1、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-regulation:I. Hormones :
2、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 Gl
3、ucagon: 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 hyperglycemiaAcetyl Choline diminishes HGP .
4、 Substrates:Glucose Auto regulation is independent of hormonal or neuroregulator mechanisms. Non-esterfied FA diminish glucose utilization and increase glucose production.,Sympathetic and parasympathetic,Autonomic , neuroglycopenic and neuroendocrine responses to hypoglycemia,THE PHYSIOLOGICAL RESPO
5、NSES TO HYPOGLYCEMIAI. 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- Homeostati
6、c effects,Mean glycemic thresholds for different responses to hypoglycemia,THE GLYCEMIC THRESHOLDS ( in nondiab) 1.The earliest response to lowered glucoseis 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. Sympt
7、oms of Hypoglycemia start (at 54 mg)6. Cognitive dysfunction develop ( at 48 mg ) -,The CNS Cognitive Dysfunction in HypoglycemiaIt 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
8、 visual stimuli, hand eye coordination - Recovery from it takes usually 40-90 min after normoglycemia is restored.,Peripheral Hemodynamic Changes in hypoglycemia:- Increased Heart rate.- Increased pulse p (lowered diast. p).- Increased myocard. contraction.- Icreased card. output.- ECG: flat or inve
9、rted T , and long QT interv(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
10、 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
11、 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 Ins
12、ulin or strong oral ( e,g. glibenclamide ) * Pts with angina or cerebro-vasc dis.* Pts on B-Blockers,Hypoglycemic UnawarenessDefinition : 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 Unawaren
13、essElevation 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 metic
14、ulous 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 preventio
15、n 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 monitori
16、ng 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
17、 times/day ! For a 24 H profileDuring initiation of intensive treatment , in pregnancy .etcA Modified Concise Profile by ” once/day over a week “ monitoringSat : overnight morning fastSun : 2H pp (brkfst)Mon : before lunchTues : 2H pp after lunchWed : before supperThrs : 2H pp after supperFriday : b
18、efore retiring to bedAny 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 Diabetes Frequency ? Controversial. With Good control : Just daily Fasting test may be suf
19、ficient 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 mgPP 100-180 mgBed time 100-140 mg,It is important to”ke
20、ep records”with SMBSTo monitor the impact of diet , exercise and changes in treatmentBut 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 )
21、 induces cerebral infarction:. with irreversible changes in the centreand 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 Hyperglycemi
22、a 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,
