Changes in Carbohydrate Metabolism in Association With Glipizide Treatment of Type 2 Diabetes

Abstract

Nineteen patients with Type 2 diabetes were treated with glipizide for 2.5-6 months, and measurements made of metabolic variables before and after glipizide treatment. For purposes of analysis, the glipizide associated decrease in fasting plasma glucose concentration was used to divide patients into 'good' responders (decrease of 4.0 mmol l-1 or more, n = 9) or 'fair' responders (decrease of 3.0 mmol l-1 or less, n = 10). Good responders had a significantly greater fall in their mean (+/- SE) hourly plasma glucose (6.3 +/- 0.6 vs 2.7 +/- 0.3 mmol l-1, p less than 0.001) and NEFA (164 +/- 40 vs 60 +/- 37 mumol l-1, p less than 0.05) concentrations from 0800 to 1600 h in response to meals (0800 and 1200 h) than did the fair responders. However, the increase in hourly plasma insulin concentration following glipizide treatment was the same in the good (323 +/- 103 to 413 +/- 124 pmol l-1) and fair (276 +/- 42 to 345 +/- 43 pmol l-1) responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Glipizide Treatment on Response to an Infused Glucose Load in Patients With NIDDM

“…Based on these findings, it has been suggested that the ability of insulin to stimulate glucose uptake increases after sulfonylurea treatment of patients with N1DDM (1-5). However, we have not been able to provide experimental evidence for this assumption in two previous studies (4,5). Instead, our results indicated that the improvement in glucose uptake after sulfonylurea treatment could be discerned when measured during glucose clamp studies in response to either basal or elevated insulin concentrations, but the incremental increase in glucose uptake when insulin levels were increased during the clamp was similar before and after treatment.…”

“…CONCLUSIONS -Results of several published studies have shown that improvement in glycemic control in sulfonylurea-treated patients with NIDDM was associated with enhanced glucose uptake measured during glucose clamp studies (1)(2)(3)(4)(5). Based on these findings, it has been suggested that the ability of insulin to stimulate glucose uptake increases after sulfonylurea treatment of patients with N1DDM (1-5).…”

“…Thus, irrespective of whether the increase in peripheral glucose disposal associated with sulfonylurea represents a direct effect or one that is secondary to a decrease in glucose toxicity, we do not know the relative importance of changes in glucose disposal rate that occur in response to varying insulin concentrations. We attempted to address this question previously by performing glucose clamp studies at two different insulin levels, before and after sulfonylurea treatment, in patients with NIDDM (4,5). Since those publications, our experience has led us to believe that the glucose clamp may not provide the sensitivity needed to make this distinction in insulin-resistant patients.…”

“…Whereas there is a good deal of evidence showing that the ability of patients with NIDDM to respond to a glucose challenge improves when they are treated with sulfonylurea compounds (1)(2)(3)(4)(5), it is not clear if this change is the specific result of sulfonylurea treatment or a nonspecific change due to improved glycemic control, irrespective of the therapeutic modality (6). A second level of uncertainty relates to whether the enhanced ability of an individual to respond to a glucose challenge associated with sulfonylurea treatment can be seen at basal insulin levels, in response to physiological hyperinsulinemia, and whether or not there is any effect of the incremental increase in insulin concentration on glucose homeostasis.…”

Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM

“…All of these changes have been previously demonstrated to occur with glipizide treatment of patients with NIDDM [27,28].…”