In diabetic rodents and nse inhibitor MB07803. In diabetic rodents and nonhuman primates, glucose decreased without any change in blood lactate. Motoshima et al. found that the protein CH5424802 kinase C inhibitor rottlerin decreased AMPK phosphorylation in adipocytes, myocytes, and hepatocytes and increased cellular glucose consumption, the latter effect is not observed with overexpression of dominant negative AMPK, which suggests this phenomenon to mediate the glucose lowering effect observed in animal models in vivo. PPAR agonists A number of studies at the ADA meeting contributed to the endeavor to unravel cardiovascular risks versus benefits of the TZDs. Bilik et al. compared 8,739 type 2 diabetic patients who were followed from 1999 to 2003 and either received or did not receive a TZD. Mortality among the patients was 5 vs.
7%, and major CV events occurred in 11 vs. 10%, respectively. A total of 817 took just rosiglitazone and 724 just pioglitazone, with major CV events in 9 and 10%, respectively. However, Wang et al. analyzed 11,283 type 2 diabetic patients receiving either metformin or a sulfonylurea alone at baseline. They found a 23% greater likelihood of a CV event among patients receiving add on rosiglitazone than among those receiving combined sulfonylureametformin treatment. Spanheimer et al. reported that 33% of patients in the PROspective pioglitAzone Clinical Trial In macroVascular Events were treated with insulin, 39% with a nitrate, and 70% with an angiotensin directed agent, with no evidence of these treatments increasing risk of stroke, myocardial infarction, or mortality. Seung Jin Han et al.
administered pioglitazone versus placebo to 75 nondiabetic renal allograft recipients for 12 months, and found a significant increase versus decrease in insulin sensitivity and a decrease versus increase in carotid intima media thickness. Bao et al. studied outcome among 3,713 diabetic patients treated with metformin alone for at least 12 months, 29 and 71% of the patients subsequently took rosiglitazone and a sulfonylurea, respectively. On average, the latter group was 2 years older, the patient groups had a similar sex distribution and prevalence of hypertension and CVD, and baseline resource utilization was similar. Comparing those adding rosiglitazone versus sulfonylurea, 74 vs. 69% were adherent to glucose lowering therapy, 23 vs. 27% experienced hospitalizations, 26 vs.
29% had ER visits, and 54 vs. 58% had outpatient visits. There was a 40% greater adjusted likelihood of adherence to rosiglitazone, and rates of both hospitalizations and ER visits were 20% lower among those who added rosiglitazone. Tint et al. administered rosiglitazone for 16 weeks to 14 type 2 diabetic patients of Chinese and Asian Indian ethnicity. Euglycemic hyperinsulinemic clamp insulin sensitivity increased 52 vs. 120%, respectively, with somewhat more weight gain in those of Asian Indian ethnicity. Kritchevsky et al. administered 30 mg pioglitazone daily versus placebo to 88 nondiabetic adults who had a BMI 27 kg/m2 and were on a calorie restricted diet for 4 months, weight loss did not differ between the pioglitazone and placebo groups, but men receiving pioglitazone had 3% reduction in percent body fat, while there was a 2% reduction in the placebo group, there was a greater reducti .