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Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
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Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 1999 by the American Academy of
Pediatrics. All rights reserved. Print ISSN: 0191-9601. Online ISSN: 1526-3347.
Neonatal Hyperglycemia
Anusha H. Hemachandra, MD, MPH* and Richard M. Cowett, MD*†
Questions to consider (feel free to
OBJECTIVES send in your answers to these ques-
After completing this article, readers should be able to: tions and any questions of your own
for the “experts” to consider and
1. Explain the relationship of the frequency of hyperglycemia with the discuss about this case)
birthweight and gestational age of the neonate. 1. Why did this infant develop
2. List factors that may decrease glucose tolerance in the neonate. hyperglycemia?
3. Describe the major mechanism(s) contributing to altered regulation of 2. What role did the infant’s
neonatal glucose metabolism.
intrauterine growth restriction play
4. List the untoward effects of hyperglycemia in the neonate.
5. Describe the beneficial effects of insulin infusion in selected neonates. in the pathogenesis of
hyperglycemia?
3. Did the clinicians decrease the
IV glucose infusion rate sufficiently
Case Study the intravenous (IV) fluid rate was to correct the hyperglycemia?
A preterm male infant was born at 225 mL/kg per day (“to maintain 4. Did the IV amino acids play a
26 weeks’ gestation weighing 900 g, hydration”) and the glucose infusion role in treating the hyperglycemia?
with a birthweight percentile below rate was 16 mg/kg per minute. The 5. Should the clinicians have
the 3rd percentile and a head cir- IV solution was changed to 5% dex- used insulin?
cumference at about the 25th per- trose, but the glucose concentration 6. Why did the infant develop
centile. His Apgar scores were 4 and remained high, increasing to hypoglycemia and possibly a hypo-
5 at 1 and 5 minutes, respectively, 17.76 mmol/L (320 mg/dL), then glycemic seizure when the IV line
and he required intubation and ven- 22.65 mmol/L (410 mg/dL). Insulin infiltrated?
tilation in the delivery room. The treatment was started at 0.05 U/kg 7. Was the delayed development
infant was given artificial surfactant per hour, along with an IV infusion in this infant directly related to the
and maintained on a respirator with of 1 g/kg per day of amino acids. hyperglycemia?
“moderate to high settings.” Several By the fourth day of life, the William W. Hay, Jr, MD
saline boluses were administered for infant continued to receive IV insu- Coeditor
hypotension, and dopamine was lin and was tolerating total paren-
started to maintain a mean arterial teral nutrition (TPN) with 5% dex-
blood pressure above 30 mm Hg. trose providing 12 mg/kg per minute Introduction
Initial serum glucose concentrations and 2 g/kg per day of amino acids Hyperglycemia has become a signif-
were in the range of 1.67 to via a central venous catheter. Glu- icant risk factor for morbidity and
2.76 mmol/L (30 to 50 mg/dL). The cose concentrations remained in the mortality as smaller and more frag-
infant was given 10% dextrose at a range of 5.55 to 8.33 mmol/L ile infants survive during the neona-
rate of 100 mL/kg per day. (100 to 150 mg/dL). One episode tal period. Historically, hyperglyce-
By the second day of life, the of hypoglycemia (glucose, mia has been attributed to excessive
serum glucose concentration was in ,0.56 mmol/L [,10 mg/dL]) with IV glucose infusion. More recent
the range of 5.55 to 8.33 mmol/L an apparent seizure was noted after studies indicate that physiologic and
(100 to 150 mg/dL), and the dex- the infant was switched to a periph- biochemical mechanisms, leading to
trose infusion, which now contained eral catheter for the TPN solution
sodium chloride and potassium ace- and it infiltrated, probably for
tate, was increased to 150 mL/kg 2 hours before being discovered.
