# Timing of coffee consumption and insulin resistance: evidence from human and animal studies

## TL;DR

Drinking coffee in the morning is linked to lower insulin resistance compared to drinking it throughout the day, based on human and mouse studies.

## Contribution

This study is the first to show that the timing of coffee consumption affects insulin resistance in both humans and animal models.

## Key findings

- Morning coffee consumption was associated with lower insulin resistance indices and a 17% reduced risk of severe insulin resistance.
- Morning coffee showed a linear inverse relationship with insulin resistance, while all-day coffee showed a J-shaped association.
- Morning coffee reduced inflammation markers and improved glucose metabolism in mice.

## Abstract

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.

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.

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).

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