Effect of lowering postprandial hyperglycemia on insulin secretion in older people with impaired glucose tolerance

Abstract

2004.-Glucose tolerance declines with age, resulting in a high prevalence of diabetes and impaired glucose tolerance (IGT) in the older population. Hyperglycemia per se can lead to impaired ␤-cell function (glucose toxicity). We tested the role of glucose toxicity in age-related ␤-cell dysfunction in older people (65 Ϯ 8 yr) with IGT treated with the ␣-glucosidase inhibitor acarbose (n ϭ 14) or placebo (n ϭ 13) for 6 wk in a randomized, double-blind study. Baseline and posttreatment studies included 1) an oral glucose tolerance test (OGTT), 2) 1-h postprandial glucose monitoring, 3) a frequently sampled intravenous glucose tolerance test (insulin sensitivity, or S I), and 4) glucose ramp clamp (insulin secretion rates, or ISR), in which a variable glucose infusion increases plasma glucose from 5 to 10 mM. The treatment groups had similar baseline body mass index; fasting, 2-h OGTT, and 1-h postprandial glucose levels; and S I. In these carefully matched older people with IGT, both fasting (5.7 Ϯ 0.2 vs. 6.3 Ϯ 0.2 mM, P ϭ 0.002) and 1-h postprandial glucose levels (6.9 Ϯ 0.3 vs. 8.2 Ϯ 0.4 mM, P ϭ 0.02) were significantly lower in the acarbose than in the placebo group. Despite this reduction of chronic hyperglycemia in the acarbose vs. placebo group, measures of insulin secretion (ISR area under the curve: 728 Ϯ 55 vs. 835 Ϯ 81 pmol/kg, P ϭ 0.9) and acute insulin response to intravenous glucose (329 Ϯ 67 vs. 301 Ϯ 54 pM, P ϭ 0.4) remained unchanged and impaired. Thus short-term improvement of chronic hyperglycemia does not reverse ␤-cell dysfunction in older people with IGT.␤-cell function; glucose intolerance; aged humans THE PREVALENCE OF TYPE 2 DIABETES and impaired glucose tolerance (IGT) increases with age (6). More than 25% of the older population meets current diagnostic criteria for type 2 diabetes (15, 24). An additional 20% of this population meets criteria for IGT, defined as a 2-h glucose level Ն7.8 mM but Ͻ11.1 mM by oral glucose tolerance testing (OGTT) and a fasting glucose Ͻ7.0 mM (15). Isolated postchallenge hyperglycemia, defined as a 2-h glucose level Ն11.1 mM by OGTT, but a fasting glucose level Ͻ7.0 mM, is particularly common in people over age 60 (1,10,11,29).IGT, as with type 2 diabetes, is characterized by both insulin resistance (13,20) and defects in ␤-cell function (13,20,30). Multiple risk factors for type 2 diabetes associated with aging may predispose older people to develop glucose intolerance and increased insulin resistance. Insulin secretory defects have been consistently demonstrated even with normal aging, with greater defects in older people with IGT (2, 6, 8). Over time, chronic exposure to hyperglycemia in older people with IGT may cause a further decline in ␤-cell function. Studies in animal models and humans suggest that chronic hyperglycemia may have adverse effects on insulin secretion, an effect called glucose toxicity (25).␣-Glucosidase inhibitors, such as acarbose, act by inhibiting enzymes in the small intestine, thereby decreasing glucose absorption and improving po...

Insulin sensitizing and α-glucoamylase inhibitory action of sennosides, rheins and rhaponticin in Rhei Rhizoma

“…The overall effect of this on the diabetic patient is that the starch-containing diet is degraded more slowly and along the full length of the small intestine. Thus, acarbose administration significantly lowered the postprandial blood glucose levels in type 2 diabetes patients than the placebo (Chang et al, 2004).…”

Treating Postprandial Hyperglycemia Does Not Appear to Delay Progression of Early Type 2 Diabetes

“…The results of our study would seem to support those of a smaller trial in which acarbose or placebo was given for 6 weeks to subjects with IGT. Despite significant reductions in postprandial hyperglycemia with acarbose in that trial, there were no differences in insulin secretion rates by glucose ramp clamp nor in the acute insulin response to intravenous glucose by frequently sampled intravenous glucose tolerance tests (21).…”

ß‐cell function and anti‐diabetic pharmacotherapy

“…The effect of α‐glucosidase inhibitors on β‐cell function has been inconsistent and controversial. No change was found in elderly patients with well‐controlled diabetes 69, 70, as well as decreased 71, or increased 72 in response to a mixed meal. The possibility that α‐glucosidase inhibitors might affect β‐cell function is based on early observation of increased glucagon‐like peptide‐1 (GLP‐1) release in healthy volunteers as well as in patients with type 2 diabetes 73–75.…”