Study of Molecular Causes of Metabolic Disorders in Obese Premenopausal Women After Breast Cancer
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- University of Copenhagen
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Insulin sensitivity status
Study Overview
Brief Summary
Epidemiological studies have revealed that 60-80% of women with breast cancer (BC) develop metabolic disorders that are similar to those observed in conditions like type 2 diabetes. These metabolic disorders, including insulin resistance, obesity, hyperinsulinemia, and glucose intolerance, are associated with increased BC recurrence and mortality. Skeletal muscle is the major site of glucose uptake in humans. The aims of the present project are to 1) determine the involvement of insulin resistance in skeletal muscle in the metabolic disorders prevalent in BC survivors, 2) identify BC-and/or treatment-induced molecular changes in skeletal muscle from BC survivors .
Detailed Description
Up to 80% of women with breast cancer (BC) develop metabolic disorders, such as insulin resistance, obesity, hyperinsulinemia, and glucose intolerance, during or after their treatment. Such disorders increase BC mortality and the likelihood of relapse 2- and 3-fold, respectively. However, it is not known why BC and/or the treatment hereof causes metabolic disorders and very few studies have investigated the underlying biological causes.
Aims:
- determine the involvement of insulin resistance in skeletal muscle in the metabolic disorders prevalent in BC survivors
- identify BC-and/or treatment-induced molecular changes in skeletal muscle
BC is a common cancer with 2.1 million new cases each year, and BC also causes the largest number of cancer-related deaths among women worldwide. Fortunately, more people are now surviving their cancer. In Denmark, the majority of the 300.000 cancer survivors, constitute a group of ~ 70,000 women who have survived BC. However, there is a severe lack of research into the physiological sequelae of cancer and/or treatment, including the metabolic health consequences of BC. Recent epidemiological studies have revealed that 60-80% of women with BC develop metabolic disorders that are similar to those observed in conditions such as type 2 diabetes (T2D) during or following their treatment. However, unlike T2D, the underlying biological causes for the development of metabolic disorders with BC and/or the treatment are poorly investigated. It is important to address this knowledge gap, as metabolic disorders increase mortality among women with BC 2-fold and increase the likelihood of BC recurrence up to 3-fold.
The investigators hypothesize that metabolic disorders in BC survivors are due to cancer and/or treatment-mediated molecular rewiring of skeletal muscle, which causes insulin resistance.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to 45 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Premenopausal women operated for breast cancer and after completing adjuvant chemotherapy and no earlier than 3 weeks after its termination
- •BMI: 25-30
- •Healthy controls will be included matched by gender, weight, age, and level of physical activity to the patient group included as subjects
Exclusion Criteria
- •Known postmenopause occurred at the time of diagnosis of breast cancer
- •Alcohol intake of> 7 items / week
- •Already known Type 2 diabetes mellitus or metabolic syndrome and medical treatment thereof.
- •Cardiovascular disease and its medical treatment
- •Impaired mobility
Arms & Interventions
Healthy control subjects
Healthy control subjects undergoing a hyperinsulinemic euglycemic clamp
Intervention: Insulin (Drug)
Breast cancer survivors
Breast cancer survivors undergoing a hyperinsulinemic euglycemic clamp
Intervention: Insulin (Drug)
Outcomes
Primary Outcomes
Insulin sensitivity status
Time Frame: 2 years
Glucose infusion rate during the hyperinsulinemic euglycemic clamp to ascertain the insulin sensitivity
Hepatic glucose production
Time Frame: 2 years
Measurements from the Hyperinsulinemic Euglycemic Clamp will be used to assess insulin effects on hepatic glucose production
Secondary Outcomes
- Proteomic changes in skeletal muscle(4 years)
- Insulin signaling(4 years)
Investigators
Lykke Sylow
Associate Professor
University of Copenhagen