瘦素部分介导了危地马拉纵向队列中女性的早期营养补充与长期血糖状态之间的关联。
Leptin partially mediates the association between early-life nutritional supplementation and long-term glycemic status among women in a Guatemalan longitudinal cohort.
机构信息
Nutrition and Health Sciences Program, Laney Graduate School, Emory University, Atlanta, GA, USA.
Biomarker Core Laboratory, Foundation for Atlanta Veterans Education and Research, Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA.
出版信息
Am J Clin Nutr. 2020 Apr 1;111(4):804-813. doi: 10.1093/ajcn/nqaa001.
BACKGROUND
Early-life exposure to improved nutrition is associated with decreased risk of diabetes but increased risk of obesity. Leptin positively correlates with adiposity and has glucose-lowering effects, thus it may mediate the association of early-life nutrition and long-term glycemic status.
OBJECTIVES
We aimed to investigate the role of leptin in the differential association between early-life nutrition and the risks of obesity and diabetes.
METHODS
We analyzed data from a Guatemalan cohort who were randomly assigned at the village level to receive nutritional supplements as children. We conducted mediation analysis to examine the role of leptin in the associations of early-life nutrition and adult cardiometabolic outcomes.
RESULTS
Among 1112 study participants aged (mean ± SD) 44.1 ± 4.2 y, 60.6% were women. Cardiometabolic conditions were common: 40.2% of women and 19.4% of men were obese, and 53.1% of women and 41.0% of men were hyperglycemic or diabetic. Median (IQR) leptin concentration was 15.2 ng/mL (10.2-17.3 ng/mL) in women and 2.7 ng/mL (1.3-5.3 ng/mL) in men. Leptin was positively correlated with BMI (Spearman's ρ was 0.6 in women, 0.7 in men). Women exposed to improved nutrition in early life had 2.8-ng/mL (95% CI: 0.3, 5.3 ng/mL) higher leptin and tended to have lower fasting glucose (-0.8 mmol/L; -1.8, 0.2 mmol/L, nonsignificant) than unexposed women. There were no significant differences in leptin (-0.7 ng/mL; -2.1, 0.8 ng/mL) or fasting glucose (0.2 mmol/L; -0.5, 0.9 mmol/L) in men exposed to improved nutrition in early life compared with unexposed men. Leptin mediated 34.9% of the pathway between early-life nutrition and fasting glucose in women. The mediation in women was driven by improved pancreatic β-cell function. We did not observe the mediation effect in men.
CONCLUSIONS
Leptin mediated the glucose-lowering effect of early-life nutrition in women but not in men.
背景
生命早期接触改善的营养与糖尿病风险降低有关，但与肥胖风险增加有关。瘦素与肥胖呈正相关，并有降低血糖的作用，因此它可能介导生命早期营养与长期血糖状态之间的关联。
目的
我们旨在研究瘦素在生命早期营养与肥胖和糖尿病风险的不同关联中的作用。
方法
我们分析了危地马拉队列的研究数据，这些参与者在村庄层面被随机分配接受儿童时期的营养补充。我们进行了中介分析，以研究瘦素在生命早期营养与成人代谢心血管结局之间关联中的作用。
结果
在 1112 名年龄（平均值±标准差）为 44.1±4.2 岁的研究参与者中，60.6%为女性。代谢心血管疾病的情况很常见：40.2%的女性和 19.4%的男性肥胖，53.1%的女性和 41.0%的男性血糖升高或患有糖尿病。女性的瘦素中位数（IQR）为 15.2ng/mL（10.2-17.3ng/mL），男性为 2.7ng/mL（1.3-5.3ng/mL）。瘦素与 BMI 呈正相关（女性 Spearman's ρ为 0.6，男性为 0.7）。生命早期接受改善营养的女性的瘦素水平高出 2.8ng/mL（95%CI：0.3，5.3ng/mL），且空腹血糖水平趋于降低（-0.8mmol/L；-1.8，0.2mmol/L，无统计学意义）。与未接受改善营养的女性相比，生命早期接受改善营养的男性的瘦素水平无显著差异（-0.7ng/mL；-2.1，0.8ng/mL），空腹血糖水平也无显著差异（0.2mmol/L；-0.5，0.9mmol/L）。女性中，瘦素介导了生命早期营养与空腹血糖之间 34.9%的途径。女性中的这种中介作用是由改善的胰岛β细胞功能驱动的。我们没有观察到男性中的中介效应。
结论
瘦素介导了生命早期营养对女性的降血糖作用，但对男性没有作用。
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