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早期补充叶酸和维生素B12可改善宫内生长迟缓大鼠的胰岛素抵抗。

Early supplementation of folate and vitamin B12 improves insulin resistance in intrauterine growth retardation rats.

作者信息

Zhang Hui, Wang Xinli, Zhang Jin, Guan Yuhong, Xing Yan

机构信息

Department of Pediatrics, Peking University Third Hospital, Beijing, China.

Department of Pediatrics, Beijing Jishuitan Hospital, Beijing, China.

出版信息

Transl Pediatr. 2022 Apr;11(4):466-473. doi: 10.21037/tp-21-498.

Abstract

BACKGROUND

Insulin sensitivity is changed during the neonatal period in small for gestational age (SGA) infants. Yet, the interventional strategies are still limited. We aimed to investigate the effects of supplementation with high folate and vitamin B12 diets in the early postnatal period on the changes in insulin sensitivity in an intrauterine growth retardation (IUGR) rat model.

METHODS

IUGR rat model was established by both low-protein diet feeding and daily diet restriction. High folate and vitamin B12 diet was supplied in IUGR as nutritional interventional group (IUGR-I), otherwise, the non-intervened IUGR group (IUGR-NI). In this study, male rats were studied in order to avoid hormonal and gender influence. At 21, 60 and 120 days, fasting plasma glucose, insulin, triglyceride, cholesterol, and homocysteine levels were measured among the control, IUGR-I, and IUGR-NI groups. Pearson analysis was used to evaluate the correlation between homocysteine and fasting blood glucose, insulin, HOMA-IR, triglyceride, and cholesterol levels.

RESULTS

We established IUGR rat model by both low protein and restricted diet feeding during pregnancy and the incidence of IUGR pups was 93.33%. There was no difference in fasting glucose, insulin, HOMA-IR, triglyceride and cholesterol levels between the control, the IUGR-NI and the IUGR-I group at day 21. At day 60, insulin, HOMA-IR and triglyceride levels in the IUGR-I group were remarkably lower than those in the IUGR-NI group, but still higher than those in the control group (F=38.34, P=0.02; F=49.48, P=0.02; F=17.93, P<0.001, respectively). At day 120, glucose, insulin, HOMA-IR and Hcy levels in the IUGR-I group were obviously lower than those in the IUGR-NI group, although still higher than those in the control group (F=21.60, P<0.001; F=164.46, P<0.001; F=75.15, P<0.001; F=35.46, P<0.001, respectively). There were no significant differences in triglyceride and cholesterol levels between the IUGR-I group and the control group at day 120. At 120-day, homocysteine in IUGR-I group was highly positively correlated with fasting glucose and HOMA-IR (r=0.863, P=0.006; r=0.725, P=0.042, respectively); Only homocysteine was positively correlated with fasting glucose in IUGR-NI group (r=0.721, P=0.044).

CONCLUSIONS

Early supplementation of folate and vitamin B12 improved insulin resistance and lipid levels in IUGR rats to some extent, along with decreasing homocysteine levels, but not enough to completely repair glucose and lipid metabolism.

摘要

背景

小于胎龄(SGA)婴儿在新生儿期胰岛素敏感性会发生变化。然而,干预策略仍然有限。我们旨在研究在出生后早期补充高叶酸和维生素B12饮食对宫内生长受限(IUGR)大鼠模型胰岛素敏感性变化的影响。

方法

通过低蛋白饮食喂养和每日饮食限制建立IUGR大鼠模型。将高叶酸和维生素B12饮食供应给IUGR作为营养干预组(IUGR-I),否则为未干预的IUGR组(IUGR-NI)。在本研究中,为避免激素和性别影响,仅研究雄性大鼠。在21、60和120日龄时,测量对照组、IUGR-I组和IUGR-NI组的空腹血糖、胰岛素、甘油三酯、胆固醇和同型半胱氨酸水平。采用Pearson分析评估同型半胱氨酸与空腹血糖、胰岛素、HOMA-IR、甘油三酯和胆固醇水平之间的相关性。

结果

我们通过孕期低蛋白和限制饮食喂养建立了IUGR大鼠模型,IUGR幼崽的发生率为93.33%。在21日龄时,对照组、IUGR-NI组和IUGR-I组之间的空腹血糖、胰岛素、HOMA-IR、甘油三酯和胆固醇水平没有差异。在60日龄时,IUGR-I组的胰岛素、HOMA-IR和甘油三酯水平显著低于IUGR-NI组,但仍高于对照组(F分别为38.34,P = 0.02;F为49.48,P = 0.02;F为17.93,P < 0.001)。在120日龄时,IUGR-I组的血糖、胰岛素、HOMA-IR和Hcy水平明显低于IUGR-NI组,尽管仍高于对照组(F分别为21.60,P < 0.001;F为164.46,P < 0.001;F为75.15,P < 0.001;F为35.46,P < 0.001)。在120日龄时,IUGR-I组和对照组之间的甘油三酯和胆固醇水平没有显著差异。在120日龄时,IUGR-I组的同型半胱氨酸与空腹血糖和HOMA-IR高度正相关(r分别为0.863,P = 0.006;r为0.725,P = 0.042);在IUGR-NI组中,仅同型半胱氨酸与空腹血糖正相关(r为0.7

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