One might initially be surprised to learn that patients with lipedema tend to have favorable metabolic profiles—lower Hba1c, an M2 macrophage anti-inflammatory phenotype (unlike the M1 inflammatory phenotype of obesity), and less visceral fat than BMI-matched controls. [1,2] How is this possible when we see progressive adipose expansion, pain, and edema?
A 2022 study (Nankam et al) showed people with lipedema had higher adiponectin, a hormone which enhances systemic insulin sensitivity by directly increasing hepatic and skeletal muscle glucose uptake and suppressing gluconeogenesis. This could explain the lower HbA1c, however a 2026 study has challenged this association finding no significant difference between adiponectin levels in the lipedema cohort and BMI-matched controls.[3] This was a fairly small study, but there at least appears to be more to the story behind this metabolic paradox.
Lipedema tissue is characterized by fibrosis, adipocyte hypertrophy, and hypoxia which can lead to localized insulin resistance—different from systemic insulin resistance. Fibrosis causes mechanical stress on adipocytes causing altered metabolic function. As adipocytes get larger, they become more hypoxic, leading to more fibrosis and insulin resistance. [4,5]
The affected tissue in lipedema is subcutaneous adipose tissue, sparing the abdomen and avoiding portal delivery of free fatty acids and inflammatory mediators that would result in hepatic and systemic insulin resistance that we see with more abdominal adiposity and visceral fat.[6] This uncoupling of localized and systemic insulin resistance may not only help explain why there are more favorable metabolic profiles, but also why lipedema fat is resistant to diet and exercise. Standard caloric restriction and even bariatric surgery leave the lipedema tissue unaffected.
Understanding these seemingly paradoxical differences in the metabolism of lipedema tissue and systemic effects compared to obesity could eventually lead to more targeted treatments, rather than trying to force lipedema to respond to traditional obesity treatments which are ineffective for lipedema.
Sources
- Nankam PA, Lavoie ME, Boudreau A, et al. Is subcutaneous adipose tissue expansion in people living with lipedema healthier and reflected by circulating parameters? Front Endocrinol (Lausanne). 2022;13:1000094. doi:10.3389/fendo.2022.1000094
- Felmerer G, Aschenbach R, Stepniewski A, et al. Increased arteriogenesis and lymphangiogenesis in lipedema characteristics. J Vasc Res. 2020;57(5):229-236. doi:10.1159/000507973
- Kempa S, Weiss TS, Tews HC, et al. Reduced serum endostatin in premenopausal women with lipedema suggests altered vascular homeostasis. Diseases. 2026;14(7):168. doi:10.3390/diseases14070168
- Kruppa, P., Gohlke, S., Łapiński, K., Garcia-Carrizo, F., Soultoukis, G. A., Infanger, M., Schulz, T. J., & Ghods, M. (2023). Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis. Frontiers in Immunology, 14, 1223264. https://doi.org/10.3389/fimmu.2023.1223264
- Poojari, A., Dev, K., & Rabiee, A. (2022). Lipedema: Insights into Morphology, Pathophysiology, and Challenges. Biomedicines, 10(12), 3081. https://doi.org/10.3390/biomedicines10123081
- Gruber H, Bauer J, Lipb A, et al. Subcutaneous adipose tissue dysfunction in lipedema: inflammation, hypoxia, and preserved systemic metabolic health. Int J Mol Sci. 2021;22(18):10012. doi:10.3390/ijms221810012
