Impaired beta-cell function in human aging: response to nicotinic acid-induced insulin resistance.
BACKGROUND
Glucose tolerance declines with age and may involve impaired beta-cell sensitivity to glucose and beta-cell compensation for insulin resistance.


OBJECTIVE
We investigated beta-cell sensitivity to glucose and beta-cell compensation for nicotinic acid-induced insulin resistance in young (age <35 yr) people with normal glucose tolerance (NGT) and old (age >60 yr) people with NGT and impaired glucose tolerance (IGT). DESIGN/PATIENTS/SETTING/INTERVENTION: Fifteen young NGT, 16 old NGT, and 14 old IGT were randomized to 2-wk treatment with nicotinic acid or placebo in a double-blind, crossover study in a university medical setting. At the end of each treatment period, participants had a frequently sampled iv glucose tolerance test and ramp clamp, in which insulin secretion rates (ISR) were determined in response to a matched 5-10 mm glucose stimulus.


METHODS
Insulin sensitivity (S(I)), acute insulin response to iv glucose (AIRg), and disposition index (AIRg x S(I), or beta-cell compensation for insulin resistance) from frequently sampled iv glucose tolerance testing, and ISR area under the curve (or beta-cell sensitivity to glucose) from ramp clamp were determined.


RESULTS
Progressive impairments in insulin secretion as assessed by AIRg, disposition index, and ISR area under the curve were identified in older people with NGT, with more marked defects in older people with IGT. Nicotinic acid treatment significantly reduced S(I) in all groups. beta-Cell compensation for nicotinic acid-induced insulin resistance was incomplete in all three groups, with greater defects in the two older groups.


CONCLUSIONS
Human aging is associated with impaired beta-cell sensitivity to glucose and impaired beta-cell compensation to insulin resistance.
Chang
Annette M
AM
5570 MSRB II, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109-0678, USA. annchang@umich.edu
Smith
Marla J
MJ
Galecki
Andrzej T
AT
Bloem
Cathie J
CJ
Halter
Jeffrey B
JB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D000960:Hypolipidemic Agents; D014280:Triglycerides; D009525:Niacin; D002784:Cholesterol; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine