成年后的代谢紊乱可能源于发育早期的营养代谢异常。大量临床研究证实低出生体重者成年后代谢紊乱的发生率增加。本课题组既往的研究发现：在中国华东人群中，低出生体重者成年后糖尿病的患病率显著增加，特别是低出生体重成年后肥胖者更易患2型糖尿病（34.5%）。与流行病学调查发现相一致：在我们建立的低出生体重高脂饮食诱导肥胖的大鼠模型上发现有糖耐量异常和胰岛素分泌的异常；进一步组织和分子水平的研究发现胰岛结构发生重构，β细胞数量减少，胰岛组织的蛋白表达谱分析有Wnt信号通路的关键蛋白的表达降低。我们籍以此发现为基础，进一步明确Wnt通路在低出生体重成年后肥胖者胰岛细胞功能损伤中的作用，并探求以调节Wnt通路来减轻胰岛细胞损伤、延缓发生糖耐量异常的可能。阐明低出生体重成年后肥胖者易患糖代谢异常的机制是对糖尿病发病机制研究的重要补充，并可为开展孕期和生长发育期干预，减少成年后代谢性疾病的发生提供理论依据。

Adult metabolic disorders may result from abnormal nutrition and metabolism in earlier stages of development. An abundance of clinical observations have demonstrated an increased incidence of metabolic disorders in adults with low birth weight. Our previous studies indicated that the east Chinese adults with low birth weight have a higher prevalence of diabetes, and especially those who have developed obesity are more vulnerable to type 2 diabetes (34.5%). Our studies in animal models confirmed the impaired glucose tolerance and abnormality in insulin secretion in high-fat diet induced obese rats with low birth weight. Further research in histological and molecular levels revealed the reconstruction of islet structure, reduction in β cells and decreased expression of key proteins in Wnt signal pathway by analysis of protein expression profile of islet tissues. Based on the above findings, we plan to further investigate the role of Wnt pathway in the impaired islet cells function of obese adults with low birth weight, and to seek the possibility of regulating the Wnt pathway to protect islet cells from injuries and delay the occurrence of impaired glucose tolerance. To understand the mechanism of glucose metabolic abnormality in patients with low birth weight and adult obesity is an important compensation to the pathogenesis of diabetes mellitus as well as a theoretical support of intervention during pregnancy and growth period for reducing the incidence of metabolic disorders in adulthood.