Sex differences in glucose-regulating neurohormonal pathways-potential impact for type 2 diabetes development

Area of Science:

• Endocrinology
• Metabolic Health
• Diabetes Research

Background:

• Men have a higher risk of developing type 2 diabetes (T2D) compared to women.
• Understanding sex differences in hormonal regulation is crucial for explaining T2D risk disparities.

Purpose of the Study:

• To investigate sex differences in counter-regulatory hormone dynamics.
• To determine the influence of sex hormones, menopausal status, and metabolic phenotypes on these differences.
• To explore the link between hormone dynamics, insulin resistance, and T2D propensity.

Main Methods:

• 22 men and 28 women (including postmenopausal) underwent clamp studies assessing counter-regulatory hormones and heart rate variability (HRV).
• Fasting plasma samples were analyzed for sex hormones (testosterone, estradiol).
• Multilinear regressions were used to identify predictors of neurohormonal responses.

Main Results:

• Men showed higher glucagon, ACTH, cortisol, and GH responses during hypoglycemia compared to women.
• Men exhibited greater sympathetic dominance and lower GH during normo- and hyperglycemia.
• Central adiposity (waist-to-hip ratio) predicted hormonal responses, while sex hormones did not.
• Postmenopausal women had lower GH and less favorable HRV than premenopausal women.

Conclusions:

• Elevated glucose-dependent counter-regulatory hormonal responses in men may contribute to higher insulin resistance and T2D risk.
• Central adiposity, rather than sex hormone profiles, partially explains observed sex differences in neurohormonal responses.
• These findings highlight potential therapeutic targets for mitigating T2D risk in men.