Low blood sugar in some diabetics boosts dementia risk

For older patients with Type 2 diabetes, an aggressive focus on keeping high blood sugar down increases the risk of driving blood sugar too low--and with that, boosting the likelihood of developing dementia, says a new study. As if that weren’t bad enough, the new research finds that dementia, in turn, increases the risk of hypoglycemic episodes.

The potential result, write a pair of experts publishing in the journal JAMA Internal Medicine, is “a vicious cycle of adverse events.”

The latest research is likely to reignite a long-simmering debate over how tightly to control blood-sugar levels in those with Type 2 diabetes. Many of the medications used to treat diabetes mellitus drive down levels of circulating glucose so robustly, they can push patients into a state of hypoglycemia, causing fainting, black-outs, driving accidents and falls. Older adults are particularly vulnerable, possibly because they are more likely to take other medications that interact with their diabetes medicine, and perhaps because small changes in their daily caloric intake may have outsized effects.

In short, in medicine as in the rest of life, too much of a good thing can be a bad thing.

In the study, researchers followed 783 diabetic adults with an average age of 74 for at least 12 years starting in 1997. None suffered from dementia at the time they entered the study, but 148 were diagnosed with dementia at some point during the study period. The researchers also looked for evidence--largely in hospital records--of subjects’ having experienced cases of severe hypoglycemia, in which glucose levels in the blood are pushed too low. In all, they found that 61 subjects had suffered at least one such episode.

The subjects who had at least one episode of hypoglycemia were roughly twice as likely to develop dementia as those who had not. The study found that African Americans, those with less than a high school education or lower cognitive scores, and those on insulin were more likely to have had a hypoglycemic episode, and were therefore at greater risk of developing dementia. But among those who had hypoglycemic events, those factors (ethnicity, educational attainment or insulin use) did not further push up the likelihood of developing dementia.

The link between hypoglycemia and dementia was even stronger in the opposite direction: once a subject had been diagnosed with dementia, he or she was 2.2 times as likely as a peer without dementia to be admitted to a hospital with hypoglycemia.

The study was led by a team of psychiatrists, neurologists and epidemiologists from UC San Francisco and the San Francisco Veterans Affairs Medical Center.

Past studies exploring a link between hypoglycemia and dementia have turned up mixed results, but there are plenty of biological and behavioral reasons to suspect the two may be related. Neurons in the brain’s cerebral cortex and hippocampus--a key node in the brain’s memory circuit--appear to be particularly vulnerable to damage when they are deprived of fuel. And since diabetes is a disorder of metabolism, the irregular supply of fuel to areas key to judgment and memory may be intensified in diabetics.

In turn, managing diabetes can be a complex task, especially for those with poor cognitive function. Doses that are missed or doubled-up, irregular diets, and diabetic medications or regimens that don’t fit their need for a simple routine can drive up the incidence of hypoglycemia, and exacerbate such patients’ mental impairment.

The authors of the study wrote that, in older diabetic patients with or at risk for cognitive impairment, physicians may want to avoid prescribing medications that are more likely to cause hypoglycemia--including insulin or sulfonylureas, which prompt the secretion of insulin (medications with the generic names chlorpropamide, glimeperide, glipizide, glyburide, tolazamide, tolbutamide).

But Doctors Kasia J. Lipska and Victor M. Montori, who wrote an invited commentary on the study, suggest that physicians and patients may need to throttle back on how aggressively they manage an older patient’s blood sugar. Slightly raising such a patient’s target blood-sugar level (measured by glycated hemoglobin), or choosing a simpler regimen of medications less prone to error might reduce hypoglycemic episodes--and thus dementia risk--without raising the risk of common diabetes complications such as kidney disease, vision loss, neuropathy or stroke.

“Involving patients in these treatment decisions may favorably shift the current glucose-centric paradigm to a more patient-centered one,” wrote Lipska and Montori. And choosing an approach that reflects what matters most to patients may make those patients more engaged and invested in the complicated task of managing diabetes, they added.