graph LR
Lifestyle_Modification["Lifestyle Modification"]
Pasteurized_Akkermansia_muciniphila_MucT_Supplementation["Pasteurized Akkermansia muciniphila MucT Supplementation"]
High_Calorie_Diet["High-Calorie Diet"]
LEP["LEP"]
MC4R["MC4R"]
Energy_Imbalance["Energy Imbalance"]
POMC["POMC"]
Obesogenic_Environment["Obesogenic Environment"]
Post_Weight_Loss_Weight_Regain["Post-Weight-Loss Weight Regain"]
Increased_Body_Mass_Index["Increased Body Mass Index"]
Intestinal_Barrier_Dysfunction_and_Metabolic_Endotoxemia["Intestinal Barrier Dysfunction and Metabolic Endotoxemia"]
LEPR["LEPR"]
GLP_1_GIP_Dual_Agonists["GLP-1/GIP Dual Agonists"]
Chronic_Low_Grade_Inflammation["Chronic Low-Grade Inflammation"]
Depletion_of_Mucosal_Symbiont_Akkermansia_muciniphila["Depletion of Mucosal Symbiont Akkermansia muciniphila"]
GLP_1_Receptor_Agonists["GLP-1 Receptor Agonists"]
Orlistat["Orlistat"]
Hypothalamic_Dysregulation["Hypothalamic Dysregulation"]
Bariatric_Surgery["Bariatric Surgery"]
Efficient_Intestinal_Energy_Harvest["Efficient Intestinal Energy Harvest"]
Naltrexone_Bupropion["Naltrexone-Bupropion"]
Depletion_of_Mucosal_Symbiont_Akkermansia_muciniphila --> Intestinal_Barrier_Dysfunction_and_Metabolic_Endotoxemia
Intestinal_Barrier_Dysfunction_and_Metabolic_Endotoxemia --> Chronic_Low_Grade_Inflammation
Efficient_Intestinal_Energy_Harvest --> Energy_Imbalance
Post_Weight_Loss_Weight_Regain --> Increased_Body_Mass_Index
High_Calorie_Diet --> Energy_Imbalance
Obesogenic_Environment --> Increased_Body_Mass_Index
Lifestyle_Modification --> Energy_Imbalance
GLP_1_Receptor_Agonists --> Hypothalamic_Dysregulation
GLP_1_Receptor_Agonists --> Energy_Imbalance
GLP_1_Receptor_Agonists --> Post_Weight_Loss_Weight_Regain
GLP_1_GIP_Dual_Agonists --> Energy_Imbalance
GLP_1_GIP_Dual_Agonists --> Post_Weight_Loss_Weight_Regain
Bariatric_Surgery --> Hypothalamic_Dysregulation
Bariatric_Surgery --> Energy_Imbalance
Orlistat --> Efficient_Intestinal_Energy_Harvest
Orlistat --> Post_Weight_Loss_Weight_Regain
Naltrexone_Bupropion --> Hypothalamic_Dysregulation
Pasteurized_Akkermansia_muciniphila_MucT_Supplementation --> Post_Weight_Loss_Weight_Regain
Pasteurized_Akkermansia_muciniphila_MucT_Supplementation --> Efficient_Intestinal_Energy_Harvest
Pasteurized_Akkermansia_muciniphila_MucT_Supplementation --> Intestinal_Barrier_Dysfunction_and_Metabolic_Endotoxemia
MC4R --> Hypothalamic_Dysregulation
LEP --> Hypothalamic_Dysregulation
LEPR --> Hypothalamic_Dysregulation
POMC --> Hypothalamic_Dysregulation
style Lifestyle_Modification fill:#fce7f3
style Pasteurized_Akkermansia_muciniphila_MucT_Supplementation fill:#fce7f3
style High_Calorie_Diet fill:#dcfce7
style LEP fill:#f3e8ff
style MC4R fill:#f3e8ff
style Energy_Imbalance fill:#dbeafe
style POMC fill:#f3e8ff
style Obesogenic_Environment fill:#dcfce7
style Post_Weight_Loss_Weight_Regain fill:#dbeafe
style Increased_Body_Mass_Index fill:#fef3c7
style Intestinal_Barrier_Dysfunction_and_Metabolic_Endotoxemia fill:#dbeafe
style LEPR fill:#f3e8ff
style GLP_1_GIP_Dual_Agonists fill:#fce7f3
style Chronic_Low_Grade_Inflammation fill:#dbeafe
