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
- Source title
- A six-month periodic fasting reduces microalbuminuria and improves metabolic control in patients with type 2 diabetes and diabetic nephropathy: a randomized controlled study
- Source authors
- Alba Sulaj; Stefan Kopf; Ekaterina Von Rauchhaupt; Elisabeth Kliemank; Maik Brune; Zoltan Kender; Hannelore Bartl; Fabiola Garcia Cortizo; Katarina Klepac; Zhe Han; Varun Kumar; Valter Longo; Aurelio Teleman; Jürgen G Okun; Jakob Morgenstern; Thomas Fleming; Julia Szendroedi; Stephan Herzig; Peter P Nawroth
- KU document title
- A six-month periodic fasting reduces microalbuminuria and improves metabolic control in patients with type 2 diabetes and diabetic nephropathy: a randomized controlled study
- KU document author field
- Not populated by the original extractor
- Style annotation
- No dedicated document-style field in this schema
- KU sequence
- 10 of 10 expected chunks
- Attribution provenance
- Source registry metadata shown for attribution; not added to the QA context
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.
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.
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 nephropathyaimed_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 dietreduced_microalbuminuria_in → patients with microalbuminuriareduced_homa_ir_in → patients with microalbuminuriareduced_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
Source positions, MinHash and extraction warnings
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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 → fibrosisimplicated_in → dicarbonyl stress and AGEassociated_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, inflammationsupports → cellular protectionactivates → lipolysisaimed_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 Heidelbergapproved_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
Source positions, MinHash and extraction warnings
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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
Source positions, MinHash and extraction warnings
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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 cyclescomprises → 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 cyclesmeasured_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 cyclesmeasured_at → Six diet cycles
Fatty acid oxidation marker
concept · ID: fatty_acid_oxidation_marker- component
- Plasma AC profile
Relationships
measured_at → Three diet cyclesmeasured_at → Six diet cycles
DNA-damage/repair marker
concept · ID: dna_damage_repair_marker- component
- yH2Ax expression in WBC
Relationships
measured_at → Three diet cyclesmeasured_at → Six diet cycles
Kidney injury and senescence marker
concept · ID: kidney_injury_and_senescence_marker- component
- suPAR
Relationships
measured_at → Three diet cyclesmeasured_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
Source positions, MinHash and extraction warnings
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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
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
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 groupshows_no_change_in → body compositionshows_no_association_between → plasma MG-H1 change and ACR changeshows_higher_baseline_ACR_than → FMD non-respondersshows_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) groupshows_no_change_in → body compositionshows_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 groupshow_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 groupshow_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-IRno_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
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 → FMDtransient_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
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 microalbuminuriaattributed_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
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 WBCno_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 intakerequires_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 losspersistent_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
Source positions, MinHash and extraction warnings
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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 carecomplementary_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