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[IP] Non-invasive Detection of Hypoglycemia Using A Novel, Fully Biocompatible and Patient Friendly Alarm System

Hypoglycemia is a common complication of diabetes treatment with either
insulin or sulfonylureas and is particularly common with intensified insulin
regimens.  Episodes are often distressing and carry the risk of serious
neurological and cardiovascular sequelae. Hypoglycemia is especially
hazardous in patients with longstanding type 1 diabetes who have lost the
early warning symptoms of falling blood glucose levels. Nocturnal episodes
are also potentially dangerous and have been implicated when diabetic
patients have been found unexpectedly dead in bed.  Hypoglycemia is one of
the complications of diabetes most feared by patients, on a par with
blindness and renal failure.

Intensive research has been devoted to the development of hypoglycemia
alarms, exploiting principles that range from detecting changes in the
electroencephalogram or skin conductance (due to sweating) to measurements
of subcutaneous tissue glucose concentrations by glucose sensors. As yet,
however, none has proved sufficiently reliable or unobtrusive to be useful
in clinical practice.

The following is a novel alarm system that can detect hypoglycemia before
the patient notices any symptoms and that operates robustly in a uniquely,
patient friendly fashion. The reports were volunteered spontaneously and
independently by the patients.

For the whole story: www.diabetesincontrol.com/issue32/item14.htm

Case 1:   A 66 year old woman developed type 2 diabetes in 1971 and was
transferred to insulin in 1979. She currently takes injections of insulins
twice daily, totaling 38 units per day, and monitors her blood glucose at
least once daily. She has no significant diabetic complications or other
illness, and drinks very little alcohol. For the past two years she has
experienced increasingly frequent hypoglycemic episodes, with excessive
sweating, generalized weakness, anxiety, and irritability. Most attacks
occur in the evening and some occur at night. She retains generally good
awareness of hypoglycemic symptoms and can usually take quick corrective
action.  But, over the past year she has noticed unusual stereotyped
behavior displayed by Candy, her 9 year old mongrel bitch, which occurs only
before hypoglycemic episodes. Candy jumps up, runs out of the room, and
hides under a chair in the hallway, and re-emerges only when the patient has
taken carbohydrate. Intriguingly, Candy acts in this way before the patient
is aware of any hypoglycemic symptoms; blood glucose concentration during
such episodes is around 30mg/dl.

Case 2:  A 47 year old woman has required insulin since type 2 diabetes was
diagnosed in 1995. She has no diabetic complications, drinks hardly any
alcohol, and takes insulin twice daily.  She has up to two hypoglycemic
episodes each week, usually with good warning and characterized by sweating,
malaise, and sometimes confusion. Episodes tend to occur during the
afternoon and sometimes at night.   Within the past year her 7 year old
mongrel bitch, Susie, has shown peculiar behavior during the patient's
hypoglycemic attacks. At night she has been nudged awake by Susie and has
then found herself to be hypoglycemic. Susie goes back to sleep only after
the patient has taken carbohydrate and her symptoms have settled;
interestingly, her husband sleeps throughout. On other occasions, Susie has
refused her favorite chocolate treats and has prevented the patient from
leaving the house until she has taken food to correct hypoglycemia. During
most of these episodes the patient has initially been unaware that she is
becoming hypoglycemic, but blood glucose is around 36mg/dl.

Case 3:  A 34 year old woman has had type 1 diabetes since 1970, complicated
by retinopathy and nephropathy. She currently takes 41 units of insulin per
day, does not smoke, and drinks very little alcohol. On average, she has two
hypoglycemic episodes per week, with sweating and light headedness; she has
reduced awareness of hypoglycemia and does not wake up during nocturnal
episodes.   Her 3 year old golden retriever, Natt, becomes very distressed
whenever she is hypoglycemic. During the day, he paces up and down and puts
his head on her lap; during nocturnal episodes, he barks and scrabbles
against the bedroom door.  Natt only settles once her hypoglycemia has been
corrected. Blood glucose concentration on two such occasions was 30 and

Over a third of dogs living with diabetic people have been reported to show
various behavioral changes during their owners' hypoglycemic episodes. The
three dogs reported here take canine glucose sensing to a new level of
sophistication. All were clearly able to sense hypoglycemia accurately under
circumstances when the patients themselves were initially unaware of falling
glucose levels. Formal calculations of sensitivity and specificity are not
possible, but each dog showed her specific behaviors only when the patient
had documented hypoglycemia. Susie and Natt deserve special mention because
they were able to detect nocturnal episodes in their owners and then
undertook further corrective action by waking them to eat thus going further
than any available glucose sensor.

These two cases hint at hitherto unsuspected ways in which hypoglycemia may
be detected, even before symptoms are noticed by people whose hypoglycemia
awareness is mostly intact. The physiological basis is uncertain, but direct
contact with the diabetic patient was not required in any of these cases.
Possible clues include olfactory changes (possibly related to sweating),
muscle tremor, or behavioral alterations such as the patient's failure to
respond to her dog in her usual way. We are attracted by the notion of the
"sixth sense" with which dogs are commonly credited, but acknowledge that
this will need to be substantiated by further research.

As well as being useful in sniffing out drugs, explosives, and agricultural
contraband, dogs have contributed generously to many aspects of medicine.
Their achievements include guiding blind people, providing rapid-response
paramedical assistance to people lost in the mountains, recognizing fits in
patients with epilepsy,  and co-authoring papers in the BMJ.  Dogs are also
beneficial to cardiovascular health a particularly important issue in
diabetic patients. Blood pressure is lowered by stroking dogs,  and pets who
drag their reluctant owners out for brisk 45-minute walkies are operating in
accord with the WHO guidelines on physical exercise.

An extended healthcare role should now be considered for man's (and woman's)
best friend. Research is urgently needed to determine whether dogs can be
trained to recognize and react to early signs of hypoglycemia. Hypoglycemia
alarm dogs could provide an important aid to patients with poor awareness of
symptoms, particularly those prone to nocturnal episodes or who live alone.
Dog bones are even a lot less expensive then blood glucose strips and you
dont have to calibrate them.

Diabetes and Endocrinology Research Group, University of Liverpool,
Department of Medicine, University Hospital Aintree, Liverpool L9 7AL,

The issue of authorship is taken seriously by responsible journals

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