Enteral feeding was started on the ABBREVIATIONS
per day because of polyuria of
6 mL/kg per hour. The infant 10th day of life. Other than the AGA: appropriate for gestational
age
remained NPO. Subsequent glucose development of chronic lung dis-
ELBW: extremely low birthweight
concentrations over the next ease, one episode of suspected
GLUT: glucose transporter
24 hours increased to more than necrotizing enterocolitis without
LBW: low birthweight
13.88 mmol/L (250 mg/dL), and pneumotosis intestinalis, and one
PNDM: permanent neonatal
glycosuria was noted. At this time, episode of Staphylococcus epidermi- diabetes mellitus
dis sepsis, the infant’s course was RQ: respiratory quotient
relatively uncomplicated. At term SGA: small for gestational age
*Department of Neonatology, The gestation, his weight remained much TNDM: transient neonatal diabetes
Children’s Hospital; Division of Pediatrics, less than the 3rd percentile, growth mellitus
The Cleveland Clinic Foundation, had shown no catch-up, and he was TPN: total parenteral nutrition
Cleveland, OH. not yet approaching a standard
†
The Robert Schwartz, MD Center for VLBW: very low birthweight
Metabolism and Nutrition and the Division growth curve for infants of YSI: Yellow Springs Instrument
of Neonatology, Department of Pediatrics, 26 weeks’ gestation. Subsequent Company glucose analyzer
MetroHealth Medical Center, Cleveland, OH. development was markedly delayed.
excess glucose production, insulin the YSI with glucose reflectance weak. In addition, the time lag
resistance, or glucose intolerance, meters among randomly selected between glucose entering the blood-
underlie the development of hyper- infants. The reflectance meters have stream and its excretion into body
glycemia in preterm infants and correlations with the YSI ranging fluids is not well documented in the
sometimes inhibit efforts to maintain from r50.88 to 0.96 for cord blood neonate. Thus, analysis of body flu-
normal glycemia in the neonate. The and from r50.64 to 0.86 for capil- ids other than blood is inappropriate
sequelae of these disturbances in lary blood (Table 1), demonstrating for the diagnosis and management
glucose metabolism are extensive. a fundamental shortcoming of hand- of hyperglycemia in the neonate.
held glucose reflectance meters to
determine blood glucose concentra-
Diagnosis tion in the neonate. More recently, Epidemiology
Hyperglycemia generally is defined improved glucose reflectance meters The incidence of hyperglycemia var-
as a whole blood glucose concentra- have become available. As with all ies widely, but nearly all studies
tion greater than 6.66 to reflectance meters, however, consis- show that low birthweight (LBW) is
6.94 mmol/L (.120 to 125 mg/dL) tently careful and accurate use is the primary significant risk factor at
or a plasma glucose concentration necessary to achieve optimal any gestational age; preterm birth
greater than 8.05 to 8.33 mmol/L performance. ranks a close second. Thus, the inci-
(.145 to 150 mg/dL), regardless of Several noninvasive techniques dence of hyperglycemia is related
the neonate’s gestational age, for measuring glucose concentration inversely to birthweight in the pre-
weight, or postnatal age. Although have been proposed and evaluated. term infant, ranging from about 2%
affected neonates often are “asymp- The first used near-infrared spectros- in infants who weigh more than
tomatic” or have signs indicative of copy, usually on a finger, the inner 2,000 g to 45% in those who weigh
other disease processes, recognizable lip, or oral mucosa. However, this less than 1,000 g and up to 80% in
signs specific to hyperglycemia may method is not very accurate. Cross- extremely low-birthweight (ELBW)
include dehydration due to an validated standard errors of predic- infants weighing less than 750 g.
osmotic diuresis, weight loss, failure tion have ranged from 2.16 to Many other factors also are asso-
to thrive, fever, glycosuria, ketosis, 3.05 mmol/L (39 to 55 mg/dL) in ciated with hyperglycemia. In most
and metabolic acidosis. The latter normoglycemic adults. More tradi- studies there is a significant relation-
three signs are particularly common tional ultraviolet and infrared spec- ship between blood glucose concen-
among infants who have transient or troscopy are impractical because of tration and the initial rates of IV
permanent neonatal diabetes limited depth of penetration and the glucose administration (Fig. 1). Over
mellitus. interfering absorption of these wave- longer periods of observation, how-
Because such clinical signs are lengths of light by many photoreac- ever, the correlation between blood
unreliable indicators of the presence tive substances. Another form of glucose concentration and the rate of
or degree of hyperglycemia, it is noninvasive glucose measurement glucose infusion decreases, as clini-
necessary to measure glucose con- involves direct analysis of body flu- cians attempt to treat the hypergly-
centration by glucose analyzers. ids other than blood (eg, saliva, cemia by decreasing the rate of glu-
Considerable controversy surrounds sweat, urine, or tears). Unfortu- cose infusion. In fact, glucose
the use of different instruments that nately, the correlation between blood administration rates as low as 3 to
have highly variable degrees of glucose concentration and glucose 4 mg/kg per minute have been asso-
accuracy and reliability. The spec- concentration in excreted fluids is ciated with persistent hyperglycemia.
