1 T VN ỏi thỏo ng l bnh ri lon chuyn húa, cú nguy c cao v cú tc phỏt trin rt nhanh Bnh c c trng bi s tng glucose mỏu hu qu ca s thiu ht bi tit insulin hoc hot ng kộm hiu qu ca insulin hoc phi hp c hai ỏi thỏo ng thai k l mt th c bit ca ỏi thỏo ng T l ỏi thỏo ng thai k ang cú chiu hng ngy cng gia tng nht l khu vc chõu Thỏi Bỡnh Dng ú cú Vit Nam ỏi thỏo ng thai k thng xut hin vo khong tun thai th 24 28 ca thai k [1], [2], [3], thai sn xut mt lng ln cỏc hormone gõy khỏng insulin ỏi thỏo ng thai k nu khụng c chn oỏn sm v iu tr kp thi s gõy nhiu tai bin cho c m v thai nhi nh tin sn git, thai cht lu, sy thai sm, thai to v tng t l t vong chu sinh[4], [5] Vỡ vy trờn th gii bnh ỏi thỏo ng thi gian mang thai ó v ang l c nhiu tỏc gi i sõu nghiờn cu Nhng nghiờn cu gn õy ó chng minh c rng mụ m khụng ch cú vai trũ d tr nng lng, m nú cũn cú chc nng nh mt c quan ni tit tit cỏc phõn t cú hot tớnh sinh hc khỏc nhau, c gi cỏc Adipokines [6], [7] Adipokines tham gia vo mt lot cỏc quỏ trỡnh nh cm mỏu, chuyn húa lipid, x va ng mch, iu chnh huyt ỏp, nhy cm insulin v chỳng c bit l cú vai trũ quan trng bnh sinh ca cỏc bnh liờn quan n ri lon chuyn húa v bnh ỏi thỏo ng Trong s cỏc Adipokines thỡ Adiponectin l mt protein c phỏt hin vo nhng nm 1990 [8], nú lm tng tớnh nhy cm insulin, chng viờm, kớch thớch s hp thu glucose c xng, gim sn xut glucose gan[9] Chớnh vỡ th nng adiponectin cú liờn quan ỏng k vi ỏi thỏo ng thai k, bộo phỡ, tng huyt ỏp Trong thai k bỡnh thng, s tit adiponectin ca m gim dn v gim nhiu hn nhng ph n b ỏi thỏo ng thai nghộn [10] Hn na nng adiponectin cng gim sau sinh nhng ph n cú tin s ỏi thỏo ng thai nghộn Nghiờn cu gn õy ó chng minh rng ph n cú nng adiponectin thỏng u m di 25% thỡ kh nng b ỏi thỏo ng thai nghộn gp 10 ln so vi nhng ph n cú nng adiponectin cao hn [11] Trong nhng nm gn õy vai trũ ca adiponectin bnh ỏi thỏo ng thai k ó c lm sỏng t mt cỏch chi tit hn Tuy nhiờn, ý ngha sinh lý ca adiponectin nhng bin chng ca thai k v mi liờn quan ca nú vi cỏc yu t nguy c gõy ỏi thỏo ng thai k cũn cha rừ rng Vit Nam hin cha cú nghiờn cu no cp n vai trũ v mi liờn quan vi cỏc yu t nguy c ỏi thỏo ng thai k ca adiponectin Xut phỏt t thc t trờn chỳng tụi tin hnh ti: Nghiờn cu nng Adiponectin huyt trờn bnh nhõn ỏi thỏo ng thai k ti bnh vin Ph Sn Trung ng vi cỏc mc tiờu: Kho st nng adiponectin huyt trờn bnh nhõn ỏi thỏo ng thai k v ph n cú thai bỡnh thng ỏnh giỏ mi liờn quan gia nng adiponectin vi mt s yu t nguy c lõm sng v cn lõm sng ỏi thỏo ng thai k CHNG TNG QUAN TI LIU 1.1 nh ngha, chn oỏn v phõn loi ỏi thỏo ng 1.1.1 nh ngha ỏi thỏo ng l tỡnh trng ri lon chuyn húa glucid, gõy tng ng huyt mn tớnh hu qu ca s thiu ht bi tit insulin hoc hot ng kộm hiu qu ca insulin hoc phi hi c hai Kốm theo cú ri lon chuyn húa protid v lipid S tng ng huyt mn tớnh ca bnh ỏi thỏo ng s gõy nhng bin chng cho cỏc c quan c bit l tim mch, mt, thn