Changes in serum potassium mediate thiazide-induced diabetes.

Changes clinical practice - Before starting hydrochlorothiazide (HCT) treatment, serum potassium levels should be monitored and potassium should be supplemented when giving HCTs.

Based on the data of the Systolic Hypertension in Elderly Program (SHEP) study, the authors found that obviously a significant loss of potassium due to the use of hydrochlorothiazides (HCTs) for treating hypertension is responsible for increased incidence of glucose intolerance and type 2 diabetes mellitus after long-term treatment with HCTs.

It has been known for more than 50 years that the use of HCTs for treating hypertension is associated with an increased risk of developing an impaired glucose tolerance or type 2 diabetes mellitus. However, mechanisms for that phenomenon remained rather unclear. While re-evaluating data of 3790 non-diabetic participants form the SHEP study, Shafi et al. found that the incidence of type 2 diabetes mellitus during the first year of HCT medication was clearly associated with a significant decrease of serum potassium levels. The authors speculate that the tissue loss of potassium could have been even higher because it takes a hard dietary regime to reduce serum potassium to critical values. It is well-known that the release of insulin from the pancreatic beta-cells is controlled via ATP-sensitive potassium channels and L-type calcium channels on the cell surface. Therefore, a decrease in serum potassium levels might be associated with a disturbed function of these channels due to tissue potassium depletion. Interestingly, the association between the use of HCTs and diabetes was observed only during the first year of treatment, not thereafter. Obviously, it depends on the initial potassium loss after starting HCT therapy if diabetes develops. Interestingly, the development of diabetes can be prevented by supplementing potassium. However, in order to further elucidate the mechanism leading to HCT-induced diabetes, further sophisticated controlled clinical trials are needed.