Review article 대한주산회지제 27 권제 2 호, 2016 Korean J Perinatol Vol.27, No.2, June, 2016 http://dx.doi.org/10.14734/kjp.2016.27.2.95 태아와신생아의포도당항상성 분당서울대학교병원소아청소년과조원임 ^ 정혜림 Glucose Homeostasis during Fetal and Neonatal Period Won Im Cho, M.D., and Hye Rim Chung, M.D., Ph.D. Departemnet of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea Glucose is essential for energy metabolism in human, especially in brain, and is a source of energy storage in the form of glycogen, fat and protein. During fetal life, the predominant source of energy is also glucose, which crosses the placenta by facilitated diffusion. There is very little endogenous glucose production under normal circumstances during fetal life. During labor, the fetus is exposed to physiological challenges that require metabolic adaptation. A healthy infant successfully manages the postnatal transition by mobilizing and using alternative. After birth, there is a rapid surge in catecholamine and glucagon levels, and a steady decrease in insulin, as blood glucose levels decline. These hormonal changes induce enzyme activities that lead to glycogenolysis and gluconeogenesis. During the first 24-48 hours of life, plasma glucose concentrations of neonates are typically lower than later in life. Distinguishing between transitional neonatal glucose regulation in normal neonates and hypoglycemia that persists or occurs for the first time beyond the first 72 hours of life is important for prompt diagnosis and treatment to avoid serious consequences. Key Words: Glucose, Fetus, Neonate, Hypoglycemia 포도당은탄수화물의일종인단당류로대사과정을통 해삼인산아데노신 (ATP) 을생성하며여분은글리코겐, 지 방및단백질의형태로체내에저장될수있어인체를비롯 한모든동물에서중심적인에너지원이다. 특히뇌는포도 당을주된에너지원으로사용하여뇌에서의산소소모량 은포도당의이용도와비례하며, 혈당이부적절하게낮을 경우에는뇌기능의저하및뇌손상이생길수있다. 1 자궁내에서태아는태반을통해전달되는영양분에의 Received: 19 June 2016, Revised: 29 June 2016 Accepted: 30 June 2016 Correspondence to: Hye Rim Chung Department of Pediatrics, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620 Korea Tel: +82-31-787-7292, Fax: +82-31-787-4054 E-mail: chyerim@hanmail.net Copyrightc 2016 by The Korean Society of Perinatology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/license/ by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided that the original work is properly cited. The Korean Journal of Perinatology pissn 1229-2605 eissn 2289-0432 e-kjp.org 존하여성장한다. 태아기에도포도당은성장과대사를위한필수적인에너지원이며, 태반을통해유입된포도당의상당한양은태아의뇌에서사용된다. 모체의심한기아상태와같은비정상적인상황이아닌일반적인상황에서태아는포도당신합성 (gluconeogenesis) 을하지못하므로, 태아는모체로부터유입되는포도당에전적으로의지하게된다. 태아는낮은산소분압환경에있으며산소소모량에근거를둔태아의에너지소모는 55 kcal/kg/day 로출생후에비해대사율이낮다. 2 태아의대사는모체의대사와밀접하게연관되어있다. 임신중기까지의모체의인슐린분비양은일반적이며증가된칼로리섭취로모체에글리코겐과지방이축적되는동화작용이주로나타난다. 그러나임신후기에는포도당과기타영양소가태아로더욱이행되어공복시모체의포도당농도및아미노산농도는낮아진다. 여러호르몬의변화로모체의인슐린저항성이증가하여임신말기에는탄수화물섭취시혈당및인슐린이오랫동안 - 95 -
