title: A randomised controlled trial for the evaluation of risk for type 2 diabetes in hypertensive patients receiving thiazide diuretics: Diuretics In the Management of Essential hypertension (DIME) study.
abstract: OBJECTIVE
  Thiazide diuretics are one of the first choice antihypertensives but not optimally utilised because of concerns regarding their adverse effects on glucose metabolism. The Diuretics In the Management of Essential hypertension (DIME) study was designed, for the first time, to assess the risk for type 2 diabetes mellitus in patients with essential hypertension during antihypertensive treatment with low-dose thiazide diuretics compared to those not treated with diuretics.
  
  
  METHODS
  Multicentre, unblinded, pragmatic, randomised, controlled trial with blinded assessment of end points and intention-to-treat analysis that was started in 2004 and finished in 2012.
  
  
  METHODS
  Hypertension clinics at 106 sites in Japan, including general practitioners' offices and teaching hospitals.
  
  
  METHODS
  Non-diabetic patients with essential hypertension.
  
  
  METHODS
  Antihypertensive treatment with low-dose thiazide diuretics at 12.5 mg/day of hydrochlorothiazide or equivalent (Diuretics group) or that without thiazide diuretics (No-diuretics group).
  
  
  RESULTS
  The primary outcome was new onset of type 2 diabetes diagnosed according to WHO criteria and the criteria of Japanese Society of Diabetes.
  
  
  RESULTS
  1130 patients were allocated to Diuretics (n=544) or No-diuretics group (n=586). Complete end point information was collected for 1049 participants after a median follow-up of 4.4 years. Diabetes developed in 25 (4.6%) participants in the Diuretics group, as compared with 29 (4.9%) in the No-diuretics group (HR 0.93; 95% CI 0.55 to 1.58; p=0.800).
  
  
  CONCLUSIONS
  Antihypertensive treatment with thiazide diuretics at low doses may not be associated with an increased risk for new onset of type 2 diabetes. This result might suggest safety of use of low doses of thiazide diuretics.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00131846.
authors.affiliation: Department of Clinical Pharmacology & Therapeutics, University of the Ryukyus, Okinawa, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Department of Internal Medicine, Hyogo Collage of Medicine, Nishinomiya, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Morimoto
authors.affiliation: Department of Cardiology, Saiseikai-Futsukaichi Hospital, Chikushino, Japan Sleep Apnea Centre, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Ando
authors.affiliation: Department of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Takishita
authors.affiliation: Division of Hypertension and Renal Medicine, National Cardiovascular Research Centre, Suita, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Kawano
authors.affiliation: Department of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimamoto
authors.affiliation: Department of Geriatric Medicine, Osaka University, Suita, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.affiliation: Department of Medicine, Keio University, Tokyo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Saruta
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D000075222:Essential Hypertension; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D016037:Single-Blind Method; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D049993:Sodium Chloride Symporter Inhibitors
keywords: essential hypertension; thiazide diuretics; type 2 diabetes