# Potential Factors of Diabetes in Gitelman Syndrome and the Choices of the Appropriate Hypoglycemic Drugs: A Literature Narrative Review

## TL;DR

This paper reviews how Gitelman syndrome may lead to diabetes and suggests suitable drugs for managing blood sugar in affected patients.

## Contribution

The paper provides a narrative review linking Gitelman syndrome to diabetes and evaluates hypoglycemic drug choices due to lack of clinical trials.

## Key findings

- Gitelman syndrome is associated with glucose metabolism issues and higher diabetes prevalence.
- Hypomagnesemia and hypokalaemia in Gitelman syndrome impair insulin secretion and sensitivity.
- Hyperaldosteronism from Gitelman syndrome contributes to metabolic disturbances and diabetes risk.

## Abstract

Gitelman syndrome (GS) is a rare, autosomal recessive salt-losing tubulopathy caused by mutations in the SLC12A3 gene. It involves dysfunction of the sodium-chloride cotransporter positioned on the apical membranes of the distal convoluted tubule cells, causing sodium shortage and mimicking the use of thiazide diuretics. Hyperaldosteronism secondary to sodium depletion and hypovolemia causes hypokalaemia and metabolic alkalosis. This is associated with inhibition of the Transient Receptor Potential Cation Channel, Subfamily M, Member 6 –TRPM6 channel, which leads to urinary magnesium leakage and hypomagnesemia, subsequently stopping PTH secretion and resulting in hypocalcemia and hypocalciuria. Gitelman syndrome frequently presents later in life, as the symptoms are usually not very threatening. However, early identification, diagnosis, and urgent intervention are essential to improve patient prognosis and quality of life. Importantly, both hypomagnesemia and hypokalaemia can impair insulin secretion and sensitivity. Furthermore, hyperaldosteronism caused by the secondary activation of the R-A-A system can also lead to these disorders. Glucose metabolism problems have been shown to prevail amongst GS patients and manifest more frequently in comparison to the general population. When it comes to the treatment used to reduce hyperglycemia in GS-related T2DM, we consider which of the available drugs are the best for those patients. The article analyses the association of Gitelman syndrome with diabetes mellitus based on the available medical literature—as there are no clinical trials or meta-analyses available for this group, it is presented as a narrative review.