Pathophysiological Models Are We There

Based on this critical review of the pediatric literature, it should be obvious that we are not yet in a position to make strong statements about the etiology of neurocognitive dysfunction in the child with diabetes. Indeed, only one attempt has been made to address some of those findings, with the "diathesis" or vulnerability model (50) offering an explanation for why it is that children with an early onset of diabetes seem to be especially likely to manifest significant brain abnormalities. According to this model, in the very young child diagnosed with diabetes, chronically elevated blood glucose levels interfere with normal brain maturation at a time when those neurodevelopmental processes are particularly labile, as they are during the first 5-7 years of life (128-131). The resulting alterations in brain organization that occur during this "sensitive period" will not only lead to delayed cognitive development and lasting cognitive dysfunction, but may also induce a predisposition or diathesis that increases the individual's sensitivity to subsequent insults to the brain, as could be initiated by the prolonged neuroglycopenia that occurs during an episode of hypoglycemia.

Data from most, but not all, research are consistent with that view. In general, children with an early onset of diabetes are more likely to manifest mild-to-moderately severe cognitive impairment on a variety of cognitive and neurophysiological measures. Furthermore, those who experienced an episode of severe hypoglycemia either during, or after, the end of this sensitive period were more likely [but not inevitably - see (98)] to show marked cognitive dysfunction as compared to either those with a later onset of diabetes (and severe hypoglycemia) or those with an early onset of diabetes but without seizures (13, 40, 51). Because some neurodevelopmental processes continue through adolescence and early adulthood (132,133), chronically elevated blood glucose levels may also adversely affect brain structure and function in individuals with a later onset of diabetes, but to a far lesser degree. Again that prediction is consistent with findings from many of the neuropsychological studies discussed previously. Compared to their nondi-abetic peers, many children and adolescents diagnosed after 6 or 7 years of age show relatively circumscribed cognitive dysfunction that is quite small in magnitude and more often than not, unrelated to the presence or absence of severe hypoglycemia.

Research is only now beginning to focus on plausible pathophysiological mechanisms. We know from animal studies that a relatively brief exposure to chronically elevated blood glucose values can lead to a series of changes in neuronal structure and in brain chemistry (114,115). Normally, brain glucose levels are tightly regulated at the blood-brain barrier (BBB) by active glucose transporters (e.g., GLUT 1) that up- or down-regulate based on glucose values in the peripheral circulation (134). Recent research has suggested that the development of diabetes per se may lead to at least transient increases in the permeability of the BBB to glucose (and other molecules) (135). Thus it is certainly plausible that around the time of diagnosis, excessive amounts of glucose rapidly flood into the brain and by disrupting normal metabolic and neurotropic processes, trigger structural and functional damage to the CNS in the diabetic child. Validation of this possibility will require additional research that uses animal models to specifically examine the neural and metabolic changes occurring in the brain shortly after the initiation of diabetes.

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook


Post a comment