COVID-19, the diagnosis rate of newly diagnosed GD increased, which may influence the epidemiological characteristics of related GD patients before initial treatment and during treatment.

The association of thyroid disease and diabetes has been classically described. However, the comorbidity of thyroid disparities and insulin resistance is not frequently assessed, especially the sequence of the occurrence of these markers. We performed a retrospective analysis to evaluate the association between thyroid disease and diabetes markers. We further investigated the sequence of occurrence of thyroid and diabetes markers to identify any predictive capabilities of these markers. We evaluated 32787 subjects who were classified based on their serum thyroid hormones and autoantibody levels. Our general prevalence results showed that HOMA-IR was elevated in overt hypothyroid subjects (43.7%) and overt hyperthyroid subjects (42.2%). HbA1C was elevated in subclinical hypothyroid subjects (19.2%), overt hypothyroid subjects (22.3%) and overt hyperthyroid subjects (21.2%). Glucose was significantly elevated in subclinical hypothyroid subjects (24.2%) and overt hyperthyroid subjects (31.0%). Insulin was only significantly elevated in overt hypothyroid subjects (15.1%). Interestingly, we found that 70.3% of subjects who had their HOMA-IR score escalated from negative (HOMA-IR<2.7) to positive (HOMA-IR>2.7) during their multiple visits had anti-TPO 369 ({+/-}242) days prior to the onset of this change. Our comprehensive study provided evidence that the presence of anti-TPO may suggest a predictive role in developing insulin resistance later in life. Strengths and limitations of the studyO_LIThe strength of our study is the large population size including a larger set of markers from both thyroid disease and diabetes. C_LIO_LIThe limitation in our study is the distorted male and female ratio. C_LI

BackgroundSubclinical hypothyroidism (SH) is biochemically defined by increased TSH, and normal thyroid hormones and its management is a matter of debate. Herein, we investigated thyroid function in euthyroid and children with SH using published data from population-based curves and a structure parameter inference approach (SPINA) model. MethodsThe study included 179 children and adolescents with SH and 311 healthy controls. The predicted and calculated secretory capacity of thyroid gland (SPINA-GT) was calculated in all euthyroid children divided into quartiles according to TSH values, and in children with SH, further subcategorized into those with mild SH (TSH: 4.5 - 10 mIU/L) and severe SH (TSH > 10 mIU/L). ResultsCalculated SPINA-GT values decreased significantly (P < 0.001) from the 1st to the 2nd quartile of normal TSH values in euthyroid children. It was also significantly decreased in mild SH compared to euthyroid children with TSH values within the upper 2 quartiles of TSH range and in severe SH compared to mild SH. ConclusionsThe implementation of SPINA model for thyroid function gives a wider perspective of thyroid glands performance within the euthyroid range of TSH, as well as in SH and add to the discussion for the long-term effects of SH and its management.

Background/AimsPrandial hyperinsulinemia after Roux-en Y gastric bypass surgery (GB), and to lesser degree after sleeve gastrectomy (SG), has been attributed to rapid glucose flux from the gut and increased insulinotropic gut hormones. However, {beta}-cell sensitivity to exogenous incretin is markedly reduced after GB. This study examines the effect of GB versus SG on prandial glycemia and {beta}-cell response to increasing concentrations of endogenous incretins. MethodsGlucose kinetics, insulin secretion rate (ISR), and incretin responses to 50-gram oral glucose ingestion were compared between 10 non-diabetic subjects with GB versus 9 matched individuals with SG and 7 non-operated normal glucose tolerant controls (CN) on two days with and without administration of 200 mg sitagliptin. ResultsFasting glucose and hormonal levels were similar among 3 groups. Increasing plasma concentrations of endogenous incretins by 2-3-fold diminished post-OGTT glycemia and increased {beta}-cell secretion in all 3 groups (p<0.05), but insulin secretion per insulin sensitivity (i.e., disposition index) was increased only in GB (p<0.05 for interaction). As a result, sitagliptin administration led to hypoglycemia in 3 of 10 GB. Yet, plot of the slope of ISR versus the increase in endogenous incretin concentration was smaller after GB compared to both SG and CN. ConclusionAugmented glycemic-induced {beta}-cell response caused by enhanced incretin activity is unique to GB and not shared with SG. However, the {beta}-cell sensitivity to increasing concentrations of endogenous incretin is smaller after bariatric surgery, particularly after GB, compared to non-operated controls, indicating a long-term adaptation of gut-pancreas axis after these procedures. HIGHLIGHTSO_ST_ABSWhat is known?C_ST_ABSGlycemic effects of gastric bypass (GB) and sleeve gastrectomy (SG) is attributed to rapid nutrient flux and enhanced insulinotropic effects of gut hormones but {beta}-cell sensitivity to exogenous GLP-1 or GIP is diminished after GB. What the present findings add?Post-OGTT {beta}-cell sensitivity to enhanced endogenous incretins by DPP4i is markedly reduced in bariatric subjects versus non-operated controls, and yet insulin secretory response (disposition index) is increased leading to hypoglycemia in GB and not SG. Significance?Blunted sensitivity to GLP-1 may represent {beta}-cell adaptation to massive elevation in GLP-1 secretion following bariatric surgery to protect against hypoglycemia. The differential effect of enhanced concentrations of incretins on post-OGTT insulin response (disposition index) among GB versus SG highlights a distinct adaptive process among the two procedures. Augmented insulinotropic effects of gut hormones on postprandial insulin secretory response after GB despite a reduced beta-cell sensitivity to plasma concentrations of GLP-1 makes a case for non-hormonal mechanisms of GLP-1 action after GB. Better understanding of long-term effects of bariatric surgery on gut-pancreas axis activity is critical in development of GLP-1-based strategies to address glucose abnormalities (both hyperglycemia and hypoglycemia) in these settings.

