In our 2022 research roundup, we’re looking ahead as much as we’re looking back. After celebrating 50 research publications in 2021, we’ve still only begun to tease apart some of the most complex questions facing researchers, clinicians, and patients.

We’re proud that Lipedema research continues to accelerate. In fact, more than half of Lipedema studies ever completed have been published in the last 4.5 years. The rigor and quality of studies continue to improve, delivering more meaningful findings that offer paths to future treatments. With growth, however, comes a responsibility to set new benchmarks for future work. As we ask more of the research in 2023, sponsors and journals may refine their priorities and help shape an exciting roadmap for high quality discoveries.

This post highlights some of the most critical findings from 2022, organized by theme to help summarize and guide specific areas with promise for people with Lipedema.

Living with Lipedema

Quality of life (QOL), or the experience of well-being, can mean many different things to people with Lipedema. Our field needs validated Lipedema-specific QOL measures that can objectively assess the impact of Lipedema and potential treatments.

Pain is one aspect of QOL where researchers made some progress in 2022. Although pain can significantly reduce QOL, Lipedema pain is not straightforward to characterize. The standard 10-point pain scale does not adequately describe the different types of pain that people report (e.g., aching, burning, sharp). Researchers sought methods to reliably assess what causes various experiences of pain in order to discover what treatments may help.

Skin hypersensitivity was one form of Lipedema pain that researchers explored, and it is worthy of a deeper dive. One LF-funded study found that nerve cell density on the skin is reduced on the abdomen, but not the thigh. However, patients experienced heightened thigh skin sensitivity compared to people without Lipedema, and patterns of sensitivity were stage-dependent [1]. People did not always feel more pain in areas with more adipose tissue (body fat), suggesting that Lipedema pain may have a systemic (whole body) component. Findings also indicate that the immune system may play a role in Lipedema pain. Pursuing these promising leads could help improve efforts to locate the sources of Lipedema pain and define potential pathways for treating it.

Diverse experiences of Lipedema

To broaden our understanding of Lipedema and gather diverse patient experiences, we created the Lipedema Foundation Registry in 2019. Last year, the LF Registry First Look presented findings from the first 521 participants who completed the survey [2]. We learned that some people report Lipedema-like symptoms throughout their bodies, not just on arms and legs, and that some women report having male relatives with Lipedema-like symptoms. Both findings remind us that we need more research into how Lipedema is expressed in different people (a kind of research called phenotyping).

Several other studies confirmed the importance of socioeconomic and demographic factors, in particular—ranging from age of onset to income. One showed that women with adolescent onset of Lipedema scored better on a measure of mental health than those with onset in adulthood, but older women and women with higher education scored higher on a measure of coping ability. [3] A second study showed that although people with Lipedema were generally more likely to experience physical and mental limitations and negative experiences with healthcare, stage 3-4 patients reported worse social and physical impairment, in turn decreasing their ability to exercise, be employed, and have positive healthcare experiences [4]. Another study highlighted the importance of looking closely at common comorbidities, or conditions that tend to occur at the same time as Lipedema, such as lymphatic conditions [5].

Findings like these reinforce the importance of our mission to improve awareness of Lipedema among patients and healthcare providers. We need more doctors to understand Lipedema, but we also need to dig deeper in future research to better tailor management and support for more kinds of Lipedema patients.

Genetic risk assessments

Researchers generally agree that genes likely play a role in Lipedema development. Our LF Registry First Look findings support that Lipedema can be passed down between generations, with 49.01% of patients reporting a parent with suspected Lipedema, and 11.58% reporting a parent with a confirmed diagnosis [2]. However, we don’t yet know which gene or genes are responsible for raising a person’s risk.

Patients likely to have a close relative with Lipedema [2]

LF is proud to have supported two milestone 2022 publications that have begun to sort out these questions. These publications offer the field’s first two genome-wide association studies (GWAS)—a type of study that examines any genetic changes that could be associated with Lipedema. The first milestone study identified a possible link to genes related to estrogen (sex hormone signaling) and adipose regulation [6]. Another study replicated these findings and revealed significant relationships with two loci linked to blood vessel formation (VEGF and GRB14-COBLL1) [7].

