Xiaojing Ma

Background: To investigate the metabolic characteristics of continuous glucose monitoring (CGM)‐derived glycemic phenotypes and their association with cardiovascular‐kidney‐metabolic (CKM) syndrome in older adults with Type 2 diabetes. Methods: Clinical and biochemical data, including estimated β‐cell function and insulin resistance, along with CGM data, were collected from 2491 adults aged ≥ 60 years with Type 2 diabetes. CKM syndrome was staged according to the American Heart Association criteria, with Stages 3–4 defined as advanced CKM syndrome. CGM‐derived glycemic phenotypes were constructed using an outcome‐guided workflow combining XGBoost feature‐importance analysis with correlation analysis and clinical interpretability. Results: The prevalence of advanced CKM syndrome was 65.0% in our population. Using an outcome‐guided and clinically interpretable workflow, time above range (TAR _>10.0 ) and mean amplitude of glycemic excursions (MAGE) were selected to represent hyperglycemic burden and glycemic variability, respectively, and were used to construct two‐dimensional CGM‐derived glycemic phenotypes. Four phenotypes were constructed through this framework and differed significantly in glycemic and metabolic profiles. Although the high TAR _>10.0 /high MAGE phenotype showed the greatest hyperglycemic burden and glycemic variability ( p < 0.001), the high TAR _>10.0 /low MAGE phenotype showed the largest point estimate of association with advanced CKM syndrome among the four phenotypes (OR 1.62, 95% CI 1.16–2.27). Notably, this phenotype also exhibited the lowest insulin sensitivity among the four phenotypes. Conclusions: CGM‐derived glycemic phenotypes demonstrated distinct metabolic profiles and differential associations with advanced CKM syndrome, suggesting that CGM data may help inform personalized management strategies for older adults with Type 2 diabetes.

Aims: Cardiovascular, kidney and metabolic diseases are pathophysiologically interrelated and are conceptualised within the cardiovascular‐kidney‐metabolic (CKM) syndrome framework. However, evidence linking continuous glucose monitoring (CGM) to CKM syndrome remains limited. This study examined the association between time in range (TIR), the core CGM metric, and advanced CKM syndrome. Materials and Methods: A total of 2497 adults aged ≥ 60 years with type 2 diabetes were included. CKM syndrome was defined according to the American Heart Association Presidential Advisory, with stages 3–4 classified as advanced CKM syndrome. Results: Participants with advanced CKM syndrome exhibited significantly lower TIR levels than those with non‐advanced CKM syndrome ( p < 0.001). After multivariable adjustment, each 1‐standard deviation decrease in TIR was independently associated with higher odds of advanced CKM syndrome (OR 1.28, 95% CI 1.16–1.42). Restricted cubic spline analyses demonstrated a linear inverse association between TIR and advanced CKM syndrome, with the estimated OR approaching unity at approximately 70%. The prevalence of advanced CKM syndrome increased progressively across TIR categories of > 70%, 50%–70% and ≤ 50% ( p for trend < 0.001). Although TIR levels of 50%–70% exceed the currently recommended target of > 50% for older adults, this range remained associated with higher odds of advanced CKM syndrome compared with TIR > 70% (OR 1.40, 95% CI 1.12–1.75). Higher TIR was not associated with increased hypoglycemia exposure. Conclusions: Lower TIR was associated with advanced CKM syndrome, supporting the potential value of CGM‐derived TIR in evaluating multisystem cardiovascular‐kidney‐metabolic burden in older adults with type 2 diabetes.

Cellular senescence contributes to obesity-associated adipose dysfunction, yet the upstream regulators of this process remain poorly understood. Here, we identified growth arrest and DNA damage-inducible protein 45 beta (Gadd45b) as an adaptive regulator of adipocyte senescence and systemic metabolic homeostasis. GADD45B expression was elevated in adipose tissue from obese human subjects and positively correlated with senescence-related markers. Adipocyte-specific Gadd45b deletion in mice caused depot-selective remodeling under high-fat diet, with inguinal fat hypertrophy but epididymal white adipose tissue (eWAT) atrophy, accompanied by enhanced DNA damage and pronounced senescence. These alterations thereby contributed to impaired lipolytic response, hepatic steatosis and insulin resistance, underscoring the vital role of Gadd45b in maintaining eWAT expandability during nutritional overload. Mechanistically, Gadd45b deficiency led to hypermethylation of fibroblast growth factor 1b (Fgf1b) promoter and reduced Fgf1 expression in eWAT, thereby exacerbating adipose senescence and metabolic abnormalities, while recombinant FGF1 treatment partially reversed these defects. Collectively, our findings establish Gadd45b as a depot-specific epigenetic regulator that sustains adipose tissue plasticity and links DNA damage responses to adipocyte senescence and metabolic homeostasis in obesity.