Won Im Cho, Hye Rim Chung : - Glucose Homeostasis during Fetal and Neonatal Period - 높은상태로유지되고글루카곤의분비는임신전에비해 억제되어있다. 3 태아기에서신생아기로의이행기에는내분비적, 대사적 변화가있어모체로부터의포도당공급이갑자기중단되는 상황에서심한저혈당으로신경계가손상을받지않도록 보호하고있다. 그러나건강한신생아에서도생후첫 24 시 간동안에는이후에는쉽게관찰되지않는낮은혈당의빈 도가높아신생아에서의 얼마나낮은혈당이임상적으로 의미가있는저혈당인가 에대해서는아직도연구들이진 행중이다. 4-10 본 1. 태아의포도당대사 태아는필요한에너지의 80% 를포도당에서얻으며나머 지 20% 를젖산과아미노산등에서얻어 11 포도당은태아에 서도가장중요한에너지원이다. 태아에서는일반적으로내인성포도당생성이없어태아 의포도당은전적으로모체로부터태반을통해전달되며, 12, 13 모체와태아의포도당환경은하나의구획개념으로생 각할수있어산모가급격하게혈당이낮아지면태아의혈 당도낮아지는선형상관관계를갖는다. 14 태아의혈중포 도당농도는모체의혈중포도당농도의약 70% 로모체에 비해 10-20 mg/dl 정도가낮다. 15 이런포도당농도의차 문 이는모체에서태아로의포도당의이동에유리하다. 태반을통한포도당의전달은포도당농도차이에따 라나트륨 - 비의존성촉진확산 (sodium-independent facilitated diffusion) 에의해이루어진다. 16 이과정은포 도당운반체 (GLUT) 에의해매개되는데, 포도당운반체들 은 SCL2A 유전자에의해아형들이조직특이적으로발 현된다. 현재까지 14 가지아형의포도당운반체가알려져 있는데, 그중태반에서의포도당의촉진확산은 GLUT1 16, 17 에의해주로이루어지며, 일부는 GLUT3 도관여한다. GLUT1 은모체쪽태반및태아쪽태반에모두발현이되 나, GLUT3 은모체쪽태반에만발현되어있는데, 각포도 당운반체의작용에대해서는아직구체적으로알려져있 지는않다. 15 임신중기이후에는태반에서태반젖샘자극호르몬 (human placenta lactogen), 프로게스테론과에스트로겐 이생성되고이로인해모체의인슐린저항성이증가된다 (Table 1). 18 모체에서인슐린저항성이증가되면결과적으 로태아로의더많은양의포도당, 아미노산, 지질이전달되 어태아가성장하고동화 (anabolism) 가효과적으로이루 어지게된다. 재태후기에태아의지방및근육조직에인슐 린의존성포도당섭취율이증가함에따라모체와태아의 포도당농도차가커져서태아로더많은포도당이전달이 된다. 한편으로재태후기에는태반의포도당전달체의용 량이증가하여더많은포도당이태아에게전달될수있으 며, 자궁의혈류증가도임신후기에태아에게더많은포도 당을공급하는데도움이된다. 15 재태기간이증가함에따 라태반에서의포도당이용이증가하여, 모체에서전달되 는포도당의 50-60% 를태반이사용하고, 40-50% 를태 아가사용하게된다. 19 재태후기인임신제 3 기가되면성장및발달을위한에 너지소모후여분의포도당이간, 심장, 골격근에글리코겐 으로저장될수있다. 20 그중간에는글리코겐을포도당으 로전환하는글리코겐 -6- 인산분해효소가풍부하게있어 Table 1. Metabolic Transition from Fetus and Neonate Metabolic function Fetus Neonate Source of nutrients Mother Endogeneous Endogenous glucose production Minimal Active Lipolysis/Ketogenesis Minimal Active Dominant metabolism Anabolism Catabolism Hormone concentration Insulin Low Low Glucagon Low High Epinephrine Low High Hormone receptor Insulin receptor density High Decrease Insulin receptor affinity High Decrease Glucagon receptor density Low Rapid increase Enzyme concentration Phosphorylase Low High PEPCK Low High Abbreviation: PEPCK, phosphoenolpyruvate carboxykinase Adopted from Indian J Endocrinol Metab 2013;17:60-8. 18-96 -
