A FREE

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• A FREE
• NAVIGATION THROUGH THE WAVES OF HYPER AND
  HYPOGLYCEMIA
• By
• Prof Morsi Arab
• University of Alexandria

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• Glucose is the predominant fuel for the Brain.
• Because the brain cannot synthesize or store
  glucose ,it has to be provided from the
  circulation

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• Factors involved in Gluco-regulation
• I. Hormones Insulin, Glucagon,
  
  
  
  
  
  
  
  
• adrenalin, Growth H. ,Cortisol .
• II. Neuro transmitters Sympathetic
• Parasypathetic., Autonomic neuropeptides
• III. Substrates Glucose, FF Acids.

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• The Glucoregulatory Hormones (main effects)
• Insulin decrease Hepatic Glucose
  production (HGP ) - and
  increase glucose
  utilization
• Glucagon stimulates HGP
• Adrenalin stimulate HGP and decrease Gluc
  utilization .
• Growth H. and Cortisol diminish Glucose
  utilization and increase glucose production .

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Sympathetic and parasympathetic

• Gluco regulation (cont )
• Sympathetic and parasympathetic activation
• Noradrenalin induces hyperglycemia
• Acetyl Choline diminishes HGP .
• Substrates
• Glucose Auto regulation is independent of
  hormonal or neuroregulator mechanisms.
  Non-esterfied FA diminish glucose utilization
  and increase glucose production.

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Autonomic , neuroglycopenic and neuroendocrine
responses to hypoglycemia
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• THE PHYSIOLOGICAL RESPONSES TO HYPOGLYCEMIA
• I. CNS
• - cognitive dysfunction
• - neurophysiological changes (EEG)
• II. Peripheral ( Extra CNS ) Effects
• - in response to autonomic ( sympathetic and
  parasympathetic
• activation) and release of catecholamines
• - Hemodynamic changes
• - Regional changes of blood flow
• - Tremors
• - Homeostatic effects

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Mean glycemic thresholds for different responses
to hypoglycemia
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• THE GLYCEMIC THRESHOLDS ( in nondiab)
• 1.The earliest response to lowered glucose
• is a diminished insulin secretion at 82
  mg)
• 2. Release of counter regulatory H (at 66mg)
• 3. Growth H (at 66 mg)
• 4. Cortisol (at 57 mg)
• 5. Symptoms of Hypoglycemia start (at 54 mg)
• 6. Cognitive dysfunction develop ( at 48 mg )
• -------------------------------------------------

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• The CNS Cognitive Dysfunction in Hypoglycemia
• It starts at a threshold of 3 m mol/L (54mg )
• but with marked individual variations.
• Affects selective tasks requiring attention,
  memory, rapid decision taking, analysis of visual
  stimuli, hand eye coordination
• - Recovery from it takes usually 40-90 min after
  normoglycemia is restored.

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• Peripheral Hemodynamic Changes in hypoglycemia
• - Increased Heart rate.
• - Increased pulse p (lowered diast. p).
• - Increased myocard. contraction.
• - Icreased card. output.
• - ECG flat or inverted T , and long
• QT interv
• (with fall of Serum Potassium ).

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• Regional changes in Blood flow in Hypoglycemia
• - Cerebral BF is 20 increased (esp. in frontal
  and parietal areas )
• Renal BF Glum filtration diminished (20)
• Increased Splanchnic BF
• - increased Hepatic BF
• - markedly diminished Splenic BF
• Markedly increased Muscle BF
• Cutaneous BF Early increased (flushing and sense
  of warmth) before sweating response ,, then
  diminished (pallor)

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• Other Changes in hypoglycemia
• Tremors (a cardinal sympathetic feature)
• Homeostatic Changes
• Increased WBC activation, viscosity,
  
  
  
• fibrinolysis and platelet
  activation
• Increased Free Radical activity.

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• In the DCCT Study severe hypoglycemic episodes
  occurred in 50 during sleep , and in 1/3rd
  during day but without warning.

