Full-paper Knowledge Units · saved output

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

Gemma 4 E4B IT · KU LoRA rank 128 · 500-word source chunks · guarded TranslateGemma 4B back-translation

Complete extractionLongest literal run: 23 words

This condition scores 82.5% (165/200) across all 20 evaluation papers. The example page does not imply that every claim in this individual paper is correct.

Gemma 4 12B IT · KU LoRA rank 128 · 500 wordsGemma 4 12B IT · KU LoRA rank 128 · 1,000 wordsGemma 4 E4B IT · KU LoRA rank 128 · 500 wordsGemma 4 E4B IT · KU LoRA rank 128 · 1,000 wordsQwen 3.8 27B FP8 · teacher · 500 wordsQwen 3.8 27B FP8 · teacher · 1,000 words

Every saved KU, entity, attribute and relationship is shown below, in original chunk order. Navigation follows the source sequence rather than publication dates. Adjacent summaries are reader navigation, not lookahead supplied to extraction. All KUs were generated before the paraphrasing stage. Download complete factual KU JSON.

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KU 1 · source words 1–493

33 entities · 39 relationships · 0 preceding KUs available during extraction

Recorded context summary

A randomized controlled study compared a fasting-mimicking diet to a Mediterranean diet in patients with type 2 diabetes and diabetic nephropathy. The fasting-mimicking diet reduced microalbuminuria and improved metabolic markers like HOMA-IR and suPAR in the short term. The study suggests that the lack of changes in the detoxification of dicarbonyl compounds and markers for DNA damage may explain the recurrence of albuminuria at follow-up.

Alba Sulaj

person · ID: alba_sulaj
affiliation
Heidelberg University Hospital

Relationships

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

Stefan Kopf

person · ID: stefan_kopf
affiliation
Heidelberg University Hospital

Relationships

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

Ekaterina Von Rauchhaupt

person · ID: ekaterina_von_rauchhaupt
affiliation
Heidelberg University Hospital

Relationships

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

Elisabeth Kliemank

person · ID: elisabeth_kliemank
affiliation
Heidelberg University Hospital

Relationships

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

Maik Brune

person · ID: maik_brune
affiliation
Heidelberg University Hospital

Relationships

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

Zoltan Kender

person · ID: zoltan_kender
affiliation
Heidelberg University Hospital

Relationships

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

Hannelore Bartl

person · ID: hannelore_bartl
affiliation
Heidelberg University Hospital

Relationships

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

Fabiola Garcia Cortizo

person · ID: fabiola_garcia_cortizo
affiliation
not specified

Relationships

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

Katarina Klepac

person · ID: katarina_klepac
affiliation
Helmholtz Center Munich

Relationships

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

Zhe Han

person · ID: zhe_han
affiliation
Heidelberg University Hospital

Relationships

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

Varun Kumar

person · ID: varun_kumar
affiliation
Heidelberg University Hospital

Relationships

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

Valter Longo

person · ID: valter_longo
affiliation
Longevity Institute

Relationships

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

Aurelio Teleman

person · ID: aurelio_teleman
affiliation
not specified

Relationships

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

Jürgen G Okun

person · ID: jurgen_g_okun
affiliation
University Hospital Heidelberg

Relationships

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

Jakob Morgenstern

person · ID: jakob_morgenstern
affiliation
Heidelberg University Hospital

Relationships

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

Thomas Fleming

person · ID: thomas_fleming
affiliation
Heidelberg University Hospital

Relationships

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

Julia Szendroedi

person · ID: julia_szendroedi
affiliation
Heidelberg University Hospital

Relationships

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

Stephan Herzig

person · ID: stephan_herzig
affiliation
not specified

Relationships

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

Peter P Nawroth

person · ID: peter_p_nawroth
affiliation
Heidelberg University Hospital

Relationships

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

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

event · ID: a_six_month_periodic_fasting_reduces_microalbuminuria_and_improves_metabolic_control_in_patients_with_type_2_diabetes_and_diabetic_nephropathy_a_randomized_controlled_study
study_type
randomized controlled study
duration
six months
follow_up
three months

Relationships

  • aimed_to_assess → whether periodic fasting reduces albuminuria in patients with type 2 diabetes and diabetic nephropathy
  • aimed_to_determine → whether reduction in albuminuria relates to activation of nephropathy-driven pathways

Fasting-mimicking diet (FMD)

method · ID: fasting_mimicking_diet_fmd
n_patients
21
duration
six months

Relationships

  • compared_to → Mediterranean diet
  • reduced_microalbuminuria_in → patients with microalbuminuria
  • reduced_homa_ir_in → patients with microalbuminuria
  • reduced_supar_in → patients with microalbuminuria

Mediterranean diet

method · ID: mediterranean_diet
n_patients
19
duration
six months

Relationships

  • compared_to → Fasting-mimicking diet (FMD)

Type 2 diabetes

other · ID: type_2_diabetes
baseline_hba1c
7.8±0.2% [62.1±2.3 mmol/mol]
model_entity_type
condition

Relationships

  • associated_with → diabetic nephropathy

Diabetic nephropathy

other · ID: diabetic_nephropathy
definition
The most common cause of terminal kidney disease
model_entity_type
condition

Relationships

  • treated_by → control of glycemia, lipidemia and blood pressure

Microalbuminuria

measurement · ID: microalbuminuria
definition
increased albumin-to-creatinine ratio (ACR)

Relationships

  • reduced_by → Fasting-mimicking diet (FMD)
  • sustained_reduction_at → three-month follow-up