조원임 정혜림 : - 태아와신생아의포도당항상성 - 혈액으로포도당을방출할수있다. 재태 120 일된태아의간 1 g 당글리코겐축적양은 24.6 mg이나재태 36주이후에는급격하게증가하여만삭시기에는 50 mg까지증가한다. 21 미숙아의경우는임신제 3기동안의글리코겐의축적이없이출생하여저혈당에취약하다. 자궁- 태반부전이있는경우에는포도당공급의부족으로포도당이태아의성장에주로쓰여글리코겐으로축적이되지는못한다. 일반적인상태에서태아의간에서는포도당신합성이이루어지지않는다. 22 태아의간에도포도당신합성에관여하는효소들이발현되어있으나성인에비하면활성도가낮은데, 특히 oxaloacetate를 phosphoenolpyruvate 로전환하여포도당신합성에관여하는 phosphoenolpyruvate carboxykinase (PEPCK) 의활성도가매우낮다. 23 하지만양에서시행한실험에서는저혈당시포도당신합성이증가되는양상이관찰되어, 24 모체가심한기아상태에있거나자궁태반부족이심한경우에는태아에서도포도당신합성이이루어질것으로추정된다. 미숙아에서는 PEPCK 의활성도가낮고, 자궁내성장지연이있는신생아에서는포도상신합성의전구체가적어서포도당신합성이적을가능성이있다. 2. 태아에서당대사의내분비적조절재태 4주의태아에서부터췌장은생성이되며, 재태 8-9 주부터베타세포와알파세포에서각각인슐린과글루카곤이생성된다. 25, 26 태아기에는알파세포가베타세포에비해더많으며, 재태중기이후베타세포가증가하여출생전에는알파세포와베타세포의비가 1:1 이된다. 재태 14-24 주사이에도베타세포에서인슐린이분비되나, 태아의혈중인슐린농도는낮게유지된다. 분만전까지는고혈당에의해태아의인슐린분비는잘변하지않는다. 27 태아의혈장의글루카곤농도는상대적으로높으며, 태아가자람에따라점차증가한다. 27 하지만글루카곤수용체의발현이적어서글루카곤에의한이화작용은감소되어있다. 인슐린수용체는태아의여러세포에광범위하게존재하는데, 고인슐린혈증이있더라도하향조절이되지않는다. 27 이러한것은재태후기의태아의빠른성장에도움을준다. 태아의글리코겐축적은주로태아의글루코코티코이드 에의해매개되며, 사람태반락토겐도영향을준다. 태아의인슐린은재태후기에는포도당의섭취와지방형성을증가시킨다. 27 3. 출생시의당대사의변화출생시모체와의급격한단절로모체로부터의포도당공급은중단된다. 이에따라신생아에서는내인성포도당생성의빠른증가와인슐린분비량의조절이요구된다. 재태중에는모체로부터포도당을비롯한영양분이연속적으로유입되었으나, 출생후에는간헐적으로영양분을섭취하게된다. 또모유수유를하는신생아의경우초유에는포도당의양은적고지방이풍부하여생후첫날의포도당의유입은태아기에비해뚜렷하게적다. 이러한상황에서신생아는호르몬의변화와효소유도를통해출생후환경에적응을하게된다. 출생시에피네프린과노르에피네프린이 3-10 배증가한다. 28 혈당이낮아지고카테콜아민이증가함에따라글루카곤분비가촉진되고, 인슐린대글루카곤의비율이변동된다. 27 생후 2시간에글루카곤농도는최대로증가하며, 27 출생후인슐린분비는최소량으로감소되어수일간낮게유지된다. 29 이와함께 PEPCK 등포도당신합성에관여하는효소들이유도되어, 30 생후 8-12 시간이경과하면포도당신합성이충분히증가하게된다. 31 생후첫 12시간까지는케톤생성이잘이루어지지않는다. 하지만생후 12시간이후에는케톤의생성이증가하여전체에너지필요양의 25% 를케톤이차지한다. 32 글루카곤과에피네프린이증가하고인슐린이감소함에따라글리코겐이분해되어포도당으로전환이된다. 따라서출생전에는간 1 g 당 50 mg의글리코겐이있는데생후 24시간경에는간 1 g 당 10 mg 미만의글리코겐만이남아있다. 생후첫 24시간에필요한포도당양의약 50% 를글리코겐에서얻으며, 피루브산염에서포도당신합성되는것이 20-30%, 지방분해로생성된글리세롤에서포도당신합성이되는것이 20% 를차지한다. 13 이러한과정으로재태중 70 mg/dl 이상으로일정하게유지되던혈당은출생 2시간후평균 56 mg/dl 까지감소했다가생후 24시간후평균약 67-70 mg/dl로다시상 - 97 -
Won Im Cho, Hye Rim Chung : - Glucose Homeostasis during Fetal and Neonatal Period - 승한다. 32 이과정중정상적인만삭아의약 30% 에서생후첫 24시간에 50 mg/dl 미만의낮은혈당이관찰되며, 20-25 mg/dl 의낮은혈당도매우드물지않게관찰되는데, 이러한생후첫 48시간이내의저혈당을이행기신생아저혈당 (transitional neonatal hypoglycemia) 이라고부른다. 4, 5 출생후낮은혈당은사람뿐만아니라모든포유류에서관찰되는데, 33 이러한출생직후낮은혈당이포도당신합성과글리코겐분해를촉진하여출생후생존에필수적이라는해석이있다. 또한낮은포도당농도로인해산화지방대사 (oxidative fat metabolism) 이촉진되고, 식욕을자극하여전반적으로공복- 포만주기에적응하도록도와줄수있다. 34 4. 신생아에서의저혈당의관리낮은혈당은생후 24-48 시간이내의신생아에서흔히볼수있는소견이나이를어떻게해석하고대응해야할지는아직해결되지않은문제이다. 4-10 특히, 후기조산아, 재태주수에비해크게태어난아기 (large for gestational age, LGA) 또는작게태어난아기 (small for gestational age, SGA), 당뇨병산모의자녀와같이무증상의저혈당이빈번한신생아에서의저혈당관리법에대해서는이견이지속되고있다. 이견이지속되는주된이유는 LGA 이외의상기무증상저혈당에대한고위험군은건강한아기에비해신경학적장기예후가나빠서신생아기에장기적위험도를평가하기어렵기때문이다. 35 오래지속된이견속에서신생아의저혈당관리에대해서는임상가들이각각의방법으로대처를해오던중 2011 년에미국소아과학회가무증상저혈당의고위험군인후기조산아, LGA, SGA 및당뇨병산모의자녀에대해조기수유및정기적인간이혈당계를이용한혈당검사를하고, 생후 4시간이내에는 <25-40 mg/dl 의혈당에서추가적인포도당을공급하고생후 4-24 시간에는 <35-45 mg/dl 에서추가적포도당을공급하여 45 mg/dl 이상의혈당을유지하도록권장하는임상지침을발표하였다 (Fig. 1). 