Symptoms of Hypoglycemia

* Central Nervous System * Outonomic :

Function Disorder : - sweating
- cognitive disorder - palpitation
- coma - tremor
- visual disturbance - starvation
- incoordination
- behavioral change * Other :
- sleepy - headache
- paresthetic - nausea
Hypoglycaemia-the hidden problem
Epidemiology and consequences of hypoglycaemia

Hypoglycaemia symptoms are common

in type 2 diabetes ( 38% of patient )¹
- Reduced quality of life
- Reduced treatment satisfaction
- Reduced therapy adherence
- More common at HbA1c < 7 %

1. Diabetes, Obesity and Metabolism 2008 Jun;10 Suppl 1:25-32.

Unrecognized Hypoglycaemia : causes
Clinical condition Mechanism
Long duration Unknown
diabetes Recurrent hypoglycaemia→destroy glucosensitive
neuron
Intensive glycemic Increase of regulatory transport of neuronal glucose
control Increase of cortisol
Alcohol Suppresion of peripheral autonomic response
Cognition disorder
Nocturnal episode Sleep
Lay position can reduce sympathoadrenal response
Children Abstract disability

Eldery Autonomic response decrease

Adrenergic sensitivity decrease
 Risk factors for hypoglycaemia
Use of insulin and sulfonylureas
Older people
Long duration diabetes
Irregular eating habits
Exercise
Have lower HbA1c
Periods of fasting e.g.Ramadan
Prior hypoglycaemia
Hypoglycaemia unawereness
Alcohol
Recent studies investigaring intensive
glycaemic control have highlighted
Variable VADT Accord Advance

Hba1c (%) 8,4 vs 6,9 7,5 vs 6.4 7,3 vs 6,5

Primary MI, stroke, death from CV Non-fatal MI, non- Non-fatal MI, non
outcome causes, new or worsening fatal stroke, CVD fatal stroke, CVD
CHF, revascularisation and death death
inoperable CAD, amputation
for ischaemic gangrene
HR ( 95% CI ) 0,87 ( 0,730-1.04 ) 0,90 ( 0,78-1.04 ) 0,94 ( 0,84-1.06 )
for primary
outcome
HR ( 95% CI ) 1.065( 0,801-1,416 ) 1,22 ( 1,01-1,46 ) 0,93 ( 0,83-1,06 )
for mortality
Hypoglycaemia in T2DM : a possible link to
increased CV risk/events

Possible mechanisms
• Haemodynamic changes :
# activation of autonomic nervous system 10-50 fold
increased secreation of adrenaline&non adrenaline

• ECG changes :
# longer QT interval hypokalemia

• Haemorheological changes :
# platelet activation
# increased viscosity
Oral antidiabetic agents&hypoglycaemic risk in
type 2 diabetes
Agents with increased hypoglycaemic potential
Those which encance insulin secreation/ beta cell function in non
glucose dependent manner
• Sulfonylureas
• Short acting secretogogues/nateglinide

Agents with minimal/low hypoglycaemic risk

Improve insulin resistance
* biguanide-metformin
* thiazolidinediones ( pioglitazone/rosiglitazone )
Incretin-based therapies-enchanceinsulin secreation in glucose-
dependentmanner
* incretin enchancers : DPP-IV inhibitors ( sitagliptin, vildagliptin,
saxagliptin, alogliptin )
Reduce glucose absorption
* alpha-glucosidase inhibitors ( acarbose, voglibose )
* ? Bile-acid sequetrans ( colesevelam )
Sulfonylureas – lack of awarness and
education
Patient receive little information on the
adverse events of oral medication :
• In a UK survey, onlu 10% of people
treated with an SU knew that it could
cause hypos

GPs and practice nurses may not be aware

of the prevalence of hypos with SUs.
Case Study 1-Hypoglucaemia event
• A.S. is a 64 year old man admitted to the
nephrology service for dizziness andhypotension
after dialysis. During his hospital stay, he
experienced labile blood glucose levels and has
a suspected hypoglycaemic seizure. The
endocrine service was consulted to assist with
these findings.

• The patient has a history of previous stroke,

remote alcohol abuse, and end-stage renal
disease requiiring hemodialysis 3 days/week
and is awating a kidney transplant. He has had
type 2 diabetes for 25 years and has been
treated with insulin for 10 years.
• At home, he takes 6 units of aspart insulin with meals
and 12 units of glargine insulin in the morning. He weight
84 kg and his last A1c result was 6,7 %.
• During the past year and a half, he reports having had
two seizures

• During the hospitalization, he was placed on his home

insulin regimen plus ahospital preprandial correction
dose of insulin. The correction dose was 2 units of aspart
for blood glucose readings that werw 151-200mg/dl,
increasing by 2 units of aspart for every 50 mg/dl
increase in blood glucose.