We have previously shown that prandial endogenous glucose production (EGP) during insulin-induced hypoglycemia is smaller in non-diabetic subjects with gastric bypass (GB), where prandial glucagon-like peptide 1 (GLP-1) concentrations are 5-10 times higher than those in non-operated controls. Here, we sought to determine the effect of endogenous GLP-1 on prandial counterregulatory response to hypoglycemia after GB. Glucose fluxes, and islet-cell and gut hormone responses before and after mixed-meal ingestion were compared during a hyperinsulinemic hypoglycemic ({bsim}3.2 mmol/l) clamp with and without a GLP-1 receptor (GLP-1R) antagonist exendin-(9-39) (Ex-9) in non-diabetic subjects with prior GB compared to matched subjects with SG and non-surgical controls. In this setting, GLP-1R blockade had no effect on insulin secretion or insulin action, whereas prandial glucagon was enhanced in all 3 groups. Ex-9 infusion raised prandial EGP response to hypoglycemia in every GB subject but had no consistent effects on EGP among subjects with SG or non-operated controls (P < 0.05 for interaction). These results indicate that impaired post-meal glucose counterregulatory response to hypoglycemia after GB is partly mediated by endogenous GLP-1, highlighting a novel mechanism of action of GLP-1R antagonists for the treatment of prandial hypoglycemia in this population.

Uric acid (UA) is traditionally regarded as a metabolic risk marker; however, its dynamic behavior during glucose-lowering therapy remains incompletely understood. We compared UA responses to a modified traditional Japanese diet (MJDD) and the DPP-4 inhibitor alogliptin in patients with early-stage type 2 diabetes mellitus (T2DM). In this prospective observational study, drug-naive patients received MJDD (n=58) or alogliptin (n=52) monotherapy for 3 months. Changes ({Delta}) in serum UA were analyzed in relation to glycemic control, insulin resistance, adipose tissue insulin resistance (adipo-IR), and beta-cell function. Both interventions significantly reduced fasting blood glucose and HbA1c while paradoxically increasing serum UA and HOMA-B. Baseline UA was the primary determinant of {Delta}UA in both cohorts. MJDD significantly reduced body mass index, insulin, free fatty acids, HOMA-R, and adipo-IR, with effects most pronounced in subjects with baseline BMI >25. In contrast, alogliptin selectively reduced adipo-IR in leaner subjects (BMI <25). Across both treatments, {Delta}UA correlated positively with {Delta}HOMA-B and inversely with {Delta}HbA1c. Notably, during MJDD, {Delta}UA showed a paradoxical negative correlation with {Delta}BMI and {Delta}FBG, and a positive correlation with {Delta}FFA. Patients exhibiting the greatest UA increases demonstrated the most marked improvements in beta-cell function and, with MJDD, the greatest weight loss. These findings indicate that MJDD and alogliptin exert distinct metabolic effects in early T2DM, yet both link rising UA to enhanced beta-cell function, suggesting that UA may serve as a dynamic pharmacometabolic biomarker reflecting therapy-specific metabolic adaptation rather than metabolic deterioration.

