hypoglycemia

1
Hypoglycemia

• 
  Mahtab Niroomand M.D.
• Shaheed Beheshti university of medical scienes

2
Agenda

• Definition
• Pathophysiology
• Prevalence
• Prevention
• Treatment

3

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4
Definition

• All episodes of an abnormally low plasma glucose
  concentration that expose the individual to
  potential harm
• A single threshold value for plasma glucose
  concentration that defines hypoglycemia in
  diabetes cannot be assigned because there are
  varying threshold for symptoms

5
Introduction

• Hypoglycemia is the most common endocrine
  medical emergency.
• Hypoglycemia is a clinical syndrome due to
  underproduction and or over utilization of
  glucose .

6
Pathophysiology

• Metabolic
  state
• 50 140 mg/ dl
• 
  G.H
• Insulin
  Cortisol
• 
  Cathecholamines
• 
  Glucagon

Liver
Fat cells
7

• Glucose is unique fuel for brain neurons
• Irreversible brain damage

Hypoglycemia
8
GI absorption
Glucose sources
Gluconeogenesis
Glycogenolysis
9
Fed state

• Liver
  glucose
• production
• 
  
• 
  Peripheral uptake
• 
  Peripheral
• 
  catabolism
• Liver uptake
• of nutrients

Insulin
Meal
10
Fasting state
Peripheral uptake Lipolysis - proteolysis
Insulin
Glucose production
Liver gluconeogenesis
Liver gluconeogenesis
11

• Defense against hypoglycemia
• B.S lt 80 Insulin
• lt 65 Glucagon
• Epinephrine
  
• G.H - Cortisol
• lt 48 Glu.auto regulation
• lt 40 Lethargy
  
• lt 30 Coma, Convulsion
• lt 20 Permanent damage
• lt 10 Death

Neuradrenergic
Neuroglycopenic
12
RESPONSE TO HYPOGLYCEMIA IN NORMAL SUBJECT

• Normal subject
• Ability to suppress insulin release
• Increase counter-regulatory hormones

13
Response to hypoglycemia in Diabetic patient

• Protective response to hypoglycemia impaired
  in many diabetic patient
• Insulin release cannot turn off
• Effectiveness of counter-regulatory reduce

14
IMPAIRMANT OF COUNTERREGULATORY RESPONSES IN
DIABETIC PATIENT

• Glucagon response to hypoglycemia markedly
  impaired first few years Normal at onset
  of Diabetes
• Patient with glucagon secretion defect
  dependent to epinephrine protection which may
  impaired due to autonomous neuropathy.

15
HYPOGLYCEMIA-ASSOCIATED AUTONOMIC FAILURE

• (1) Reduced counter regulatory hormone responses,
  which result in impaired glucose generation
• (2) Hypoglycemia unawareness, which precludes
  appropriate behavioral responses, such as eating.

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Hypoglycemia unawareness is reversible and
require more than 2 weeks avoidance of
hypoglycemia.
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Hypoglycemia-Associated Autonomic Failure(HAAF)

• Reduced counterregulatory hormone responses,
  which result in impaired glucose generation
• Hypoglycemia unawareness, which precludes
  appropriate behavioral responses, such as eating

20
TIDMAbsolute insulin deficiency
Insulin -
Glucagon -
Insulin therapy
Hypoglycemia
Hypoglycemia
defective glucose unawareness
counter regulation
Autonomic Response
Symptoms
Epinephrine
21
Pathophysiology of glucose counter-regulation

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Etiology
23
Etiology in adults

• 1. Fasting ( more than 5 hours P.P )

2. Postprandial (Less than 5 hours P.P)
24
Fasting hypoglycemia

• a. Underproduction
• Alcoholism
• Organ failure
• Diffuse hepatic failure
• Uremia
• Endocrine deficiency
• G.H
• Glucocorticoid
• Catecholamines
• Glucagon
• Hypothyroidism
• Drugs
• Inanition

• b. Over utilization
• Prolong exercise
• Sever sepsis
• Mesenchymal tumors
• Hepatoma - Sarcoma
• Lymphoma - Carcinoma
• Hyperinsulinism
• Drugs
• Autoimmune insulin syn.
• Insulinoma
• Insulin receptor Ab.

