Changes in growth hormone, insulin, andthyroxine values, and in energy metabolism of marasmic infants

TROPICA L PED IA TRICS

DerrickB.Jelliffe,

Editor

Changes in growth hormon4 insulin, and thyroxine values, and in energy metabolism of marasmic infants Changes in energy metabolism at integrated and tissue level, as well as changes in plasma growth hormone, insulin, [ree larry acids, and glucose and in serum thyroxine and [ree thyroxine index were investigated in ten marasmic in[ants. Caloric expenditure was significantly reduced at the time of admission. Caloric expenditure correlated linearly with increased caloric intake (both expressed per unit o] body weight) throughout the study. The endocrine adaptations were characterized by a subnormal and delayed insulin response and an enhanced secretion o[ growth hormone to arginine in[usion; serum thyroxine and the [ree thyroxine index were at the upper limits o[ normal. The chronic caloric deficiency prior to admission was associated with low concentrations of muscle glycogen, creatine phosphate, and adenosine triphosphate. The latter two showed positive linear correlations with caloric intake per unit o[ body weight during recovery. It is suggested that the hormonal changes are a secondary adaptive mechanism which maintains muscle composition as close to normal as possible. When caloric intake was restored to an effective level, an opposite sequence o[ endocrine events was observed.

Adalberto Parra,* Mexico City, Mexico, Cutberto Garza,** Yolanda Garza, Houston, Texas, Jos~ Luis Saravia, Mexico City, Mexico, Carlton F. Hazlewood,

and Buford L. Nichols, Houston, Texas

From the Section o[ Protein Hormones, Departamento de Investigacidn Scientlfica, and Hospital de Pediatrfa, C.M.N., I.M.S.S., and the Department of Pediatrics, Section of Nutrition and Gastroenterology, Baylor College o[ Medicine, and Clinical Research Center, Texas Children Hospital. Supported in part by the Instituto Mexicano del Seguro Social and by grants #am the National Dairy Council, the David Underwood Trust, and National Institutes o/Health Grant RR-O0188. Presented in part at the Eleventh Annual Reunion o[ the Sociedad Mexicana de Nutrici6n y Endocrinologla, Acapulco, Gro., Mdxico, November 26 and 27, 1971. e"Reprint address: Instituto Mexlcano det Seouro Soclat, CentTo Mddico Nacional. Departmento de Investigaddn Cient~fica, Apartado Postal 73-032 M~xica 73 D. F. ~Recipient o[ a Goldberger Jellowship in honor o] Nevin S. Scrimshaw.

T i~ E p v B i~ i s i-i E i) data on abnormalities in the energy metabolism of malnourished infants are conflicting: M6nckeberg and associates 1 reported lowered oxygen consumption in malnourished children, whereas Levine and co-workers z found normal or even higher than normal consumption. These discrepancies may be due either to differences in clinical material and methodology or to expression of oxygen consumption on the basis of actual weight, age, or even height, Furthermore, during rehabilitation of these infants a slower than expected weight gain is common despite an adequate caloric Vol, 82, No. 1, pp. 133-142

134

Parra et al.

intake, a When malnourished patients are studied 3 to 6 weeks after hospital admission, a relationship between rate of recovery and total caloric intake has been observed?, 4 These changes in energy expenditure and energy requirement take place against the backdrop of altered body composition, 5' G altered carbohydrate metabolism, 7 and changes in endocrine function, s, ~a Despite the significant contributions of these previous reports to the understanding of adaptation in the marasmic child, the interaction of these factors remains poorly understood. The relative significance of these adaptations needs clarification for the clinician charged with the care of malnourished infants. Consequently, the present study was undertaken to demonstrate the relationship between altered intake and expenditure of calories and some of the hormones involved in modulation of energT metabolism in marasmic infants. ~ MATERIAL

AND METHODS

Ten male infants ages 2.5 to 9.0 months with advanced third-degree malnutrition *~ of the marasmic type were studied in the Hospital de Pediatria, Instituto Mexicano del Seguro Social. Parents' informed consent was obtained for all subjects studied. All infants were full term; the lowest birth weight was 2.5 Kg. All patients had a body weight far below the third percentile for the Mexican population, n and their linear growth was severely affected. Striking muscle wasting and loss of subcutaneous fat were characteristic. None had any acute cutaneous or mucosal lesions of the type seen in kwashiorkor, and the lowest serum albumin concentration was 3.0 Gin. per 100 ml. Acute gastrointestinal distress with severe diarrhea was the common factor for hospitaiization; however, at time of admission to the study the diarrhea had been controlled and intravenous fluids were no longer necessary. Except for Patients A. V. S. and R. S. C., who were on a lactose-free milk ~Detailed tables on body weight increments and muscle tissue composition can be obtained directly from Dr, Parra.