Macroalbuminuria

measurement · ID: macroalbuminuria
definition
increased albumin-to-creatinine ratio (ACR)

Relationships

  • not_significantly_reduced_by → Fasting-mimicking diet (FMD)

HOMA-IR

measurement · ID: homa_ir
change_after_six_months
-3.8 (95% CI -5.6, -2.0)

Relationships

  • reduced_by → Fasting-mimicking diet (FMD)
  • sustained_reduction_at → three-month follow-up

suPAR

measurement · ID: supar
change_after_six_months
-156.6 pg/ml (95% CI -172.9, -140.4 pg/ml)

Relationships

  • reduced_by → Fasting-mimicking diet (FMD)

Markers of dicarbonyl detoxification

measurement · ID: markers_of_dicarbonyl_detoxification
components
MG-H1, glyoxalase-1, hydroxyacetone

Relationships

  • no_change_observed_after → six months

DNA-damage/repair

measurement · ID: dna_damage_repair
components
yH2Ax

Relationships

  • no_change_observed_after → six months

Senescence

measurement · ID: senescence
marker
suPAR

Relationships

  • reduced_by → Fasting-mimicking diet (FMD)

SGLT2 inhibitors

method · ID: sglt2_inhibitors
class
sodium-glucose cotransporter-2 inhibitors

Relationships

  • exert_nephroprotection_to_some_degree → diabetic nephropathy

ACE inhibitors

method · ID: ace_inhibitors
class
Angiotensin-Converting Enzyme inhibitors

Relationships

  • exert_nephroprotection_to_some_degree → diabetic nephropathy
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Previous KU: Start of paper
Next KU: The study investigates whether a six-month periodic fasting-mimicking diet reduces albumin-to-creatinine ratio in type 2 diabetes patients with diabetic kidney disease. It aims to link ACR reduction to changes in dicarbonyl detoxification, fatty acid oxidation, DNA damage, and senescence markers. The randomized, controlled, open study was conducted at the University Hospital in Heidelberg and involved patients with well-controlled diabetes and high ACR (American College of Rheumatology) scores.

KU 2 · source words 494–987

6 entities · 14 relationships · 1 preceding KUs available during extraction

Recorded context summary

The study investigates whether a six-month periodic fasting-mimicking diet reduces albumin-to-creatinine ratio in type 2 diabetes patients with diabetic kidney disease. It aims to link ACR reduction to changes in dicarbonyl detoxification, fatty acid oxidation, DNA damage, and senescence markers. The randomized, controlled, open study was conducted at the University Hospital in Heidelberg and involved patients with well-controlled diabetes and high ACR (American College of Rheumatology) scores.

Diabetic kidney disease (DKD)

concept · ID: diabetic_kidney_disease_dkd
progression
only possible to slow once established
remission_therapy
lacking

Relationships

  • caused_by → hyperglycemia
    mechanisms
    activation of sorbitol pathway, activation of hexosamine pathway, increase in oxidative stress
  • results_in → fibrosis
  • implicated_in → dicarbonyl stress and AGE
  • associated_with → increased DNA-damage, persistent DNA-damage signaling, senescence

Periodic fasting-mimicking diet (FMD)

method · ID: periodic_fasting_mimicking_diet_fmd
duration
six months
frequency
periodic
intervention_duration
five days

Relationships

  • reduces → oxidative damage, inflammation
  • supports → cellular protection
  • activates → lipolysis
  • aimed_to_reduce → ACR

Randomized controlled open study

method · ID: randomized_controlled_open_study
location
Hospitals specializing in endocrinology, diabetes, metabolism, and clinical chemistry, Heidelberg University Hospital
ethics_approval
Ethic-Nr. S-682/2016
registration_id
DRKS00014287

Relationships

  • conducted_at → University Hospital of Heidelberg
  • approved_by → ethics committee of the University Hospital of Heidelberg

Study population

other · ID: study_population
condition
type 2 diabetes
control_status
Good control of blood sugar and blood pressure
treatment_status
optimized according to current guidelines
recruitment_criteria
increased albumin-to-creatinine ratio (ACR) from two consecutive spot urine samples according to KDIGO guidelines
model_entity_type
group

Relationships

  • received → individual dietary counseling before baseline visit
    guideline
    American Diabetes Association

ACR

measurement · ID: acr
definition
albumin-to-creatinine ratio
assessment_method
two consecutive spot urine samples according to KDIGO guidelines

Relationships

  • measured_at → baseline and each month after diet cycle
    timing
    sixth day after five-day diet intervention
  • measured_at → refeeding timepoints
    timing
    one week after third and after sixth diet cycle

Markers of dicarbonyl detoxification, fatty acid oxidation, DNA-damage/repair, and senescence

measurement · ID: markers_of_dicarbonyl_detoxification_fatty_acid_oxidation_dna_damage_repair_and_senescence
purpose
investigate relationship with ACR reduction

Relationships

  • measured_at → baseline and refeeding timepoints
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Previous KU: A randomized controlled study compared a fasting-mimicking diet to a Mediterranean diet in patients with type 2 diabetes and diabetic nephropathy. The fasting-mimicking diet reduced microalbuminuria and improved metabolic markers like HOMA-IR and suPAR in the short term. The study suggests that the lack of changes in the detoxification of dicarbonyl compounds and markers for DNA damage may explain the recurrence of albuminuria at follow-up.
Next KU: The study utilized stratified randomization based on BMI and HbA1c to assign participants to either a Fasting-Mimicking Diet or a Mediterranean Diet. The FMD was a plant-based diet with specific macronutrient compositions for different days, while the M-Diet maintained caloric intake and was adapted using the Mediterranean Diet Score. Participants on insulin therapy discontinued short-acting insulin and reduced long-acting insulin by 50% during FMD, with glycemic and blood pressure control monitored to maintain comparability between groups.