v h thn kinh 1.1.2 Tiờu chun chn oỏn bnh ỏi thỏo ng Khuyn cỏo tiờu chun chn oỏn ỏi thỏo ng ca T chc y t th gii (1998) [12] Chn oỏn T cn c vo tiờu chun sau: Glucose mỏu lỳc ( sau nhn n ớt nht l gi ) 7.0 mmol/l (126mg/dl), lm xột nghim ln liờn tip hoc: Glucose mỏu gi sau ung 75g glucose 11.1 mmol/l (200mg/dl) hoc: Glucose mỏu bt k 11.1 mmol/l (200mg/dl) kốm theo cỏc triu chng ca tng glucose mỏu Tiờu chun chn oỏn ỏi thỏo ng theo khuyn cỏo ca Hi ỏi thỏo ng Hoa K ( 2010 ) [13] Chn oỏn T da vo tiờu chun sau: HbA1c 6.5% Xột nghim c lm ti phũng xột nghim s dng phng phỏp chun Glucose mỏu lỳc 7.0mmol/l ( 126mg/dl ) Glucose mỏu lỳc c inh ngha l glucose mỏu nh lng thi im nhn ớt nht gi, xột nghim lm ớt nht ln Glucose mỏu gi sau ung 75g glucose 11.1mmol/l (200mg/dl) Bnh nhõn cú cỏc triu chng c in ca tng glucose huyt kốm theo xột nghim glucose mỏu ngu nhiờn 11.1mmol/l (200mg/dl) T nm 2010, Hip hi T M ó chp nhn xột nghim ch s HbA1c nh mt cụng c chn oỏn v sng lc ỏi thỏo ng cựng vi xột nghim glucose mỏu Ch cú cỏc xột nghim HbA1c c thc hin t phũng xột nghim t tiờu chun mi c s dng cho mc ớch chn oỏn v sng lc bnh T [13] 1.1.3 Phõn loi ỏi thỏo ng Phõn loi ỏi thỏo ng theo Hi ỏi thỏo ng Hoa k (ADA) 2004 [14] ỏi thỏo ng type (ỏi thỏo ng ph thuc insulin) ỏi thỏo ng type chim khong 5-10%, phn ln xy tr em v ngi tr tui vy cú th gp la tui 80-90 õy l kt qu ca s phỏ hy t bo bờta ca tuyn ty (do t hoc vụ cn ) dn n s thiu ht gn nh tuyt i insulin ỏi thỏo ng type (ỏi thỏo ng khụng ph thuc insulin) ỏi thỏo ng type chim khong 90-95% s bnh nhõn b ỏi thỏo ng Bnh c c trng bi ri lon hot ng hay tit insulin Nng insulin mỏu bỡnh thng hoc cao trng hp khỏng insulin chim u th; hoc nng insulin mỏu gim trng hp cú khim khuyt kh nng tit insulin Cỏc týp c bit khỏc: bao gm Gim chc nng t bo bờta khim khuyt gen: t MODY n MODY T th MODY khim khuyt gen lm gim chc nng t bo bờta gõy gim tit insulin Gim hot tớnh ca insulin khim khuyt gen: Tng khỏng insulin type A Bnh lý ty ngoi tit: Viờm ty, chn thng hay ct b ty, ung th tuyn ty, s kộn ty, bnh nhim sc t st Bnh ni tit: To u chi, hi chng Cushing, u tit glucagon, cng giỏp, u tit aldosterone, u tit somatostatin Tng ng huyt thuc, húa cht: Vacor, pentamidin, corticoid, hormone tuyn giỏp, thiazid, thuc ng giao cm bờta Nhim trựng: Rubella bm sinh, cytomegalovirus Mt s hi chng di truyn ụi kt hp vi T: Hi chng Down, hi chng Klinefelter, hi chng turner, lon dng trng lc c ỏi thỏo ng thai k 1.2 Tng quan v ỏi thỏo ng thai k 1.2.1 nh ngha ỏi thỏo ng thai k (TTK) l tỡnh trng ri lon dung np glucose bt k mc no, phỏt hoc phỏt hin ln u tiờn lỳc mang thai nh ngha ny c ỏp dng dự ngi bnh cú cn phi iu tr bng insulin hay ch cn iu chnh ch n v dự cho din bin sau cũn tn ti hay khụng nh ngha ny khụng loi tr trng hp bnh nhõn ó cú ri lon dung np glucose t trc (nhng cha c phỏt hin) hay xy ng thi vi quỏ trỡnh mang thai [1] 1.2.2 Lch s phỏt hin, nghiờn