trophotometric glucose oxidase
method is the gold standard, but
using a central hospital laboratory to TABLE 1. Accuracy of Reflectance Meters Versus the Yellow
analyze the repeated blood samples Springs Instruments Co. Glucose Analyzer
necessary to manage the sick neo-
nate, often moment to moment, may DIFFERENCE BETWEEN CORD HEEL STICK
be impractical. One alternative may MEANS (%) BLOOD BLOOD P VALUE
be the use in the nursery of the Yel- Refectance meter
low Springs Instrument Company Glucometer M 29.3 223.2
glucose analyzer (YSI), which has Diascan S 0.4 20.4
excellent correlation (r50.99) with Accu-Chek II 1.2 16.4
the manual, laboratory-performed One Touch 35.2 25.6
spectrophotometric glucose oxidase
method. In contrast, glucose reagent Correlation coefficient
strips and glucose reflectance Glucometer M 0.88 0.64 ,0.05
meters, whether read visually or Diascan S 0.96 0.71 ,0.01
using a built-in algorithm, have Accu-Chek II 0.91 0.71 ,0.05
much weaker correlations with the One Touch 0.92 0.86 NS
laboratory glucose oxidase method From Lin HC, Maguire C, Oh W, Cowett R. Accuracy and reliability of glucose reflec-
(r50.70 to 0.83). tance meters in the high risk neonate. J Pediatr. 1989;115:998 –1000.
Several studies have compared
hepatic glucose production and pro- enhancing cellular glucose uptake. Complications
moting peripheral glucose utiliza- In the newborn rat, GLUT-4 does Neonatal hyperglycemia has been
tion. LBW infants often require not reach adult levels until day 14 associated with a wide spectrum of
exogenous insulin to resolve hyper- or 15. Decreased skeletal muscle sequelae, ranging from the clinically
glycemia despite an almost twofold expression of GLUT-4 also may manageable (dehydration) to the
rise in endogenous plasma insulin contribute to the insulin resistance devastating (death). Although rare
concentration. In most preterm and hyperglycemia seen in ELBW/ today, previous reports of intracra-
infants, endogenous glucose produc- LBW infants. Similarly, deceased nial hemorrhage and death among
tion cannot be inhibited completely cardiac expression of GLUT-4 has preterm infants who were markedly
(no more than 50% to 60%) by any been seen in experimental conditions hyperglycemic and other reports
level of insulinemia, and only very in the fetus in response to chronic documenting abnormal neurodevel-
high concentrations of insulin (more hyperglycemia, perhaps providing a opmental outcome in such infants
than 10-fold above normal) enhance mechanism to limit excessive glu- indicated a much worse severity of
peripheral glucose utilization. Post- cose uptake. illness and much more ominous
insulin receptor defects are consid- Enzyme regulation also is an prognosis than occurs today. For
ered most likely to be responsible. important component for establish- example, among selected groups of
Studies of multiple species in the ing neonatal glucose homeostasis. preterm infants ranging from 24 to
early newborn period demonstrate Preterm neonates may have imma- 34 weeks’ gestational age who had
severe and protracted hyperglycemia
that hepatocytes express a relatively ture biochemical pathways that
in earlier reports, more than 50%
high amount of GLUT-1 but rela- metabolize glucose incompletely.
subsequently died. The predominant
tively low levels of GLUT-2. The The fetal liver produces noninsulin-
cause of death was intracranial hem-
decreased GLUT-2 expression may dependent hexokinase in preference orrhage. Hyperglycemia causes a
limit hepatocyte sensitivity and to glucokinase. In response to insu- rise in serum osmolarity; each incre-
responsivity to an increase in insulin lin, only a small amount of glucoki- ment of 1 mmol/L (18 mg/dL) in
concentration that accompanies nase is available for glucose trans- blood glucose concentration
hyperglycemia, resulting in an port. The enzymes necessary for accounts for a rise of 1 mOsm/L in
inability to decrease hepatic glucose converting glucose to glycogen, serum osmolarity. If serum osmolar-
production. which increase in activity with ity exceeds 300 mOsm/L (roughly, a
GLUT-4 is found in insulin- increasing gestational age, may be serum glucose value of 22.2 mmol/L
sensitive tissues, primarily skeletal deficient in the immature neonate. [400 mg/dL]), rapidly shifting water
muscle, heart, and adipose tissue. These enzymes include phosphoglu- may cause cerebral hemorrhage.
