The Role of Testosterone Therapy in the Prevention and Management of Type 2 Diabetes

Introduction:

Type 2 diabetes (T2D) is one of the fastest-rising chronic illnesses globally, attributable greatly to (abdominal) obesity. Obesity is a significant risk factor for testosterone deficiency (TD), which promotes fat storage, insulin resistance (IR), and control of glycemia, creating a vicious loop. Because obesity and T2D are often seen together, the term ‘diabesity’ was coined to characterize this disease. Weight loss through lifestyle modifications is a fundamental approach for obesity and T2D. To avoid diabetes, however, a significant weight loss of around 10 percent is necessary, as well as maintaining the lost body weight.

The major concern is that long-term weight loss maintenance is poor, with patients regaining half of their lost weight after one year and roughly three-quarters of their lost weight after three years. After completing a weight-reduction program, less than 3 percent of participants retained their lost weight at all yearly checkups for four to five years. As a result, as seen by the continued and rising incidence of these dysmetabolic disorders, lifestyle modification alone is insufficient to treat or prevent obesity or T2D.

What Is the Role of Type 2 Diabetes In Systemic Diseases?

• The most common kind of diabetes is type 2 diabetes mellitus (T2DM) is linked with various problems such as cardiovascular disease, peripheral neuropathy, stroke, infection, chronic renal failure, and retinopathy.

• As a result, both diabetes prevention and management are crucial. Standard T2DM treatment comprises lifestyle changes, oral hypoglycemic medications, and insulin injections to compensate for the advancing-cell failure.

What Is the Relation between Low Testosterone and Insulin Resistance (IR)?

Men with low testosterone have elevated resistance to insulin, which is one of the underlying reasons for T2D. The substantial negative relationship between testosterone and IR is age-independent, and low testosterone levels are related to IR even in young non-obese males. Serum testosterone levels in males have been linked to insulin sensitivity throughout the entire glucose tolerance spectrum, independent of age.

• Bidirectional Link between Low Testosterone, Obesity, and Type 2 Diabetes:

  1. The relative strength of the bidirectional link between low testosterone and diabetes is an issue of scientific debate, that is, whether obesity (and to a lesser extent T2D, particularly if left uncontrolled) has a higher impact on decreasing testosterone, or whether low testosterone has a higher impact on the accumulation of the fat and IR. However, this is insignificant in practical practice.

  2. The bidirectional relationship between low testosterone and diabetes generates a vicious cycle in which one disease exacerbates the other, regardless of which developed first. The crucial question in clinical practice is how to interrupt this vicious cycle most sustainably and effectively.

What Are the Real-World Evidence Studies of Testosterone Therapy (TTh) For the Prevention of T2D?

• Testosterone therapy(TTh) regularly leads to a considerable decrease in fat mass and an increase in lean mass, body composition alterations that have positive metabolic consequences. Real-world evidence analyses of men with hypogonadism have demonstrated that treatment with testosterone undecanoate injections for eight to eleven years completely suppressed the progression of prediabetes to T2D by restoring normoglycemia, and enhanced glucose metabolism in men with T2D, with 34.3 percent experiencing remission.

Is hba1c an Accurate Marker of Glycemic Control in Men with Low Testosterone?

• An increasing number of studies show that using HbA1c as an end metric to assess the efficacy of testosterone therapy (TTh) on glycemic control in males having testosterone deficiency (TD) can be deceiving.

• HbA1c levels are connected to blood glucose levels and the lifecycle of red blood cells (RBCs). At any given average blood glucose level, a shorter lifespan of RBC reduces HbA1c, but a longer RBC lifespan raises HbA1c.

• It has been demonstrated that males with TD may have shorter RBC life and, therefore, false-negative HbA1C readings, but TTh can prolong RBC lifespan.

• This might explain the inconsistency of results in earlier RCTs evaluating the impact of TTh on HbA1c in males with TD and T2D, as well as testosterone for diabetes mellitus study, which discovered that TTh dramatically decreased the occurrence of T2D without any change in HbA1c.

What Are the Current Guidelines on Testosterone Therapy for Diabetics?

• The Endocrine Society in 2018 proposed guidelines that testosterone treatment be reserved for well-documented cases of hypogonadism. The 2018 guidelines vary from the 2010 guidelines in that they conduct a more thorough analysis of testosterone's effectiveness and safety using RCTs published within the previous three years.

• The recommendations also note that there is still a lot of ambiguity regarding the benefits and hazards of testosterone treatment and inefficient testosterone management practices. A proper diagnostic testing and monitoring strategy are essential in all situations.

What Is the Role of Testosterone Replacement Therapy in the Treatment of Obesity and Type 2 Diabetes?

• Long-term studies investigating the effect of TRT on poor metabolic health yield encouraging outcomes. One research examined men with low testosterone and either metabolic syndrome or type 2 diabetes for around six years. Those who maintained healthy testosterone levels following TRT demonstrated improvement significantly in:

  1. Glycemic management (reduction in fasting glucose levels).

  2. Weight reduction.

  3. Decreased cardiovascular risk.

These findings confirm the advantages of treating low testosterone first, improving the chances of breaking the cycle of low testosterone, obesity, and diabetes.

Conclusion:

According to various studies, increased testosterone levels can dramatically reduce the incidence of T2DM in males, and testosterone is an essential preventive factor against T2DM in men. Furthermore, additional study is needed to determine the efficacy of testosterone therapy on lowering T2DM risk in persons with testosterone deficiency and the effect of testosterone therapy on enhancing clinical outcomes in male T2DM patients.