Polycystic Ovary Syndrome in Type 1 Diabetes

NCT07490964 | Not Yet Recruiting

• 1 other identifier: PI250434
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. OUTCOMES 1.1 Insulin sensitivity (hyperinsulinaemic euglycaemic clamping). 1.2 Body composition (dual-energy x-ray absorptiometry, bioelectrical impedance analysis \& sonographic studies). 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.

Conditions

Type 1 Diabetes Mellitus; Polycystic Ovary Syndrome (PCOS)

Keywords

Hyperandrogenism; Type 1 diabetes; Pathogenesis; Steroidogenesis; Insulin resistance; Body composition; Genetics; Epigenetics

Outcome Measures

Primary Outcomes (6)

• Differences in insulin sensitivity between study subgroups

  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.

  At baseline

• Fat mass percentage

  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).

  At baseline

• Phase angle 50 KHz

  Methodology: Bioelectrical impedance analysis by Monitor VitalScan Medeia® System device (United States, CA).

  At baseline

• Peritoneum-vertebral column fat thickness

  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).

  At baseline

• Trunk fat mass %

  Dual energy X-ray absorptiometry (DEXA). Hologic QDR Explorer® equipment.

  At baseline

• Differences in ovarian and adrenal steroidogenesis between study subgroups

  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.

  At baseline

Secondary Outcomes (4)

• Identify genomic variants in genes/proteins related to insulin signalling and action, adiposity, inflammation, steroidogenesis, and PCOS itself

  At baseline

• Description of differential DNA methylation patterns in deep subcutaneous adipose and skeletal muscle tissues (Epigenomics)

  At baseline

• Description of differential gene expression profiles in adipose and muscle tissues (Transcriptomics)

  At baseline

• Description of differential proteomic profiles in adipose and muscle tissue (Proteomics)

  At baseline

Other Outcomes (4)

• Insulin requirements/day adjusted for weight

  At baseline

• Time in range

  Since 4 weeks prior to inclusion in study

• Ambulatory blood pressure

  At baseline

Study Arms (5)

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.

Other: Type 1 diabetes mellitus; Other: Sex dimorphism

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.

Other: Type 1 diabetes mellitus; Other: Elevated circulating androgen levels; Other: Sex dimorphism

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.

Other: Type 1 diabetes mellitus; Other: Elevated circulating androgen levels; Other: Sex dimorphism

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.

Other: Elevated circulating androgen levels; Other: Sex dimorphism

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.

Other: Sex dimorphism

Interventions

Type 1 diabetes mellitus OTHER

A diagnosis of type 1a diabetes mellitus

Men with T1D and normal gonadal function of similar age, BMI, and duration of diabetes.; Non--hyperandrogenic women with type 1 diabetes; Women with type 1 diabetes and polycystic ovary syndrome

Elevated circulating androgen levels OTHER

Androgen excess exposition due to a diagnosis of polycystic syndrome or male sex

Men with T1D and normal gonadal function of similar age, BMI, and duration of diabetes.; Women with PCOS of similar age and BMI.; Women with type 1 diabetes and polycystic ovary syndrome

Sex dimorphism OTHER

Effects of sex on outcomes measures

Men with T1D and normal gonadal function of similar age, BMI, and duration of diabetes.; Non--hyperandrogenic women with type 1 diabetes; Non-hyperandrogenic control women with regular menses of similar age and BMI; Women with PCOS of similar age and BMI.; Women with type 1 diabetes and polycystic ovary syndrome

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Premenopausal adult women with type 1 diabetes mellitus presenting with or without polycystic ovary syndrome.

You may qualify if:

• Premenopausal women between 18 and 45 years old.
• 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.

You may not qualify if:

• 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.
• Women between 18 and 45 years old.
• 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.
• Honeymoon period of T1D.
• Pregnancy/lactation.
• Thyroid hormone dysfunction or hyperprolactinaemia.
• Diagnosis of non-classical congenital adrenal hyperplasia or other secondary causes of hyperandrogenism.
• Men with T1D and normal gonadal function of similar age, BMI, and duration of diabetes.

Sponsors & Collaborators

• Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal: lead
• Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders: collaborator
• University of Alcala: collaborator

Study Sites (1)

Department of Endocrinology and Clinical Nutrition, Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo, Km 9.1, 28034-Madrid (Spain)

Madrid, Madrid, 28034, Spain

Location

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• Lim SS, Davies MJ, Norman RJ, Moran LJ. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2012 Nov-Dec;18(6):618-37. doi: 10.1093/humupd/dms030. Epub 2012 Jul 4.

  PMID: 22767467 BACKGROUND

• Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018 Sep 1;33(9):1602-1618. doi: 10.1093/humrep/dey256. Erratum In: Hum Reprod. 2019 Feb 1;34(2):388. doi: 10.1093/humrep/dey363.

  PMID: 30052961 BACKGROUND

• Chiaffarino F, Cipriani S, Dalmartello M, Ricci E, Esposito G, Fedele F, La Vecchia C, Negri E, Parazzini F. Prevalence of polycystic ovary syndrome in European countries and USA: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2022 Dec;279:159-170. doi: 10.1016/j.ejogrb.2022.10.020. Epub 2022 Oct 28.

  PMID: 36343588 BACKGROUND

• Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab. 2000 Jul;85(7):2434-8. doi: 10.1210/jcem.85.7.6682.

  PMID: 10902790 BACKGROUND

• Bayona A, Martinez-Vaello V, Zamora J, Nattero-Chavez L, Luque-Ramirez M, Escobar-Morreale HF. Prevalence of PCOS and related hyperandrogenic traits in premenopausal women with type 1 diabetes: a systematic review and meta-analysis. Hum Reprod Update. 2022 Jun 30;28(4):501-517. doi: 10.1093/humupd/dmac011.

  PMID: 35237802 BACKGROUND

• Escobar-Morreale HF, Bayona A, Nattero-Chavez L, Luque-Ramirez M. Type 1 diabetes mellitus and polycystic ovary syndrome. Nat Rev Endocrinol. 2021 Dec;17(12):701-702. doi: 10.1038/s41574-021-00576-0. No abstract available.

  PMID: 34561669 BACKGROUND

• 2018 ESC/ESH Guidelines for the management of arterial hypertension. Rev Esp Cardiol (Engl Ed). 2019 Feb;72(2):160. doi: 10.1016/j.rec.2018.12.004. No abstract available. English, Spanish.

  PMID: 30704723 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma, whole blood, subcutaneous adipose tissue, and musculoskeletal tissue

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Polycystic Ovary Syndrome; Hyperandrogenism; Insulin Resistance

Interventions

Sex Characteristics

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; 46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Adrenogenital Syndrome; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena

Study Officials

• Manuel Luque-Ramírez, PhD, MD, MBA

  Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) & CIBERDEM & Universidad de Alcalá de Henares

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manuel Luque-Ramírez, Principal Investigator, PhD, MD, MBA

CONTACT

+34 913368000; manuel.luque@salud.madrid.org

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical researcher

Study Record Dates

• First Submitted: March 12, 2026
• First Posted: March 24, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 22, 2026

Record last verified: 2026-03

Locations

ES (1)