ABSTRACT

Background:
The role of coffee consumption timing in insulin resistance (IR), a key driver of cardiovascular-metabolic diseases, remains unclear. This study aimed to investigate the association between the timing of coffee consumption and IR in a large population-based study and animal experiments.

Methods:
This study comprised two phases. First, we performed a secondary data analysis of the US National Health and Nutrition Examination Survey (NHANES), involving a cross-sectional sample of 20,460 adults with complete dietary data. Temporal coffee consumption patterns were identified via two-step clustering and associated with insulin resistance indices using multivariable-adjusted regression models. Subsequently, findings were validated experimentally using mouse models.

Results:
Two distinct coffee consumption patterns were identified: morning-type (36%) and all-day-type (11%). After multivariable adjustment, only the morning-type pattern was significantly associated with lower IR indices (TyG: β = -0.04; METS-IR: β= -0.59; TG/HDL-C: β= -0.29) and a 17% lower risk of sever IR (OR = 0.83). Stratified analyses confirmed robustness across coffee intake levels. Notably, coffee consumption timing significantly modified the dose-response relationship between coffee intake amounts and IR indices. Morning-type showed a linear inverse relationship with IR indices, while all-day-type exhibited a J-shaped association. Mediation analysis revealed that inflammatory markers, specifically white blood cell (WBC) count and neutrophil-to-lymphocyte ratio (NLR), partially mediated the beneficial effects of morning coffee consumption on insulin resistance. In mice, morning coffee administration reduced fasting plasma glucose and serum insulin levels, improved glucose tolerance, and lowered proinflammatory cytokines (IL-1β, IL-6, ICAM-1, MCP-1).

Conclusion:
Drinking coffee in the morning may be more strongly associated with a lower insulin resistance than drinking coffee later in the day.

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