ueda2016 workshop - hypoglycemia1 -lobna el toony
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Hypoglycemia
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Hypoglycemia In Diabetes
Lobna F El toonyProfessor of Internal Medicine
Head of Internal Medicine Department
Head of Diabetes &Endocrinology Unit
Assuit University
Hypoglycemia
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Hypoglycemia
“The Greates t L imiting Factor In Diabetes
Management”
Hypoglycemia
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Hypoglycemia
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Hypoglycemia… is common
Common ; up to 30- 60% in DM patients
Type 1 > Type 2 …But !
Intensive DM control (lower HbA1c…?)
Elderly
Duration of disease
Asymptomatic in 50% + …Unawareness !
Nocturnal …very common !
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What is hypoglycemia?
Hypoglycemia
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Hypoglycemia
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Hypoglycemia
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HypoglycemiaDefinition (Cont.)
In addition, a BG that falls > 100 mg/dL in one hour may be accompanied by symptoms of hypoglycemia.
For example, a BG level of 120 mg/dL may
elicit signs and symptoms of hypoglycemia if
the BG has fallen from 220 mg/dL an hourearlier.
Hypoglycemia
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1. Development of neurogenic or neuroglycopenic symptoms
2. Low blood glucose (<70mg/dl ) if on insulin or
secretagogue)
3. Response to carbohydrate load
Neurogenic
(autonomic)
Neuroglycopenic
Trembling Difficulty Concentrating
Palpitations Confusion
Sweating Weakness
Anxiety Drowsiness
Hunger Vision Changes
Nausea Difficulty Speaking
Dizziness
Definition of Hypoglycemia
Hypoglycemia
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Copyright © 2015 AACE. May not be reprinted in any form without express written permission from AACE.
Symptoms of Hypoglycemia
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ClassificationBlood Glucose
Level (mg/dL)
Typical Signs and Symptoms
Mild hypoglycemia ~60-70• Neurogenic: palpitations, tremor, hunger,
sweating, anxiety, paresthesia
Moderate hypoglycemia ~50-60• Neuroglycopenic: behavioral changes, emotional
lability, difficulty thinking, confusion
Severe hypoglycemia <50*
• Severe confusion, unconsciousness, seizure, coma, death
• Requires help from another individual
*Severe hypoglycemia symptoms should be treated regardless of blood glucose level.
Q6. How should hypoglycemia be managed?
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Why Hypoglycemia
Prevention And Treatment
Are Important?
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Hypoglycemia
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Copyright © 2015 AACE. May not be reprinted in any form without express written permission from AACE.
Consequences of Hypoglycemia CV events
Cardiac autonomic neuropathy Cardiac ischemia Angina Fatal arrhythmia
Cognitive, psychological changes (eg, confusion, irritability)
Accidents Falls Recurrent hypoglycemia and hypoglycemia unawareness Refractory diabetes Dementia (elderly)
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Q6. How should hypoglycemia be managed?
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Hypoglycemia
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Physical Morbidity Of
Hypoglycemia
Decreased
performance
E rrors in judgment
Hypoglycemia
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Physical Morbidity Of Hypoglycemia
Accident Risk
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How The Body Protect Its elf
From Hypoglycemia?
Hypoglycemia
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Hypoglycemia
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What Happen In Diabetes ?
Hypoglycemia
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Hypoglycemic Symptoms
Autonomic s ymptoms :
After few years of diabetes duration (2-5 years).
Glucagon secretion is impaired in type 1 (irreversible).
Epinephrine secretion becomes the primary mechanism
for raising low blood glucose levels.
Over the course of type 1 diabetes (10-12 Ys)-, epinephrine
res pons e to hypoglycemia becomes diminis hed or
delayed resulting in:
↓Hypoglycemic symptom awareness (Hypoglycemia
Unawarenes s )
↑↑Severe hypoglycemic episodes
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Vicious circle where recurrent hypoglycemia during intensive treatment of type 1
diabetes causes hypoglycemia unawareness and impaired counterregulation,
ultimately increasing the risk for severe hypoglycemia.
