Introduction
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Syndromic lipomatosis, such as those encountered in type 1 Multiple Endocrine Neoplasia or certain genetically determined multiple lipomatosis [4];
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Multiple symmetric lipomatosis, most often linked to alcohol (Madelung or Launois-Bensaude disease);
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Dercum's disease, also known as adiposis dolorosa or Ander’s syndrome;
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Mesosomatic lipomatosis (LMS), also called Roch-Leri lipomatosis [5];
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Hibernomas, epidural lipomatosis and familial angiolipomatosis.
Patients and methods
Study design
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Patients with Dercum’s disease (DD group).
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Patients with Roch-Leri mesosomatic lipomatosis (LMS group).
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Normal weight control subjects (BMI (Body Mass Index) > 18 kg/m2 but < 25 kg/m2) (Lean group).
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Obese control subjects without lipoma (BMI > 25 kg/m2) (Obese group).
Patients and controls
Outcomes
Clinical parameters
Metabolic parameters
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Fasting blood glucose (FBG), liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyl transferase [GGT]), triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels were measured using routine methods.
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Fasting insulin levels were measured by monoclonal immunoradiometric assay (Bi-INS-IRMA; Cisbio, Bedford, MA, USA) and fasting C-peptide using radioimmunoassay (RIA-coat C-peptide [Mallinckrodt France SARL, Paris, France], detection limit: 0.2 ng/mL).
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Leptin levels were measured by radioimmunoassay using commercial kits (Human Leptin RIA, EMD Millipore, Billerica, MA, USA). Intra- and inter-assay coefficients of variation (CVs) were < 8.5%.
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Diabetes and glucose intolerance were assessed by subjecting participants who were not already being treated for diabetes at inclusion to a 75-g oral glucose tolerance test (OGTT), which was interpreted according to the American Diabetes Association’s criteria.
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HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) was calculated according to the formula: insulin (mIU/L) x glucose (mmol/L)/22.5.
Body composition parameters
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Body fat percentage was measured by dual-energy X-ray absorptiometry (DEXA; Lunar DPX-IQ, GE Healthcare, Chicago, IL, USA).
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Total and intra-abdominal fat, an estimation of subcutaneous and visceral fat, were measured from fat surface areas of 1-cm reconstructed slices of abdominal L4 magnetic resonance imaging (MRI).
Immunohematological parameters
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Personal history of immunoinflammatory disease (note that a history of autoimmune disease was an exclusion criteria for the control group).
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Blood count as well as platelets according to routine techniques.
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Lymphocyte immunophenotyping using flow cytometry (Navios flow cytometer, Beckman Coulter).
Statistical analysis
Results
Characteristics of the groups
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52 for other types of lipodystrophy syndromes:
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29 genetically-determined among which 23 LMNA-related,
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8 cases of Launois-Bensaude,
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2 cases of lipedema, 2 Barraquer-Simons and 1 Lawrence syndromes,
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10 from unknown origin.
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four because of insufficient data or persistent diagnostic doubt.
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9 patients with Dercum's disease (3 men and 6 women)
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and 11 patients with Roch-Leri lipomatosis (7 men and 4 women).
