Effects of in UTERO Exposure to Glucocorticoids

Study Overview
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Brief Summary
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The main objective of this study is to show that the fetal exposure to excess of glucocorticoids is associated with a deficiency of the function beta insulin in the offspring adult.

Detailed Description
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The main objective of this study is to show that the fetal exposure to excess of glucocorticoids is associated with a deficiency of the function beta insulin in the offspring adult 23 subjects of exposed offspring will be compared to 23 controls

Official Title
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Study of the Effects in Carbohydrate Metabolism and Renal Function of in UTERO Exposure to Glucocorticoids in Adult Offsprings (GLUCODEX)

Conditions
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21-hydroxylase; Defect

Intervention / Treatment
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* Procedure: Euglycemic hyperinsulinemic clamp


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Over 18 years Aged Males Women of childbearing age with a reliable and effective contraception for over 2 months Taking dexamethasone between the 6th and the 24th week of gestation by the mother with bloc 21-hydroxylase or normal pregnancy for control subjects Normal blood pressure and heart rate measured at rest: systolic blood pressure <= 150 mmHg, diastolic blood pressure <= 90 mmHg, heart rate between 55 and 90 beats/mn. Normal laboratory tests or not clinically significant abnormality NFS, platelets PT, aPTT, fibrin TP, TCA, Serum electrolytes, urea, creatinine Uric acid Triglycerides, total cholesterol, HDL cholesterol Fating bood glucose <= 6.9 mmol/l (exclusion criteria for diabetes from the American Diabetes Association) during the OGTT. Negative blood HCG Accepting the constraints of the protocol and had signed informed and free consent. Affiliated to the Social Security. Exclusion Criteria: Affected offspring of 21-hydroxylase enzyme block Taking dexamethasone until pregnancy term by the mother of the subject Type 2 diabetes in one of the two parents and/or 1 of the 4 grandparents Pregnancy, Breastfeeding Body Mass Index (weight/height2)> 50 kg/m2 Poisoning smoking (>10 cigarettes per day, whatever the duration of intoxication) Any drug taken apart from minor analgesics (aspirin, paracetamol) for less than 8 days at the inclusion and oral contraception Taking recent (less than 3 months) glucocorticoids either taken orally, by inhalation or percutaneously Current infections or recent infections (<10 days) Neoplastic disorders (with the exception of carcinoma in situ of the cervix or cutaneous epithelioma), haematological, cardiovascular, psychiatric, neurological Having donated blood or participated in a trial within 2 months preceding their inclusion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: exposed offspring<br> | Procedure: Euglycemic hyperinsulinemic clamp<br>* Euglycemic hyperinsulinemic clamp will be performed at day 2<br>|
| Other: controls<br> | Procedure: Euglycemic hyperinsulinemic clamp<br>* Euglycemic hyperinsulinemic clamp will be performed at day 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose Tolerance | the tolerance will be measured by the area under the curve (AUC) of insulin secretion flow | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity |  | 3 days | 
| Flow measurement of insulin secretory response to intravenous glucose |  | 3 days | 
| Measurement of the secretion of insulin and glucagon in response to arginine |  | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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offspring of 21-hydroxylase enzyme block