Abstract 985: Renin-Angiotensin System (RAS) Blockade Ameliorates Diuretic Induced Hyperglycemia in Obese Hypertensive Normoglycemic or Prediabetic Individuals
In hypertensive patients, the negative metabolic effects of hydrochlorothiazide (HCTZ) therapy are thought to be heightened in those most susceptible to the development of diabetes. The purpose of this analysis was to compare the fasting and postprandial metabolic response to HCTZ therapy in patients with normal fasting glucose levels (<100 mg/dL) to those in the prediabetic range (≥100 and <126 mg/dL). The study was conducted in 399 obese, hypertensive patients without diabetes who were randomized to combination therapy for 16 weeks with either valsartan/HCTZ (320/25 mg) or amlodipine/HCTZ (10/25 mg). Patients treated with amlodipine/HCTZ group had an elevated fasting and postprandial glycemic response when compared to treatment with valsartan/HCTZ therapy (which was not different from baseline). Regardless of whether baseline fasting plasma glucose levels were in the normal or pre-diabetic range, fasting glucose increased from baseline in the amlodipine/HCTZ more than in the valsartan/HCTZ group (Table⇓). The addition of valsartan to HCTZ therapy also ameliorated the glycemic response to an oral glucose challenge in both normal and pre-diabetic patients. This was achieved through a heightened early phase insulin response in patients on valsartan/HCTZ therapy compared to amlodipine/HCTZ. In conclusion, the benefit of using the RAS blocker, valsartan, to ameliorate the negative metabolic effects associated with HCTZ therapy was observed regardless of the baseline fasting plasma glucose level.