KU 3 · source words 988–1,439

8 entities · 8 relationships · 2 preceding KUs available during extraction

Recorded context summary

The study utilized stratified randomization based on BMI and HbA1c to assign participants to either a Fasting-Mimicking Diet or a Mediterranean Diet. The FMD was a plant-based diet with specific macronutrient compositions for different days, while the M-Diet maintained caloric intake and was adapted using the Mediterranean Diet Score. Participants on insulin therapy discontinued short-acting insulin and reduced long-acting insulin by 50% during FMD, with glycemic and blood pressure control monitored to maintain comparability between groups.

Fasting-Mimicking Diet (FMD)

other · ID: fasting_mimicking_diet_fmd
type
plant-based
day_1_composition
4600 kJ (11% protein, 46% fat, 43% carbohydrates)
days_2_to_5_composition
3000 kJ (9% protein, 44% fat, 47% carbohydrate)
model_entity_type
diet

Relationships

  • mimics → fasting-like effects on glucose and ketone bodies

Mediterranean Diet (M-Diet)

other · ID: mediterranean_diet_m_diet
caloric_intake
no change compared to pre-study diet
adaptation_method
Mediterranean Diet Score (MDS)
model_entity_type
diet

Relationships

  • control_group_diet → Fasting-Mimicking Diet

Randomization Procedure

method · ID: randomization_procedure
version
2.0.3
source
Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz
stratification_variables
[ "BMI (cut-off 30.0 kg/m²)", "HbA1c (cut-off 7.0%)" ]

Relationships

  • assigns_to → intervention or control group

Study Population

other · ID: study_population
weight_loss_criterion
less than 10%
insulin_therapy_protocol
discontinue short-acting insulin; reduce long-acting insulin by 50% during FMD
model_entity_type
group

Relationships

  • monitors → glycemic levels and blood pressure

Glycemic Monitoring

method · ID: glycemic_monitoring
device
Accu-Check Guide® (Roche)
frequency
at least 4 measurements daily (fasting and 2-hour postprandial)
reporting
24-hour telephone platform for hypo- or hyperglycemic episodes

Relationships

  • triggers_medication_reduction → antihyperglycemic medication (if fasting plasma glucose reduces by >20%)

Blood Pressure Monitoring

method · ID: blood_pressure_monitoring
reduction_criterion
hypotension (systolic < 100 mmHg and diastolic < 60 mmHg)

Relationships

  • triggers_medication_reduction → antihypertensive medication

Health Assessment

method · ID: health_assessment
quality_of_life_tool
A brief health assessment questionnaire (SF-12 questionnaire) consisting of 12 questions.
symptom_tool
Patient Health Questionnaire (PHQ)

Relationships

  • assesses → health-related quality of life and physical health

Blood Chemistry Analysis

method · ID: blood_chemistry_analysis
sample_state
fasting
processing_location
Central laboratory of the Heidelberg University Hospital
measurement_device
StatStrip® Glucose/Ketone Measurement System (Nova® Biomedical)

Relationships

  • measures → beta-hydroxybutyrate
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Previous KU: The study investigates whether a six-month periodic fasting-mimicking diet reduces albumin-to-creatinine ratio in type 2 diabetes patients with diabetic kidney disease. It aims to link ACR reduction to changes in dicarbonyl detoxification, fatty acid oxidation, DNA damage, and senescence markers. The randomized, controlled, open study was conducted at the University Hospital in Heidelberg and involved patients with well-controlled diabetes and high ACR (American College of Rheumatology) scores.
Next KU: The study defined the primary endpoint as the absolute difference in change of albumin-to-creatinine ratio between the fasting-mimicking diet and Mediterranean diet groups after six cycles. Secondary endpoints included changes in metabolic markers, dicarbonyl detoxification products, and DNA damage markers. The study utilized an intention-to-treat analysis with ANCOVA adjusted for baseline characteristics, and a sample size of 40 was calculated to detect a 30% reduction in ACR.

KU 4 · source words 1,440–1,932

9 entities · 15 relationships · 3 preceding KUs available during extraction

Recorded context summary

The study defined the primary endpoint as the absolute difference in change of albumin-to-creatinine ratio between the fasting-mimicking diet and Mediterranean diet groups after six cycles. Secondary endpoints included changes in metabolic markers, dicarbonyl detoxification products, and DNA damage markers. The study utilized an intention-to-treat analysis with ANCOVA adjusted for baseline characteristics, and a sample size of 40 was calculated to detect a 30% reduction in ACR.

