HIPOGLICEMIA

Physiologic Re sponse s to Decrea sing Plasma Glucose Concentrations Glycemic Threshold, mmol/L (mg/dL) 4.4-4.7 (80-85) 3.6-3.9 (65-70) 3.6-3.9 (65-70) 3.6-3.9 (65-70) 2.8-3.1 (50-55) Role in the Prevention or Correction of Hypoglycemia (Glucose Counterregulation) Primary glucose regulatory factor/ first defense against hypoglycemia Primary glucose counterregulatory factor Involved, critical when glucagon is deficient Involved, not critical

Response Insulin Glucagon Epinephrine Cortisol and growth hormone Symptoms

Physiologic Effects Ra (Rd) Ra Ra, Rd Ra, Rd Exogenous glucose

Prompt behavioral defense (food ingestion) (Compromises behavioral defense) Cognition 2.8 ( 50) NOTE: R a, rate of glucose appearance, glucose production by the liver and kidneys; Rd, Rate of glucose disappearanc glucose utilization by insulin-sensitive tissues such as skeletal muscle, and by the central nervous system (where glucoregulatory hormones have no direct effect on glucose utilization).

HIPOGLICEMIA
COMPLICATIE METABOLICA ACUTA IN

DZ

( tratat )

ALTE SITUATII

hG POSTPRANDIALA (REACTIVA) (ALIMENTARA)

hG INTERPRANDIALA (DE STARVARE) (DE FOAME)

Causes of Hypoglycemia

Drugs Especially insulin, sulfonylureas, ethanol Sometimes pentamidine, quinine Rarely salicylates, sulfonamides, and others Endogenous hyperinsulinism Insulinoma Other cell disorders Secretagogue (sulfonylurea) Autoimmune (autoantibodies to insulin, insulin receptor, cell?) Ectopic insulin secretion Critical illnesses Hepatic, renal, or cardiac failure Sepsis Starvation and inanition Endocrine deficiencies Cortisol, growth hormone Glucagon and epinephrine (type 1 diabetes) Non--cell tumors Fibrosarcoma, mesothelioma, rhabdomyosarcoma, liposarcoma, other sarcomas Hepatoma, adrenocortical tumors, carcinoid Leukemia, lymphoma, melanoma, teratoma Disorders of infancy or childhood Transient intolerance of fasting Infants of diabetic mothers (hyperinsulinism) Persistent hyperinsulinemic hypoglycemia of infancy Inherited enzyme defects Postprandial Reactive (after gastric surgery) Ethanol-induced Autonomic symptoms without true hypoglycemia Factitious Insulin, sulfonylureas

DEFINITIA SI DIAGNOSTICUL HIPOGLICEMIEI

HIPOGLICEMIE = nivele plasmatice ale glucozei : < 2,5 - 2,8 mmol/L ( 45 - 50 mg/dL) DIAGNOSTIC = TRIADA WHIPPLE 1). Concentratii plasmatice ale glicemiei

2). Simptomatologie caracteristica prezenta

3). Disparitia simptomatologiei odata cu corectarea glicemiei

SIMPTOMATOLOGIA SINDROAMELOR

HIPOGLICEMICE

SIMPTOME DE NEUROGLICOPENIE

SIMPTOME NEUROGENE (SN AUTONOM)

SIMPTOMATOLOGIA SINDROAMELOR HIPOGLICEMICE I SIMPTOME DE NEUROGLICOPENIE

- deprivarea SNC de glucoza

- modificari de comportament
- confuzie - fatigabilitate exitus

- convulsii
- pierderi de cunostinta

SIMPTOMATOLOGIA SINDROAMELOR HIPOGLICEMICE II

SIMPTOME NEUROGENE (SN AUTONOM)

- raspunsul, reactia SNV (autonom) la hipoglicemie

A). ADRENERGICE Mediate de : - palpitatii - NE eliberata din - tremor neuronii postggl. S - anxietate
- E eliberata din MSR

B). COLINERGICE Mediate de : - hiperhidroza - fibre nn. - foame colinergice S - parestezii

SIMPTOMATOLOGIA SINDROAMELOR

HIPOGLICEMICE
- Pts. cu DZ invata sa recunoasca simptomele
- Recunoasterea simptomatologiei rara in alte cauze de hG
- Simptomele mai pronuntate la crize iterative

DEFINITIA SI DIAGNOSTICUL HIPOGLICEMIEI

HIPOGLICEMIE = nivele plasmatice ale glucozei : < 2,5 - 2,8 mmol/L ( 45 - 50 mg/dL) DIAGNOSTIC = TRADA WHIPPLE 1). Concentratii plasmatice ale glicemiei

2). Simptomatologie caracteristica prezenta

3). Disparitia simptomatologiei odata cu corectarea glicemiei

DIAGNOSTIC CONCLUDENT
- o valoare a glicemiei ( < 2,5 - 2,8 mmol/L / < 45 - 50 mg/dL), - inregistrata in cursul unui episod cu simptomatologie caracteristica hG, - mai ales daca, odata cu corectarea glicemiei, - o valoare N a G in lipsa simptomatologia se amelioreaza sau dispare - FPG

simptomatologiei caracteristice NU EXCLUDE DIAGNOSTICUL

- valori ale FPG - sageata hiperglicemica < 100 mg/dL, cu revenire rapida

- OGTT curba de tip plat (ATENTIE !!! 5% din indivizii N)

- alte teste !!!