Clinical characteristics of the Dercum’s disease group
Characteristics at diagnosis | Dercum (n = 9) | LMS (n = 11) | p |
---|---|---|---|
Clinical data | |||
Sex-ratio (M/F) | 0.5 (3 M/6F) | 1.75 (7 M/4F) | 0.005 |
Age (years) | 30.8 [16–50] | 31.2 [18–68] | 0.69 |
Weight (kg) | 89 [58–98] | 100 [55–142] | 0.42 |
BMI (kg/m2) | 32 [27–59] | 31 [25–35] | 0.71 |
Number of lipomas > 10 (%; n/N) | 89% (8/9) | 82% (9/11) | > 0.9 |
Encapsulated—fibrotic—ecchymotic (%; n/N) | 89–11–11% (9/9) | 100–9–9% (11/11) | > 0.9 |
History of surgery (%; n/N) | 56% (7/9) | 54.5% (6/11) | > 0.9 |
Lipomas sites | |||
Forearm/arm (%; n/N) | 56% (5/9) | 82% (9/11) | 0.042 |
Back | 56% (5/9) | 27% (3/11) | 0.87 |
Abdomen | 44% (4/9) | 55% (6/11) | 0.99 |
Thigh | 67% (6/7) | 73% (8/11) | > 0.99 |
Flank/ Lumbar fossa | 44% (4/9) | 36% (4/11) | > 0.99 |
Legs | 11% (1/9) | 27% (3/11) | 0.80 |
Other | 44% (4/9) | 9% (1/11) | 0.048 |
Personal history | |||
Treated hypertension (%; n/N) | 22% (2/9) | 64% (7/11) | 0.33 |
Diabetes (%; n/N) | 33% (3/9) | 9% (1/11) | 0.28 |
Treated dyslipidemia (%; n/N) | 11% (1/9) | 45% (5/11) | 0.16 |
Family history | |||
History of lipomatosis | 11% (1/9) | 27% (3/11) | > 0.9 |
History of diabetes | 55% (5/9) | 9% (1/11) | > 0.9 |
Clinical characteristics of the Roch-Leri group
Comparison of the Dercum’s disease and the Roch-Leri groups
Clinical phenotype
Metabolic phenotype
Metabolic characteristics | Dercum (n = 9) | LMS (n = 11) | Lean controls (n = 18) | p Dercum versus Lean | p LMS versus Lean | p Dercum versus LMS |
---|---|---|---|---|---|---|
Clinical data | ||||||
Age (years) | 30.8 [16–50] | 31.2 [18–68] | 32.8 [19–65] | 0.35 | 0.16 | 0.69 |
Weight (kg) | 89 [58–98] | 100 [55–142] | 69 [49–83] | 0.01 | 0.001 | 0.42 |
BMI (kg/m2) | 32.5 [27–59] | 31 [25–35] | 22 [17–25] | 0.0005 | 0.0002 | 0.71 |
Systolic Blood Pressure (mmHG) | 130 [130–160] | 140 [115–150] | 115 [103–146] | 0.013 | 0.001 | 0.42 |
Diastolic Blood Pressure (mmHG) | 78.6 [60–90] | 79.7 [70–95] | 72.5 [68–89] | 0.04 | 0.04 | 0.93 |
Metabolic data | ||||||
Triglycerides (g/L) | 1.22 [0.65–9.42] | 1.37 [0.74–2.63] | 0.87 [0.56–2.77] | 0.07 | 0.83 | 0.98 |
HDL-c (g/L) | 0.45 [0.34–0.55] | 0.48 [0.41–0.82] | 0.53 [0.38–0.72] | 0.17 | > 0.99 | 0.15 |
LDL-c (g/L) | 1.46 [0.83–2.72] | 1.22 [0.91–1.87] | 1.16 [0.92–1.4] | 0.03 | 0.72 | 0.20 |
AST (IU/L) | 27 [18–43] | 25 [21–81] | 22 [17–29] | 0.05 | 0.09 | > 0.9 |
ALT (IU/L) | 26 [14–75] | 28,5 [11–78] | 17 [10–31] | 0.05 | 0.09 | 0.72 |
