Carbohydrate oxidation rates in patients with anorexia nervosa

Carbohydrate Sumihisa

Oxidation

Kubota,

Hajime

Sunao Twenty-one

hospitalized

days and divided period,

whereas

as control

respiratory

glucose-stimulated both AN groups be increased Copyright

I

tance.’

Others

response

of group

refeeding

TOLERANCE

have reported

as group rate

NC. These tends

is commonly

of increased

insulin

rcsis-

increased sensitivity to insureturn

to normal after weight gain.J have been many reports detailing

ments for weight gain in AN.‘-“’

caloric rcquirc-

Some patients

rcquirc

much higher caloric intake than the total estimated basis of basal metabolic rics without

abnormal

requirements behaviors

the mechanism

patients with AN

is unclear.

mine why caloric requirements Stordy et al” reported gain weight more rapidly weight before

their

caloor hu-

of glucose utilization

We have attempted :irc vCable

;I

on the

plus rxpended

such as vomiting

limia. At present,

in

to deter-

in AN.

that previously obese AN patients th:m those who were of normal

illness hegan. In ltddition.

that the expected increase in metabolic

they noted

rate after ;I glucose

meal ~21s lower in previously obese patients thnn in patients carbohydrate

oxidation

ratesI

I’) in AN

patients during :I glucose challenge to better understand the relationships between carbohydrate metabolism. the endocrine system, and body weight gain.“~“’ SUBJECTS

Group

AND

AN-b

indicate

that

body weight

All patients

period.

A third

group

AN-a

showed

compared

with

rapidly

were

group

showed

significant

group

then fed for 10

in some

over the IO-day

of normal virtually

increases

NC. Serum

insulin sensitivity

women the

same

in basal

insulin

and

responses

in both liver and muscle

patients

in may

due to this mechanism.

wmt: caloric Intahe. Patients admitted for fewer th;ln been monitored inclusion

their ideal hotly weight.

program. patient5 with AN wc ohserved hy

video monitor for self-induced vomitin:! and hulimla. Thev C~~-c 1dx) hv evaluating hwlogicxl

and urinr

chloride

parameters. q.

levels. Patients

Wr

have treated many AN

inexplicably intake grwtrr

vomitlnp

OI

were excluded from this \tud\.

patients.

do not gain wright

\rrum amylasr

who \rlf-induced

were bulimic during the test prrlod

In our rsprrwnce.

drsplte

wmt’

an appropriate

caIorIc

than the lotal needed to pam weleht cstimatcd on

the hasis of basal metabolic rrquiremenrs without disturbance

of glucose

plus expended cal~~rie\

utilization.

We thcrrfore

dnGdcd 2 I

AN patients into two groups hased on weight gain. and a third group of IO age-match& diabetes mrllitus than 1”;

)

healthy women wth no fxm~ly hi‘;torv [,I

qetvrd as the control group (NC‘: Tahlc

first group (AN-a)

hody weight over the IO-day ferdinp was comprtsrd

of

wrragc

caloric Intake of AN-a

(42.1 -t 4.0 kcalikg;d:

r:ltlo

pcric,tl. ;tnd the

I I patient\ \bhrj

more than 7.O’C’hody weight during the wmr kcalid

I )_ The

included IO patlcnts who pained very little (Ias

wcond group (AN-h)

gained

interval.

patient< wa\ 1.1(+

t

t-1-1

of ~lucoae to ~;II to protein.

I Y I:J1:6h R). and the IO-day increase in body wright avera@

0.01

e O.Ohkg. The average caloric Intake of AN-h patlcnth w;tb _. ’ I’1_ 154 kcal/d (5X.h 2 1.3 kcalikgid:

ratto of glucor

iOO:hS:XO g). and their body wrights I.755

.YtrhjrcY.\

therapeutic

hasi< hrlore

average weight at thr heginning of the

Irk -+ I .5f~’hrlow

monitored

f 0.I7

METHODS

tn the study. Thrlr

In-our

10 day\ had

for at least IO days on an outpatlrnt

studv period was 30.

The

with no history of obesity. WC measured

NC.

Kobayashi,

little or no body weight

the same

of 50 g of glucose,

results

with some investiga-

’ and all have reported that these abnormalities

Thcrc

during

Nobuyuki T. Aoki

challenge.

