Avoiding hypoglycaemic episodes in vulnerable elderly patients with diabetes should be a top priority for doctors, according to a keynote speaker at the recent Diabetes Masterclass in Kilkenny.

Prof William Molloy, professor of medicine and chair of the Centre for Gerontology and Rehabilitation at UCC, said that hypoglycaemia is a common problem in elderly diabetes patients and may significantly increase the risk of falls, fractures, cardiovascular events, and cognitive impairment, including dementia.

However, tailoring treatment targets and strategies around individual circumstances should reduce the risk of hypoglycaemia, advised Prof Molloy, who is also a medical consultant in Cork University and South Infirmary Hospitals.

“There is a high prevalence of type 2 diabetes in the elderly and this is going to continue increasing as more people live longer. At the moment, 16% of the population in Ireland is aged over 65. By 2050, it will be about 25%, and approximately 10% will be aged over 85,” he told the Masterclass, which was hosted by Novartis at the Lyrath Hotel, Kilkenny.

“I run memory clinics and I see a lot of patients with diabetes. Increasingly, we are seeing a condition called mild cognitive impairment; this is where people get memory loss but they don’t have functional impairment. 

“Dementia is easy to diagnose, you have cognitive impairment that is so severe it interferes with your ability to function, so the person gets lost or they can’t pay their bills, they forget their medications, etc. There has to be a functional impairment. 

“However, before you get dementia there is this condition called mild cognitive impairment, where the person recognises that their memory is getting worse and family members say they fear there’s a change. When you do ‘mini mentals’ you won’t pick it up, but it becomes apparent when you do more subtle tests such as name as many animals as you can. Normally, a person will name more than 16 animals but a person with mild cognitive impairment will probably remember only 10; a person with dementia might only recall between five to 10. 

“We are seeing an increase in cases of mild cognitive impairment in our clinics, and more and more we are to trying to prevent dementia. As I said, we see a lot of diabetes patients and our priority for them in that regard would be hypoglycaemic control,” Prof Molloy stressed.

Illustrating his clinical reasoning for this, he discussed results from research on the relationship between hypoglycaemia and dementia, published in Journal of the American Medical Association in 2009. In this study of more than 16,500 people with type 2 diabetes (average age, 65 years), researchers in California investigated whether previous hypoglycaemic episodes, severe enough to require a visit to the emergency department (ED) or hospitalisation, are associated with an increased risk of dementia. Hypoglycaemic episodes were recorded over 22 years (1980-2002), with a further four years of follow-up for diagnosis of dementia. 

“Basically, if there was a diagnosis of hypoglycaemia on their hospital chart, they looked at the incidence of dementia occurring between 2003 and 2007. They found that, compared with patients with no hypoglycaemia, patients with single or multiple episodes had a graded increase in risk of dementia,” said Prof Molloy.

Patients with one hypoglycaemic episode had a 26% increased risk; two episodes correlated with an 80% increased risk; and three or more hypoglycaemic episodes were associated with nearly double the risk for dementia.

“When you’re dealing with diabetes and the elderly, this idea of individualising treatment is very important, you’ve got to take their aging into account. If the patient is otherwise fit and healthy, they can generally be treated with the same goals and targets as those for younger adults, but for the frail elderly who have cognitive impairment, depression, issues with drug tolerance and side effects, co-morbidities, polypharmacy, and compromised renal function, it is important to individualise treatment goals. Achieving good glycaemic control is challenging in this patient group, but avoiding hypoglycaemia is the big issue.

“You may have an elderly patient who forgets her medication, doubles up on her medication, forgets to eat and so on – it’s the inability to control, that’s the killer with the elderly, and that’s your problem. You’re always going to be dealing with that,” he said.

Hypoglycaemic episodes may include dizziness, disorientation, fainting or seizures. While most hypoglycaemia is mild and self-managed, more severe episodes will require medical intervention and, possibly, hospitalisation. In fact, hypoglycaemia accounts for 20% of all hospitalisation for people with diabetes.

Prof Molloy discussed a number of antidiabetic medications and their roll in the management of hypoglycaemia in older adults. He said that metformin, which prevents the liver from producing glucose and helps to improve the body’s sensitivity towards insulin, is very efficacious, does not cause hypoglycaemia, is well tolerated in the elderly and has good compliance rates. 

The dipeptidyl peptidase-IV (DPP4) inhibitors work by reducing glucagon and blood glucose levels. “DPP4 is efficacious and well tolerated in the elderly and compliance is good. It can’t cause hypoglycaemia because of is mechanism of action. When the blood sugar falls it just stops working, which is a great intelligent drug. It also adds on nicely to metformin; the two are a great combo,” he remarked.

“The sulphonylureas are not a good idea in the elderly because of the problems with hypoglycaemia,” Prof Molloy added. “The mechanism of action of sulphonylureas means that hypoglycaemia and weight gain can be relatively common side effects. There are 10 to 14 times more hypoglycaemic episodes with sulphonylureas compared to the newer DPP4 inhibitors.

“In Ireland, if you’re on sulphonylureas or an insulin you have to register with your driving license authority. If you’re a truck driver or drive for a living, they can ask for your diary to see if you get hypoglycaemic. They can take your licence and doctors have to report people too. So sulphonylureas have seen their day to be honest.”

In contrast, Prof Molloy pointed out that the labelling information for vildagliptin, one of the new DPP4 inhibitors, states there are no restrictions in very elderly patients. They had the most data in people over 75 and no differences were observed in overall safety, tolerability or efficacy between these patients and younger patients. “The drug is not affected by age at all. The only thing you have to adjust for is renal function, and it won’t cause hypoglycaemia,” he noted.

DPP4 is a protein that, in humans, is encoded by the DPP4 gene. DPP4 plays a major role in glucose metabolism, but is also found on the surface of cells in the airways, such as the lungs and kidneys, it is associated with immune regulation, and appears to work as a suppressor in the development of cancer and tumours

During question and answer time, a doctor in the audience raised concerns regarding the impact of DPP4 inhibitors in other organs. Dr Molloy said that he shared some of those concerns: “I don’t know the answer to your question. Only time will tell from longitudinal studies what these drugs will do to other organs and system-wide. I share your concern but it can’t stop us, we wouldn’t be able to wait for 10-year follow-up studies on these drugs before licensing them – no drug would ever get licensed. 

“The post marketing surveillance is when we sometimes catch these side effects, both good and bad. We have to wait and see, but the evidence so far shows that it works and it works well,” Prof Molloy said.