# Glycaemic, appetite and circadian benefits of a dairy-enriched diet with high-protein breakfast and early daytime-restricted carbohydrate intake in type 2 diabetes: a randomised crossover trial

## TL;DR

A dairy-rich diet with high-protein breakfast and early carbohydrate intake improved blood sugar control and appetite in people with type 2 diabetes.

## Contribution

This study shows that dairy-based diets with structured meal timing can enhance circadian gene expression and metabolic health in type 2 diabetes.

## Key findings

- The YesMilk diet increased expression of circadian clock genes BMAL1, REV-ERBα, and CRY1.
- The YesMilk diet improved fasting glucose and glucose management while reducing hunger and sweet cravings.
- Participants showed better time in range for glucose levels and lower HbA1c indicators with the YesMilk diet.

## Abstract

The circadian timing of food intake and the composition of dietary protein sources may jointly influence metabolic regulation. Our aim was to examine the effects of a dairy-enriched vs non-dairy isoenergetic diet with structured meal timing on circadian clock gene expression, glycaemic management and appetite regulation in individuals with type 2 diabetes.

In a randomised, crossover trial, 25 participants with type 2 diabetes and HbA1c ≥48 mmol/mol (6.5%), treated either with stable doses (≥3 months) of oral glucose-lowering agents or managed by diet, followed two 4 week dietary phases, one including dairy-based protein sources (YesMilk) and one excluding them (NoMilk), with a 3–4 week washout. Participants were randomly assigned to one of two intervention sequences using simple randomisation (coin flip), either starting with the YesMilk diet followed by the NoMilk diet, or vice versa. Due to the open-label design, allocation was not concealed from investigators or participants. The study was powered for the primary outcome of circadian clock gene expression in peripheral blood mononuclear cells. Secondary outcomes included glycaemic indices derived from continuous glucose monitoring (CGM) and appetite scores. The study was conducted via the Diabetes Unit at Wolfson Medical Center, Israel.

Twenty-nine individuals were screened; 25 met eligibility criteria and were randomised to YesMilk or NoMilk dietary interventions in a crossover design. Thirteen participants began with the YesMilk dairy diet, all of whom completed both phases. Of the 12 who began with the NoMilk diet, six completed the study. Nineteen participants completed both intervention phases. Compared with the NoMilk phase, the YesMilk diet upregulated BMAL1 (+1.8-fold, p=0.0003), REV-ERBα (also known as NRD1D1) (+2.2-fold, p<0.001) and CRY1 (+1.4-fold, p=0.03), with higher PER1 expression (p=0.01 between diets at 4 weeks). Glycaemic variables improved under the YesMilk diet, with fasting glucose reduced by ~1.7 mmol/l, glucose management indicator reduced by 0.7%, and time in range increased by 9% compared with baseline (all p<0.05). Hunger and sweet craving scores decreased by 15–20% (p<0.05).

A dairy-enriched diet aligned with structured meal timing enhanced circadian clock gene expression and improved glycaemic and appetite-related variables in individuals with type 2 diabetes. These findings support a mechanistic link between dietary protein source, circadian regulation and metabolic health, warranting confirmation in larger, long-term studies.

ClincalTrials.gov NCT03772067

The Israeli Ministry of Health provided funding.

The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-025-06658-2.