More work remains to show that the linked genes are not just statistically associated with Lipedema but play a role in its development. Each genetic study will strengthen our research foundation and help pinpoint Lipdema’s genetic and molecular causes. Eventually, this advanced understanding could lead to the development of a genetic test for Lipedema risk assessment.

Imaging and diagnostics

Many doctors are unfamiliar with the characteristics of Lipedema, and even those who are familiar with Lipedema have inadequate tools available to diagnose it. Patients pay for these issues with delayed diagnoses. For this reason, doctors need more finely tuned objective tools to reliably diagnose Lipedema and enable earlier intervention. Research in 2022 explored some emerging tools that can help us sharpen the focus of future research:

DEXA (dual x-ray absorptiometry): This platform assesses body composition (the ratio of adipose tissue to muscle), which holds promise as a diagnostic approach. One recent study defined optimal cut-off values for fat mass indices independent of Lipedema stage and type [8].
Lymphangiography: Visualizing the lymphatic system might help settle the longstanding debate about the role of lymphatic function in Lipedema. Some studies indicate that edema, or excess fluid, contributes to Lipedema (hence the name), putting it in the same category of conditions as lymphedema, a reported comorbidity in 29% of women [2]. Other studies (about a third) suggest that edema is so minor that it is unlikely to be clinically significant. So where do we land? In the last 2 years, 6 out of 8 studies pointed to edema as a meaningful factor. In 2022, 3 studies—including 2 funded by LF—supported lymphatic imaging as a tool to help distinguish between patterns of edema in Lipedema and lymphedema [9,10,11].

Nutrition and metabolism

We know that Lipedema is not the same as obesity, but we need to better understand the contribution of metabolic factors to get people the right treatments. One 2022 study provided the best data to date that metabolism may in fact be altered, but in an unexpected way.

The study showed that women with Lipedema have normal glucose metabolism (the conversion of carbohydrates into energy), which suggests that typical weight management strategies may not be relevant for Lipedema patients. However, it also found higher levels of cholesterol (including higher levels of low-density lipoprotein (LDL) and systemic inflammation markers (an indication of immune response throughout the entire body) [12]. Previously, inflammation was thought to be localized to the affected tissue. These nuanced findings point to an important interaction between metabolic and immune factors that can help lead to more precise future research.

Immune function in Lipedema

The immune system is a hot topic of Lipedema research—emerging in studies of pain, metabolism, and more. Macrophages are a type of immune cell detected in tissue affected by Lipedema, but it’s not clear why and how their buildup occurs and what it means for patients. Determining the direction of causality (whether macrophage accumulation causes Lipedema or is caused by Lipedema) will help disentangle the complex interplay between immune function, metabolism, and adipose proliferation.

In one LF-funded study, researchers took activated macrophages and put them in laboratory conditions with adipose stem cells and found that macrophages changed the proliferation and differentiation of the stem cells (how they multiply and develop into other cell types) [13]. When a drug that affects macrophages was added, cells stopped accumulating lipids (fatty compounds like cholesterol and triglyceride). While these findings don’t prove that macrophages cause Lipedema, they do set the stage for deeper dives in 2023 and beyond.

Lipedema treatment

For patients, the significance of research often comes down to treatment options. Several studies upheld compression as an effective non-surgical treatment modality [14,15,16]. Both compression garments and machine-assisted compression can deliver benefits for QOL and potential changes to body composition.

We’ve learned that compression can lead to pain reduction and often limb volume changes, but these changes may need to be somewhat large to be perceptible by patients. This means that if studies use crude measurements or have high variability in their patient populations, they may not be able to detect even relatively significant changes in volume. This finding can help improve the design of future studies.

Other potential benefits of compression to explore include changes in skin thickness, tissue sodium, and even skin temperature. We’ll also need to investigate which treatment outcomes are most important to diverse groups of patients.

Looking to the future

As our body of research grows, we’re learning more about what questions we need to answer, how we can answer them, and what standards we need to apply in designing and funding new studies. Our field is undergoing a renaissance and a refinement; we’re asking more specific questions that get closer to the core of the complex and often misunderstood condition of Lipedema. We need to listen to people who live with Lipedema and do more work to understand what outcomes translate into meaningful benefits.