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• Who are the special groups at high risk because
  of hypoglycemia ( esp. if without warning or
  monitoring )
• The Elderly, esp. on Insulin or
  strong oral ( e,g.
  glibenclamide )
• Pts with angina or cerebro-vasc dis.
• Pts on B-Blockers

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• Hypoglycemic Unawareness
• Definition loss of the known warning autonomic
  symptoms which were present before.
• Occurs in 50 of very long standing Type 1 DM and
  in 25 of all DM .

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• Hypoglycemic Unawareness
• Elevation of the Hypoglycemic threshold means
  that more profound hypoglycemia is needed to
  induce awareness

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• Hypoglycemic Unawareness (cont. )
• Patients with history of hypoglycemic
  unawareness have 6-folds risk of getting severe
  hypoglycemia

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• After development of Hypoglycemic unawareness
  , the meticulous avoidance of hypoglycemic
  episodes leads to restoration of awareness .

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• Self Monitoring of Blood Glucose (SMBG)
• It is an essential tool in management, unless
  unaffordable or unavailable
• 1961 first suggested ---1970s technical
  revolution supported by studies relating
  glycemic control to prevention of complications .

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• SMBG
• Advantage over Glycated HB it shows the
  excursions , not just an average.
• In strict glycemic control management proper
  pt. selection is essential
• ( motivated - accepting frequent
  
  
  performance of SMBG sufficiently educated
  skilled staff assistance )

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• Frequency of monitoring in SMBG
• Individualized
• More frequent with insulin Trt -
  unstable DM (brittle) - pts at high risk
  .
• In Tight Glycemic Control
• 4 times or more ( once /wk overnight) .
  at any time if hypoglyc. is suspected .
  before performing critical activities
• 
  (e.g. driving)
  
  

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• The More Frequent Monitoring
• 7- 9 times/day ! For a 24 H profile
• During initiation of intensive treatment , in
  pregnancy .etc
• A Modified Concise Profile by once/day over a
  week monitoring
• Sat overnight morning fast
• Sun 2H pp (brkfst)
• Mon before lunch
• Tues 2H pp after lunch
• Wed before supper
• Thrs 2H pp
  after supper
• Friday
  before retiring to bed
• Any day when hypoglyc episode is
  suspected
• (especially at early
  morning hours )
• Any day to monitor the effect of
  exercise , change of treatment , or
• dietary irregularities

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• SMBG IN TYPE 2 Diabetes
• Frequency ? Controversial.
• With Good control Just daily Fasting test
  may be sufficient to detect onset of disruption
  of control.
• Otherwise, (at initiation of additional oral
  agent, increasing doses or initiating insulin
  therapy ) more frequent monitoring is needed ,
  to see a day profile.
• Reasonable targets
• Fasting 80-120 mg
• PP 100-180 mg
• Bed time 100-140 mg

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• It is important tokeep recordswith SMBS
• To monitor the impact of diet , exercise and
  changes in treatment
• But too much data may induce
  
  Data Overload ,
• transfer to Graphic Display .

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• The Future ?
• A Continuous Monitoring System
• Gluco-watch

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• STRESS HYPERGLYCEMIA IN STROKE
• Cerebral ischemia ( bld flow lt 15ml /100g /min )
  induces cerebral infarction.
  
• with irreversible changes in the centre
• and reversible changes surrounding it.
• The Hyperglycemia is usually mild (lt 200 mg)
• but it enhances the isch. cerebral damage
• There is no known threshold for the hyperglyc.
  
  level which enhances this risk.

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• Associated Hyperglycemia with stroke leads to
• 1. slower recovery of the reversible changes.
• 2. increased capil. permeability --.increases the
  risk of hemorrhagic transformation.
• 3. increases by 5 folds the risk in
  thrombolytic therapy ( by fatal or nonfatal
  hemorrhage .

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• Clinical trials are not yet conclusive but
  probably control of hyperglycemia affects the
  safety and efficacy of stroke interventions

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Alexandrie Palais du Montazah
Thank You