Introduction
Type 2 diabetes mellitus (T2DM) is the most common type of diabetes. According to studies, the pathophysiology of type 2 diabetes mellitus may be significantly influenced by endogenous sex hormones. Some research suggested a potential connection between testosterone and the risk of developing type 2 diabetes. The investigation discovered that low testosterone levels were linked to higher type 2 diabetes mellitus risk in men but lower type 2 diabetes mellitus risk in women. When compared to non-diabetics, type 2 diabetes mellitus patients had significantly lower testosterone levels on average.
According to recent studies, metabolic syndrome is more likely to occur in Caucasian and Asian men with low serum testosterone levels. Low serum testosterone levels are associated with undesirable clinical outcomes, such as cardiovascular disease (CVD) and early mortality, in Caucasian and Japanese males. The Endocrine Society's Clinical Practice Guideline, published in 2010, addressed testosterone replacement therapy for adult males with androgen deficiency syndrome in the context of the significant prevalence of low serum testosterone levels in patients with type 2 diabetes.
What Is the Role of Testosterone in Uncontrolled Type 2 Diabetes?
The link between low levels of serum testosterone and type 2 diabetes, both featuring obesity and insulin resistance as key characteristics, can be explained by several mechanisms.
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Testosterone reduced insulin resistance by increasing catecholamine-induced lipolysis in vitro by lowering lipoprotein lipase activity and triglyceride uptake in human abdominal tissue in vivo. Both in vitro and in vivo studies revealed that hypertriglyceridemia increased free fatty acids and decreased insulin clearance.
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It aided in the development of insulin resistance and hyperinsulinemia (higher levels of insulin in the blood).
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Thus, testosterone may enhance insulin resistance by encouraging lipolysis (release of fatty acids from the breakdown of lipids and other fats) and myogenesis (it is the growth of skeletal muscle, especially during embryonic development).
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Testosterone was found to influence the genes involved in glucose metabolism in the skeletal muscle of mice in microarray experiments, which reduced systemic insulin resistance.
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Hepatic androgen receptor signaling prevented the onset of insulin resistance in mice.
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The body composition is altered, and body fat is decreased by androgen, which lowers insulin resistance.
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The vicious cycle of obesity and low serum testosterone level in obese men may be exacerbated by the peripheral conversion of testosterone to estrogen.
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It may reduce the intensity of luteinizing hormone pulses and centrally restrict testosterone production.
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Hypothalamic - Pituitary-gonadal axis dysregulation brought on by genetic-environmental interactions can result in low testosterone, changes in body composition, insulin resistance, and low-grade inflammation, all of which raise cardiovascular risk.
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This atypical metabolic environment can change the level of sex hormone-binding globulin, which lowers the bioavailability of testosterone.
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Low testosterone may be linked to decreased erythropoiesis, which could activate cell cycle signaling pathways, including angiotensin II, to raise cardiovascular risk.
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On the other hand, variations in assay standards might make it difficult to accurately measure and interpret the level of free and total testosterone.
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Adipose tissue may control Leydig's cell function because it is an endocrine organ. Leptin, an adipokine, has been found to be negatively associated with men's serum testosterone levels in order to achieve this.
What Are the Effects of Age on Serum Testosterone Level?
Sex hormone levels are known to diminish with age, and this is probably due to a combination of abnormalities in the pituitary, hypothalamus, and testicles. In older men, reduced testicular response to gonadotropins was accompanied by altered and inhibited hypothalamic pulse generator pulsatility. A significant, independent, and prolonged effect of age on blood total testosterone levels was seen in several studies. In Caucasian men, there has also been documented evidence of an age-independent, substantial graded negative relationship between serum testosterone levels and insulin levels.
What Is the Association Between Testosterone and Metabolic Syndrome?
An increased prevalence of MES is frequently linked to low testosterone levels. Insulin resistance, hypertension, dyslipidemia, and obesity (especially central adiposity) are among the metabolic risk factors grouped together as a metabolic end-stage syndrome (MES), which is partly caused by modernization and changing lifestyles. The prognostic usefulness of MES for the continued type 2 diabetes and cardiovascular disease development, while there is an ongoing dispute as to whether this is due to the additive or multiplicative effects of these components. More recent research revealed a connection between this condition and other illnesses such as cancer, non-alcoholic fatty liver disease, rheumatoid arthritis, chronic kidney disease, and even non-alcoholic steatosis.
How Is Testosterone Therapy Beneficial in Treating Type 2 Diabetes Mellitus?
In hypogonadal males with type 2 diabetes, testosterone replacement therapy lowers insulin resistance and enhances glycemic control. In hypogonadal men, testosterone replacement therapy lowers total cholesterol, although high-density lipoprotein cholesterol does not alter significantly. Men with chronic heart failure who receive testosterone replacement therapy are demonstrated to have an immediate decrease in peripheral vascular resistance and an increase in cardiac index. The insulin resistance evaluation model based on homeostasis, total cholesterol, and low-density lipoprotein cholesterol showed that testosterone supplementation reduced cardiovascular risk, including a reduction in insulin resistance. Although better glycemic control could be anticipated from a reduction in insulin resistance, the effects of a decrease in hemoglobin A1c (a secondary outcome) were not evident at the conclusion of the study because most participants had controlled type 2 diabetes (hemoglobin A1c 6.5 percent). The effect was complicated by changes in anti-diabetic medications that were ethically permitted.
Conclusion
In hypogonadal males with type 2 diabetes, testosterone therapy decreases insulin resistance and enhances glycemic management. A decrease in HbA1c (hemoglobin A1c) in type 2 diabetic patients was linked to fewer microvascular problems and myocardial infarction, according to the United Kingdom Prospective Diabetes Study (UKPDS). Additionally, testosterone therapy can reduce ischemia in men with chronic stable angina. However, men with coronary artery disease have much lower amounts of free and accessible testosterone. Thus, testosterone replacement treatment in hypogonadal type 2 diabetes males may enhance glycemic control and lower microvascular and cardiovascular events in these patients.