When translocated by insulin to the comutase, uridine diphosphoglucose Cellular damage from such an insult
cell membrane, GLUT-4 helps to (UDPG) pyrophosphorylase, and apparently is augmented by pre-
decrease glucose concentration by UDPG glycogen synthetase. existing hyperglycemia. Observa-
tions in neonatal rats have shown studied five clinically stable neo- that 40 to 60 kcal/kg per day is nec-
that moderate hyperglycemia signifi- nates of less than 28 weeks’ gesta- essary to spare protein for subse-
cantly increases morphologic dam- tion. Each received glucose infu- quent somatic growth.
age throughout the forebrain with sions of 6 mg/kg per minute, It is appropriate to feed infants
induced ischemic events. The patho- followed by infusions of 9 mg/kg who have hyperglycemia unless
physiology of increased ischemic per minute, during which time the other clinical problems are consid-
damage during hyperglycemia is investigators traced the appearance ered severe enough to prevent feed-
unclear; hypotheses include hyperos- of leucine and phenylalanine in the ing. Early introduction of IV amino
molarity, excessive lactic acidosis, blood as markers of proteolysis. acids by parenteral infusion has
and decreased regional cerebral They reported that proteolysis was been associated with decreased inci-
blood flow. not suppressed during glucose infu- dence and severity of hyperglycemia
Hyperosmolarity also can lead to sion, even with near-complete sup- and hyperkalemia. There is consider-
a potential osmotic diuresis that pression of glucose production. It is able theoretical rationale for this
results in polyuria and dehydration. unclear if the continuation of prote- approach; certain amino acids, such
The increase in serum osmolarity olysis in the infant who has hyper- as leucine, valine, isoleucine, glu-
associated with hyperglycemia theo- glycemia is a benefit or a detriment; tamine, and arginine, are known
retically puts the tiny infant at risk high rates of proteolysis and protein insulin secretagogues. Furthermore,
for osmotic diuresis and dehydra- turnover may be part of the normal such amino acids probably are nec-
tion. Most short-term studies have growth process, which is desirable, essary for the normal growth and
failed to observe such an effort in particularly in the LBW neonate. development of the pancreas and the
LBW infants who have hyperglyce- Suppression of proteolysis does not pancreatic islet and beta cells. At
mia; hyperglycemic periods of appear to be associated with hyper-
least glutamine and perhaps leucine
greater than 5 hours may be neces- glycemia, but further studies are
also may promote insulin action and
sary to detect a diuretic effect. required to evaluate the implications
the disposal of glucose in skeletal
Another potential effect of of these data.
aggressive glucose administration is muscle.
steatosis and associated impairment Enteral feeding has been shown
in secretion of hepatic triglycerides. Treatment to promote pancreatic function and
Although steatosis rarely causes The treatment of neonatal hypergly- the secretion of insulin. Even mini-
clinical signs in the neonate, it can cemia must be based on the diagno- mal amounts, such as in “minimal
be detected by modest elevations of sis and suspected etiology of the enteral feeding” regimens, induces
liver transaminases. condition in each case. Hyperglyce- the gut production of “enteroinsular
Hyperglycemia also might jeopar- mia detected by reagent strips read hormones,” also known as “incre-
dize respiratory function by raising visually should be confirmed by tins,” including gastric inhibitory
the respiratory quotient (RQ), the laboratory methods. The exogenous polypeptide and pancreatic polypep-
ratio between CO2 generated and O2 glucose infusion rate and medica- tide. These hormones increase insu-
consumed. Carbohydrate oxidation tions being administered should be lin secretion by direct actions on the
results in an RQ of 1.0. Because noted. Urine output, urine glucose pancreatic beta cells. Such observa-
lipogenesis produces CO2 without concentration, and plasma glucose tions warrant efforts to feed preterm
consuming CO2, the resulting concentration should be measured to infants who have hyperglycemia,
increase in CO2 production requires assess the potential for dehydration even if full enteral feedings cannot
an increase in minute ventilation and osmotic diuresis. Serum electro- or should not be attempted.