(n = 10) gained

responses

to increase

Nozaki,

and Thomas

a 50-g glucose

AN-a

ingestion

oxidation

Takehiro

Nervosa

Company-

nervosa (AN),

the presence

underwent

gain. Group

Following

With Anorexia

Nakagawa,

(n = 11). did gain weight

(NC).

and that

GLUCOSE

tors postulating

AN-b

than those

in AN patients,

found in anorexia

(AN) patients

and carbohydrate

lower

Ishimoto-Goto,

Tetsuya

on weight

(NPRQ)

‘iI>1993 by W. B. Saunders

MPAIRED

lin,’

group, subjects

NPRQ were

based

quotient

Junko

Matsubayashi, nervosa

groups

the second

(n = 10) served nonprotein

anorexia

into two

Tamai,

Rates in Patients

f

10 fat to protcln.

increased by an wera~r ot

I. If)

kg over IO days. The average caloric intake of group NC ~,II\ 2 126 kc;tl/d (2X.9 2 2.S kc;~l!kg/d).

The

reawn tor differ-

enceh In caloric intake and dietary compoGtion hctwecn the twc,

Twenty-one female AN patlent

(age. 21.1) 2 I.5 year.\) trtxtrd

(\N groups was that. as stated prrv~ously. they had hem hohplta-

.is inp;ttlrnts at our hospital from IYXh to IYXY particlpatrd in thia

lrrd

study: on admis.rion. all were severelv emaciated. All patients had

Intake according to their own choler. Groups were not whdividrd

hcrn hospitalized

until after the IO-day feeding period.

for

I to 100dayshrforr

inltiatwn

of the \tudy

for varying prrlods

and hai

Ixcome

adju5tcd 11) ;I cert;lln

permd. Some patients entered the hospital on an rmergencv basic. resulting

in varying durations

at a time when all patients

of testing. This study was performed had stabilized

at approximately

the

the beginning

At Il-hour supine

of the IO-day study

fast. participants position.

prrlod.

alter

voided at 7:00 a~. ;wumtxl

C~ 11- ((1

a rrcumhent

and then ingested SO g of glucose at X:00

Venous blood samples were drawn tor glucose and insulin

\r,t.

mcasurc-

mcnt\ every 30 minutes over the next 3 hour!,. Oxygen consumpticm (co?) and carbon dioxide production measured on a Rrspiromonitor Osaka. Japan) usiny a facr mak: gas pressure.

temperature.

RM300

The

nonprotein

(Minato

,rrspiratory

rupired

;11r wcrs

Medical Sclcnce.

Vo? and CC02 wet-e corrected for

and moisture.

the end of the test for measurement (N).

(~cxt~) in Urine

of urinq

quotient

wa\ collected kit nitrogen

(NPRO)

content

and carhohy-

drw Cc) and lipid (L) oxidation rates were calculated using the following formulas’?: 6 = J.55iic.trl - 3.7 I Go2~ :.N7N: i =L l.h7 928

Metabohsm, Vol42.

No 8 (August), 1993: pp 928.931

CARBOHYDRATE

OXIDATION

RATES IN AN PATIENTS

929

T,able 1. Clinical Data of AN Patients and NC Subjects Weight Gall% Ideal

10 Days

Calmc

Intake

Age

Height

Weight

Body

IV)

(cm)

lkg)

Weight

21.1

157.7

34.79

68.9

-0.01

1,465

42.2

(n = 11)

21.0

155.1

36.19

71.4

t1.16

2.121

58.6

(II

20.9

156.6

49.82

97.5

1,755

35.2

Group

Post-OGTT kcalid

(kg)

-

kcalikg

AN-a

AN-b

(n = 10) AN-b

NC

NC = 10)

AN-a

Abbrevwtion: OGTT, oral glucose tolerance test

(+oz

- ‘Jc 0:)

h.046I). formula” (VU,:

-

l.Y2$I;

‘When NPRQ wax

used

and NPRQ

values were to

= (+cw2

\ - 4.XYti)/(+oz

-

greater than I. the following

calculate

oxidation

rate:

c

=

I.34

- UXN).

All

values

are expressed

variables were compared differences

were

as the

mean

lr

SEM.

using repeated-measures

evaluated

by Tukey’s

Continuous

ANOVA.

studentized

1 -1-Y-~

0

and

30

60

range test.