Primary endpoint

measurement · ID: primary_endpoint
definition
Absolute difference of change of ACR from baseline to after six diet cycles between FMD and M-Diet group
subgroup_analysis
Micro-versus macroalbuminuria levels at baseline

Relationships

  • comprises → Absolute difference of change of ACR after three diet cycles
  • comprises → Absolute difference of change of ACR after six diet cycles

Secondary endpoints

measurement · ID: secondary_endpoints
markers
HOMA-IR, plasma MG-H1, plasma MG, Glo-1 activity, pGlo-1 expression in WBC, hydroxyacetone in RBC, plasma AC profile, yH2Ax expression in WBC, suPAR

Relationships

  • measured_at → Three diet cycles
  • measured_at → Six diet cycles

Dicarbonyl detoxification markers

concept · ID: dicarbonyl_detoxification_markers
components
Glo-1 activity, pGlo-1 expression in WBC, hydroxyacetone in RBC

Relationships

  • measured_at → Three diet cycles
  • measured_at → Six diet cycles

Fatty acid oxidation marker

concept · ID: fatty_acid_oxidation_marker
component
Plasma AC profile

Relationships

  • measured_at → Three diet cycles
  • measured_at → Six diet cycles

DNA-damage/repair marker

concept · ID: dna_damage_repair_marker
component
yH2Ax expression in WBC

Relationships

  • measured_at → Three diet cycles
  • measured_at → Six diet cycles

Kidney injury and senescence marker

concept · ID: kidney_injury_and_senescence_marker
component
suPAR

Relationships

  • measured_at → Three diet cycles
  • measured_at → Six diet cycles

Power calculation

method · ID: power_calculation
required_sample_size
34
estimated_dropout_rate
15%
final_sample_size
40
detection_threshold
30% reduction in ACR
standard_deviation
30%
significance_level
alpha=5%
power
at least 80%

Relationships

  • performed_in → PASS 16.0.12

Statistical analysis

method · ID: statistical_analysis
population
Intention-to-treat
missing_value_handling
Not imputed
available_case_analysis
Performed
variable_representation
Mean±SEM for normal, median with IQR for log-normal, frequencies for categorical
comparison_method
The ANCOVA analysis was adjusted for age, gender, weight loss, and the initial value of the outcome variable.
multiple_testing_procedure
Hierarchical test procedure for secondary endpoints
software
R (version 3.6.1 2019-07-05)
visualization_tools
R core packages, tiduverse, pheatmap, GraphPad Prism version 5.00

Relationships

  • performed_on → FMD and M-Diet group

Study population

event · ID: study_population
randomization_period
March 2018 to May 2020
total_randomized
41
FMD_group_size
21
M-Diet_group_size
20
discontinuation_reason
Erysipelas
discontinuation_count
1
completed_three_cycles
38
completed_study
33
follow_up_count
31
follow_up_time
112±31 days

Relationships

  • excluded_from_analysis → 1 patient from M-Diet group
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Previous KU: The study utilized stratified randomization based on BMI and HbA1c to assign participants to either a Fasting-Mimicking Diet or a Mediterranean Diet. The FMD was a plant-based diet with specific macronutrient compositions for different days, while the M-Diet maintained caloric intake and was adapted using the Mediterranean Diet Score. Participants on insulin therapy discontinued short-acting insulin and reduced long-acting insulin by 50% during FMD, with glycemic and blood pressure control monitored to maintain comparability between groups.
Next KU: The study found that a six-month periodic fasting-mimicking diet significantly reduced microalbuminuria and improved metabolic control in type 2 diabetes patients with diabetic nephropathy. The fasting-mimicking diet resulted in a 17% reduction in HbA1c and a 60% decrease in HOMA-IR in non-insulin-treated participants. The study found that the main reason for participants withdrawing was related to restrictions imposed as a result of the COVID-19 pandemic.

KU 5 · source words 1,933–2,387

10 entities · 16 relationships · 4 preceding KUs available during extraction

Recorded context summary

The study found that a six-month periodic fasting-mimicking diet significantly reduced microalbuminuria and improved metabolic control in type 2 diabetes patients with diabetic nephropathy. The fasting-mimicking diet resulted in a 17% reduction in HbA1c and a 60% decrease in HOMA-IR in non-insulin-treated participants. The study found that the main reason for participants withdrawing was related to restrictions imposed as a result of the COVID-19 pandemic.

Fasting-Mimicking Diet (FMD)

method · ID: fasting_mimicking_diet_fmd
duration
six months
withdrawal_reason
Covid-19 pandemic restrictions

Relationships

  • reduces → microalbuminuria
    reduction_after_six_cycles
    54%
    reduction_after_three_cycles
    37%
  • reduces → HbA1c
    reduction_after_six_cycles
    17%
    reduction_after_three_cycles
    0%
  • reduces → HOMA-IR
    reduction_after_six_cycles
    60%
    reduction_after_three_cycles
    0%
  • reduces → urea levels
    reduction_after_three_cycles
    11.8 mg/dl
    reduction_after_six_cycles
    17.9 mg/dl
  • reduces → suPAR
    reduction_after_three_cycles
    214.8 pg/ml
    reduction_after_six_cycles
    156.6 pg/ml
  • improves → eGFR based on cystatin C
    difference_after_six_cycles
    8.3 ml/min/1.73m²
    difference_after_three_cycles
    2.4 ml/min/1.73m²
  • maintains → LDL, HDL, and triglyceride levels
    change
    no change

Mediterranean Diet (M-Diet)

method · ID: mediterranean_diet_m_diet
caloric_intake
maintained
adaptation
Mediterranean Diet Score

Relationships

  • compared_to → Fasting-Mimicking Diet (FMD)

Type 2 diabetes

other · ID: type_2_diabetes
status
controlled
model_entity_type
condition

Relationships

  • associated_with → Diabetic nephropathy

Diabetic nephropathy

other · ID: diabetic_nephropathy
status
elevated ACR
model_entity_type
condition

Relationships

  • treated_by → Fasting-Mimicking Diet (FMD)

