Article - Replacing dietary carbohydrate with protein and fat improves lipoprotein subclass profile and liver fat in type 2 diabetes independent of body weight: evidence from 2 randomized controlled trials.

Plain Language Summary

Elevated blood lipids are linked to poor liver health and the generation of heart disease in individuals with type 2 diabetes (T2D). In this study, two randomised controlled trials aimed to determine the effect of replacing carbohydrates in the diet with protein and fat in individuals with type 2 diabetes (T2D). The study focused on how this dietary change could improve the profile of lipoproteins, which are particles that carry fats in the blood, and reduce liver fat without affecting body weight.

The results showed that a moderate reduction in carbohydrates can lead to beneficial changes in fat levels in the liver and blood, which are important for managing T2D, independent of body weight changes. The study also showed that individuals with T2D often experience dyslipidemia, a condition characterised by unhealthy levels of fats in the blood, which can lead to liver issues and heart disease. By shifting the diet towards more protein and fat, participants showed improvements in their lipoprotein profiles and liver fat content.

It was concluded that carbohydrate restriction may benefit both individuals with metabolic-associated steatotic liver disease and those with T2D. This study could be used by healthcare professionals to consider carbohydrate-reduced, high-protein diets to lower liver fat. These findings support individualised dietary management focusing on macronutrient quality rather than caloric restriction alone.

Expert Review

Reviewer: Karin Elgar

10th Sep 2025

Conflict of interest

None

Take home message

A reduced carbohydrate/high protein diet (30% CHO, 30% protein) may benefit patients with T2DM with improved lipid profiles and liver health.

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction

The aim was to evaluate the effect of a 6-week carbohydrate-reduced high-protein diet (CRHP, 30% carbohydrates, 30% protein, 40% fat) on lipid profiles, with an emphasis of lipoprotein density subclasses, in patients with type 2 diabetes mellitus (T2DM) compared to a conventional diabetes diet (CD, 50%, 17% and 33%, respectively).

Methods

Secondary analysis of two open-label, randomised controlled trials (RCT) in adults with T2DM:

1) isoenergetic diet crossover RCT in 30 participants who had a CRHP diet and a CD diet.

2) hypocaloric diet parallel RCT of 72 participants split into two groups, where one group followed the CRHP diet the other followed the CD diet. The weight loss goal was 6%.

In both studies, all meals were provided to participants.
Outcome measures included: triacylglycerol (TAC), total cholesterol, HDL and LDL cholesterol and density profiles of lipoproteins.

Results

There was no difference between groups in weight maintenance or weight loss in either study.
In the isocaloric study, patients on CRHP improved significantly more than the CD group in various subclasses of lipoproteins : TAG-rich lipoproteins (TRL, mean -33%, 95% CI (-48%, -14%), LDL5 (-16%; (-26%, -4%)), HDL3 particles (-8%; (-14%, -0.7%)), HDL2/HDL3 ratio (10%; (0%, 22%)), and LDL1 (-20%; (-35%, -2%)).
In the hypocaloric study, patients on the CRHP improved significantly more in LDL5 (-13%; (-22%, -3%) and HDL2/HDL3 ratio (11%; (0.7%, 22%)), with a trend to reduced TRL (-16%; (-30%, 1%).
Intrahepatic TAG (IHTG) content reduced significantly more in the CRHP group than the CD group in both studies (-55%; (-74%, -22%) in the isocaloric study; -26% (-45%, 0%) in the hypocaloric study). Changes in IHTG correlated with changes in lipoprotein subclasses.
In both studies, glycaemic and lipid markers improved significantly more in the CRHP compared to the CD group.

Conclusion

A CRHP diet may improve metabolic dysfunction–associated steatotic liver disease and dyslipidaemia in patients with T2DM independent of weight loss, resulting in reduced atherogenicity.

Clinical practice applications

A reduced carbohydrate/high protein diet (30% CHO, 30% protein) could be considered for patients with T2DM to improve lipid profiles and liver health.

Considerations for future research

Longer-term studies in a real-life situation (meals not provided) are needed to confirm the long-term safety and efficacy of as well as compliance with a reduced carbohydrate diet.

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Abstract

BACKGROUND

Dyslipidemia with elevated concentrations of triacylglycerol-rich lipoproteins (TRLs), small-dense LDL, and reduced HDL is linked to hepatic steatosis and promotes atherogenesis in type 2 diabetes (T2D).

OBJECTIVES

We aimed to analyze whether moderate carbohydrate restriction reduces liver fat in T2D independent of changes in body weight and whether this is accompanied by parallel improvements in plasma lipoprotein subclasses.

METHODS

We determined the density profile of circulating lipoproteins in patients with T2D from 2 previous randomized controlled trials. In the isoenergetic study, 30 participants were allocated in a crossover design to 6 + 6 wk of an isocaloric carbohydrate-reduced high-protein (CRHP, C/P/F = 30/30/40 E%) or conventional diabetes (CD, C/P/F = 50/17/33 E%) diet aimed at weight maintenance. In the hypoenergetic study, 72 participants were allocated in a parallel-group design to 6 wk of a hypocaloric CRHP or CD diet aimed at matched ∼6% weight loss. Both studies provided all meals from a metabolic kitchen to maximize adherence.

RESULTS

In the isoenergetic study, the CRHP diet reduced TRL (mean: -33%; 95% CI: -48%, -14%) and LDL (mean: -16%; 95% CI: -26%, -4%) and increased HDL/HDL (mean: 10%; 95% CI: 0%, 22%) compared with the CD diet. In the hypoenergetic study, weight loss induced by CRHP diet tended to reduce TRL (mean: -16%; 95% CI: -30%, 1%), reduced LDL (mean: -13%; 95% CI: -22%, -3%), and increased HDL/HDL (mean: 11%; 95% CI: 1%, 22%) compared with an equivalent weight loss induced by CD diet. The CRHP diet decreased intrahepatic triacylglycerol (IHTG) more than the CD diet (isoenergetic: -55%; 95% CI: -74%, -22%; hypoenergetic: -26%; 95% CI: -45%, 0%), and changes in IHTG correlated directly with changes in TRL and LDL (r = 0.36-0.55; P < 0.01 for all) in both studies.

CONCLUSIONS

Replacing dietary carbohydrate with protein and fat improves dyslipidemia in T2D independently of changes in body weight, by inducing an atheroprotective shift in the lipoprotein particle profile possibly facilitated by reduced IHTG accumulation. These trials were registered at clinicaltrials.gov as NCT02764021 (https://clinicaltrials.gov/study/NCT02764021?term=NCT02764021&rank=1) and NCT03814694 (https://clinicaltrials.gov/study/NCT03814694?term=NCT03814694&rank=1).