Cognitive Impairment and Diabetes and Autism

Recurrent/moderate hypoglycemia induces hippocampal dendritic injury, microglial activation, and cognitive impairment in diabetic rats

Abstract (provisional full PDF available at link)


Recurrent/moderate (R/M) hypoglycemia is common in type 1 diabetes. Although mild or moderate hypoglycemia is not life-threatening, if recurrent, it may cause cognitive impairment. In the present study, we sought to determine whether R/M hypoglycemia leads to neuronal death, dendritic injury, or cognitive impairment.


The experiments were conducted in normal and in diabetic rats. Rats were subjected to moderate hypoglycemia by insulin without anesthesia. Oxidative stress was evaluated by 4-Hydroxy-2-nonenal immunostaining and neuronal death was determined by Fluoro-Jade B staining 7 days after R/M hypoglycemia. To test whether oxidative injury caused by NADPH oxidase activation, an NADPH oxidase inhibitor, apocynin, was used. Cognitive function was assessed by Barnes maze and open field tests at 6 weeks after R/M hypoglycemia.


The present study found that oxidative injury was detected in the dendritic area of the hippocampus after R/M hypoglycemia. Sparse neuronal death was found in the cortex, but no neuronal death was detected in the hippocampus. Significant cognitive impairment and thinning of the CA1 dendritic region was detected 6 weeks after hypoglycemia. Oxidative injury, cognitive impairment, and hippocampal thinning after R/M hypoglycemia were more severe in diabetic rats than in non-diabetic rats. Oxidative damage in the hippocampal CA1 dendritic area and microglial activation were reduced by the NADPH oxidase inhibitor, apocynin.


The present study suggests that oxidative injury of the hippocampal CA1 dendritic region by R/M hypoglycemia is associated with chronic cognitive impairment in diabetic patients. The present study further suggests that NADPH oxidase inhibition may prevent R/M hypoglycemia-induced hippocampal dendritic injury.


A recent Harvard study showed diabetes mellitus type I (DM1) 0.79% vs. 0.34% autism patients v controls.

Further readings

Type 1 Diabetes and Autism Is there a link?

“Our data suggest that the prevalence of autism spectrum disorder in children with type 1 diabetes attending the Diabetes Clinic at The Hospital for Sick Children, Toronto, may be greater than that in the general population (0.9% [95% CI 0.3–1.5] vs. 0.34–0.67) (4,6). Certain factors may account for this finding, including a common autoimmune pathogenesis.”

“We read with interest the article of Freeman et al. (1) reporting a higher prevalence of autism spectrum disorder in pediatric patients with type 1 diabetes in Toronto than in the general population (0.9% [95% CI 0.3–1.5 vs. 0.34–0.67]).

…a pattern similar to that observed by Freeman et al. (1) has been found in patients with type 1 diabetes aged <14 years from six Italian centers of pediatric diabetology equally distributed in the Italian Peninsula and in Sicily (0.72% [0.69–0.75]). The diagnosis of autism spectrum disorder was confirmed in all cases using the DSM-IV (Diagnostic and Statistic Manual of Mental Disorders-IV).”

Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders.

We examined whether metabolic conditions (MCs) during pregnancy (diabetes, hypertension, and obesity) are associated with autism spectrum disorder (ASD), developmental delays (DD), or impairments in specific domains of development in the offspring.

All MCs were more prevalent among case mothers compared with controls. Collectively, these conditions were associated with a higher likelihood of ASD and DD relative to controls (odds ratio: 1.61 [95% confidence interval: 1.10-2.37; odds ratio: 2.35 [95% confidence interval: 1.43-3.88], respectively). Among ASD cases, children of women with diabetes had Mullen Scales of Early Learning (MSEL) expressive language scores 0.4 SD lower than children of mothers without MCs (P < .01). Among children without ASD, those exposed to any MC scored lower on all MSEL and Vineland Adaptive Behavior Scales (VABS) subscales and composites by at least 0.4 SD (P < .01 for each subscale/composite).


Maternal MCs may be broadly associated with neurodevelopmental problems in children. With obesity rising steadily, these results appear to raise serious public health concerns.

This entry was posted in Autism, co-morbid, diabetes, Immune System, Inflammation, Physiology and tagged , , , . Bookmark the permalink.

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