madman
Super Moderator
Insulin plays a central role in blood glucose regulation, with insulin resistance contributing to the progression of prediabetes to diabetes, underscoring the importance of early intervention. Androgens, primarily synthesized in the testis under pituitary gland influence, impact male reproductive function. Testosterone, crucial for sexual development and secondary male characteristics, declines with age, leading to issues like anemia, sexual dysfunction, and reduced bone density. Sex-specific differences in glucose metabolism highlight males’ lower insulin sensitivity and less effective glucose utilization compared to females due to androgenic effects. Testosterone’s intricate role extends to potential benefits in glycemic control, fat mass reduction, and muscle strength increase in men with diabetes. However, cautious consideration of testosterone therapy is crucial, especially in the presence of underlying health conditions, warranting further research for clear guidelines in managing hyperglycemia.
Introduction
A body of evidence from studies in human male subjects [1–3] and animal models [4] suggests that low blood testosterone levels may induce insulin resistance and type 2 diabetes mellitus. Possible causality may also go in the opposite direction, since research data also indicate that hyperglycemia may lead to hypogonadism in males [5,6]. From a physiological perspective, this bidirectional relationship between testosterone insufficiency and dysglycemia is complex and largely unknown. It can be attributed in part to effects on body composition, including mainly changes in visceral fat and muscle mass. However,direct actions of androgens on insulin synthesis and action are also possible. Hence, it is reasonable to hypothesize that the administration of testosterone may be able to arrest the exacerbation of metabolic syndrome and prediabetes in obese individuals and improve glycemic management in people with overt diabetes mellitus. Indeed, contemporary research efforts have focused on elucidating the mutual relationship between androgen action and glucose homeostasis and, by extension, the contribution of testosterone to cardiometabolic health [7]. In order to answer these questions,it is appropriate to review and understand the physiology of glycemic regulation, the mechanism of androgenic synthesis and action, as well as their interrelationship within the body’s homeostasis.
*Physiology of Insulin
*Glucose Homeostasis and Insulin Resistance
*Diabetes Mellitus
*Synthesis and Secretion of Androgens
*Actions of Testosterone
*Sex-Specific Differences in Glucose Metabolism
*The Impact of Androgens on Glycemia
*Treatment of Hyperglycemia with Testosterone
Conclusion
The intricate and multidirectional link between testosterone and glucose homeostasis may entail multiple pathways (Fig. 2, Ref. [76]). The relationship between testosterone and insulin sensitivity—either directly or through effects on inflammation, energy expenditure, and hormone secretion—is a key element. Comorbidities related to aging may increase insulin resistance and lower testosterone levels. Moreover, variations due to age, ethnicity, and lifestyle choices significantly impact androgen synthesis and the risk of developing diabetes, underscoring the importance of these factors in clinical considerations.
The current evidence and recommendations regarding the use of exogenous testosterone in treating dysglycemia are vague. Future research should test the effectiveness and safety of androgens in clinical trials. Optimal glycemic control, lifestyle interventions, and treatment of comorbidities remain the first-line approach to the management of men with hyperglycemia and low testosterone levels. When reliable studies provide favorable evidence regarding the risk-benefit ratio of testosterone therapy, the latter may become an option. Currently, it can be occasionally considered only in men with diabetes and low circulating testosterone when lifestyle measures and anti-diabetic medications fail to achieve satisfying glycemic control. However,what constitutes a sufficient circulating testosterone level is unknown, and thus, prior discussion with the candidate recipient is necessary.
Introduction
A body of evidence from studies in human male subjects [1–3] and animal models [4] suggests that low blood testosterone levels may induce insulin resistance and type 2 diabetes mellitus. Possible causality may also go in the opposite direction, since research data also indicate that hyperglycemia may lead to hypogonadism in males [5,6]. From a physiological perspective, this bidirectional relationship between testosterone insufficiency and dysglycemia is complex and largely unknown. It can be attributed in part to effects on body composition, including mainly changes in visceral fat and muscle mass. However,direct actions of androgens on insulin synthesis and action are also possible. Hence, it is reasonable to hypothesize that the administration of testosterone may be able to arrest the exacerbation of metabolic syndrome and prediabetes in obese individuals and improve glycemic management in people with overt diabetes mellitus. Indeed, contemporary research efforts have focused on elucidating the mutual relationship between androgen action and glucose homeostasis and, by extension, the contribution of testosterone to cardiometabolic health [7]. In order to answer these questions,it is appropriate to review and understand the physiology of glycemic regulation, the mechanism of androgenic synthesis and action, as well as their interrelationship within the body’s homeostasis.
*Physiology of Insulin
*Glucose Homeostasis and Insulin Resistance
*Diabetes Mellitus
*Synthesis and Secretion of Androgens
*Actions of Testosterone
*Sex-Specific Differences in Glucose Metabolism
*The Impact of Androgens on Glycemia
*Treatment of Hyperglycemia with Testosterone
Conclusion
The intricate and multidirectional link between testosterone and glucose homeostasis may entail multiple pathways (Fig. 2, Ref. [76]). The relationship between testosterone and insulin sensitivity—either directly or through effects on inflammation, energy expenditure, and hormone secretion—is a key element. Comorbidities related to aging may increase insulin resistance and lower testosterone levels. Moreover, variations due to age, ethnicity, and lifestyle choices significantly impact androgen synthesis and the risk of developing diabetes, underscoring the importance of these factors in clinical considerations.
The current evidence and recommendations regarding the use of exogenous testosterone in treating dysglycemia are vague. Future research should test the effectiveness and safety of androgens in clinical trials. Optimal glycemic control, lifestyle interventions, and treatment of comorbidities remain the first-line approach to the management of men with hyperglycemia and low testosterone levels. When reliable studies provide favorable evidence regarding the risk-benefit ratio of testosterone therapy, the latter may become an option. Currently, it can be occasionally considered only in men with diabetes and low circulating testosterone when lifestyle measures and anti-diabetic medications fail to achieve satisfying glycemic control. However,what constitutes a sufficient circulating testosterone level is unknown, and thus, prior discussion with the candidate recipient is necessary.
