Sn xut v tn sinh

glucose trn bnh nhn

SRAT falciparum th no

BV Bo Lc BV Ch Ry & AMC H Lan

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

Glucose concentration

Glucose production
(GLY + GNG)

Glucose consumption

C ch gy h ng huyt/SR
Tng 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 [6,62
H2]GLUCOSE

Glucose C6H12O6

CHO
l
HCOH
l
HOCH
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?
F

Constant
concentration

Rd ?

Isotopic equilibrium: Ra?

F
Ra?

Rd ?

F tracer

Ep
Ra tracee

(Enrichment at plateau)

GCMS: Gas chromography-Mass spectrometry

GNG: H2O method

2

H- O- H
H2O

Deuterium

Gluconeogenesis
Glycerol
Lactate
Alanine

Dihydroxyacetone-3-P

H 2O

pyruvate

CHO
l
HCOH
l

CH2OP
Glyceraldehyde-3-P
oxaloacetate

phosphoenolpyruvate

GNG + Glycogenolysis = GP
Dihydroxyacetone-3-P

CHOH
l
CO
l
CH2OP

CHO
l
HCOH
l
CH2OP

glycogen

CH2OP
CH O
l
l
HCOH
CO
l
l
HOCH H2O HOCH
l
l
HCOH
HCOH
l
l
HCOH
HCOH
l
l
CH2OP
CH2OP
fructo-1,6-bisP

G-6-P

5/2

Glucose

[6,6-2H2]gluc.bolus
5 1g 2H2O/kg
[6,6-2H2]gluc.PIV

8.40

V n
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
61
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

FFAs (mmol/l)

0.8 0.06

TNF- (pg/ml)

6.6 2

101 10

n.s

0.9 0.07

n.s

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

Cortisol (nmol/l)

1080 163

188 18

Epinephrine (nmol/l) 0.27 0.13 0.14 0.04

Norepinephrine(nmol/l) 4.8 3.5

1 0.1

n.s
0.003
n.s
n.s

Glucose metabolism
Glucose production
(mol/kg/min)

30
25

Glycogenolysis

20
15

27.41.2

5.70.4

10
5
0

Gluconeogenesis

8.10.2
(58%)

malaria

controls

Increased glucose clearance in

CM
Glucose

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 concentration
G lucose concentration (m m ol/l)

at 20h of fasting
7.2
6.9
6.6
6.3
6.0
5.7
5.4
5.1
4.8
4.5
4.2
3.9
3.6
3.3
3.0

n=7
P=0.004

42%
n=6

Glucose metabolism in CM
42%
Glucose pr
oduction
(GNG)

Glucose c
onsumptio
n

SR cng nng GP & GNG cng tng

Glucose production
(mol/kg/min)

30
25

Gluconeogenesis

20

Glycogenolysis

15
10
5
0

27.41.2
5.70.4

87%
8.10.2
(58%)

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. <2 pg/ml
(chng).

Khng th

Tin cht (precursors)?

Alanine & glycerol: n.s.

Lactate: 2.55 vs. 0.72

Khng th

c th?

Kt lun
SRAT

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