ABSTRACT 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.
ABSTRACT Background To examine medication use and simultaneous achievement of glycemic, blood pressure and lipid targets across body mass index (BMI) categories in Chinese adults with Type 2 diabetes. Methods This BMI‐focused secondary cross‐sectional analysis included 8590 adults with evaluable BMI recruited from 60 hospitals in the iCaReMe China Registry. The primary comparison was obesity versus normal weight for simultaneous achievement of HbA1c < 7.0%, blood pressure < 130/80 mmHg and LDL cholesterol < 2.6 mmol/L. Missing data were handled by multiple imputation (20 datasets; 20 iterations per chain), and associations were estimated with center‐clustered generalized estimating equations (GEE). Results The cohort comprised 99 (1.2%) adults with underweight, 2725 (31.7%) normal weight, 3663 (42.6%) overweight, and 2103 (24.5%) obesity. Among 6683 with all three observed components, 332 (5.0%) achieved the composite. Compared with normal weight, the pooled adjusted OR for obesity was 0.55 (95% CI 0.39–0.78); each 1‐kg/m 2 higher BMI was associated with an OR of 0.93 (0.90–0.96). For obesity, component‐specific ORs were 0.72 (0.61–0.85) for HbA1c, 0.47 (0.40–0.55) for blood pressure and 1.05 (0.91–1.22) for LDL‐C. Sensitivity analyses supported the composite finding, with no evidence of nonlinearity ( p = 0.904). Conclusions Obesity was associated with lower odds of simultaneous target attainment, with component‐specific associations for glycemia and blood pressure but not LDL‐C. GLP‐1 receptor agonists and SGLT2 inhibitors were used more often at higher BMI; these prescribing patterns do not establish treatment effectiveness. Trial Registration: ChiCTR2300073764.
ABSTRACT Diabetic cardiomyopathy is characterized by progressive metabolic dysfunction, myocardial fibrosis, impaired calcium handling, and ventricular remodeling, yet effective strategies for reversing established cardiac injury remain limited. Exercise training has emerged as a promising non‐pharmacological approach, although its clinical application is constrained by heterogeneous intervention protocols, inconsistent dose reporting, and limited evidence from well‐characterized diabetic cardiomyopathy populations. This narrative review synthesizes current preclinical and clinical evidence on exercise‐based management of diabetes‐associated myocardial dysfunction, with particular emphasis on underlying mechanisms, exercise prescription, and translational implementation. Experimental studies indicate that exercise may improve myocardial function through enhanced mitochondrial biogenesis and metabolic flexibility, attenuation of oxidative stress and inflammatory‐fibrotic signaling, restoration of calcium homeostasis, and regulation of apoptosis, pyroptosis, and microRNA‐related pathways. Clinical evidence, derived predominantly from individuals with Type 2 diabetes and subclinical or early cardiac abnormalities, suggests that combined aerobic and resistance training can improve cardiorespiratory fitness, insulin sensitivity, vascular function, and selected indices of left ventricular performance. High‐intensity interval training may provide additional benefits in appropriately selected patients, but its safety and effectiveness require individualized assessment. To improve translation, exercise intensity should be reported using physiologically comparable metrics, while treatment response should be evaluated through integrated measures of cardiac imaging, functional capacity, biomarkers, glycemic control, and adverse events. Overall, exercise represents a biologically plausible and clinically relevant adjunctive strategy for diabetic cardiomyopathy, particularly in early‐stage disease; however, adequately powered trials in clearly defined patient populations are still needed to establish optimal dose, safety, and long‐term cardiovascular benefit.
ABSTRACT Background Diabetic nephropathy (DN) is a major microvascular complication of Type 2 diabetes, with renal tubular epithelial cells (RTECs) apoptosis playing a pivotal role in its progression. The aqueous extract of Trametes robiniophila Murr. (Huaier) has shown renoprotective effects, but its specific molecular mechanisms in DN remain to be fully elucidated. Objective This study aimed to investigate the therapeutic effects of Huaier aqueous extract on DN and verify whether its anti‐apoptotic mechanism is mediated through the Wnt/β‐catenin pathway using the pathway activator SKL2001. Methods In vivo, KKAy Type 2 diabetic mice were treated with Huaier (5 g/kg/day) for 12 weeks to evaluate renal function and histopathology. In vitro, HK‐2 cells were treated with high glucose and palmitate (HG + PA) to induce injury. The Wnt/β‐catenin pathway activator SKL2001 was employed to determine if activating this pathway could abolish the protective effects of Huaier. Results Bioinformatics analysis indicates that the regulation of apoptosis is the primary mechanism by which Huaier improves DN. In vivo, Huaier reduced UACR and improved renal histopathology in KKAy mice. Consistently, TUNEL staining and molecular analysis confirmed that Huaier significantly suppressed RTECs apoptosis within the renal tissues. In vitro experiments demonstrated that Huaier significantly inhibited HG + PA‐induced oxidative stress, mitochondrial dysfunction, and RTECs apoptosis. Notably, the administration of SKL2001 effectively reversed these protective effects, leading to increased β‐catenin expression and elevated apoptosis levels despite Huaier treatment. Conclusion Huaier aqueous extract mitigates RTECs apoptosis and renal injury in Type 2 diabetic nephropathy by suppressing the Wnt5a/β‐catenin signaling pathway.
ABSTRACT Background Urinary liver‐type fatty acid‐binding protein (L‐FABP) reflects proximal tubular stress and has been proposed as a biomarker of diabetic kidney disease. We examined whether urinary L‐FABP provides information on longitudinal kidney function beyond urinary albumin‐to‐creatinine ratio (UACR). Methods This retrospective cohort study included patients with type 2 diabetes who had UACR and urinary L‐FABP measured simultaneously at the initial visit and underwent outpatient follow‐up. The analysis included patients with at least three eGFR measurements over at least 2 years. eGFR trajectories were evaluated using linear mixed‐effects models with random intercepts and slopes. UACR and L‐FABP were analyzed as log(1 + x)‐transformed continuous variables. Results The analysis included 1,031 patients (age 58.1 years; 65.1% men), with a median follow‐up of 4.76 years and a median of 10 eGFR measurements. Urinary L‐FABP correlated with UACR (Spearman ρ = 0.526; p < 0.001). Both biomarkers were independently associated with lower baseline eGFR. In a model without UACR, higher L‐FABP was associated with faster eGFR decline (−0.98 mL/min/1.73 m²/year per unit increase in log[1 + L‐FABP]; p < 0.001). After adjustment for continuous UACR, the association was attenuated and no longer significant (−0.19; 95% CI, −0.49 to 0.11; p = 0.221), whereas UACR remained independently associated with eGFR decline. Results were unchanged after further adjustment for baseline eGFR and lipid parameters. Conclusions Urinary L‐FABP was associated with baseline kidney impairment but did not independently predict eGFR trajectory after continuous UACR was taken into account. Urinary L‐FABP reflects kidney injury severity, although its incremental prognostic value beyond quantitatively assessed albuminuria was limited in this cohort.
