Periodic fasting induced reconstitution of metabolic flexibility improves albuminuria in patients with type 2 diabetes

Sep 26, 2025Molecular metabolism

Periodic fasting may improve kidney protein levels by restoring metabolic flexibility in type 2 diabetes patients

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

A 6-month periodic fasting regimen may improve albuminuria in individuals with type 2 diabetes and diabetic nephropathy.

Periodic fasting was associated with a sustained shift toward enhanced fatty acid oxidation and lipid utilization in responders.
Responders exhibited persistent increases in short-chain acylcarnitines and cholesteryl esters, indicating more efficient lipid oxidation.
Elevated levels of glycine and serine in responders suggested enhanced cellular maintenance and a metabolic shift favoring lipid over carbohydrate.
Non-responders showed only transient and limited metabolic shifts, indicating variability in response to the dietary intervention.
Distinct metabolic response patterns were identified, supporting the potential for personalized dietary strategies in diabetes management.

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OBJECTIVE: Metabolic inflexibility has been shown to be associated with type 2 diabetes (T2D) and diabetic nephropathy (DN). However, data are lacking, proving that reconstitution of metabolic flexibility by using a 6-month periodic fasting (PF) regimen may improve albuminuria.

METHODS: In this post hoc analysis of a randomized-controlled trial, we investigated whether the PF regimen enhanced metabolic flexibility in individuals with T2D and DN showing improvement of albuminuria (responders) compared to non-responders. Participants followed every month either a 5-day fasting-mimicking diet or a Mediterranean diet for 6 months. LC-MS/MS-based comprehensive metabolic profiling was performed in plasma samples before, during, and after the intervention. Changes in metabolomic patterns and enriched signalling pathways were analysed between study groups.

RESULTS: PF induced a sustained shift toward enhanced fatty acid oxidation, lipid utilization, and amino acids turnover, particularly in responders. Responders exhibited persistent elevations in short-chain acylcarnitines and cholesteryl esters, indicating more efficient lipid oxidation and tighter integration of lipid metabolism with the tricarboxylic acid cycle. Increased glycine and serine levels suggested enhanced cellular maintenance, a protein-sparing effect, and a metabolic shift favouring lipid over carbohydrate. In contrast, non-responders demonstrated only transient and limited metabolic shifts. Unsupervised clustering identified distinct metabolic response patterns, reinforcing the potential of personalized dietary interventions.

CONCLUSIONS: These findings demonstrate that diet-induced restoration of metabolic flexibility is associated with improved albuminuria in T2D, suggesting broader implications for precise nutritional strategies in diabetes management.

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Periodic fasting induced reconstitution of metabolic flexibility improves albuminuria in patients with type 2 diabetes

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