25
2. Postprandial (Less than 5 hours P.P)
G.I surgery (alimentary) Inborn error of
metabolism Galactosemia
Fructose intolerance
Glycogen storage dis. Fructose
1,6 diphosphatase def. Autoimmun insulin
syn. Functional (idiopathic)
Insulinoma (rarely) Prediabetes

• 2. Postprandial (Less than 5 hours P.P)
• G.I surgery (alimentary)
• Inborn error of metabolism
• Galactosemia
• Fructose intolerance
• Glycogen storage dis.
• Fructose 1,6 diphosphatase def.
• Autoimmun insulin syn.
• Functional (idiopathic)
• Insulinoma (rarely)
• Prediabetes

26

• Drugs are the most common cause of hypoglycemia
• Insulin
• S.U
• Alcohol
• Sulfonamides
• Salicylates
• Quinine
• Pentamidine
• Beta blockers

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HYPOGLYCEMIA IN DIABETES
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HYPOGLYCEMIA IN DIABETES

• Never occurs in patients on diet and exercise .
• Rare occurs a glucosidase inhibitors,
  biguanides and thiazolidinediones.
• exceptions elderly
• chronically ill
  patients
• prolonged fasting.
• More frequent occurs on s.urea and especially
  insulin

29
HYPOGLYCEMIA IN DIABETES

• Insulin (or oral agent) doses are excessive, ill
  timed, or of the wrong type
• 2) Influx of exogenous glucose is reduced (e.g.,
  during an overnight fast or following missed
  meals or snacks)
• 3) Insulin-independent glucose utilization is
  increased (e.g., during exercise)
• 4) Insulin sensitivity is increased (e.g., with
  effective intensive therapy, in the middle of the
  night, late after exercise, or with increased
  fitness or weight loss)
• 5) Endogenous glucose production is reduced
  (e.g., following alcohol ingestion)
• 6) Insulin clearance is reduced (e.g., in renal
  failure).

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• Clinical Manifestation

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Clinical manifestation

• 1. Neuroadrenergic ( B.S lt 55 - 60 )
• Sweating
• Hunger
• Tremor
• Tingling
• Palpitation
• Anxiety
• Hypertension

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• 2. Neuroglycopenia ( B.S lt 45 - 50 )
• Nonspecific
• Headach - restlessness -
  aggressiveness - bizarre
• behavior - weakness
• Focal sign
• Monoplegia - babinski - paresthesia -
  diplopia -
• trismus - vision loss
• Global sign
• Stupor - convulsion - flaccidity -
  hypothermia -
• decerebrate rigidity - coma

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Symptoms thresholds

• The level of glucose that produces symptoms of
  hypoglycemia varies from person to person.

34

• Diagnosis

35
Classification
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Harm of Clinically significant hypoglycemia

• Falling
• Motor vehicle accidents and other injueries
• Increased risk of dementia (older adults)

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Diagnosis

• 1. Pseudohypoglycemia
• a. Lab.error
• b.Over utilization
• Leukemoid reaction - Leukemia
• Hemolytic crisis - Polycytemia
  Vera
• c. Incorrect method for analysis
• Lipemic serum

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• Definition
• Hypoglycemia is threshold dependent
• B.S less than 45 - 50 mg/dl with
  symptoms
• recovery with treatment.
• ( Whipple triad )

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Differential Diagnosis

• T.I.A
• Epilepsy
• Orthostatic hypotension
• Arrhythmia

40

• Treatment

41
Treatment

• Urgent Treatment necessary.
• When possible sample for documentation of
  plasma glucose should be obtained prior to
  treatment
• glucose administration need not delay until
  the result for initial sample report.

