Vitamin D status and sarcopenia in older adults: population-based evidence for synergy with diabetes and experimental validation in an aged diabetic rat model

BACKGROUND: Vitamin D deficiency is common in older adults and may contribute to sarcopenia, but whether diabetes modifies this association and the underlying mechanisms remain unclear. METHODS: We used a population-based and experimental validation framework. In epidemiological analyses, 7,520 older adults from two nationally representative cohorts were included (HRS wave 13, n = 3,246; ELSA wave 6, n = 4,274). Sarcopenia was defined according to EWGSOP2 criteria using low grip strength and low muscle mass estimated by a validated anthropometric equation standardized by BMI. Serum 25(OH)D was categorized as low (≤50 nmol/L) or higher (>50 nmol/L). Multivariable logistic regression with multiple imputation was used to assess overall and diabetes-stratified associations, as well as multiplicative and additive interactions. For experimental validation, an aged diabetic rat model with vitamin D deficiency was established, followed by vitamin D3 supplementation (2000 IU). Glycometabolic indices, muscle function and morphology, intramuscular lipid deposition, and senescence-related markers in gastrocnemius muscle were evaluated. RESULTS: Low 25(OH)D was associated with higher odds of sarcopenia overall. Among participants with diabetes, this association was stronger and reached statistical significance in ELSA (HRS: OR = 1.778, 95% CI 0.843-3.750; ELSA: OR = 2.242, 95% CI 1.055-4.764). In ELSA, the joint exposure to low 25(OH)D and diabetes was associated with increased sarcopenia odds (OR = 1.66, 95% CI 1.06-2.61), with evidence of additive interaction (RERI = 1.08, 95% CI 0.25-1.97). In aged diabetic rats, vitamin D deficiency aggravated hyperglycemia, insulin resistance, intramuscular lipid accumulation, and muscle senescence, whereas vitamin D3 supplementation improved muscle strength, myofiber cross-sectional area, and lipid infiltration. CONCLUSIONS: Low vitamin D status was associated with higher sarcopenia risk, particularly in diabetes. Experimental findings further support a protective role of vitamin D against diabetes-related muscle deterioration.