The increasing prevalence of diabetes is of particular concern in women of childbearing age because of the short and long-term consequences of maternal diabetes for the health of the offspring, such as a greater risk of developing metabolic impairments and cognitive deficits. In addition, maternal diet during pregnancy and lactation might contribute to preventing or ameliorating adverse offspring outcomes. Recently, we described that access to snacks exacerbates glucose intolerance in mildly hyperglycemic pregnant dams. Therefore, we hypothesized that these offspring would show greater impairment in metabolic and behavioral outcomes across the lifespan. Neonatal STZ treatment was employed to induce maternal mild hyperglycemia in females. After mating, normo- and hyperglycemic dams were given access either to standard chow or standard show plus snacks. Male and female offspring were evaluated on postnatal days (PND) 30, 90, and 360. Offspring behavior was assessed in the marble burying task, the open field test, the elevated plus maze, and sucrose preference. Glucose tolerance and morphometric analyses were also carried out. Maternal hyperglycemia increased body weight and fat deposition only on PND 30, while retroperitoneal fat deposition was reduced in the offspring of snack-fed dams. However, maternal snack intake reduced offspring body weight and length on PND 90. Fasting glucose was increased in females born to hyperglycemic, snack-fed dams on PND 90. Glucose clearance was altered by both maternal conditions in male offspring on PND 30, however, this sex difference was reversed on PND 90, with maternal hyperglycemia impairing glucose clearance only in females. In addition, maternal hyperglycemia reduced anxiety-like behavior in female offspring on PND 30, especially in the offspring of snack-fed dams, while maternal snack intake reduced sucrose preference in both males and females in adulthood. These results suggest that the effects of maternal hyperglycemia during pregnancy and lactation on offspring outcomes were not exacerbated by snack intake. Although additive effects of the two maternal conditions were hypothesized, the absence of such effects could be related to the mild maternal hyperglycemia induced by STZ treatment even when combined with snack intake. While maternal hyperglycemia alone impaired some offspring outcomes, its association with snack intake did not aggravate those impairments but rather resulted in outcomes more similar to those of offspring born to normoglycemic dams. Finally, females were found to be more susceptible to both the effects of maternal hyperglycemia and snack intake on metabolism and behavior.

中文翻译：

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与零食摄入相关的母亲轻度高血糖对后代整个生命周期代谢和行为的影响

糖尿病患病率的上升在育龄妇女中尤其令人担忧，因为孕产妇糖尿病会对后代的健康产生短期和长期的影响，例如出现代谢障碍和认知缺陷的风险更大。此外，怀孕和哺乳期间的母亲饮食可能有助于预防或改善不良后代结局。最近，我们描述了吃零食会加剧轻度高血糖怀孕母鼠的葡萄糖不耐受。因此，我们假设这些后代在整个生命周期中的代谢和行为结果会表现出更大的损害。新生儿 STZ 治疗用于诱导女性产妇轻度高血糖。交配后，血糖正常和高血糖的母鼠可以吃标准食物或标准表演加零食。在出生后第 30 天、第 90 天和第 360 天对雄性和雌性后代进行评估。在大理石埋葬任务、旷场测试、高架十字迷宫和蔗糖偏好中评估后代的行为。还进行了葡萄糖耐量和形态测定分析。母体高血糖仅在 PND 30 时增加体重和脂肪沉积，而零食喂养的母鼠的后代腹膜后脂肪沉积减少。然而，母体零食摄入量在 PND 90 时降低了后代的体重和身长。在 PND 90 时，高血糖、零食喂养的母鼠所生的雌性小鼠的空腹血糖有所增加。在 PND 30 时，雄性后代的葡萄糖清除率因两种母体状况而改变，然而，这种性别差异在 PND 90 时逆转，母亲高血糖仅损害女性的葡萄糖清除率。此外，母体高血糖减少了 PND 30 雌性后代的焦虑样行为，尤其是零食喂养的母鼠的后代，而母体零食摄入量降低了成年雄性和雌性对蔗糖的偏好。这些结果表明，怀孕和哺乳期间母亲高血糖对后代结局的影响并没有因零食摄入而加剧。尽管假设这两种产妇状况存在累加效应，但这种效应的缺失可能与 STZ 治疗（即使与零食摄入相结合）引起的轻度产妇高血糖有关。虽然母亲高血糖本身会损害一些后代的结果，但它与零食摄入的相关性并没有加剧这些损害，而是导致了与血糖正常的母鼠所生的后代更相似的结果。最后，发现女性更容易受到母亲高血糖和零食摄入对新陈代谢和行为的影响。