The Journal of Pediatrics January 1973

preparation for a period of two weeks after hospitalization, all infants received a similar milk formula and pureed diet, supplemented with vitamins throughout the study. Corn syrup was added in order to assure an adequate caloric intake. At admission, this formula provided at least 2 to 3 Gm. of protein per kilogram per day, and 130 calories per kilogram of body weight per day (except for Patients J. Z. N. and R. H. L. who had a lower caloric intake). The amount of food ingested was liberally increased throughout the study according to the infant's appetite. The daily caloric intake ranged from 111 to 261 calories per kilogram of body weight at admission and 185 to 316 calories at the time of discharge from the study. Caloric, carbohydrate, protein, and fat content of the diet offered and of that not consmned was calculated from specific tables for Mexican foodstuffla; the difference was expressed as intake. Table I shows pertinent clinical data of the infants during hospitalization. The first or admission study was performed immediately after the diarrhea had been controlled (3 to 5 days after hospitalization). Body weight on admission to the hospital and on admission to the study were not significantly different. The second or discharge study was done whenever the infant had shown a consistent increase in body weight. At each time, the studies were done on two subsequent days, according to the following protocol: The night before Day 1, a polyethylene catheter was placed in the superficial femoral vein and kept permeable with a slow intravenous drip of saline solution. This procedure was performed in order to obtain blood samples during the different tests without repeated venipunctures. Day I. After an 8 hour overnight fast, a percutaneous needle muscle biopsy (quadriceps) was performed according to the technique of Nichols and associates? a Muscle tissue was immediately weighed and frozen in liquid nitrogen. Glycogen, ~4 adenosine triphosphate, and creatine phosphate concentrations were measured ~; these three

Volume 82 Number 1

Metabolic studies in marasmic in[ants

135

T a b l e I. Clinical d a t a ~

Patient

ChronSkin fold thickness Creati- Serum t Serum ~ a k e ologic (ram.) nine protein albumin Protein I Calories age Weight Height Subheight (Gin.~ (Gin.~ (Gm./ ] (Kg,/ (moo (Kg.) (cm.) Triceps scapular index 100 ml.) 100 ml.) Kg./day) l day)

A. V.S.

4.0 6.0

2.790 3.570

52.3 54.3

3.2 3.8

2.9 2.7

0.48 1.13

5.6 6.8

3.0 4.0

2.4 12.3

130 288

J. C.V.

3.7 5.7

3.790 3.900

55.5 57.1

4.7 6.6

3.7 3.4

0.62 0.73

6.4 7.0

3.0 3.7

2.9 4.2

130 187

M. G.C.

4.8 6.7

2.390 3.720

50.4 53.0

1.7 3.6

1.5 2.7

0.86 1.35

6.1 6.6

4.1 3.6

6.0 7.2

166 185

M. C.P.

3.7 5.2

3.500 4.120

57.8 58.6

2.6 4.1

2.2 3.3

0.60 1.02

6.3 5.9

4.0 3.6

4.6 5.9

148 247

A. B.V.

9.0 10.2

4.440 5.150

64.7 65.4

2.4 4.5

1.9 3.1

0.65 0.83

5.3 6.4

3.0 3.9

7.3 I0.0

175 316

J. Z.N.

4.2 6.0

3.420 4.810

57.0 57.3

4.3 6.2

2.9 4.0

0.70 0.93

7.0 6.4

4.6 3.8

2.7 7.7

113 267

S. N.O.

4.7 6.2

2.800 3.950

53.7 54.5

1.6 3.5

1.7 2.7

0.49 0.64

5.9 6.4

3.7 3.8

2.6 5.0

130 216

R. S.C.

3.5 4.3

2.920 3.850

55.3 56.1

2.9 3.2

2.3 2.7

0.89 0.97

6.0 6.0

3.2 3.2

7.2 10.3

188 228

R. H.L.

2.5 4.1

3.880 4.250

60.6 61.2

2.2 3.0

2.2 2.2

0.22 0.49

6.3 6.1

3.4 3.0

2.1 5.9

111 213

M. H.M.

3.0 4.0

3.405 4.480

54.7 56.8

3.0 5.7

2.6 3.6

0.67 0.88

5.6 6.1

3.0 4.0

5.9 5.8

261 242

~For each patient, top fine of data are values at time of admission to study; second line shows values at time of discharge.