IntroductionPostbariatric hypoglycaemia (PBH) is an increasingly recognized late metabolic complication of Roux-en-Y gastric bypass (GB) surgery. PBH typically manifests with a fact occurring post-meal hyperglycaemic peak, followed by a disproportionately exaggerated insulin response leading to low glucose levels. On this basis, we evaluated the effect of a single dose of empagliflozin 10mg vs. placebo on parameters of insulin kinetics. Materials and methodsInsulin secretion, hepatic insulin extraction and total insulin clearance were evaluated after a single of empagliflozin 10mg vs. placebo followed by a standardized liquid mixed meal were evaluated in 11 subjects with confirmed PBH after GB over 3h. Parameters of interest were calculated using established mathematical models. Indices were compared between the groups using the Wilcoxon signed-rank test. ResultsTotal beta-cell responsiveness tends to be lower with empagliflozin vs. placebo (24.83{+/-}11.00 vs. 27.15{+/-}9.68 [10-9 min-1], p=0.150). Total first-pass hepatic insulin extraction increased after empagliflozin compared to placebo (49.6{+/-}14.2 vs. 39.7{+/-}12.1 %, p=0.006), while no significant effect of empaglizflozin on basal first-pass hepatic insulin extraction was observed (79.7{+/-}7.1 vs. 81.1{+/-}6.6 %, p=0.521). Total insulin clearance resulted to be significantly lower after empagliflozin compared to placebo (3.91{+/-}1.58 vs. 3.00{+/-}1.27 l/min, p=0.002). ConclusionThe present analysis suggests that the hypoglycaemia-attenuating effect of SGLT2-inhibition in patients with PBH is mainly mediated by an increment in insulin clearance, with also a tendency to a reduction in insulin secretion.

ContextA comprehensive evaluation of thyroid disease and health through multimodal assessment is warranted. ObjectiveTo clarify the epidemiology and clinical significance of abnormal findings on thyroid examinations in a medical checkup setting. DesignProspective cohort study conducted between April 1, 2016, and December 31, 2021. SettingJapanese adults undergoing self-paid medical checkups at the Preemptive Medicine and Lifestyle Disease Research Center, Kyoto University Hospital Main Outcome MeasuresAll subjects underwent thyroid function tests, ultrasonography, and 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET); anti-thyroperoxidase antibody (TPOAb) titers were measured in a subset of subjects. ResultsIn the original cohort of 4,407 subjects (2,643 males and 1,764 females), the prevalence of thyroid dysfunction, increased blood flow on ultrasonography, diffuse thyroid FDG uptake, and thyroid nodules was 5.81%, 2.45%, 3.43%, and 39.71%, respectively; all were more frequent in females. Among 2,420 subjects with TPOAb measurements, TPOAb positivity was 7.19% and was significantly associated with thyroid dysfunction only at titers [&ge;] 128 IU/mL. Multivariate analyses identified age, sex, and thyroid volume as major determinants of thyroid function. Using data from 1,840 subjects without any thyroid abnormalities, we established sex-specific reference ranges for thyroid dimensions and found their correlations with age and body size. ConclusionsThis cohort provides epidemiological and physiological insights into thyroid health by integrating findings from thyroid function tests, ultrasonography, FDG-PET, and TPOAb measurements. Furthermore, the present study highlights the associations across abnormal findings, relationships within thyroid physiology, and the clinical relevance of high-titer TPOAb.

Previous studies implicate immune dysregulation in the metabolic changes accompanying obesity and type 2 diabetes. This study investigated the interplay between metabolic and immunological parameters during the progression of type 2 diabetes in an obese Mexican American cohort from Starr County, Texas. Individuals matched for age, gender, and BMI were stratified into five categories: diabetes-free, isolated impaired glucose tolerance, combined glucose impairment (fasting or post-load), type 2 diabetes without complications, and type 2 diabetes with lower extremity complications. Buffy samples were analyzed via Luminex Multiplex Assay for IL-4, IL-17A, MCP-1, and HMGB1. HMGB1 levels were significantly elevated in individuals with prediabetes and the combined glucose intolerance group compared to the diabetes-free group and those with diabetes. Elevated HMGB1 levels positively correlated with Homeostatic Model Assessment (HOMA) for insulin resistance (p = 0.03) and showed a moderate negative correlation with insulin sensitivity (p = 0.060). IL-17A levels were elevated in the diabetes group without complications compared to those with combined glucose impairment. The combined diabetes group exhibited the poorest glycemic control. In summary, HMGB1 is a potential early marker of insulin resistance and diabetes progression in Mexican Americans from an underserved community. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/25329883v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@5a7dd3org.highwire.dtl.DTLVardef@fac385org.highwire.dtl.DTLVardef@13a89aforg.highwire.dtl.DTLVardef@2548ff_HPS_FORMAT_FIGEXP M_FIG C_FIG

