Lactation and Glucose Tolerance After GDM Pregnancy

描述（由申请人提供）：哺乳对糖耐量有直接的有利影响，这种影响可能在断奶后持续存在，以预防女性2型糖尿病（DM）的发展。妊娠期葡萄糖耐受不良的发展，被称为妊娠糖尿病（GDM），是2型糖尿病后续发展的一个强有力的预测因素。在美国，妊娠期糖尿病的发生率约为3-5%，每年影响135,000名妇女。产后5年内，既往患有GDM的女性有20% ~ 50%会发展为2型糖尿病。GDM妊娠后2型糖尿病的危险因素包括胰腺b细胞功能障碍、妊娠期及产后早期葡萄糖耐受不良的严重程度、糖尿病家族史、母亲肥胖、复发性GDM和体重增加。哺乳期降低母体葡萄糖和胰岛素水平，提高葡萄糖耐量和处置指数，表明细胞功能较好，胰岛素抵抗程度较高。泌乳的强度和持续时间是否会降低糖尿病的后续风险很少被研究。以前的研究受限于定性测量的泌乳（曾经与从未），目前的状态（是与否），或一生中几个月的泌乳。没有前瞻性研究评估哺乳期强度（补充喂养）和/或持续时间与妊娠期糖尿病后2型糖尿病发展的关系。我们提出了一项前瞻性队列研究，将在北加州Kaiser Permanente医疗保健系统中招募1098名最近诊断为GDM且产后6-8周无2型DM的妇女。妇女将每年随访两年，进行2小时75克口服葡萄糖耐量试验。我们将确定与不哺乳相比，长时间、高强度的哺乳是否与2型糖尿病的发病率较低有关，是否与空腹和负荷后2小时血糖和胰岛素水平、胰岛素抵抗指数、体重、腰围和血浆脂联素的更有利的变化有关。由于随机化是不可行的，严格评估泌乳强度和持续时间控制多个潜在的混杂因素是最有效的研究设计。这些发现对有GDM病史的女性的潜在公共卫生影响是巨大的，因为只有不到50%的美国女性会在4个月内哺乳。哺乳是一种可改变的行为，可以转化为一种实用的、低成本的干预措施，有可能加强产后干预措施，促进健康的饮食摄入和增加身体活动。

DESCRIPTION (provided by applicant): Lactation has immediate favorable effects on glucose tolerance that may persist after weaning to prevent development of type 2 diabetes mellitus (DM) in women. Development of glucose intolerance during pregnancy, known as gestational diabetes (GDM), is a strong predictor of subsequent development of type 2 DM. In the U.S., GDM occurs in about 3-5% of all pregnancies and affects 135,000 women per year. Within 5 years after delivery, 20 to 50% of women with previous GDM will develop type 2 DM. Risk factors for type 2 DM after GDM pregnancy include pancreatic b-cell dysfunction, severity of glucose intolerance during pregnancy and early postpartum periods, family history of DM, maternal obesity, recurrent GDM and weight gain. Lactation lowers maternal glucose and insulin levels, improves glucose tolerance and the disposition index, indicating better-cell function for their degree of insulin resistance. Whether the intensity and duration of lactation reduces subsequent risk of DM has rarely been examined. Previous studies are limited by qualitative measures of lactation (ever vs. never), current status (yes vs. no), or lifetime months of lactation. No prospective studies have assessed lactation intensity (supplemental feedings) and/or duration in relation to development of type 2 DM after recent GDM pregnancy. We propose a prospective cohort study that will enroll 1,098 women with a recent GDM diagnosis who are free of type 2 DM at 6-8 weeks postpartum in the Kaiser Permanente Health Care System in northern California. Women will be followed annually for two years to administer the 2 hr 75 g oral glucose tolerance test. We will determine whether prolonged, intensive lactation compared with no lactation is associated with a lower incidence of type 2 DM, and more favorable changes in fasting and 2-hr post load plasma glucose and insulin levels, indices of insulin resistance, body weight, waist girth and plasma adiponectin. Because randomization is not feasible, the rigorous assessment of lactation intensity and duration controlling for multiple potential confounders is the most valid study design. The potential public health impact of these findings for women with a history of GDM is substantial given that less than 50% of U.S. women lactate for four months. Lactation is a modifiable behavior that may be translated into a practical, low-cost intervention that has the potential to enhance postpartum interventions that promote healthy dietary intakes and increased physical activity.