management of hypoglycaemia

1. CURRENT TRENDS MANAGEMENT OF
HYPOGLYCAEMIA IN DIABETES
MELLITUS
Presented by Firm 4
Grand Round
Internal Medicine Department
LAUTECH Teaching Hospital, Ogbomoso

2. Outline
• Introduction
• Epidemiology
• Causes
• Risk factors
• Investigations
• Management
• Recommendations
• References

3. Introduction
• Diabetes Mellitus is a group of disorders with a
common pathway of chronic hyperglycaemia due
to dysfunction of beta cells, hence insulin
production and or insulin sensitivity.
• Hypoglycaemia is low blood sugar <2.2mmol/L,
or 40mg/dL.However in diabetes, action should
be taken at </= 4mmol/L or 72mg/dL…JBDS
2018

4. Epidemiology
• Hypoglycaemia is the commonest complication
of insulin & sulphonylureas.
• Most other classes scarcely cause
hypoglycaemia.
• T1 DM Patients have averagely 2 episodes of
mild hypoglycaemia per week
• It was less common in insulin treated Type 2
Diabetes Mellitus, however T2DM are more
likely to be admitted for sever hypoglycaemia
than T1DM (30%to 10%)...Donnelly at al 2005

5. Epidemiology
• Hypoglycaemia is the commonest side effect of
insulin or sulfonylureas therapy used to treat
diabetes mellitus. Because of their modes of
action (i.e. they prevent glucose from rising
rather than lowering glucose concentrations);
metformin, pioglitazone, DPP-4 inhibitors,
acarbose, SLGT-2 inhibitors and GLP1
analogues prescribed without insulin or insulin
secretagogue (sulfonylurea and metaglidine)
therapy are unlikely to result in hypoglycaemia.

6. Epidemiology
• Hypoglycaemia presents a major barrier to
satisfactory long term glycaemic control and
remains a feared complication of diabetes
treatment. Hypoglycaemia results from an
imbalance between glucose supply, glucose
utilisation and current insulin levels.
Hypoglycaemia must be excluded in any person
with diabetes who is acutely unwell, drowsy,
unconscious, unable to co-operate, presenting
with aggressive behaviour or seizures.

8. Physiological responses to decreasing
plasma glucose concentrations
Response Glycaemic threshold,mmol/L
• Decreased insulin
• Increased glucagon
• Increased epinephrine
• Increased cortisol and GH
• Symptoms
• Decreased cognition
• 4.4-4.7
• 3.6-3.9
• 3.6-3.9
• 3.6-3.9
• 2.8-3.1
• <2.8

9. Causes
• Hypoglycaemia occurs as a consequence of 3
factors
1. Behavioural issues
2. Impaired counter regulatory systems
3. Complications of diabetes

10. Behavioral issues
• Insulin (insulin secretagogues)doses excess, ill-
timed, wrong type
• Reduced exogenous glucose-overnight fast,
missed meals or snacks
• Alcohol excess especially on empty stomach-
reduces endogenous glucose production
• Rigorous exercise
• The patient stack their insulin up

11. Behavioural issues
• Lipohypertrophy at injection site causing
variable insulin absorption.
• Breast feeding in diabetic mothers
• Fictitious (deliberately induced)

12. Counter regulatory issues
• Failure of insulin level to decrease-in
absolute endogenous insulin deficiency
• Impaired glucagon response >5yrs DM
• Impaired sympatho-adrenal responses-
• Aging, autonomic neuropathy or hypoglycaemic
unawareness further blunt it

13. Counterregulatory issues
• Cortisol deficiency
• Occasionally Addison disease develops in type 1
DM, in this case insulin requirement falls
significantly
• This functional and reversible disorder is
distinct from classical diabetic autonomic
neuropathy, a structural and irreversible
disorder

14. Complications of diabetes
• Autonomic neuropathy-failure of sympatho-
adrenal responses
• Gastroparesis-if insulin is given before the meal,
the real insulin action may occur before
absorption of the food
• Renal failure-decreased insulin clearance and loss
of renal contribution to gluconeogenesis in
postabsorptive state

15. Complications of Diabetes

16. Endocrine causes
• Pituitary insufficiency
• Adrenal insufficiency
• Premenstrual insulin insensitivity

17. Clinical presentation
Autonomic symptoms
sympathetic
• Palpitation
• Anxiety
• Tremulousness
• Sweating
• Tachycardia
• Pallor

