were confirmed to be adipocytes by light microscopy. Gene expression levels were determined by quantitative real-time PCR. Results: Although adipocyte size measurements between IR and IS groups did not differ significantly, the IR group had a higher small to large cell ratio (1.66Ϯ 1.03 vs. 0.94 Ϯ 0.50, P ≤0.05). Adiponectin, PPAR␥1, PPAR␥2, and GLUT4 all showed 2-3 fold lower levels of expression in the IR group (n=5) compared to the IS group (n=5). In contrast, there were no significant differences in Adipsin and SREBP-1c expression in both groups. Conclusions: Our observation of a bimodal distribution of small and large cells in both IR and IS groups, and a larger ratio of small adipocytes in IR compared to IS individuals is a novel finding. Gene expression analysis suggests that there is probably a decrease in differentiation since GLUT4 and Adiponectin, known markers of terminal adipocyte differentiation, were significantly decreased in the IR group. However since SREBP-1c and Adipsin were not differentially expressed in both groups more work will need to be done to further characterize the adipocyte differences in the IR and IS groups and to determine the significance of adipocyte size and insulin resistance status.

PurposeThe insulin sensitizer rosiglitazone (RSG) has been shown to improve endothelial function and reduce vascular inflammation. However, no study has prospectively looked at its overall effect on cardiovascular events.MethodsThis was a non-randomized open label prospective parallel pilot study. Patients with known coronary artery disease, dysmetabolic syndrome and type 2 diabetes were recruited for the study. Patients who were medical candidates for RSG were given RSG (RSG group) in addition to routine medical care and followed in an intensive outpatient cardiovascular prevention program. If they were not medical candidates for RSG they were followed with routine medical care (control group).ResultsControl group (Baseline): mean body mass index (BMI) 29.2, mean age 66, n = 18 male and 4 female, mean HgbA1c 7.47, mean low density lipoprotein level (LDL) 100. RSG Group (baseline): mean BMI 31.6, mean age 63, n = 13 male and 6 female, mean HgbA1c 7.28, mean LDL 76. After one year, the control group had a higher LDL and mean Hba1c. Control Group (1 year later): mean HgbA1c 7.63, mean LDL 96. RSG group (1 year later): mean HgbA1c 7.23, mean LDL 86. Cardiovascular events were significantly lower in the RSG group after one year: control = 9 events, RSG = 4 events, p≤.01) Mortality was significantly lower in the RSG group after one year: RSG group = no deaths, control = 7 deaths, p ≤.01).ConclusionLower LDL and HbA1c were seen in the RSG group. Our pilot data reveals improved cardiovascular outcomes were seen with the use of RSG. Given the small number of total cardiovascular events, short duration of this analysis and open label design, further double blind randomized placebo controlled trials with larger population over a larger period of time are warranted.

PurposeMeasurement of the carotid artery intima-media thickness (IMT) using high resolution B-mode ultrasonagraphy has emerged as a useful tool for assessing coronary atherosclerosis and cardiac risk. A primary contributor towards coronary atherogenesis in patients with diabetes is endothelial cell dysfunction. The insulin sensitizer and peroxisome proliferator-activated receptor γ (PPARγ) ligand, rosiglitazone (RSG), has been shown to improve endothelial function in preclinical and clinical trials. It has been argued that such improvements may be secondary to corresponding improvements in glucose control over time. We hypothesized that RSG would reduce IMT over a period of 6 months and improve blood vessel health through its positive effect on the endothelium.MethodsRSG 2-4 mg was given daily for 6 months to 15 insulin resistant diabetics (9 male). IMT was measured at baseline and again at 6 months. Each IMT measurement was initiated by the SonoCalc operator at a location in the adventitia of the segment to be measured. Various sonographic interfaces were then initially outlined automatically. If any substantial variance was detected by the operator between the SonoCalc automated IMT border and a border that would have appeared more correct, progressively controlled edit options were employed to achieve satisfactory semi-automatic SonoCalc measurements. The automated and semi-automated SonoCalc software program computed the average thickness of the intima-media complex in each application mode.ResultsA trend for improvement in IMT was seen after 6 months. Mean diameter of the intima-media complex at baseline was 0.882 mm while the corresponding measurement at 6 months was 0.862 mm, representing a decrease in 0.02 mm. Although a positive observation, the trend in decreased IMT was not statistically significant (P = 0.198).ConclusionsIn conclusion, our preliminary data demonstrates trends in improvements in IMT with RSG in insulin resistant type 2 diabetics after 6 months of therapy. Further evaluation will need to be performed with a larger sample size or a longer duration of study to confirm these results.

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