determinations were p e r f o r m e d for all patients on the same day. O n e hour after the muscle biopsy, 0.5 Gm. per kilogram of body weight of L-arginine m o n o h y d r o c h l o r i d e ~ was infused over 30 minutes t h r o u g h the polyethylene catheter. H e p a r i n i z e d blood samples were obtained through the catheter at minus 15, 0, 15, 30, 45, 60, a n d 90 minutes. T h e first 0.2 ml. of blood at each sampling time was discarded to avoid a dilution error. Blood samples were i m m e d i a t e l y centrifuged a n d the p l a s m a was separated a n d kept frozen at - 2 0 ~ C. for future analysis. Plasma i m m u n o r e a c t i v e insulin values were d e t e r m i n e d using the m e t h o d of Yalow a n d Berson, ~ a n d growth h o r m o n e levels were measured according to the m e t h o d of Schaleh a n d Parker, 1~ using a ~L-Arglnine monohydrochloride was infused as a sterile 10 p e r cent aqueous solutlon. L-Arginlne was Mndly supplied by SICA, S, A. and processed by Abbott Laboratories of M6xieo.

slight modification. 18 Plasma glucose was d e t e r m i n e d by a glucose oxidase method. 19 Free fatty acids were measured according to the m e t h o d of Laurell a n d Tibbling. 2~ T h e measurements were done in duplicate, and all p l a s m a samples for h u m a n growth hormone and immunoreactive insulin were analyzed in one single radioimmunoassay. D a y 2. After an 8 h o u r overnight fast, venous blood was obtained through the polyethylene catheter located in the superficial femoral vein to determine serum T3 binding capacity 21 using R e s - O - M a t - T a 1125 ( M a l linckrodt Chemical Works, St. Louis, M o . ) . Serum thyroxine levels were measured by a resin sponge technique, 22 a n d the free thyroxine index was then calculated. T o t a l serum protein and albumin concentrations were measured by cellulose acetate electrophoresis. 23 After the initial blood sample was obtained, a n intravenous glucose tolerance test (1.0 Gin. of glucose p e r kilogram of

136

Parra et al,

The Journal of Pediatrics January 1973

54

13-,{/} I,~1 if)

2.0

v

1.0 r

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Fig. 1. Changes in arm muscle area (O) and triceps skin fold thickness (e). Each point represents the average increment observed during sequential periods of 10 to 12 days (mean -+ S.E.M.).

t

x tLl r

rv o

58

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(.9 d (D

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body weight) '-'4 was performed and venous blood samples were obtained at 0, 5, 10, 20, 30, 45, and 60 minutes. Glucose was determined by a glucose oxidase method, 19 and clearance rates were estimated according to the method described by LoebY a Additional indices obtained during the study were: 1. Twenty-four-hour urinary creatinine excretion was measured three times a week. 26 The urine was collected in a chilled bottle. T h e values obtained were averaged for periods of 10 days and the creatinine height index was determined2 r 2. Oxygen consumption and COe production were measured two or three times a week using a Noyons diaferometer (Kipp and Zonen, Delft, Holland Model MG4-6601) previously calibrated to the altitude and temperature in Mexico City. T h e determinations were performed after overnight fasting for 8 hours and during a m i n i m u m period of 30 minutes. T h e infants were lightly sedated with oral chloralhydrate (50 mg. per kilogram of body weight) and placed in the chamber on foam rubber covered by diapers. Either the patient was apathetically awake throughout the test or fell asleep before or soon after the start of the test. W h e n an infant was restless the test was postponed until the next day. Duplicate determinations

0 PERIODS

Fig. 2. Changes in basal caloric expenditure from admission to discharge from the study. Each point represents the average of the values obtained in all patients during sequential periods of 10 to 12 days (mean +- S.E.M.). were performed in five infants with a variation of 0 to 4 per cent. 3. Daily caloric, carbohydrate, protein, and fat intake were estimated in each infant. ~2 The individual values for creatinine excretion, caloric expenditure, and caloric intake were subdivided into periods of 10 to 12 days and pooled in a total of four periods throughout the study. 4. T h e anthropometric measurements obtained were: daily body weight, weekly body length, skin fold thickness (subscapular and triceps), and mid-upper arm circumference2 s Harpender's calipers and anthropometric equipment were used. Anthropometric measurements were determined by the same observer (Y. G.) throughout the study. The data recorded on each occasion were the averages of three sequential measurements. Based on Mid-upper arm circumference measurements, the arm muscle area (square centimeters) was calculated according to a

Volume 82 Number 1

Metabolic studies in marasmic in]ants

60-

137

r = 0.599 y - 19.794 p

+ 0.108

X

( 0.001

>.