style Depletion_of_Mucosal_Symbiont_Akkermansia_muciniphila fill:#dbeafe
style GLP_1_Receptor_Agonists fill:#fce7f3
style Orlistat fill:#fce7f3
style Hypothalamic_Dysregulation fill:#dbeafe
style Bariatric_Surgery fill:#fce7f3
style Efficient_Intestinal_Energy_Harvest fill:#dbeafe
style Naltrexone_Bupropion fill:#fce7f3
graph LR
Sleep_Fragmentation["Sleep Fragmentation"]
MAPK_Cascade_Activation["MAPK Cascade Activation"]
NLRP3_Inflammasome_Activation["NLRP3 Inflammasome Activation"]
Ocular_Surface_Inflammation_and_Dry_Eye_Disease["Ocular Surface Inflammation and Dry Eye Disease"]
CPAP["CPAP"]
Non_Anatomic_Endotypic_Traits["Non-Anatomic Endotypic Traits"]
Sympathetic_Overactivation["Sympathetic Overactivation"]
Intermittent_Hypoxia["Intermittent Hypoxia"]
Systemic_Inflammation["Systemic Inflammation"]
TLR4_Upregulation["TLR4 Upregulation"]
Upper_Airway_Collapse["Upper Airway Collapse"]
MyD88_Dependent_NF_κB_Activation["MyD88-Dependent NF-κB Activation"]
Upper_Airway_Collapse --> Sleep_Fragmentation
Upper_Airway_Collapse --> Intermittent_Hypoxia
Intermittent_Hypoxia --> TLR4_Upregulation
Intermittent_Hypoxia --> Sympathetic_Overactivation
Intermittent_Hypoxia --> Systemic_Inflammation
Intermittent_Hypoxia --> Ocular_Surface_Inflammation_and_Dry_Eye_Disease
TLR4_Upregulation --> MyD88_Dependent_NF_κB_Activation
TLR4_Upregulation --> MAPK_Cascade_Activation
MyD88_Dependent_NF_κB_Activation --> Systemic_Inflammation
MyD88_Dependent_NF_κB_Activation --> NLRP3_Inflammasome_Activation
MAPK_Cascade_Activation --> Systemic_Inflammation
Sleep_Fragmentation --> Intermittent_Hypoxia
Non_Anatomic_Endotypic_Traits --> Sleep_Fragmentation
Non_Anatomic_Endotypic_Traits --> Upper_Airway_Collapse
NLRP3_Inflammasome_Activation --> Systemic_Inflammation
CPAP --> Sleep_Fragmentation
CPAP --> Upper_Airway_Collapse
style Sleep_Fragmentation fill:#dbeafe
style MAPK_Cascade_Activation fill:#dbeafe
style NLRP3_Inflammasome_Activation fill:#dbeafe
style Ocular_Surface_Inflammation_and_Dry_Eye_Disease fill:#dbeafe
style CPAP fill:#fce7f3
style Non_Anatomic_Endotypic_Traits fill:#dbeafe
style Sympathetic_Overactivation fill:#dbeafe
style Intermittent_Hypoxia fill:#dbeafe
style Systemic_Inflammation fill:#dbeafe
style TLR4_Upregulation fill:#dbeafe
style Upper_Airway_Collapse fill:#dbeafe
style MyD88_Dependent_NF_κB_Activation fill:#dbeafe
name: com_Obesity__Obstructive_Sleep_Apnea
creation_date: "2026-08-19T00:00:00Z"
curation_status: CANDIDATE
notes: >-
Split out of `kb/disorders/Obstructive_Sleep_Apnea.yaml`'s `environmental:`
block (dismech#8551): that entry listed `Obesity` as an "exposure" acting on
obstructive sleep apnea (OSA), but obesity is a first-class `Disease` entry
in its own right (`kb/disorders/Obesity.yaml`), a body state rather than
something external to the organism the patient is exposed to. Modeling the
relationship as a disease-disease comorbidity avoids a near-tautological
"exposure" edge that ECTO/XCO can never bind a term for. Directionality is
A_BEFORE_B: weight gain is shown prospectively to precede and predict
worsening sleep-disordered breathing, and weight loss predicts improvement,