Microalbuminuria

measurement · ID: microalbuminuria
reduction_after_six_cycles
54%
reduction_after_three_cycles
37%

Relationships

  • subgroup_of → Diabetic nephropathy

Macroalbuminuria

measurement · ID: macroalbuminuria
reduction_after_six_cycles
434.0 mg/g
reduction_after_three_cycles
176.2 mg/g

Relationships

  • subgroup_of → Diabetic nephropathy

Albumin-to-creatinine ratio (ACR)

measurement · ID: albumin_to_creatinine_ratio_acr
difference_after_six_cycles
110.3 mg/g
difference_after_three_cycles
62.5 mg/g

Relationships

  • primary_endpoint → study

HOMA-IR

measurement · ID: homa_ir
reduction_after_six_cycles
60%

Relationships

  • measured_in → non-insulin treated participants

Fasting plasma glucose (FPG)

measurement · ID: fasting_plasma_glucose_fpg
change
no change

Relationships

  • compared_to → M-Diet group

Cystatin C

measurement · ID: cystatin_c
eGFR_difference_after_six_cycles
8.3 ml/min/1.73m²

Relationships

  • used_to_calculate → eGFR
Source positions, MinHash and extraction warnings
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Previous KU: The study defined the primary endpoint as the absolute difference in change of albumin-to-creatinine ratio between the fasting-mimicking diet and Mediterranean diet groups after six cycles. Secondary endpoints included changes in metabolic markers, dicarbonyl detoxification products, and DNA damage markers. The study utilized an intention-to-treat analysis with ANCOVA adjusted for baseline characteristics, and a sample size of 40 was calculated to detect a 30% reduction in ACR.
Next KU: The FMD group experienced greater weight loss than the M-Diet group, though body composition remained unchanged between groups. Plasma MG-H1 levels decreased significantly in the FMD group after three cycles, but this change did not correlate with ACR reduction. Participants who showed a reduction in ACR (Area Under the Curve) in the group with FMD (Fat-induced Modalkrankheit) had higher initial ACR values compared to those who did not respond to the treatment. Only the reduction in HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) was maintained in the subsequent investigation.

KU 6 · source words 2,388–2,864

9 entities · 18 relationships · 5 preceding KUs available during extraction

Recorded context summary

The FMD group experienced greater weight loss than the M-Diet group, though body composition remained unchanged between groups. Plasma MG-H1 levels decreased significantly in the FMD group after three cycles, but this change did not correlate with ACR reduction. Participants who showed a reduction in ACR (Area Under the Curve) in the group with FMD (Fat-induced Modalkrankheit) had higher initial ACR values compared to those who did not respond to the treatment. Only the reduction in HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) was maintained in the subsequent investigation.

Fasting-Mimicking Diet (FMD) group

other · ID: fasting_mimicking_diet_fmd_group
weight_loss_3_cycles
-5.6 kg (-5.9%)
weight_loss_6_cycles
-7.2 kg (-7.5%)
body_composition_change
no change compared to M-Diet group
plasma_MG-H1_reduction_3_cycles
62%
baseline_ACR_responders
85.7 mg/g
baseline_ACR_non_responders
271 mg/g
baseline_ACR_M-Diet_responders
55.5 mg/g
baseline_ACR_M-Diet_non_responders
563.0 mg/g
follow_up_HOMA-IR_change
-1.9 [-3.7, -0.1]
model_entity_type
study_group

Relationships

  • compared_to → Mediterranean Diet group
  • shows_no_change_in → body composition
  • shows_no_association_between → plasma MG-H1 change and ACR change
  • shows_higher_baseline_ACR_than → FMD non-responders
  • shows_higher_baseline_ACR_than → M-Diet responders

Mediterranean Diet (M-Diet) group

other · ID: mediterranean_diet_m_diet_group
weight_loss_3_cycles
-0.7 kg (-0.8%)
weight_loss_6_cycles
-1.1 kg (-1.2%)
body_composition_change
no change compared to FMD group
baseline_ACR_responders
55.5 mg/g
baseline_ACR_non_responders
563.0 mg/g
model_entity_type
study_group

Relationships

  • compared_to → Fasting-Mimicking Diet (FMD) group
  • shows_no_change_in → body composition
  • shows_no_association_between → plasma MG-H1 change and ACR change

Responders (ACR reduction)

other · ID: responders_acr_reduction
definition
participants with at least 30% improvement in ACR
baseline_ACR_FMD
85.7 mg/g
baseline_ACR_M-Diet
55.5 mg/g
model_entity_type
study_subgroup

Relationships

  • show_distinct_AC_profile_in → FMD group
  • show_distinct_AC_profile_in → M-Diet group

Non-responders (ACR reduction)

other · ID: non_responders_acr_reduction
baseline_ACR_FMD
271 mg/g
baseline_ACR_M-Diet
563.0 mg/g
model_entity_type
study_subgroup

Relationships

  • show_distinct_AC_profile_in → FMD group
  • show_distinct_AC_profile_in → M-Diet group

Acetylcarnitine levels (C2)

other · ID: acetylcarnitine_levels_c2
change_in_responders
The value increased after three dietary cycles in the FMD group.
model_entity_type
metabolic_marker

Relationships

  • distinct_response_in → FMD responders

Plasma MG-H1

other · ID: plasma_mg_h1
reduction_in_FMD_3_cycles
62%
no_association_with_ACR_change
in M-Diet and FMD groups
model_entity_type
biomarker

