molecular hydrogen treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial

Acarbose, which is clinically widely used to treat Type 2 Diabetes, is thought to act at the small intestine by competitively inhibiting enzymes that delay the release of glucose from complex carbohydrates, thereby specifically reducing post prandial glucose excursion. The major side-effect of treatment with acarbose, flatulence, occurs when undigested carbohydrates are fermented by colonic bacteria, resulting in considerable amount of molecular hydrogen.

We propose that enteric benefits of acarbose is partly attributable to be their ability to neutralise oxidative stress via increased production of molecular hydrogen H2 in the gastrointestinal tract.

CONTEXT:

The worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns.

OBJECTIVE:

To evaluate the effect of decreasing postprandial hyperglycemia with acarbose, an alpha-glucosidase inhibitor, on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance (IGT).

DESIGN, SETTING, AND PARTICIPANTS:

International, multicenter double-blind, placebo-controlled, randomized trial, undertaken in hospitals in Canada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel, and Spain from July 1998 through August 2001. A total of 1429 patients with IGT were randomized with 61 patients (4%) excluded because they did not have IGT or had no postrandomization data, leaving 1368 patients for a modified intent-to-treat analysis. Both men (49%) and women (51%) participated with a mean (SD) age of 54.5 (7.9) years and body mass index of 30.9 (4.2). These patients were followed up for a mean (SD) of 3.3 (1.2) years.

INTERVENTION:

Patients with IGT were randomized to receive either placebo (n = 715) or 100 mg of acarbose 3 times a day (n = 714).

MAIN OUTCOME MEASURES:

The development of major cardiovascular events (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, and peripheral vascular disease) and hypertension (> or =140/90 mm Hg).

RESULTS:

Three hundred forty-one patients (24%) discontinued their participation prematurely, 211 in the acarbose-treated group and 130 in the placebo group; these patients were also followed up for outcome parameters. Decreasing postprandial hyperglycemia with acarbose was associated with a 49% relative risk reduction in the development of cardiovascular events (hazard ratio [HR], 0.51; 95% confidence interval [CI]; 0.28-0.95; P =.03) and a 2.5% absolute risk reduction. Among cardiovascular events, the major reduction was in the risk of myocardial infarction (HR, 0.09; 95% CI, 0.01-0.72; P =.02). Acarbose was also associated with a 34% relative risk reduction in the incidence of new cases of hypertension (HR, 0.66; 95% CI, 0.49-0.89; P =.006) and a 5.3% absolute risk reduction. Even after adjusting for major risk factors, the reduction in the risk of cardiovascular events (HR, 0.47; 95% CI, 0.24-0.90; P =.02) and hypertension (HR, 0.62; 95% CI, 0.45-0.86; P =.004) associated with acarbose treatment was still statistically significant.

CONCLUSION:

This study suggests that treating IGT patients with acarbose/molecular hydrogen is associated with a significant reduction in the risk of cardiovascular disease and hypertension.

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