Wannamethee S G, Lawlor D A, Whincup P H, Walker M, Ebrahim S, Davey-Smith G
Department of Primary Care and Population Science, Royal Free and University College Medical School, Rowland Hill St, NW3 2PF London, UK.
Diabetologia. 2004 Jan;47(1):12-8. doi: 10.1007/s00125-003-1270-x. Epub 2003 Nov 26.
AIMS/HYPOTHESIS: It has been proposed that genetic factors involved in insulin action could explain part of the link between low birthweight and risk of cardiovascular disease and diabetes in adulthood. To confirm this we examined the association between offspring birthweight and paternal insulin resistance and diabetes in late adulthood.
We did a cross-sectional survey of 4252 men who were 60 to 79 years of age and from 24 British towns. Of these, 2788 men provided details of their offsprings' birthweight and sex.
Offspring birthweight was inversely associated with paternal insulin resistance defined by the homeostasis model assessment (HOMA) score and with Type 2 diabetes in late adulthood. Fathers of offspring in the highest quartile of sex-standardised birthweight SD scores had a 34% reduction in odds of having a high HOMA insulin resistance score (OR=0.66, 95% CI: 0.47 to 0.92) compared with fathers of offspring in the lowest quartile after adjustment for potential confounders. A stronger inverse association was seen between offspring birthweight and risk of paternal diabetes (adjusted OR=0.59, 95% CI: 0.39 to 0.88 top quartile vs lowest quartile). For each increase of offspring-birthweight SD score the odds of high HOMA scores decreased by 13% (OR=0.87, 95% CI: 0.78 to 0.98) and the odds for diabetes by 17% (OR=0.83, 95% CI: 0.72 to 0.95), after full adjustment.
CONCLUSIONS/INTERPRETATION: Offspring birthweight is inversely associated with paternal insulin resistance and diabetes in late adulthood, supporting the hypothesis that genetic factors related to insulin action contribute to the association between birthweight and adult cardiovascular disease and diabetes risk.
目的/假设：有人提出，参与胰岛素作用的遗传因素可以解释低出生体重与成年后患心血管疾病和糖尿病风险之间的部分联系。为了证实这一点，我们研究了成年后期子代出生体重与父亲胰岛素抵抗及糖尿病之间的关联。
我们对来自英国24个城镇的4252名60至79岁男性进行了横断面调查。其中，2788名男性提供了其子女的出生体重和性别的详细信息。
子代出生体重与通过稳态模型评估（HOMA）评分定义的父亲胰岛素抵抗以及成年后期的2型糖尿病呈负相关。在对潜在混杂因素进行调整后，性标准化出生体重标准差得分处于最高四分位数的子代的父亲，与处于最低四分位数的子代的父亲相比，HOMA胰岛素抵抗评分高的几率降低了34%（OR=0.66，95%CI：0.47至0.92）。子代出生体重与父亲患糖尿病风险之间存在更强的负相关（调整后的OR=0.59，95%CI：0.39至0.88，最高四分位数与最低四分位数相比）。在进行全面调整后，子代出生体重标准差得分每增加1个单位，HOMA评分高的几率降低13%（OR=0.87，95%CI：0.78至0.98），患糖尿病的几率降低17%（OR=0.83，95%CI：0.72至0.95）。
结论/解读：子代出生体重与成年后期父亲的胰岛素抵抗和糖尿病呈负相关，支持了与胰岛素作用相关的遗传因素促成出生体重与成年心血管疾病和糖尿病风险之间关联的假设。