Relationships

  • no_change_in → plasma MG, Glo-1 activity, pGlo-1 expression in WBC, hydroxyacetone levels in RBC, yH2Ax levels in WBC

Refeeding period

event · ID: refeeding_period
timing
one week after third and sixth diet cycle
comparable_markers
HbA1c, FPG, LDL, HDL, triglyceride, HOMA-IR, eGFR, ACR, plasma MG-H1, suPAR

Relationships

  • comparable_between → FMD and M-Diet groups

Follow-up period

event · ID: follow_up_period
sustained_reduction
HOMA-IR
no_change_in
body weight or body composition

Relationships

  • sustains_reduction_in → HOMA-IR
  • no_change_in → body weight or body composition

Antihyperglycemic medication

other · ID: antihyperglycemic_medication
increase_in_FMD_group
increased for all but three participants
model_entity_type
treatment

Relationships

  • increase_in → FMD group
Source positions, MinHash and extraction warnings
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Previous KU: The study found that a six-month periodic fasting-mimicking diet significantly reduced microalbuminuria and improved metabolic control in type 2 diabetes patients with diabetic nephropathy. The fasting-mimicking diet resulted in a 17% reduction in HbA1c and a 60% decrease in HOMA-IR in non-insulin-treated participants. The study found that the main reason for participants withdrawing was related to restrictions imposed as a result of the COVID-19 pandemic.
Next KU: The study found that the diet, which was similar to fasting, was safe and well-tolerated, with most participants reporting no negative side effects. It led to a reduction in the use of medications to lower blood sugar and blood pressure in the group that followed the fasting-like diet, compared to the group that followed a Mediterranean diet. The FMD also caused a transient increase in blood ketones and a distinct response in fatty acid oxidation markers among ACR responders.

KU 7 · source words 2,865–3,363

8 entities · 12 relationships · 6 preceding KUs available during extraction

Recorded context summary

The study found that the diet, which was similar to fasting, was safe and well-tolerated, with most participants reporting no negative side effects. It led to a reduction in the use of medications to lower blood sugar and blood pressure in the group that followed the fasting-like diet, compared to the group that followed a Mediterranean diet. The FMD also caused a transient increase in blood ketones and a distinct response in fatty acid oxidation markers among ACR responders.

Fasting-Mimicking Diet (FMD)

method · ID: fasting_mimicking_diet_fmd
safety_profile
well tolerated
adverse_event_rate
71 to 95% reported no adverse effects
common_symptoms
weakness, muscle pain, dizziness, headache
grade_3_or_higher_adverse_events
none reported
hypoglycemic_episodes
10% (grade 1) and 5% (grade 2) in FMD group
blood_ketones_increase
3-fold after three and six diet cycles
ACR_reduction_response
distinct response in fatty acid oxidation markers among responders

Relationships

  • reduces → antihyperglycemic medication use
    after_three_cycles
    57% of participants
    after_six_cycles
    67% of participants
  • reduces → antihypertensive medication use
    after_three_cycles
    10% of participants
    after_six_cycles
    10% of participants
  • increases → blood ketones
    after_three_cycles
    3-fold
    after_six_cycles
    3-fold

Mediterranean Diet (M-Diet)

method · ID: mediterranean_diet_m_diet
hypoglycemic_episodes
11% (grade 1) and 11% (grade 2) in M-Diet group
antihyperglycemic_medication_increase
5% after three cycles, 21% after six cycles
antihypertensive_medication_increase
5% after three cycles, 10% after six cycles
MDS_compliance
6.1 after three and six diet cycles

Relationships

  • increases → antihyperglycemic medication use
    after_three_cycles
    5% of participants
    after_six_cycles
    21% of participants
  • increases → antihypertensive medication use
    after_three_cycles
    5% of participants
    after_six_cycles
    10% of participants

ACR

measurement · ID: acr
change_reversal
reversed to baseline values at follow-up

Relationships

  • reduced_by → FMD
  • transient_reduction_in → MG-H1 plasma levels

MG-H1 plasma levels

measurement · ID: mg_h1_plasma_levels
change_reversal
reversed to baseline values at follow-up

Relationships

  • transient_reduction_in → ACR responders

suPAR

measurement · ID: supar
change_reversal
reversed to baseline values at follow-up

Relationships

  • transient_reduction_in → ACR responders

dicarbonyl detoxification markers

measurement · ID: dicarbonyl_detoxification_markers
change_reversal
no difference observed

Relationships

  • no_difference_observed_in → FMD vs M-Diet

DNA-damage/repair markers

measurement · ID: dna_damage_repair_markers
change_reversal
no difference observed

Relationships

  • no_difference_observed_in → FMD vs M-Diet

HOMA-IR

measurement · ID: homa_ir
sustained_improvement
sustained improvement observed at follow-up

Relationships

  • improved_by → FMD
Source positions, MinHash and extraction warnings
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Previous KU: The FMD group experienced greater weight loss than the M-Diet group, though body composition remained unchanged between groups. Plasma MG-H1 levels decreased significantly in the FMD group after three cycles, but this change did not correlate with ACR reduction. Participants who showed a reduction in ACR (Area Under the Curve) in the group with FMD (Fat-induced Modalkrankheit) had higher initial ACR values compared to those who did not respond to the treatment. Only the reduction in HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) was maintained in the subsequent investigation.
Next KU: The study found that the fasting-mimicking diet (FMD) only reduced microalbuminuria in patients with type 2 diabetes and diabetic nephropathy, with effects reversing after refeeding. The reduction in microalbuminuria was comparable to that seen with SGLT-2 inhibitors, but FMD did not affect macroalbuminuria, suggesting a point of no return after established renal damage. The diet led to reduced medication use and improved metabolic control, which was attributed to the diet itself, though independent pathways may be involved.

