Aim: To assess whether periodic fasting reduces albuminuria and activates nephropathy-driven pathways in patients with type 2 diabetes and diabetic nephropathy.
Methods: Forty 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 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 AC) , 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.
Results: Difference 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.
Conclusions: When accompanied by intensive diabetes care, FMD improves microalbuminuria, HOMA-IR and suPAR. Lack of changes in markers of dicarbonyl detoxification and DNA-damage/repair might explain the relapse of albuminuria at follow-up.
A.Sulaj: None. Z.Han: None. V.Kumar: None. V.Longo: Stock/Shareholder; L-Nutra Inc. A.Teleman: None. J.G.Okun: None. J.Morgenstern: None. T.H.Fleming: None. J.M.Szendroedi: Consultant; Boehringer Ingelheim International GmbH. S.Herzig: None. S.Kopf: Board Member; Novo Nordisk, Speaker's Bureau; AstraZeneca, Recordati S.p.A. E.V.Rauchhaupt: None. E.Kliemank: None. M.Brune: None. Z.Kender: None. H.Bartl: None. F.Garcia-cortizo: None. K.Klepac: None.
German Research Foundation DFG (236360313 and 255156212) German Center for Diabetes Research DZD (82DZD07C2G)