1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...
1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...
1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...
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39<br />
with significant improvement in AIR g and increased disposition index (AIR g x 1/HOMA-<br />
IR), the restoration of the first-phase insulin response to glucose being independent of the<br />
correction of glucose toxicity. Clinical studies using rosi- or pioglitazone have<br />
demonstrated a beneficial effect of both agents in improving insulin sensitivity and<br />
recovery or improvement of beta-cell function which are sustained in some individuals over<br />
time. The addition of rosiglitazone improved the first-phase insulin response to glucose in<br />
poorly controlled patients previously treated with maximum doses of<br />
sulfonylurea+metformin. However, the addition of insulin had no effect on beta-cell<br />
function, despite a similar reduction in HbA1c.<br />
The several trials on prevention of diabetes with TZDs include the following:<br />
Troglitazone and Pioglitazone on Prevention of Diabetes (TRIPOD and PIPOD), in<br />
which troglitazone (withdrawn in 2000, because of hepatotoxicity) and subsequently<br />
pioglitazone delayed or prevented the onset of diabetes. The class effect of TZDs on<br />
reducing insulin secretory demands (decrease in insulin output during FSIVGTT) through a<br />
decrease in insulin resistance preserved beta-cell function and prevented DM2. The<br />
Diabetes Prevention Program (DPP) was a clinical trial of DM2 prevention, from 1996 to<br />
1998, in individuals at high risk of diabetes, involving adults with IGT, who were<br />
randomized to placebo, metformin, troglitazone or intensive lifestyle intervention.The<br />
diabetes incidence rate was 3.0 cases/100 person-years in troglitazone group (mean of 0.9<br />
years), compared with 12.0, 6.7 and 5.1 cases /100 person-years in placebo, metformin and<br />
intensive lifestyle participants. The trial of TZD therapy in the prevention/delay of DM2<br />
in patients with IFG+ IGT, in which 101 subjects received troglitazone for an average of<br />
10 months (at which point the drug was withdrawn) then randomly switched to<br />
rosiglitazone or pioglitazone for a mean of 36 months. The cumulative incidence rate of<br />
diabetes after the 3 years was 2.97% after TZDs vs.26.8% in the control group: IFG+ IGT<br />
(p