Conquer Your Diabetes: Prevention, Control and Remission, written by Dr. Martin Abrahamson and Dr. Sanjiv Chopra, Professors of Medicine at Harvard Medical School, delves into the details of overcoming diabetes, including the best approaches to prevention, control, and remission.Continue reading
Hypoglycaemia and driving – an overview of management and guidance
The burden of hypoglycaemia on people with diabetes extends beyond its clinical consequences. Read on to learn about the quality-of-life impact of hypoglycaemia and the unanswered questions that remain.Continue reading
The place of hybrid closed loops in diabetes management
Like any diabetes intervention, hybrid closed loops have their strengths and limitations. Read on to learn more about the place of hybrid closed loops in diabetes management.Continue reading
Understanding how hypoglycaemia impacts quality of life in people with type 1 diabetes
The burden of hypoglycaemia on people with diabetes extends beyond its clinical consequences. Read on to learn about the quality-of-life impact of hypoglycaemia and the unanswered questions that remain.Continue reading
First comes knowledge
Reducing the risk of hypoglycaemia depends on having the right information—and using it.Continue reading
Connecting hypoglycemia and CVD risk
Reducing the risk of hypoglycaemia is a multifaceted challenge. For starters, health providers need to understand which behaviours raise and decrease the risk, so they can communicate this information to individuals with diabetes and the people who care for them.Continue reading
Children and teens are a lot of wonderful things. “Easy” is not one of them. When dealing with pediatric diabetes, clinicians should prepare for a different clinical picture, different behaviours, and different thresholds for hypoglycaemic symptoms. They should also anticipate a high level of parental stress and worry. With decades of experience treating and researching pediatric diabetes, Tim Jones describes salient issues in pediatric diabetes and hypoglycaemia management—and offers guidance to clinicians treating this population.
Physicians treating pediatric diabetes are a bit like veterinarians: unable to count on their young patients to describe symptoms and feelings, they must rely on third parties (i.e. parents, caregivers, pet owners) to fill in the clinical picture. Parents, for their part, face the daily challenge of subduing their children’s restless energy and willfulness in the service of diabetes management.
Not just small adults
Children with diabetes differ in several obvious ways from their adult counterparts. For one thing, their organs are still “under construction”—including that all-important pancreas—and their body systems haven’t matured yet. Accordingly, children may differ from adults in their response to dropping blood glucose—for example, developing a counterregulatory response and subjective symptoms at a higher glucose level than adults.
Children’s behaviour can also complicate diabetes treatment: think of the toddler who refuses to eat after an insulin dose or the preschooler who won’t sit still for a shot. To add a further layer of complication, odd behaviours in children don’t necessarily mean the same thing they do in adults. An adult speaking incoherently raises immediate red flags for hypoglycaemia. A babbling or sputtering child, meanwhile, could be showing signs of low blood glucose—or simply be playing make-believe.
As parents know all too well, adolescence brings its own set of diabetes management challenges. Embarrassed at the mere thought of a hypoglycaemic episode, a teenager may prioritize hypo avoidance over meeting glucose targets. Some teenagers may loosen their vigilance in general, putting themselves at risk of harmful glucose swings in either direction. In fact, the DCCT trial revealed severe hypoglycaemia to be more prevalent in young people than in adults. At the same time, clinicians and parents can find reassurance in knowing that, despite the higher rates, long-term cognitive function did not decline in the youngest cohort of DCCT patients.1
While plenty of adults thrive on diabetes gadgets and gizmos, it’s in children that the technology really comes into its own. By automating key functions of diabetes management, high-tech aids such as insulin pumps and continuous glucose monitoring (CGM) systems sidestep many of children’s unpredictable and confusing behaviours. Several pediatric studies have also found technology to yield modest gains in glucose control. In an analysis of over 16,000 children participating in the type-1 diabetes SWEET registry, for example, pump-treated children had lower HbA1C and required less insulin than children on multiple daily injections.2
As the technology keeps improving, so too do the options for high-tech interventions. In a study conducted earlier this year, children with type 1 diabetes used a remote monitoring system that let them share weekly information about blood glucose, insulin delivery and physical activity with their medical teams. Compared to the control group of conventionally managed children, the remotely monitored group experienced better glucose control and quality of life over the course of the 6-month study.3
Parents may need treatment, too—for anxiety. While it’s natural for the parent of a child with diabetes to worry about hypoglycaemia, the worry often becomes all-consuming, thus weakening the parent’s effectiveness as a guide and steadying force. As several studies have found, this fear of hypoglycaemia (FOH) can compromise diabetes control itself. In one such study, published in the journal Diabetic Medicine, parents with significant FOH-related distress had children with higher blood glucose levels. Perhaps surprisingly, these children also had a higher frequency of problematic hypoglycaemic episodes in the past year.4
For clinicians, monitoring the frequency and severity of hypoglycaemia in patients with diabetes is simply part of good care. It also falls to physicians to explore whether parents are fearful of hypoglycaemia as not all parents will readily admit it. If FOH is an issue, clinicians and diabetes educators need to arm parents with strategies to bring the anxiety down to manageable levels. Proven approaches include systematic hypoglycaemia education and cognitive behavioural therapy to address the FOH head-on.5 At the same time, parents need to be warned that an episode of severe hypoglycaemia puts the child at increased risk of a further episode.