supporting obesity as a modifiable antecedent risk state for OSA. Evidence
is carried over unchanged from the original `environmental:` entry rather
than dropped. The reciprocal arm is deliberately not modeled: OSA also
promotes weight gain through sleep fragmentation, daytime somnolence and
leptin resistance, so the real relationship is bidirectional. A_BEFORE_B is
recorded because the cited prospective cohort measures only the
weight-to-SDB direction, and the weight-loss finding quoted below is that
same direction inverted rather than the reverse arm. A B_BEFORE_A record
would need its own source.
disease_a:
slug: Obesity
preferred_term: obesity disorder
term:
id: MONDO:0011122
label: obesity disorder
disease_b:
slug: Obstructive_Sleep_Apnea
preferred_term: obstructive sleep apnea syndrome
term:
id: MONDO:0007147
label: obstructive sleep apnea syndrome
directionality: A_BEFORE_B
effect_direction: RISK
hypotheses:
- description: >-
Increased adiposity, particularly upper-airway and visceral fat
deposition, narrows the pharyngeal airway and increases its
collapsibility during sleep; weight gain prospectively predicts
worsening sleep-disordered breathing and weight loss predicts
improvement, supporting obesity as a modifiable antecedent risk state
for obstructive sleep apnea.
evidence:
- reference: PMID:11122588
reference_title: "Longitudinal study of moderate weight change and sleep-disordered breathing"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "A 10% increase in weight predicted a 6-fold (95% CI, 2.2-17.0) increase in the odds of developing moderate-to-severe SDB"
explanation: >-
Wisconsin Sleep Cohort, measured prospectively at 4-year intervals. The
reciprocal finding -- 10% weight loss predicting a 26% AHI reduction --
is what makes this exposure modifiable rather than merely associated.
Carried over unchanged from the original
`Obstructive_Sleep_Apnea.yaml` `environmental:` entry.
association_signals:
- source: LITERATURE
method: LITERATURE_ASSOCIATION
population: >-
Wisconsin Sleep Cohort: 690 randomly selected employed Wisconsin residents
(mean age 46 at baseline, 56% male), evaluated twice at four-year intervals
between July 1989 and January 2000.
directionality: A_BEFORE_B
effect_direction: RISK
statistics:
metrics:
- metric_type: OR
metric_value: 6.0
metric_ci_lower: 2.2
metric_ci_upper: 17.0
notes: >-
Odds of developing moderate-to-severe sleep-disordered breathing
(apnea-hypopnea index at or above 15 events per hour) per 10% weight
gain, relative to stable weight. The wide interval is the small cohort,
not a weak signal. Measured prospectively, so the exposure precedes the
outcome by design rather than by assumption.
evidence:
- reference: PMID:11122588
reference_title: "Longitudinal study of moderate weight change and sleep-disordered breathing"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "A 10% increase in weight predicted a 6-fold (95% CI, 2.2-17.0) increase in the odds of developing moderate-to-severe SDB"
explanation: >-
States the effect size recorded in the metric above, in a cohort
followed forward from a disease-free baseline.