cu chn oỏn ỏi thỏo ng thai k [1], [2] Vo u th k XIX, nm 1828, Bennwitz ln u tiờn cụng b mt trng hp ỏi thỏo ng phỏt hin thi gian mang thai ú l mt thai ph 22 tui, mang thai ln th 4, cú triu chng a niu vo thỏng th cựng vi cỏc triu chng khỏc nh khỏt nc, da khụ Tin s ln mang thai trc sinh hon ton bỡnh thng Bnh nhõn c chn oỏn l ỏi thỏo ng v c iu tr bng ch n kiờng Thai ph thỏng nhng thai nhi cht cuc v cõn nng ca thai > 4.0kg Nm 1882, Matthews Ducan ln u tiờn cụng b nghiờn cu bnh ỏi thỏo ng ph n cú thai ti hi ngh sn khoa Anh Quc Nghiờn cu cho thy rng 22 ln mang thai 15 thai ph cú biu hin ỏi nhiu thỡ kt qu l cú 13 thai nhi t vong, v mt ph n cht sau ú nm ỏi thỏo ng Ti nhng nm 1940-1950, cỏc nghiờn cu ti M v Scotland ó khng nh: tng ng mỏu ngi m lm tng t l t vong tr s sinh Ngoi ra, cỏc tỏc gi cng ch rng thi k mang thai cú s thay i tớnh nhy cm vi insulin Nm 1954 nghiờn cu u tiờn v bt thng chuyn húa carbonhydrat thai ph c tin hnh ti Boston Nghim phỏp sng lc vi 50g glucose ln u tiờn c s dng Nm 1964 O'Sullivan v Mahan a tiờu chun chn oỏn ỏi thỏo ng thai kyfduwaj trờn cỏc kt qu lm nghim phỏp dung np glucose trờn 752 thai ph Nm 1979 tiờu chun chn oỏn ỏi thỏo ng thai k ca O'Sullivan v Mahan da vo kt qu dung np glucose, ung 100g glucose, sau gi nh lng ng huyt ó c Hi ph khoa M khuyn cỏo s dng, y ban quc gia v ỏi thỏo ng ca M cng ó cụng nhn iu ny Thut ng Gestational Diabetes Mellitus ỏi thỏo ng thai k ln u tiờn c a bi Jorgen Pedersen nm 1967, nhng mói n nm 1980 mi c chớnh thc cụng nhn ti Hi ngh th gii ln th nht v ỏi thỏo ng thai k ti Chicago Nm 1980, t chc y t th gii ln u tiờn a tiờu chun chn oỏn ỏi thỏo ng thai k Sau ú nhiu nghiờn cu v chn oỏn, iu tr v theo dừi ỏi thỏo ng thai k cỏc nc trờn th gii ln lt c cụng b 1.2.3 Tỡnh hỡnh mc bnh TTK T l ỏi thỏo ng thai k thay i khỏc tựy theo quc gia, vựng, theo chng tc v tựy theo tiờu chun chn oỏn no T l dao ng t 114% [1], [2], [15], [16] Bng 1.1: T l ỏi thỏo ng thai k ca mt s quc gia trờn th gii [1], [2] Quc gia Nm T l TTK (%) an Mch 1975 17 Bc Ailen 1980 0.2 M 1980 12.3 Thy in 1984 1.3 Anh 1984 Australia 1988 2.4 Ti Vit Nam cha cú s liu thng kờ trờn ton quc v t l TTK, nhiờn qua mt s nghiờn cu ti Thnh ph H Chớ Minh v H Ni cho thy t l ỏi thỏo ng thai k ca cỏc thai ph khụng h thp v cú chiu hng gia tng Bng 1.2: T l ỏi thỏo ng thai k qua cỏc nghiờn cu nc [1], [17], [18] Tỏc gi Nm a im T l (%) Ngụ Th Kim Phng 1999 Qun TP H Chớ Minh 3.9 Ng.T.Kim Chi v CS 2000 BV Ph Sn H Ni 3.6 T Vn Bỡnh v CS 2002-2004 BV Ph Sn TW v BV Ph Sn H Ni 5.7 V Bớch Nga v CS 2006-2008 BV Ph Sn TW v Khoa sn BV Bch Mai 7.8 1.2.4 Sinh lý bnh ca ỏi thỏo ng thai k [1], [2] Mang thai l yu t thun li thỳc y s xut hin cỏc ri lon iu hũa ng mỏu tng tỡnh trng khỏng insulin ỏi thỏo ng thai k cú th xy tỡnh trng khỏng insulin sinh lý ny tng kch phỏt v cựng xut hin song song vi s thiu ht insulin tng i Sinh lý bnh ỏi thỏo ng