Parents also play a crucial role in helping their older children transition to self-management. If the parent has always taken responsibility, some children may reach adolescence without understanding hypoglycaemia. Parents should be encouraged to provide age-appropriate explanations to their children and help them transition to self-monitoring and self-care.
It goes without saying that anyone involved in caring for the affected child—from parents and babysitters to teachers and daycare workers—should have an action plan to deal with hypoglycaemic episodes. When people have the right information, they feel more in control—and stress levels go down all around.
- Musen G et al. Impact of diabetes and its treatment on cognitive function among adolescents who participated in the Diabetes Control and Complications Trial. Diabetes Care 2008; 31:1933.
- Szypowska A. Insulin pump therapy in children with type 1 diabetes: analysis of data from the SWEET registry. Pediatr Diabetes 2016; Suppl 23:38.
- Gandrud L et al. Intensive remote monitoring versus conventional care in type 1 diabetes: A randomized controlled trial. Pediatric Diabetes 2018; 19:1086.
- Haugstvedt A et al. Fear of hypoglycaemia in mothers and fathers of children with Type 1 diabetes is associated with poor glycaemic control and parental emotional distress: a population-based study. Diabet Med 2010; 27:72.
- Driscoll KA. Fear of Hypoglycemia in Children and Adolescents and Their Parents with Type 1 Diabetes. Curr Diab Rep 2016; 16:77.
Dead in bed syndrome
Dead in bed syndrome understandably strikes terror in the hearts of people with type 1 diabetes and their families. Clinicians, for their part, may find it difficult to discuss the syndrome with patients and thus avoid the topic. Fortunately, the syndrome is rare enough that the key message to patients is reassurance. In this insight piece, a globally recognized clinician and researcher suggests how clinicians might handle the topic.
There are very few things more upsetting, in the life of a physician, than having to speak with the parents of a young person who died. I still remember vividly the day I spoke to the parents of a 21 year old who died from ‘dead in bed’ (DIB) syndrome. They had found me on the Internet, and visited me in my city of Sheffield, UK to learn more about the syndrome. In addition to being devastated, they were angry. It seemed that nobody had told them about the syndrome, and they insisted the family should have been warned of the risks.
What followed was a difficult discussion in which I tried to explain the risks and benefits of bringing up the syndrome to young people with diabetes and their families. I noted that this mode of death was very rare and that discussing it was liable to cause disproportionate fear, thus eroding everyone’s quality of life.
At the same time, I took the parents’ words to heart: is there a way for professionals to discuss the syndrome with families without unduly scaring them?
What and why
DIB syndrome denotes the sudden, unexplained nighttime deaths of people under 40 with type 1 diabetes. The patient is found dead in an undisturbed bed after having gone to sleep without undue medical concerns. DIB accounts for an estimated 6% of deaths in people with type 1 diabetes under 40.1 It bears noting that death from any cause is infrequent in this group, making DIB a very rare condition. Indeed, a UK survey, in 1991 of all deaths of people under 40 identified 22 deaths consistent with DIB syndrome—fewer than 1 in 10,000.2 What’s more, sudden unexplained death with no cause found at post-mortem can also occur in young people without diabetes, though one study found that it was about 10 times more frequent in diabetes.