90

(min)

TIME

where appmpriate. Fig 2. Carbohydrate oxidation rates before and during 50-g oral glucose tolerance tests in AN patients and NC subjects; group factor, P = .0086 (ANOVA). Tukey’s studentized range test: lcP c .05 Y NC; +bP < .05 Y AN-b. (i)--C ) AN-a; (0-O) AN-b; (<:----I?) NC.

RESULTS

NPRQ There was no significant difference between AN-a and NC groups at any time point. In contrast, the NPRQ in the AN-b group was strikingly greater than that in the other two groups
~‘ctrbol~vdr~~t~~ and Lipid Oxidation Hates Befol-e glucohc ingestion, carbohydrate oxidation rates were hl + I.3 mg/min in the NC group. 55 2 12 mgimin in the AN-a group, and 122 ? 13 mg/min in the AN-b group. After glucose ingestion. these rates increased in each group, with the rate in group AN-a being lower than that in the other two groups (Fig 2). Lipid oxidation rates before glucose ingestion were 5 I ? 1.3, I

uI;c,l,,,

l.Zj

5 mg/min in the NC group, 26 2 3 mg,‘min in the AN-a group, and 19 t 6 mgimin in the AN-b group. As expected. the lipid oxidation rate following glucose ingestion decreased in each group (Fig 3).

At 30 minutes, blood glucose levels of AN-a patients were lower than those of group NC: however. no subsequent significant differences were found. Circulating blood glucose levels of the AN-b group were lower than those of the NC group at 0.30, and 90 minutes (Fig 4). In general, circulating insulin levels in the AN-a group were lower than those in the NC group and signiticantly lower in the AN-b group than in the NC group (Fig 5).

AN-b

60 E E

-~ 0

-----1-

50

T ’

_~~__~___.__~

---I----

30

60

90

120

150

160

TIME (min) Fig 1. NPRQ before and during 50-g oral glucose tokr6nC6 t&S in AN patients and NC subjects; group factor, P = .OOOl WJOVN. Tukey’s studentized range test: lcP 4 .05 Y NC; ((I--f>) AN-a; (0-O) AN-b; (I-‘----K’) NC.

0

30

.-

120

90

60 TIME

150

160

(min)

Fig 3. Lipid oxidation rates before and during 50-g oral glucose tolerance tests in AN patients and NC subjects; group factor, P = .OOOl (ANOVA). Tukey’s studentized range test: ‘+’ < .05 Y NC; lbP < .05 Y AN-b. ((:I--I) AN-a; (0-O) AN-b; ((_‘----s.?)NC.

KUBOTA ET AL

930

140, g

130 :

\ E

120

$ 2

110 IOOi

2WI i E

T

/ ,,’ ,,:,r

90 1’ 60

,4 T‘. c *c

: ,-,’

-I

AN-a

NC

p,Y

AN-b

*C

70

b

3’0

i-60

IlO

90

TIME

150

lb0

(min)

Fig 4. Plasma glucose levels before and during 50-g oral glucose tolerance tests in AN patients and NC subjects; group factor, P = .0308 (ANOVA). Tukey’s studentized range test: *‘P < .05 Y NC; lbP < .05 Y AN-b. (c)-G) AN-a; (O-O) AN-b; (O----O) NC.

DISCUSSION

This investigation was performed at a time when weight was increasing in AN-b patients: they gained 1.13 kg (mean) over a lo-day period after the test. The difference between AN patients whose weight increased and patients whose weight remained steady is not clear. The difference in weight gain may have been influenced by other factors in addition to the diffcrcnce in caloric intake. We performed this study to clarify this question, and our results may explain the difl’erence. In this study. the basal NPRQ of AN patients who gained weight (group AN-b) was much higher than that in the other two groups. Thus, measurement of the resting or basal NPRQ may be an excellent predictor of weight gain in patients with AN who are hospitalized in wards without video monitors and in outpatients. '01

30 AN-a

I

NC

20 1

AN-b

IO i

0

30

60

-/

90 TIME

120

150

160

(min)

Fig 5. Plasma insulin levels before and during 50-g oral glucose tolerance tests in AN patients and NC subjects; group factor, P = .0510 (ANOVA). Tukey’s studentized range test: lcP c .05 v NC. (G-G) AN-a; (0-O) AN-b; (O----O) NC.

