All about hypoglycaemia in patients with diabetes

1. HYPOGLYCEMIA AMONG
DIABETIC PATIENTS
Dr. Ahmed Elshebiny, MD
Assistant Professor of Internal Medicine,
Diabetes and Endocrinology, KFU, KSA
Lecturer, Internal Medicine, Menoufia university , Egypt
Former Clinical Research Fellow, Joslin Diabetes Center, USA

2. HYPOGLYCEMIA
AMONG
PATIENTS WITH
DIABETES MELLITUS
It increases both morbidity and mortality.
6% of deaths in younger people with type 1
diabetes
found “ Dead in Bed ”
limiting factor in the glycaemic management
of diabetes.
Recurrent hypoglycemia in Diabetes can lead
to hypoglycemia unawareness.
It is preferable to prevent rather than to treat
hypoglycemia
requiring the practice of hypoglycemia risk
reduction.

3. THE FIRST PART: UNDERSTANDING HYPOGLYCEMIA
1. What are the physiological mechanisms that protect
against low blood sugar?
2. How are these mechanisms “impaired” in hypoglycemia?
3. What are the clinical presentations of hypoglycemia?
4. What is the prevalence and impact of hypoglycemic
attacks among patients with diabetes?
5. What are the causes and risk factors for “iatrogenic
hypoglycemia” in patients with DM ?

4. THE SECOND PART: PREVENTION AND MANAGEMENT OF
HYPOGLYCEMIC ATTACKS
1. What is the clinical importance of hypoglycemia unawareness and how it
could be reversed?
2. What are the guidelines for the management of acute attacks in different
settings e.g., at home, or in hospital and how can we prevent further attacks
of hypoglycemia?
3. How can we benefit from new technology in prevention and management
of hypo attacks?
4. What are the updates in pharmacological therapy of hypoglycemia?

5. UNDERSTANDING HYPOGLYCEMIA IN PATIENTS WITH DM
Hypoglycemia Definition, Clinical presentations, Severity
Epidemiology
Impact and complications
Pathophysiology
Risk factors

6. DEFINITION AND CLASSIFICATIONS
Hypoglycemia • Blood glucose level below 3.9 mmol/L( 70mg /dl)
Mechanism
• Imbalance between glucose supply, utilization and
current insulin levels
Symptoms • Symptomatic or a symptomatic
Severity • Mild , Moderate and Severe attacks
Classifications • Diabetic, Non-diabetic / Fasting, postprandial
(Oxford Handbook of Endocrinology and Diabetes: John Wass, Catharine Owen, 3rd edition, 2014)

7. EPIDEMIOLOGY
Type 1 DM
• An average of 2 attacks /week of
symptomatic hypos.
• One attack/ year of severe disabling attack.
• Responsible for 6-10% of deaths in type 1
DM
Type 2 DM
• Less frequent
• More prevalent
• More with insulin or with insulin
secretagogues
• Less with metformin, thiazolidinediones,
SGLT 2inhibitors, alpha glucosidase
inhibitors, DDP 4 inhibitors and GLP I
receptor agonists
(Davis, HA et al : Hypoglycemia during therapy of Diabetes, Endotext , 2021)

8. IMPACT OF HYPOGLYCEMIA

9. COMPLICATIONS OF HYPOGLYCEMIA
Increased
Mortality
Arrythmia Worsen CAD
Procoagulant
state
Possible
greater risk of
dementia

10. GLUCOSE HOMEOSTASIS
(Hawkes CP, et al, Novel Preparations of Glucagon for the Prevention and Treatment of Hypoglycemia. Curr
Diab Rep. 2019)

11. Physiological and behavioral defenses against hypoglycemia in humans
(Davis, HA et al : Hypoglycemia during therapy of Diabetes, Endotext , 2021)

12. PATHOPHYSIOLOGY
Therapeutic
hyperinsulinemia
Defective
counter-
regulation
HAAF
Increased
sensitivity to
insulin
Reduced
glucose intake

13. MANIFESTATIONS OF HYPOGLYCEMIA
Autonomic
Sweating
Hunger
Palpitations
Anxiety
Trembling
Neuroglycopenic
Drowsiness, lethargy, confusion
Behavioral changes
Visual symptoms
Focal neurological abnormalities, Seizures or coma
(Menoufia University, Endocrinology Unit, Essentials of Diabetes and Endocrinology, 2018
)

14. A REGIONAL STUDY BY KFU INTERNS
The attacks had classic symptoms in only 54.4%
Only 52.2% of patients consulted with their physicians when
they had the hypo events
Hypoglycemia in a year was reported in 22.5% of patients
Hypo attacks were more frequent in insulin treated type 1
DM(82.5%) compared to type 2 DM(12.5 %)
Study population
400 diabetic patients both type 1 and type 2 DM