KU 8 · source words 3,364–3,841

7 entities · 8 relationships · 7 preceding KUs available during extraction

Recorded context summary

The study found that the fasting-mimicking diet (FMD) only reduced microalbuminuria in patients with type 2 diabetes and diabetic nephropathy, with effects reversing after refeeding. The reduction in microalbuminuria was comparable to that seen with SGLT-2 inhibitors, but FMD did not affect macroalbuminuria, suggesting a point of no return after established renal damage. The diet led to reduced medication use and improved metabolic control, which was attributed to the diet itself, though independent pathways may be involved.

Fasting-Mimicking Diet (FMD)

method · ID: fasting_mimicking_diet_fmd
effect_on_microalbuminuria
reduction
effect_on_macroalbuminuria
no change
effect_on_ACR_overall_group
no change
effect_on_ACR_in_microalbuminuria_patients
reduction
effect_on_ACR_in_macroalbuminuria_patients
no change
effect_on_medication_use
Reducing medication to lower blood sugar and blood pressure
effect_on_glycemic_control
improved
effect_on_blood_pressure_control
improved
effect_on_albuminuria_after_refeeding
reversal of changes
effect_on_renal_function_parameters_long_term
no sustained effect

Relationships

  • comparable_to_SGLT2_inhibitors_on → reduction in microalbuminuria
  • attributed_to → improved metabolic control

SGLT-2 inhibitors

method · ID: sglt_2_inhibitors
effect_on_microalbuminuria
reduction
effect_on_macroalbuminuria
not specified
effect_on_ACR_in_microalbuminuria_patients
reduction
effect_on_ACR_in_macroalbuminuria_patients
not specified

Relationships

  • induction_of_mild_ketogenesis_orchestrates → nephroprotective effects

Macroalbuminuria

concept · ID: macroalbuminuria
status
established fibrosis and loss of renal architecture
implication
presumed point of no return

Relationships

  • not_affected_by → FMD

Acetylcarnitine levels (C2)

measurement · ID: acetylcarnitine_levels_c2
increase_during_fasting
pronounced activation of lipolysis
role_uncertainty
marker of high compliance or substrate for renal metabolism

Relationships

  • discriminates_between → responders and non-responders to ACR improvement

Glycine

concept · ID: glycine
role_in_responders
increase in concentration
protective_effect
on renal tubular injury
potential_mechanism
enhances Glo-1 function and restores antioxidant defense

Relationships

  • associated_with → normoalbuminuria in diabetes

Glo-1 activity in WBC

measurement · ID: glo_1_activity_in_wbc
change_in_study
no change observed

Relationships

  • potential_enhancement_by → glycine

Fatty acid oxidation and ketogenesis

other · ID: fatty_acid_oxidation_and_ketogenesis
role_in_nephroprotection
explained by kidney metabolism reliance on lipolysis and ketone bodies
model_entity_type
biological_process

Relationships

  • orchestrated_by → mild ketogenesis
Source positions, MinHash and extraction warnings
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Previous KU: The study found that the diet, which was similar to fasting, was safe and well-tolerated, with most participants reporting no negative side effects. It led to a reduction in the use of medications to lower blood sugar and blood pressure in the group that followed the fasting-like diet, compared to the group that followed a Mediterranean diet. The FMD also caused a transient increase in blood ketones and a distinct response in fatty acid oxidation markers among ACR responders.
Next KU: The study found that the lack of change in methylglyoxal detoxification pathways and DNA repair during fasting-mimicking diet cycles correlates with the rapid increase in albuminuria after refeeding. The authors suggest that a sustained metabolic redirection, rather than just caloric restriction, is responsible for the observed changes. The study highlights the complexity of fasting interventions in type 2 diabetes, noting that while the control group was isocaloric, the FMD group experienced greater weight loss, which was statistically adjusted for.

KU 9 · source words 3,842–4,333

11 entities · 14 relationships · 8 preceding KUs available during extraction

Recorded context summary

The study found that the lack of change in methylglyoxal detoxification pathways and DNA repair during fasting-mimicking diet cycles correlates with the rapid increase in albuminuria after refeeding. The authors suggest that a sustained metabolic redirection, rather than just caloric restriction, is responsible for the observed changes. The study highlights the complexity of fasting interventions in type 2 diabetes, noting that while the control group was isocaloric, the FMD group experienced greater weight loss, which was statistically adjusted for.

plasma methylglyoxal

other · ID: plasma_methylglyoxal
change_during_fmd
no change
model_entity_type
biomarker

Relationships

  • lack_of_change_in → dicarbonyl detoxification

dicarbonyl detoxification

other · ID: dicarbonyl_detoxification
pathways_observed
Glo-1 activity, pGlo-1 expression, hydroxyacetone
model_entity_type
metabolic_process

Relationships

  • lack_of_increase_in → Glo-1 activity or pGlo-1 expression in WBC
  • no_change_in → hydroxyacetone in RBC

Glo-1 activity or pGlo-1 expression in WBC

measurement · ID: glo_1_activity_or_pglo_1_expression_in_wbc
change_during_fmd
no increase