While the etiology of DIB syndrome remains unclear and may vary from case to case, evidence to date suggests that the deaths could be caused by disturbances in cardiac repolarization (and thus rhythm) triggered by nighttime hypoglycaemia, with a possible contribution from cardiac autonomic neuropathy. Although epinephrine, produced when the body responds to hypoglycaemia is an important defence mechanism against severe hypoglycaemia, some studies have suggested that it may contribute to abnormal cardiac repolarization. Genetic studies have not uncovered any significant associations to date, though the numbers may be too small to tease out culprit genes.
So how does a physician discuss this frightening but rare syndrome with families? Let’s start with patients with frequent severe nocturnal hypoglycaemic episodes or parents who have witnessed their child having a nocturnal hypoglycaemic seizure. In my view, it is reasonable to ask whether they worry about nocturnal death from severe hypoglycaemia, then move into a discussion of DIB, emphasizing how rare it is.
And what about patients without a history of severe hypoglycaemia? In our current medicolegal climate, it makes sense to at least enquire whether they ever worry about the possiblity that a severe hypoglycaemic episode during the night might have serious consequences. However, the discussion should focus on reassurance.
In all cases, patients should be educated about strategies to minimize the risk. The greater their sense of control, the less likely they will live in fear. Above all, patients should know about measures to avoid nocturnal hypoglycaemia, such as monitoring blood glucose before going to sleep and larger bedtime snacks to compensate for borderline values. Such measures are especially important in people with IAH. The increasing use of continuous glucose monitoring as a clinical tool would provide further reassurance.
In patients with prolonged QT intervals at rest, medications associated with further prolongation should be discontinued. Some studies suggest that medications that act on the renin-antiogensin system, such as ACE inhibitors and angiotensin receptor blockers, have beneficial effects on cardiovascular autoregulation and may thus reduce the risk of DIB syndrome.3
On a health-systems level, coordinated collection of data from people who died of DIB syndrome—for instance, through patient registries—will enable us to identify at-risk individuals and better understand the condition.
- Dead in bed syndrome. Diabetes.co.uk. Accessed at https://www.diabetes.co.uk/diabetes-complications/dead-in-bed-syndrome.html
- Tattersall RB, Gill GV. Unexplained deaths of type 1 diabetic patients. Diabet Med 1991; 8:49-58.
- Weston PJ. Dead in bed syndrome: a review of the evidence. Diabetes Manage 2012; 2:233-41.
The Sniff Test – Benefits and limitations of diabetes alert dogs
Dogs serve an important role in enhancing human health and well-being, from guiding people with disabilities and calming people on the autism spectrum to sensing allergens and other potential medical emergencies—such as hypoglycaemia. The use of diabetes alert dogs (DADs) has been steadily gaining in popularity, and research is yielding new insights into their benefits and limitations. In this article, an expert on hypoglycaemia detection strategies provides a balanced overview of DADs and evidence-based guidance on their use.
Dogs help humans in many ways: they provide companionship, comfort, and motivation to be more physically active. Service dogs go a step further and help people stay safe. It’s hardly surprising, then, that so many people with diabetes have taken an interest in diabetes alert dogs (DADs)—dogs trained to smell chemical changes in the human body when blood glucose falls outside the normal range.
I believe that DADs have value. At the same time, they should not be regarded as a panacea or substitute for vigilant glucose monitoring with reliable technologies. In order to provide informed advice to their patients, health providers need to understand how DADs have fared in scientific studies and to balance this information with the well-established contribution of dogs to human well-being.
The role of DADs in hypoglycaemia
Early detection of hypoglycemia is critical for the prevention of more severe and potentially dangerous episodes. Patients and their families, especially parents of children with type 1 diabetes, are understandably eager to find better tools to avoid severe hypoglycaemia. While technologies such as continuous glucose monitoring (CGM) can help in this regard, a growing number of people with type 1 diabetes are turning to DADs, in some cases as a substitute for CGM.
DADs are especially popular with people who have impaired awareness of hypoglycaemia (IAH), defined as a compromised ability to perceive or experience hypoglycemic symptoms. DADs can alert these individuals to check their blood glucose and treat hypoglycaemia before it becomes serious. While DADs cannot and should not replace glucose monitoring devices, they provide an extra layer of protection—at least in theory.