9

g

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o z ~.

40-

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30-

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CALORIC

i 200 INTAKE

1

( r

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Fig. 3. Correlation between daily caloric intake and basal daily caloric expenditure per unit of body weight. Each point represents the average value obtained in each patient during sequential periods of 10 to 12 days. previous report. 29 This measurement has been satisfactorily used as a public health index of malnutrition in early childhood. 29 Statistical analysis was performed by means of pair test analysis. Values expressed in the text and figures represent mean • S.E.M. RESULTS

Body weight and basal calorie expenditure. The observed weight gains of the marasmic infants during each of the four periods throughout the study were equal or greater than normal in 31 out of 39 observations. The theoretical weight gains (grams per kilogram per day) were based on the fiftieth percentile in tables for Mexican population? 1 As seen in Fig. 1, during Periods 2 and 3 the arm muscle area had an increment of 0.37 + 0.09 cmY (p < 0.01), and a further increment was observed during Period 4. Although triceps skin fold thickness did not increase significantly during Period 2, there were increments of 0.81 + 0.22 mm. and up to 1.70 +_ 0.22 mm. during Periods 3 and 4, respectively (Fig. 1); the latter increment was the greatest (p < 0.01). Creatinine height index increased markedly throughout the study, even though the serum protein

albumin, and globulin values remained unchanged (Table I). At admission the basal caloric expenditure (calories expended for basal metabolism) was 38.5 +_ 2.7 calories per kilogram of body weight. Throughout the study, there was a general trend to increase calorie expenditure up to a maximum of 48.0 +_ 3.3 calories per kilogram of body weight during Period 3 with a subsequent plateau in Period 4 (Fig. 2). Basal caloric expenditure and intake pet" unit of body weight had a linear correlation (r = 0.599, p < 0.001) (Fig. 3). Arginine tolerance test. Plasma human growth hormone concentrations in two fasting samples (-15 and 0 minutes) were 6.7 +_ 1.7 and 7.0 +_ 2.4 m~g per milliliter, respectively, on admission, whereas at discharge they were 2.2 + 1.1 and 2.5 • 1.2 m/xg per milliliter (p < 0.05). Fasting plasma immunoreactive insulin values were 7.6 ~ 2.0 and 8.2 +_ 2.3 ~U per milliliter, respectively, on admission, as compared to 12.3 i 2.3 and 11.8 + 2.2 ~U per milliliter at discharge (p > 0.05). On admission, fasting free fatty acid levels were 1.03 _+ 0.14 and 1.20 + 0.31 mEq. per liter, respectively, as compared to 1.21 • 0.25 and 1.09 +_ 0.22 mEq. per liter

138

Parra et al.

The ]ournal of Pediatrics January 1973

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Fig. 4. Plasma human growth hormone (HGH), insulin, h'ee fatty acids (FFA), and glucose levels in response to L-arginine infusion (shaded area) at admission ( t ) and at discharge from the study (O) (mean -+ S.E.M.). at discharge (p > 0.05). Fasting plasma glucose values at admission were 64.0 _+ 5.7 and 7t.7 _+ 7.5 rag. per 100 ml., respectively, and at discharge were 71.6 + 2.9 and 75.5 _+ 5.3 rag. per 100 ml. (p > 0.05). As shown in Fig. 4 plasma human growth hormone levels during arginine stimulation were significantly greater on admission than at discharge at intervals of 15 (p < 0,005), 45 (p < 0.005), and 60 minutes (p < 0.05). On the other hand, plasma immunoreactive insulin levels were significantly lower on admission at 30 minutes (p < 0.001). No significant changes in plasma glucose or free fatty acid occurred throughout the arginine infusion tests in either period. Rate of glucose utilization (Kt). On admission, the mean rate of glucose utilization (Table I I ) was 2.97 _+ 0.13 per cent per minute, as compared to 3.30 +_ 0.18 per cent per minute at discharge (p < 0.01). Although a significant correlation between peak immunoreactive insulin and Kt values was not demonstrated, the poorest immunoreactive insulin responses to arginine were generally observed in the infants with the lowest Kt values.