Aims: There is uncertainty whether traditional glycemic metrics remain associated with long‐term outcomes among patients with type 2 diabetes who achieve recommended continuous glucose monitoring (CGM) targets. This study was aimed to investigate the association of glycated albumin (GA) and ratio of glucose management indicator to GA (GMI/GA) with risks of all‐cause mortality in type 2 diabetes achieving CGM targets. Materials and Methods: A total of 3482 patients with type 2 diabetes who met CGM targets, defined as time in range (TIR) >70%, time below range (TBR _{) >10.0} ) p for nonlinearity = 0.042). Compared with the reference third quartile (0.36–0.40), participants in the lowest quartile (<0.30) had 40% higher risk of all‐cause mortality (HR = 1.40, 95% CI 1.10–1.80). Conclusion: Among patients achieving CGM targets, elevated GA and lower GMI/GA were associated with higher risks of all‐cause mortality. These findings suggest that traditional glycemic metrics may complement CGM metrics in the assessment of long‐term risks.

Aims: Similar to blood, saliva contains a broad range of biomarkers and may offer a non‐invasive, repeatable specimen for endocrine and metabolic assessment. This review aims to synthesise and evaluate recent advances in the clinical translation of salivary biomarkers, while providing a critical assessment of the diagnostic reliability and clinical potential of key salivary biomarkers. Materials and Methods: PubMed, Web of Science and ScienceDirect were searched for English‐language articles published up to July 2025, with emphasis on studies from 2020 to 2025. We included articles with a focus on the clinical translation of salivary biomarkers for endocrine and metabolic disorders. The relevant studies on the physiology underlying the synthesis and transport of salivary biomarkers were also identified. Results: Late‐night salivary cortisol is the most clinically established marker and is guideline‐endorsed for Cushing's syndrome, while salivary cortisone may improve the diagnostic accuracy. Salivary glycaemic biomarkers, such as glucose, 1,5‐anhydroglucitol, fructosamine, glycated albumin and α‐amylase, show potential for diabetes screening or monitoring. Salivary uric acid, inflammatory factors and adipokines may reflect hyperuricaemia, obesity and metabolic inflammation. However, most biomarkers remain exploratory and their clinical translation is limited by inconsistent collection procedures, oral disease, medication effects and analytical platforms. Conclusions: Salivary biomarkers offer a promising non‐invasive approach for assessment of endocrine and metabolic disorders. Standardised procedures and large‐scale multicentre validation are needed to define reliable clinical cutoffs and perform comparisons with blood‐based reference standards. Applications for machine learning and wearable sensing technology can further promote clinical translation.

Graphical Objective: We aimed to explore the association between thyroid indicators and pre-sarcopenic obesity, pre-sarcopenia, and visceral obesity in a community-based euthyroid cohort. Methods: A total of 1,280 euthyroid residents (42.3% men) aged over 40 years were recruited in 2013–2014 and re-examined in 2015–2016. Thyroid indicators were analyzed. Visceral fat area was quantified using magnetic resonance imaging, and skeletal muscle mass was calculated using a bioelectrical impedance analyzer. Pre-sarcopenic obesity was defined as the coexistence of pre-sarcopenia and visceral obesity. Results: During a mean follow-up of 2.1 years, 127 (14.8%), 156 (21.3%), and 120 (20.1%) participants developed new-onset pre-sarcopenic obesity, pre-sarcopenia, and visceral obesity, respectively. Compared with those with the lowest tertile of baseline serum fT3 levels, participants with the highest tertile had an elevated risk of pre-sarcopenic obesity (risk ratio (RR): 1.82, 95% confidence interval (CI): 1.20–2.76) and pre-sarcopenia (RR: 1.49, 95% CI: 1.04–2.15). Moreover, a 1 standard deviation increase in serum fT3 levels over 2.1 years was positively associated with incident pre-sarcopenic obesity (RR: 1.40, 95% CI: 1.28–1.53) and pre-sarcopenia (RR: 1.29, 95% CI: 1.18–1.40), respectively. Conclusion: Elevated serum fT3 levels were associated with increased risks of pre-sarcopenic obesity and pre-sarcopenia in euthyroid Chinese participants.

