A fasting-mimicking diet programme reduces liver fat and liver inflammation/fibrosis measured by magnetic resonance imaging in patients with type 2 diabetes

Abstract

Background & aims: This study aimed to assess whether a fasting-mimicking diet (FMD) programme as an adjunct to usual care can reduce liver fat and liver inflammation/fibrosis as measured by Magnetic Resonance Imaging (MRI) in patients with type 2 diabetes.

Methods: This study analyses secondary outcomes of the Fasting In diabetes Treatment (FIT) trial, which was a randomised, controlled, assessor-blinded trial in which people with type 2 diabetes using metformin only and/or diet alone for glycaemic control were randomised to receive 5-consecutive day cycles of FMD monthly as adjunct to usual care or usual care only for twelve months. Laboratory measurements, anthropometric measurements and MRI were performed at baseline, 6 and 12 months. Two MRI-derived biomarkers were measured: proton density fat-fraction (PDFF), a biomarker for liver fat, and iron content corrected T1 (cT1), a biomarker for liver inflammation/fibrosis.

Results: Data were available of 89 participants who completed baseline visits including MRI (n = 48 in the FMD group and n = 41 in the control group). Intention-to-treat analyses, using linear mixed models, revealed significant adjusted estimated treatment effects of the FMD on PDFF (-2.8 %, 95 % CI -4.7 to -0.8, p < 0.01) and cT1 (-29.9 ms, 95 % CI -51.8 to -8.0, p < 0.01) at 12 months. In a post-hoc analysis, more participants in the FMD group compared to the control group transitioned from high to low risk for liver disease and cardiovascular disease based on PDFF ≥5.6 %. In the FMD and control group combined, every percent decrease in PDFF was associated with a decrease in HbA1c of 0.75 mmol/mol (95 % CI 0.51 to 0.99), fasting glucose of 0.14 mmol/L (95 % CI 0.08 to 0.20), triglycerides of 0.04 mmol/L (95 % CI 0.02 to 0.07), total cholesterol of 0.03 mmol/L (95 % CI 0.01 to 0.05) and weight of 0.52 kg (CI 0.33 to 0.70). Every millisecond decrease in cT1 was associated with a decrease in HbA1c of 0.05 mmol/mol (95 % CI 0.02 to 0.08), fasting glucose of 0.01 mmol/L (95 % CI 0.00 to 0.02) and weight of 0.04 kg (CI 0.01 to 0.06).

Conclusion: Following an FMD programme for 5-consecutive days per month for twelve months reduces both liver PDFF and cT1 MRI-derived biomarkers in patients with type 2 diabetes, indicating a reduction in liver fat and liver inflammation/fibrosis. Decreases in PDFF and cT1 are associated with decreases in HbA1c, fasting glucose, triglycerides and weight. Decrease in PDFF was also associated with a decrease in total cholesterol. Monthly cycles of an FMD appear to be a valuable adjunct to regular treatment of type 2 diabetes.

Trial registration: ClinicalTrials.gov: NCT03811587.

Keywords: Diet; Liver fat; MASLD; MRI; Primary care; Type 2 diabetes.