Issue 164 Item 8 Rosiglitazone Improves Insulin Sensitivity, Glucose Control and

Rosiglitazone improves insulin sensitivity and glucose control, while lowering circulating vascular/inflammatory markers.

Researchers led by James Chu, MD, of Stanford University School of Medicine, in Palo Alto, California, evaluated the effects of rosiglitazone on circulating vascular and inflammatory markers in subjects with insulin resistance (IR). They then related these changes to changes in IR and fasting plasma glucose.

They enrolled 29 subjects with IR and a steady-state plasma glucose level greater than 180 mg/dL after a 3-hour insulin suppression test. Fifteen of the subjects had Gp A (glucose production) with fasting plama glucose level lower than 126 mg/dL. Fourteen had a Gp B (basal glucose production) level of 126 and 150 mg/dL.

The investigators also measured at baseline and after 3 months of rosiglitazone therapy the levels of fasting C-reactive protein, interleukin-6, plasminogen activator inhibitor-1 (PAI-1), ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule 1), as well as the levels of E-, L-, and P-selectin, which are three membrane-attached calcium-dependent lectins that initiate rolling adhesion of leukocytes on the vascular wall by binding to cell-surface carbohydrate ligands.

They compared changes in the markers to changes in steady-state plasma glucose, binding proteins, fasting plasma glucose, insulin, free fatty acids, and lipids.

The study showed that rosiglitazone produced a decrease in fasting plasma glucose by 8% to 23% and a decrease in C-reactive protein by 38% to 55%. This suggests cardiovascular benefit, said Dr. Chu.

The results also showed that rosiglitazone therapy led to lower steady-state plasma glucose and fasting plasma glucose, respectively, in Gp A (242 to 184 mg/dL; 105 to 97 mg/dL) and Gp B (255 to 164 mg/dL; 142 to 119 mg/dL) (all P<0.01). In both Gps A and B, 3 markers fell after rosiglitazone treatment: C reactive protein (3.6 to 1.6 mg/L, P<0.01; 2.5 to 1.5 mg/L, P<0.02); PAI-1 (6.6 to 2.1 ng/mL, P<0.02; 5.0 to 1.8 ng/mL, P<0.07); and E-selectin (50 to 41 ng/mL, P<0.01; 54 to 48 ng/mL, P<0.07).

They found no clear correlation between decreases in the markers and changes in insulin resistance or fasting plasma glucose level. "There was no constant relationship between changes in the markers and other metabolic or [coronary heart disease] risks." said Dr. Chu.

However, the researchers noted that their data indicated that rosiglitazone treatment had a direct effect on metabolic measures, lowering glucose and circulating markers, and indicating a decrease in selected protein levels.

Dr. Chu noted that this study raises the core questions of whether rosiglitazone therapy decreases cardiovascular risk of insulin resistant syndrome and whether it also decreases the potential for development of diabetes.

Presented at the American Diabetes Association 63rd Scientific Sessions.
[Study title: Vascular and Inflammatory Markers in Rosiglitazone-Treated Insulin-Resistant Subjects Are Independent of Changes in Insulin Sensitivity or Glycemic Control. Abstract 325-OR]

===============================

FACT: All packaged foods sold across America will have to carry labels indicating trans-fatty acid content under new US government regulations "This is just the beginning of a lot more rules and regulations about [nutrition labeling]. We are moving now very rapidly," Health and Human Services Secretary Tommy Thompson told a news conference. The new requirement, which takes effect as of January 2006