thai k tng t nh sinh lý bnh ca ỏi thỏo ng type 2, bao gm khỏng insulin v bt thng v tit insulin 1.2.4.1 Bi tit cỏc hormone thi gian mang thai Sn xut cỏc hormone cú khuynh hng tng thi gian mang thai v phn ln cỏc hormon ny u gúp phn khỏng insulin v gõy ri lon chc nng t bo beeta ca ty Na u thai k cú s tng nhy cm vi insulin to iu kin cho s tớch tr m ca c th m Vo na sau ca thai k cú hin tng khỏng insulin, ng thi nhu cu insulin ca cỏc thai ph cng tng thai cng phỏt trin gõy thiu ht insulin tng i S kt hp ca hai yu t trờn lm thai ph cú xu hng dn ti ỏi thỏo ng na sau ca thai k ỏi thỏo ng thai k thng xut hin vo khong tun th 24 ca thai k, m rau thai sn xut mt lng ln cỏc hormone gõy khỏng insulin Vai trũ ca estrogen v progesterone vi s khỏng insulin Vo giai on sm ca thai k, estrogen v progesterone u c tng bi tit nhng tỏc ng ca hai loi hormon ny trờn hot ng ca insulin li khỏc Estrogen cú th lm tng ỏp ng ca c i vi tỏc dng ca insulin progesterone thỡ li l cht i khỏng nh tỏc dng ca insulin, lm gim s nhy cm ca mụ vi insulin, vỡ vy hai hormone ny cú th trung hũa tỏc dng ca Nu ngi bỡnh thng s dng c hai hormone ny s lm tng nng ceton, tng triglyceride v tng acid bộo t m khụng lm thay i nng ng mỏu Vai trũ ca cortisol vi s khỏng insulin Nng cortisol tng mang thai, vo giai on cui ca thai k, nng cortisol tng gp ln ngi khụng mang thai Rizza v cng s s dng k thut kp clamp nghiờn cu nhng ngi c truyn liu cao cortisol, cỏc tỏc gi nhn thy cú s tng sn xut glucose gan v gim nhy cm vi insulin [19] Vai trũ ca prolactin vi s khỏng insulin Trong thi gian mang thai, nng prolactin tng cao gp 7-10 ln [20] Skouby thm dũ mi liờn quan gia nng prolactin v tỡnh trng dung np glucose thai ph bỡnh thng v thai ph ỏi thỏo ng thai k bng cỏch tin hnh lm nghim phỏp dung np glucose vo na sau ca thai k v sau Kt qu nghiờn cu cho thy rng: vo na sau ca giai on mang thai, nng ng mỏu lỳc ca thai ph ỏi thỏo ng thai k cao hn mt cỏch cú ý ngha so vi nhúm chng, cũn sau ung ng thỡ ỏp ng tit insulin nhúm ỏi thỏo ng thai k li gim hn mt cỏch cú ý ngha so vi nhúm chng S khỏc v chuyn húa glucose hai nhúm cng rừ rt hn giai on sau Trong ú nng prolactin cựng thi im ca hai nhúm hon ton khụng cú s khỏc Nng prolactin cng khụng b ri lon thi gian lm nghim phỏp dung np glucose Tỏc gi i n kt lun rng khụng cú mi liờn quan gia tỡnh trng dung np glucose v nng prolactin [21] Nh vy prolactin khụng gi vai trũ quan trng c ch bnh sinh ỏi thỏo ng thai k Vai trũ ca lactogen (HPL: human placental lactogen) vi s khỏng insulin Lactogen (HPL) cú cu trỳc húa hc v chc nng dch ging nh GH Nng HPL vo thi im cui ca thai k gp 1000 ln nng ca GH Ngoi tỏc dng ng húa protein v ly gii m, HPL cũn cú tỏc dng lờn tuyn vỳ v hong th Dựng mt liu HPL nht cú th gõy tỡnh trng ri lon dung np glucose nh t 12 gi Vai trũ ca leptin vi s khỏng insulin Leptin l mt protein, TLPT 16kDa, c mụ m bi tit Nú úng mt vai trũ quan trng