Serum thyroxine. On admission, serum thyroxine (Table I I ) was 10.3 _+ 1.2 /zg per 100 ml., whereas at discharge the value was 7.1 _+ 0.6 /~g per milliliter (p < 0.05). On the other hand, the free thyroxine index on admission was 8.8 _+ 1.2 and at discharge was4.8 _+0.5 (p < 0.01). Muscle tissue composition. Muscle glycogen, adenosine triphosphate, and creatine phosphate concentrations (Table I I ) were higher at discharge than on admission to the study (p < 0.025). Since muscle creatine phosphate and adenosine triphosphate concentrations showed a linear correlation (r = 0.667, p < 0.005), both parameters were pooled as a measure of production of highenergy phosphate bonds. Muscle creatine phosphate plus adenosine triphosphate concentrations, at time of discharge, plotted against the free thyroxine index, showed a negative linear correlation (r = -0.695, p < 0.05). A positive linear correlation between caloric intake (calories per kilogram per day) and muscle creatine phosphate plus adenosine triphosphate concentrations at the time of discharge was observed (r = 0.729, p < 0.005).

Volume 82 Number 1

DISCUSSION

In the present study basal caloric expenditure (expressed as calories per kilogram of actual body weight per day) was significantly reduced in the marasmic infants, when tested 3 to 5 days after hospital admission. Although this observation conflicts with previous reports, 2, a0 it is necessary to stress that the same phenomenon has occasionally been observed in malnourished infants immediately on hospital admission, a~ The reduced basal caloric expenditure observed at admission is very unlikely to be the result of a falsely high body weight (due to overhydration), since body weights were similar both on admission to the hospital and on admission to the study (3 to 5 days after). This reduction in basal caloric expenditure seems not to reflect the calorie needs for recovery but appears to represent an adjustment to chronic starvation, al This idea is supported by the close correlation between caloric intake and basal expenditure per unit body weight observed in the patients throughout the study. Serial determinations of the basal caloric expenditure revealed an increase followed by a plateau which was maintained despite a constant weight gain. Although one can never be absolutely certain of the correctness of any gross indirect measurements of body composition (as exemplified by skin fold thickness and arm muscle area), any relative changes in those parameters are probably real? 2 The present results would suggest that during recovery there is an augmentation of the cellular phase, as suggested by mass of muscle tissue, that accounts for oxygen consumption, as and at later stages a less metabolically active tissue (i.e., fat) is accumulated. It should be emphasized that in the present study, basal calories and not total expended calories were measured. One could expand on this from Fig. 3 and point out that 30 per cent of ingested calories were expended for basal metabolism in Period 1 and only 17 per cent in Period 4. Because these children were confined to cribs and the activity level did not significantly vary, the increase

Metabolic studies in marasmic in[ants

139

in nonbasal calories must be mainly for growth. The rapid growth rates generally observed in these patients undoubtedly were the result of high caloric intakes, which are similar to or even higher than those previously suggested?, ~1. ~4 Fasting plasma human growth hormone, immunoreactive insulin, glucose, and free fatty acid values were similar to those previously reported in marasmic or normal infants of a comparable age. a5 The human growth hormone response to arginine infusion on admission is difficult to evaluate since there are no normal values in the literature for this age group. However, the values reported in this study are compatible with previous reports? 6 All of the marasmic infants had a peak human growth hormone response of at least 7.0 m/zg per milliliter, which is considered a normal response for older children? 7 Furthermore, the human growth hormone values of the probands could be considered within a physiologic range 3~ and lower than those observed in children with kwashiorkor. 9 An abnormal immunoreactive insulin response to arginine in malnourished infants has been suggested previously. 6 In the present study a subnormal and delayed immunoreactive insulin response to arginine at admission was clearly observed. This type of response is similar to that which has been previously documented in malnourished infants, 8 after total starvation, 3~ or during restricted carbohydrate intake in aduhs. 4~ Other investigators 41 have fully discussed the importance of the sequence of hormonal responses following a meal or infusions of amino acids. In the marasmic infants this critical phasing of the hormonal responses was disrupted at admission by the slow peak response of insulin simultaneously with the peak response of growth hormone resulting in a blunting of insulin effectiveness. Thus the hormones would tend to neutralize their antagonistic actions on carbohydrate and fat metabolism in order to maintain normal blood glucose concentrations, especially to perfuse the brain. Previous investigators have observed that some thyroid tests are abnormal in marasmic

