Meeting NewsPerspective

Dementia increases risk for death from hypoglycemia in older adults with diabetes

Older adults with diabetes and dementia were 67% more likely to die vs. those with diabetes but without dementia, according to findings presented at the European Association for the Study of Diabetes annual meeting.

Katharina Mattishent

“Our study confirms that coexisting dementia in older people with diabetes and hypoglycemia is associated with an increased risk in mortality compared to those who do not have dementia,” Katharina Mattishent, MBBS, MRCP, a clinical research fellow with the Alzheimer’s Society at Norwich Medical School, University of East Anglia, United Kingdom, told Endocrine Today. “Most clinicians will probably have had some inkling that hypoglycemia might result in some harmful effects in older people with dementia. However, the true extent of harm from hypoglycemia has never been studied in such a large population. We believe that the serious consequences of hypoglycemia may have been underestimated, and our findings will prove to be an eye-opener.”

In a retrospective study, Mattishent and colleagues analyzed data from 19,995 patients with type 1 or type 2 diabetes aged at least 65 years, either with or without dementia, diagnosed with a first hypoglycemic episode between April 1997 and March 2016, using information from the U.K. Clinical Practice Research Datalink and the Hospital Episode Statistics. The cohort was stratified into three groups: patients with diabetes and dementia but no hypoglycemic episodes (n = 6,134); patients with comorbid dementia and diabetes at first hypoglycemic episode (n = 1,679); and patients with diabetes but without dementia at first hypoglycemic episode (n = 12,182). Researchers followed patients for up to 5 years and used Cox proportional hazard regression models to compare whether the presence or absence of hypoglycemic episodes was associated with mortality in patients with dementia and diabetes, and whether hypoglycemic episodes have a different association with mortality in patients with diabetes and dementia vs. those with diabetes but without dementia.

During follow-up, 11,716 patients died.

Researchers found that, compared with patients with diabetes and dementia but no hypoglycemic episodes, those with both conditions who did experience a hypoglycemic episode were 66% more likely to die of any cause over 5 years (HR = 1.66; 95% CI, 1.51-1.81). Additionally, in comparing both groups of patients with diabetes that experienced hypoglycemic episodes, those with comorbid dementia were 67% more likely to die of any cause over 5 years vs. those with diabetes but without dementia (HR = 1.67; 95% CI, 1.54-1.8).

In a press release announcing the findings, the researchers noted that the study is observational, and no firm conclusions can be drawn regarding cause and effect. Additionally, the databases may not have captured all hypoglycemia events and lifestyle factors may not have been reliably entered. The Clinical Practice Research Datalink database also does not specify the severity of dementia.

“The results of our study highlight the importance of management strategies tailored toward avoidance of hypoglycemic episodes rather than just chasing tight glycemic targets in this vulnerable group,” Mattishent said. “We suggest that a two-pronged approach of deintensification of management regimes and intensification of monitoring should be considered as a means to reduce hypoglycemia.”

Mattishent said better monitoring can be achieved through intermittent or occasional use of continuous glucose monitoring to help identify hypoglycemia.

“We recognize that this would necessitate a major change in the current approach to using continuous glucose monitoring,” she said. “In this particular patient group, it could be considered for intermittent use, especially when a new medication is introduced that carries a high risk of hypoglycemia, or when the dose of an existing medication is increased.” – by Regina Schaffer

Reference:

Mattishent K, et al. Abstract #913. Presented at: European Association for the Study of Diabetes Annual Meeting; Oct. 1-5, 2018; Berlin.

For more information:

Katharina Mattishent, MBBS, MRCP, can be reached at Floor 2, Bob Champion Research and Educational Building, James Watson Road, University of East Anglia, Norwich Research Park, Norwich NR4 7UQ; email: K.Mattishent@uea.ac.uk.

Disclosure: Mattishent reports no relevant financial disclosures.

Older adults with diabetes and dementia were 67% more likely to die vs. those with diabetes but without dementia, according to findings presented at the European Association for the Study of Diabetes annual meeting.

Katharina Mattishent

“Our study confirms that coexisting dementia in older people with diabetes and hypoglycemia is associated with an increased risk in mortality compared to those who do not have dementia,” Katharina Mattishent, MBBS, MRCP, a clinical research fellow with the Alzheimer’s Society at Norwich Medical School, University of East Anglia, United Kingdom, told Endocrine Today. “Most clinicians will probably have had some inkling that hypoglycemia might result in some harmful effects in older people with dementia. However, the true extent of harm from hypoglycemia has never been studied in such a large population. We believe that the serious consequences of hypoglycemia may have been underestimated, and our findings will prove to be an eye-opener.”