that may compromise the fragile lytes should be determined to calcu- If severe hyperglycemia persists,
ELBW/LBW infant. Studies in late fluid replacement therapy. exogenous insulin administration
infants have demonstrated this Weight should be measured to deter- may be warranted. Guidelines about
increase in CO2 production, but the mine hydration status. when to use insulin treatment and
clinical significance remains unclear. When the blood glucose concen- how to provide this form of therapy
Another complication of hyper- tration is in the range of 6.9 to remain highly controversial and vary
glycemia is electrolyte imbalance. 19.43 mmol/L (125 to 350 mg/dL), widely among clinicians and institu-
A significant finding in neonates reducing exogenous glucose admin- tions. Many consider insulin treat-
who have glycosuria is an increase istration should be sufficient to ame- ment unnecessary, others use it spar-
in sodium excretion due to increased liorate the hyperglycemia. The rate ingly if at all, and many use it
filtered sodium load, even with min- of infusion should be decreased according to fairly liberal guidelines,
imal glycosuria. Creatinine clearance gradually, by 1 to 2 mg/kg per considering that it also might pro-
is altered significantly during the minute every 2 to 4 hours, with fre- vide a positive protein balance,
infusion. Hyperglycemia theoreti- quent monitoring of plasma or blood improve nutrition, and control glu-
cally can trigger partial suppression glucose concentrations until normo- cose concentration. Reasonable
of endogenous glucose production, glycemia is achieved or until the guidelines indicate that insulin treat-
which is accompanied in adults by glucose infusion rate reaches 3 to ment should be reserved until
suppression of whole-body proteoly- 4 mg/dL and hyperglycemia remains plasma glucose concentrations
sis. In neonates, however, this does severe (.19.43 mmol/L [.350 mg/ exceed 16.7 to 22.2 mmol/L (300 to
not appear to be the case. Hertz et al dL]). It is important to remember 400 mg/dL) despite reducing the
glucose infusion rate to less than infants who initially responded to SUGGESTED READING
3 to 4 mg/kg per minute. insulin therapy have developed Adam PAJ, Teramo K, Raiha N, Gitlin D,
The usual method of insulin resistance to insulin within hours to Schwartz R. Human fetal insulin metabo-
lism early in gestation: response to acute
administration involves a continuous days. Despite increasing insulin elevation of the fetal glucose concentration
infusion, beginning at 0.02 to infusion rates to as high as 16 U/kg and placental transfer of human insulin
0.05 U/kg per hour. Although higher per hour, resistance persisted. None I-131. Diabetes. 1969;18:409 – 414
infusion rates have been used, they of these neonates was septic, but all Anand KJS. Neonatal hyperglycemia during
usually are not necessary and were receiving antibiotic therapy for surgery. J Pediatr. 1987;110:999
increase the risks of hypokalemia other conditions as well as ventilator Anand KJS, Sippell WG, Aynsley-Green A.
Randomised trial of fentanyl anesthesia in
and subsequent hypoglycemia. support. preterm babies undergoing surgery: effects
Hypokalemia can be prevented by One major caveat regarding con- on the stress response. Lancet. 1987;1:
the addition of potassium to IV tinuous insulin infusion is the vari- 243–248
solutions during the infusion. Nor- able delivery of insulin due to its Binder ND, Raschko PK, Benda GI, Rey-
mal infusion rates of potassium usu- adsorption to the walls of plastic nolds JW. Insulin infusion with parenteral
nutrition in extremely low birth weight
ally are sufficient, but during insulin tubing in the IV pump. An infant infants with hyperglycemia. J Pediatr.
treatment, frequent monitoring of may require initially increased rates 1989;114:273–280
serum potassium concentrations is of insulin infusion to overcome this Cohen MH, Nihill MR. Postoperative ketotic
warranted. Small IV boluses of loss. This increased rate can lead to hyperglycemia during prostaglandin E1
potassium (0.1 mEq potassium as hypoglycemia as the infusion contin- infusion in infancy. Pediatrics. 1983;71:
842– 844
potassium chloride or potassium ues and the rate of adsorption slows Collins JW, Hoppe M, Brown K, Edidin DV,
acetate) can be added every 1 to markedly. One approach to prevent Padbury J, Ogata ES. A controlled trial of
2 hours if hypokalemia is significant or limit this problem is to flush the insulin infusion and parenteral nutrition in
and persistent. Urine flow rates insulin delivery system with diluted extremely low birth weight infants with
should be good before repeating insulin 2 hours before beginning glucose intolerance. J Pediatr. 1991;118:
potassium doses. therapy. Others have mixed the insu- 921–927
Conrad PD, Sparks JW, Osberg I, Abrams L,
Hypoglycemia is a potentially lin infusion with albumin at a con- Hay WW Jr. Clinical application of a new
severe problem if insulin is adminis- centration of 0.3 g/100 mL of solu- glucose analyzer in the neonatal intensive
tered through a single IV line. If it tion to decrease adsorption. care unit: comparison with other methods.
