Effect of Gender Affirming Hormone Therapy on Glucose Metabolism

Study Overview
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Brief Summary
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The study will test: whether estrogen treatment in transwomen is associated with improved insulin sensitivity and beta cell function whether testosterone treatment in transmen is associated with worsening insulin sensitivity and beta cell function whether estrogen therapy leads to enhanced immune response in older transwormen

Detailed Description
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All subjects will participate in a 2-hour oral glucose tolerance test (OGTT) and DXA scan for estimation of lean body mass. Only the transgender subjects will have a repeat OGTT two weeks after discontinuation of Gender Affirming Hormone Therapy (GAHT). Beta cell function will be correlated with the Estrogen/Testosterone ratio to evaluate the relationship between sex hormones and beta cell function. Plasma Glucagon-like peptide 1 (GLP-1) response during the OGTT will be measured to evaluate if estrogen treatment modulates insulin secretion by increasing GLP-1 secretion.

Official Title
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Effect of Gender Affirming Hormone Therapy on Glucose Metabolism

Conditions
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Transgender Persons

Intervention / Treatment
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* Drug: Botnia Clamp
* Other: Withdrawal of Gender Affirming Hormone Therapy (GAHT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers: healthy male or female MTF transgender FTM transgender Non-diabetic (A1c<6.5%), fasting glucose <126mg/dl and OGTT after 2 hr <200mg/dl) Stable hormone treatment (estrogen or testosterone) for at least 6 months Exclusion Criteria: History of or newly diagnosed diabetes mellitus For healthy volunteers, not current treatment with estrogen or testosterone For FTM transgender, no recent cardiovascular event: acute coronary syndrome (ACS), stroke (CVA) For MTF and FTM transgender, less than 6 months of stable hormone treatment Anemia with hemoglobin (Hb) <11.0 hematocrit (Hto) < 34 and Glomerular Filtration rate (GFR) <30

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: MTF and FTM non-diabetic transsexuals will be compared to healthy female and male subjects respectively.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy Volunteer Male<br>Healthy male currently on no testosterone treatment | Drug: Botnia Clamp<br>* This clamp technique is designed to obtain independent measures of insulin secretion and insulin sensitivity during the same test. In brief, 0.3g/kg body wt of a 20% glucose solution is given at time 0. Blood samples for the measurement of plasma glucose and serum insulin are obtained at -10, 0, 2, 4, 6, 8, 10, 20, 30, 40, 50, 60, 120, and 180 min.<br>* Other names: Glucose solution and insulin;|
| Active Comparator: Healthy Volunteer Female<br>Healthy female currently on no estrogen treatment | Drug: Botnia Clamp<br>* This clamp technique is designed to obtain independent measures of insulin secretion and insulin sensitivity during the same test. In brief, 0.3g/kg body wt of a 20% glucose solution is given at time 0. Blood samples for the measurement of plasma glucose and serum insulin are obtained at -10, 0, 2, 4, 6, 8, 10, 20, 30, 40, 50, 60, 120, and 180 min.<br>* Other names: Glucose solution and insulin;|
| Active Comparator: MTF group<br>MTF transgender currently on estrogen treatment | Drug: Botnia Clamp<br>* This clamp technique is designed to obtain independent measures of insulin secretion and insulin sensitivity during the same test. In brief, 0.3g/kg body wt of a 20% glucose solution is given at time 0. Blood samples for the measurement of plasma glucose and serum insulin are obtained at -10, 0, 2, 4, 6, 8, 10, 20, 30, 40, 50, 60, 120, and 180 min.<br>* Other names: Glucose solution and insulin;Other: Withdrawal of Gender Affirming Hormone Therapy (GAHT)<br>* GAHT, either estrogen or testosterone therapy will be withdrawn after the Botnia Clamp.<br>|
| Active Comparator: FTM group<br>FTM transgender group currently on testosterone treatment | Drug: Botnia Clamp<br>* This clamp technique is designed to obtain independent measures of insulin secretion and insulin sensitivity during the same test. In brief, 0.3g/kg body wt of a 20% glucose solution is given at time 0. Blood samples for the measurement of plasma glucose and serum insulin are obtained at -10, 0, 2, 4, 6, 8, 10, 20, 30, 40, 50, 60, 120, and 180 min.<br>* Other names: Glucose solution and insulin;Other: Withdrawal of Gender Affirming Hormone Therapy (GAHT)<br>* GAHT, either estrogen or testosterone therapy will be withdrawn after the Botnia Clamp.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of Chronic estrogen therapy on insulin secretion | Change in GLP-1 in response to glucose | Baseline to 180 minutes | 
| Effects of Chronic estrogen therapy on insulin sensitivity | Change in beta cell function | Baseline to 6 months | 
| Effects of Chronic testosterone therapy on insulin secretion | Change in GLP-1 in response to glucose | Baseline to 180 minutes | 
| Effects of Chronic testosterone therapy on insulin sensitivity | Change in beta cell function | Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune response change | Withhold GAHT for 2 weeks after Botnia Clamp | Baseline to 6 months |