1 40

Parra et aI,

The Journal o[ Pediatrics ]anuary 1973

Table II. Hormone values and muscle tissue composition

Admission study Muscle Kt glucose (mg./lO0 ml./min.) 2.27 0.39 0.13 < 0.01

Free

Values Mean S.D. S.E.M. p Value ~

Thyroxine (#g/lO0 ml.) I0.3 3.7 1.2 < 0.05

Abbreviations: A T P

=

thyroxine index 8.8 3.6 1.2 < 0.01

adenosine triphosphate,

CP

=

ATP (mM./IO0 Gm. f[dt) 1.15 0.50 0.16 < 0.025

(mM./lO0 Gin. [[dt) 1.46 0.69 0.23 < 0.025

Glycogen (Gm./lO0 Gin. Hdt) 5.63 4.64 1.46 ( 0.025

creatine phosphate, ffdt = fat-free dry tissue.

*Admission versus discharge.

infants22, ~3 The thyroid tests employed in the present study did not reveal abnormalities. Although a significant elevation in serum thyroxine and free thyroxine index was present at admission, the values were within the normal range (unpublished data). Thus an increase in oxygen consumption was not to be expected? 4 There are numerous reports confirming changes in muscle composition in the malnourished state. TM 45 The decreased concentration of adenosine triphosphate and creatine phosphate at admission coincided with reduced basal caloric expenditure. Both total basal oxygen consumption and the phosphorylation products of mitochondrial metabolism increased during recovery. This suggests that quantitative changes in tissue metabolism may contribute to the altered basal metabolic rate. T h e previously discussed changes in body composition are, therefore, only a partial explanation of the metabolic adaptations to chronic caloric deficiency. O n the other hand, the low muscle glycogen concentrations observed in the patients studied might be related to a peripheral lack of insulin efficacy? a T h e prompt response of the metabolic and endocrine alterations upon refeeding suggests that the environmental component (i.e., caloric intake) is one of the key factors in the induction and recovery of these adaptations. Thus the hormonal changes observed in this study may represent a secondary adaptive mechanism in an effort to maintain muscle function as close to normal as possible. W h e n caloric intake is restored to an

effective level, an opposite sequence of events occurred. Finally, it must be emphasized that in the clinical management of marasmic infants an effective level of caloric intake must be assured in order to favor a rapid recovery.40, 41 The discussion and criticisms of Drs. Silvestre Frenk, George Graham, Robert Blizzard, and Donald Cheek are gratefully recognized. We acknowledge the collaboration of the residents, physicians, and nurses of the Hospital de Pediatria and are especially grateful to all personnel from the Nutrition Ward for their most valuable assistance. Mr. Alejandro Ludlow performed the statistical analysis for the study, and Dr. Rodrigo Rodrlguez performed the thyroid studies. Mr. Robert C. Ferris ('Cambridge Nuclear Corporation) provided human growth hormone-1125 and insulin-1125, and Dr. Robert M. Blizzard supplied the human growth hormone antiserum (RB1238). The National Pituitary Agency through Dr. A. E. Wilhelmi provided us with the human growth hormone standard (NIH-GH-SH1216 C). The secretarial work was done by Miss Luz Maria Luna. REFERENCES

1. MSnckeberg, F., Beas, F., Horwitz, I., Dabacens, A., and Gonzfilez, M.: Oxygen consumption in infant malnutrition, Pediatrics 33: 554, 1964. 2. Levine, S., Wilson, J., and Gottschall, G.: The respiratory metabolism in infancy and childhood. VIII. The respiratory exchange in marasmus: Basal metabolism, Am. J. Dis. Child. 35: 615, 1928. 3. McLaren, D. S.: A fresh look at proteincalorie malnutrition, Lancet 2: 485, 1966. 4. Ashworth, A., Bell, R., James, W. P. T., and Waterlow, J. C.: Calorie requirements of

Volume 82 Number 1

Metabolic studies in marasmic inf.ants

14 1

Discharge study Muscle Thyroxine (#g/lO0 ml.)

Free thyroxine index

Kt glucose (mg./lO0 ml./min.)

ATP (mM./lO0 Gin. #dr)

7.1 1.9 0.6

4.8 1.7 0.5

3.30 0.54 0.18

1.92 0.70 0.23

5.

6.

7. 8. 9.

10.

ll.

12.

13.

14.

15. 16. 17.

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13.12 8.22 2.74

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