Rosiglitazone Improves Insulin
Sensitivity, Glucose Control and Inflammation
Rosiglitazone improves insulin sensitivity
and glucose control, while lowering circulating
vascular/inflammatory markers.
Researchers led by James Chu, MD, of Stanford
University School of Medicine, in Palo Alto, California,
evaluated the effects of rosiglitazone on circulating
vascular and inflammatory markers in subjects
with insulin resistance (IR). They then related
these changes to changes in IR and fasting plasma
glucose.
They enrolled 29 subjects with IR and a steady-state
plasma glucose level greater than 180 mg/dL after
a 3-hour insulin suppression test. Fifteen of
the subjects had Gp A (glucose production) with
fasting plama glucose level lower than 126 mg/dL.
Fourteen had a Gp B (basal glucose production)
level of 126 and 150 mg/dL.
The investigators also measured at baseline and
after 3 months of rosiglitazone therapy the levels
of fasting C-reactive protein, interleukin-6,
plasminogen activator inhibitor-1 (PAI-1), ICAM-1
(intercellular adhesion molecule-1), VCAM-1 (vascular
cell adhesion molecule 1), as well as the levels
of E-, L-, and P-selectin, which are three membrane-attached
calcium-dependent lectins that initiate rolling
adhesion of leukocytes on the vascular wall by
binding to cell-surface carbohydrate ligands.
They compared changes in the markers to changes
in steady-state plasma glucose, binding proteins,
fasting plasma glucose, insulin, free fatty acids,
and lipids.
The study showed that rosiglitazone produced
a decrease in fasting plasma glucose by 8% to
23% and a decrease in C-reactive protein by 38%
to 55%. This suggests cardiovascular benefit,
said Dr. Chu.
The results also showed that rosiglitazone therapy
led to lower steady-state plasma glucose and fasting
plasma glucose, respectively, in Gp A (242 to
184 mg/dL; 105 to 97 mg/dL) and Gp B (255 to 164
mg/dL; 142 to 119 mg/dL) (all P<0.01). In both
Gps A and B, 3 markers fell after rosiglitazone
treatment: C reactive protein (3.6 to 1.6 mg/L,
P<0.01; 2.5 to 1.5 mg/L, P<0.02); PAI-1
(6.6 to 2.1 ng/mL, P<0.02; 5.0 to 1.8 ng/mL,
P<0.07); and E-selectin (50 to 41 ng/mL, P<0.01;
54 to 48 ng/mL, P<0.07).
They found no clear correlation between decreases
in the markers and changes in insulin resistance
or fasting plasma glucose level. "There was
no constant relationship between changes in the
markers and other metabolic or [coronary heart
disease] risks." said Dr. Chu.
However, the researchers noted that their data
indicated that rosiglitazone treatment had a direct
effect on metabolic measures, lowering glucose
and circulating markers, and indicating a decrease
in selected protein levels.
Dr. Chu noted that this study raises the core
questions of whether rosiglitazone therapy decreases
cardiovascular risk of insulin resistant syndrome
and whether it also decreases the potential for
development of diabetes.
Presented at the American Diabetes Association
63rd Scientific Sessions.
[Study title: Vascular and Inflammatory Markers
in Rosiglitazone-Treated Insulin-Resistant Subjects
Are Independent of Changes in Insulin Sensitivity
or Glycemic Control. Abstract 325-OR]
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