In contrast. there was no diffcrcnce in NPRQ between AN patients who gained little body weight and the NC group. However, the AN-a group exhibited only a somewhat lower level of glucose oxidation than the control group, even though the AN-a group’s caloric intake in kilocalories per kilogram was greater than that in the NC group. The key observations in this study arc the very high stimulated NPRQ and carbohydrate oxidation rates seen in the AN-b group. According to the formula 3!;: glucose + 4 0, + palmitate + I I C02,“’ the NPRQ value seems to bc much higher than 1.0 in the case of lipogencsis. The data suggest that hepatic glucose processing enzymes (cg, glucokinase and phosphofructokinase) are present in larger amounts in the AN-b group than in AN-a and NC groups: in other words, AN-a patients lack this capacity. These observations may explain why AN patients have a difficult time increasing body weight. We have occasionally found patients with AN who did not gain weight in the course of therapy despite appropriate caloric intake, as have others.5m4 Dempsey ct al” report that the number of cxccss calories required to gain a kilogram of body weight ranges from 5,569 to IS.619 kcalikg with a mean of 9.768 kcalikg, and that the caloric cost of weight gain is variable in AN. This variability may be explained by a difference in hcpatic glucose oxidation capacity.” It has been reported that anaerobic glycolysis in rat liver is dccreascd by prolonged fasting.‘j The NPRQ is lower in AN-a than in AN-b patients, and thcrc may be a lower hepatic glucose oxidation rate in AN-a than in AN-b patients. If this is true, the lower hepatic glucose oxidation rate in AN-a patients may be due to a decrease in hepatic glycolytic enzymatic pathway activity caused by prolonged fasting. The fact that the difference between AN-a and AN-b patients was only caloric intake shows the necessity of increasing caloric intake, especially high-glycemic index foods, to increase the activity of glycolytic enzymes.‘J,25 In the AN-a group, circulating insulin levels were low. and differences in NPRQ and blood glucose levels were not significant compared with those of the NC group. This low level of insulin suggests increased sensitivity to insulin in AN-a patients, as has been previously rcported.J On the other hand, AN-b patients showed a marked increase in the NPRQ and carbohydrate oxidation rate. but with lower levels of insulin than the NC group, ic. they showed cvcn greater insulin sensitivity than AN-a patients. In normal subjects at rest, the increase in qc.o, seen after glucose intake mostly reflects glucose oxidation in the liver.‘h In view of the high NPRQ and carbohydrate oxidation rate values shown by AN-b patients, it is highly likely that glucose was being extensively used for hcpatic lipid synthesis, ie, more dietary glucose was hcing taken up by the liver for lipid synthesis. However. increased muscle glucose uptake secondary to increased insulin sensitivity could also explain the more modest increase in circulatory glucose levels in AN-b patients. The lipid oxidation rate was negative in AN-b patients, and it is likely that lipid synthesis was greater than lipid

CARBOHYDRATE

OXIDATION

RATES IN AN PATIENTS

931

oxidation.” Thus, eating 700 additional calories per day and active lipogenesis may be responsible for the 116-g/d increase of body weight in AN-b patients. In conclusion, this study shows a very high stimulated NPRQ and increased carbohydrate oxidation rate in the AN group who gained weight. and a low carbohydrate

oxidation rate in the group that did not gain weight. These data suggest that there is a significant presence of hepatic glucose-processing enzymes in AN-b patients, and that AN-a patients display a relative lack of these enzymes. These observations may explain why some AN patients have a difficult time increasing body weight.

