title: Antihypertensive drug therapy and the risk of lower extremity amputations in pharmacologically treated type 2 diabetes patients.
abstract: OBJECTIVE
  The objective of this study was to determine the association between different antihypertensive drug therapies and lower extremity amputations (LEAs) in type 2 diabetes patients.
  
  
  METHODS
  Data were obtained from the PHARMO Record Linkage System comprising pharmacy records and data on hospitalisations for all 450,000 residents of eight Dutch cities. In a nested case-control study among 12,140 type 2 diabetes patients who used antihypertensive drugs, 26 cases with a first LEA and 94 controls without a LEA matched on age, sex and calendar time were identified. Logistic regression was used to estimate the relative risk of LEA and to adjust for potential confounding factors.
  
  
  RESULTS
  Among type 2 diabetes patients who used antihypertensive drugs, subjects who used thiazide diuretics, alone or in combination, had a higher risk of LEA compared to subjects who used Angiotensin Converting Enzyme (ACE) inhibitor monotherapy (crude odds ratio (OR): 6.11 [95% confidence interval (CI): 1.32-28.27]). The use of thiazide diuretics was also associated with an increased risk of LEA when compared to the use of any non-thiazide antihypertensive drug (adjusted OR: 7.04 [1.10-45.30]). The increased risk of LEA associated with the use of thiazides compared to the use of non-thiazides depended on the duration of use (adjusted OR(< or = 365 days), 4.82 [0.61-38.34] and adjusted OR(>365 days), 26.16 [1.02-674.02], p-trend = 0.01).
  
  
  CONCLUSIONS
  Treatment with thiazide diuretics compared to treatment with other antihypertensive drugs was associated with excess amputations in type 2 diabetes patients. Due to several limitations of this study, our findings do not preclude the use of thiazides in type 2 diabetes mellitus patients as yet.
authors.affiliation: Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
authors.forename: Joëlle A
authors.initials: JA
authors.lastname: Erkens
authors.forename: Olaf H
authors.initials: OH
authors.lastname: Klungel
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Stolk
authors.forename: José A
authors.initials: JA
authors.lastname: Spoelstra
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Leufkens
mesh_terms: D000368:Aged; D000671:Amputation, Surgical / Q000706:statistics & numerical data*; D000959:Antihypertensive Agents / Q000145:classification / Q000627:therapeutic use*; D001581:Benzothiadiazines; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004232:Diuretics; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016015:Logistic Models; D035002:Lower Extremity / Q000473:pathology / Q000601:surgery*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000627:therapeutic use; D012306:Risk; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents; D001581:Benzothiadiazines; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D007703:Peptidyl-Dipeptidase A