vic iu tit tiờu th nng lng, hn na leptin cũn tham gia vo chc nng ni tit, viờm, phn ng dch, sinh sn Do ú nú lm tng nhy cm insulin qua nh hng n bi tit insulin, s dng glucose, tng hp glycogen v chuyn húa acid bộo Nng leptin ph n cú thai cao hn ngi khụng mang thai, nht l vo ba thỏng gia v ba thỏng cui ca thai k Kautzky v cng s tin hnh nghiờn cu o nng leptin ba nhúm: cỏc thai ph b ỏi thỏo ng thai k, cỏc thai ph khụng ỏi thỏo ng thai k v ph n khụng cú thai Cỏc tỏc gi thy nng leptin 10 cao nht nhúm ỏi thỏo ng thai k, thp nht ngi khụng cú thai v s khỏc cú ý ngha thng kờ [22] 1.2.4.2 Cỏc giai on thai k v nh hng ca tng ng mỏu lờn s phỏt trin ca thai nhi Mi thai k bỡnh thng kộo di khong thỏng (40 tun) Thai k c chia thnh ba giai on, mi giai on kộo di thỏng [1], [17], [23] Ba thỏng u thai k Giai on nang trng gm tun u ca thai k Trong giai on ny, trng c th tinh hỡnh thnh nhng mm mng ca rau thai v gn vo thnh t cung ca ngi m Cng giai on ny tim ca thai c hỡnh thnh v bt u bm mỏu, h tiờu húa, xng sng, ty sng v nóo cng bt u c hỡnh thnh Khi c khong tun, thai nhi s cú mt, mi, mm v li Cỏnh tay, cng tay, bn tay, u gi, cng chõn v bn chõn bt u hỡnh thnh K t sau tun th ca thai k c gi l giai on bo thai, giai on ny cỏc c quan c th thai nhi dn phỏt trin v trng thnh S iu hũa glucose giai on u thai k cú ý ngha to ln i vi s hỡnh thnh v úng ca ng thn kinh Tng ng mỏu nng cú th gõy cỏc d tt nh: ng thn kinh h, s nh, phự mng ngoi tim Ngoi tng ng mỏu cựng vi tng ceton mỏu cũn gõy nhiu d tt bm sinh khỏc thỏng u thai k Túm li, cỏc ri lon chuyn húa giai on hỡnh thnh t chc d dn n cỏc khuyt tt cho thai nhi Vỡ vy, cn kim tra ng mỏu cho nhng thai ph cú nguy c cao b ỏi thỏo ng thai k t ln khỏm thai u tiờn giai on ny [1] Ba thỏng gia thai k Thai nhi tip tc phỏt trin v trng thnh Nhp tim thai tr nờn mnh hn, cỏc c v xng c hỡnh thnh, túc v lụng my bt u mc, thai nhi c ng nhiu hn Ngi m cng cú th cm nhn c c ng ca thai tun th 18 õy cng l giai on tt c cỏc t bo nóo cú mt sut cuc i u c hỡnh thnh v l giai on cú vai trũ quan trng n s phỏt trin 40 D KIN KT LUN D KIN KIN NGH TI LIU THAM KHO Nga, V.B., Nghiờn cu ngng glucose mỏu lỳc sng lc ỏi thỏo ng thai k v bc u ỏnh giỏ hiu qu iu tr Lun ỏn tin s y hc, Chuyờn ngnh Ni - Ni tit, Trng H Y H Ni, 2009 Quõn, .T., ỏi thỏo ng thai nghộn Bnh ni tit chuyn húa thng gp, 2005 Nxb Y hc: p 54-75 Metzger, B.E., Summary and recommendations of the Third International Workshop-Conference on Gestational Diabetes Mellitus Diabetes, 1991 40 Suppl 2: p 197-201 Coustan, D.R., Making the diagnosis of gestational diabetes mellitus Clin Obstet Gynecol, 2000 43(1): p 99-105 Magee, M.S., et al., Influence of diagnostic criteria on the incidence of gestational diabetes and perinatal morbidity JAMA, 1993 269(5): p 609-15 Matsuzawa, Y., K Hibi, and K Kimura, Risk assessment for cardiovascular disease - microvascular dysfunction Circ J, 2010 74(7): p 