Six-Month Periodic Fasting in Patients With Type 2 Diabetes and Diabetic Nephropathy: A Proof-of-Concept Study.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 35661214 · doi:10.1210/clinem/dgac197
What was done
A proof-of-concept randomized controlled trial evaluated 40 adults with type 2 diabetes and elevated albumin-to-creatinine ratio (ACR). Participants were randomly assigned to receive either a monthly fasting-mimicking diet (FMD) or a Mediterranean diet for 6 months, followed by a 3-month follow-up. The primary outcome was change in ACR at 6 months assessed by ANCOVA adjusted for age, sex, weight loss, and baseline value, with prespecified subgroup analysis by baseline microalbuminuria versus macroalbuminuria. Exploratory outcomes included HOMA-IR and circulating markers of dicarbonyl detoxification, DNA damage/repair (phosphorylated histone H2AX), lipid oxidation (acylcarnitines), and senescence (soluble urokinase plasminogen activator receptor [suPAR]).
What was found
Change in ACR across the full cohort at 6 months did not differ significantly between groups (110.3 [99.2, 121.5] mg/g; P = 0.45). In prespecified subgroup analysis, FMD reduced ACR in patients with baseline microalbuminuria (-30.3 [-35.7, -24.9] mg/g; P ≤ 0.05) but not in those with macroalbuminuria (434.0 [404.7, 463.4] mg/g; P = 0.23). FMD also decreased HOMA-IR (-3.8 [-5.6, -2.0]; P ≤ 0.05) and suPAR (-156.6 [-172.9, -140.4] pg/mL; P ≤ 0.05), with no changes in dicarbonyl detoxification or DNA damage markers. At the 3-month follow-up, only the HOMA-IR reduction was sustained (-1.9 [-3.7, -0.1]; P ≤ 0.05). FMD was tolerated with 71% to 95% of participants reporting no adverse effects.
Why it matters
Periodic fasting using a fasting-mimicking diet may improve insulin sensitivity and early-stage microalbuminuria in type 2 diabetes, though benefits did not extend to macroalbuminuria.
Limits
The primary outcome was negative overall; albuminuria benefit was restricted to a subgroup analysis in a small trial (n = 40). Most biomarker improvements reverted after intervention cessation, and hard clinical renal endpoints were not evaluated.
Cited by
- supports Implementing a 5-day fasting-mimicking diet once per month provides long-lasting improvements in insulin sensitivity and metabolic biomarkers lasting weeks to over a month.