Type 1 Diabetes MellitusPolycystic Ovary Syndrome (PCOS)
Investigational drug(s) / intervention(s)
Type 1 diabetes mellitusElevated circulating androgen levelsSex dimorphism
Type 1 diabetes mellitus: A diagnosis of type 1a diabetes mellitus
Elevated circulating androgen levels: Androgen excess exposition due to a diagnosis of polycystic syndrome or male sex
Sex dimorphism: Effects of sex on outcomes measures
Study summary
BACKGROUND Functional ovarian hyperandrogenism, including the polycystic ovary syndrome (PCOS), is very prevalent in women with type 1 diabetes (T1D). The pathogenic mechanisms of this association remain unclear.
HYPOTHESIS Individual factors expose or protect women with T1D to/from the development of androgen excess and PCOS. Such androgen excess in women with T1D may increase their cardiometabolic risk.
MAIN OBJECTIVE Unveiling the pathogenic mechanisms behind functional hyperandrogenism in women with T1D from a sex/gender-medicine and sexual dimorphism perspective.
MATERIAL AND METHOS We have designed a cross-sectional comparative clinical study, including 5 groups of study subjects with 12 participans per group:
i) Women with T1D \& PCOS. ii) Women with T1D without PCOS. iii) Men with T1D and normal gonadal function. iv) Women with PCOS without diabetes mellitus v) Non-hyperandrogenic control women without T1D. All groups will show similar age and body mass index. T1D groups will be matched for duration of disease.
1.3 Ovarian and adrenal steroidogenesis. 2.1 Differential pattern in genetic variants related with insulin signalling and response, inflammation, adiposity, gonadal function, steroidogenesis, and PCOS itself by whole exome sequencing.
2.2 Microbiopsy studies in deep subcutaneous adipose tissue and skeletal muscle tissue: 2.2.1 Differential DNA methylation patterns in genes associated with PCOS. 2.2.2 Differential transcriptomic pattern in genes associated with PCOS.
2.2.3 Differential proteomic patterns in adipose and muscle tissues. 3. Interaction between T1D and PCOS on parameters of metabolic control (intersticial blood glucose monitoring) and morbidities associated with T1D itself.
Eligibility
Sex
ALL
Min age
18 Years
Max age
45 Years
Healthy volunteers
Accepted
1. Non--hyperandrogenic women with type 1 diabetes INCLUSION CRITERIA
* Premenopausal women between 18 and 45 years old.
* Diagnosis of type 1a diabetes at least 12 months before inclusion in the study, confirmed by positive autoimmunity and complete insulin deficiency.
* Treatment with subcutaneous insulin therapy (multiple doses or continuous infusion).
* Availability of metabolic control data (continuous interstitial blood glucose monitoring) at least in the month prior to study entry.
* Menarche at least three years prior to study entry. EXCLUSION CRITERIA
* Honeymoon period of T1D.
* Pregnancy or lactation.
* Thyroid hormone dysfunction or hyperprolactinaemia.
* Diagnosis of non-classical congenital adrenal hyperplasia or other secondary causes of hyperandrogenism.
* Diagnosis of other serious chronic disease.
* Treatment with oral contraceptives or glucocorticoid therapy in the 3 months prior to inclusion in the study.
2. Women with type 1 diabetes and polycystic ovary syndrome INCLUSION CRITERIA
* Women between 18 and 45 years old.
* Diagnosis of type 1a diabetes at least 12 months before inclusion in the study, confirmed by positive autoimmunity and complete insulin deficiency.
* Treatment with subcutaneous insulin therapy (multiple doses or continuous infusion).
* Availability of metabolic control data (continuous interstitial blood glucose monitoring) at least in the month prior to study entry.
* Menarche at least three years prior to study entry.
* PCOS diagnosis based on the 2012 American NIH consensus criteria, including the Rotterdam and AE-PCOS.
EXCLUSION CRITERIA
* Honeymoon period of T1D.
* Pregnancy/lactation.
* Thyroid hormone dysfunction or hyperprolactinaemia.
* Diagnosis of non-classical congenital adrenal hyperplasia or other secondary causes of hyperandrogenism.
* Diagnosis of other serious chronic disease. reatment with oral contraceptives or glucocorticoid therapy in the 3 months prior to inclusion in the study.