18. Clinical presentation
• Parasympathetic
• Nausea
• hunger

19. Clinical presentation
• Neuroglycopenic – often preceded by
adrenergic
• As early warning signs
• Blurred vision
• Diplopia
• Speech difficulty
• Headache
• Tiredness/fatigue
• Muscle weakness
• irritability

20. Clinical presentation
• Hallucination
• Tingling or numbness in tongue and lips
• Vivid dreams or nightmares
• Focal impairment e.g. hemiplegia
• Confusion
• Seizure
• Coma
• Death

21. Impaired Hypoglycaemic
Awareness
• Impaired awareness of hypoglycaemia (IAH)
• It is an acquired syndrome associated with insulin
treatment resulting in the warning symptoms of
hypoglycaemia becoming diminished in intensity,
altered in nature or lost altogether. This increases
the vulnerability of affected individuals of
progression to severe hypoglycaemia.
• Its prevalence increases with duration of diabetes
and is much more common in type 1 than in type 2
diabetes (Graveling and Frier, 2010).

22. Hypoglycaemic unawareness
• Caused by the attenuated sympathoadrenal
response(largely the reduced sympathetic neural
response) to hypoglycaemia
• Loss of the warning adrenergic and cholinergic
symptoms symptoms that previously allowed the
patient to recognise the developing
hypoglycaemia
• This occurs especially during aggressive
glycaemic control

23. Impaired awareness
• This is common amongst diabetics with tight
control and HbA1c in non diabetic range (5.7-
6.4mmol/mol).
• With frequent exposure to hypoglycaemia,
cerebral autoregulatory mechanism for glucose
threshold is adjusted to a lower level for thr onset
of symptoms of hypoglycaemia.
• Risk increases with increasing duration on insulin
therapy; upto 25% in Type 1 DM & about 10% in
insulin treated Type 2 DM.

24. Hypoglycaemic unawareness
• With repeated episodes of hypoglycaemia, there
is cerebral adaptation and autonomic symptoms
do not occur until the blood glucose level is
much lower
• The first symptoms are often due to
neuroglycopenia
• This condition is called hypoglycaemia
unawareness

25. Hypoglycaemia unawareness
• This can be reversed by keeping the blood sugar
high for period of several weeks
• Reversible by as little as 2-3weeks of scrupulous
avoidance of hypoglycemia in most of the
affected patients

26. Causes of hypoglycaemia in patients
without diabetes
• Drugs-insulin/insulin
secretogogues,alcohol,ACEIs, ARBs, B-
adrenergic receptor antagonists, quinine,
quinolone, indomethacin
• Critical illness-renal, cardiac or hepatic failure,
sepsis
• Hormonal deficiencies-Addison disease,
hypopituitarism

27. Causes
• Non beta cell tumors- hepatomas,adrenocortical
carcinomas,carcinoids
• Endogenous hyperinsulinaemia-primary beta
cell tumors(insulinoma),insulin autoimmune
hypoglycemia-antibody to insulin or to the
insulin receptor,ectopic insulin secretion,insulin
secretagogues

28. Others
• Functional beta cell disorder(Nesidioblastosis)
• Postgastric bypass
• Accidental,surreptitous or malicious
hypoglycaemia

29. Insulin secretagogues
• Sulphonylureas-glimeperide, glipizide,
glibenclamide
• Nonsulphonylureas- Repaglinide, nateglinide
• GLP-1 agonist- Exentide, Liraglutide
• Dipeptidyl peptidase-4 inhibitors - saxaglipin,
sitaglipin, vidaglipin, linagliptin

31. Risk factors
• Prior episode of severe
hypoglycemia
• Current low A1C (<6.0%)
• Hypoglycemia unawareness
• Long duration of insulin
therapy
• Autonomic neuropathy
• Chronic kidney disease
• Low economic status,
• C peptide negativity(
indicating complete insulin
deficiency
• Food insecurity
• Low health literacy
• Preschool-age children unable
to detect and/or treat mild
hypoglycemia on their own
• Adolescence
• Sleep
• Pregnancy
• Elderly
• Cognitive impairment
• Genetic e.g. ACE genotype

32. Morbidity of severe hypoglycaemia
• CNS
• Impaired cognitive function
• Coma
• Convulsions
• Intellectual decline
• Transient ischaemic attack
• Brain damage
• Focal neurological deficit.
• Heart
• Arrhythmias
• MI
• Eyes:
• Vitreous haemorrhage
• Worsening retinopathy
• Others
• Accidents including RTC.
• Hypothermia

