Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
Diabet Med. 2017 Oct;34(10):1392-1399. doi: 10.1111/dme.13417. Epub 2017 Jul 21.
To examine the associations of intrauterine exposure to maternal diabetes and obesity with offspring insulin resistance, β-cell function and oral disposition index in a longitudinal observational study of ethnically diverse offspring.
A total of 445 offspring who were exposed (n=81) or not exposed (n=364) to maternal diabetes in utero completed two fasting blood measurements at mean (sd) ages of 10.5 (1.5) and 16.5 (1.2) years, respectively, and an oral glucose tolerance test at the second visit. We used linear mixed models and general linear univariate models to evaluate the associations of maternal diabetes and pre-pregnancy BMI with offspring outcomes.
Maternal diabetes in utero predicted increased insulin resistance [18% higher updated homeostatic model assessment of insulin resistance (HOMA2-IR), P=0.01; 19% lower Matsuda index, P=0.01 and 9% greater updated homeostatic model assessment of β-cell function (HOMA2-β), P=0.04]. Each 5-kg/m increase in pre-pregnancy BMI predicted increased insulin resistance (11% greater HOMA2-IR, P<0.001; 10% lower Matsuda index, P<0.001; 6% greater HOMA2-β, P<0.001). Similar results were obtained in a combined model with both exposures. After adjustment for offspring BMI, only maternal diabetes was associated with higher HOMA2-IR (β=1.12, P=0.03) and lower Matsuda index (β=0.83, P=0.01). Neither exposure was associated with early insulin response or oral disposition index.
Intrauterine exposure to diabetes or obesity is associated with greater offspring insulin resistance than non-exposure, supporting the hypothesis that fetal overnutrition results in metabolic abnormalities during childhood and adolescence.
在一项对不同种族后代进行的纵向观察研究中，研究子宫内暴露于母体糖尿病和肥胖与后代胰岛素抵抗、β细胞功能和口服处置指数的关系。
共有 445 名在子宫内暴露（n=81）或未暴露（n=364）于母体糖尿病的后代分别在平均（标准差）年龄为 10.5（1.5）岁和 16.5（1.2）岁时完成了两次空腹血液测量，并在第二次就诊时进行了口服葡萄糖耐量试验。我们使用线性混合模型和一般线性单变量模型来评估母体糖尿病和孕前 BMI 与后代结局的关系。
子宫内暴露于母体糖尿病预测胰岛素抵抗增加[更新后的稳态模型评估胰岛素抵抗（HOMA2-IR）高 18%，P=0.01；Matsuda 指数低 19%，P=0.01；更新后的稳态模型评估β细胞功能（HOMA2-β）高 9%，P=0.04]。孕前 BMI 每增加 5kg/m2，预测胰岛素抵抗增加[HOMA2-IR 高 11%，P<0.001；Matsuda 指数低 10%，P<0.001；HOMA2-β 高 6%，P<0.001]。在包含两种暴露因素的综合模型中也得到了类似的结果。在校正后代 BMI 后，只有母体糖尿病与更高的 HOMA2-IR（β=1.12，P=0.03）和更低的 Matsuda 指数（β=0.83，P=0.01）相关。两种暴露因素均与早期胰岛素反应或口服处置指数无关。
子宫内暴露于糖尿病或肥胖与后代更高的胰岛素抵抗相关，而与非暴露相关，这支持了胎儿营养过剩会导致儿童和青少年时期代谢异常的假说。
