Enhanced Metabolic Risks in Patients with Obesity and Nutritional Deficiencies in the U.S.: A TriNetX Study.

BACKGROUND/

OBJECTIVES

Nutrient deficiencies associated with progression from obesity to metabolic dysfunction are poorly characterized. Using electronic health records (TriNetX Research Network), we evaluated the association between key nutritional deficiencies and metabolic outcomes among patients with obesity.

METHODS

Deficiencies assessed included protein-energy malnutrition, deficiencies in vitamin D, calcium, magnesium, and vitamin B12, and prior underweight status. Outcomes included severe obesity, prediabetes, type 2 diabetes, metabolic syndrome, metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction-associated steatohepatitis (MASH). After matching propensity scores, cohorts with the double burden of malnutrition (DBM) were compared with a reference cohort of patients with obesity but no history of nutritional deficiencies.

RESULTS

The most prevalent types of DBM were vitamin D deficiency (10.6%), protein deficiency (8.9%) and calcium deficiency (7.5%). Incidence rates of obesity and all types of DBM increased from 2023 to 2025. Although middle-aged White and Black/African American patients represented the largest demographic groups, adults aged >70 years exhibited higher incidence rates of protein, calcium, magnesium, and B12 deficiencies. Vitamin D deficiency (median hazard ratio [HR] 3.09; IQR 2.32-5.66), vitamin B12 deficiency (median HR 2.49; IQR 2.16-6.08), and prior underweight (median HR 2.23; IQR 1.76-3.98) were associated with the highest burden of metabolic diseases.

CONCLUSIONS

These findings underscore the interplay between nutritional deficiencies and metabolic disease risk in obesity and support targeted interventions for populations affected by DBM, especially older adults, and in the context of racial and socioeconomic disparities.