Miljkovic Iva, Cvejkus Ryan, An Ping, Thyagarajan Bharat, Christensen Kaare, Wojczynski Mary, Schupf Nicole, Zmuda Joseph M
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States.
Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States.
Front Clin Diabetes Healthc. 2022 Apr 11;3:753986. doi: 10.3389/fcdhc.2022.753986. eCollection 2022.
Little is known about the risk of type 2 diabetes (T2D) among the offspring of individuals with exceptional longevity. We determined the incidence of and potential risk and protective factors for T2D among the offspring of probands and offspring's spouses (mean age=60 years, range 32-88 years) in the Long Life Family Study (LLFS), a multicenter cohort study of 583 two-generation families with a clustering of healthy aging and exceptional longevity. Incident T2D was defined as fasting serum glucose ≥126 mg/dl, or HbA1c of ≥6.5%, or self-reported with doctor diagnosis of T2D, or the use of anti-diabetic medication during a mean follow-up 7.9 ± 1.1 years. Among offspring (n=1105) and spouses (n=328) aged 45-64 years without T2D at baseline visit, the annual incident rate of T2D was 3.6 and 3.0 per 1000 person-years, respectively, while among offspring (n=444) and spouses (n=153) aged 65+ years without T2D at baseline, the annual incident rate of T2D was 7.2 and 7.4 per 1000 person-years, respectively. By comparison, the annual incident rate of T2D per 1000 person-years in the U.S. general population was 9.9 among those aged 45-64, and 8.8 among those aged 65+ years (2018 National Health Interview Survey). Baseline BMI, waist circumference, and fasting serum triglycerides were positively associated with incident T2D, whereas fasting serum HDL-C, adiponectin, and sex hormone binding globulin were protective against incident T2D among the offspring (all P<0.05). Similar associations were observed among their spouses (all P<0.05, except sex hormone binding globulin). In addition, we observed that among spouses, but not offspring, fasting serum interleukin 6 and insulin-like growth factor 1 were positively associated with incident T2D (P<0.05 for both). Our study suggests that both offspring of long-living individuals and their spouses, especially middle-aged, share a similar low risk for developing T2D as compared with the general population. Our findings also raise the possibility that distinct biological risk and protective factors may contribute to T2D risk among offspring of long-lived individuals when compared with their spouses. Future studies are needed to identify the mechanisms underlying low T2D risk among the offspring of individuals with exceptional longevity, and also among their spouses.
对于长寿个体后代患2型糖尿病(T2D)的风险,我们所知甚少。在长寿家族研究(LLFS)中,我们确定了先证者及其后代配偶(平均年龄 = 60岁,范围32 - 88岁)中T2D的发病率以及潜在风险和保护因素。LLFS是一项多中心队列研究,涉及583个两代家庭,这些家庭呈现出健康老龄化和长寿的聚集现象。新发T2D的定义为空腹血清葡萄糖≥126 mg/dl,或糖化血红蛋白(HbA1c)≥6.5%,或自我报告经医生诊断为T2D,或在平均随访7.9 ± 1.1年期间使用抗糖尿病药物。在基线访视时无T2D的45 - 64岁后代(n = 1105)和配偶(n = 328)中,T2D的年发病率分别为每1000人年3.6例和3.0例,而在基线时无T2D的65岁及以上后代(n = 444)和配偶(n = 153)中,T2D的年发病率分别为每1000人年7.2例和7.4例。相比之下,在美国普通人群中,45 - 64岁人群T2D的年发病率为每1000人年9.9例,65岁及以上人群为每1000人年8.8例(2018年国家健康访谈调查)。基线体重指数(BMI)、腰围和空腹血清甘油三酯与新发T2D呈正相关,而空腹血清高密度脂蛋白胆固醇(HDL - C)、脂联素和性激素结合球蛋白对后代新发T2D具有保护作用(所有P < 0.05)。在其配偶中也观察到类似的关联(除性激素结合球蛋白外,所有P < 0.05)。此外,我们观察到,在配偶而非后代中,空腹血清白细胞介素6和胰岛素样生长因子1与新发T2D呈正相关(两者P均< 0.05)。我们的研究表明,与普通人群相比,长寿个体的后代及其配偶,尤其是中年人,患T2D的风险较低。我们的研究结果还提出了一种可能性,即与配偶相比,长寿个体后代中不同的生物学风险和保护因素可能导致T2D风险。未来需要开展研究,以确定长寿个体后代及其配偶中T2D风险较低的潜在机制。