Thiazolidinediones in patients with type 2 diabetes mellitus and heart failure.

PURPOSE: A review of the significant findings related to the use of the thiazolidinediones (TZDs) in the treatment of patients with type 2 diabetes mellitus and heart failure was conducted. SUMMARY: TZDs are antihyperglycemic medications that increase insulin sensitivity and improve the underlying defect of insulin resistance and type 2 diabetes mellitus, and they have the potential to slow or decrease the cardiovascular damage that results from these conditions. TZDs are also implicated in weight gain; however, this is accompanied by an improvement in insulin sensitivity and, therefore, its clinical significance is unclear. Edema has been well characterized in patients treated with TZDs. Edema is more common in patients treated with a TZD in combination with insulin and higher doses of TZDs. Because of the potential for fluid retention and worsening edema, clinical studies have excluded patients with New York Heart Association (NYHA) functional class III or IV heart failure. In patients at risk for heart failure or those who have NYHA functional class I or II symptoms, initiation of therapy should be at the lower dose for TZDs with close monitoring of weight gain, edema, and other signs of worsening heart failure. CONCLUSION: Current data suggest that TZDs may be used cautiously in patients with type 2 diabetes mellitus who are at risk for heart failure or who have NYHA functional class I or II heart failure. Patients with NYHA functional class III or IV heart failure should not receive TZDs.

Cardiovascular risk factors associated with insulin resistance: effects of oral antidiabetic agents.

Patients with type 2 diabetes mellitus have a greater risk of cardiovascular disease than nondiabetic individuals. These patients are often insulin resistant and have an associated clustering of risk factors that contribute to cardiovascular disease. The risk factors include dyslipidemia, hypertension, altered hemostasis, and chronic inflammation. A primary objective in the management of type 2 diabetes mellitus is normalization of blood glucose levels; however, some of the oral drugs used to control blood glucose levels have significant effects on these risk factors. In this article, we review the current data involving the modification of these cardiovascular risk factors by the biguanide (metformin), the thiazolidinediones (troglitazone, rosiglitazone, and pioglitazone), the alpha-glucosidase inhibitors (miglitol, acarbose), and the insulin secretagogs (glyburide [glibenclamide], glipizide, chlorpropamide, tolbutamide, tolazamide, glimepiride, repaglinide, and nateglinide). Generally, the thiazolidinediones improve hemostasis and endothelial function and reduce blood pressure, while having variable effects on dyslipidemia. Metformin improves dyslipidemia and altered hemostasis and decreases plasma C-reactive protein levels with little or no effect on blood pressure. Data on the effects of the alpha-glucosidase inhibitors and insulin secretagogs are sparse; however, these drugs appear to have little or no effect on cardiovascular risk factors.

Forearm endothelial response in smokeless tobacco users compared with cigarette smokers and nonusers of tobacco.

STUDY OBJECTIVE: To compare brachial artery flow-mediated dilation (FMD) in subjects who use smokeless tobacco, smoke cigarettes, or do not use any tobacco product. DESIGN: Cross-sectional study. SETTING: University-affiliated outpatient clinic. SUBJECTS: Seventeen apparently healthy volunteers who for more than 1 year smoked at least 10 cigarettes/day, used at least two containers of smokeless tobacco/week, or did not use any tobacco product. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics of subjects were similar among the three groups except for mean age and serum cotinine level. Baseline brachial artery diameter, endothelium-dependent FMD induced by reactive hyperemia, and endothelium-independent dilation induced by administration of sublingual nitroglycerin were measured. Mean FMD over baseline was 4.1% +/- 0.7% in subjects who used smokeless tobacco, 3.9% +/- 5.1% in cigarettes smokers, and 12.2% +/- 5.7% in nonusers of tobacco (p=0.01). Endothelium-independent dilation induced by nitroglycerin was not statistically different among the three groups. CONCLUSION: Brachial artery FMD, a surrogate for endothelial dysfunction, was significantly impaired in smokeless tobacco users and cigarette smokers compared with nonusers of tobacco.