MENOPAUSE, IDDM, AND AUTOIMMUNITY--THE FAD STUDY

家族性自身免疫和糖尿病（FAD）研究表明，桥本甲状腺炎（由甲状腺过氧化物酶或甲状腺球蛋白自身抗体高水平、缺乏药物治疗时TSH升高和/或阳性病史或检查确定）在1型糖尿病成年女性中的患病率高于其非糖尿病姐妹或母亲。这些发现表明，1型糖尿病女性患者维持免疫自我耐受性的能力可能会过早丧失。这也可能反映了受影响个体早期发生的许多慢性并发症之一。因此，我们可以预期，其他生物年龄较大的指标可能在1型糖尿病女性患者中也很常见。FAD研究的自我报告数据支持这一假设。1型糖尿病女性的平均绝经年龄比非糖尿病女性年轻近10岁（41.6岁比49.9岁，p < 0.05）。据我们所知，这是科学文献中第一个关于1型糖尿病和早期绝经之间关系的正式报告。此外，这些数据对公共卫生的重要性是巨大的，这一点必须得到证实。鉴于心血管疾病和其他已知与长期糖尿病相关的并发症的高发，1型糖尿病年轻女性过早自然绝经可能会加剧心肌梗死的风险。我们有唯一一个明确的1型糖尿病女性队列，该队列足够大，年龄合适，可以实现以下具体目标：1)验证一个极其重要的发现，即1型糖尿病患者的绝经期（即12个月无月经且卵泡刺激素水平升高）发生的平均年龄明显低于非糖尿病女性；2)评估1型糖尿病患者与非糖尿病女性在月经出血模式、更年期症状和绝经年龄决定因素方面的潜在差异；3)比较绝经过渡期对1型糖尿病女性主要心血管疾病危险因素和自身免疫性甲状腺疾病风险的影响。

The Familial Autoimmune and Diabetes (FAD) Study has shown that the prevalence of Hashimoto's thyroiditis, defined by high titres of thyroid peroxidase or thyroglobulin autoantibodies, elevated TSH in the absence of medication, and/or a positive history or exam, is higher among adult women with type 1 diabetes than their non-diabetic sisters or mothers. These findings suggest that one's ability to maintain immunological self-tolerance may be lost prematurely among women with type 1 diabetes. This may also reflect one of the many chronic complications that occur at an early age among affected individuals. One would, therefore, expect that other indicators of advanced biological age may be common among women with type 1 diabetes. Self-report data from the FAD Study support this hypothesis. The mean age at menopause for women with type 1 diabetes was nearly ten years younger than that for their non-diabetic sisters (41.6 vs. 49.9 years, p less than 0.05). To our knowledge, this is the first formal report of an association between type 1 diabetes and early menopause in the scientific literature. Moreover, the public health importance of these data, which must be confirmed, is enormous. Given the high incidence of cardiovascular disease and other complications known to be associated with long-term diabetes, an early natural menopause is likely to exacerbate the risk of myocardial infarction among young women with type 1 diabetes. We have the only defined cohort of type 1 diabetic women that is sufficiently large and of the appropriate age to address the following Specific Aims: 1) To validate the extremely important finding that menopause, defined by 12 months without menstruating and elevated FSH levels, occurs at a significantly younger average age among type 1 diabetic compared to non-diabetic women, 2) to evaluate potential differences in menstrual bleeding patterns, menopausal symptomatology and the determinants of age at menopause among type 1 diabetic compared to non-diabetic women, and 3) to evaluate the effect of the menopause transition on major cardiovascular disease risk factors and risk of autoimmune thyroid disease among type 1 diabetic compared to non-diabetic women.