BackgroundThe glycemic-independent actions of glucagon-like peptide 1 (GLP-1) in the prandial state in humans are largely unknown. Protein ingestion stimulates beta-cell secretion without changing plasma glucose concentration. We examined the contribution of endogenous GLP-1 to glucose metabolism and beta-cell response to protein ingestion under basal glucose concentrations, and whether these responses are affected by rerouted gut after gastric bypass (GB) or sleeve gastrectomy (SG). MethodsInsulin secretion rate (ISR) and glucose fluxes during a 50-gram oral protein load were compared between 10 non-diabetic individuals with GB, 9 matched subjects with SG and 7 non-operated controls (CN) with and without intravenous infusion of exendin-(9-39) [Ex-9], a specific GLP-1 receptor (GLP-1R) antagonist. ResultsBlocking GLP-1R increased plasma glucose concentration before and after protein ingestion and decreased beta-cell sensitivity to glucose in the first 30 minutes of protein ingestion (p<0.05) in all 3 groups. However, reduction in the premeal ISR by Ex-9 infusion only was observed in CN (p<0.05 for interaction), whereas diminished prandial ISR3h by GLP-1R blockade was observed in GB and SG and not in controls (p<0.05 for interaction). Also, GLP-1R blockade enhanced post-protein insulin action in GB and SG, but not in CN. Endogenous glucose production (EGP) during the first hour after protein ingestion was increased in all 3 groups but EGP3h was accentuated by Ex-9 infusion only in GB (p<0.05 for interaction). ConclusionThese findings are consistent with both a glucose-independent pancreatic and extra-pancreatic role for GLP-1 during protein ingestion in humans that are exaggerated by bariatric surgery. Trial registrationThis study was registered at Clinical Trials.Gov: NCT02823665

BackgroundDespite bariatric surgerys success for most patients, up to 30% do not experience optimal weight loss outcomes. Reasons remain incompletely understood. Thyroid hormones, due to their role in energy expenditure, have received study. Yet research to date is inconclusive regarding the impact of standard thyroid markers (e.g., thyroid stimulating hormone, or TSH) on weight regulation after bariatric surgery. This prospective observational study investigates whether the early development of euthyroid sick syndrome (ESS) predicts reduced longer-term post-bariatric weight loss. ESS develops during periods of stress (e.g., critical illness, severe infection, famine) and is thought to serve a protective function by suppressing metabolism and conserving weight. Levels of metabolically active free triiodothyronine (FT3) drop, levels of non-catabolic reverse 3,3,5-triiodothyronine (rT3) rise, and TSH levels remain euthyroid. Reductions in the ratio of FT3 to rT3 significantly predict outcomes in critically ill patients with ESS yet have been unexamined in intentional weight loss among post-bariatric patients. Hence this hypothesis-generating preliminary study investigated whether early changes in the FT3:rT3 ratio predict weight changes at 1-2 years post-bariatric surgery MethodsTwenty-three adult patients undergoing Roux-en-Y gastric bypass (n=12) or sleeve gastrectomy (n=11) were recruited from a bariatric surgery clinic. The TSH, FT4, FT3, rT3, and self-reported hypothyroid symptoms were collected 2-weeks pre-surgery and between 2 weeks to 3 months post-surgery. Body mass index was measured pre-surgery and 1-2 years post-surgery. ResultsReductions in the FT3:rT3 ratio from pre- to early post-surgery significantly predicted reduced weight loss at 1 (p= 0.03) and 2 years (p= 0.02) post-surgery. No other thyroid-related markers nor hypothyroid symptoms were predictive. ConclusionsAlthough replication with larger samples is needed due to sizeable study attrition, this small exploratory study provides provocative support that early changes in the FT3:rT3 ratio associated with ESS predict longer-term reductions in post-bariatric surgery weight loss. Clinical implications are discussed.

