This article originally posted 02 November, 2004 and appeared in Issue 232
Rosiglitazone May Improve Beta-Cell Function in Type 2 Diabetes
Rosiglitazone improves pancreatic β-cell response after six months as reflected by measures of insulin sensitivity and first-phase insulin response.
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"In a previous study, we found observational evidence of improvement in
beta-cell function when rosiglitazone was added to a failing oral
antihyperglycemic regimen consisting of sulfonylureas and metformin," write
Fernando Ovalle, MD, FACE, and David S.H. Bell, MB, from the University of
Alabama at Birmingham School of Medicine. "We have also shown, in a
prospective observational study, that triple oral antihyperglycemic therapy,
with a TZD [thiazolidinedione], metformin, and sulfonylurea, leads to prolonged
improvements in glycemic control in subjects at both three and five years and
that this maintenance of control may be due to increased endogenous insulin
production."
In this prospective trial, 17 subjects with type 2 DM, inadequately
controlled with a maximized oral antihyperglycemic double regimen of glimepiride
and metformin, were randomized to the addition of rosiglitazone or insulin to
their treatment regimens for six months. Measurement of fasting plasma glucose,
fasting proinsulin, and insulin levels; frequently sampled intravenous glucose
tolerance test; and glucagon stimulation test for C-peptide were performed at
baseline and at six months.
Nine subjects received an additional dose of 8-mg rosiglitazone, and eight
subjects received one additional injection of insulin (premixed 70/30) before
their evening meal. Both groups were well-matched for duration of DM, body mass
index (BMI), and glycosylated hemoglobin (HbA1c) before treatment (8.7% ± 0.3%
and 9.0% ± 0.3%; not significant) and after six months (7.8% ± 0.5% and 7.8%
± 0.3%; not significant).
After six months of treatment, the rosiglitazone group had a significant
improvement in acute insulin response to glucose (+15.3 μIU/mL/10 minute; P
< .001), leading to an increase in the disposition index from 0.18 at
baseline to 4.18 at six months (P = .02). Although the proinsulin-to-insulin
ratio decreased by 36% in the rosiglitazone group (P = .03), it did not change
significantly in the insulin treatment group.
"Rosiglitazone, but not insulin, induced a recovery of pancreatic
beta-cell function, as evidenced by the restoration of the first-phase insulin
response to glucose, improvement in the disposition index, and a decrease in the
proinsulin-to-insulin ratio in subjects with type 2 diabetes in whom oral
antihyperglycemic therapy failed," the authors write. "This
improvement was independent of the correction of glucotoxicity."
Diabetes Care. 2004;27:2585-2589
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