SEMIOLOGIA HIPOGLICEMIEI
- paloare - diaforeza
- tahicardie

- TA
- modificari de comportament / constienta (neuroglicopenice) - deficite neurologice tranzitorii de focar

CAUZE ALE SINDROAMELOR HIPOGLICEMICE

hG din DZ

hG POSTPRANDIALA (REACTIVA)

hG DE STARVARE (FOAME)

DZ 1

hG din DZ

- pts. la care se incearca un control glicemic near-normal cateva episoade/sapt. (simptomatice / asimptomatice)

- glicemia < 2,8 mmol/L (50 mg/dL) - 10% din timp

- 25% din pts. sufera un episod de hG severa (dizabilitate, convulsii, coma) / an recuperare completa deficiente cognitive persistente

rar : defecte neurologice permanente

- 2 - 4% din decesele asociate DZ hG

- teama de hG morbiditate psihosociala

hG din DZ
DZ 2
- rar, episoade tranzitorii insulinonecesitanti

sulfonilureice (T1/2 )
repaglinide

- sulfonilureice ( T1/2 ) - clorpropamid ocazional, episoade de hG severa (24 - 36h)

- gliburid

FACTORI DE RISC IN APARITIA hG DIN DZ

EXCESUL DE INSULINA
- I / ADO : - doza excesiva - timing inadecvat

(DCCT)

- produs inadecvat - influx de G exogena : - postul alimentar nocturn

- mese sarite - utilizare de G (efort fizic ) - sensibilitatii la I - TI / - noaptea / - dupa efort fizic / / - greutate / fitness - productiei de G endogena - ingestia de alcool - Cl insulina - insuficienta renala

INSUFICIENTA SN AUTONOM ASOCIATA hG

- raspuns contrareglator fiziologic si comportamental inadecvat in hG indusa de excesul de I
2 componente

Raspuns contrareglator hormonal

generarii de G
Lipsa de avertizare a hG - hypoglycemia unawareness

impiedica raspunsuri comportamentale adecvate alimentatia

GLICOSTAT CONTRAREGLATOR INADECVAT

- raspunsul contrareglator hormonal e alterat fundamental la toti pts. cu DZ 1 cert (absenta peptidului C) pe masura ce pts. devin I-deficienti (luni/ani) nivelele circulante de I / glicemie functie pasiva dep. de I exogena administrata Pierderea 1-ului mecanism de aparare Glicemia I in hG raspunsul glucagonului la G - cauza ??? / - deficitul cel. cel. - anomalie functionala / NU deficit absolut raspunsul la alti stimului = pastrat Pierderea celui de-al 2lea mecanism de aparare in hG

GLICOSTAT CONTRAREGLATOR INADECVAT

raspunsului E la G - anomalie de prag - e rezultatul unui episod recent de hG in antecedente + - componenta anatomica aditionala - pts. cu neuropatie vegetativa (autonoma) DZ Pierderea celui de-al 3-lea mecanism de aparare in hG

eveniment FP critic
- pts. cu deficit Glucagon + E episoade severe de hG de 25 x > f.d. pts. cu deficit Glucagon, dar raspuns E intact

LIPSA DE AVERTIZARE A hG - HYPOGLYCEMIA ANAWARENESS

pierderea simptomelor de avertizare induse de hG alerteaza individul cu privire la iminenta instalarii unei crize comportament adecvat (mananca)

1-ma manifestare de hG = neuroglicopenia

prea tarziu pentru prevenirea crizei

asociata cu episoade frecv. de hG severa

HYPOGLYCEMIA ANAWARENESS

RASPUNSULUI CONTRAREGLATOR AL E

- reversibile dupa cel putin 2 saptamani de evitare scrupuloasa a hG

- pragul de G - revine la valori mai

hG REACTIVA (POSTPRANDIALA)
- autolimitata
copii cu defecte enzimatice (intoleranta la F, galactozemie)

post chirurgie gastrica (hG alimentara)

administrarea unui inhibitor de -glicozidaza idiopatica diagnostic !!! - auto-diagnosticarea (G postprandial tardiv) digestia glucidelor

- nu OGTT !!! (5% din pts. N, asimptomatici au G < 2,4 mmol/L = = 43 mg/dL / 100 g. glucoza p.o.) - Testul pranzului standard documentarea triadei Whipple - hG iterative cauze ??? sensibilitate la raspunsul autonom postprandial N