Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.
OBJECTIVE
To determine the effects of rosiglitazone on insulin sensitivity, glucose tolerance and ambulatory blood pressure when administered to subjects with persistent impaired glucose tolerance (IGT).


METHODS
Eighteen subjects with persistent IGT were randomized to receive rosiglitazone 4 mg twice daily or matching placebo for 12 weeks. Evaluation at baseline and at the end of treatment included measurement of whole body insulin sensitivity during a euglycaemic hyperinsulinaemic clamp and deriving an insulin sensitivity index. Changes in glucose and insulin concentration were determined after oral glucose tolerance test (OGTT) and mixed meal tolerance tests, and 24-h ambulatory blood pressure was monitored.


RESULTS
Rosiglitazone significantly improved the insulin sensitivity index by 2.26 micro g/kg per min per pmol/l relative to placebo (P = 0.0003). Four of nine subjects receiving rosiglitazone reverted to normal glucose tolerance and 5/9 remained IGT, although four of these had improved 2-h glucose values. In the placebo group, 1/9 subjects progressed to Type 2 diabetes and 8/9 remained IGT. Following OGTT and meal tolerance test, glucose and insulin area under curve were reduced over 3 and 4 h, respectively. Compared with placebo, ambulatory blood pressure decreased significantly in the rosiglitazone group by 10 mmHg systolic (P = 0.0066) and 8 mmHg diastolic (P = 0.0126).


CONCLUSIONS
Consistent with its effects in patients with Type 2 diabetes, rosiglitazone substantially improved whole body insulin sensitivity and the glycaemic and insulinaemic responses to an OGTT and meal tolerance test in subjects with persistent IGT. Furthermore, rosiglitazone reduced systolic and diastolic ambulatory blood pressure in these subjects.
Bennett
S M A
SM
Department of Diabetes & Metabolism, Diabetes Resource Centre, University of Newcastle, North Tyneside General Hospital, Rake Lane, North Shields, Tyne & Wear NE29 8NH, Newcastle upon Tyne, UK. stuart.bennett@northumbria-healthcare.nhs.uk
Agrawal
A
A
Elasha
H
H
Heise
M
M
Jones
N P
NP
Walker
M
M
Wilding
J P H
JP
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D005260:Female; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000188:drug therapy* / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D006946:Hyperinsulinism / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone