AUTHOR=Lin Chen-Ying , Zhai Ya-Jie , Wu Fan , An Hao-Hua , Chen Tong , Qiu Hui-Na , Li Jing-Bo , Lin Jing-Na 

TITLE=Interaction and overall effects of underweight, low muscle mass, malnutrition, and inflammation on early-onset mild cognitive impairment in type 2 diabetes

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 17 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1498478

DOI=10.3389/fnagi.2025.1498478

ISSN=1663-4365

ABSTRACT=IntroductionThis study systematically explores the overall impact and interactions of body composition and nutritional inflammatory indices on early-onset mild cognitive impairment (EOMCI) in type 2 diabetes mellitus (T2DM).MethodsA cross-sectional study included 816 T2DM patients. Body composition indices included body mass index (BMI), waist circumference (WC), a body shape index (ABSI), body roundness index (BRI), visceral fat area (VFA), body fat percentage (BF%), and skeletal muscle mass index (SMMI). Nutritional inflammatory indices included the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), C-reactive protein-albumin-lymphocyte index (CALLY), and fibrinogen-to-albumin ratio (FAR). K-means clustering and quantile g-computation (QGC) assessed the combined impact, with interactions evaluated by simple slope analysis.ResultsK-means clustering revealed two distinct patterns: Low-pattern and High-pattern. The Low-pattern group exhibited significantly lower body composition indices (BMI 24.6 vs. 27.7 kg/m2; WC 88 vs. 99 cm; ABSI 0.081 vs. 0.084; BRI 3.89 vs. 5.02; VFA 91 vs. 112; BF% 29% vs. 31%; SMMI 9.38 vs. 10.48 kg/m2; all P < 0.001) and poorer nutritional status with higher inflammation (GNRI 97.9 vs. 104.6; PNI 47.9 vs. 53.1; CALLY index 4 vs. 5; FAR 0.082 vs. 0.072; all P < 0.05). This group had a higher prevalence of EOMCI (32% vs. 23%, P = 0.006). After adjusting for confounders, the Low-pattern group had a 1.45-fold increased risk of EOMCI (OR 1.45, 95% CI 1.01–2.08). QGC analysis demonstrated that the combined overall effect of body composition and nutritional inflammatory indices was negatively associated with EOMCI risk. A one-quintile increase in all indices was linked to a significant 31.3% reduction in EOMCI risk (95% CI −44.4%, −15.0%). Interaction analysis revealed that abdominal obesity (ABSI > 0.08), combined with malnutrition (low GNRI), significantly increased EOMCI risk (Pinteraction = 0.018). Similarly, low muscle mass (SMMI < 11.33 kg/m2), when combined with malnutrition and high inflammation (low CALLY index), further exacerbated EOMCI risk (Pinteraction = 0.028).DiscussionThe findings suggest that in T2DM patients, the interactions and overall effects of underweight, reduced muscle mass, abdominal obesity, malnutrition, and elevated inflammation are significantly associated with an increased risk of EOMCI. Integrated management of these factors is essential to mitigate EOMCI risk.