8 임상에서는빠른결과를알기위해간이혈당계과혈당측정지를이용한전혈혈당을측정하는경우가많다. 혈당측정지 Fig. 1. Screening for and management of postnatal glucose homeostasis in late-preterm (gestational age 34 36 +6 weeks) and term smallfor-gestational age infants and infants who were born to mothers with diabetes, large-for-gestational age infants. Modified from Pediatrics 2011;127:575-9. 8-98 -
조원임 정혜림 : - 태아와신생아의포도당항상성 - 를이용해검사한혈당은검사실에서검사한혈장혈당과 상관관계가있으나, 기본적으로 10-20 mg/dl 의오차가 있고혈당이낮아지면오차가더커져간이혈당계만으로 혈당을판단하면오류가생길수있다. 36, 37 따라서 2011 년 미국소아과학회에서는저혈당의위험이있는신생아에서는 간이혈당계를이용하여선별검사를하고, 의미있게낮은 혈당이발견되면처치를함과동시에검사실에서정확한혈 장혈당을확인하라고권고하였다. 8 이행기신생아저혈당에서대부분회복이되는생후 3 일 이후에도저혈당이있을경우에는또다른접근이필요하 다. 이러한저혈당은고인슐린혈증, 뇌하수체기능저하증, 에 너지대사장애와같은선천성및유전성저혈당과관련이 있을가능성이있고, 생후수개월이내의저혈당은신경학 적후유증과관련이있는데, 특히고인슐린혈증성저혈당의 경우 25-50% 에서신경학적장애가있어, 이시기의저혈 38, 39 당을적기에발견하고처치하는것은중요하다. 이에 2015 년에미국소아내분비학회에서는지속적저혈 당의고위험군을정의하였고 (Table 2), 이들에대해서는 생후 48 시간이후지속적저혈당의여부를평가하고지속 적저혈당을배제한후퇴원을할것을권고하였다. 5 위험이있는신생아에서는퇴원전 6-8 시간금식을한후에혈장혈당이 >60 mg/dl이유지되는것으로지속적저혈당을배제할수있다. 저혈당이있은후저혈당에대한자율신경계반응이감소하는저혈당관련자율신경기능상실 (hypoglycemia associated autonomic failure) 이발생하고, 일반적으로저혈당에대한신경반응은혈장혈당이 50-70 mg/dl에서발생하는것을고려하여선천성저혈당이있는모든소아에서는치료의목표를혈당을 70 mg/ dl 이상으로유지하는것으로권장하였다. 정상적인신생아에서생후첫 1시간의평균혈당은약 55 mg/dl 인데, 이는소아및성인에서의신경저혈당증발생의역치와유사하며생후수시간동안신생아는이에대해내성이있는것으로알려져있다. 또한정상신생아에서는생후 48시간이내에는대부분혈당이 70 mg/dl 이상으로유지된다. 40 이를고려하여선천성저혈당질환이없는고위험군에서는생후첫 48시간까지는신경저혈당증 (neuroglycopenic symptom) 의역치를고려하여혈장혈당을 50 mg/dl 이상으로유지하고, 생후 48시간이후에는저혈당에대한자 Table 2. Neonates at Increased Risk for a Persistent Hypoglycemia Disorder Neonates at increased risk of hypoglycemia and require glucose screening 1. Symptoms of hypoglycemia 2. Large for gestational age (even without maternal diabetes) 3. Perinatal stress a. Birth asphyxia/ischemia; cesarean delivery for fetal distress b. Maternal preeclampsia/eclampsia or hypertension c. Intrauterine growth restriction (small for gestational age) d. Meconium aspiration syndrome, erythroblastosis fetalis, polycythemia, hypothermia 4. Premature or postmature delivery 5. Infant of diabetic mother 6. Family history of a genetic form of hypoglycemia 7. Congenital syndromes (eg, Beckwith-Wiedemann), abnormal physical features (eg, midline facial malformations, microphallus) Neonates in whom to exclude persistent hypoglycemia before discharge 1. Severe hypoglycemia (eg, episode of symptomatic hypoglycemia or need for IV dextrose to treat hypoglycemia) 2. Inability to consistently maintain preprandial PG concentration >50 mg/dl up to 48 hours of age and >60 mg/dl after 48 hours of age 3. Family history of a genetic form of hypoglycemia 4. Congenital syndromes (eg, Beckwith-Wiedemann), abnormal physical features (eg, midline facial malformations, microphallus) Adopted from J Pediatr 2015;167:238-45. 5-99 -