Pituitary thyrotropes are specialized cells that produce thyroid stimulating hormone (TSH), a critical factor for growth and maintenance of metabolism. The transcription factors POU1F1 and GATA2 have been implicated in thyrotrope fate and transcriptional regulation of the beta subunit of TSH, Tshb, but no transcriptomic or epigenomic analyses of these cells has been undertaken. The goal of this work was to discover key transcriptional regulatory elements that drive thyrotrope fate. We identified the transcription factors and epigenomic changes in chromatin that are associated with differentiation of POU1F1-expressing progenitors into thyrotropes, a process modeled by two cell lines: one that represents an early, undifferentiated Pou1f1 lineage progenitor (GHF-T1) and one that is a committed thyrotrope that produces TSH (TT1). We generated and compared RNA-seq, ATAC-seq, histone modification (including H3K27Ac, H3K4Me1, and H3K27Me3), and transcription factor (POU1F1) binding in these two cell lines to identify regulatory elements and candidate transcriptional regulators. We identified POU1F1 binding sites that were unique to each cell line. POU1F1 binding sites are commonly associated with bZIP transcription factor consensus binding sites in GHF-T1 cells and Helix-Turn-Helix (HTH) or basic Helix-Loop-Helix (bHLH) factors in TT1 cells, suggesting that these classes of transcription factors may recruit or cooperate with POU1F1 binding to unique sites. We validated enhancer function of novel elements we mapped near Cga, Pitx1, Gata2, and Tshb by transfection in TT1 cells. Finally, we confirmed that an enhancer element near Tshb can drive expression in thyrotropes of transgenic mice, and we demonstrate that GATA2 enhances Tshb expression through this element. These results extend the ENCODE multi-omic profiling approach to an organ that is critical for growth and metabolism, which should be valuable for understanding pituitary development and disease pathogenesis.

Type 2 diabetes mellitus is caused by the disruption of insulin secretion and resistance. One aspect that plays an important role in this disease is self-management education. Good self-care behavior facilitates controlled diabetes management and prevents complications as well as ensures a better life quality. This literature aims to study the philosophy of diabetes self-management based care interventions to improve the quality of life viewed from philosophical perspectives. A literature search was performed on Scopus, PubMed, ProQuest, and Science Direct using keywords including type 2 diabetes mellitus, diabetes self-management and quality of life. The inclusion criteria are peer-reviewed articles in English that discuss diabetes self-management and quality of life. Articles published within the last five years (2017-2021). Research such as a randomized controlled trial (RCT) and full text method. Based on the philosophy study self care interventions, eight articles showed that self-management interventions provide significant effectiveness for lifestyle changes and self-care for type 2 diabetes mellitus patients. Eight articles were selected based on an axiological philosophical study approach, six of which discussed self-management interventions effect on self-care behavior, and two measured the quality of life of type 2 diabetes mellitus patients. Almost all the articles stated an increase in self-care behaviors and quality of life after receiving self-management interventions. Successful diabetes self-management depends on individual self-care activities to control symptoms presented. Furthermore, regular self-management activities prevent complications from arising. Therefore, patients compliance with diabetes self-management is needed to improve their life quality.

BackgroundDifferentiating parathyroid adenoma from hyperplasia is critical for surgical planning, but conventional imaging often cannot reliably distinguish these lesions. Ultrasound elastography offers quantitative assessment of tissue stiffness and may improve preoperative characterization. PurposeTo evaluate the diagnostic accuracy of ultrasound elastography in differentiating parathyroid adenoma from hyperplasia. MethodsA systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. PubMed, Scopus, and Embase were searched through July 2025, for studies assessing elastography for parathyroid lesion differentiation. Data on sensitivity, specificity, and other diagnostic metrics were extracted and pooled using a bivariate random-effects model in R software. ResultsFive studies comprising 579 parathyroid lesions were included, of which four studies with 352 adenomas and 202 hyperplasias were eligible for pooled analysis. Pooled sensitivity and specificity of elastography were 83.3% (95% CI: 74.3-89.6%) and 79.1% (95% CI: 65.5-88.3%), respectively, with an area under the SROC curve of 0.88 (95% CI: 0.79-0.92). Pooled likelihood ratios were 4.14 for a positive test and 0.216 for a negative test. Fagan nomogram analysis showed that, for a patient with a 50% pre-test probability of adenoma, a positive result increased post-test probability to 81%, while a negative result decreased it to 18%. ConclusionUltrasound elastography demonstrates good diagnostic performance in distinguishing parathyroid adenomas from hyperplasia and may help inform preoperative planning.