33. MANAGEMENT

35. Steps in managing hypoglycaemia
• Recognize autonomic or neuroglycopenic
symptoms
• Confirm if possible (blood glucose <4.0
mmol/L)
• Treat with “fast sugar” (simple carbohydrate) (15
g) to relieve symptoms
• Retest in 15 minutes to ensure the BG >4.0
mmol/L and retreat (see above) if needed
• Eat usual snack or meal due at that time of day
or a snack with 15 g carbohydrate plus protein

36. Work up
• RBS
• HbA1C
• C peptide assay
• Anti Adrenal Cortex Abs
• TFT
• Serum E/U/Cr
• Urinalysis
• Drugs & Alcohol screening

37. Management
• Whipped triad:
• Features of Hypoglycaemia
• +
• Confirmation by a rapid strip test
• +
• Resolution of features when glucose is
administered.

38. Management
• Treatment of acute hyloglycaemia depends
majorly
• On severity
• Level of consciousness
• Ability to swallow

39. Management
• If recognized early, oral carbohydrate(simple)
suffices to correct hypoglycaemia
• Give parenteral if oral intake is not possible
• Give oral glucose load as soon as patient can
swallow.
• Note that full recovery may not immediately
occur
• Cognitive function may take up to 1hr to be fully
restored.

40. Management
• Hypoglycemia unawareness can develop during
the moderate or severe hypoglycemic episodes
and it is usually characterized by the presence of
cognitive symptoms in the absence of autonomic
symptoms. Age, duration of diabetes and
previous hypoglycemic episodes can all lead to
the development of hypoglycemic unawareness.

41. Treatment
In conscious patients
Evidence suggests that 15 g of glucose (monosaccharide) is
required to produce an increase in Blood Glucose of
approximately 2.1 mmol/L within 20 minutes, with
adequate symptom relief for most people
• 15 g of glucose in the form of glucose tablets
• 15 mL (3 teaspoons) or 3 packets of sugar dissolved in
water
• 150 mL of juice or regular soft drink
• 6 Lifesavers (1 = 2.5 g of carbohydrate)
• 15 mL (1 tablespoon) of honey
• Notice the "rule of 15"
• JBDS 2018

42. Glucose gel

43. "Sugar tax" concept
• Due to government's SOFT DRINK INDUSTRY
LEVY (SDIL) recommends low sugar content.
• Companies reduce amount of sugar in their
products before of by April 2018 e.g. Lucozade,
Ribena
• Sugar content <15g
• These drinks formerly approved for treating
hypoglycaemia can no longer do so.
•

45. Treatment
• Treat with 1 mg of glucagon subcutaneously or
intramuscularly
• Call for help
• Discuss with diabetes health-care team

46. Treatment
• Severe hypoglycaemia: unconscious
• Treat with 10-25 g (20-50 mL of D50W) of
glucose intravenously over 1-3 minutes
▫ 25mL glucose 50%; or • 50mL glucose 20%; or •
100mL glucose 10% preferred as less irritant
Give IV of 2-5 ml/kg of 10% Dextrose (rate: 2-
3ml/min) as a maintenance till B.sugar >90
mg/dL& & the patient is fully alert.
▫ Children: 2-5 mL/kg of glucose intravenous
infusion 10% (200-500 mg/kg of glucose)

47. Treatment
• 10% or 20% glucose solutions are preferred.
• Using 10% glucose resulted in lower post
treatment glucose levels (6.2 versus 9.4 mmol/L)
(Moore and Woollard, 2005
• The risk of extravasation injury with any
hypertonic solution may make 10% dextrose safer
than 50% glucose (Wood, 2007). Glucose 10%
preparations are considerably less hypertonic than
the 50% preparation and therefore less destructive
to the venous endothelium (Nolan, 2005).

48. Treatment
• A Japanese study using rabbit ears found that
increasing the duration of infusion decreased the
tolerance of peripheral veins to solutions of
increased osmolality (Kuwahara et al., 1998)
• 10% glucose has an osmolality of 506mOsm/L
compared with 2522mOsm/L for 50% dextrose
(Nehme and Cudini, 2009).