Hypoglycemia
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Recognize R is k Factors for Severe Hypoglycemia
Risk factors in Type 1 DM
patients
Risk factors in Type 2 DM
patients
Adolescence Elderly
Children unable to detect and/or
treat mild hypoglycemia
Poor health literacy, Food
insecurity
A1C <6.0% Increased A1C
Long duration of diabetes Duration of insulin therapy
Prior episode of severe
hypoglycemia
Severe cognitive impairment
Hypoglycemia unawareness Renal impairment
Autonomic neuropathy Neuropathy
Hypoglycemia
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Hypoglycemia
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Hypoglycemia In Type 2 Diabetes
Hypoglycemia
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Factors That R is k of Hypoglycemia in Type 2 DM
Advanced age.
Poor nutrition.
Hepatic disease.
Renal Disease.
Hypothyroidism and/or adrenal insufficiency.
Postpartum bleeding can lead to pituitary damage.
Hypoglycemia
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Hypoglycemia
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Setting for hypoglycemia
Identification of the precipitating factors
is important to prevent future events
Mismatch Between Insulin ,
Food & Exercise
Hypoglycemia
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Hypoglycemia
Medications Common with
Diabetics who are treated with
Insulin releasing pills (sulfonylureas, Meglitinides, or Nateglinide)
Insulin
Very unlikely with Lifestyle changes (TLC) only
Using alone medications like :
( ex: Metformin ,DPP4I, GLP-1 + ,SGLT2 -)
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High risk of hypoglycemia is obtained from commonly used combination SU/Met
CI=confidence interval; Glyb=glyburide; Met=metformin; repag=repaglinide; SU=sulfonylurea; TZD=thiazolidinediones.
Bolen S, et al. Ann Intern Med. 2007;147:386–399
Met vs Met + TZD
Weighted absolute risk difference
0.20.150.150.50
3 (1557)
5 (1495)
6 (2238)
8 (2026)
3 (1028)
5 (1921)
8 (1948)
9 (1987)
Studies
(participated)
0.00 (-0.01 to 0.01)
0.02 (-0.02 to 0.05)
0.03 (0.00 to 0.05)
0.04 (0.0 to 0.09)
0.08 (0.00 to 0.16)
0.09 (0.03 to 0.15)
0.11 (0.07 to 0.14)
0.14 (0.07 to 0.21)
Pooled effect
(95% CI)
SU vs repag
Glyb vs other SU
SU vs Met
SU + TZD vs SU
SU vs TZD
SU + Met vs SU
SU + Met vs Met
Drug 1 more harmfulDrug 1 less harmful
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DRUGS CAUS ING HYPOGLYCE MIA
E STABLIS HE D
DRUGS :
DIS ORDE R DRUG
DM Insulin, SU, other secretogogues, metformin, alcohol
Infection Pentamidine, Quinine, Sulphonamides
Arrhythmias Quinidine, dispyramide, cibenzoline
Pain Acetylsalicylic acid
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Hypoglycemia
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Ins ulin
Hypoglycemia
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Hypoglycemia
. Insulin Program Setup (Meal/Bolus)
Blood Sugar Rise After
Eating Carbs
Analog (Humalog or
Novolog taken with
meal)
Regular (taken 30 min.
pre-meal)
NPH / Lente (taken 4
hours prior)
Only rapid analogs work when needed – right after eating!
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Premixed Insulin
2 Peaks
8 am 12 4 pm 8pm 12 4am 8am 12
. . . . . .. .
Coincide with hypoglycemic events
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Conventional Therapy: traditional regimens
50-70% don’t attain target A1c Erratic blood glucose values Requires fixed life style
Danner T et al Diabetes Care (2001)
8 12 16 20 24 4 8
Hypergl
.Hypogl. Hypergl
.
Hypogl.
Premixed Premixed
Hypoglycemia
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Compared to biphasic human insulins
More patient convenience regarding administration
Better pharmacokinetics and pharmacodynamics
Lower incidence of hypoglcemia
8 am 12 4 pm 8pm 12 4am 8am 12
. . . . . .. .