AMP-activated protein kinase (AMPK) is a critical cellular and whole body energy sensor activated by energy stress, including hypoglycemia, which is frequently experienced by people with diabetes. Previous studies using direct delivery of an AMPK activator to the ventromedial hypothalamus (VMH) in rodents increased hepatic glucose production. Moreover, recurrent glucoprivation in the hypothalamus leads to blunted AMPK activation and defective hormonal responses to subsequent hypoglycemia. These data suggest that amplifying AMPK activation may prevent or reduce frequency hypoglycemia in diabetes. We used a novel brain-permeable AMPK activator, R481, which potently increased AMPK phosphorylation in vitro. R481 significantly increased peak glucose levels during glucose tolerance tests in rats, which were attenuated by treatment with AMPK inhibitor SBI-0206965 and completely abolished by blockade of the autonomic nervous system. This occurred without altering insulin sensitivity measured by hyperinsulinemic-euglycemic clamps. Endogenous insulin secretion was not altered by R481 treatment. During hyperinsulinemic-hypoglycemic clamp studies, R481 treatment reduced exogenous glucose requirements and amplified peak glucagon levels during hypoglycemia. These data demonstrate that peripheral administration of the brain permeable AMPK activator R481 amplifies the counterregulatory response to hypoglycemia in rats, which could have clinical relevance for prevention of hypoglycemia.

Cushings syndrome (CS) is a rare disease caused by excess cortisol levels with high cardiovascular morbidity and mortality. Hypertension is a frequent feature of Cushings syndrome, promoting hypercortisolism-associated cardiovascular events. Adipose tissue is a highly plastic tissue with most of the major cell types strongly affected in their function by the excess cortisol exposure. We hypothesized that the molecular and cellular changes of visceral adipose tissue (VAT) in response to cortisol excess can impact on systemic blood pressure levels in patients with CS. We, therefore, investigated gene expression signatures in VAT from patients with CS collected during curative adrenal surgery identifying significant alterations. During active CS we observed a strong downregulation of gene programs associated with immunity and inflammation in the VAT. In addition, we observed an clustering of the patients based on VAT gene expression profiles into two groups (CSLow and CSHigh) according to blood pressure levels. The two clusters showed significant differences in gene expression pattens of the renin-angiotensin-aldosterone-system (RAAS). Renin (REN) was the strongest regulated gene compared to control patients and its expression correlated with increased blood pressure observed in our patients while systemic renin plasma levels were suppressed indicative of an abnormal blood pressure and volume status in response to VAT RAAS activation. Here we show for the first time a relevant contribution of the local RAAS system on systemic blood pressure levels in patients with CS. Patients from the CSHigh group had still a significant increased blood pressure levels 6 months into remission, highlighting the importance of local tissue effects on long-term systemic effects observed in CS.

Most diabetes mellitus patients experience psychological problems resulting from the disease, disease management, and complications. Inadequate management of psychological problems may place patients at greater risk for depression. This systematic review aims to identify the effects of mindful interventions in controlling glycemic levels and psychological well-being in diabetes mellitus patients. The systematic review conducted on the study used the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. This systematic review uses the Scopus, Web of Science, Science Direct, and Google Scholar databases. The keywords used are diabetes mellitus type 2, mindfulness-based stress reduction, AND/OR, glycemic control, blood glucose, glycated hemoglobin, and psychological well-being. The words used are adjusted to the Medical Subject Heading (MeSH). The articles used are published in English in 2014 - 2023, full-text, and are research articles. The search results showed that most mindfulness interventions used were MBSR (Mindfulness-Based Stress Reduction) for 8 weeks taught by professionals. Mindfulness is provided by trained professionals and taught again using communication media, namely CDs or mobile applications. Mindfulness has a significant effect on reducing fasting blood sugar levels and HbA1c in type 2 DM patients. Mindfulness improves psychological well-being and reduces depression, anxiety, resilience, and emotional health in diabetes patients. Mindfulness is a therapy that can be used to manage the psychological problems of DM patients where with good emotional control the patient can control glycemic levels to normal limits

