Abstract 4434: Association of Elevated Serum Glucose Levels with Hypokalemia Independent of Treatment in Hypertensive Patients: Implications for the Development of New Diabetes
Thiazide diuretics can produce impaired glucose tolerance and are associated with an increased risk of developing diabetes. Although increased serum glucose concentrations during thiazide therapy have been linked to thiazide-induced hypokalemia, whether hypokalemia per se is associated with elevations of serum glucose over time has not been examined. Baseline and annual serum glucose levels were examined as a function of quartiles of serum potassium (K) levels in 6947 patients in the LIFE study with no history of diabetes who did not develop diabetes during the study. Patients were randomized to losartan vs atenolol-based treatment and additional hydrochlorothiazide (HCTZ) therapy as needed. Serum glucose was highest in the quartile with lowest serum K at baseline and throughout the study and decreased across quartiles of K (Table⇓). The association between hypokalemia and elevated serum glucose was highly significant at baseline and each year of the study and was independent of randomized and HCTZ treatment, serum creatinine, and of baseline levels and changes in blood pressure and ECG left ventricular hypertrophy. Repeated measures analysis of covariance further demonstrated that serum glucose increased over time (p<0.001) and that the relationship of serum glucose to quartiles of K was significant over time (p=0.001) and varied across quartiles (p=0.003 for the interaction between glucose over time and quartiles of K). Elevated serum glucose levels are associated with hypokalemia during antihypertensive therapy, independent of the potential impact of treatment with losartan vs atenolol and with HCTZ and of baseline glucose levels and other potential factors that could influence glucose levels. These findings suggest that hypokalemia per se may be a stimulus to development of abnormal glucose tolerance and provide insights into the relationship between antihypertensive treatment and development of diabetes.