Biphasic insulin analoguesBiphasic Aspart: Aspart + NPAspart (30/70 Novomix)Biphasic Lispro: Lispro + NPLispro (25/75 humalogue mix)
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Nocturnal Hypoglycemia
Hypoglycemia
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Nocturnal Hypoglycemia
Causes:1. Exercise during the previous day.
2. Failure to eat a bedtime snack.
3. Predinner injections of intermediate-acting insulin (NPH, Lente) may peak in action during the night and cause relative hyperinsulinemia overnight.
4. Insulin requirements decrease between midnight and 3 AM.
5. S ignificant increases in physical activity, combined with failure to increase carbohydrate consumption and/orreduce the insulin dose.
6. Concomitant use of sulfa antibiotics (TMP, Septrin, Bactrim) with a sulfonylurea cause profound and refractory hypoglycemia.
Hypoglycemia
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Intermediate acting insulins:
NPH and Lente
Day time Peak Nocturnal Peak
Dawn phenom8 am 12 4 pm 8pm 12 4am 8am
B D
. . . . .Morning
Hyperglycemia
High Insulin
Sensitivity
Hyperglycemia
.
2 Peaks
Nocturnal Hypoglycemia
Hypoglycemia
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Prevention of Nocturnal Hypoglycemia
Do not skip presleep snacks.
Measure presleep blood glucose levels regularly.
Increase the carbohydrate content of the snack.
If daytime physical activity was increased.
Eat additional slowly absorbed carbohydrate snack before bed time.
Move the Predinner NPH or Lente to presleeprather than decreasing the predinner dose.
Reduction in evening regular insulin dose.
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4:00
25
50
75
16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
Pla
sm
a In
su
lin
µU
/ml)
12:008:00
Time
NPH/
Lente
REGREG REGNPH/
Lente
Bas al + Meal-related InsulinNPH/lente + Regular
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4:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
12:008:00
Time
Glargine
Pla
sm
a In
su
lin
Aspart Aspart Aspart
or or or
Lispro Lispro Lispro
Bas al-bolus Treatment Program Rapid-acting & Long-acting Analogs
Lower Incidence of hypoglycemia
Hypoglycemia
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Hypoglycemia
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The use of Subcutaneous glucose
sensors for continuous glucose
monitoring with sophisticated
software may make it possible
to trigger an alarm when
hypoglycemia risk is
detected..
Hypoglycemia Prevention(cont.)
Hypoglycemia
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Setting for hypoglycemiaFood intake
Skipped or delayed meals
Vomiting after meal & meds intake
Mismatch:
Wrong dose or too high a dose of medications
for the amount of food;
Too little carbohydrate
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Snack Or not To snack?
وجبة خفيفةاإلفطار
الغذاءوجبة خفيفة
العشاءوجبة خفيفة
10-15%30–35%25-30% 10%10% 10%
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Snack Or Not To Snack ?
With Twice daily mixture of NPH +R
Use snack at time of inappropriate hyperinsulinemia (10-11 am & at bedtime).
With Multiple Daily Injections (MDI) or Ins ulin Pumps
No need for snacks. They may increase the BG before the next meal.
In adults no need for snacks.
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Physical activity
Hypoglycemia
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Setting for hypoglycemia
Unplanned / Excess exercise
without snack / Rx adjustment
Excessive insulin / OHA doses
Organ Failure Medications
Alcohol use
Identification of the precipitating factors is
important to prevent future events
Hypoglycemia
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When adequate insulin level is present, muscular activity lowers BG during, immediately after and /or several hrs after exercise
This has been attributed to increased insulin levelsoriginating from subcutaneous depots and increased insulin sensitivity by enhancing receptor site binding. Particularly if the patient takes a hot shower after exercising.
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Hypoglycemia Prevention
Strategies
Hypoglycemia
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Hypoglycemia Management
Prevention = Education
Education …Education …Education
Hypoglycemia
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Hypoglycemia-Prevention
Patient education and empowerment
Frequent self-monitoring of blood glucose (SMBG)
Flexible and rational insulin (and other drug)
regimens
Individualized glycemic goals
Professional guidance and support.