Won Im Cho, Hye Rim Chung : - Glucose Homeostasis during Fetal and Neonatal Period - 율신계증상 (neurogenic symptom) 의역치를고려하여혈장혈당을 60 mg/dl 이상으로유지하는것을권장하였다. 전혈혈당은혈장혈당에비해 10-15% 정도낮아, 41 2015 년미국소아과학회의지침에서의생후첫 48시간까지는혈장혈당을 50 mg/dl 이상으로유지하라는권고내용은간이혈당기로측정한전혈혈당을 45 mg/dl 이상으로유지하라고한 2011 년의미국소아과학회의권고내용과실제적으로는동일하다. 2015 년미국소아내분비학회의저혈당관리지침에서도첫째로낮은혈당에대한뇌의이상반응은케톤등대체에너지원의존재및이전저혈당등에의해다양한혈당범위에서발생하고, 둘째로뇌손상이발생하는명백한하나의낮은혈당의역치나기간은없고, 셋째로혈당측정법에따른기술적문제에따른하나의혈당수치의해석문제가있는점으로인해저혈당의진단기준을특정한혈장포도당농도로제시하지는않았다. 결론태아기에도포도당은가장중요한에너지원으로전적으로모체로부터전달된다. 출생을전후로하여개체의포도당대사에는큰변화가생겨모체로부터의연속적포도당공급이갑자기중단된상황에서도개체를보호하며이과정은다양한내분비적변화에의해이루어진다. 신생아기에는낮은혈당의빈도가낮지않아서이에대한해석및대처법이필요하다. 신생아저혈당에대한이견이지속되는중에도최근고위험신생아를정의하고이에대한대처법을제시하고자하는노력들이있어서이에대한숙지가필요하며, 주산기당대사에대해서는세부적으로알려져있지않은부분들이많아이에대한연구가필요하다. References 1) Filan PM, Inder TE, Cameron FJ, Kean MJ, Hunt RW. Neonatal hypoglycemia and occipital cerebral injury. J Pediatr 2006;148:552-5. 2) Sinclair JC. Metabolic rate and temperature control in the newborn. Baltimore: Williams and Wilkins, 1976:558-77. 3) Galerneau F, Inzucchi SE. Diabetes mellitus in pregnancy. Obstet Gynecol Clin North Am 2004;31:907-33. 4) Stanley CA, Rozance PJ, Thornton PS, De Leon DD, Harris D, Haymond MW, et al. Re-evaluating "transitional neonatal hypoglycemia": mechanism and implications for management. J Pediatr 2015;166:1520-5. 5) Thornton PS, Stanley CA, De Leon DD, Harris D, Haymond MW, Hussain K, et al. Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children. J Pediatr 2015;167:238-45. 6) Boardman JP, Wusthoff CJ, Cowan FM. Hypoglycaemia and neonatal brain injury. Arch Dis Child Educ Pract Ed 2013;98:2-6. 7) Hawdon JM. Definition of neonatal hypoglycaemia: time for a rethink? Arch Dis Child Fetal Neonatal Ed 2013;98:F382-3. 8) Adamkin DH. Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics 2011;127:575-9. 9) Rozance PJ. Update on neonatal hypoglycemia. Curr Opin Endocrinol Diabetes Obes 2014;21:45-50. 10) Hay WW, Jr, Raju TN, Higgins RD, Kalhan SC, Devaskar SU. Knowledge gaps and research needs for understanding and treating neonatal hypoglycemia: workshop report from Eunice Kennedy Shriver National Institute of Child Health and Human Development. J Pediatr 2009;155:612-7. 11) Morriss FH Jr, Makowski EL, Meschia G, Battaglia FC. The glucose/oxygen quotient of the term human fetus. Biol Neonate 1974;25:44-52. 