title: Effect of lowering postprandial hyperglycemia on insulin secretion in older people with impaired glucose tolerance.
abstract: 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 beta-cell function (glucose toxicity). We tested the role of glucose toxicity in age-related beta-cell dysfunction in older people (65 +/- 8 yr) with IGT treated with the alpha-glucosidase inhibitor acarbose (n = 14) or placebo (n = 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 +/- 0.2 vs. 6.3 +/- 0.2 mM, P = 0.002) and 1-h postprandial glucose levels (6.9 +/- 0.3 vs. 8.2 +/- 0.4 mM, P = 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 +/- 55 vs. 835 +/- 81 pmol/kg, P = 0.9) and acute insulin response to intravenous glucose (329 +/- 67 vs. 301 +/- 54 pM, P = 0.4) remained unchanged and impaired. Thus short-term improvement of chronic hyperglycemia does not reverse beta-cell dysfunction in older people with IGT.
authors.affiliation: Department of Internal Medicine, University of Michigan, 1111 CCGC Bldg., 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0926, USA.
authors.forename: Annette M
authors.initials: AM
authors.lastname: Chang
authors.forename: Marla J
authors.initials: MJ
authors.lastname: Smith
authors.forename: Cathie J
authors.initials: CJ
authors.lastname: Bloem
authors.forename: Andrzej T
authors.initials: AT
authors.lastname: Galecki
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Halter
mesh_terms: D020909:Acarbose / Q000627:therapeutic use*; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002908:Chronic Disease; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005951:Glucose Tolerance Test; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism*; D007328:Insulin / Q000097:blood*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007328:Insulin; D020909:Acarbose