Another link between cognition deficit and diabetes: The case of Autism.

In a previous entry, I mentioned the recent breakthrough making the connection between Diabetes and the Central Nervous System where it was shown that the nervous system was stopping insulin from being efficiently used leading to type 2 diabetes. It looks as though the connection is not one way. According to this paper, using an hormone that affects insulin sensitivity has some affect on subjects with Autism. From the paper:

The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator activated receptor gamma (PPARgamma), a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos) is an FDA-approved PPARgamma agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS.
...
There were no adverse effects noted and behavioral measurements revealed a significant decrease in 4 out of 5 subcategories (irritability, lethargy, stereotypy, and hyperactivity). Improved behaviors were inversely correlated with patient age, indicating stronger effects on the younger patients. CONCLUSIONS: Pioglitazone should be considered for further testing of therapeutic potential in autistic patients.

This is very surprising, because it has been shown that similar medication (like Lovastatin) could improve substantially the cognitive abilities of people with NF1. That drug (Lovastatin) is generally used for reducing the amount of cholesterol and certain fatty substances in the blood.

What's the link between Neurofribromatisis and Autism ? Genetically, Nf-1 and some form of Autism have been linked through the breakdown of the nervous system signaling in the brain. Matthew Belmonte and Thomas Bourgeron explain:

It is often tacitly assumed that the relation between gene expression and cellular phenotype, or the relation between individual neuronal properties and emergent neural phenotype, is monotonic and independent. That is to say, we assume that (i) an abnormal loss of function in a gene or in a cellular process ought to produce a phenotype opposite to that found in the case of an abnormal gain of function, and (ii) this relation between dosage and phenotype is the same regardless of the individual's genetic, environmental or developmental context. We make these assumptions of monotonicity and independence for the same practical reason that a physicist posits a frictionless surface, a statistician contrives a stationary process, or a novelist invents thematic characters and plots: they simplify complex relationships for which we have no exact models, and they are often close enough to reality to make useful predictions about real-world processes. They are, however, fictions.

For counterexamples to such assumptions, we can look to pharmacology, where the classic dose-response curve is the strongly non-monotonic 'inverted-U' surrounding an optimal dosage, and where a drug's kinetics and therapeutic effect can depend strongly on competitive or synergistic factors arising from other drugs or from individual variation. Careful characterization of neurodevelopmental disorders suggests similar dose-response relations between genes and developmental processes. Such relations are especially likely to exist, and to evoke profound effects, in the case of genes that regulate the activity of large networks of genes or proteins. Several instances of such genes are relevant to autism.

The tumor suppressors TSC1/TSC2 and NF1 are GTPase-activating proteins with widespread effects on cell survival, cell structure and cell function, whose disruption causes tuberous sclerosis and type-1 neurofibromatosis, both of which are comorbid with autism. Knocking out Kras in Nf1-deficient mice (an Nf1+/- and Kras+/- double-knockout) restores the wild phenotype, illustrating the importance of interactions at the network level. Both NF1 and the TSC complex negatively regulate the phosphoinositide-3 kinase pathway, as does the tumor suppressor PTEN. Mutations in PTEN, a regulator of cell size and number, have been identified in people with autism and macrocephaly, and PTEN knockouts produce anxiety behaviors, deficits in social behaviors and increased spine density reminiscent of the FXS phenotype. These cases illustrate the crucial nature of appropriate gene dosage in establishing optimal numbers of neurons and synapses during development.

The fact that pioglitazone is more capable in kids early on would fit with the idea that the plastiticty of the brain/central nervous system signaling can made more normal early on and that it becomes more difficult as time passes.

References:
[1] Boris M, Kaiser C, Golblatt A, Elice MW, Edelson SM, Adams JB, Feinstein DL. Effect of pioglitazone treatment on behavioral symptoms in autistic children. J Neuroinflammation. 2007 Jan 5;4(1):3

[2] Matthew K Belmonte, Thomas Bourgeron,
Fragile X syndrome and autism at the intersection of genetic and neural networks Nature Neuroscience - 9, 1221 - 1225 (2006)