49. Treatment
• Glucagon
Glucagon should not be used at concentrations greater
than 1 mg/mL (1 unit/mL)
• < 25 kg or < 8yr gives ½ vial (0.5 mg)
• > 25 kg or > 8yrs, give full vial (1 mg) 1mg (IV,
intramuscular or subcutaneous)
takes 5-10 minutes to work, as it has short duration of
action(15-20 minutes)
• Cover with I.V. hypertonic glucose
it relies on glycogen stores therefore it may not be
effective in:
Cachectic patients
Alcoholic, liver disease
Young children
Hypoglycemia due to fatty acid oxidation or glycogen
storage disorders, Chronic hypoglycemia

50. Glucagon

51. Treatment
• Patients with oral hypoglycemic overdose
differ from insulin overdose hypoglycemia, in
that admission should be for at least 72 hrs
due to the prolonged effect of these oral
agents, the admission might be extended
further to 3 – 5 days if the condition is
associated with renal or hepatic disease

52. Treatment
• Retest in 15 minutes to ensure the BG >4.0
mmol/L and retreat with a further 15 g of
carbohydrate if needed
• Once conscious, eat usual snack or meal due at
that time of day or a snack with 15 g
carbohydrate plus protein

53. "Hypo" boxes
• These boxes are often in a prominent place e.g. on
resuscitation trolleys and are brightly coloured for
instant recognition.
• They contain all the equipment required to treat
hypoglycaemia from cartons of fruit juice to IV
cannulas.
• Areas of good practice have successfully used
“hypo boxes” for the management of
hypoglycaemia (Baker, 2007).
• There are now commercially available hypo boxes.

54. "Hypo" box

55. Hypoglycaemia Audit form
• Form to be filled after each episode of
hyloglycaemia.
• Useful in the hospital setting
• Filled the health care professional.
• Details the findings and the steps followed to
correct the hypoglycaemia.
• Completed form is returned to Diabetes
Department.

57. Hypoglycaemia episode label

58. Treatment
• Severe hypoglycaemia
• Treat with oral “fast sugar” (simple
carbohydrate) (20 g) to relieve symptoms
• Retest in 15 minutes to ensure the BG> 4.0
mmol/L and retreat with a further 15 g of
carbohydrate if needed
• Eat usual snack or meal due at that time of day
or a snack with 15 g carbohydrate plus protein

59. Prevention
• Patient Education
• Educate on causes and risk factors for
hypoglycaemia
• Treatment
• Need to have access to glucose( glucagon)
• Need for regular glucose monitoring
• Need to reduce dose of insulin before exercise,
and ingest extra CHO

60. Prevention
• Advice during air travels:
• Carry a fast acting CHO( Non perishable,fit for
containers) - screwtop glucose drinks, packets of
powdered glucose, confectionaries(foil wrapped in
hot climate).
• Companions should carry additional CHO &
Glucagon.
• Perform frequent blood glucose monitoring, carry
spare meter, visually read strips).
• Use fast acting insulin analogues for long distance
air travels.

61. Prevention
• Relatives Education:
• Educate about signs and symptoms of
hypoglycaemia
• Educate on how to manage: how to give
glucagon etc

62. Prevention
• Timing of insulin
• Deferring dose of basal intermediate insulin till
11pm or use of fast acting before evening meal.
• Long acting insulin should be taken with breakfast
instead of bed time, that it's action is waning using
the night
• Patients should measure blood glucose before
retiring into bed
• To take a CHO snack if reading is less than
6mmol/L

63. Prevention
• Adults who have poor glycaemic control may
start to experience symptoms of hypoglycaemia
above 4.0mmol/L.
• There is no evidence that the thresholds for
cognitive dysfunction are reset upwards;
therefore the only reason for treatment is
symptomatic relief.

64. Prevention
• Adults who are experiencing hypoglycaemia
symptoms but have a blood glucose level greater
than 4.0mmol/L –
▫ Treat with a small carbohydrate snack only e.g. 1
medium banana, a slice of bread or normal meal if
due.
• All adults with a blood glucose level less than
4.0mmol/L with or without symptoms of
hypoglycaemia should be as will be later
discussed.

65. DAFNE
• DAFNE (dose adjustment for normal
eating)
• It is a course for people with type 1 diabetes
designed to teach patients how to adjust their
insulin doses according to their carbohydrate
consumption (carbohydrate counting).
• DAFNE principles suggest that hypoglycaemia
is treated at the level of 3.5mmol/L and that long
acting carbohydrate is not always required
(DAFNE

66. Guidance
• The Joint British Diabetes Societies for
Inpatient care (JBDS) suggest a target blood
glucose of 6-10mmol/L, therefore this guidance
recommends that in the hospital environment, a
blood glucose of 4.0mmol/L or less is treated as
hypoglycaemia in all patients with diabetes.
• In outpatients however, 3.5mmol/L is advised as
the cut off.

