Yu, Yan – Diabetic Hypoglycemia – Clinical Findings – FINAL.pptx
? Epinephrine(Released within seconds as [glucose] falls further) Growth hormone, ? Cortisol (if hypoglycemia persists for minutes)Glucagon should ? when [glucose] falls. But here, glucagon release is inhibited by 1) diabetic auto-immune destruction of Alpha cells & 2) the high insulin.43210Plasma Glucose concentration (mmol/L)Liver should ? glycogenolysis & gluconeogenesisPeripheral vaso-constrictionPlasma [glucose] stays lowActivation of sympathetic (adrenergic) receptors across body, triggering Neurogenic symptomsPlasma [glucose] ?Excess subcutaneous insulin or insulin-secretagogue ?? [insulin] in the bloodOver time: [insulin] in the DM patient depends only on how much was injected or how much secretagogue was consumed; not on the body’s physiological state.[Insulin] stays high in excessively-treated DM patientsPlasma [glucose] normally ?, but…High insulin transports plasma glucose into cells!In pts with existing diabetic autonomic neuropathy, epi-nephrine secretion will already be ?Brain does not get enough glucose, ? neuron function ? Neuroglycopenic symptomsTx: glucose intake![Glucose] returns to normalIf no glucose intake:Hypoglycemia-unawareness: No autonomic Sx felt so hypoglycemia not treated early ? pts present later on with more severe hypoglycemia and neuroglycopenic sxBrain cells kept chronically euglycemic due to GLUT1 receptor over-expression (despite rest of body being hypoglycemic)With many hypoglycemic events over time:Brain feels no need to ? glucose, so it ? autonomic epinephrine secretion!This is the normal sequence of hormone responses to ?ing plasma glucose levels.But this normal hormonal response will be blunted over time if there is 1) continued hypoglycemia dampening the sympathetic nervous system, and 2) long-standing diabetic neuropathy! (To be explained later in this flow chart)Abbreviations: [ ] = concentrationTx = TreatmentDM = Diabetes mellitusDiabetic Hypoglycemia: Pathogenesis and Clinical FindingsConfusionCan’t concentrateWeaknessSlurred speech? coordination (staggering, etc)SeizuresComa, deathAdrenergic symptoms (epinephrine-mediated):Anxiety, irritability, trembling, pallor (skin vasoconstriction), palpitations, ? systolic BP, tachycardia Cholinergic symptoms(Acetylcholine-mediated):Sweating, hunger, tingling, blurry visionNote: In pts w/out DM, endogenous insulin secretion normally stops when blood [glucose] drops to <4mmol/LAuthor: Yan YuReviewers: Peter Vetere, Gillian Goobie, Hanan Bassyouni** MD at time of publicationLegend:Published June 14, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsMany hypoglycemic events over time blunt epinephrine secretion further.Hypoglycemia unawareness can be reversedIf pt stays hypoglycemia-free for >6 weeks, brain restores its ability to detect low glucose levels? peripheral glucose delivery and uptake (saving more glucose for the brain)Lack of glucagon effect reinforces hypoglycemia
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