Gamma-GT (IU/L) | 83 [58–125] | 74 [30–139] | 18.7 [11–28] | 0.0001 | 0.0001 | 0.54 |
Fasting blood glucose (g/L) | 1 [0.92–1.33] | 0.98 [0.84–1.32] | 0.86 [0.77–1.01] | 0.0028 | 0.057 | 0.27 |
Fasting insulin (µIU/L; n/N) | 8.1 [6.3–14-4] (7/9) | 7.35 [6.3–35.8](7/11)a | 4.6 [1.2–9.2] (18/18) | 0.004 | 0.014 | 0.68 |
Fasting C-peptide (ng/mL; n/N) | 3.2 [2.46–4.33](7/9) | 2.57 [1.57–5.21](7/11)a | 1.75 [1–3.7] (18/18) | 0.016 | 0.04 | 0.84 |
HOMA-IR (n/N) | 2.67 [1.02–4.2] (7/9) | 1.67 [1.4–11.6](7/11)a | 1 [0.25–2.18](18/18) | 0.0008 | 0.02 | 0.62 |
Leptin (ng/mL) | 47.9 [6.7–224] | 28.5 [13–110.8] | 5.1 [4.1–16.1] | 0.003 | 0.0002 | > 0.9 |
Anthropometric data | ||||||
Fat mass estimated in DEXA (%; n/N) | 37.1 [27.9–44.5](6/9) | 34.3 [31.5–42.8] (8/11) | 22.9[17.9–34.9] (18/18) | 0.008 | 0.004 | > 0.9 |
Intra/total abdominal fat ratio (n/N) | 0.36 [0.20–0.98](8/9) | 0.31[0.24–0.6] (5/11) | 0.19[0.10–0.60] (18/18) | 0.04 | 0.03 | 0.87 |
Immunohematological phenotype
Characteristics at diagnosis | Dercum (n = 9) | LMS (n = 11) | Lean controls (n = 18) | p DD versus Lean | p LMS versus Lean | p DD versus LMS |
---|---|---|---|---|---|---|
History | ||||||
Dysimmune disorders (%; n/N) | 22% (2/9) | 45% (5/11) | 0% (18/18) | – | – | – |
Paraclinical | ||||||
Hemoglobin (g/dL) | 14.3 [12.5–15.4] | 14.6 [12–15.4] | 15 [12.1–17.3] | 0.07 | 0.41 | 0.46 |
Platelets (103/mm3) | 266 [211–310] | 220 [104–255] | 210 [176–338] | 0.005 | 0.39 | 0.10 |
Leukocytes (103/mm3) | 7.8 [5–9.1] | 5.8 [5.2–9.8] | 5.4 [4.3–11.1] | 0.02 | 0.49 | 0.19 |
CRP (mg/L) | 3 [3–18] | 3 [3–10] | 3 [3, 4] | 0.11 | 0.65 | 0.52 |
Leukocyte differential: (/mm3) | ||||||
Lymphocytes | 1939 [1100–2000] | 1832 [600–2300] | 1950 [1600–3300] | > 0.9 | 0.72 | 0.63 |
Monocytes | 500 [500–700] | 400 [400–600] | 400 [300–900] | 0.21 | > 0.9 | 0.33 |
Nuclear neutrophils | 5200 [2600–10000] | 3300 [2500–4600] | 2800[1200–3260] | 0.50 | 0.35 | 0.14 |
Eosinophils | 150 [0–300] | 100 [0–500] | 100 [0–1600] | > 0.9 | 0.26 | 0.20 |
Basophils | 52 [30–100] | 19 [0–37] | 0 [0–14] | 0.001 | 0.57 | 0.001 |
Lymphocytes subpopulations (n/N) | (5/9) | (7/11) | (18/18) | |||
CD3+ | 1420 [1105–1904] | 867 [513–1584] | 1444[913–2607] | > 0.9 | 0.009 | 0.04 |
CD4+ | 1255 [790–1710] | 636.5 [328–922] | 866 [367–1653] | 0.23 | 0.048 | 0.03 |
CD8+ | 479 [454–788] | 227[140–310] | 546 [284–943] | > 0.9 | 0.014 | 0.007 |
B Lymphocytes | 204.5 [140–760] | 227 [101–310] | 211 [103–528] | > 0.9 | > 0.9 | 0.93 |