1296-7 Trayhurn, P and I.S Wood, Adipokines: inflammation and the pleiotropic role of white adipose tissue Br J Nutr, 2004 92(3): p 347-55 Scherer, P.E., et al., A novel serum protein similar to C1q, produced exclusively in adipocytes J Biol Chem, 1995 270(45): p 26746-9 Zavalza-Gomez, A.B., et al., Adipokines and insulin resistance during 10 pregnancy Diabetes Res Clin Pract, 2008 80(1): p 8-15 Catalano, P.M., et al., Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism Diabetologia, 2006 11 49(7): p 1677-85 Lain, K.Y., et al., First trimester adipocytokine concentrations and risk of developing gestational diabetes later in pregnancy Clin Endocrinol 12 (Oxf), 2008 69(3): p 407-11 Alberti, K.G and P.Z Zimmet, Definition, diagnosis and classification of diabetes mellitus and its complications Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO 13 consultation Diabet Med, 1998 15(7): p 539-53 Jorgensen, M.E., et al., New diagnostic criteria for diabetes: is the change from glucose to HbA1c possible in all populations? J Clin 14 Endocrinol Metab, 2010 95(11): p E333-6 American Diabetes, A., Diagnosis and classification of diabetes 15 mellitus Diabetes Care, 2004 27 Suppl 1: p S5-S10 American Diabetes, A., Gestational diabetes mellitus Diabetes Care, 16 2000 23 Suppl 1: p S77-9 American Diabetes, A., Gestational diabetes mellitus Diabetes Care, 17 2000 27 Suppl 1: p 88-90 Bỡnh, T.V., N. 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NGUYN TH THANH HNG Nghiên cứu nồng độ Adiponectin huyết bệnh nhân đái tháo đờng thai kỳ bệnh viện Phụ Sản Trung ơng Chuyờn ngnh: Húa sinh Mó s: CNG LUN VN THC S Y HC Ngi hng dn khoa hc: PGS.TS NG TH NGC DUNG H NI - 2014 CC CH VIT TT ADA : Hip hi ỏi thỏo ng M (American Diabetes Association) AMPK : AMP-activated protein kinase T : ỏi thỏo ng TTK : ỏi thỏo ng thai k HDL C : Lipoprotein t trng cao HOMA IR : Ch s khỏng insulin IADPSG : Nhúm nghiờn cu ca Hip hi ỏi thỏo ng v thai nghộn quc t IDF : Hip hi ỏi thỏo ng Quc t RBP4 : Retinol binding protein LDL C : Lipoprotein t trng thp NPDNH : Nghim phỏp dung np ng huyt PPAR- : Peroxisome proliferator-activated receptor- TLPT : Trng lng phõn t TZDs : Thiazolidinediones WHO : T chc y t Th gii YTNC : Yu t nguy c MC LC PH LC DANH MC BNG ... tháo đường thai kỳ bệnh viện Phụ Sản Trung ương với mục tiêu: Khảo sảt nồng độ adiponectin huyết bệnh nhân đái tháo đường thai kỳ phụ nữ có thai bình thường Đánh giá mối liên quan nồng độ adiponectin. .. tháng cuối thai kỳ Kautzky cộng tiến hành nghiên cứu đo nồng độ leptin ba nhóm: thai phụ bị đái tháo đường thai kỳ, thai phụ không đái tháo đường thai kỳ phụ nữ thai Các tác giả thấy nồng độ leptin... trẻ sinh từ thai phụ đái tháo đường thai kỳ cao thai phụ không bị đái tháo đường Nghiên cứu Langer cộng tiến hành Mỹ từ 1990 – 1999 2775 thai phụ có 555 thai phụ đái tháo đường thai kỳ chẩn đoán