Lipedema: friend and foe
Item Type Article
Authors Torre, Yanira Sanchez-De la; Wadeea, Rita; Rosas, Victoria;
Herbst, Karen L
Citation Hormone Molecular Biology and Clinical Investigation, Volume
33, Issue 1, 20170076, ISSN (Online) 1868-1891, DOI: https://
doi.org/10.1515/hmbci-2017-0076.
DOI 10.1515/hmbci-2017-0076
Publisher WALTER DE GRUYTER GMBH
Journal HORMONE MOLECULAR BIOLOGY AND CLINICAL
INVESTIGATION
Rights Copyright © 2018 Walter de Gruyter GmbH, Berlin/Boston.
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Link to Item http://hdl.handle.net/10150/636233
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Original Article
Yanira Sanchez-De la Torre
1
/ Rita Wadeea
1
/ Victoria Rosas
2
/ Karen L. Herbst
1
Lipedema: friend and foe
Abstract:
Background: Lipedema is a chronic disorder presenting in women during puberty or other times of hormonal
change such as childbirth or menopause, characterized by symmetric enlargement of nodular, painful subcuta-
neous adipose tissue (fat) in the limbs, sparing the hands, feet and trunk. Healthcare providers underdiagnose
or misdiagnose lipedema as obesity or lymphedema.
Materials and methods: The benets (friend) and negative aspects (foe) of lipedema were collected from pub-
lished literature, discussions with women with lipedema, and institutional review board approved evaluation
of medical charts of 46 women with lipedema.
Results: Lipedema is a foe because lifestyle change does not reduce lipedema fat, the fat is painful, can become
obese, causes gait and joint abnormalities, fatigue, lymphedema and psychosocial distress. Hypermobility as-
sociated with lipedema can exacerbate joint disease and aortic disease. In contrast, lipedema fat can be a friend
as it is associated with relative reductions in obesity-related metabolic dysfunction. In new data collected, li-
pedema was associated with a low risk of diabetes (2%), dyslipidemia (11.7%) and hypertension (13%) despite
an obese average body mass index (BMI) of 35.3 ± 1.7 kg/m
2
.
Conclusion: Lipedema is a painful psychologically distressing fat disorder, more foe than friend especially
due to associated obesity and lymphedema. More controlled studies are needed to study the mechanisms and
treatments for lipedema.
Keywords: gynoid fat, hypermobility, lipedema, lymphedema, women
DOI: 10.1515/hmbci-2017-0076
Received: November 9, 2017; Accepted: December 28, 2017
Introduction
Lipedema (lipoedema in Europe) is a chronic condition of painful fat transmitted in an autosomal dominant
matter with a sex preference for women [1] that manifests as symmetrical enlargement of the limbs, sparing
the hands, feet and trunk [2]. Men with lipedema have been reported in the literature only as case reports and
tend to have conditions associated with higher estrogen and lower relative testosterone levels, such as male
hypogonadism and liver disease [3], [4], [5]. What makes lipedema fat unique is that it is resistant to reduction
by diet and exercise called “persistent fat”; in fact loss of non-lipedema fat can result in a dramatic size disparity
between the trunk and enlarged fat on the limbs.
Lipedema fat was rst described by Drs. Allen and Hines in 1940 as offering “abnormally poor resistance to the
passage of uid into the tissue from the blood thus permitting edema to occur” [6]. This denition suggests lipedema is
a connective tissue disorder where loss of elastic recoil in adipose tissue allows uid to collect rather than exit
into lymphatics. This loss of recoil is seen when dye is injected into lipedema tissue; instead of forming a small
rounded spot before entering lymphatics, the dye seeps into the tissue forming ame-like structures [7]. A 1.5
million base pair deletion of chromosomal 7q11.23 resulting in the loss of a series of genes including ELN for
elastin, an important component of connective tissue, results in Williams syndrome, a constellation of signs and
symptoms including a lipedema phenotype in both males and females [8]. The association of lipedema tissue
with loss of elasticity supports lipedema as a connective tissue disorder, though because of the complexity of
adipose tissue, other connective tissue mutations or mutations affecting connective tissue structure are likely
important in lipedema as well. Consistent with loss of elasticity, aortic stiffness develops in Williams syndrome
[9] and in lipedema [10]. Increases in uid and fat in the area of lipedema can result in deformations of the
tissue (Figure 1) hindering ambulation and self-care.
Karen L. Herbst
1
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Figure 1: Woman with Stage 3 lipedema and genu valgum of the right knee and overpronation of the right foot.
