NEWS & VIEWS the report by Diana et al.1 can be applied to the routine clinical practice of children and adults with Graves disease. Apart from some concerns about variabil ity in the way patient details were interpreted in the different centres, in particular what is meant by ‘euthyroid Graves ophthalmo pathy’, this retrospective study has been well performed. Single standardized assays for anti-TSH‑R antibodies were used and it is clear from the results that the preva lence of TSI and TBII, as revealed by their respective tests, are impressively high in all groups of patients with Graves disease in the study and always negative in control groups. The most important point of the study (although not recognized as such by the authors), however, is the relationship of anti-TSH‑R antibodies to ophthalmopathy; unfortunately, the findings do not enlighten us about the pathogenesis of this complex eye disorder. University of Sydney, Nepean Hospital, PO Box 63, 68 Derby Street, Penrith, NSW 2751, Australia. [email protected] Competing interests The author declares no competing interests. 1.
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Diana, T. et al. Clinical relevance of thyroidstimulating autoantibodies in pediatric patients with Graves’ disease—a multicentre study. J. Clin. Endocrinol. Metab. http://dx.doi.org/ 10.1210/jc.2013-4026. Lytton, S. D., Li, Y., Olivo, P. D., Kohn, L. D. & Kahaly, G. J. Novel chimeric thyroid-stimulating hormone-receptor bioassay for thyroidstimulating immunoglobulins. Clin. Exp. Immunol. 162, 438–446 (2010). Lytton, S. D. et al. A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves’ orbitopathy. J. Clin. Endocrinol. Metab. 95, 2123–2131 (2010). Tjiang, H., Lahooti, H., McCorquodale, T., Parmar, K. R. & Wall, J. R. Eye and eyelid abnormalities are common in patients with Hashimoto’s thyroiditis. Thyroid 20, 287–290 (2010). Subekti, I., Boedisantoso, A., Moeloek, N. D., Waspadji, S. & Mansyur, M. Association of TSH receptor antibody, thyroid stimulating antibody, and thyroid blocking antibody with clinical activity score and degree of severity of Graves ophthalmopathy. Acta Med. Indones. 44, 114–121 (2012). Uretsky, S., Kennerdell, J. S. & Gutai, J. P. Graves’ ophthalmopathy in children and adolescents. Arch. Ophthalmol. 98, 1963–1964 (1980). Kim, W. B. et al. The prevalence and clinical significance of blocking thyrotropin receptor antibodies in untreated hyperthyroid Graves’ disease. Thyroid 10, 579–586 (2000). Kiljanski, J., Nebes, V., Kennerdell, J. S. & Wall J. R. Graves’ hyperthyroidism, ophthalmopathy and pretibial myxoedema may be components of a multi-system autoimmune disorder. Orbit 15, 129–136 (1996).
258 | MAY 2014 | VOLUME 10
DIABETES
Cognitive decline and T2DM —a disconnect in the evidence? Mark W. J. Strachan and Jacqueline F. Price
Type 2 diabetes mellitus is associated with an increased risk of cognitive decline and dementia. Observational data suggest that hyperglycaemia, hypertension and dyslipidaemia might be involved in the causal pathway underlying this link, but data from the ACCORD MIND investigators challenge these findings. Why are the findings of observational and intervention studies so disconnected? Strachan, M. W. J. & Price, J. F. Nat. Rev. Endocrinol. 10, 258–260 (2014); published online 1 April 2014; doi:10.1038/nrendo.2014.38
Unequivocal evidence exists of a link between type 2 diabetes mellitus (T2DM), cognitive decline and dementia.1 This asso ciation has been the subject of numerous observational investigations and one such study has even suggested that diab etes mellitus is one of the largest potentially modifiable risk factors in the aetiology of dementia.2 Observational studies have sug gested potential mechanisms that underlie this association. Given the complexity of the phenotype of T2DM, it is not surpris ing that multiple factors have been impli cated (Figure 1); foremost amongst these are the classic vascular risk factors.3 How ever, few randomised clinical trials have tested interventions that might improve or slow the decline of cognitive function in patients with T2DM. The Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial is, therefore, enormously important as it is by some margin the largest intervention study on cognitive impair ment in diabetes mellitus. The investiga tors previously reported that intensive glycaemic control had no effect on cogni tive function4 and have now reported data on the effect of intensive blood pressure and lipid interventions.5 The ACCORD study was a landmark trial investigating the effect of intensive management of blood glucose on cardio vascular outcomes in people with T2DM who were already at high risk of cardio vascular events, either because of prevalent cardiovascular disease or because of preva lent risk factors for cardiovascular disease. The study included 10,251 participants who were randomly assigned to undergo either intensive or less intensive glycaemic control (targets HbA 1c