Cushings disease is caused by the overproduction of cortisol. The effects of this disease are well known in a general population, including high blood pressure, diabetes, and weight gain. Cushings disease causes both obesity and metabolic related symptoms, and it can be difficult to discern the obesity-dependent from the obesity-independent mechanisms of Cushings disease. To identify patients with Cushings disease, we identified 476 Michigan Medicine patients between January 1st 2000-2025 along with propensity-matched control cases. We stratified our participants by obesity status and into a Cushings disease group and a control group. As expected, the Cushings group had an elevated BMI compared to the control group (34 kg/m2 vs 29 kg/m2). We found a higher proportion of females diagnosed with Cushings compared to males (287 vs 72). Cushings disease was associated with an increase in the fasting glucose levels in both non-obese and obese patients. In both the obese, and non-obese patients, there was an increase in ALT and AST levels regardless of Cushings disease status, but the increase due to Cushings disease was much greater in the patients with obesity (73.4 vs 35.1 mg/dL). Cushings disease also had a moderating effect on blood pressure, with participants a BMI under 30 kg/m2 increasing by 12.6 mmHg and participants with obesity increasing by only 7.9 mmHg. These findings highlight the need to consider obesity status when evaluating the effects of Cushings disease.

PurposeTo investigate the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and nonarteritic anterior ischaemic optic neuropathy (NAION) in type 2 diabetes, examining treatment recency and cumulative duration. MethodsThis nationwide registry-based nested case-control study utilised Danish health registries (1996-2023). Among 201,776 metformin-treated adults initiating second-line antihyperglycaemic therapy, 123 incident NAION cases were matched to 4,920 controls by birth year and sex (incidence-density sampling). Conditional logistic regression estimated adjusted hazard rate ratios (HRs) for GLP-1RA exposure by recency (current 0-90 days; recent 91-365 days) and cumulative duration, adjusting for socioeconomic factors, hypertension, hypercholesterolaemia, sleep apnoea, and diabetes duration. ResultsGLP-1RA use occurred in 63/123 cases (51.2%) and 1,688/4,920 controls (34.3%). Ever use was associated with a higher NAION rate than other second-line therapies (HR 2.13, 95% CI 1.43-3.18). Current use was associated with elevated rates (HR 2.28, 95% CI 1.49-3.48), whereas the estimate for recent use was imprecise (HR 1.69, 95% CI 0.88-3.25). By cumulative duration, no clear evidence of an increase was seen within 0-[1/2] years (HR 0.80, 95% CI 0.32-2.05), and rates were highest at [1/2]-1 year (HR 3.63, 95% CI 2.06-6.40) and 1-1[1/2] years (HR 3.52, 95% CI 1.73-7.17). Findings were consistent after HbA1c adjustment and in a new-user analysis. ConclusionGLP-1RA use is associated with a higher NAION rate in type 2 diabetes. This association appears time-dependent, being most pronounced during current treatment and peaking after 6-18 months of cumulative exposure.

BackgroundCachexia is a multifactorial syndrome of involuntary weight loss, skeletal muscle wasting, and metabolic dysregulation, commonly seen in advanced cancer and other chronic diseases. Despite its prevalence and prognostic significance, effective treatment strategies remain limited, and there is no standardized model of outpatient care in the US. ObjectiveTo describe the structure, patient characteristics, and outcomes of a multidisciplinary cancer cachexia clinic embedded within an academic endocrinology practice. MethodsWe conducted a retrospective analysis of 103 patients referred to a single-center cachexia clinic over five years. Patients underwent comprehensive assessments including weight trajectory, nutritional status, physical performance (5x sit-to-stand test, handgrip strength), and received individualized interventions involving nutrition counseling, resistance training, and pharmacologic management. ResultsThe median patient age was 69.7 years, with 64.1% having a cancer diagnosis (61.0% with metastases). Median monthly weight loss decreased from -0.5 kg/month in the 6 months pre-enrollment to 0.0 kg/month after 3 months post enrollment (p < 0.0001), indicating significant stabilization. The 5x sit-to-stand test improved (p = 0.022), though handgrip strength remained unchanged. Patients prescribed an exercise video program trended toward greater weight gain ({beta} = +1.988, p = 0.079), while those prescribed protein powder tended to experience more weight loss ({beta} = -2.102, p = 0.113), although this difference was not statistically significant. ConclusionA multimodal cachexia clinic can stabilize weight loss and improve physical function in medically complex patients. These findings support the integration of interdisciplinary approaches to cachexia management and provide a framework for evaluating future interventions in routine clinical settings.