Early developmental pathways of obesity and diabetes risk
Early developmental pathways of obesity and diabetes risk
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DOI：
10.1017/s0029665107005721
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发表时间：
2007-08-01
影响因子：
7
通讯作者：
Ong, K. K.
中科院分区：
文献类型：
--
作者：
Dunger, D. B.;Salgin, B.;Ong, K. K.
在许多人群中，出生时的大小和出生后体重增加的模式与成人患2型糖尿病的风险有关，但推测的病理生理联系仍不清楚。对当代人群的研究表明，婴儿体重的快速增加可能伴随着胎儿生长受限，是儿童肥胖和胰岛素抵抗发展的重要风险因素。雅芳妊娠和儿童纵向研究的数据显示，快速追赶体重增加会导致胰岛素抵抗的发展，早在我一岁时，伴随着中央腹部脂肪块积累的增加。相比之下，反映β细胞在胰岛素抵抗增加的情况下维持胰岛素分泌能力的倾向指数，与出生时的体重指数比出生后追赶体重增加的关系要密切得多。出生时体重指数最低的婴儿在8岁时性情指数降低，与空腹NEFA水平上升有关。性情指数还与儿童身高增长和胰岛素样生长因子-I(IGF-I)水平密切相关；胰岛素分泌量减少与身材发育减慢有关，8岁时相对较矮的身高与IGF-I水平降低有关。IGF-I可能在维持胰岛β细胞质量方面起重要作用，最近对胰腺β细胞IGF-I受体基因敲除的研究和成人观察性研究表明，低IGF-I水平预示着随后发生2型糖尿病的风险。然而，由于胰岛素分泌都是IGF-I水平的重要决定因素，因此可能很难确定因果关系。总而言之，尽管婴儿期体重的快速增加和儿童肥胖率的增加会增加发生胰岛素抵抗的风险，但出生前和出生后的β细胞团决定因素可能最终是个体在胰岛素抵抗增加的情况下保持胰岛素分泌能力的最重要决定因素，从而导致2型糖尿病的风险。
Size at birth and patterns of postnatal weight gain have been associated with adult risk for the development of type 2 diabetes in many populations, but the putative pathophysiological link remains unknown. Studies of contemporary populations indicate that rapid infancy weight gain, which may follow fetal growth restriction, is an important risk factor for the development of childhood obesity and insulin resistance. Data from the Avon Longitudinal Study of Pregnancy and Childhood shows that rapid catch-up weight gain can lead to the development of insulin resistance, as early as I year of age, in association with increasing accumulation of central abdominal fat mass. In contrast, the disposition index, which reflects the beta-cells ability to maintain insulin secretion in the face of increasing insulin resistance, is much more closely related to ponderal index at birth than postnatal catch-up weight gain. Infants with the lowest ponderal index at birth show a reduced disposition index at aged 8 years associated with increases in fasting NEFA levels. The disposition index is also closely related to childhood height gain and insulin-like growth factor-I (IGF-I) levels; reduced insulin secretory capacity being associated with reduced statural growth, and relatively short stature with reduced IGF-I levels at age 8 years. IGF-I may have an important role in the maintenance of beta-cell mass, as demonstrated by recent studies of pancreatic beta-cell IGF-I receptor knock-out and adult observational studies indicating that low IGF-I levels are predictive of subsequent risk for the development of type 2 diabetes. However, as insulin secretion is all important determinant of IGF-I levels, cause and effect may be difficult to establish. In conclusion, although rapid infancy weight gain and increasing rates of childhood obesity will increase the risk for the development of insulin resistance, prenatal and postnatal determinants of beta-cell mass may ultimately be the most important determinants of an individual's ability to maintain insulin secretion in the face of increasing insulin resistance, and thus risk for the development of type 2 diabetes.