Relationships

  • reflects_lack_of_change_in → plasma methylglyoxal

hydroxyacetone in RBC

measurement · ID: hydroxyacetone_in_rbc
change_during_fmd
no change

Relationships

  • reflects_alternative_mg_detoxification_pathways → aldo-keto reductase

DNA-damage/repair

other · ID: dna_damage_repair
change_during_fmd
no reconstitution
model_entity_type
metabolic_process

Relationships

  • potential_explanation_for → rapid increase of ACR after termination of FMD

suPAR

other · ID: supar
change_after_fmd
fast increase
model_entity_type
biomarker

Relationships

  • marker_of → accelerated aging and senescence

Fasting-Mimicking Diet (FMD)

other · ID: fasting_mimicking_diet_fmd
duration_cycles
six
metabolic_effect
sustained redirection of metabolism
model_entity_type
dietary_intervention

Relationships

  • unlikely_to_be_only_due_to → reduced energy intake
  • requires_longer_period_for → nephropathy reversal

FMD group

other · ID: fmd_group
weight_loss
higher and significant compared to baseline and control group
model_entity_type
study_group

Relationships

  • experienced_greater_weight_loss_than → control group

control group

other · ID: control_group
diet_type
isocaloric
weight_loss
mild
model_entity_type
study_group

Relationships

  • received_isocaloric_diet_in_contrast_to → FMD group

albuminuria reduction

other · ID: albuminuria_reduction
overall_group_change
no significant change
subgroup_change
significant reduction in microalbuminuria
model_entity_type
clinical_outcome

Relationships

  • less_likely_affected_by → weight loss
  • persistent_at_refeeding → weight loss

microalbuminuria subgroup

other · ID: microalbuminuria_subgroup
baseline_predictor
development of diabetic nephropathy
model_entity_type
study_subgroup

Relationships

  • showed_significant_reduction_in → ACR
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Previous KU: The study found that the fasting-mimicking diet (FMD) only reduced microalbuminuria in patients with type 2 diabetes and diabetic nephropathy, with effects reversing after refeeding. The reduction in microalbuminuria was comparable to that seen with SGLT-2 inhibitors, but FMD did not affect macroalbuminuria, suggesting a point of no return after established renal damage. The diet led to reduced medication use and improved metabolic control, which was attributed to the diet itself, though independent pathways may be involved.
Next KU: The study concludes that the fasting-mimicking diet can reduce albuminuria and improve metabolic control in type 2 diabetes patients with microalbuminuria when combined with intensive diabetes care. The authors suggest that the lack of change in dicarbonyl detoxification and DNA-damage markers may cause albuminuria to relapse after six cycles, necessitating longer fasting periods. Future research should use larger cohorts and investigate renal cell metabolism, as the current study lacked kidney biopsies.

KU 10 · source words 4,334–4,701

7 entities · 8 relationships · 9 preceding KUs available during extraction

Recorded context summary

The study concludes that the fasting-mimicking diet can reduce albuminuria and improve metabolic control in type 2 diabetes patients with microalbuminuria when combined with intensive diabetes care. The authors suggest that the lack of change in dicarbonyl detoxification and DNA-damage markers may cause albuminuria to relapse after six cycles, necessitating longer fasting periods. Future research should use larger cohorts and investigate renal cell metabolism, as the current study lacked kidney biopsies.

Fasting-Mimicking Diet (FMD)

method · ID: fasting_mimicking_diet_fmd
effect_on_albuminuria
reduces microalbuminuria
effect_on_metabolic_control
improves glycemic and blood pressure control, sustained reduction in insulin resistance
relapse_mechanism
lack of changes in dicarbonyl detoxification and DNA-damage/repair markers
suggested_duration
They could potentially be continued for an extended period.

Relationships

  • integrated_with → intensive diabetes care
  • complementary_to → current guidelines

Type 2 diabetes patients with microalbuminuria

other · ID: type_2_diabetes_patients_with_microalbuminuria
condition
microalbuminuria
treatment_context
intensive diabetes care
model_entity_type
population

Relationships

  • benefited_by → Fasting-Mimicking Diet (FMD)

Dicarbonyl detoxification markers

measurement · ID: dicarbonyl_detoxification_markers
change_during_fasting
lack of changes
change_after_refeeding
lack of changes

Relationships

  • associated_with → relapse of albuminuria

DNA-damage/repair markers

measurement · ID: dna_damage_repair_markers
change_during_fasting
lack of changes
change_after_refeeding
lack of changes

Relationships

  • associated_with → relapse of albuminuria

Renal cell metabolism

concept · ID: renal_cell_metabolism
study_limitation
not explored
reason
no kidney biopsies collected

Relationships

  • future_research_focus → larger cohorts

Future studies

method · ID: future_studies
required_cohort_size
larger cohorts
required_focus
generalizability of dietary interventions

Relationships

  • address_effect_of → fasting regimes in albuminuria of type 2 diabetes patients

Incomplete lipid oxidation markers

measurement · ID: incomplete_lipid_oxidation_markers
effect_on_albuminuria_improvers
distinct effects observed

Relationships

  • potential_for → new therapeutic strategies
Source positions, MinHash and extraction warnings
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Previous KU: The study found that the lack of change in methylglyoxal detoxification pathways and DNA repair during fasting-mimicking diet cycles correlates with the rapid increase in albuminuria after refeeding. The authors suggest that a sustained metabolic redirection, rather than just caloric restriction, is responsible for the observed changes. The study highlights the complexity of fasting interventions in type 2 diabetes, noting that while the control group was isocaloric, the FMD group experienced greater weight loss, which was statistically adjusted for.
Next KU: End of paper