妊娠33-38周时出生 第一型糖尿病风险较高


  【24drs.com】在瑞典针对所有出生病历进行了40年广泛研究的研究者表示,不论家庭因素如何,胎龄和第一型糖尿病之间似乎有所关联。
  
  第一作者、爱尔兰科克大学流行病学者Ali Khashan博士表示,这个关联可能和早期发育受限或由于肠道菌群改变而造成的胰岛素阻抗性有关。
  
  他指出,关于生命初期对发生糖尿病之风险的影响,我们的研究提供了新的和有趣的资料。
  
  这篇研究在线发表于10月30日的糖尿病照护期刊。
  
  Khashan博士强调三个主要发现,第一,晚期早产和早期足月产的婴儿,发生第一型糖尿病的风险增加。他指出,这个关联虽然小,无法由不可测量的家族干扰因素,如遗传和生活方式、与兄弟姐妹共享等因素解释。
  
  第二,胎龄大和第一型糖尿病风险增加之间的关联,不太可能是因果,但是可能可以用兄弟姐妹共享的家族因素来解释。
  
  第三,反之,研究者发现,胎龄33周前出生的婴儿(极早产)和/或出生体重小于1500公克者、或胎龄小者,似乎可免于发生第一型糖尿病。
  
  他指出,这是有趣的,且值得进一步研究,因为它可以帮助[我们]了解影响发生第一型糖尿病的胎儿发展。
  
  Khashan博士解释进行研究的原因时表示,目前有关胎龄、出生体重、第一型糖尿病之间之可能关联的资料是不一致且矛盾的,所以他的研究团队希望检视这些关联,而进行了这次迄今最大型的世代研究、纳入超过300万名新生儿。
  
  他指出,除了使用这最大型的人口基础研究,还校正了多项重要的潜在干扰因素,所以我们可以检视极早产和极低出生体重对于第一型糖尿病的影响。
  
  我们也可以进行手足对照研究,让我们能够间接地考虑兄弟姐妹共享、不可测量的遗传和环境因素的影响。
  
  分析方法根据两个步骤:人口基础世代研究,纳入瑞典在1973-2009年间、几乎全部的单胞胎活产病历,资料来源是瑞典医学出生登记(Swedish Medical Birth Register),这是公认的高质量资料来源;其中,对确认有第一型糖尿病诊断的孩童(来自瑞典全国病患登记(Swedish National Patient Register))和他们没有糖尿病的兄弟姊妹配对,进行巢式病例对照研究。
  
  这项世代研究共有3,624,675名单胞胎活产孩童,其中13,944人诊断有第一型糖尿病,兄弟姊妹配对案例对照研究包括了82%(13,944人中的11,403人)的第一型糖尿病例与配对的17,920名兄弟姊妹对照组。
  
  根据不同的准则,使用统计模式辨识发生第一型糖尿病的相对风险。
  
  这篇研究并未包括妈妈们在怀孕期间生活型态的可能干扰因素的相关资料。
  
  但是,研究者解释,使用兄弟姊妹当对照组让我们可以校正手足间共享的无法测量的因素,例如:家庭环境、饮食、生活型态、母亲的特征、遗传因素等。
  
  Khashan博士报告指出,我们发现,未足月早产(胎龄33-36周;糖尿病相对风险[RR]值为1.18)和足月早产(胎龄37-38周;RR为1.12)与第一型糖尿病风险增加之间有小但显著的关联,纳入兄弟姊妹对照组之后,此关联依旧显著。
  
  研究者也发现,极低出生体重(RR, 0.66)、胎龄小(RR, 0.83)、极早产(胎龄小于33周)(RR, 0.67)呈现相反的关联性,与第一型糖尿病风险降低有关。
  
  Khashan博士解释,胎龄大的婴儿第一型糖尿病风险增加(RR, 1.14),但是,一旦纳入兄弟姊妹对照组的家庭因素,这个影响似乎消失。
  
  作者们写道,至于造成观察到这个关联的可能机转,可能是未足月早产和器官系统的结构变化有关,以及表观遗传的改变,导致第一型糖尿病风险增加。
  
  资料来源:http://www.24drs.com/
  
  Native link:Birth at 33-38 Weeks Equals Higher Risk of Type 1 Diabetes

Birth at 33-38 Weeks Equals Higher Risk of Type 1 Diabetes

By Becky McCall
Medscape Medical News

Gestational age and type 1 diabetes appear to be linked, independent of familial factors, say researchers who conducted an extensive study on nearly all births in Sweden over 4 decades.

