Prevalence of Hyperandrogenism in Type 1 Diabetes

NCT04979377 | Completed

• 1 other identifier: DM1PCOS
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators aim to estimate the prevalence of functional ovarian hyperandrogenism \[idiopathic hyperandrogenism, idiopatic hirsutism, and polycystic ovary syndrome (PCOS)\] in adult patients with type 1 diabetes (T1DM) in an observational cross-sectional study. Study population is comprised of premenopausal adult women with a diagnosis of T1DM, consecutively recruited from a Diabetes outpatient clinic at a tertiary hospital in Spain, Europe.

Conditions

Type 1 Diabetes; Polycystic Ovary Syndrome; Hyperandrogenism; Hirsutism; Oligomenorrhea; Ovulation Disorder

Keywords

Polycystic ovary syndrome; Hyperandrogenism; Type 1 diabetes; Prevalence; Hirsutism; Ovulatory dysfunction; Testosterone; Insulin

Outcome Measures

Primary Outcomes (3)

• Prevalence of PCOS in T1DM

  Prevalence of PCOS in women with T1DM according to ESHRE-ASRM/Rotterdam criteria

  2020-2022

• Prevalence of classic PCOS in T1DM

  Prevalence of PCOS in women with T1DM according to classic NIH criteria

  2020-2022

• Prevalence of hyperandrogenic PCOS in T1DM

  Prevalence of PCOS in women with T1DM according to AES-PCOS criteria

  2020-2022

Secondary Outcomes (10)

• Prevalence of related traits in women with T1D

  2020-2022

• Influence fo the onset of type 1 diabetes on hyperandrogenism

  2020-2022

• Influence of Insulin Requirements on hyperandrogenism

  2020-2022

• Influence of metabolic control on hyperandrogenism

  2020-2022

• Influence of body composition on hyperandrogenism

  2020-2022

Study Arms (1)

Adult premenopausal women with type 1 diabetes mellitus

One-hundred and fifty women aged from 18 to 45 years old consecutively recruited from a type 1 diabetes clinic at a tertiary hospital of Madrid, Spain

Other: Clinical hyperandrogenism assessment; Diagnostic Test: Total testosterone (ng/dL); Diagnostic Test: A1c (%); Diagnostic Test: Total cholesterol; Other: Body mass index (BMI) (kg/m2); Diagnostic Test: Frequency of chronic vascular complications [n (%)]; Diagnostic Test: Polycystic ovary morphology; Diagnostic Test: Cardiovascular autonomic reflex tests (CARTs); Diagnostic Test: Sex hormone-binding globulin (SHBG) (nmol/L); Diagnostic Test: Dehydroepiandrosterone-sulphate (IQL) (ng/mL); Other: Waist circumference (cm); Other: Waist-to-hip ratio; Other: Body composition; Diagnostic Test: Mean glucose (mg/dL); Diagnostic Test: Time in target range (hours); Diagnostic Test: Time in hyperglycemia (hours); Other: Insulin dose (UI/Kg); Other: Insulin sensitivity; Diagnostic Test: High-density lipoprotein (HDL) (mg/dL); Diagnostic Test: Low-density lipoprotein (LDL) (mg/dL); Diagnostic Test: Triglycerides (mg/dL)

Interventions

Clinical hyperandrogenism assessment OTHER

Modified Ferriman-Gallwey scale

Also known as: Hirsutism score

Adult premenopausal women with type 1 diabetes mellitus

Total testosterone (ng/dL) DIAGNOSTIC_TEST

Circulating total testosterone (LC-MS/MS or IQL-CDC method) at follicular phase

Also known as: Sex steroid profile

Adult premenopausal women with type 1 diabetes mellitus

A1c (%) DIAGNOSTIC_TEST

High Performance Liquid Chromatography (HPLC)

Also known as: Metabolic control

Adult premenopausal women with type 1 diabetes mellitus

Total cholesterol DIAGNOSTIC_TEST

Determined by enzymatic methods

Also known as: Lipid profile

Adult premenopausal women with type 1 diabetes mellitus

Body mass index (BMI) (kg/m2) OTHER

Defined as body weight divided by the square of body height, and expressed in kg/m2

Also known as: Anthropometrics and body composition

Adult premenopausal women with type 1 diabetes mellitus

Frequency of chronic vascular complications [n (%)] DIAGNOSTIC_TEST

Retinopathy, nephropathy, neuropathy, and macrovascular disease.

