A six-month periodic fasting reduces microalbuminuria and improves metabolic control in patients with type 2 diabetes and diabetic nephropathy: a randomized controlled study

AimNovel dietary interventions focused on fasting, have gained scientific and public attention. Periodic fasting has emerged as a dietary modification promoting beneficial effects on metabolic syndrome. This study aimed to assess whether periodic fasting reduces albuminuria in patients with type 2 diabetes and diabetic nephropathy and determine whether a reduction in albuminuria relates to activation of nephropathy-driven pathways. MethodsForty patients with type 2 diabetes (HbA1c 7.8{+/-}0.2% [62.1{+/-}2.3 mmol/mol]) and increased albumin-to-creatinine ratio (ACR) were randomized to fasting-mimicking diet (FMD) (n=21) or Mediterranean diet (n=19) for six months with three-month follow-up. Primary endpoint was the difference of the change in ACR from baseline to after six months between study groups. Subgroup analysis for patients with micro-versus macroalbuminuria at baseline was performed. Secondary endpoints comprised HOMA-IR, circulating markers of dicarbonyl detoxification (MG-H1, glyoxalase-1 and hydroxyacetone), lipid oxidation (acylcarnitines), DNA-damage/repair, (yH2Ax) and senescence (suPAR). Comparison was done by ANCOVA adjusted for age, sex, weight loss and baseline values of the respective outcome. ResultsDifference of change in ACR between FMD and control group after six months was 110.3mg/g (95% CI 99.2, 121.5mg/g; P=0.45) in all patients, -30.3mg/g (95% CI -35.7, -24.9mg/g; P[≤]0.05] in patients with microalbuminuria, and 434.0mg/g (95% CI 404.7, 463.4mg/g; P=0.23) in those with macroalbuminuria at baseline. FMD led to change in HOMA-IR of -3,8 (95% CI -5,6, -2.0; P[≤]0.05) and in suPAR of - 156.6pg/ml (95% CI -172.9, -140.4pg/ml; P[≤]0.05) after six months, while no change was observed in markers of dicarbonyl detoxification or DNA-damage/repair. Change in AC profile was related to patient responsiveness to ACR improvement. At follow-up only HOMA-IR reduction (-1.9 [95% CI -3.7, -0.1], P[≤]0.05) was sustained. ConclusionsWhen accompanied by intensive diabetes care, FMD improves microalbuminuria, HOMA-IR and suPAR levels. Lack of changes in markers of dicarbonyl detoxification and DNA-damage/repair might explain the relapse of albuminuria at follow-up. Trial registrationGerman Clinical Trials Register (Deutsches Register Klinischer Studien DRKS), DRKS-ID: DRKS00014287