becomes disconnected, the infused J Pediatr. 1989;114:281–287
insulin lasts much longer in the cir- Cowett RM, Farrag HM. Neonatal glucose
culation than the infused glucose or Conclusion metabolism. In: Cowett RM, ed. Principles
of Perinatal-Neonatal Metabolism. 2nd ed.
endogenously produced glucose, Hyperglycemia is a frequent compli- New York, NY: Springer-Verlag; 1998:
leading to potentially severe hypo- cation in the often small and 683– 672
glycemia. Although this has been an growth-restricted preterm infant that Cowett AA, Farrag HM, Gelardi NL, Cowett
infrequent complication of insulin can be a formidable problem to RM. Hyperglycemia in the micropremie:
evaluation of the metabolic disequilibrium
treatment, it remains a serious treat. When the neonate also is criti- during the neonatal period. Prenatal Neo-
potential risk. Obviously, blood glu- cally ill, vulnerability to the compli- natal Med. 1997;2:360 –365
cose concentration should be mea- cations of hyperglycemia multiplies. Cowett RM, D’Amico L. Capillary (heelstick)
sured repetitively and frequently Hyperglycemia may be a primary versus venous blood sampling for the
(every 1 to 2 hours or whenever cause of pathology or a marker of determination of glucose concentration in
the neonate. Biol Neonate. 1992;62:32–36
signs of possible hypoglycemia severe stress. Efforts to prevent Cowett RM, Oh W, Pollak A, Schwartz R,
develop) during the administration hyperglycemia should include gen- Stonestreet BS. Glucose disposal of low
of insulin to the neonate. eral measures to improve the health birth weight infants: steady state hypergly-
VLBW infants younger than of the infant and attempts to treat cemia produced by constant intravenous
30 weeks’ gestational age can pathophysiologic conditions and dis- glucose infusion. Pediatrics. 1979;63:
389 –396
increase glucose tolerance using eases. Feeding early, both parenter- Dorchy H. Permanent neonatal diabetes melli-
insulin infusion therapy. After one ally and enterally, helps improve tus: lack of complications after a 20 year
treatment of 3 to 6 hours in dura- insulin production and insulin sensi- follow-up. Eur J Pediatr. 1992;151:151
tion, such infants have been shown tivity as well as general metabolism. Duckrow RB, Beard DC, Brennan RW.
to increase glucose tolerance by When hyperglycemia is severe and Regional cerebral blood flow decreases
during hyperglycemia. Ann Neurol. 1985;
50% to 300% and were able to prolonged, insulin in carefully 17:267–272
maintain normoglycemia thereafter. titrated IV infusions has been suc- Farrag HM, Nawrath LM, Healy JE, et al.
ELBW very preterm infants may not cessful in decreasing the circulating Persistent glucose production and greater
demonstrate such dramatic improve- plasma glucose concentration. This peripheral sensitivity to insulin in the neo-
nate vs. the adult. Am J Physiol. 1997;272:
ment in glucose tolerance, although approach should not be used in iso- E86 –E93
reports have noted that observations lation, however, without first trying Ferguson AW, Milner RDG. Transient neona-
were made on much sicker infants measures to promote endogenous tal diabetes in sibs. Arch Dis Child. 1971;
who probably had much higher con- insulin production and action to treat 45:80 – 85
centrations of counterregulatory hor- other illnesses and to decrease IV Ferrara TB, Coyser RJ, Hackstra RE. Side
effects and long-term follow-up of cortico-
mones. Other factors may contribute glucose infusion from abnormally steroid therapy in very low birth weight
to persistent glucose intolerance, high rates above 12 to 14 mg/kg per infants with bronchopulmonary dysplasia.
including insulin resistance. A few minute. J Perinat. 1990;10:137–142
Fosel S. Transient and permanent neonatal Leisti J, Raivio K, Krohn K. Neonatal hyper- nates: pharmacologic availability of insulin
diabetes. Eur J Pediatr. 1995;154:944 –948 glycemia and chromosome deletion in intravenous solutions. J Pediatr. 1994;
Gelardi NL, Rapoza RE, Cowett RM. Insulin (46,XX,Dq-). J Pediatr. 1976;88:989 –990 124:818 – 820
resistance, determined with the euglycemic Lilien LD, Rosenfield RL, Baccaro MM, Srinivasan G, Jain R, Pildes RS, Kannan CR.