NK Lymphocytes | 207.5 [40–225] | 210 [124–300] | 292 [136–450] | 0.049 | 0.31 | 0.53 |
Comparison of the Dercum’s group with the lean control group
Metabolic characteristics
Immunohematological characteristics
Comparison of the Roch-Leri -group with the lean control group
Metabolic characteristics
Immunohematological characteristics
Comparison of immuno-hematological parameters of the lipomatosis ad lean groups with the obese control group
Metabolic characteristics | Dercum(n = 9) | LMS(n = 11) | Obese controls(n = 8) | p DD versus obese | p LMS versus obese | p obese versus lean |
---|---|---|---|---|---|---|
Clinical data | ||||||
Sex ratio (M/W) | 0.5 (3 M/6F) | 1.75 (7 M/4F) | 0.5 (4 M/4F) | > 0.99 | > 0.99 | 0.09 |
Age (years) | 30.8 [16–50] | 31.2 [18–68] | 46.5 [23–64] | 0.44 | 0.21 | > 0.99 |
BMI (kg/m2) | 32 [27–59] | 31 [25–35] | 34.1 [31–43] | > 0.99 | > 0.99 | 0.002 |
Treated hypertension (%; n/N) | 22% (2/9) | 64% (7/11) | 38%(3/8) | > 0.99 | > 0.99 | 0.27 |
Diabetes (%; n/N) | 33% (3/9) | 9% (1/11) | 25% (2/8) | > 0.99 | > 0.99 | 0.75 |
Treated dyslipidemia (%; n/N) | 11% (1/9) | 45% (5/11) | 38% (3/8) | > 0.99 | > 0.99 | 0.22 |
Paraclinica | ||||||
Hemoglobin (g/dL) | 14.3 [12.5–15.4] | 14.6 [12–15.4] | 14.9[12.8–16.6] | 0.47 | > 0.99 | > 0.99 |
Platelets (103/mm3) | 266 [211–310] | 220 [104–255] | 242 [221–283] | 0.8 | 0.51 | 0.09 |
Leukocytes (103/mm3) | 7.8 [5–9.1] | 5.8 [5.2–9.8] | 6.9 [5.1–11.3] | 0.97 | 0.74 | 0.06 |
CRP (mg/L) | 3 [3–18] | 3 [3–10] | 6.3 [3–10] | > 0.99 | > 0.99 | > 0.99 |
Leukocyte differential: (/mm3) | ||||||
Lymphocytes | 1939 [1100–2000] | 1832 [600–2300] | 2141 [1500–3300] | 0.71 | 0.46 | 0.97 |
Monocytes | 500 [500–700] | 400`[400–600] | 400 [300–700] | > 0.99 | > 0.99 | > 0.99 |
Nuclear neutrophils | 5200 [2600–10000] | 3300 [2500–4600] | 4050 [2600–7100] | > 0.99 | > 0.99 | 0.16 |
Eosinophils | 150 [0–300] | 100 [0–500] | 188 [100–400] | > 0.99 | 0.35 | > 0.99 |
Basophils | 52 [30–100] | 19 [0–37] | 22 [0–100] | 0.03 | 0.97 | 0.14 |
Lymphocytes subpopulations (n/N) | (5/9) | (7/11) | (8/8) | |||
CD3+ | 1420 [1105–1904] | 867 [513–1584] | 1688[1215–1982] | 0.94 | 0.02 | 0.84 |
CD4+ | 1255 [790–1710] | 636.5 [328–922] | 979 [785–1454] | 0.96 | 0.01 | 0.77 |
CD8+ | 479 [454–788] | 227[140–310] | 493 [209–992] | > 0.99 | 0.02 | 0.89 |
B Lymphocytes | 204.5 [140–760] | 227 [101–310] | 199 [152–346] | 0.73 | > 0.99 | > 0.99 |
NK Lymphocytes | 207.5 [40–225] | 210 [124–300] | 287 [226–634] | 0.06 | 0.31 | > 0.99 |