Project: The association between Lipedema and cardiometabolic health: Translational epidemiologic research

Principal Investigator: Ioanna Yiannakou, PhD, MS, RD
Preventive Medicine & Epidemiology
Postdoctoral Associate
Boston University Chobanian and Avedisian School of Medicine
Boston, MA, United States

Summary

This project aims to establish the first clinical definition of Lipedema phenotype using a scalable physician-led remote assessment framework in a community-based U.S. cohort and determine its association with cardiometabolic health. Leveraging the Framingham Heart Study, this work will improve Lipedema identification, determine its true prevalence, and cardiometabolic comorbidity.

Background

There are currently no gold standard criteria for diagnosing Lipedema. Lipedema has not been previously assessed in the community, and thus its true prevalence is still unknown. Further, early-stage Lipedema presents with lower-body subcutaneous adiposity, but progression may involve increased abdominal visceral fat. Although Lipedema is thought to have lower cardiometabolic risk due to its gynoid fat distribution, its relationship to cardiometabolic outcomes remains unclear.

Methodology

Using a clinical epidemiological study design within the Framingham Heart Study (FHS), this study will: (1) Develop a clinical definition of Lipedema phenotype through a remote standardized assessment framework, and compare its performance against dual-energy X-ray absorptiometry (DXA); (2) Examine associations of both phenotype assessment approaches with cardiometabolic biomarkers and conditions cross-sectionally and over time.

Eligible female participants will complete a modified image-based screening questionnaire, including previously validated and new screening questions, selection of body sample images, and upload of leg photographs that FHS physicians will review remotely following a standardized framework to confirm a remote clinical definition of Lipedema phenotype. Medical records will validate self-reported diagnosis. Diagnostic performance will be evaluated against five DXA-indexes through ROC analyses (nested case-control). Associations with cardiometabolic risk will be evaluated using multivariable linear and Cox regression models in pooled and cohort-specific samples. Effect modification by adiposity and menopausal status will be tested.

Expected outcomes

We hypothesize that the newly-derived clinical definition of Lipedema phenotype will perform comparatively well against a DXA-derived phenotype. Additionally, females with Lipedema phenotype and higher abdominal adiposity will exhibit the most adverse cardiometabolic profile compared to females without Lipedema and with lower abdominal adiposity (reference group). Females with Lipedema but lower abdominal adiposity, as well as those without Lipedema but with higher abdominal adiposity, will have an intermediate cardiometabolic risk, worse than the reference group but less severe than those with both Lipedema and higher abdominal adiposity.

Practical implementations of results

This study will pioneer a scalable, remote standardized framework to define the Lipedema phenotype and establish a more accessible alternative to existing DXA-based modalities. The project will determine Lipedema prevalence in a community-based cohort, improve understanding of its cardiometabolic consequences, and advance approaches for disease assessment. Ultimately, this work will provide clinicians and patients with clearer diagnostic guidance, identify when formal imaging is warranted, and support future prevention and treatment strategies for this understudied condition.

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