Department of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, the Netherlands.
Aging Cell. 2011 Feb;10(1):114-21. doi: 10.1111/j.1474-9726.2010.00650.x. Epub 2010 Dec 7.
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.
胰岛素抵抗是各种与年龄相关疾病的危险因素。在莱顿长寿研究中，我们招募了长寿兄弟姐妹及其后代。此前，我们发现与对照组相比，长寿兄弟姐妹的后代具有更好的葡萄糖耐量。在这里，我们比较了长寿兄弟姐妹的后代组和对照组的非空腹血清中胰岛素和葡萄糖之间的关系（n = 1848 名受试者），并使用两步高胰岛素-正常血糖钳夹法（n = 24 名受试者）来定量胰岛素作用。后代组和对照组在性别分布、年龄和体重指数方面相似。我们观察到 ln（胰岛素）水平与非空腹葡萄糖之间存在正双相线性关系，与对照组相比，在 10.7mU L（-1）胰岛素之后，斜率更陡（P = 0.02）。在钳夹研究中，需要更高的葡萄糖输注率来维持高剂量胰岛素输注期间的血糖正常（P = 0.036），这反映了更高的全身胰岛素敏感性。在调整性别、年龄和脂肪量后，后代的胰岛素介导的葡萄糖处置率（GDR）高于对照组（42.5 ± 2.7 与 33.2 ± 2.7 μmol kg（-1）min（-1），平均值 ± SE，P = 0.025）。两组之间胰岛素介导的内源性葡萄糖产生和脂肪分解的抑制没有差异（均 P > 0.05）。此外，GDR 与父母的平均死亡年龄显著相关。总之，长寿兄弟姐妹的后代具有增强的外周葡萄糖处置能力。未来的研究将集中于鉴定潜在的生物分子机制，以促进老年健康。