In practice, it can take time and (in some cases) a lot of money to find a well-trained DAD. As with all purchases, caveat emptor applies here, as there are no standards regulating the training and performance of DADs. Ideally, the dog should be no younger than 1.5 years, adequately trained to perform distinct “alert behaviours”, and obtained from an organization willing to provide references from past clients.1
There’s a further reason for caution: while patient surveys and anecdotal reports almost uniformly praise DADs for their ability to detect lows and improve diabetes control,2,3 clinical-trial evidence for the accuracy of DADs remains scant and inconclusive. Here’s what we know so far.
Only a few studies have tested the accuracy of DADs under experimental conditions. In one study, trained dogs were largely unable to identify a “hypoglycaemic scent” in skin swabs obtained from subjects with type 1 diabetes (who were not the owners of the dogs).4 However, a later, similar study found that DADs’ ability to recognize hypoglycaemia in human perspiration samples was statistically significant.5
In a different type of study, 18 DAD owners completed diaries of DAD alerts during the first year after they obtained their dogs.6 Diary readings included daily blood glucose readings and DAD alerts (in response to perceived low or high glucose). Results showed that DAD alerts had a sensitivity of just 57%, with a slightly better sensitivity to low than to high glucose, and a specificity just under 50%.6 In addition, high variability was observed across DADs, suggesting that dog’s detection abilities may vary widely.
Because CGM readings are a reliable method of detecting hypoglycaemia, it makes sense to study how DADs compare to CGM. At least two studies have done just that. In the first, participants reported a high level of satisfaction with their DADs, but the dogs provided timely alerts in just 36% cases of hypoglycaemia (sensitivity), and showed a high rate of false positives.7 Time to detection was also significantly longer with DADs than with CGM (median difference of 22 minutes).7 The second study also found low sensitivity and specificity (with high inter-dog variability), and rate-of-change analyses indicated that the dogs were responding to absolute blood glucose levels rather than rapid changes in glucose.8
Most diabetes health providers already have or will soon have patients interested in using DADs and need to be prepared to discuss the science behind DAD performance in a balanced way. While the evidence to date suggests that DADs are not as accurate as tools such as CGM, an appraisal of DADs must also consider their demonstrated benefits which include improvements in quality of life and diabetes control. . We cannot discount these positive reports and more research is needed to understand how DADs help people to manage their diabetes more effectively.
- Cattet J, Hardin DS. Diabetes alert dogs: buyer beware. Diabetes forecast 2014. Accessed at http://www.diabetesforecast.org/2014/11-nov/diabetes-alert-dogs-buyer.html
- Petry NM et al. Perceptions about professionally and non-professionally trained hypoglycemia detection dogs. Diabetes Res Clin Pract 2015;109:389-96.
- Gonder-Frederick LA et al. Diabetic alert dogs: a preliminary survey of current users. Diabetes Care 2013:e47. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609496/.
- Dehlinger K et al. Can trained dogs detect a hypoglycemic scent in patients with type 1 diabetes? Diabetes Care 2013;36:e98-9.
- Hardin DS et al. Dogs can be successfully trained to alert to hypoglycemia samples from patients with type 1 diabetes. Diabetes Ther 2015;6:509-17.
- Gonder-Frederick LA et al. Variability of Diabetes Alert Dog Accuracy in a Real-World Setting. J Diabetes Sci Technol 2017. doi:1932296816685580.
- Los EA et al. Reliability of Trained Dogs to Alert to Hypoglycemia in Patients With Type 1 Diabetes. J Diabetes Sci Technol 2016. doi:1932296816666537.
- Gonder-Frederick LA et al. Diabetes alert dogs (DADs): an assessment of accuracy and implications. Diabet Res Clin Pract 2017; 134:121-30.
A Blow to the Brain
Impaired awareness of hypoglycaemia (IAH) is a common, frustrating, and potentially dangerous problem for people with diabetes who use insulin. While researchers have yet to unravel the physiological underpinnings of IAH, neuroimaging studies have shed light on how the brain responds to hypoglycaemia—and how these responses may change as IAH sets in. In this article, two internationally recognized experts on the physiology and psychology of IAH review some of the patterns identified in neuroimaging studies and suggest how this knowledge could help lift hypoglycaemia’s clinical burden.
