Today, let’s talk about a paper by a group of researchers in Germany. One of the authors, Dr. Manuel Cornely, has published many papers about lipedema. The title of the paper is: Is subcutaneous adipose tissue expansion in people living with lipedema healthier and reflected by circulating parameters? It was published in the journal Frontiers in Endocrinology in October 2022.
The authors wanted to test the hypothesis that women with lipedema have distinct blood panel values compared to women without lipedema. They state that “it remains unknown whether and to what extent the excessive expansion of adipose tissue in lipedema influences whole-body metabolic health in these patients.” Because the expansion of adipose tissue in obesity is often accompanied by metabolic dysregulation, the authors wanted to know if this is also the case in lipedema. To do this, they studied blood markers including glucose and lipid metabolism, inflammation, and oxidative stress, and compared these values with those from the control group.
Who were the participants in this study?
Thirteen women diagnosed with lipedema and 13 age- and BMI-matched controls were included in the study. Here are some characteristics of the lipedema group. Age ranged from 24 to 71 years and BMI ranged from 23.7 to 41.5. All of the women in the lipedema group presented with bilateral and symmetrical enlargement of their legs. The severity of their presentation by stage was as follows: two participants were in stage 1, another two participants were in stage 2, and nine participants were in stage 3. There was an association between an older age and a higher lipedema stage.
What were the methods used in this study?
Basic measures, such as height, weight, and limb volume, were collected on each participant. Blood draws were performed between 8:00 to 10:00 AM after an overnight fast. The number of hours of fasting was not reported. Biomarkers of glucose and lipid metabolism, liver function, inflammation and oxidative stress, and sex hormones were assessed. An additional 92 blood parameters of inflammation were also assessed.
What are the notable findings?
Glucose metabolism – Although HbA1c, which is a measure of average blood sugar over the last 3 months, was lower in the lipedema group compared to controls, the lipedema group showed higher levels of fasting insulin and adiponectin. Higher levels of insulin in the blood may be an indication of insulin resistance, while higher levels of adiponectin indicate insulin sensitivity. Due to a technical issue, however, they were not able to perform tests for insulin sensitivity, an unfortunate limitation of this study.
Sex hormones – There was a huge variability in sex hormone levels in participants in each group and therefore the researchers did not find a significant difference between the groups. Unfortunately at the time of the blood draw, the current phase of the participant’s menstrual cycle was not noted and likely accounts for this variability. This was another regrettable limitation of the study.
Lipid profile – Both total cholesterol and LDL were higher in the lipedema group. There was not a significant difference in triglycerides or HDL between the groups.
Liver enzymes – The lipedema group had higher levels of liver enzymes even when adjusted for age.
Markers of oxidative stress – They found that some biomarkers of inflammation and oxidative stress were elevated in the lipedema group while others were not. TNFα was elevated, for instance, but CRP was not.
Correlations between biochemical markers and metabolic parameters – interestingly, insulin, TNFα, total cholesterol, and LDL levels were all associated with age in the lipedema group but not in the control group.
Systemic inflammation – Overall, there was a higher inflammatory profile in the lipedema group. 21 inflammatory proteins were significantly upregulated in the lipedema group. Another interesting result was that no inflammatory protein levels were higher in the control group compared to the lipedema group.
What did the researchers conclude?
The researchers concluded that:
- Higher inflammation and oxidative stress parameters may reflect inflammatory processes in the subcutaneous adipose tissue (SAT) in patients with lipedema.
- Elevated inflammation in lipedema may potentially contribute to insulin resistance in SAT which is compensated for by higher insulin secretion.
- The activation of inflammatory and oxidative stress pathways and impaired glucose metabolism (as indicated by elevated insulin) may be counterbalanced by protective factors such as higher adiponectin secretion.
- Total cholesterol and LDL were higher for lipedema compared to controls. A less favorable lipid profile could be reflective, among others, of a dysregulated liver function or higher liver fat accumulation. This was suggested by the elevated liver enzymes in the lipedema group. Unfortunately, they did not test for fat accumulation around the liver (fatty liver disease).
There were some seemingly contradictory findings. For instance, higher fasting insulin usually indicates insulin resistance, but the lipedema group also had higher adiponectin levels associated with insulin sensitivity. Another contradiction is that adiponectin levels usually decrease as subcutaneous fat increases, but this was not so with the lipedema group. The authors hypothesize this may have more to do with where the fat is deposited rather than the total amount of fat. Lower body fat is typically more metabolically healthy than abdominal obesity.
What are my takeaways from this study?
Although the data was unfortunately inconclusive regarding the sex hormone levels in lipedema due to the lack of uniformity in the timing of blood draws to the phase of the participants’ menstrual cycle, there was a lot of interesting new information in this study. This study confirmed what other studies have shown as far as lower HbA1c and reduced incidence of type 2 diabetes but was one of the first to show elevated insulin levels. Elevated insulin, in combination with elevated adiponectin, may indicate that patients with lipedema have an ability for accumulating excessive fat tissue without developing metabolic dysfunction.
This study also seemed supportive of the hypothesis that lipedema fat has elevated levels of oxidative stress and inflammation. We still need more studies on blood levels in lipedema, but this study was a great start.
~ Leslyn Keith, OTD, CLT-LANA
Board President, Director of Research | The Lipedema Project