Adult premenopausal women with type 1 diabetes mellitus

Polycystic ovary morphology DIAGNOSTIC_TEST

Sonographic assessment

Adult premenopausal women with type 1 diabetes mellitus

Cardiovascular autonomic reflex tests (CARTs) DIAGNOSTIC_TEST

Cardioautonomic function assessement by Vital scan HW7-HW6T:

Also known as: Cardiovascular function

Adult premenopausal women with type 1 diabetes mellitus

Sex hormone-binding globulin (SHBG) (nmol/L) DIAGNOSTIC_TEST

Circulating SHBG (IQL) at follicular phase

Also known as: Sex steroid profile

Adult premenopausal women with type 1 diabetes mellitus

Dehydroepiandrosterone-sulphate (IQL) (ng/mL) DIAGNOSTIC_TEST

Circulating DHEAS (IQL) at follicular phase

Also known as: Sex steroid profile

Adult premenopausal women with type 1 diabetes mellitus

Waist circumference (cm) OTHER

Waist circumference measurement made at the top of the iliac crest

Also known as: Anthropometrics and body composition

Adult premenopausal women with type 1 diabetes mellitus

Waist-to-hip ratio OTHER

Waist circumference divided by hip circumference (measurement should be taken around the widest portion of the buttocks)

Also known as: Anthropometrics and body composition

Adult premenopausal women with type 1 diabetes mellitus

Body composition OTHER

Vital Scan HW7-HW6T

Also known as: Bioimpedanciometry

Adult premenopausal women with type 1 diabetes mellitus

Mean glucose (mg/dL) DIAGNOSTIC_TEST

Continuous glucose monitoring (GCM) records

Also known as: Metabolic control

Adult premenopausal women with type 1 diabetes mellitus

Time in target range (hours) DIAGNOSTIC_TEST

Continuous glucose monitoring (GCM) records

Also known as: Metabolic control

Adult premenopausal women with type 1 diabetes mellitus

Time in hyperglycemia (hours) DIAGNOSTIC_TEST

Continuous glucose monitoring (GCM) records

Also known as: Metabolic control

Adult premenopausal women with type 1 diabetes mellitus

Insulin dose (UI/Kg) OTHER

Daily insulin dose divided by body weight

Also known as: Metabolic control

Adult premenopausal women with type 1 diabetes mellitus

Insulin sensitivity OTHER

Equation that relies on routine clinical measures: A1c, presence of hypertension, and waist circumference

Also known as: Estimated glucose disposal rate (eGDR)

Adult premenopausal women with type 1 diabetes mellitus

High-density lipoprotein (HDL) (mg/dL) DIAGNOSTIC_TEST

Enzymatic methods after precipitation of serum with phosphotungstic acid and Mg2+

Also known as: HDL-cholesterol

Adult premenopausal women with type 1 diabetes mellitus

Low-density lipoprotein (LDL) (mg/dL) DIAGNOSTIC_TEST

Estimated by the Friedewald's equation.

Also known as: Lipid profile

Adult premenopausal women with type 1 diabetes mellitus

Triglycerides (mg/dL) DIAGNOSTIC_TEST

Determined by enzymatic methods

Also known as: Lipid profile

Adult premenopausal women with type 1 diabetes mellitus

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Premenopausal women with T1DM consecutively recruited from a Diabetes outpatient clinic at a tertiary hospital.

You may qualify if:

• Age between 18 and 45 years old
• Treatment with subcutaneus insulin therapy (multiple dose or continuous subcutaneous insulin infusion).
• Menarche at least 2 years before the study.

You may not qualify if:

• Honey moon period.
• Altered thyroid hormone or prolactin levels.
• Congenital adrenal hyperplasia.
• Severe chronic disease.
• Oral contraceptive or glucocorticoid therapy in the previous 3 months.

Sponsors & Collaborators

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

Study Sites (1)

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

Location

Related Publications (12)

• Escobar-Morreale HF, Roldan B, Barrio R, Alonso M, Sancho J, de la Calle H, Garcia-Robles R. High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2000 Nov;85(11):4182-7. doi: 10.1210/jcem.85.11.6931.

  PMID: 11095451 BACKGROUND

• Roldan B, Escobar-Morreale HF, Barrio R, de La Calle H, Alonso M, Garcia-Robles R, Sancho J. Identification of the source of androgen excess in hyperandrogenic type 1 diabetic patients. Diabetes Care. 2001 Jul;24(7):1297-9. doi: 10.2337/diacare.24.7.1297. No abstract available.