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Diana, T. et al. Clinical relevance of thyroidstimulating autoantibodies in pediatric patients with Graves’ disease—a multicentre study. J. Clin. Endocrinol. Metab. http://dx.doi.org/ 10.1210/jc.2013-4026. Lytton, S. D., Li, Y., Olivo, P. D., Kohn, L. D. & Kahaly, G. J. Novel chimeric thyroid-stimulating hormone-receptor bioassay for thyroidstimulating immunoglobulins. Clin. Exp. Immunol. 162, 438–446 (2010). Lytton, S. D. et al. A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves’ orbitopathy. J. Clin. Endocrinol. Metab. 95, 2123–2131 (2010). Tjiang, H., Lahooti, H., McCorquodale, T., Parmar, K. R. & Wall, J. R. Eye and eyelid abnormalities are common in patients with Hashimoto’s thyroiditis. Thyroid 20, 287–290 (2010). Subekti, I., Boedisantoso, A., Moeloek, N. D., Waspadji, S. & Mansyur, M. Association of TSH receptor antibody, thyroid stimulating antibody, and thyroid blocking antibody with clinical activity score and degree of severity of Graves ophthalmopathy. Acta Med. Indones. 44, 114–121 (2012). Uretsky, S., Kennerdell, J. S. & Gutai, J. P. Graves’ ophthalmopathy in children and adolescents. Arch. Ophthalmol. 98, 1963–1964 (1980). Kim, W. B. et al. The prevalence and clinical significance of blocking thyrotropin receptor antibodies in untreated hyperthyroid Graves’ disease. Thyroid 10, 579–586 (2000). Kiljanski, J., Nebes, V., Kennerdell, J. S. & Wall J. R. Graves’ hyperthyroidism, ophthalmopathy and pretibial myxoedema may be components of a multi-system autoimmune disorder. Orbit 15, 129–136 (1996).
258 | MAY 2014 | VOLUME 10
DIABETES
Cognitive decline and T2DM —a disconnect in the evidence? Mark W. J. Strachan and Jacqueline F. Price
Type 2 diabetes mellitus is associated with an increased risk of cognitive decline and dementia. Observational data suggest that hyperglycaemia, hypertension and dyslipidaemia might be involved in the causal pathway underlying this link, but data from the ACCORD MIND investigators challenge these findings. Why are the findings of observational and intervention studies so disconnected? Strachan, M. W. J. & Price, J. F. Nat. Rev. Endocrinol. 10, 258–260 (2014); published online 1 April 2014; doi:10.1038/nrendo.2014.38
Unequivocal evidence exists of a link between type 2 diabetes mellitus (T2DM), cognitive decline and dementia.1 This asso ciation has been the subject of numerous observational investigations and one such study has even suggested that diab etes mellitus is one of the largest potentially modifiable risk factors in the aetiology of dementia.2 Observational studies have sug gested potential mechanisms that underlie this association. Given the complexity of the phenotype of T2DM, it is not surpris ing that multiple factors have been impli cated (Figure 1); foremost amongst these are the classic vascular risk factors.3 How ever, few randomised clinical trials have tested interventions that might improve or slow the decline of cognitive function in patients with T2DM. The Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial is, therefore, enormously important as it is by some margin the largest intervention study on cognitive impair ment in diabetes mellitus. The investiga tors previously reported that intensive glycaemic control had no effect on cogni tive function4 and have now reported data on the effect of intensive blood pressure and lipid interventions.5 The ACCORD study was a landmark trial investigating the effect of intensive management of blood glucose on cardio vascular outcomes in people with T2DM who were already at high risk of cardio vascular events, either because of prevalent cardiovascular disease or because of preva lent risk factors for cardiovascular disease. The study included 10,251 participants who were randomly assigned to undergo either intensive or less intensive glycaemic control (targets HbA 1c