3. Men with T1D and normal gonadal function of similar age, BMI, and duration of diabetes.
INCLUSION CRITERIA
* Age between 18 and 45 years old.
* Diagnosis of type 1a diabetes at least 12 months before inclusion in the study, confirmed by positive autoimmunity and complete insulin deficiency.
* Treatment with subcutaneous insulin therapy (multiple doses or continuous infusion).
* Availability of metabolic control data (continuous interstitial blood glucose monitoring) at least in the month prior to study entry.
EXCLUSION CRITERIA
* Honeymoon period of T1D.
* Thyroid hormone dysfunction or hyperprolactinaemia.
* Diagnosis of non-classical congenital adrenal hyperplasia.
* Diagnosis of male hypogonadism.
4. Women with PCOS of similar age and BMI. INCLUSION CRITERIA
* Women between 18 and 45 years old.
* Menarche at least three years prior to study entry.
* PCOS diagnosis based on the 2012 American NIH consensus criteria, including the Rotterdam and AE-PCOS.
EXCLUSION CRITERIA
* Pregnancy/lactation.
* Previously known carbohydrate metabolism abnormalities (prediabetes or type 2 diabetes).
* Thyroid hormone dysfunction or hyperprolactinaemia.
* Diagnosis of non-classical congenital adrenal hyperplasia or other secondary causes of hyperandrogenism.
* Diagnosis of other serious chronic disease.
* Treatment with oral contraceptives or glucocorticoid therapy in the 3 months prior to inclusion in the study.
5. Non-hyperandrogenic control women with regular menses of similar age and BMI. INCLUSION CRITERIA
* Women between 18 and 45 years old.
* Menarche at least three years prior to study entry.
* Presence of regular menses.
* Lack of signs or symptoms of functional hyperandrogenism. EXCLUSION CRITERIA
* Pregnancy/lactation.
* Previously known carbohydrate metabolism disturbances.
* Thyroid hormone dysfunction or hyperprolactinaemia.
* Diagnosis of non-classical congenital adrenal hyperplasia or other secondary causes of hyperandrogenism.
* Diagnosis of other serious chronic disease.
* Treatment with oral contraceptives or glucocorticoid therapy in the 3 months prior to inclusion in the study.
Primary outcome measure(s)
Differences in insulin sensitivity between study subgroups — At baseline Study of sensitivity to insulin action by hyperinsulinaemic euglycaemic clamp. Clamping will be conducted in the follicular phase fo women's study participants. In this protocol free fatty acids will be also determined in stored samples.
Fat mass percentage — At baseline Body composition studies: Fat mass percentage with respect to total body weight.
Methodology: Bioelectrical impedance analysis by Monitor VitalScan Medeia® System device (United States, CA).
Phase angle 50 KHz — At baseline Methodology: Bioelectrical impedance analysis by Monitor VitalScan Medeia® System device (United States, CA).
Peritoneum-vertebral column fat thickness — At baseline Ultrasound assessment of fat compartments, determined using Toshiba Nemio ZG SSA-580ª ultrasound equipment (Toshiba Medical Systems, S.A., Alcobendas, Madrid) following the protocol previously validated and reported by our research group (PMID: 23386652).
Trunk fat mass % — At baseline Dual energy X-ray absorptiometry (DEXA). Hologic QDR Explorer® equipment.
Differences in ovarian and adrenal steroidogenesis between study subgroups — At baseline The circulating sex steroid profile will be assessed at baseline and at 60 minutes after stimulation of adrenal steroidogenesis with administration of 250 mcg i.v. of 1-24 ACTH. This profile will be determined in serum samples by liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) at the Laboratory of Clinical Biology, Ghent University, Belgium, using a triple-quadrupole mass spectrometer (AB Sciex, Toronto, Canada). The 24h urine steroid metabolomic profile will be analysed by gas chromatography-mass spectrometry (GC-MS). The analytical procedure will be performed by pre-extraction of urine (solid phase extraction with Sep-Pak C18 columns), followed by hydrolysis, solid phase re-extraction and double derivatization of the steroids to their methoxymethyltrimethylsilyl derivatives. The extracts obtained will be injected into the Shimadzu GCMS QP2010 instrument.
Trial sites (1)
Facility
City
Region
Status
Department of Endocrinology and Clinical Nutrition, Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo, Km 9.1, 28034-Madrid (Spain)
Madrid
Madrid
Recruiting
More Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal trials in Spain
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.