Neuroimaging studies are helping us understand how impaired awareness of hypoglycaemia affects the brain—and mind
Habituation is a physiological blunting process that occurs in response to repeated stimuli. Hypoglycaemia offers a case in point. Normally, the body and brain mount a strong counterregulatory response to a falling blood glucose that helps preserve glucose levels; however, recurrent episodes of hypoglycaemia may blunt this response on various levels, with the result that the affected person does not experience the expected warning signals in a timely fashion. This phenomenon, known as impaired awareness of hypoglycaemia (IAH), affects about a quarter of people with type 1 diabetes and 10% of those with type 2 diabetes who use insulin.
The brain’s responses to hypoglycaemia serve the adaptive purpose of preserving brain function and protecting the brain against structural damage. The progressive loss of awareness, however, is maladaptive in that it impairs the affected person’s ability to self-treat, thus raising the risk that the hypoglycaemia will become severe.
The hypoglycaemic brain in action
While the pathophysiology of IAH remains unclear, the science of neuroimaging offers intriguing clues. The technology identifies brain regions that become active in response to a stimulus, using a variety of markers—such as localized changes in blood flow or metabolic rate—to detect changes in brain activity. When studied in the context of hypoglycaemic stress, neuroimaging can help us understand some of the brain changes accompanying IAH and help us devise better ways of managing the problem.
In individuals without diabetes, experimentally-induced hypoglycaemia causes several regions of the brain to become active, including the basal ganglia, hypothalamus, pituitary, thalamus, and parts of the frontal cortex. Other regions, especially those involved in forming memories, may become deactivated. Neuroimaging studies have found these responses to differ in people with type 1 diabetes and between those with and without IAH.
In a study of men with type 1 diabetes, for example, subjects with IAH showed subtle differences not only in regions associated with the awareness of physiological responses to hypoglycaemia, but in regions associated with executive control, reward, memory, and emotional significance.1 In addition, differences in operculum activation in the IAH group raised the possibility that this group may be less driven to eat than those with intact awareness of hypoglycaemia.1
Another study involving people with type 1 diabetes found even more striking discrepancies: those with preserved awareness of hypoglycaemia showed changes in prefrontal cortex and angular gyrus activity in response to mild hypoglycaemia, but those with IAH failed to show any such changes.2
These alterations in neural activity have metabolic correlates. In one study, subjects with IAH showed increases in global cerebral blood flow compared to those without IAH and to healthy controls.3 The researchers speculated that “an increase in global cerebral blood flow may enhance nutrient supply to the brain, hence suppressing symptomatic awareness of hypoglycemia.”3 Another study saw brain levels of the non-glucose metabolic fuel lactate fall by about 20% in subjects with IAH—but not in those with normal awareness of hypoglycaemia and people without diabetes.4
Inside the patient’s head
Taken together, findings from neuroimaging studies underscore the fact that the experience of IAH goes beyond reduced awareness of symptoms. Affected individuals fail to perceive their condition as unpleasant or dangerous and lack the motivation to treat it. They may also fail to create normal memories of these incidents. These aberrations may prevent patients from engaging in healthy behaviours to avoid hypoglycaemia in the future, thus exacerbating and perpetuating the problem.
Strategies to help people with IAH “override” the perceptual distortions experienced in IAH may be the most effective clinical approach to reducing the occurrence of IAH and of hypoglycaemia itself. As a successful example, a pilot intervention targeting motivation and cognitions in people with resistant IAH (called DAFNE-HART) significantly improved hypoglycaemia awareness,5 supporting the hypothesis that problematic perceptions are key in persistent IAH.
- Dunn JT et al. The impact of hypoglycaemia awareness status on regional brain responses to acute hypoglycaemia in men with type 1 diabetes. Diabetologia 2018; 61:1676–87.
- Hwang JJ et al. Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia. J Clin Invest 2018; 128:1485-95.
- Wiegers EC et al. Cerebral blood flow response to hypoglycemia is altered in patients with type 1 diabetes and impaired awareness of hypoglycemia. J Cereb Blood Flow Metab 2017; 37:1994-2001.
- Wiegers EC et al. Brain Lactate concentration falls in response to hypoglycemia in patients with type 1 diabetes and impaired awareness of hypoglycemia. Diabetes 2016; 65:1601-5.
- de Zoysa N et al. A psychoeducational program to restore hypoglycemia awareness: the DAFNE-HART pilot study. Diabetes Care 2014;37:863-6.