• That afternoon, he had a witnessed seizure. He was

stabilized and routine laboratory testing was performed.
His blood glucose measured 42 mg/dl during the seizure.
Case Study 1 : Quetions
Does hypoglycaemia induce seizure ?
• There is relationship between insulin, seizures
and coma
• In animal study the pancreatic extract ( insulin
)→hyper-excitable and clonic convulsive
seizures lasting for several minutes, ranging
from total convulsions to only jerks and twitches.

• → insulin therapy could induce seizure.

Case Study 1 : Quetions
Does hypoglycemia induce seizure ?
What is the frequency of unconscious events in patients with diabetes ?
• Difficult to pinpoint exact incidence, because
• Seizures are not always witnessed and are often reported after the
fact in children. 75% of hypoglycemic seizures are reported as
occuring at night.

• Recording of blood glucose levels before, during/after seizures

rarely occurs. Witout this information it is difficult to determine
wheither a low blood glucose level was the cause of the seizure.

• Along durationof diabetes is often accompanied by comorbid

conditions associated with micro&macrovascular injuries. These
injuries could be detrimental to nerve conduction & futher confound
the relationship between hypoglycemia diabetes & seizure.

• Because of compensatorymechanism in the body, particulary in type

2 diabetes, euglycemia/even hyperglycemia may occur during &
after a seizure.
Case Study 1 : Quetions

* Does hypoglycemia induce seizure ?

* What is the frequency of unconscious events in
patients with diabetes ?
* Do patients with diabetes experince seizures for
reason other than hypoglycemia ?
* What variables determine when a seizure may
accour in patients with diabetes ?
* Several factors nocturnal timing, sleep status and
preceding duration of hypoglycemia.
 Case Study 1
After his seizure. A.S was transferred to the hospital’s
intensive care unit. While there, he had an
electroencephalogram that showed some abnormal
conduction pathways. He was euglycemic for the reminder
of his hospitalization, his nausea resolved, and his
hydration and volume status normalized, he was
discharged to home in his usual state of health.

Neither the neurology nor the endocrinology service

unequivocally stated that hypoglycemia caused gis seizure
because of his confoudingpast alcohol abuse, metabolic
derangements with end stage-renal disease, and previous
stroke with residual tissue injury noted on magnetic
resonance imaging. He will be evaluated as an outpatient
for a nwely identified seizure disorder.
Case 2
Patient K is a defense attorney in a busy,
prestigous law firm.she has dealt with type 1
diabetes since her diagnosis at the age of 13
years. She was started on an insulin pump in
order to level out her blood glucose control and
improve her overail health and has been happy
with the results. Patients K is invited to play in a
softball game prior to the barbeque at the annual
neighborhood picnic. She feels it would be a litte
exercise because she has spent much of the
day sitting anda relaxing while talking with her
friends. In the middle of the game, the patient
suddenly becomes weak, diaphhoretic, shaky,
and confused-clear signs of hypoglycemia.
Case Study 2

What are the possible causes of hypoglycemia

state ?
Several factors most likely contributed to patient K
hypoglicemia, the most significant being her
engagement in exercise 9 unplanned ) prior to
eating her meal in addition. The patient is away
from the stress of her job and is relaxing whichis
lowering her stress hormones. Together, these
conditions are to blame for hypoglycemic
episode.
Case Study 3
Patient G is a white man, 85 years of age, with a long
history of type 2 diabetes. The nurse conduct a home
health care visit for home assessment and medication
evaluation. The patient indicates that his blood glucose
levels are consistently in the high 200s, including in the
mornings and night. The nurse reviews the medications
remaining in his weekly pill box to assess medication
adherence and notes he has been missing multiple
medications throughout the week, including the
medication to help control his blood glucose levels.
Patient g states that when he realizes he has missed the
medication. He is afraid to take it. The nurse informs the
patient’s physician of the findings, and the patient’s
regimen is changed to replaginide 2 mg just prior to each
of the three biggest meals. The instructions are given to
Patient G, and he states understanding and is able to
verbalize when to take the medication
Case Study 3

The nurse returns to Patient G;s home 3 days later

to assess his tolerance to the new medication.
When the nurse arrives at 9 a.m., the patient is
in a state of confusion, diaphoresis, and
shakiness. His blood glucose level is 48 mg/dL.

The nurse provides adequate treatment and

Patient G is then able to help determine what
precipitated the episode of hypoglycemia. The
patient reports that he took the repaglinide pill at
7.15 a.m., but he had not consumed breakfast.
Case Study 3
What happen and what di you suggest to this
patient ?

The nurse works with patient G to develop a plan

to avoid skipping meals.
They decide that the patient will make his
breakfast each day and elicit the assistence of
his daughter to remind him to take the
repaglinide when she talks to him each morning.
The daughter also agress to check in after lunch
and dinner to assure that the patient is taking the
meals.
Managing T2DM with concomitant disease

The Goal is :
1. The lower HbA1C and prevebt complications
of diabetes
2. Short-term : Hypoglycemia
3. Long-term : micro and macro vascular
complication

Non-pharmacologic – enchanced Lifestyle