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| ID | Type | Description | Link |
|---|---|---|---|
| IDRCB 2025-A02210-49 | Other Identifier | ANSM |
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Diagnostic case-control study (1 case for 2 controls). Inclusion of patients with severe insulin resistance syndrome of genetic origin, then inclusion of controls: patients examined for PCOS in day hospital with matching age (+/- 5 years) and Body mass index (+/- 5kg/m2).
Hyperandrogenism and/or menstrual cycle disorders are the leading cause of female infertility and are associated with cardiovascular comorbidities. The most common cause of hyperandrogenism is polycystic ovary syndrome (PCOS), which affects 10% of women. However, PCOS can also be the presenting symptom of rare, multisystemic conditions such as extreme insulin resistance (IR) syndromes, with or without lipodystrophy. Among these extreme IR syndromes, familial partial lipodystrophy type 2 (FPLD2), of genetic origin, requires early screening and management to prevent diabetes, hypertriglyceridemia, and cardiovascular complications, which occur in 50%, 68%, and 45% of women, respectively, as well as serious comorbidities in certain genetic forms (risk of sudden death). Associated metabolic complications are often difficult to control and necessitate the use of orphan drugs when standard treatments are insufficiently effective. Furthermore, family genetic counseling should be provided. Currently, there is a significant delay in the diagnosis of these rare and still poorly understood diseases. This diagnostic delay is associated with a delay in the screening and treatment of complications related to these diseases, with a risk of early cardiovascular morbidity and mortality that is difficult to assess at present due to the rarity of the disease.
The main objective is to identify the differences, in the insulin resistant profile, associated with the diagnosis of PCOS coupled with a severe insulin resistance syndrome, when compared to a diagnosis of "classic" PCOS.
The secondary objective is to describe the metabolic and hormonal phenotype of patients with familial partial lipodystrophy type 2 (FPLD2) and to compare it with that of women presenting a "classic" PCOS.
25 cases and 50 age- and BMI-matched controls will be included in the study. Up to 6 additional control patients could be included if a control patient becomes a case based on the results of the genetic analysis. Otherwise, these patients will not be included.
A maximum of 81 patients in total will be included.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Case | Other | Patient with a Lipodystrophy Familial Partial due to a known pathogenic variant of the LMNA gene |
|
| Control | Other | Patient consulting for polycystic ovary syndrome in day hospital matched on age +/-5 years and BMI+/-5 kg/m2 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Genetic analysis | Genetic | Analyses of the insulin resistance and lipodystrophy gene panel revealed pathogenic or highly susceptible variants in control PCOS patients |
|
| Measure | Description | Time Frame |
|---|---|---|
| Measure of Insulinemia rate during an orally induced hyperglycemia | Measure of Insulinemia rate in order to compare the association between the profile of insulin secretion (Insulinemia , C-peptide and glycaemia) during an orally induced hyperglycemia and the known diagnosis of lipodystrophy linked to a mutation of the LMNA (FPLD2) gene. | Day 0 |
| Measure of C-peptide rate during an orally induced hyperglycemia | Measure of C-peptide rate in order to compare the association between the profile of insulin secretion (Insulinemia, C-peptide and glycaemia) during an orally induced hyperglycemia and the known diagnosis of lipodystrophy linked to a mutation of the LMNA (FPLD2) gene. | Day 0 |
| Measure of glycaemia rate during an orally induced hyperglycemia | Measure of glycaemia rate in order to compare the association between the profile of insulin secretion (Insulinemia, C-peptide and glycaemia) during an orally induced hyperglycemia and the known diagnosis of lipodystrophy linked to a mutation of the LMNA (FPLD2) gene. | Day 0 |
| Research of mutation of the LMNA (FPLD2) gene | Research of mutation of the LMNA (FPLD2) gene in order to compare the association between the profile of insulin secretion (Insulinemia, C-peptide and glycaemia) during an orally induced hyperglycemia and the known diagnosis of lipodystrophy linked to a mutation of the LMNA (FPLD2) gene. | Day 0 |
| Measure | Description | Time Frame |
|---|---|---|
| Measure of BMI | Measure of BMI in order to determine fatty tissue distribution in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Measure of waist circumference |
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Inclusion Criteria:
Case (n=25):
- Patient with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene.
