Effects of aging and type 2 diabetes on resting and post occlusive hyperemia of the forearm; the impact of rosiglitazone

Abstract

BACKGROUND: Both Diabetes and ageing are associated with reduced vascular endothelial function. The exact relationship between the 2 and any improvements from the insulin sensitizer rosiglitazone have not been explored. METHODS: Thirty controls and sixteen subjects with type 2 diabetes participated in a series of experiments to examine the interrelationships between age, diabetes and endothelial cell function. In subjects with diabetes, the insulin sensitizer rosiglitazone (RSG), a drug also known to improve vascular function, was administered for 3 months to see how it altered these relationships. Resting forearm flows (RF) and blood flows after 4 min of vascular occlusion (PF) were measured as an index of endothelial cell function. RESULTS: RF, measured by venous occlusion plethysmography, was negatively correlated to both age and diabetes. Administration of RSG for 3 months was associated with an increase in the blood flow response to venous occlusion so that it was not significantly different than that of age matched controls. Total PF in control subjects, compared to subjects with diabetes, averaged 56.58 +/- 12.57 and 13.6 +/- 8.01 cc/100 cc tissue per min respectively, and were significantly different (p < 0.01). After 3 months on RSG, differences between PF in the two groups were no longer evident. CONCLUSION: These studies suggest a different mechanism causing a reduction in vascular reactivity with aging and diabetes.

Figure 1

This figure shows the blood flow recorded for 2 minutes following the release of an arterial occlusion cuff on the brachial artery in control subjects (diamonds) and subjects with diabetes (squares). Illustrated here are the average results for all subjects in each group +/- standard deviation. Flows are expressed in cc/100 ml muscle per minute and the time scale on the bottom is the flow number. Flows are recorded every 12 seconds starting at 3 seconds post occlusion.

Figure 2

This figure shows the blood flow in the forearm of the subjects with diabetes at rest (cc/ 100 ml tissue/minute) before taking rosiglitazone (pre) and at two weeks (2 w), four weeks (4 w), and three months (3 m) taking 4 ml per day of Rosiglitazone. All data is shown with the appropriate standard deviation.

Figure 3

This figure illustrates the excess flow above rest during a two minute period after the release of an occlusion cuff on the brachial artery of control subjects and subjects with diabetes. Individual data points are shown on control subjects and subjects with diabetes prior to initiation of a three month administration of rosiglitazone (pre rsg) and after 2 weeks (2 w), four weeks (4 w), and three months (3 m). Data is plotted in relationship to the age of the subject. The regression lines are calculated by the method of least squares. On the control subjects the regression line was flow = -0.518 age + 77.78. Prior to administration of rosiglitazone of the subjects with diabetes the regression equation was flow = -0.253 age + 31.01. After two weeks of administration of rosiglitazone the regression equation was blood flow = -0.348 age + 41.6. After 4 weeks of rosiglitazone the regression equation was blood flow = -0.243 age + 50.27. Finally after 3 months of rosiglitazone was post occlusion flow = -0.274 age + 64.94