Impaired vascular reactivity in African-American patients with type 2 diabetes mellitus and microalbuminuria or proteinuria despite angiotensin-converting enzyme inhibitor therapy.

BACKGROUND: Microalbuminuria, an early indicator of diabetic nephropathy that reflects other vascular abnormalities, usually improves or resolves with angiotensin-converting enzyme inhibitor (ACEI) therapy. Persistent microalbuminuria despite ACEI therapy may be associated with poor prognosis for cardiovascular disease and mortality. African-Americans are reported to respond less well to ACEI and are at increased risk of disease progression. METHODS AND RESULTS: We compared flow-mediated dilatation (FMD) and nitroglycerine-dependent dilatation (NDD) in African-American diabetic subjects with persistent microalbuminuria (n = 35) despite ACEI therapy and those in whom microalbuminuria had resolved (n = 15). The two groups were not statistically different in terms of blood pressure, age, sex, lipids, and hemoglobin A1c. FMD was reduced in the microalbuminuria group, compared with subjects without microalbuminuria (4.2 vs. 11.4%; P < 0.0001). Similarly, NDD was reduced in the microalbuminuria group, compared with subjects without microalbuminuria (10.8 vs.16.6%; P = 0.011). The FMD in African-American patients with persistent microalbuminuria was also significantly lower than in clinically similar Caucasian patients whose microalbuminuria had persisted despite ACEI therapy (4.2 vs. 7.5%; P = 0.03). On multiple regression analysis, persistent microalbuminuria is the only predictor of abnormal endothelial function in these patients. CONCLUSIONS: Our study clearly demonstrates that African-American type 2 diabetic subjects with persistent microalbuminuria have severely impaired FMD and NDD, compared with matched patients who had microalbuminuria that was eliminated by ACEI. This may explain the poor prognosis for cardiovascular disease in patients who have persistent microalbuminuria. Alternative strategies for reducing microalbuminuria in high-risk patients who do not respond adequately to ACEI therapy such as African-Americans are needed.

Nontraditional risk factors for cardiovascular disease in diabetes.

People with type 2 diabetes are disproportionately affected by cardiovascular disease (CVD), compared with those without diabetes. Traditional risk factors do not fully explain this excess risk, and other "nontraditional" risk factors may be important. This review will highlight the importance of nontraditional risk factors for CVD in the setting of type 2 diabetes and discuss their role in the pathogenesis of the excess CVD morbidity and mortality in these patients. We will also discuss the impact of various therapies used in patients with diabetes on nontraditional risk factors.

Hormones and homocysteine.

Hyperhomocysteinemia is a well-established risk factor for cardiovascular disease. Various factors, both modifiable and non-modifiable, interact with the homocysteine metabolism and determine the plasma homocysteine concentrations. These include genetic abnormalities, age, sex and various nutritional and hormonal determinants, all of which play a role in atherosclerosis and accelerated peripheral and cardio-vascular disease (CVD). Several hormones modulate homocysteine metabolism and hence may play a role in the pathogenesis of CVD. The mechanisms involved are unclear. The association of hyperhomocysteinemia with diabetes mellitus is complex and may explain some of the risk of CVD in diabetics not explained by traditional risk factors. Much conflicting data exists in the literature on the role of insulin on homocysteine metabolism, although insulin affects the enzymes regulating the homocysteine metabolism. Treatment of hyperhomocysteinemia with vitamins lowers plasma homocysteine concentrations. Little data is available on the effect of this intervention on cardiovascular outcomes. This review briefly outlines the homocysteine metabolism, summarizes its hormonal determinants, and discusses the role of hyperhomocysteinemia in diabetes, hyperlipidemia and other endocrine disorders.