  PMID: 11423519 BACKGROUND

• Codner E, Escobar-Morreale HF. Clinical review: Hyperandrogenism and polycystic ovary syndrome in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2007 Apr;92(4):1209-16. doi: 10.1210/jc.2006-2641. Epub 2007 Feb 6.

  PMID: 17284617 BACKGROUND

• Escobar-Morreale HF, Roldan-Martin MB. Type 1 Diabetes and Polycystic Ovary Syndrome: Systematic Review and Meta-analysis. Diabetes Care. 2016 Apr;39(4):639-48. doi: 10.2337/dc15-2577.

  PMID: 27208367 BACKGROUND

• Codner E, Soto N, Lopez P, Trejo L, Avila A, Eyzaguirre FC, Iniguez G, Cassorla F. Diagnostic criteria for polycystic ovary syndrome and ovarian morphology in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2006 Jun;91(6):2250-6. doi: 10.1210/jc.2006-0108. Epub 2006 Mar 28.

  PMID: 16569737 BACKGROUND

• Codner E, Iniguez G, Villarroel C, Lopez P, Soto N, Sir-Petermann T, Cassorla F, Rey RA. Hormonal profile in women with polycystic ovarian syndrome with or without type 1 diabetes mellitus. J Clin Endocrinol Metab. 2007 Dec;92(12):4742-6. doi: 10.1210/jc.2007-1252. Epub 2007 Sep 25.

  PMID: 17895317 BACKGROUND

• Gaete X, Vivanco M, Eyzaguirre FC, Lopez P, Rhumie HK, Unanue N, Codner E. Menstrual cycle irregularities and their relationship with HbA1c and insulin dose in adolescents with type 1 diabetes mellitus. Fertil Steril. 2010 Oct;94(5):1822-6. doi: 10.1016/j.fertnstert.2009.08.039. Epub 2009 Sep 30.

  PMID: 19796762 BACKGROUND

• Codner E, Merino PM, Tena-Sempere M. Female reproduction and type 1 diabetes: from mechanisms to clinical findings. Hum Reprod Update. 2012 Sep-Oct;18(5):568-85. doi: 10.1093/humupd/dms024. Epub 2012 Jun 17.

  PMID: 22709979 BACKGROUND

• Nattero-Chavez L, Alonso Diaz S, Jimenez-Mendiguchia L, Garcia-Cano A, Fernandez-Duran E, Dorado Avendano B, Escobar-Morreale HF, Luque-Ramirez M. Sexual Dimorphism and Sex Steroids Influence Cardiovascular Autonomic Neuropathy in Patients With Type 1 Diabetes. Diabetes Care. 2019 Nov;42(11):e175-e178. doi: 10.2337/dc19-1375. Epub 2019 Sep 17. No abstract available.

  PMID: 31530659 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.

  PMID: 30052961 BACKGROUND

• Escobar-Morreale HF, Carmina E, Dewailly D, Gambineri A, Kelestimur F, Moghetti P, Pugeat M, Qiao J, Wijeyaratne CN, Witchel SF, Norman RJ. Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update. 2012 Mar-Apr;18(2):146-70. doi: 10.1093/humupd/dmr042. Epub 2011 Nov 6.

  PMID: 22064667 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

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma and DNA archive samples for further analyses. Registry number (Instituto de Salud Carlos III): C.0005860

MeSH Terms

Conditions

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

Interventions

Body Mass Index; Body Composition; Cardiovascular Physiological Phenomena; Waist Circumference; Waist-Hip Ratio; Time; Insulin

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; Hair Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Virilism; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Menstruation Disturbances; Pathologic Processes; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Anthropometry; Investigative Techniques; Physiological Phenomena; Biometry; Epidemiologic Measurements; Public Health; Environment and Public Health; Biochemical Phenomena; Chemical Phenomena; Metabolism; Circulatory and Respiratory Physiological Phenomena; Body Size; Physical Phenomena; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Manuel Luque-Ramírez, PhD, MD, MBA

  CIBERDEM, Instituto de Salud Carlos III

  STUDY DIRECTOR

• Héctor F Escobar-Morreale, PhD, MD

  University of Alcalá

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Principal investigator

Study Record Dates

• First Submitted: July 7, 2021
• First Posted: July 28, 2021
• Study Start: March 9, 2020
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: March 17, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Since study ending with no time limit restriction
• Access Criteria: Reasonable request

Locations

ES (1)