Adaptive thermogenesis in beige adipocytes is essential for maintaining energy homeostasis and preventing obesity. Emerging evidence suggests that human visceral adipose tissue harbors adipocytes with beige-like thermogenic features, enabling analysis of thermogenic gene regulation in humans. Isocitrate dehydrogenase 3A (IDH3A) is a rate-limiting enzyme of the tricarboxylic acid cycle, yet its function in adipocytes remains poorly defined. In this study, we examined IDH3A expression in human visceral adipose tissue and generated adipocyte-specific IDH3A knockout mice to investigate its role in beige adipocyte thermogenesis and metabolic regulation. IDH3A expression in human visceral fat was inversely associated with adiposity and adverse metabolic traits. Moreover, IDH3A expression was induced in human and mouse adipocytes following thermogenic stimulation. Adipocyte-specific IDH3A deletion in mice impaired beige fat thermogenic capacity, led to cold intolerance, and exacerbated diet-induced metabolic dysfunction. Mechanistically, IDH3A deficiency increased DNA methylation at the Bckdha promoter, resulting in the repression of this key branched-chain amino acid (BCAA) catabolic gene and impaired BCAA catabolism. Notably, restoring BCKDHA in IDH3A-deficient adipocytes rescued respiration and thermogenic function. Together, in addition to its canonical enzymatic role, our findings identify IDH3A as a critical regulator of BCAA catabolism that facilitates adaptive thermogenesis under metabolic stress conditions. Article Highlights: IDH3A expression in human visceral fat exhibits a negative correlation with metabolic dysfunction indicators. IDH3A is induced during thermogenic activation, yet its role in adipose tissue is not well characterized. Adipocyte-specific deletion of IDH3A impairs adaptive thermogenesis and metabolic homeostasis by disrupting BCKDHA-mediated BCAA catabolism. Overexpression of BCKDHA restores the thermogenic program in IDH3A-deficient beige adipocytes.

Aims: The potential benefit of integrating continuous glucose monitoring (CGM) data with conventional glycaemic indicators in diabetes care remains to be determined. This study aimed to investigate the association between 1,5‐anhydroglucitol (1,5‐AG), a 1–2 weeks glycaemic marker with monitoring duration comparable to CGM, and diabetic retinopathy (DR). Materials and Methods: The cross‐sectional study included 5491 adults with type 2 diabetes. Participants were stratified by serum 1,5‐AG levels (< 6.0 μg/mL, 6.0–10.0 μg/mL, and ≥ 10.0 μg/mL). Time in range (TIR) and glucose variability measures, including standard deviation (SD), coefficient of variation (CV), and mean amplitude of glycaemic excursions (MAGE), were calculated from CGM data. Results: Overall, the median serum 1,5‐AG level was 3.4 (1.7–7.1) μg/mL, with a DR prevalence of 25.3% ( n = 1387). The prevalence of DR increased with descending 1,5‐AG levels ( p for trend < 0.001). Compared to patients with 1,5‐AG levels ≥ 10.0 μg/mL (reference), the adjusted odds ratio (OR) for DR was 1.64 (95% CI 1.35–2.01) in individuals with 1,5‐AG < 6.0 μg/mL. In subgroup analyses stratified by TIR tertiles (< 58%, 58%–80%, and ≥ 80%), low 1,5‐AG levels remained significantly associated with an elevated risk of DR in both the highest (OR = 1.44, 95% CI 1.09–1.91) and middle TIR tertiles (OR = 1.64, 95% CI 1.13–2.42). Regarding CGM‐derived glucose variability metrics, while CV and SD were associated with DR in the overall population, none of MAGE, CV, or SD was significantly associated with DR in the highest TIR tertile. Conclusions: Serum 1,5‐AG is significantly associated with the prevalence of DR in type 2 diabetes. For patients with TIR ≥ 80%, 1,5‐AG may reveal additional risk of DR.