Inclusion Criteria:

• Prehypretensive prediabetic subjects (25-70 years old) defined as otherwise normal subjects with a mean SiSBP of 120-139 mmHg and fasting blood glucose of 6.1-6.9 mmol/L at screening and after two weeks of placebo therapy (Week -2)

Exclusion Criteria:

• Hypertension or clinically significant renal disease
• Cerebrovascular accident within the past year, or current transient ischemic attacks
• Myocardial infarction within the past year; percutaneous coronary angioplasty or coronary artery bypass surgery within last 6 months
• Clinically significant AV conduction disturbances and/or arrhythmias (e.g. second- or third-degree AV block; sick-sinus syndrome or clinically significant bradycardia- resting heart rate < 45 beats/minute), tachyarrhythmias; clinically significant arrhythmias, presence of accessory bypass tract (e.g. Wolff-Parkinson-White syndrome)
• Angina pectoris
• Current or prior history of heart failure or known left ventricular ejection fraction <40%
• History of unexplained syncope or known syncopal disorder (e.g., Stokes-Adams Syndrome)
• Known history of hemodynamically significant obstructive valvular disease or hypertrophic cardiomyopathy
• Use of agents that may cause alteration of blood pressure is prohibited. This includes nitrates, or alpha or beta-blockers. Calcium channel blockers are allowed as second line therapy if hypertension develops during the study Major psychotropic agents and antidepressants are not permitted
• Cimetidine is not permitted (famotidine and ranitidine and proton pump inhibitors are allowed).
• NSAIDs are permitted if taken on a stable regimen. Aspirin in small doses (< 1 g/day) as cardioprotective agent and acetaminophen are permitted
• Oral or inhaled steroids, ACTH, immunosuppressants or lithium are not allowed
• Serum creatinine concentration >200 μmol/L (adjusted for age and weight)
• Urine dipstick or microscopic findings suggestive of significant renal or other disease.
• Hematuria should be evaluated, the etiology established/documented, and treatment rendered as appropriate prior to entry
• Off-treatment serum potassium concentration >5.5 mmol/L or <3.5 mmol/L
• AST (SGOT) or ALT (SGPT) >2 x normal upper limit
• Clinically significant laboratory values outside of the established normal range including but not limited to the following parameters: hemoglobin, platelet count or white blood cell count
• Known hypersensitivity or contraindication to losartan or thiazide diuretics
• History of clinically important malabsorption or gastrointestinal resection
• Current urinary tract infection
• Smoking 10 cigarettes or more.
• Pregnancy or lactating females. Females of childbearing age who are not surgically sterilized and are using effective contraception may enter only if an exclusionary pregnancy test is done within 72 hours of the first double-blind dose of test agent. Pregnancy tests will then be done monthly throughout the study.
• Vasculitis or vasculopathy: collagen-vascular diseases, chronic hepatitis B antigenemia, circulating immune complexes, complement disorders, amyloidosis, scleroderma, etc. Neoplasms, Acquired Immunodeficiency Syndrome (AIDS), or HIV positive
• Bleeding or platelet disorder
• Known absence of one kidney
• Subjects abusing or who within past two years abused alcohol or other drug substances
• Mentally or legally incapacitated subjects
• Subjects who have participated in another investigational drug trial, including those using marketed drugs (i.e. patient has signed a consent form), within the 28 days prior to start of placebo therapy
• Subjects who, in the opinion of the investigator, will not cooperate fully, keep appointments or are unreliable
• Inability or unwillingness to sign the Patient Consent Form
• Phase V of Korotkoff sounds cannot be detected