A FREE

NAVIGATION THROUGH THE WAVES OF HYPER AND

HYPOGLYCEMIA

By

Prof Morsi Arab

University of Alexandria

Glucose is the predominant fuel for the Brain.

Because the brain cannot synthesize or store glucose ,it has to be provided from the circulation

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.

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 .

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 .

Autonomic , neuroglycopenic and neuroendocrine

responses to hypoglycemia

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

Mean glycemic thresholds for different responses to hypoglycemia

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.

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 ).

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)

Other Changes in hypoglycemia :

Tremors (a cardinal sympathetic feature)

Homeostatic Changes:

Increased : WBC activation, viscosity,

fibrinolysis and platelet activation

Increased Free Radical activity.

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

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

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 .

Hypoglycemic Unawareness

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

Hypoglycemic Unawareness (cont. )

Patients with history of hypoglycemic unawareness have 6-folds risk of getting severe hypoglycemia

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

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 .

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 )

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)

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

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

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 “.

The Future ?

A Continuous Monitoring System

“ Gluco-watch “

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.

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 .

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

Alexandrie – Palais du Montazah

Thank You