title: Anemia due to coadministration of renin-angiotensin-system inhibitors and PPARγ agonists in uncomplicated diabetic patients.
abstract: Therapy with either angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB) or thiazolidinediones (TZD) is associated with dose-dependent decrements in hematocrit and hemoglobin levels. We aimed to investigate the impact of the coadministration of TZD and ACEI/ARB on hematocrit and hemoglobin values in uncomplicated patients with type 2 diabetes mellitus and normal serum creatinine.Data from patients with type 2 diabetes currently followed, were reviewed and patients treated with ACEI/ARB and/or TZD were identified. For the purpose of this study the following 4 groups of 30 stable non-anemic diabetic patients each matched for age, gender, and BMI were formed. Group ACEI/ARB included patients on ACEI/ARB without TZD, group TZD included patients on TZD and antihypertensive agents other than ACEI/ARB, group ACEI/ARB/TZD consisted of patients on combined therapy with ACEI/ARB and TZD and the control group C included patients never exposed to ACEI/ARB or TZD. Clinical and laboratory data were collected prior to initiation of treatment and after 6 months.Neither hematocrit nor hemoglobin showed any significant change from baseline at the end of the study in group C. In both group ACEI/ARB and group TZD a small, but statistically significant reduction in hematocrit (~ 1% point) and hemoglobin levels (~ 0.3 g/dl) was seen. A greater statistically and clinically important reduction in hematocrit (~ 3% points) and hemoglobin (~ 1 g/dl) levels was observed in group  ACEI/ARB/TZD. Furthermore, incident anemia at the end reached 7% in group TZD and 23% in group ACEI/ARB/TZD.Coadministration of RAS inhibitors and PPAR-γ agonists should be considered in the differential diagnosis of hematocrit lowering and anemia in uncomplicated type 2 diabetic patients with normal serum creatinine. Further studies are required to clarify the mechanism(s), the cardiovascular consequences and the cost utility of anemia workup in such patients.
authors.affiliation: 2nd Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Centre, Athens University Medical School, Attikon University Hospital, Haidari, Greece. atraptis@med.uoa.gr
authors.forename: A E
authors.initials: AE
authors.lastname: Raptis
authors.forename: D
authors.initials: D
authors.lastname: Bacharaki
authors.forename: M
authors.initials: M
authors.lastname: Mazioti
authors.forename: K P
authors.initials: KP
authors.lastname: Marathias
authors.forename: K P
authors.initials: KP
authors.lastname: Markakis
authors.forename: S A
authors.initials: SA
authors.lastname: Raptis
authors.forename: G D
authors.initials: GD
authors.lastname: Dimitriadis
authors.forename: D V
authors.initials: DV
authors.lastname: Vlahakos
mesh_terms: D000368:Aged; D000740:Anemia / Q000139:chemically induced*; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D006454:Hemoglobins; D047495:PPAR gamma; D013844:Thiazoles