12) Marconi AM, Cetin I, Davoli E, Baggiani AM, Fanelli R, Fennessey PV, et al. An evaluation of fetal glucogenesis in intrauterine growth-retarded pregnancies. Metabolism 1993;42:860-4. 13) Kalhan SC, Parimi P, Van Beek R, Gilfillan C, Saker F, Gruca L, et al. Estimation of gluconeogenesis in newborn infants. Am J Physiol Endocrinol Metab 2001;281:E991-7. 14) Whaley WH, Zuspan FP, Nelson GH. Correlation between maternal and fetal plasma levels of glucose and free fatty acids. Am J Obstet Gynecol 1966;94:419-21. 15) Hay WW Jr. Placental-fetal glucose exchange and fetal glucose metabolism. Trans Am Clin Climatol Assoc 2006; 117:321-39. 16) Devaskar SU, Mueckler MM. The mammalian glucose transporters. Pediatr Res 1992;31:1-13. 17) Gao L, Lv C, Xu C, Li Y, Cui X, Gu H, et al. Differential regulation of glucose transporters mediated by CRH receptor type 1 and type 2 in human placental trophoblasts. Endocrinology 2012;153:1464-71. - 100 -
조원임 정혜림 : - 태아와신생아의포도당항상성 - 18) Rao PN, Shashidhar A, Ashok C. In utero fuel homeostasis: Lessons for a clinician. Indian J Endocrinol Metab 2013; 17:60-8. 19) Hauguel S, Desmaizieres V, Challier JC. Glucose uptake, utilization, and transfer by the human placenta as functions of maternal glucose concentration. Pediatr Res 1986;20:269-73. 20) Hay WW Jr, Sparks JW. Placental, fetal, and neonatal carbohydrate metabolism. Clin Obstet Gynecol 1985;28:473-85. 21) Capková A, Jirásek JE. Glycogen reserves in organs of human foetuses in the first half of pregnancy. Biol Neonat 1968;13:129-42. 22) Kalhan S, Parimi P. Gluconeogenesis in the fetus and neonate. Semin Perinatol 2000;24:94-106. 23) Girard J. Gluconeogenesis in late fetal and early neonatal life. Biol Neonate 1986;50:237-58. 24) Hay WW Jr, Sparks JW, Quissell BJ, Battaglia FC, Meschia G. Simultaneous measurements of umbilical uptake, fetal utilization rate, and fetal turnover rate of glucose. Am J Physiol 1981;240:E662-8. 25) Edlund H. Pancreatic organogenesis--developmental mechanisms and implications for therapy. Nat Rev Genet 2002;3:524-32. 26) Sperling MA, Ganguli S, Leslie N, Landt K. Fetal-perinatal catecholamine secretion: role in perinatal glucose homeostasis. Am J Physiol 1984;247:E69-74. 27) Kronenberg HM, Melmed S, Polonsky KS, Larsen PR. Wiiliams textbook of endocrinology. 11th ed. Philadelphia: Saunders Co; 2007. 28) Rosenn BM, Miodovnik M, Khoury JC, Siddiqi TA. Counterregulatory hormonal responses to hypoglycemia during pregnancy. Obstet Gynecol 1996;87:568-74. 