15. RISK FACTORS FOR HYPOGLYCEMIA IN
DM
Conventional
• Excess medications, ill-timed or wrong
type
• Decreased exogenous glucose delivery
• Increased insulin sensitivity
• Decreased endogenous glucose
production
• Decreased insulin clearance
• Diabetic autonomic neuropathy
Risk factors indicative of HAAF
• The degree of insulin deficiency and
duration of diabetes
• History of severe hypoglycemia
• Hypoglycemia unawareness
• Aggressive glycemic therapy
(Davis, HA et al : Hypoglycemia during therapy of Diabetes, Endotext , 2021)

16. PREVENTION AND MANAGEMENT OF HYPOGLYCEMIC ATTACKS
Hypoglycemia
in Diabetic
patients
Hypoglycemia unawareness
Guidelines for management of acute attacks outside the hospital
In-hospital management of hypoglycemia
Prevention of further attacks
Special groups and situations
New technology
Updates of pharmacological management

17. Clinical case
Clinical data
A 42-year-old man was brought to the emergency department in a coma. A bedside glucose test
revealed capillary glucose of 2.5 mmol/ L. He received IV 20% glucose with subsequent dramatic
improvement in his consciousness. The patient has had type 1 diabetes mellitus treated by
subcutaneous insulin injections for the past 22 years. He is on three-time insulin glulisine before
meals (6 IU before each meal) and a two-time insulin detemir (10 IU Twice daily). He reported
frequent low blood sugar readings when he tests his sugar at home. This happens despite not
having any significant symptoms of hypoglycemia. His blood pressure is 120/80 mmHg and
clinical examination revealed no significant abnormalities.

18. Clinical case (cont.)
Laboratory data
Normal liver kidney and thyroid function, Normal electrolytes , HbA1c is :
60.7 mmol/mol (7.7%) (Less than 48 mmol/mol)
(< 6.5 %)
Question?
What is the most appropriate next-step decision regarding his insulin
regimen?

19. HYPOGLYCEMIA UNAWARENESS
Recurrent frequent
hypoglycemia over time
can lead to (HAAF).
Sympathoadrenal processes no
longer trigger symptoms of
hypoglycemia,
Strict avoidance of
hypoglycemia by adjusting
glucose goals to higher targets
on a short-term basis (2 - 4
weeks) can allow the symptoms
of hypoglycemia to return
(Kreider, K.E., Pereira, K. and Padilla, B.I., 2017. Practical approaches to diagnosing, treating and preventing hypoglycemia in diabetes. Diabetes Therapy, 8(6), pp.1427-1435.)
Hypoglycemia unawareness
Scores

20. MANAGEMENT OF ACUTE ATTACKS IN ADULTS “ OUTSIDE THE
HOSPITAL”
1. Recognize autonomic or neuroglycopenic symptoms
2. Confirm if possible (blood glucose <4.0 mmol/L)
3. Treat with “fast sugar” (simple carbohydrate) (15 g) to relieve symptoms
4. Retest in 15 minutes to ensure the BG >4.0 mmol/L and retreat (see above) if
needed
5. Eat usual snack or meal due at that time of day or a snack with 15 g carbohydrate
plus protein

21. EXAMPLES OF 15 G CARBOHYDRATE

22. MANAGEMENT OF ACUTE ATTACKS IN ADULTS “ OUTSIDE THE
HOSPITAL” (CONT.)
Able to swallow
• (simple carbohydrate) (15 g) to
relieve symptoms
• Repeat after 15 min if needed
• Eat the usual next meal or a
snack of 15 g carbs plus protein
Severe attack with inability to
swallow
• Injection of 1 mg Glucagon by
relative
• Call emergency

