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.
ABSTRACT Background Undergoing perioperative ischemia‐reperfusion injury (I/RI), the prevalence of adverse cardiac events is high due to increased myocardial vulnerability in diabetic patients. However, the specific mechanisms of increased myocardial vulnerability in diabetes are still unknown. Objective To investigate the specific mechanisms underlying increased myocardial vulnerability in diabetes and to explore potential myocardial protective strategies. Methods In this study, we repeatedly verified through single‐cell sequencing, fluorescence in situ staining, metabonomics, and animal experiments. Results Here we show for the first time that the cardiomyocyte subtype (C6 cardiomyocyte) is a cardiomyocyte characterized by myocardial contraction, and the reduction of its number and metabolic heterogeneity is the basis of myocardial ischemia‐reperfusion injury in diabetes. Among them, TXNIP/PDK4 mediated metabolic reprogramming is an important reason for myocardial vulnerability in diabetes, and through regulating TXNIP/PDK4, we optimize myocardial energy metabolism. It can significantly improve the vulnerability of diabetes myocardium, play a good role in myocardial protection, and has clinical transformation potential.
ABSTRACT Background Cardiovascular‐kidney‐metabolic (CKM) risk stratification may identify patients with type 2 diabetes mellitus (T2DM) who require more intensive primary prevention, but real‐world data from Vietnam are limited. We aimed to describe advanced CKM risk and risk‐factor control in Vietnamese patients with T2DM without established cardiovascular disease (CVD). Methods This multicenter cross‐sectional study enrolled 1436 adults with T2DM without CVD in Vietnam. Advanced CKM risk was defined as 10‐year total CVD risk ≥ 20% or eGFR < 60 mL/min/1.73 m2. Guideline‐based control of HbA1c, blood pressure, LDL‐C, triglycerides, and non‐HDL‐C was evaluated. Logistic regression assessed associations between advanced CKM risk and target achievement. Results Advanced CKM risk was identified in 551 patients (38.4%). Despite a relatively low prevalence of BMI ≥ 25 kg/m2 (26.9%), hypertriglyceridemia was the most common metabolic abnormality, affecting 88.0% of participants. Risk‐factor control was generally low, with 33.3% achieving glycemic control, 33.5% blood pressure control, 18.8% LDL‐C control, 12.0% triglyceride control, and 21.1% non‐HDL‐C control. After adjustment, advanced CKM risk was associated with poorer blood pressure control (adjusted OR = 0.466, 95% CI = 0.359–0.603, p < 0.001) and triglyceride control (adjusted OR = 0.677, 95% CI = 0.473–0.969, p = 0.033), but not with achievement of HbA1c, LDL‐C, non‐HDL‐C, or combined lipid control. Conclusions Advanced CKM risk was common among Vietnamese patients with T2DM without established CVD and was consistently associated with poorer blood pressure control. CKM‐based risk assessment may identify high‐risk patients earlier and support guideline‐directed risk‐factor management. Frequent hypertriglyceridemia with relatively low obesity supports a CKM‐based strategy tailored to this metabolic risk pattern.
ABSTRACT Aims To evaluate the longitudinal prognostic value of small‐ and large‐fiber peripheral nerve assessments for accelerated renal decline in patients with Type 2 diabetes (T2D). Methods An initial cross‐sectional analysis evaluated concurrent neuro‐renal associations, while a subsequent longitudinal cohort assessed accelerated renal progression (eGFR loss > 3 mL/min/1.73 m2/year) using paired baseline and follow‐up data. Prognostic predictors were selected via LASSO regression. Model utility was assessed using area under the curve (AUC), net reclassification improvement (NRI), and decision curve analysis (DCA). Results Cross‐sectional sudomotor small‐fiber dysfunction accurately mirrored concurrent renal impairment (β = 0.18, 95% CI: 0.10–0.26, p < 0.001). Longitudinally, ESCF demonstrated no independent prognostic value for accelerated renal decline, and its apparent longitudinal association with future eGFR was completely attenuated after adjusting for baseline renal function. LASSO regression retained right peroneal motor amplitude, serum albumin, platelet count, and SGLT2i use as robust prognostic factors. Notably, subgroup analyses revealed this large‐nerve predictive capacity was significant primarily in patients with established DKD (p for interaction = 0.006). Incorporating this neurofunctional phenotype into standard clinical models yielded a modest AUC improvement but achieved a clinically relevant continuous NRI of 30.35%, successfully recalibrating risk profiles. DCA confirmed a superior net clinical benefit. Conclusion A distinct prognostic dissociation exists within the diabetic neuro‐renal axis. Sudomotor small‐fiber dysfunction primarily reflects established microvascular impairment, whereas large motor nerve degeneration demonstrates independent prognostic value for future accelerated renal decline. Incorporating this neurofunctional phenotype into traditional clinical models yields substantial individualized risk reclassification, thereby potentially aiding in identifying high‐risk individuals.
