Identification of Women With Severe Insulin Resistant Syndromes of Genetic Origin Among Patients With "Classic" Polycystic Ovary Syndrome (PCOS)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 81
- Locations
- 1
- Primary Endpoint
- Measure of Insulinemia rate during an orally induced hyperglycemia
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Case
Patient with a Lipodystrophy Familial Partial due to a known pathogenic variant of the LMNA gene
Intervention: Genetic analysis (Genetic)
Case
Patient with a Lipodystrophy Familial Partial due to a known pathogenic variant of the LMNA gene
Intervention: Biological analysis (Other)
Case
Patient with a Lipodystrophy Familial Partial due to a known pathogenic variant of the LMNA gene
Intervention: imaging test (Other)
Control
Patient consulting for polycystic ovary syndrome in day hospital matched on age +/-5 years and BMI+/-5 kg/m2
Intervention: Standard intervention (Other)
Outcomes
Primary Outcomes
Measure of Insulinemia rate during an orally induced hyperglycemia
Time Frame: Day 0
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.
Measure of C-peptide rate during an orally induced hyperglycemia
Time Frame: Day 0
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.
Measure of glycaemia rate during an orally induced hyperglycemia
Time Frame: Day 0
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.
Research of mutation of the LMNA (FPLD2) gene
Time Frame: Day 0
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.
Secondary Outcomes
- Measure of BMI(Day 0)
- Measure of waist circumference(Day 0)
- Measure of hip circumference(Day 0)
- Measure of skin fold thickness(Day 0)
- Measure of the percentage of total body fat at DEXA(Day 0 and up to 1 month)
- Measure of the android to gynoid ratio at DEXA(Day 0 and up to 1 month)
- Determine biological differences in concentration of fasting blood glucose(Day 0)
- Determine biological differences in concentration of fasting blood insulin(Day 0)
- Determine biological differences in concentration of ASAT/ALAT (Aspartate Aminotransferases) /ALAT(Alanine Aminotransferases)(Day 0)
- Determine biological differences in concentration of Gamma GT (Gamma-glutamyl transpeptidase)(Day 0)
- Determine biological differences in concentration of leptinemia(Day 0)
- Determine biological differences in concentration of adiponectinemia(Day 0)
- Determine biological differences in concentration of triglyceridemia(Day 0)
- Determine biological differences in concentration of HDL cholesterolemia(Day 0)
- Determine differences in hormonal concentrations of testosterone(Day 0)
- Determine differences in hormonal concentrations of FSH (Follicle-Stimulating Hormone)(Day 0)
- Determine differences in hormonal concentrations of LH (Luteinizing Hormone)(Day 0)
- Determine differences in hormonal concentrations of AMH (Anti-Müllerian Hormone)(Day 0)
- Determine differences in hormonal concentrations of cortisol(Day 0)
- Determine differences in hormonal concentrations of cortisone(Day 0)
- Determine differences in hormonal concentrations of pregnenolone(Day 0)
- Determine differences in hormonal concentrations of 17-alpha hydroxypregnenolone(Day 0)
- Determine differences in hormonal concentrations of 16-hydroxyprogesterone(Day 0)
- Determine differences in hormonal concentrations of delta 4 androstenedione(Day 0)
- Determine differences in hormonal concentrations of 11 betahydroxyandrostenedione(Day 0)
- Determine differences in hormonal concentrations of DHEA (Dehydroepiandrosterone)(Day 0)
- Determine differences in hormonal concentrations of 11-deoxycortisol(Day 0)
- Determine differences in hormonal concentrations of 21-deoxycortisol(Day 0)
- Determine differences in hormonal concentrations of dihydrotestosterone(Day 0)
- Determine differences in hormonal concentrations of corticosterone(Day 0)
- Determine differences in hormonal concentrations of 21-deoxycorticosterone(Day 0)
- Determine differences in hormonal concentrations of aldosterone(Day 0)
- Determine the follicular count on pelvic ultrasound or pelvic MRI(Day 0)