23. Algorithm for the Management of Hypoglycaemia in Adults with Diabetes in Hospital
Hypoglycaemia is a serious condition and should be treated as an emergency regardless of level of consciousness
Hypoglycaemia is defined as blood glucose of <4.0mmol/L (if not <4.0mmol/L but symptomatic give a small carbohydrate snack for symptom relief)
See full guideline “The Hospital Management of Hypoglycaemia in Adults with Diabetes Mellitus” at www.diabetes.org.uk/joint-british-diabetes-society
Mild Moderate Severe
Adults who are conscious, orientated
and able to swallow
Check ABCDE, stop IV insulin (if running)
Give 15-20g of quick acting carbohydrate,
such as 5-7 Dextrosol® tablets or 4-5 Lift
GlucoTabs® or 150-200ml pure fruit juice**
Test blood glucose level after 10-15 minutes
and if still less than 4.0mmol/L repeat
treatment as above up to 3 times. If still
hypoglycaemic, call doctor and consider IV
dextrose or IM glucagon as per “severe”
pathway
Patient conscious and able to swallow, but
confused, disorientated or aggressive
Patient unconscious/fitting or very
aggressive or nil by mouth (NBM)
Check ABCDE, stop IV insulin (if running)
If capable and cooperative, treat as for mild
hypoglycaemia. If not capable and cooperative
but can swallow give 2 tubes of 40% glucose gel
(squeezed into mouth between teeth and gums).
Test blood glucose level after 10-15 minutes and
if still less than 4.0mmol/L repeat as above up to
3 times. If still hypoglycaemic, call doctor and
consider IV dextrose or IM glucagon as per
“severe” pathway
Check ABCDE, stop IV insulin, request
medical support urgently.
Give 100ml 20% dextrose or 200ml 10%
dextrose over 15 minutes
If IV access not possible use 1mg
Glucagon IM*
Recheck glucose after 10 minutes and if
still less than 4.0mmol/L, repeat
treatment as above
JBDS-IP The Hospital managements of hypoglycemia in adults with diabetes mellitus, 2021

24. Algorithm for the Management of Hypoglycaemia in Adults with Diabetes in Hospital
Mild Moderate Severe
Adults who are conscious, orientated
and able to swallow
Patient conscious and able to swallow, but
confused, disorientated or aggressive
Patient unconscious/fitting or very
aggressive or nil by mouth (NBM)
Check glucose after 10-15 minutes. Once blood glucose level are now > 4.0mmol/L or
above: Give 20g of long acting carbohydrate e.g. two biscuits, slice of bread, 200-
300ml milk or next carbohydrate containing meal. Give 40g if IM glucagon has been
used. For patients with enteral feeding tube give 20g quick acting carbohydrate via
enteral tube e.g. 50-70ml Ensure® Plus juice or Fortijuce®.
If glucose now 4.0mmol/L or above,
follow up treatment as described on
the left.
If NBM, once glucose >4.0mmol/L
give 10% glucose infusion at
100ml/hr until no longer NBM or
reviewed by doctor
DO NOT omit subsequent insulin doses. Continue regular capillary blood
glucose monitoring for 24-48 hours. Review insulin and/or oral
hypoglycaemic doses. If previously on IV insulin, would generally
consider restarting insulin once blood glucose >4.0 but may require
review of regimen. Give hypoglycaemia education and refer to inpatient
diabetes team.
*Glucagon may take up to 15 minutes to work
and may be ineffective in treating hypoglycaemia
in undernourished patients, in severe liver
disease, sulfonylurea induced hypoglycaemia and
in repeated hypoglycaemia.
First step management as previously mentioned

25. MINISTRY OF HEALTH
GUIDELINES FOR IN-
HOSPITAL
HYPOGLYCEMIA

26. PREVENTION OF RECURRENCE OF
HYPOGLYCEMIA
 Acknowledge the problem
 Consider the conventional risk factors
 Consider the risk factors indicative of HAAF
 Relevant principles of glycemic management
 Individualized glycemic goals
 Structured patient education

27. SPECIAL CIRCUMSTANCES
Exercise
Nocturnal hypoglycemia
Elderly
Pregnant
Drivers

28. HYPOGLYCEMIA WITH EXERCISE
 Interspersing intense exercise
 Adding carbohydrate ingestion
 Cutting insulin dose

29. ROLE OF NEW TECHNOLOGY
• Can predict
hypos
CGM
• Improves
hypoglycemia
CSII
• Reduce hypos
while maintain
good glycemic
control
SAP
• In problematic
hypoglycemia
that did not
respond to
other measures
Islet
transplantation
• Usually with a
kidney
transplant
Pancreas
transplantation
(Kreider, K.E., Pereira, K. and Padilla, B.I., 2017. Practical approaches to diagnosing, treating and preventing hypoglycemia in diabetes. Diabetes Therapy, 8(6), pp.1427-1435.)

30. NEW GLUCAGON PREPARATIONS

31. MESSAGE
TO
PATIENTS
WITH
DIABETES
Know the signs and
symptoms of a low blood
glucose level.
Carry a source of fast
acting carbohydrate
Wear diabetes
identification
Talk with your diabetes
health-care team about
prevention and
emergency treatment of a
severe low blood glucose
(2018 Diabetes Canada CPG – Chapter 14.
Hypoglycemia)

32. TAKE HOME
MESSAGE
Hypoglycemia increases the
morbidity and mortality and
impairs the quality of life
Always ask the patient in
every contact about hypo
attacks and implement
strategies to improve patients'
education.
Apply hypoglycemia risk
reduction strategies