MENOPAUSE, IDDM, AND AUTOIMMUNITY--THE FAD STUDY

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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.