REFERENCES

1. Crisp AH, Ellis J. Lowy C: Insulin response to a rapid intravenous injection of dextrose in patients with anorexia nervosa and obesity. Postgrad Med J 43:97-102, 1967 2. Zuniga-Guajardo S, Garfinkel PE. Zinman B: Changes in insulin sensitivity and clearance in anorexia nervosa. Metabolism 35:1096-1100.1986 3. MNecklenburg RS, Loriaux DL, Thompson RH, et al: Hypothalamic dlysfunction in patients with anorexia nervosa. Medicine 53:147-159. 1974 4. Scheen AJ, Castillo M, Lefebvre PJ: Insulin sensitivity in anorexia nervosa: A mirror image of obesity? Diabetes Metab Rev 4:681-690. 1988 5. Bessard T, Schutz Y. Jequier E: Energy expenditure and postprandial thermogenesis in obese women before and after weight loss. Am J Clin Nutr 38:680-693, 1983 6. Kaye WH. Gwirtsman HE, Obarzanek E. et al: Caloric intake necessary for weight maintenance in anorexia nervosa: Nonbulimits require greater caloric intake than bulimics. Am J Clin Nutr 441435443, 1986 7. Kaye WH. Gwirtsman HE. Obarzanek E. et al: Relative importance of calorie intake needed to gain weight and level of physical activity in anorexia nervosa. Am J Clin Nutr 47:987-994, 1988 X. Walker J, Roberts SL, Halmi KA, et al: Caloric requirements for weight gain in anorexia nervosa. Am J Clin Nutr 32:1396-1400. 1979 9. Forbes BG, Kreipe RE, Lipinski BA, et al: Body composition changes during recovery from anorexia nervosa: Comparison of two dietary regimens. Am J Clin Nutr 40:1137-l 145. 1984 10. Theodore EW, Madelyn HF. Donna H, et al: Abnormal caloric requirements for weight maintenance in patients with anorexia and bulimia nervosa. Am J Psychiatry 148:1675-1682, 1991 11. Stordy BJ, Marks V. Kalucy RS. et al: Weight gain, thermic effect of glucose and resting metabolic rate during recovery from anorexia nervosa. Am J Clin Nutr 30:138-146. 1977 12. Ferrannini E: The theoretical bases of indirect calorimetry: A review. Metabolism 37:2X7-301. 1988 13. Jequier E: Long-term measurement of expenditure in man: Direct or indirect calorimetry? Recent Adv Obes Res 3:130-135, 19x1

14. Garby L. Astrup A: The relationship between the respiratory quotient and the energy equivalent of oxygen during simultaneous glucose and lipid oxidation and lipogenesis. Acta Physiol Stand 129:443-444,1987 15. Sotherland PR: The reliability surements. Respir Physiol60:387-391,

of respiratory 1985

quotient

mea-

16. Stein TP: Why measure the respiratory quotient of patients on total parenteral nutrition? J Am Coil Nutr 4:501-503. 1985 17. Boer JO, Es AJH, Raaij JMA, et al: Energy requirements and energy expenditure of lean and overweight woman, measured by indirect calorimetry. Am J Clin Nutr 46:13-21. 1987 18. Ravussin E, Lillioja S. Knowler WC, et al: Reduced rate of energy expenditure as a risk factor for body-weight gain. N Engl J Med 8:467-472, 1988 19. Brooke OG, Ashworth A: The influence the postprandial metabolic rate and respiratory 27:407-415, 1972 20. Robert WM: Biochemistry: A Functional Philadelphia, PA. Saunders, 1983

of malnutrition on quotient. Br J Nutr Approach

(ed 3).

21. Dempsey DT, Crosby LO, Pertschuk MJ, et al: Weight gain and nutritional efficacy in anorexia nervosa. Am .I Clin Nutr 39~236-242. 1984 22. Aoki TT, Vlachokosta FV, Foss MC. et al: Evidence for restoration of hepatic glucose processing in type I diabetes mellitus. J Clin Invest 71:837-839, 1983 23. Hers HJ. Hue L: Gluconeogenesis glycolysis. Annu Rev Biochem 52:617-653.

and related 1983

aspects

of

24. Nose 0, Tipton JR, Ament ME, et al: Effect of the energy source on changes in energy expenditure, respiratory quotient. and nitrogen balance during total parenteral nutrition in children. Pediatr Res 21538.541, 1987 25. Ireton-Jones CS, Turner WWJ: The use of respiratory quotient to determine the efficacy of nutrition support regimens. J Am Diet Assoc 87: 180-183, 1987 26. Meistas MT, Vlachokosta FV. Gleason RE, et al: Role of muscle in CO2 production after oral glucose administration in man. Diabetes 34:960-963, 1985 27. Ebiner JR: Comparison of carbohydrate utilization in man using indirect calorimetry and mass spectrometry after an oral load of IOOg naturally labelled [ 13C] glucose. Br J Nutr 31:419-429. 1Y79