hyperinsulinemic clamp, is present Pildes RS. Hyperglycemia in stressed Glucose homeostasis during anesthesia and
throughout the newborn period in the small premature neonates. J Pediatr. 1979; surgery in infants. J Pediatr Surg. 1986;
lamb. Pediatr Res. 1998;43:259A 94:454 – 459 21:718 –721
Gentz JCH, Warrner R, Persson BEH, Corn- Lin HC, Maguire C, Oh W, Cowett R. Accu- Srinivasan G, Singh J, Gattamanchi G, Yeh
blath M. Intravenous glucose tolerance, racy and reliability of glucose reflectance TF, Pildes RS. Plasma glucose changes in
plasma insulin, free fatty acids, and meters in the high risk neonate. J Pediatr. preterm infants during oral theophylline
B-hydroxybutarate in underweight new- 1989;115:998 –1000 therapy. J Pediatr. 1983;103:473– 476
born infants. Acta Paediatr Scand. 1969; Louik C, Mitchell AA, Epstein MF, Shapiro Stonestreet BS, Rubin L, Pollak A, Cowett
58:481– 490 S. Risk factors for neonatal hyperglycemia RM, Oh W. Renal functions of low birth
Goldman SL, Hirata T. Attenuated response associated with 10% dextrose infusion. weight infants with hyperglycemia and
to insulin in very low birth weight infants. Am J Dis Child. 1985;139:783–786 glucosuria produced by glucose infusions.
Pediatr Res. 1980;14:50 –53 Myers RE. A unitary theory of causation of
Pediatrics. 1980;66:561–567
Gottschalk ME, Schatz DA, Clare-Salzer M, anoxic and hypoxic brain pathology. Adv
Tyrala EE, Chen X, Boden G. Glucose
Kaufman DL, Ting GSP, Geffner ME. Neurol. 1979;26:195–213
metabolism in the infant weighing less
Permanent diabetes without serological Ostertag SG, Jovanovic L, Lewis B, Auld
than 1100 grams. J Pediatr. 1994;125:
evidence of autoimmunity after transient PAM. Insulin pump therapy in the very
neonatal diabetes. Diabetes Care. 1992;15: low birth weight infant. Pediatrics. 1986; 283–287
1273–1276 78:625– 630 Vileisis RA, Cowett RM, Oh W. Glycemic
Hertz DE, Karn CA, Liu YM, Liechty EA, Persson B, Gentz J. The pattern of blood lip- response to lipid infusion in the premature
Denne SC. Intravenous glucose suppresses ids, glycerol, ketone bodies during the neonate. J Pediatr. 1982;100:108 –112
glucose production but not proteolysis in neonatal period, infancy, and childhood. Widness JA, Cowett RM, Zeller P, Susa JB,
extremely premature newborns. J Clin Acta Paediatr Scand. 1966;55:353–358 Rubenstein AH, Schwartz R. Permanent
Invest. 1993;92:1752–1758 Pulsinelli WA, Waldman S, Rawlinson D, neonatal diabetes in an infant of an
Hughes SJ. The role of reduced glucose Plum F. Moderate hyperglycemia aug- insulin-dependant mother. J Pediatr. 1982;
transporter content and glucose metabo- ments ischemic brain damage: a neuro- 100:926 –929
lism in the immature secretory responses pathologic study in the rat. Neurology. Wilkins E, Atanosov P. Glucose monitoring:
of fetal rat pancreatic islets. Diabetologia. 1982;32:1239 –1246 state of the art and future possibilities.
1994;37:134 –140 Schlach DS, Kipnis DM. Abnormalities asso- Med Eng Phys. 1996;18:273–288
James T, Blessa M, Boggs TR. Recurrent ciated with elevated plasma nonesterified Zarif M, Pildes RS, Vidyasagar D. Insulin
hyperglycemia associated with sepsis in a fatty acids. J Clin Invest. 1965;44:2010 and growth-hormone responses in neonatal
neonate. Am J Dis Child. 1979;133: Simeon PS, Geffner ME, Levin SR, Lindsey hyperglycemia. Diabetes. 1976; 25:
645– 646 AM. Continuous insulin infusions in neo- 428 – 433
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