The medial thigh and knee lipedema fat tissue likely contributed to stress on both legs. Photo by Dr. med. Josef J. Stutz.
Lipedema is underdiagnosed by healthcare providers and is often misdiagnosed as obesity or lymphedema.
The name, lipedema, sounds like lipidemia or lipemia, alteration of blood fats, increasing confusion when
patients bring up lipedema and providers hear a different diagnosis. The prevalence and incidence of lipedema
are unknown though it is thought to be common; lymphedema and lymphatic and vascular clinics report a
prevalence rate for lipedema of 6.5–18.8% in their patients [1], [11], [12], [13], [14], [15], [16], [17]. A small study
in Germany of 62 women in a single company resulted in a prevalence rate for lipedema of 9.7% [18].
Lipedema generally manifests during puberty, although it can appear at other times of hormonal change
such as childbirth or menopause. This evidence plus the predominant occurrence of lipedema in females sug-
gests importance of sex hormones in the development of this disorder. Indeed, the distribution of lipedema fat
is in the female gynoid distribution (lower abdomen, hips, buttocks, thighs and lower leg), resulting in dispro-
portion between the upper and lower body with a waist to hip ratio <1. Lipedema fat is present on the arms in
80% of women with lipedema [2], but the gynoid distribution of lipedema fat dominates. There are three stages
of lipedema and four types (Figure 2). The skin in lipedema can be smooth but the underlying fat is increased
and contains pearl-sized nodules (Stage 1); or the skin can be indented over pearl-sized fat nodules and larger
fat masses (Stage 2); or the skin can contain divots and folds over pearl-sized fat and larger fat masses with
characteristic deforming fat lobules (Stage 3). Stage 4 is characterized by the development of lymphedema with
lipedema better known as lipolymphedema and can occur with any stage [2]. Approximately 80% of women
with lipedema have lipedema fat on their arms (Type IV) therefore this type of lipedema occurs jointly with
lipedema affecting the legs. Lipedema fat can occur around the hips and buttocks (Type I), waist to knees like
riding breeches (Type II) or waist to the ankles (Type III). It is rare to see lipedema fat dominate on the lower
legs (Type V) [19].
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Figure 2: There are three stages and ve types of lipedema.
In Stage 1, the skin is smooth but there are pearl-sized nodules in the fat underneath. In Stage 2, there is retraction of the
skin due to brosis of connective tissue bers surrounding fat lobules and pearl-sized and larger masses in the fat tis-
sue. In Stage 3, there are pearl-sized nodules, larger masses and lobules of the skin and fat. The fourth Stage in lipedema
is not shown, as it is the development of lymphedema that can occur at any stage. Lymphedema occurs in Stage 3 more
than Stage 2 or Stage 1 and is known as lipo-lymphedema [20]. Five Types describe the location of lipedema fat. Type IV is
found often combined with Type II or III.
This paper will highlight the benets and the downsides, the friend and foe aspects, of lipedema.
Methods
This study was approved by the University of Arizona human subjects protection program. The following bene-
ts and downsides of lipedema were collected from discussions during clinic visits with women with lipedema
on benets (friend) and downsides (foe) of lipedema, a review of medical charts of women with lipedema at
Banner University of Arizona Medical Center over 6 months from 12 April 2017 to 12 October 2017, and us-
ing search terms “lipedema” and “lipoedema” in the database National Center for Biotechnology Information
(NCBI) [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Infor-
mation; [1988] – [cited 2017 Oct 01]. Available from: https://www.ncbi.nlm.nih.gov/.
Hypertension was noted for blood pressure ≥140/90 mm Hg or use of antihypertensive medication. Di-
abetes was identied by hemoglobin A
1C
(A
1C
) or history of diabetes (including gestational) with use of an-
tidiabetic medication. Pre-diabetes was identied by A
1C
6.5% or higher, history or use of medication for pre-
diabetes, specically metformin [21] as no other medications were used. Data are presented ± standard error
of the mean. Differences between means were analyzed by non-parametric analysis of variance (ANOVA) and
the Kruskal-Wallis test followed by a Dunn’s multiple comparison test.
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Friend: the upside of lipedema fat
Women with lipedema report little if any benet in having lipedema. The following are potential benets of
lipedema.
1. Low risk of diabetes despite higher body mass index (BMI): A study of 160 participants with lipedema
showed a low prevalence of diabetes of 6 ± 0.2% despite an average BMI of 39 ± 12 kg/m
2
[20] compared
to 10.7% of women with diabetes with a similar age range. The risk of diabetes was even lower at 2 ± 0.1%
in a smaller study of 51 participants with lipedema who had a similar average BMI of 38 ± 2 kg/m
2
[22].
