Maternal diabetes and offspring autism risk

The systematic review and meta-analysis reported by Xu and colleagues* caught my eye recently. Concluding that: "maternal diabetes was significantly associated with a greater risk of ASD in the offspring" my interest was truly piqued.

Insulin @ Wikipedia  

Diabetes in relation to autism has cropped up a few times on this blog. I've talked about the possibility of a more general connection (see here) and also more specific as part of some of the CHARGE results (see here).

Indeed those CHARGE results, based on the study by Paula Krakowiak and colleagues** (open-access) I remember generated quite a bit of discussion at the time of their publication given the suggested link with various facets making up metabolic syndrome in mums.

I'm not really surprised by the Xu results when you think that the association between gestational diabetes and offspring autism risk has been talked about before based on some pretty strong association data. I note for example, that the study by Lyall and colleagues*** (open-access) flagged up this association - "gestational diabetes was associated with a significantly increased risk of ASD" - based on quite a nice sample size. That and the paper by Hannah Gardener and colleagues**** (open-access) who suggested that gestational diabetes was perhaps one of several factors which might elevate offspring risk as per the Krakowiak results.

The question of mechanism of effect is slightly less clear it has to be said. In my first post on autism and diabetes, quite a lot was made of the connection between type 1 diabetes and autism as per the familial autoimmune connection (have a look at my Money post for example). Granted this doesn't really add anything more specific than to say that autoimmune conditions can 'club together' (see here) which might take us down some other avenues particularly when talking about at least some autism comorbidity (see here). That and the implication that autism might also be an autoimmune condition***** as some have implied.

As to any mechanism of gestational diabetes being linked to the aetiology of autism, well I'm afraid I can't offer anything too concrete at this point. There is some speculation that gestational diabetes might be linked to other cognitive and developmental issues as per the research on ADHD (Attention-deficit hyperactivity disorder)****** and schizophrenia*******. Indeed, that paper by Van Lieshout & Voruganti (open-access) on gestational diabetes and risk of offspring schizophrenia suggests: "at least 3 prenatal mechanisms: hypoxia, oxidative stress and increased inflammation" of potential effect. Suffice to say that all of them have also been banded around as being involved with cases of autism at various times (particularly the roles of inflammation and oxidative stress). I might also draw reader's attention to the paper by Nousen and colleagues******** too.

The take-home message whilst still one of caution in singling out one particular factors as being linked to autism (or should that be the autisms?) is that maternal diabetes should be registering on the various investigations into pregnancy and birth factors linked to offspring autism risk to further explore mechanisms. Whether altering the presentation of maternal diabetes (lifestyle changes or even reviewing medication*********) might also impact on offspring outcome is another question which should be on the lips of autism research...

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* Xu G. et al. Maternal Diabetes and the Risk of Autism Spectrum Disorders in the Offspring: A Systematic Review and Meta-Analysis. J Autism Dev Disord. 2013 Sep 22.

** Krakowiak P. et al. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics. 2012 May;129(5):e1121-8. doi: 10.1542/peds.2011-2583.

*** Lyall K. et al. Pregnancy complications and obstetric suboptimality in association with autism spectrum disorders in children of the Nurses' Health Study II. Autism Res. 2012 Feb;5(1):21-30. doi: 10.1002/aur.228.

**** Gardener H. et al. Prenatal risk factors for autism: comprehensive meta-analysis. Br J Psychiatry. 2009 Jul;195(1):7-14. doi: 10.1192/bjp.bp.108.051672.

***** Ashwood P. & Van de Water J. Is autism an autoimmune disease? Autoimmun Rev. 2004 Nov;3(7-8):557-62.

****** Nomura Y. et al. Exposure to gestational diabetes mellitus and low socioeconomic status: effects on neurocognitive development and risk of attention-deficit/hyperactivity disorder in offspring. Arch Pediatr Adolesc Med. 2012 Apr;166(4):337-43. doi: 10.1001/archpediatrics.2011.784.

******* Van Lieshout RJ. & Voruganti LP. Diabetes mellitus during pregnancy and increased risk of schizophrenia in offspring: a review of the evidence and putative mechanisms. J Psychiatry Neurosci. 2008 Sep;33(5):395-404.

******** Nousen EK. et al. Unraveling the Mechanisms Responsible for the Comorbidity between Metabolic Syndrome and Mental Health Disorders. Neuroendocrinology. 2013. Sept 21.

********* Barnard KB. et al. Antidepressant Medication as a Risk Factor for Type 2 Diabetes and Impaired Glucose Regulation. Systematic review. Diabetes Care. 2013; 36: 3337-3345.

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Xu G, Jing J, Bowers K, Liu B, & Bao W (2013). Maternal Diabetes and the Risk of Autism Spectrum Disorders in the Offspring: A Systematic Review and Meta-Analysis. Journal of autism and developmental disorders PMID: 24057131