29) Sperling MA, DeLamater PV, Phelps D, Fiser RH, Oh W, Fisher DA. Spontaneous and amino acid-stimulated glucagon secretion in the immediate postnatal period. Relation to glucose and insulin. J Clin Invest 1974;53:1159-66. 30) Granner D, Andreone T, Sasaki K, Beale E. Inhibition of transcription of the phosphoenolpyruvate carboxykinase gene by insulin. Nature 1983;305:549-51. 31) Stanley CA, Anday EK, Baker L, Delivoria-Papadopolous M. Metabolic fuel and hormone responses to fasting in newborn infants. Pediatrics 1979;64:613-9. 32) Alkalay AL, Sarnat HB, Flores-Sarnat L, Elashoff JD, Farber SJ, Simmons CF. Population meta-analysis of low plasma glucose thresholds in full-term normal newborns. Am J Perinatol 2006;23:115-9. 33) Adamkin DH. Neonatal hypoglycemia. Curr Opin Pediatr 2016;28:150-5. 34) Rozance P, Hay NW. Neonatal hypoglycemia answers but more questions. J Pediatr 2012;16:775-6. 35) Rozance PJ, Hay WW Jr. New approaches to management of neonatal hypoglycemia. Matern Health Neonatol Perinatol 2016;2:3. 36) Giep TN, Hall RT, Harris K, Barrick B, Smith S. Evaluation of neonatal whole blood versus plasma glucose concentration by ion-selective electrode technology and comparison with two whole blood chromogen test strip methods. J Perinatol 1996;16:244-9. 37) Maisels MJ, Lee C. Chemstrip glucose test strips: correlation with true glucose values less than 80 mg/dl. Crit Care Med 1983;11:293-5. 38) Menni F, de Lonlay P, Sevin C, Touati G, Peigne C, Barbier V, et al. Neurologic outcomes of 90 neonates and infants with persistent hyperinsulinemic hypoglycemia. Pediatrics 2001; 107:476-9. 39) Meissner T, Wendel U, Burgard P, Schaetzle S, Mayatepek E. Long-term follow-up of 114 patients with congenital hyperinsulinism. Eur J Endocrinol 2003;149:43-51. 40) Cornblath M, Reisner SH. Blood glucose in the neonate and its clinical significance. N Engl J Med 1965;273:378-81. 41) Sacks DB. Carbohydrates, in Tietz textbook of clinical chemistry, edited by Burtis CA, Ashwood ER, 2nd ed. Philadelphia: WB Saunders. 1994. - 101 -
Won Im Cho, Hye Rim Chung : - Glucose Homeostasis during Fetal and Neonatal Period - = 국문초록 = 포도당은사람의에너지대사에서중추적인역할을한다. 태아기에도포도당은대사와성장을위한가장중요한에너지원이다. 태아는일반적인상태에서는포도당을내인성으로만들지못하며, 전적을모체로부터태반을통해촉진확산이되어유입되는포도당에의존한다. 재태후기에는모체의인슐린저항성과태반의혈류증가등의도움으로태아로더많은포도당이유입되어태아의성장및동화작용에이용된다. 출생시에는갑작스러운포도당의유입의중단으로신생아의혈당이낮아지고이에적응하기위해카테콜아민, 부신피질호르몬과글루카곤의분비가증가하고인슐린분비는낮게유지되며, 이에따라신생아에서의내인성포도당생성이증가하여혈당이유지되게된다. 건강한신생아에서도생후 1-2 일에는혈당이낮으나이후에는혈당이정상화되나, 이시기에얼마나낮은혈당이임상적으로의미가있는저혈당인가에대해서는이견이많다. 특히, 신생아기의지속성저혈당은신경발달의문제를초래할수있어, 이시기에저혈당을적시에진단하고치료하는것은신생아의장기적예후에중요하다. 중심단어 : 포도당, 태아, 신생아, 저혈당 - 102 -