PMID- 16430721
OWN - NLM
STAT- MEDLINE
DCOM- 20060605
LR  - 20221207
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 64
IP  - 2
DP  - 2006 Feb
TI  - The IGF-I system and the renal and haemodynamic effects of losartan in 
      normotensive patients with type 2 diabetes mellitus: a randomized clinical trial.
PG  - 203-8
AB  - OBJECTIVE: Losartan has been shown to protect the diabetic kidney, at least 
      partly independent of changes in blood pressure. Imbalances in the IGF-I system 
      are associated with the development of diabetic nephropathy. We investigated 
      whether renal as well as haemodynamic effects of losartan are associated with 
      changes in the IGF-I system in normotensive patients with type 2 diabetes 
      mellitus (T2DM). DESIGN AND PATIENTS: This randomized, double-blind 
      placebo-controlled clinical trial involved 74 normotensive patients with T2DM and 
      microalbuminuria. Thirty-eight patients were assigned to receive losartan and 36 
      patients were assigned to receive placebo for 10 weeks. MEASUREMENTS: Serum 
      levels of total and free IGF-I, IGFBP-3, creatinine and haemoglobin A(1c) 
      (HbA(1c)), as well as urinary albumin excretion rate, creatinine clearance and 
      blood pressure, were measured prior to the start of treatment and after 10 weeks 
      of treatment. RESULTS: At baseline, serum levels of IGFBP-3 were elevated and 
      serum levels of free IGF-I were reduced. Losartan tended to reduce IGFBP-3 levels 
      and to increase free IGF-I levels, although neither effect was statistically 
      significant. These effects were more pronounced in a subanalysis of 18 
      losartan-treated patients with stable metabolic parameters, with a decrease in 
      IGFBP-3 from 133.2 to 122.6 nmol/l (P=0.006) and an increase in free IGF-I levels 
      by 8% (ns). Serum levels of total IGF-I were unaffected. The change in IGFBP-3 
      was inversely correlated to the change in creatinine clearance (r=-0.4; P=0.02). 
      Total and free IGF-I inversely correlated to systolic blood pressure (r= -0.46; 
      P=0.007 and r=0.26; P=0.14 respectively). Furthermore, changes in total IGF-I and 
      IGFBP-3 correlated to changes in serum creatinine levels in the metabolically 
      stable patients (r=0.58, P=0.02 and r=0.6, P=0.01, respectively). Changes in the 
      IGF-I system were unrelated to a reduction in microalbuminuria associated with 
      losartan. CONCLUSIONS: Losartan lowered the elevated levels of IGFBP-3, although 
      only significantly in the metabolically stable patients. A tendency towards an 
      increase in free IGF-I levels was also observed, but this change was small and 
      not statistically significant. These changes were not related to reduction in 
      microalbuminuria, but might contribute to effects of losartan on creatinine 
      clearance and blood pressure of losartan in normotensive patients with T2DM.
FAU - Zandbergen, Adrienne A M
AU  - Zandbergen AA
AD  - Department of Internal Medicine, Erasmus University Medical Centre Rotterdam, the 
      Netherlands. adrienne_zandbergen@yahoo.com
FAU - Lamberts, Steven W J
AU  - Lamberts SW
FAU - Baggen, Marinus G A
AU  - Baggen MG
FAU - Janssen, Joop A M J L
AU  - Janssen JA
FAU - Boersma, Eric
AU  - Boersma E
FAU - Bootsma, Aart H
AU  - Bootsma AH
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - AYI8EX34EU (Creatinine)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Albuminuria/metabolism
MH  - Angiotensin II Type 1 Receptor Blockers/*therapeutic use
MH  - Blood Pressure/drug effects
MH  - Creatinine/metabolism
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Diabetic Nephropathies/*drug therapy/metabolism
MH  - Double-Blind Method
MH  - Female
MH  - Glycated Hemoglobin/analysis
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Protein 3/blood
MH  - Insulin-Like Growth Factor I/analysis/*metabolism
MH  - Losartan/*therapeutic use
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
EDAT- 2006/01/25 09:00
MHDA- 2006/06/06 09:00
CRDT- 2006/01/25 09:00
PHST- 2006/01/25 09:00 [pubmed]
PHST- 2006/06/06 09:00 [medline]
PHST- 2006/01/25 09:00 [entrez]
AID - CEN2449 [pii]
AID - 10.1111/j.1365-2265.2006.02449.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2006 Feb;64(2):203-8. doi: 
      10.1111/j.1365-2265.2006.02449.x.