42
Treatment ( emergency )

• 1. Conscious patient
• Ingestion of 5-20 gr. Soft drink or
  sugar
• 2. Unconscious patient
• a) Bolus
• I.V 0.5 - 1
  g/kg of hypertonic glucose
• b) maintenance
• 5 - 10 g/h of
  glucose infusion.
• c) Glucagon
• 0.5 - 1 mg
  I.v - I.m - S.c ( repeat )
• 3. Post hypoglycemic coma
• Hydrocortison
  100 mg /t.I.d
• 20 Mannitol
  200 cc/20 min

43
Treatment(emergency)

• For treatment of BG lt70 mg/dl in a patient who is
  alert and able to eat and drink, administer 1520
  g of rapid-acting carbohydrate such asa
  one1530 g tube glucose gel or (4 g) glucose
  tabs
• (preferred for patients with end stage renal
  disease).
• 46 ounces orange or apple juice.
• 6 ounces regular sugar sweetened soda.

44
Treatment(emergency)

• For treatment of BG lt70 mg/dl in an alert and
  awake patient who is NPO or unable to swallow,
  administer 20 ml dextrose 50 solution iv and
  start iv dextrose 5 in water at 100 ml/h.

45
Treatment (emergency)

• For treatment of BG lt70mg/dl in a patient with an
  altered level of consciousness, administer 25 ml
  dextrose 50 (1/2 amp) and start iv dextrose 5
  in water at 100 ml/h.
• In a patient with an altered level of
  consciousness and no available iv access, give
  glucagon 1 mg im. Limit, two times.
• Recheck BG and repeat treatment every 15 min
  until glucose level is at least 80 mg/dl

46
Treatment (emergency)

• hypoglycemic patient cause by regular insulin
  excess-nutritional deficit or alcohol can be
  stabilized and discharged.
• hypoglycemia caused by intermediate or long
  acting insulin, First generation or second
  generation sulfonylurea at risk for prolong
  hypoglycemia

47
ADA Recommendation

• Individuals at risk for hypoglycemia should be
  asked about symptomatic and asymptomatic
  hypoglycemia at each encounter

48
ADA Recommendation

• Glucose (1520 g) is the preferred treatment for
  the conscious individual with hypoglycemia
  (glucose alert
• value of lt70 mg/dL), although any form of
  carbohydrate that contains glucose may be used.
• Fifteen minutes after treatment, if SMBG shows
  continued hypoglycemia, the treatment should be
  repeated.

49
ADA Recommendation

• Once SMBG returns to normal, the individual
  should consume a meal or snack to prevent
  recurrence of hypoglycemia

50
ADA Recommendation

• Glucagon should be prescribed for all individuals
  at increased risk of clinically
• significant hypoglycemia, defined as blood
  glucose ,54 mg/dL,so it is available should it be
  needed.
• Caregivers, school personnel,or family members of
  these individuals should know where it is and
  when and how to administer it.
• Glucagon administration is not limited to health
  care professionals

51
ADA Recommendation

• Hypoglycemia unawareness or one or more episodes
  of severe hypoglycemia should trigger
  reevaluation of the treatment regimen. E

52
ADA Recommendation

• Insulin-treated patients with hypoglycemia
  unawareness or an episode of clinically
  significant hypoglycemia should be advised to
  raise their glycemic targets to strictly avoid
  hypoglycemia for at least several weeks in order
  to partially reverse hypoglycemia unawareness and
  reduce risk of future episodes. A

53
ADA Recommendation

• Ongoing assessment of cognitive function is
  suggested with increased vigilance for
  hypoglycemia by the clinician, patient, and
  caregivers if low cognition or declining
  cognition is found. B

54
Prevention
55

• Patient education
• Close observation and control
• SMBG
• Sick day monitoring

56

• Case study

57
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61

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62

• Lab data
• CBC nl
• Na 146
• K 6
• BUN 120
• Cr 3

63

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64

• Poor intake
• Prerenal azotemia
• Metformine

65

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66

• Long duration of DM.
• Hypoglycemia unawareness
• ß blocker usage

67
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• Admission for at least 72 hours
• Serum DW5 100 cc / h
• saline for hydration

