Growth Hormone and Its Role in Diabetes Development

Fig 1: Diabetes Awareness Month promotional graphic highlighting the importance of education and early detection. From “November Is Diabetes Awareness Month,” by NEW Health

Introduction

Growth hormone (GH) is essential for growth and metabolic balance. When GH levels

become excessive, either from internal overproduction or external administration, it can disrupt normal glucose regulation. This condition, often referred to as GH induced diabetes, occurs because GH significantly reduces insulin sensitivity and increases glucose production (1,2).

How GH Affects Glucose Regulation

GH has strong anti insulin actions. It promotes hyperglycemia through several mechanisms (2,3,4):

• Increased hepatic gluconeogenesis (3)

• Increased lipolysis which raises free fatty acids and interferes with insulin signaling (4)

• Reduced insulin mediated glucose uptake in muscle tissue (1,5)

These factors create systemic insulin resistance, which is the primary mechanism behind GH induced disturbances in glucose metabolism.

Fig 2:Overview of the mechanisms linking acromegaly, growth hormone excess and glucose dysregulation. From “Diabetes Secondary to Acromegaly: Physiopathology, Clinical Features and Effects of Treatment,”

Situations Where GH Leads to Diabetes

a. Acromegaly

Chronic elevation of GH and IGF 1 is strongly associated with insulin resistance, impaired glucose tolerance and diabetes. Between 20 and 50 percent of patients develop diabetes (1,6,7).

b. GH Therapy

Physiologic GH replacement is generally safe, but high dose therapy increases the risk of hyperglycemia (8,9). Supraphysiologic GH use in athletes and bodybuilders also increases insulin resistance (9).

c. Metabolic Risk Factors

People with pre existing metabolic risk such as obesity, family history of diabetes, PCOS or previous gestational diabetes have a significantly greater likelihood of developing GH related glucose abnormalities (10,11).

Clinical Presentation

Patients may develop the following signs (2,6):

• Elevated fasting glucose

• Increased HbA1c

• Polyuria, polydipsia and fatigue

• Worsening of pre existing insulin resistance

In acromegaly, altered glucose regulation may appear early and may be one of the first metabolic consequences to be detected (6,7).

Diagnosis

Diagnosis follows standard ADA and WHO diabetes criteria (12,13):

• Fasting glucose at or above 7.0 mmol L

• HbA1c at or above 6.5 percent

• Two hour OGTT at or above 11.1 mmol L

Routine glucose monitoring is recommended for people receiving long term GH therapy or those with acromegaly (5,8).

Management Strategies

a. Treat Excess GH

• Surgical removal of pituitary adenoma when present (1,6)

• Somatostatin analogs, GH receptor antagonists and dopamine agonists can reduce GH and improve glucose metabolism (7,14)

Correcting GH excess often improves insulin sensitivity.

b. Manage Diabetes

• Lifestyle modification including diet and exercise

• Metformin as first line therapy for insulin resistance (12)

• Other agents such as GLP 1 agonists may be beneficial (13)

c. Monitor and Adjust GH Therapy

In GH treated patients, careful dose titration or reduction can improve glycemic control (8,9).

Key Points for Learning

• GH induced diabetes results mainly from insulin resistance produced by GH effects on liver, muscle and fat.

• Greatest risk occurs in acromegaly, high dose GH treatment or GH misuse.

• Regular screening is essential in at risk individuals.

• Treating GH excess significantly improves glucose levels.

References

1. Melmed, S. (2009). Acromegaly: Pathogenesis and treatment. Journal of Clinical Investigation, 119(11), 3189–3202. https://doi.org/10.1172/JCI39375

   
   

2. Clemmons, D. R. (2010). Metabolic actions of growth hormone. Endocrinology and Metabolism Clinics of North America, 39(1), 47–57. https://doi.org/10.1016/j.ecl.2009.11.003

   
   

3. Møller, N. (2003). Growth hormone and glucose metabolism. Hormone Research, 60(Suppl. 1), 37–41. https://doi.org/10.1159/000071222

   
   

4. Vijayakumar, A., Yakar, S., & Leroith, D. (2011). The intricate role of growth hormone in metabolism. Frontiers in Endocrinology, 2, Article 32. https://doi.org/10.3389/fendo.2011.00032

   
   

5. Kopchick, J. J., Andry, J. M., & Laron, Z. (2019). Growth hormone actions: An update. Molecular and Cellular Endocrinology, 499, 110606. https://doi.org/10.1016/j.mce.2019.110606

   
   

6. Chanson, P., Salenave, S., & Kamenicky, P. (2014). Acromegaly. Handbook of clinical neurology, 124, 197–219. https://doi.org/10.1016/B978-0-444-59602-4.00014-9

   
   
   
   

7. Katznelson, L., Laws, E. R., Melmed, S., Molitch, M. E., Murad, M. H., Utz, A., & Wass, J. A. H. (2014). Acromegaly: An Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism, 99(11), 3933–3951. https://doi.org/10.1210/jc.2014-2700

   
   

8. Yuen, K. C. J., Popovic, V., & Hoffman, A. R. (2013). Effects of growth hormone therapy on glucose metabolism. Clinical Endocrinology, 78(1), 17–29. https://doi.org/10.1111/cen.12151

   
   

9. Holt, R. I. G., & Sonksen, P. H. (2010). Growth hormone use in sport. Endocrinology and Metabolism Clinics of North America, 39(1), 11–23. https://doi.org/10.1016/j.ecl.2009.11.002

   
   

10. De Leo, V., Musacchio, M. C., Cappelli, V., Massaro, M. G., Morgante, G., & Petraglia, F. (2016). Genetic, hormonal and metabolic aspects of PCOS: an update. Reproductive biology and endocrinology : RB&E, 14(1), 38. https://doi.org/10.1186/s12958-016-0173-x

    
    

11. Bellamy, L., Casas, J. P., Hingorani, A. D., & Williams, D. (2009). Type 2 diabetes mellitus after gestational diabetes: A systematic review and meta-analysis. The Lancet, 373(9677), 1773–1779. https://doi.org/10.1016/S0140-6736(09)60731-5

    
    

12. American Diabetes Association. (2023). 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes 2023. Diabetes Care, 46(Suppl. 1), S19–S40. https://doi.org/10.2337/dc23-S002

    
    

13. World Health Organization. (2006). Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. WHO Press.

    
    

14. Higham, C. E., Johannsson, G., & Shalet, S. M. (2016). Management of endocrine disease: Long term safety of growth hormone replacement therapy. Clinical Endocrinology, 84(6), 702–710. https://doi.org/10.1111/cen.13061

Figure 1:NEW Health. (2021, November 1). November is Diabetes Awareness Month [Web page]. NEW Health. https://newhealth.org/our-community/november-is-diabetes-awareness-month/

Figure 2:Ferraù, F., Albani, A., Ciresi, A., Giordano, C., & Cannavò, S. (2018). Diabetes secondary to acromegaly: Physiopathology, clinical features and effects of treatment. Frontiers in Endocrinology, 9, 358. https://doi.org/10.3389/fendo.2018.00358

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