The effect of short-term alpha-glucosidase inhibition on carbohydrate and lipid metabolism in type II (noninsulin-dependent) diabetics.

With use of the alpha-glucosidase inhibitor bay g 5421 (acarbose), it is possible to improve glycemic profiles in diabetics without a concomitant increase in insulin levels or weight reduction. We have taken advantage of this feature to test whether an improvement in glycemic control alone can ameliorate some of the known abnormalities of type II diabetes (ie, impaired insulin secretion, elevated rate of basal hepatic glucose output, peripheral insulin resistance). We have studied eight type II diabetics (mean +/- SE fasting serum glucose 193 +/- 25 mg/dL) before and after 2 weeks of acarbose therapy (100 mg with each meal). Assessment of endogenous insulin secretion, peripheral and hepatic insulin sensitivity, and adipose tissue lipoprotein lipase (ATLPL) activity were performed. Results showed significant lowering of postprandial glucose excursions above basal but no change in basal serum glucose levels, marked reduction in fasting and day-long triglyceride levels and in spite of a reduction in ATLPL activity, an increase in hepatic sensitivity to insulin's ability to suppress hepatic glucose output, and no effect on peripheral insulin sensitivity. In conclusion, inhibition of carbohydrate digestion with alpha-glucosidase inhibitors ameliorates many of the metabolic abnormalities in type II (noninsulin-dependent diabetics), suggesting that agents of this type can be of therapeutic value.