Sn xut v tn sinh glucose trn bnh nhn SRAT falciparum th noBV Bo Lc BV Ch Ry & AMC H Lan

Vn H ng huyt: 8% trn bnh nhn SRAT; 12-30% trn bnh nhi; thng gp trn thai phSRAT (SM): Mt t thiu ng nhtDavis et al.: GP tng 50% (18 SM, ch 4 CM) H ng huyt GP tng ?

Glucose concentrationGlucose production(GLY + GNG)Glucose consumption

C ch gy h ng huyt/SRTng insuline do dng quinine?Tng nhu cu glucose?Cn kit glycogen &/ thng tn kh nng tn sinh glucose (gluconeogenesis: GNG)?

GLUCOSE PRODUCTION (GP)O GP BNG ISOTOPE [6,6-2H2]GLUCOSE

Glucose C6H12O6 CHO l HCOH lHOCH l HCOH l HCOH l CH2OH

[6,6-2H2]glucose CHO l HCOH l HOCH l HCOH l HCOH l HCH l OH

Rate of disappearance?Rd ?FConstant concentration

Isotopic equilibrium: Ra?Rd ?FRa?= (Enrichment at plateau)GCMS: Gas chromography-Mass spectrometry

GNG: 2H2O methodH- O- H2H2ODeuterium

Gluconeogenesis CHO lHCOH l CH2OPGlycerolDihydroxyacetone-3-PGlyceraldehyde-3-PLactateAlaninepyruvatephosphoenolpyruvateoxaloacetateH2O

GNG + Glycogenolysis = GP CHO lHCOH l CH2OPCHOHlCOlCH2OPglycogenDihydroxyacetone-3-P+ CH2OP l CO lHOCH l HCOH l HCOH l CH2OPG-6-P2Glucose5/2 CHO l HCOH lHOCH l HCOH l HCOH l CH2OPfructo-1,6-bisPH2O

024688.40[6,6-2H2]gluc.PIV[6,6-2H2]gluc.bolus5 1g 2H2O/kg

Vn SRAT (SM): Mt t thiu ng nht.Davis et al.: GP tng 50% (18 SM, ch 4 CM)Cerebral malaria-SRAT th no.

Kt qu: Lm sng Bnh nhn (7) Chng (6) p ------------------------------------------------------------------------- Tui 32 5 34 4 n.s Gii (nam/n) 6/1 5/1 BMI 19.3 0.7 21.6 0.9 n.s Thn nhit (0C) 38.2 0.6 36.6 0.2 n.s P. falcip.(per l) 99849 60742 (-)

Lm sng (tt) Bnh nhn Chng p -------------------------------------------------------------------------- Glasgow 6 1 15 0.001

Haemoglobin (mmol/l) 7.8 0.6 9.5 0.4 0.06

Serum AST (U/l) 183 65 54 5 n.s

Serum ALT (U/l) 123 28 53 9 n.s

Creatinine (mol/l) 124 18 106 9 n.s____________________________________________

Xt nghim Bnh nhn Chng p------------------------------------------------------- Alanine (mol/l) 286 29 286 34 n.s

Lactate(mmol/l) 2.55 0.82 0.72 0.06 0.003

Glycerol (mol/) 88 6 101 10 n.s

FFAs (mmol/l) 0.8 0.06 0.9 0.07 n.s

TNF- (pg/ml) 6.6 2 2 0.005

Xt nghim (tt) Bnh nhn Chng p -------------------------------------------------------- Insulin (pmol/l) 49 11 34 6 n.s

Glucagon (ng/l) 132 33 59 4 n.s

Cortisol (nmol/l) 1080 163 188 18 0.003

Epinephrine (nmol/l) 0.27 0.13 0.14 0.04 n.s

Norepinephrine(nmol/l) 4.8 3.5 1 0.1 n.s

Glucose metabolism

Increased glucose clearance in CMGlucose clearance (thanh thi glucose) tng 41%: 4.1 vs. 2.9 ml/kg/min (Bnh et al.: 42%; Davis et al.: 72%)(Clearance rate = Rd/concentration l s ml huyt tng b ly ht glucose trong 1 pht)(Rd = Ra (GP) + I (exogenous infusion))

Glucose concentrationat 20h of fasting

Glucose metabolism in CM

Glucose production(GNG)Glucose consumption42%

SR cng nng GP & GNG cng tng

Ti sao?

Hormone?Cortisol kch thch GNG.CM: 1080 vs 188 nmol/l 100% GNG Uncomplicated Pf: 530 nmol/l

Khng th

Cytokines?TNF-Alpha & IL-6 kch thch GP in vivo.TNF-Alpha: CM: 6.6 vs.

Tin cht (precursors)?Alanine & glycerol: n.s.Lactate: 2.55 vs. 0.72 c th?

Khng th

Kt lunSRAT P. falcip. th no kch thch tn to glucose rt nhiu so vi SR thng.Tuy mc tiu th glucose c tng nhng t hn nn dn n tng ng huyt.Cc yu t cytokines, cortisol, glucagon hay tin cht to glucose u khng phi l nguyn nhn ca s gia tng GNG. Bn thn bnh SR P.falcip khng phi l nguyn nhn trc tip gy h ng huyt. (QJM 2001;94: 709-15)

Thanks for attention

CM: 27.4; UM: 16.4; Pf/preg: 16.7; Preg: 12.4; controls: 13.8 mol/kg/min. CM vs. healthy controls: p=0.004; Uncomplicated malaria vs. healthy controls: p=0.02; Pf/pregnancy vs. healthy pregnancy: ns.CM vs. healthy controls: p=0.004; Uncomplicated malaria vs. healthy controls: p=0.02; Pf/pregnancy vs. healthy pregnancy: ns.GP:100% in CM, p=0.003; 19% in non-severe: p=0.01-0.003; 35% in preg: p=0.002 (vs healthy preg.)