In a retrospective study, Mattishent and colleagues analyzed data from 19,995 patients with type 1 or type 2 diabetes aged at least 65 years, either with or without dementia, diagnosed with a first hypoglycemic episode between April 1997 and March 2016, using information from the U.K. Clinical Practice Research Datalink and the Hospital Episode Statistics. The cohort was stratified into three groups: patients with diabetes and dementia but no hypoglycemic episodes (n = 6,134); patients with comorbid dementia and diabetes at first hypoglycemic episode (n = 1,679); and patients with diabetes but without dementia at first hypoglycemic episode (n = 12,182). Researchers followed patients for up to 5 years and used Cox proportional hazard regression models to compare whether the presence or absence of hypoglycemic episodes was associated with mortality in patients with dementia and diabetes, and whether hypoglycemic episodes have a different association with mortality in patients with diabetes and dementia vs. those with diabetes but without dementia.

During follow-up, 11,716 patients died.

Researchers found that, compared with patients with diabetes and dementia but no hypoglycemic episodes, those with both conditions who did experience a hypoglycemic episode were 66% more likely to die of any cause over 5 years (HR = 1.66; 95% CI, 1.51-1.81). Additionally, in comparing both groups of patients with diabetes that experienced hypoglycemic episodes, those with comorbid dementia were 67% more likely to die of any cause over 5 years vs. those with diabetes but without dementia (HR = 1.67; 95% CI, 1.54-1.8).

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In a press release announcing the findings, the researchers noted that the study is observational, and no firm conclusions can be drawn regarding cause and effect. Additionally, the databases may not have captured all hypoglycemia events and lifestyle factors may not have been reliably entered. The Clinical Practice Research Datalink database also does not specify the severity of dementia.

“The results of our study highlight the importance of management strategies tailored toward avoidance of hypoglycemic episodes rather than just chasing tight glycemic targets in this vulnerable group,” Mattishent said. “We suggest that a two-pronged approach of deintensification of management regimes and intensification of monitoring should be considered as a means to reduce hypoglycemia.”

Mattishent said better monitoring can be achieved through intermittent or occasional use of continuous glucose monitoring to help identify hypoglycemia.

“We recognize that this would necessitate a major change in the current approach to using continuous glucose monitoring,” she said. “In this particular patient group, it could be considered for intermittent use, especially when a new medication is introduced that carries a high risk of hypoglycemia, or when the dose of an existing medication is increased.” – by Regina Schaffer

Reference:

Mattishent K, et al. Abstract #913. Presented at: European Association for the Study of Diabetes Annual Meeting; Oct. 1-5, 2018; Berlin.

For more information:

Katharina Mattishent, MBBS, MRCP, can be reached at Floor 2, Bob Champion Research and Educational Building, James Watson Road, University of East Anglia, Norwich Research Park, Norwich NR4 7UQ; email: K.Mattishent@uea.ac.uk.

Disclosure: Mattishent reports no relevant financial disclosures.

    Perspective

    Michal Schnaider Beeri

    Although retrospective, I believe this study was nicely and well planned, and the very large number of participants is a significant strength. Their main results are of public health importance, as they show that the combination of dementia with hypoglycemia is a “killer.” Diabetes with dementia and hypoglycemia significantly increases mortality compared with either having diabetes with hypoglycemia but without dementia or compared to having diabetes and dementia without having hypoglycemia.

    The study does not discuss potential mechanisms underlying such an association; however, one may speculate a few directions. It is well-established that hypoglycemia increases mortality risk. Due to memory impairment, dementia may “lead” to hypoglycemia by not causing someone to not take medications as prescribed (for example, forgetting that they injected insulin and injecting again) thus increasing mortality risk. The American Diabetes Association has reacted to this problem and increased the threshold of poor glycemic control to an HbA1c of 8% in patients with mild cognitive impairment.

    The study is somewhat limited by not reporting the number of hypoglycemic episodes, which may be greater in dementia patients. In addition, the authors have not provided the cause of death, which would be of interest, as dementia patients have higher mortality irrespective of diabetes or hypoglycemia status. Neuronal loss does not necessarily lead to death. For example, stroke, unless located in a brain region crucial for life, does not lead to death and Alzheimer’s patients typically do not die of the disease itself, but rather of complications of pneumonia and sepsis. However, glucose is the fuel of neurons and it is possible that hypoglycemia increases mortality in dementia patients as their brains are already dramatically compromised, so very low glucose exposure to the brain may have irreparable damage.

    In any case, as the authors conclude, the inter-relationship between dementia and hypoglycemia must be viewed with great caution by those who care for dementia patients — from physicians to caregivers — who should closely monitor HbA1c fluctuations, as the consequences may be irreversible.

    • Michal Schnaider Beeri, PhD
    • Professor of psychiatry, Icahn School of Medicine at Mount Sinai

    Disclosures: Schnaider Beeri reports no relevant financial disclosures.

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