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Transcript of A FREE NAVIGATION THROUGH THE WAVES OF HYPER AND HYPOGLYCEMIA By Prof Morsi Arab University of...
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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-regulationFactors 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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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 inPeripheral Hemodynamic Changes in hypoglycemia:hypoglycemia:
- Increased - Increased Heart rateHeart rate.. - Increased - Increased pulse ppulse p (lowered diast. p). (lowered diast. p). - Increased - Increased myocardmyocard. contraction.. contraction. - Icreased - Icreased card. outputcard. output.. - - ECGECG: flat or inverted T , and long : flat or inverted T , and long QT intervQT interv (with fall of Serum Potassium ).(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 DiabetesFrequency ? 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 to”keep records”with 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 < 15ml /100g /min ) induces cerebral infarction:.
with irreversible changes in the centre
and reversible changes surrounding it.
* The Hyperglycemia is usually mild (< 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