Identification of Women With Severe Insulin Resistant Syndromes of Genetic Origin Among Patients With "Classic" Polycystic Ovary Syndrome (PCOS)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Genetic analysis, Biological analysis, imaging test, Standard intervention.
- Who it may be relevant to
- Registry conditions: Polycystic Ovary Syndrome, Familial Partial Lipodystrophy, LMNA (LaMin Nuclear A) Related Disorders. Basic parameters: 18 years — 45 years · Female.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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).
Detailed description
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.
Interventions
- Genetic Genetic analysis
Analyses of the insulin resistance and lipodystrophy gene panel revealed pathogenic or highly susceptible variants in control PCOS patients - Other Biological analysis
Measurement of adipokines - Other imaging test
DEXA (Dual-Energy X-ray Absorptiometry) - Other Standard intervention
Standard intervention
Primary outcome measures
- Measure of Insulinemia rate during an orally induced hyperglycemia [Time frame: Day 0]
- Measure of C-peptide rate during an orally induced hyperglycemia [Time frame: Day 0]
- Measure of glycaemia rate during an orally induced hyperglycemia [Time frame: Day 0]
- Research of mutation of the LMNA (FPLD2) gene [Time frame: Day 0]
Secondary outcome measures (12)
- Measure of BMI [Time frame: Day 0]
- Measure of waist circumference [Time frame: Day 0]
- Measure of hip circumference [Time frame: Day 0]
- Measure of skin fold thickness [Time frame: Day 0]
- Measure of the percentage of total body fat at DEXA [Time frame: Day 0 and up to 1 month]
- Measure of the android to gynoid ratio at DEXA [Time frame: Day 0 and up to 1 month]
- Determine biological differences in concentration of fasting blood glucose [Time frame: Day 0]
- Determine biological differences in concentration of fasting blood insulin [Time frame: Day 0]
- Determine biological differences in concentration of ASAT/ALAT (Aspartate Aminotransferases) /ALAT(Alanine Aminotransferases) [Time frame: Day 0]
- Determine biological differences in concentration of Gamma GT (Gamma-glutamyl transpeptidase) [Time frame: Day 0]
- Determine biological differences in concentration of leptinemia [Time frame: Day 0]
- Determine biological differences in concentration of adiponectinemia [Time frame: Day 0]
Eligibility criteria
Inclusion criteria
- Women aged ≥ 18 years and < 45 years ;
- Discontinuation of estrogen-progestin therapyfor at least 3 months ;
- Signed informed consent ;
- Social security affiliation.
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
- \- Severe renal insufficiency (GFR < 30 ml/min) ;
- Hepato-cellular insufficiency (TP < 50%) ;
- Taking corticosteroids or antiretrovirals ;
- Menopausal women ;
- Taking estrogen-progestin therapy;
- Diabetic patients on insulin : type 1 diabetes or pancreatectomised patients
- Other known causes of hyperandrogenism (21-hydroxylase block, Cushing's syndrome, ovarian tumor).
- Pregnant woman
- Breastfeeding woman
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Diagnostic
Study locations
France · 1 center
- Service Endocrinologie, Hôpital St Antoine — Paris
Identifiers
NCT: NCT07412028 · APHP241600 · IDRCB 2025-A02210-49