Hypoglycemia
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Hypoglycemia
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Hypoglycemia-Prevention
Self-monitoring of blood glucose (SMBG)
Keeping some sugar or sweet handy
Teach patient/care-giver
Medical alert identification
Glucagon Emergency kit.
Hypoglycemia
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Hypoglycemia
Prevention Strategies
Continuous Glucose Monitoring
Alarms to alert user/family of pending lows
Hypoglycemia
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Hypoglycemia
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Hypoglycemia
Prevention Strategies
. Meal/Snack Timing Vs Insulin
Major issue w/a.m. NPH/Lente
Minor issue w/Lantus or Levemir
Not usually an issue with pump use
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Treatment Of Hypoglycemia
Hypoglycemia
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guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca
Copyright © 2013 Canadian Diabetes Association
Recommendation 1
1. Mild to moderate hypoglycemia should be treated
by oral ingestion of 15 g carbohydrate; glucose or
sucrose tablets/solutions are preferable to orange
juice and glucose gels [Grade B, Level 2]
Patients should retest blood sugar in 15 minutes
and retreat with another 15 g of carbohydrates if BG
remains <4.0 mmol/L [Grade D, Consensus]
Hypoglycemia
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15 g of glucose in the form of glucose
tablets
15 mL (3 teaspoons) or 3 packets of sugar
dissolved in water
175 mL (3/4 cup) of juice or regular soft
drink
15 mL (1 tablespoon) of honey
E xamples of 15 g S imple Carbohydrate
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Role of 15 minutes
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca
Copyright © 2013 Canadian Diabetes Association
Recommendation 2
2. Severe hypoglycemia in a conscious person
should be treated by oral ingestion of 20 g of
carbohydrate, preferable as glucose tablets or
equivalent.
Blood sugar should be retested in 15 minutes, and
then retreated with a further 15 g of glucose if BG
remains <4.0 mmol/L [Grade D, Consensus]
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca
Copyright © 2013 Canadian Diabetes Association
3. Severe hypoglycemia in an unconscious
individual:
– No IV access: 1 mg of glucagon should be
administered subcutaneously or intramuscularly.
Caregivers or support persons should call for
emergency services and the episode should be
discussed with the diabetes healthcare team as
soon as possible [Grade D, Consensus]
– With IV access: 10-25 g (20-50 cc of D50W) of
glucose should be given intravenously over 1-3
minutes [Grade D, Consensus]
Recommendation 3
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca
Copyright © 2013 Canadian Diabetes Association
Recommendation 5
5. 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 [Grade D, Consensus].
If a meal is > 1 hour away, a snack (including 15 g
of carbohydrate and protein source) should be
consumed [Grade D, Consensus]
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca
Copyright © 2013 Canadian Diabetes Association
Recommendation 6
6. Patients receiving antihyperglycemic agents that
may cause hypoglycemia should be counseled
about strategies for prevention, recognition and
treatment of hypoglycemia related to driving and
be made aware of provincial driving regulations [Grade D, consensus]
2013
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ADA 2015 - HYPOGLYCEMIA
Hypoglycemia unawareness or one or more episodes of severe hypoglycemia
should trigger reevaluation of the treatment regimen. E
Action:Raise their glycemic targets
to avoid further hypoglycemia for at least several weeks Aiming to partially reverse hypoglycemia unawareness and reduce
risk of future episodes. A
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Take-Home Messages
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Take home mes s ages
The Patient with chronic disease like diabetes has a
very good chance of living a long life, especially if he
has good glycemic control.
Hypoglycemia can occur with very little warning.
The patient should be aware of these.
With good education , matching insulin ,
food and physical activity , most patients will
survive these problems after exclusion of co-
morbid conditions.
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Take home mes s ages
Know the risk factors /setting
Beware of nocturnal , exercise-induced and
unawareness forms
Treat and try to prevent recurrence
Educate your self , your patients and their families
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