68
Thank you
69
Diagnosis

• 1. Overnight F.B.S
• 2. 72 hours fasting test
• Admit and discontinue all nonessential
  medication.
• Patient may consume calorie and caffeine free
  liquids and should ambulate.
• Baseline glucose - Insulin - G.H - (Glucagon -
  Cortisol).
• Check B.S every 6 hours (B.S gt60) then every 1
  hour.
• The fast is ended at 72 hrs. or earlier if the
  patient has a B.S lt45 with neuroglicopenic
  symptoms and check B.S - Insulin - G.H -
  Proinsulin - C.Peptid - Glucagon - Cortisol - S.U.

70

• 2. Reactive or alimentary
• Omit simple sugar and alcohol.
• Frequent small high protein - low
  C.H.O. meal
• Fiber
• Drug
• Anticholinergic drugs Atropin
• 
  Propantheline
• A- glucosidase inh.
• 
  Acarbose - Miglitol

71
Etiologic management

• 1. Fasting
• Tumors Surgery
• Autoimmune Glucocorticoid -
  Plasmapheresis
• Insulinoma
• Surgery
• Drug
• Diazoxide
• Dilantin
• Calcium
  blockers
• Octerotide
• 
  Chemotherapy

72

• B.S lt 45 mg/dl
  Insulinlt6 uU/m with symptoms
  Autoimmune
• 
  Tumors
• Insulin gt6uU/ml
  Endocrine
• 
  def.
• 
  Organ failure..
• lt 200 pmol/L
  gt 200pmol/L
• Autoimmune
• Insulin inj.
• 
  Iatrogenic Insulinoma
  

Hyperinsulinism
C.peptide
_
S.U

73

• 
  Clinical suspicion
• Medication Fasting
  P.P
• Systemic illness
• Sepsis - Malignancy
  mixed meal
• 
  --
• B.S gt 45 B.S lt 45
  motility Idiopathatic
• exclude with symptom
  study Exclude
• 
  Insulin
• 
  C.Peptide
• 
  S.U

72 hr test
74

• 2. Clinical data
• Fasting or p.p
• With or without activity
• First attack or recurrent
• D.H
• F.H of diabetes
• Signs and symptoms
• Reversible or irreversible
• Neurologic deficit
• Weight loss or weight gain
• PH.Exam.

75

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76
??? 72?????

• ?? ?? 12???? ?? ???? ??? ????? ???????? ?? .
• ???????? ??????
• B.S 32 mg / dl
• Insulin 21 uU / ml
• C. Peptide 860 pmol / L
• Proinsulin 19 Pmol / L
• S.U Negative
• ?? ????? ?????????? ??????? ??????????? ???????
  ?????.

77
Fasting hypoglycemia

• a. Underproduction
• Alcoholism
• Organ failure
• Diffuse hepatic failure
• Uremia
• Endocrine deficiency
• G.H
• Glucocorticoid
• Catecholamines
• Glucagon
• Drugs

• b. Over utilization
• Prolong exercise
• Malnutrition
• Sever sepsis
• Mesenchymal tumors
• Hepatoma - Sarcoma
• Lymphoma - Carcinoma
• Hyperinsulinism
• Drugs
• Autoimmune insulin syn.
• Insulinoma
• Insulin receptor Ab.

78

• 2. Postprandial (Less than 5 hours P.P)
• G.I surgery (alimentary)
• Inborn error of metabolism
• Galactosemia
• Fructose intolerance
• Glycogen storage dis.
• Fructose 1,6 diphosphatase def.
• Autoimmun insulin syn.
• Functional (idiopathic)
• Insulinoma (rarely)
• Prediabetes

79
Classification

• 1- Ill appearance
• Mesenchymal tumors
• Organ failure
• Sepsis
• T.P.N
• Dialysis
• 2 - Healthy appearance
• Drugs
• Hyperinsulinism
• Functional
• Endocrinopathies...