Longevity Science
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ANDROMAN
Last Updated
2025-10-20 11:49:00

Diabetes II (T2D)

Type 2 diabetes (T2D) is a chronic metabolic disease characterized by persistently high blood sugar levels caused by the body's inability to use insulin properly (insulin resistance) and/or insufficient insulin production by the pancreas.

Low testosterone and type 2 diabetes form a bidirectional vicious cycle where each condition worsens the other. Men with low testosterone develop increased visceral fat and insulin resistance, raising their diabetes risk, while diabetes itself—through mechanisms involving inflammation, insulin resistance, and obesity—further suppresses testosterone production by disrupting the brain-testicular hormone axis and increasing testosterone conversion to estrogen in fat tissue. This creates a self-perpetuating loop where declining testosterone leads to more belly fat and worse blood sugar control, which in turn causes even lower testosterone levels, making both conditions progressively harder to treat without addressing the underlying hormonal imbalance.

Bidirectional Bandage: Type 2 Diabetes ↔ Low Testosterone

T2D → Low Testosterone Insulin resistance and hyperinsulinemia suppress the hypothalamic-pituitary-gonadal axis. Chronic low-grade inflammation in T2D reduces LH/FSH secretion. Increased leptin and cytokine levels inhibit testicular testosterone production.

Low Testosterone → T2D Lower testosterone reduces muscle mass → lower insulin sensitivity. Promotes visceral fat → worsens insulin resistance. Decreased energy/motivation → less physical activity. Worsens glucose management and β-cell function.

Vicious circle: T2D promotes hormonal suppression → lower testosterone → more fat/insulin resistance → exacerbation T2D → etc.

Effect of TRT

  • Diabetes remission: 34% of men with T2D and hypogonadism achieved complete remission, meaning they discontinued all diabetes medications and maintained normal glucose levels (Observational registry study - lower quality).
  • Prevention of diabetes progression: Long-term TRT completely prevented progression from prediabetes to T2D over 8 years in hypogonadal men, with 0% progressing to diabetes in treated group vs 40% in untreated (Observational registry study - lower quality).
  • 40% risk reduction: TRT combined with lifestyle intervention reduced T2D risk by 40% in older men with prediabetes and abdominal obesity (RCT - high quality evidence from T4DM trial).
  • Improved glycemic control: Significant reductions in HbA1c (from 9.4% to 5.8%), fasting glucose, and insulin resistance (HOMA-IR) over 11 years, with 83% reaching HbA1c target of <6.5% (Observational registry study - lower quality).
  • Cardiovascular benefits: Reduced mortality (7.4% vs 16.1%), fewer heart attacks (0.4% vs 5.7%), and improved lipid profiles with sustained weight loss (Observational registry study - lower quality).
  • Mixed evidence on metabolic effects: Higher testosterone levels associated with 35% lower diabetes risk, but intervention trials show variable results for glucose control depending on age and study design (Meta-analysis of observational studies - moderate quality; Mixed RCT results - moderate quality).

Key limitation: Most dramatic effects come from uncontrolled observational studies, while the highest-quality RCT evidence shows more modest but significant prevention benefits.

Remission of type 2 diabetes following long‐term treatment with injectable testosterone undecanoate in patients with hypogonadism and type 2 diabetes: 11‐year data from a real‐world registry study (32558149) (2020) (Observational Study)
  • Long-term testosterone therapy in men with low testosterone and type 2 diabetes led to significant improvements in blood sugar control and insulin sensitivity.
  • About one-third of treated men achieved full remission of their diabetes, meaning they no longer needed medication and had normal blood sugar levels.
  • Treated men also saw reductions in weight, waist size, and risks of heart attacks, strokes, and other diabetes complications compared to untreated men.
  • No remissions or improvements occurred in the untreated group, highlighting testosterone as a potential additional therapy for diabetic men with low testosterone.
Testosterone and the prevention of type 2 diabetes mellitus: therapeutic implications from recent trials (39285839) (2024) (Review)
  • The T4DM study showed that testosterone treatment, combined with lifestyle changes, reduced type 2 diabetes risk by 40% in older men with belly fat and prediabetes.
  • Other trials found modest improvements in insulin sensitivity and body composition with testosterone therapy.
  • However, not all studies showed clear benefits for blood sugar control, and results vary by age and trial design.
  • Testosterone may help prevent diabetes in high-risk men, but more research is needed on its cost-effectiveness and combination with other treatments like GLP-1 drugs.
Testosterone Therapy in Men With Hypogonadism Prevents Progression From Prediabetes to Type 2 Diabetes: Eight-Year Data From a Registry Study (30862651) (2019) (Observational Study)
  • Long-term testosterone therapy completely prevented men with low testosterone and prediabetes from developing full type 2 diabetes over 8 years.
  • It improved blood sugar levels, cholesterol, and quality of life symptoms, while the untreated group saw worsening and 40% progressed to diabetes.
  • Treated men had fewer heart attacks and deaths compared to untreated men.
  • Testosterone shows strong potential to prevent diabetes in men with low levels and prediabetes.
Testosterone level and risk of type 2 diabetes in men: a systematic review and meta-analysis (29233816) (2017) (Systematic Review and Meta-Analysis)
  • Higher testosterone levels significantly lower the risk of type 2 diabetes in men, based on 13 studies with over 16,000 participants.
  • Low testosterone is linked to insulin resistance, obesity, and poor glucose control, increasing diabetes risk.
  • The study suggests low testosterone causes diabetes, not just the reverse, and testosterone therapy might help prevent it.
  • More trials are needed to confirm if boosting testosterone reduces diabetes risk in men with low levels.
Predictive value of serum testosterone for type 2 diabetes risk assessment in men (27230668) (2016) (Prospective Cohort Study)
  • Low testosterone predicts higher risk of developing type 2 diabetes in men over 5 years, independent of other risk factors.
  • A testosterone level below 16 nmol/L identifies about 43% of men at high risk, with good sensitivity for prediction.
  • Screening for low testosterone could spot men who might benefit from preventive lifestyle changes or treatments.
  • Testosterone may improve insulin sensitivity and body composition, helping prevent diabetes.
New evidence for the effect of type 2 diabetes and glycemic traits on testosterone levels: a two-sample Mendelian randomization study (37900148) (2023) (Mendelian Randomization Study)
  • Type 2 diabetes is linked to lower total testosterone and sex hormone-binding globulin levels in both men and women.
  • Higher fasting insulin and HbA1c levels are associated with reduced testosterone, especially in men.
  • These effects are independent of obesity and lipid issues, pointing to direct impacts from high blood sugar and insulin resistance.
  • Insulin and metformin treatments may help improve low testosterone in diabetic patients.
Impact of Metabolic Syndrome Factors on Testosterone and SHBG in Type 2 Diabetes Mellitus and Metabolic Syndrome (30057912) (2018) (Cross-Sectional Study)
  • Belly fat is the main reason for low testosterone in men with type 2 diabetes or metabolic syndrome, regardless of diabetes itself.
  • Low testosterone is tied to obesity, insulin resistance, and poor blood sugar control in these men.
  • The link between low testosterone and diabetes may be two-way, involving obesity and metabolic issues.
  • Losing weight around the waist could help raise testosterone levels and improve diabetes symptoms.
Type 2 Diabetes and Testosterone Therapy (No PMID) (2019) (RCT and Review)
  • Strong evidence links low testosterone to obesity, type 2 diabetes, and metabolic syndrome in men.
  • Testosterone therapy can improve blood sugar control, reduce fat, and lessen diabetes symptoms.
  • It may prevent or reverse diabetes in men with low testosterone, but long-term safety needs confirmation.