Control (n=50), :
- patient consulting for polycystic ovary syndrome (PCOS according to the Rotterdam criteria) in day hospital matched on age +/-5 years and BMI+/-5 kg/m2.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sophie LAMOTHE, Doctor | Contact | 0149282406 | +33 | sophie.lamothe@aphp.fr |
| Camille VATIER, Doctor | Contact | 0149282406 | +33 | camille.vatier@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Sophie LAMOTHE | APHP | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Service Endocrinologie, Hôpital St Antoine | Paris | 75012 | France |
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| Biological analysis | Other | Measurement of adipokines |
|
| imaging test | Other | DEXA (Dual-Energy X-ray Absorptiometry) |
|
| Standard intervention | Other | Standard intervention |
|
Measure of waist circumference in order to determine fatty tissue distribution in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group
| Day 0 |
| Measure of hip circumference | Measure of hip circumference in order to determine fatty tissue distribution in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Measure of skin fold thickness | Measure of skin fold thickness in order to determine fatty tissue distribution in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Measure of the percentage of total body fat at DEXA | Measure of the percentage of total body fat at DEXA in order to determine fatty tissue distribution in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 and up to 1 month |
| Measure of the android to gynoid ratio at DEXA | Measure of the android to gynoid ratio at DEXA in order to determine fatty tissue distribution in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 and up to 1 month |
| Determine biological differences in concentration of fasting blood glucose | Determine biological differences in concentration of fasting blood glucose in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine biological differences in concentration of fasting blood insulin | Determine biological differences in concentration of fasting blood insulin in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine biological differences in concentration of ASAT/ALAT (Aspartate Aminotransferases) /ALAT(Alanine Aminotransferases) | Determine biological differences in concentration of ASAT/ALAT in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine biological differences in concentration of Gamma GT (Gamma-glutamyl transpeptidase) | Determine biological differences in concentration of Gamma GT in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine biological differences in concentration of leptinemia | Determine biological differences in concentration of leptinemia in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine biological differences in concentration of adiponectinemia | Determine biological differences of plasma total adiponectin hydroxyprogesterone in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine biological differences in concentration of triglyceridemia | Determine biological differences of concentration triglyceridemia in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine biological differences in concentration of HDL cholesterolemia | Determine biological differences of concentration HDL cholesterolemia in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of testosterone | Determine differences in hormonal concentrations of testosterone in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of FSH (Follicle-Stimulating Hormone) | Determine differences in hormonal concentrations of FSH in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of LH (Luteinizing Hormone) | Determine differences in hormonal concentrations of LH in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of AMH (Anti-Müllerian Hormone) | Determine differences in hormonal concentrations of AMH in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of cortisol | Determine differences in hormonal concentrations of androgens and steroids (cortisol measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of cortisone | Determine differences in hormonal concentrations of cortisone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of pregnenolone | Determine differences in hormonal concentrations of pregnenolone, measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of 17-alpha hydroxypregnenolone | Determine differences in hormonal concentrations of 17-hydroxyprogesterone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of 16-hydroxyprogesterone | Determine differences in hormonal concentrations of 16-hydroxyprogesterone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of delta 4 androstenedione | Determine differences in hormonal concentrations of delta 4 androstenedione measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of 11 betahydroxyandrostenedione | Determine differences in hormonal concentrations of 11 betahydroxyandrostenedione measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of DHEA (Dehydroepiandrosterone) | Determine differences in hormonal concentrations of DHEA measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of 11-deoxycortisol | Determine differences in hormonal concentrations of 11-deoxycortisol measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of 21-deoxycortisol | Determine differences in hormonal concentrations of 21-deoxycortisol measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of testosterone | Determine differences in hormonal concentrations of testosterone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of dihydrotestosterone | Determine differences in hormonal concentrations of dihydrotestosterone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of corticosterone | Determine differences in hormonal concentrations of corticosterone, measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of 21-deoxycorticosterone | Determine differences in hormonal concentrations of 21-deoxycorticosterone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine differences in hormonal concentrations of aldosterone | Determine differences in hormonal concentrations of aldosterone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| Determine the follicular count on pelvic ultrasound or pelvic MRI | Determine the follicular count on pelvic ultrasound in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group | Day 0 |
| ID | Term |
|---|---|
| D011085 | Polycystic Ovary Syndrome |
| D052496 | Lipodystrophy, Familial Partial |
| ID | Term |
|---|---|
| D010048 | Ovarian Cysts |
| D003560 | Cysts |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D000083083 | Laminopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008060 | Lipodystrophy |
| D012875 | Skin Diseases, Metabolic |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D008052 | Lipid Metabolism, Inborn Errors |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D005820 | Genetic Testing |
| D057919 | Biological Oxygen Demand Analysis |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
| D005821 | Genetic Techniques |
| D033142 | Genetic Services |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
| D003954 | Diagnostic Services |
| D011314 | Preventive Health Services |
| D004784 | Environmental Monitoring |
| D004781 | Environmental Exposure |
| D004787 | Environmental Pollution |
| D011634 | Public Health |
| D004778 | Environment and Public Health |
| D015980 | Public Health Practice |
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