Incretin hormones are hormones produced by the gut in response to food intake. These hormones
help the body to control the metabolism of glucose (sugar). In particular, two incretin
hormones (GLP-1 and GIP) cause the pancreas to secrete more insulin in response to high blood
glucose levels. This helps the body to metabolize the glucose more effectively, lowering
blood sugar levels. GLP-1 and GIP do not work as well in patients with type 2 diabetes (T2DM)
as in subjects who do not have diabetes. This study tests whether a medicine called
pioglitazone (Actos), which is commonly used to treat T2DM, improves the ability of GIP to
increase insulin secretion.
To address this question the investigators will recruit patients with T2DM whose diabetes is
controlled with either diet and exercise or with metformin (another medicine commonly used to
treat T2DM). Subjects will undergo measurement of body fat by DEXA scanning and a series of
studies to characterize their metabolism. These studies include an oral glucose tolerance
test (a test sometimes used to diagnose diabetes), a mixed-meal challenge (to measure how
much GLP-1 and GIP are produced in response to a meal) and measurement of insulin secretion
in response to glucose and GIP given through a vein. The investigators will also obtain small
samples of fat (from just under the skin of the belly) using a needle to measure levels of
the receptor for GIP. Subjects will then be randomly assigned to 12 weeks of treatment with
either pioglitazone or matching placebo (an inactive tablet that does not contain
medication). The dose of pioglitazone will be increased during the first 4 weeks to the
maximum prescribed dose of 45 mg per day. Subjects will be seen every 2-4 weeks during the
treatment phase of the study. After 12 weeks of treatment all studies performed at the
beginning of the study will be repeated. The pioglitazone treatment will continue until the
end of testing, approximately 4 weeks.
The results of this study may give us information about why glucose control deteriorates in
T2DM. This information might also lead to new ways to prevent or treat T2DM.