妊娠33-38週時出生 第一型糖尿病風險較高


  【24drs.com】在瑞典針對所有出生病歷進行了40年廣泛研究的研究者表示,不論家庭因素如何,胎齡和第一型糖尿病之間似乎有所關聯。
  
  第一作者、愛爾蘭科克大學流行病學者Ali Khashan博士表示,這個關聯可能和早期發育受限或由於腸道菌群改變而造成的胰島素阻抗性有關。
  
  他指出,關於生命初期對發生糖尿病之風險的影響,我們的研究提供了新的和有趣的資料。
  
  這篇研究線上發表於10月30日的糖尿病照護期刊。
  
  Khashan博士強調三個主要發現,第一,晚期早產和早期足月產的嬰兒,發生第一型糖尿病的風險增加。他指出,這個關聯雖然小,無法由不可測量的家族干擾因素,如遺傳和生活方式、與兄弟姐妹共享等因素解釋。
  
  第二,胎齡大和第一型糖尿病風險增加之間的關聯,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來解釋。
  
  第三,反之,研究者發現,胎齡33週前出生的嬰兒(極早產)和/或出生體重小於1500公克者、或胎齡小者,似乎可免於發生第一型糖尿病。
  
  他指出,這是有趣的,且值得進一步研究,因為它可以幫助[我們]瞭解影響發生第一型糖尿病的胎兒發展。
  
  Khashan博士解釋進行研究的原因時表示,目前有關胎齡、出生體重、第一型糖尿病之間之可能關聯的資料是不一致且矛盾的,所以他的研究團隊希望檢視這些關聯,而進行了這次迄今最大型的世代研究、納入超過300萬名新生兒。
  
  他指出,除了使用這最大型的人口基礎研究,還校正了多項重要的潛在干擾因素,所以我們可以檢視極早產和極低出生體重對於第一型糖尿病的影響。
  
  我們也可以進行手足對照研究,讓我們能夠間接地考慮兄弟姐妹共享、不可測量的遺傳和環境因素的影響。
  
  分析方法根據兩個步驟:人口基礎世代研究,納入瑞典在1973-2009年間、幾乎全部的單胞胎活產病歷,資料來源是瑞典醫學出生登記(Swedish Medical Birth Register),這是公認的高品質資料來源;其中,對確認有第一型糖尿病診斷的孩童(來自瑞典全國病患登記(Swedish National Patient Register))和他們沒有糖尿病的兄弟姊妹配對,進行巢式病例對照研究。
  
  這項世代研究共有3,624,675名單胞胎活產孩童,其中13,944人診斷有第一型糖尿病,兄弟姊妹配對案例對照研究包括了82%(13,944人中的11,403人)的第一型糖尿病例與配對的17,920名兄弟姊妹對照組。
  
  根據不同的準則,使用統計模式辨識發生第一型糖尿病的相對風險。
  
  這篇研究並未包括媽媽們在懷孕期間生活型態的可能干擾因素的相關資料。
  
  但是,研究者解釋,使用兄弟姊妹當對照組讓我們可以校正手足間共享的無法測量的因素,例如:家庭環境、飲食、生活型態、母親的特徵、遺傳因素等。
  
  Khashan博士報告指出,我們發現,未足月早產(胎齡33-36週;糖尿病相對風險[RR]值為1.18)和足月早產(胎齡37-38週;RR為1.12)與第一型糖尿病風險增加之間有小但顯著的關聯,納入兄弟姊妹對照組之後,此關聯依舊顯著。
  
  研究者也發現,極低出生體重(RR, 0.66)、胎齡小(RR, 0.83)、極早產(胎齡小於33週)(RR, 0.67)呈現相反的關聯性,與第一型糖尿病風險降低有關。
  
  Khashan博士解釋,胎齡大的嬰兒第一型糖尿病風險增加(RR, 1.14),但是,一旦納入兄弟姊妹對照組的家庭因素,這個影響似乎消失。
  
  作者們寫道,至於造成觀察到這個關聯的可能機轉,可能是未足月早產和器官系統的結構變化有關,以及表觀遺傳的改變,導致第一型糖尿病風險增加。
  
  資料來源: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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