67. Guidance
• Diabetes Canada
• Reinforcement of the importance of counselling
individuals on insulin or insulin secretagogues
and their support persons on the risk,
prevention, recognition and treatment of
hypoglycemia
• New information
• on strategies to reduce the risk of hypoglycaemia

68. Recommendations
• All people with diabetes currently using or
starting therapy with insulin or insulin
secretagogues and their support persons should
be counselled about the risk, prevention,
recognition and treatment of hypoglycemia. Risk
factors for severe hypoglycemia should be
identified and addressed.

69. Recommendation
• The Diabetic Health Care (DHC) team should
review the person with diabetes’ experience with
hypoglycemia at each visit including an estimate
of cause, frequency, symptoms, recognition,
severity and treatment, as well as the risk of
driving with hypoglycemia

70. Recommendations
• In people with diabetes at increased risk of
hypoglycemia, the following strategies may
be used to reduce the risk of hypoglycemia:
• Avoidance of pharmacotherapies
associated with increased risk of recurrent
or severe hypoglycemia
• A standardized education program
targeting rigorous avoidance of
hypoglycemia while maintaining overall
glycemic control

71. Recommendations
• Mild to moderate hypoglycemia should be
treated by the oral ingestion of 15 g
carbohydrate, preferably as glucose or sucrose
tablets or solution. These are preferable to
orange juice and glucose gels.
• People with diabetes should retest Blood
Glucose in 15 minutes and re-treat with another
15 g carbohydrate if the Blood Glc level remains
<4.0 mmol/L

72. Recommendations
• 5. Increased frequency of Self Monitoring of
blood glucose (SMBG) including periodic
assessment during sleeping hours.
• Less stringent glycemic targets with avoidance of
hypoglycemia for up to 3 months
• A psycho-behavioural intervention program
(blood glucose awareness training)
• Structured diabetes education and frequent
follow-up

73. Recommendations
• 6. Severe hypoglycemia in a conscious
person with diabetes
• Should be treated by oral ingestion of 20 g
carbohydrate, preferably as glucose tablets or
equivalent. BG should be retested in 15 minutes
and then re-treated with another 15 g glucose if
the BG level remains <4.0 mmol/L

74. Recommendations
• 7. Severe hypoglycemia in an unconscious
individual with diabetes
• With no intravenous access: 1 mg glucagon should
be given subcutaneously or intramuscularly.
• Caregivers or support persons should call for
emergency services and the episode should be
discussed with the DHC team as soon as possible.
• With intravenous access: 10-25 g (20-50 mL of
D50W) of glucose should be given intravenously
over 1-3 minutes

75. Recommendations
• 8 Once the hypoglycemia has been reversed, the
person should have the usual meal or snack that
is due at that time of the day to prevent repeated
hypoglycemia. If a meal is >1 hour away, a snack
(including 15 g carbohydrate and a protein
source) should be consumed.
• 9. For individuals with diabetes at risk of severe
hypoglycemia, support persons should be taught
how to administer glucagon.

76. Recommendations
• Identify the risk factor or cause resulting in
hypoglycaemia.
• Take measures to avoid hypoglycaemia in the future.
The DISN or Inpatient Diabetes Team can be
contacted to discuss this.
• Unless the cause is easily identifiable and both the
nursing staff and patient are confident that steps
can be taken to avoid future events, a medical or
DISN review should be considered. If the
hypoglycaemia event was severe or recurrent, or if
the patient voices concerns then a review is
indicated.

77. Recommendations
• Please DO NOT omit the next insulin injection
or start variable rate intravenous insulin
infusion to ‘stabilise’ blood glucose. If unsure of
subsequent diabetes treatment, discuss with the
diabetes team/ DISN e.g. it may be safe to omit a
meal time bolus dose of rapid acting insulin if
the patient is declining food and has taken their
usual basal insulin.

78. Recommendations
• Medical team (or DISN if referred) to consider
reducing the dose of insulin prior to the time of
previous hypoglycaemia events. This is to prevent
further hypoglycaemia episodes occurring.
• Please DO NOT treat isolated spikes of
hyperglycaemia with ‘stat’ doses of rapid acting
insulin. Instead maintain regular capillary blood
glucose monitoring and adjust normal insulin
regimen only if a particular pattern emerges.

79. References
• 2018 Clinical Practice Guidelines,
Hypoglycemia, Chapter 14, Diabetes
Canada,Jean-François Yale MD etal
• Joint British Diabetes Society 2018 guideline on
Hospital management of hypoglycaemia in
diabetes mellitus,
• Davidson's principles and practice of medicine,
21st Edition, Chapter 21, pages 812-815