Familial longevity is marked by enhanced insulin sensitivity.
Insulin resistance is a risk factor for various age-related diseases. In the Leiden Longevity study, we recruited long-lived siblings and their offspring. Previously, we showed that, compared to controls, the offspring of long-lived siblings had a better glucose tolerance. Here, we compared groups of offspring from long-lived siblings and controls for the relation between insulin and glucose in nonfasted serum (n = 1848 subjects) and for quantitation of insulin action using a two-step hyperinsulinemic-euglycemic clamp (n = 24 subjects). Groups of offspring and controls were similar with regard to sex distribution, age, and body mass index. We observed a positive bi-phasic linear relationship between ln (insulin) levels and nonfasted glucose with a steeper slope from 10.7mU L(-1) insulin onwards in controls compared to offspring (P = 0.02). During the clamp study, higher glucose infusion rate was required to maintain euglycemia during high-dose insulin infusion (P = 0.036) in offspring, reflecting higher whole-body insulin sensitivity. After adjustment for sex, age, and fat mass, the insulin-mediated glucose disposal rate (GDR) was higher in offspring than controls (42.5 ± 2.7 vs. 33.2 ± 2.7 micromol kg(-1) min(-1) , mean ± SE, P = 0.025). The insulin-mediated suppression of endogenous glucose production and lipolysis did not differ between groups (all P > 0.05). Furthermore, GDR was significantly correlated with the mean age of death of the parents. In conclusion, offspring from long-lived siblings are marked by enhanced peripheral glucose disposal. Future research will focus on identifying the underlying biomolecular mechanisms, with the aim to promote health in old age.
Department of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, the Netherlands.
Carolien A
CA
Wijsman
Maarten P
MP
Rozing
Trea C M
TC
Streefland
Saskia
S
le Cessie
Simon P
SP
Mooijaart
P Eline
PE
Slagboom
Rudi G J
RG
Westendorp
Hanno
H
Pijl
Diana
D
van Heemst
D000328:Adult; D032721:Adult Children; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition / Q000502:physiology; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008066:Lipolysis / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008136:Longevity / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D012307:Risk Factors
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose