DAME-Trial
The effect of transdermal 17-β-estradiol/progesterone supplementation on glucose regulation in peri- and postmenopausal women with type 1 and type 2 diabetes
Background and Rationale
2 out of 3 of women with T1D experience changes in their glucose regulation after menopause. During the menopausal transition, estrogen levels significantly decline in women. This estrogen deficiency is associated with adverse metabolic changes, including increased insulin resistance, altered lipid profiles, and central adiposity. These metabolic changes may exacerbate glycemic dysregulation in women with type 1 and 2 diabetes.
Some metabolic changes associated with the menopausal transition may be mitigated by menopausal hormone therapy (MHT). MHT has shown to have favorable effects on insulin sensitivity, glucose metabolism, and liver steatosis in healthy postmenopausal women. In postmenopausal women with type 2 diabetes (T2D), oral MHT has been suggested to have a beneficial effect on fasting glucose, HbA1c and insulin resistance. The beneficial effect on glucose metabolism of MHT is most likely from estrogen. To date, however, little attention has been devoted to the effect of MHT on glycaemic regulation in peri- and postmenopausal women with diabetes.
Study Objectives
The primary objective is to determine the effect of MHT (transdermal 17-β-estradiol combined with oral micronized progesterone) on glucose regulation in peri- and early postmenopausal women with diabetes mellitus (type 1 or 2) and climacteric symptoms.
Secondary objectives are:
- the influence of menopausal symptoms on glucose regulation and changes in insulin sensitivity
- cardiovascular risk factors
- liver steatosis,
- sleep quality
- (diabetes related) quality of life.
Study Design & Study Population
The DAME-trial is an open-label cross-over clinical trial. The study visits take place at Amsterdam UMC, location AMC and the study has a duration of 28 weeks. All participants undergo an intervention period of 12 weeks with estradiol/progesterone therapy and 16 weeks without therapy. Peri- and postmenopausal women with type 1 or type 2 diabetes who use insulin and experience menopausal symptoms are eligible to participate in this study.
Menopausal Hormone therapy (MHT) consists of 50 mcg/24h 17-β-estradiol transdermal patch (administered twice a week) in combination with continuous (for postmenopausal women) or sequential 14 days/month (for perimenopausal women) oral micronized progesterone 200mg.
Study Procedures and Data Collection
The study consists of five study visits (week 0, 10, 12, 26 and 28) and the following assessments are performed:
- 2x continuous glucose monitoring
- 2x 24H blood pressure measurements (at home)
- 2x hyperinsulinemic euglycemic clamp to measure insulin sensitivity
- Blood samples
- Questionnaires
Visit 1, 2 and 4 take between 30 minutes and one hour, visit 3 and 5 take 8 hours. Participants receive a reimbursement for travel costs.
Inquiries about this study can be sent to diabetesmenopauze@amsterdamumc.nl