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?

http://www.medicinenet.com/script/main/art.asp?articlekey=392&page=1#toca

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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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?

Hypoglycemia

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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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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?

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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.

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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.

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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

Hypoglycemia

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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)

Hypoglycemia

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Nocturnal Hypoglycemia

Hypoglycemia

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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.

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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


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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.

Hypoglycemia

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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.

Hypoglycemia

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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

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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.

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-Prevention

Self-monitoring of blood glucose (SMBG)

Keeping some sugar or sweet handy

Teach patient/care-giver

Medical alert identification

Glucagon Emergency kit.

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Hypoglycemia

Prevention Strategies

Continuous Glucose Monitoring

Alarms to alert user/family of pending lows

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

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



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]



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

http://www.childrenwithdiabetes.com/gifs/products/glucagonkitredopen.jpg

http://www.childrenwithdiabetes.com/gifs/products/glucagonkitredopen.jpg



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]



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

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 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.

Hypoglycemia

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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

Ueda2016 workshop - hypoglycemia1 -lobna el toony

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