The link could be related to insulin resistance developing as a consequence of early-life growth restriction or attributed to altered gut microbiota, lead author Dr Ali Khashan, PhD, an epidemiologist from University College Cork, Ireland, told Medscape Medical News.

"Our study provides new and intriguing data on the early life influences on the risk of developing diabetes," he added.

The work was published online October 30 in Diabetes Care.

Dr Khashan highlighted the three key findings. First, late preterm birth and early-term birth babies are at increased risk of type 1 diabetes. "This association, although small, cannot be explained by unmeasured familial confounding factors, such as genetic and lifestyle factors, shared by siblings," he pointed out.

Second, an association seen between large-for-gestational-age babies and increased risk for type 1 diabetes is unlikely to be causal and may be explained by familial factors shared by siblings, he said.

Third, and conversely, the researchers found that babies born before 33 gestation weeks (very preterm) and/or with birth weight of less than 1500 g, or small for gestational age, seem to be protected against type 1 diabetes.

"This is intriguing and deserves further investigation, as it may help [us to] understand the fetal programming effect on the development of type 1 diabetes," he noted.

Novel Sibling Control Study

Explaining the reasons for conducting the study, Dr Khashan said existing data on the potential association between gestational age, birth weight, and type 1 diabetes is inconsistent and contradictory, so his team wanted to examine these associations using the largest cohort study to date, which included more than three million births.

"In addition to using a very large population-based study and adjusting for several important potential confounders, we were able to examine the effects of very preterm birth and very low birth weight on type 1 diabetes," he noted.

"We were also able to conduct a sibling control study, which may have allowed us to, indirectly, account for unmeasured genetic and environmental factors shared by siblings."

The analytical approach was based on two steps: a population-based cohort study which included nearly all live singleton births in Sweden between 1973 and 2009, sourced from the Swedish Medical Birth Register, widely considered a high-quality data source; and within this, a nested case-control study where children with a diagnosis of type 1 diabetes were identified (from the Swedish National Patient Register) and matched with their siblings who did not have diabetes, as controls.

The cohort study consisted of 3,624,675 singleton live children, of which 13,944 were diagnosed with type 1 diabetes. The sibling-matched case-control study included 82% of the type 1 diabetes cases (11,403 of 13,944) matched with 17,920 sibling controls.

Statistical modeling was used to identify the relative risks for developing type 1 diabetes according to different criteria.

The study did not include information on possible confounders due to maternal lifestyle during pregnancy.

But using the sibling controls "allowed us to adjust for unmeasured factors that are shared by siblings, such as family environment, diet, lifestyle, maternal characteristics, and genetic factors," the researchers explain.

Preterm and Early-Term Birth Increase Risk; Very Preterm Reduces Risk

"We found a small but significantly increased risk of type 1 diabetes in relation to preterm (33 to 36 weeks' gestation; relative risk [RR] of diabetes, 1.18) and early term (37 to 38 weeks; RR, 1.12) birth, and this remained significant after accounting for sibling controls," reported Dr Khashan.

The researchers also found that very low birth weight (RR, 0.66), small for gestational age (RR, 0.83), and very preterm birth (less than 33 weeks' gestation) (RR, 0.67) conversely appeared to be associated with a reduced risk of type 1 diabetes.

Babies that were large for gestational age had an increased risk of type 1 diabetes (RR, 1.14), but this effect disappeared once familial factors were accounted for in the sibling controls, explained Dr Khashan.

With respect to possible mechanisms driving the observed associations, the authors write, "It is possible that preterm birth is associated with structural change within organ systems and epigenetic changes leading to higher risk of type 1 diabetes."

The authors declare no relevant financial relationships.

Diabetes Care. Published online October 30, 2015.

    
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