Growing the Lipedema Foundation

A comparison of criteria for Lipedema diagnosis [17]

2022 was a year of milestones for LF: We issued more than a dozen new awards, launched a new request for proposals (RFP), and went live with Legato and Legwork, our resources for finding publications and clinical trials. We published the LF Registry First Look – a formalized patient engagement report – which now includes over 700 responses, and developed a Patient’s Bill of Rights to help guide people through the landscape of Lipedema diagnosis and treatment. We completed a massive comparison of diagnostic criteria and shared facts and resources during June’s Lipedema Awareness Month. We attended conferences, retreats, and networking events to develop partnerships to serve patients, culminating in December’s three-day Scientific Retreat in Virginia.

Above all, we remain committed to supporting collaborative research that addresses the gaps in the field and look forward to another great year that helps improve the lives of people with Lipedema.

CITED REFERENCES AND LINKS

(1) Chakraborty, A., Crescenzi, R., Usman, T. A., Reyna, A. J., Garza, M. E., Al-Ghadban, S., Herbst, K. L., Donahue, P. M. C., & Rutkowski, J. M. (2022). Indications of Peripheral Pain, Dermal Hypersensitivity, and Neurogenic Inflammation in Patients with Lipedema.

(2) Lipedema Foundation. First Look Registry Report. Accessed February 13, 2023 .

(3) Falck, J., Rolander, B., Nygårdh, A., Jonasson, L.-L., & Mårtensson, J. (2022). Women with lipoedema: a national survey on their health, health-related quality of life, and sense of coherence.

(4) Clarke, C., Kirby, J. N., Smidt, T., & Best, T. (2022). Stages of lipoedema: experiences of physical and mental health and health care.

(5) Rockson, S. G., Zhou, X., Zhao, L., Hosseini, D. K., Jiang, X., Sweatt, A. J., Kim, D., Tian, W., Snyder, M. P., & Nicolls, M. R. (2022). Exploring disease interrelationships in patients with lymphatic disorders: A single center retrospective experience.

(6) Grigoriadis, D., Sackey, E., Riches, K., Zanten, M. van, Brice, G., England, R., Mills, M., Dobbins, S. E., Lipoedema Consortium, G. E. R. C., Jeffery, S., Dong, L., Savage, D. B., Mortimer, P. S., Keeley, V., Pittman, A., Gordon, K., Ostergaard, P., & Lee, L. L. (2022). Investigation of clinical characteristics and genome associations in the ‘UK Lipoedema’ cohort.

(7) Klimentidis, Y. C., Chen, Z., Gonzalez-Garay, M. L., Grigoriadis, D., Sackey, E., Pittman, A., Ostergaard, P., & Herbst, K. L. (2022). Genome-wide association study of a lipedema phenotype among women in the UK Biobank identifies multiple genetic risk factors.

(8) Buso, G., Favre, L., Vionnet, N., Gonzalez-Rodriguez, E., Hans, D., Puder, J. J., Dubath, C., Eap, C.-B., Raffoul, W., Collet, T.-H., & Mazzolai, L. (2022). Body Composition Assessment by Dual-Energy X-Ray Absorptiometry: A Useful Tool for the Diagnosis of Lipedema.

(9) Crescenzi, R., Donahue, P. M. C., Garza, M., Patel, N. J., Lee, C., Guerreso, K., Hall, G., Luo, Y., Chen, S., Herbst, K. L., Pridmore, M., Aday, A. W., Beckman, J. A., & Donahue, M. J. (2022). Subcutaneous Adipose Tissue Edema in Lipedema Revealed by Noninvasive 3T MR Lymphangiography.

(10) Zaleska, M. T., Olszewski, W. L., & Krzesniak, N. E. (2022). Lower Limb Lipedema-Superficial Lymph Flow, Skin Water Concentration, Skin and Subcutaneous Tissue Elasticity.

(11) Rasmussen, J. C., Aldrich, M. B., Fife, C. E., Herbst, K. L., & Sevick-Muraca, E. M. (2022). Lymphatic function and anatomy in early stages of lipedema.