Assessment of immune function in individuals without and with obesity and normoglycemia, glucose intolerance, or type 2 diabetes: primary findings of the NutrIMM study, a single-arm controlled feeding trial

Obesity and type 2 diabetes (T2D) are associated with immune dysfunction, increasing infection susceptibility and impairing immune responses. However, the independent effects of obesity and hyperglycemia on immune dysregulation remain unclear, particularly under controlled dietary conditions. The Nutrition and Immunity study investigated the effects of obesity and hyperglycemia on immune cell function, phenotype, and systemic inflammation in individuals with obesity with or without T2D, compared with lean individuals with normoglycemia. This single-arm controlled feeding trial included 112 participants across 4 groups: lean-normoglycemic (Lean-NG), obese-normoglycemic (OB-NG), obese-glucose intolerant (OB-GI), and obese-T2D. Participants followed a standardized isocaloric North American diet for 4 wk. Blood samples were collected at baseline and week 4. One-way and repeated measures analysis of variance assessed group differences and/or dietary effects. Linear regression analyses examined associations between glucose control and immune function. C-reactive protein levels were higher in the OB-NG group [mean difference (MD): 4.1 mg/L; 95% confidence interval (CI): 1.7, 6.6], OB-GI group (MD: 3.1 mg/L; 95% CI: 0.82, 5.4), and OB-T2D (MD: 2.7 mg/L; 95% CI: 0.3, 5.1) compared with Lean-NG, whereas interleukin (IL)-2 secretion was lower in OB-T2D group (MD: -2086.4 pg/mL; 95% CI: -4375.9, -37.4). OB-T2D also exhibited higher neutrophils (MD: 0.7%; 95% CI: 0.01, 0.12), Systemic Immune-Inflammation Index (MD: 155.3; 95% CI: 0.90, 309.7), and system inflammation response index (MD: 0.58, 95% CI: 0.20, 0.97) compared with Lean-NG, and a lower proportion of naïve CD8+ T cells than OB-NG (MD: -13.7%; 95% CI: -27.3, -0.14). Regression analysis showed an association between hyperglycemia and reduced immune function, particularly for IL-2 (β = -0.296, P = 0.037) and interferon-gamma secretion (β = -0.325, P = 0.017). Immune function is compromised in obesity and worsens in T2D, suggesting both obesity and poor glucose control drive immune dysfunction. Addressing metabolic health may help mitigate immune dysfunction and inflammation in obesity-related conditions. This trial was registered at clinicaltrials.gov as NCT04291391 (https://www. gov/study/NCT04291391?term=NCT04291391&rank=1).