Gynoid fat has been shown to be negatively correlated with insulin resistance after total fat adjustment,
whereas the opposite was found for abdominal fat, suggesting that lipedema fat may have a protective
effect against diabetes [23]. Data tabulated for this study also suggests that the risk of diabetes is low in
lipedema (∼2%) for an average BMI of 35.3 ± 1.7 kg/m
2
; the risk of pre-diabetes increased in Stages 2 and
3 (Table 1), suggesting that the risk of diabetes may increase with stage. Research on insulin sensitivity in
women with lipedema is needed preferably using the gold standard glucose clamp procedure.
2. Normal blood pressure despite obese BMI: In this study, hypertension was present in less than 30% of
women with Stages 2 and 3 and not present in women with Stage 1 lipedema (Table 1). National data sug-
gests hypertension rates in women of any BMI age 40–59 year was 32.4% [24]; higher hypertension rates
of 60% were reported for obese Caucasian women mean age 63 year [25]. The presence of hypertension in
women with Stages 2–3 is concerning and larger populations should be studied to better understand the
risk of hypertension with lipedema stage.
3. Gynoid shape and cardiovascular disease (CVD): Lipedema fat in the absence of abdominal obesity con-
fers a gynoid shape with a greater amount of fat in the gynoid area, hips, buttocks and legs, compared to the
upper body [26]. The presence of gynoid fat confers lower cardiovascular disease (CVD) risk compared to
android fat (abdominal obesity) [27]. The use of body shape along with weight has been shown to provide a
better estimate of risk of morbidity than weight alone [28]. Women with lipedema may therefore have lower
CVD risk due to gynoid fat (Table 1). The presence of CVD in women with lipedema should be studied to
better understand any risk of lipedema fat.
4. Resistance of lipedema fat to loss by lifestyle changes: Lipedema fat resists loss by extreme dieting and/or
over-exercise [6], [29]. This persistent fat is especially frustrating for women with lipedema, when women
without lipedema can lose weight by less extreme measures. What is concerning is that women with li-
pedema nd it difficult to lose weight prior to a needed surgery or other procedures. This aspect of lipedema
is a foe, but there may be an evolutionary benet to a woman having lipedema fat [30]. For example, in times
of famine, women with lipedema could have retained fat maintaining fertility and the ability to breast-feed
their children, passing on their genes within the population.
5. Normal lipid panel despite higher BMI: Women with gynoid fat had lower fasting triglyceride-rich
lipoprotein, and lower triglyceride levels and smaller chylomicron particle size after a mixed test meal pro-
viding 40 g triglycerides than women with android obesity [31], suggesting that gynoid fat protects against
abnormal blood lipids that would confer a cardiovascular risk. The majority of women with lipedema in the
current study had a normal lipid prole (Table 1), where only 11.7% had high total cholesterol ≥240 mg/dL
(considered high) compared to 33.5% of females in the general population [32] and even higher percentages
when females were obese [33].
6. Buoyancy: Lipedema fat offers dramatic buoyancy in water making water activities enjoyable. Women who
cannot swim to the bottom of a swimming pool or scuba dive without a very heavy weight belt do not nd
this benecial.
7. Compassion: Women with lipedema, recognizing the existence of persistent fat, have developed compas-
sion for people who are overweight and obese and their struggles with weight loss. This compassion is
important in our society that is rampant with fat bias [34], [35].
8. Soft skin: Many women with lipedema have joint hypermobility or possibly Ehlers-Danlos hypermobility
type (EDS-HT) syndrome [2], [20]. Individuals with EDS-HT are well-known to have soft skin [36].
9. Beautiful face: Women with lipedema state that they have fewer wrinkles and a more youthful face than
women without lipedema.
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![Figure 2: There are three stages and five types of lipedema. In Stage 1, the skin is smooth but there are pearl-sized nodules in the fat underneath. In Stage 2, there is retraction of the skin due to fibrosis of connective tissue fibers surrounding fat lobules and pearl-sized and larger masses in the fat tissue. In Stage 3, there are pearl-sized nodules, larger masses and lobules of the skin and fat. The fourth Stage in lipedema is not shown, as it is the development of lymphedema that can occur at any stage. Lymphedema occurs in Stage 3 more than Stage 2 or Stage 1 and is known as lipo-lymphedema [20]. Five Types describe the location of lipedema fat. Type IV is found often combined with Type II or III.](/figures/figure-2-there-are-three-stages-and-five-types-of-lipedema-rm6a2yrb.webp)