A COMPARISON OF I~LATERaNALAND CORD BLOOD GLUCOSE LEVELS IN DL~BETIC AND NON-DIABETIC NIGERIANS IN RELATION TO BIRTH XArEIGHT AND MATERNAL BODY MASS 1NDEX JoNes O. AKPAN Departme.nt of Pha,macob~,, College of Medical Sciences, University of Cc,labar, Calabar, eVigeria
Pregnancy exerts a diabetogenic effect even in normal females..Mthough reports ~ show no elevation of the fasting blood glucose, postabsorptive glucose levels during glucose tolerance testing showed a general rise with the progression of pregnancy. Newborn infants of diabetics or women with gestatJonal diabetes are frequently longer and heavier than those of nondiabetics. The excess length and weight have been attributed to overproduction of insulin by the fetal pancreas in response to maternal hyperglycemia 8. Glucose crosses the placenta (but insulin does not), so tha~ the fetal pancreas, usually normal, is constantly stimulated to produce insulin and it is the anabotic effect of the insulin and glucose which is probably responsible for the large size of the babies of poorly controlled diabetic mothers. Evidence however suggests that the association between maternal prediabetas and large babies is incidental, at least in some circumstances, to the relationship of maternal adiposity to birth weight. Epidemiological studies also show that the association, between parity and diabetes is in some societies partly or wholly incidental to the association of paritT and obesity -~,~. Tills study was designed to compare maternal and cord blood glucose levels in diabetic and nondiabetic multiparous Nigerian women in relation to baby weight and maternal body mass index (BMI). Hospitals and health Centers located in re'ban centers were chosen for the study. Pregnant women native to Nigeria or other African countries were included in the study,. All women were of Negro o r i o n and the confirmed pregnancies were fathered by males of Negro orion. Key-words: Bb~h weight; Body mass index (BMI) ; Cord blood gh~cose; Magerr~a! blo~d glucose; Pregma.r~t diabet.ic a'rzd no~>diabetic z~qr"~ger~ar~s.
Received: April 13, 1988. Acta diabetol, lat. 26, 95d02, 1989. 95
BIRTH ~nG~IGHT AND MATERN~a~L BLOOD GLUCOSE AND BMI IN DIABETES
MATERIALS AND METHODS The survey was carried out between 1981 and 1987 in General Hospital and Health Centers strate~cally located in urban areas in southern Nigeria. Two hundred and eighty-nine pregnant diabetic and 360 pregnant non-diabetic cases were studied during the period. The std~jects were age-matched into three age groups of 20-24, 25-35 and 36 or over years, respectively. Height, weight and number of pregnancies of each subject were recorded. Each subject's family history" was recorded with particular emphasis on the existence of" diabetic relatives, other metabolic diseases and abnormal pregnancies (e.g. parity', still-birth, miscarriages and size of previous babies). All the subjects included in this study- had been seen at a prenatal clinic and had had at least one normal delive W. The pregnant subjects were recruited in the first trimester. After an overnight fast, blood was dra~vT~ from every subject and a 75 g OGTT was carried out for screening. The 2-h capillary" whole blood glucose following a 75 g OGTT and the fasting blood glucose were measured with dextrostix reagent strip and read in glucometer Model 558t (.Ames Department, Miles Laboratories, Elkhart/IN, U.S.A.). Subjects showing a 2-h blood glucose level of 200 mg/dt (11.1 retool/i) or greater were considered to be clearly diabetics. Those presenting t20 mg/dI (6.67 retool/l) or lower were considered non-diabetic. Borderline cases (t22-190 mg/dl) (6.8t0.5 retool/i) were not included in this study. The subjects were then further divided into diabetics and non-diabetics. Confirmed pregnant diabetics were managed mainly with either insulin or dietary control. Dieta W intake was regulated to allow about 25-30 kcal/kg body weight. Carbohydrates (200 g daily) consisting mostly of local non-refined starchy foods contributed 40-45% of the total calorie intake. Gestation period of each subject was closely monitored throughout the study along anthropometric data (weight, height, age, and number o f births). Umbilical cord and maternal blood samples were collected immediately after each delivery whether or not the subject was diabetic or non-diabetic. The umbilical cord was cut about 2 cm from fetal e n d and about 3 cm from placental end, respectively. Blood from umbilical cord cut at a perpendicular axis, was collected from the fetal end and from the placental end. Maternal blood was obtained by sterile capillary puncture at the finger tip. The blood glucose level was determined immediately by means of dextrosfix reagent strips read in Ames gtucometer ~. Statistical analyses of data were performed and the results were evaluated by Student's t-test and by linear regression. Maternal BMI was determined by dividing maternal weight in kg by the square of the maternal height in m (xkg/(ym) 2). The maternal BMI against the baby weight (ratio) was obtained by dividing maternal BMI by the baby weight in kg. RESULTS The means +_ SEM of variable parameters in different age groups of diabetic multiparous Nigerian women are summarized in tab. 1. Diabetes meltitus was confirmed by means of a 2-h whole blood glucose following the 75 g OGTT. The 2-h blood glucose level of 11.1 mmol/1 or greater was considered 96
J. o..ad~;%N
matemaI age (~ears~ variable parameters
1
maternal body weigh~ (kg)
2
maternal height (m)
3
matern~ BMI
20-24 (n==55)
25-35 (n=79)
36-over (n=155)
67.3 ±_ 0.4
58.7 ± 0.7
70.5 ± 0A
t.53 ± t 28,8 ± 0.5
1,55 ± 0.S
1.49 ± 0.9
2S.5 ± 0.9
31.8 ± 0.5
4
gesta~iona[ age (days)
281.4
264.5
265.6
5
birth weight (kg)
4.4 z 0,5
4.7 ± 0.7
5.1 ± 0.6
6
cord blood glucose at fetal end (mmol,'l)
4.9 ± 0,5
4.8 2 0.6
5,2 ± 0,7
7
cord Mood glucose at placental end (retool'l)
5,8 ± 0.4
5.7 ± 0.5
6.t
8
materna! fhsnng blood glucose (retool/t)
6.8 i 0.9
6.8 ±: 0.7
79 ± t.9
9
mama-halBMI/birth weigh~
6.5
6.1
6.2
~-- 0.8
N~b. 1 - Variable parameters in different age g r o u p s o f diabetic multiparous w o m e n in Nigeria.
diabetic. Borderline cases (6.8-10.5 retooL/l) were not included in the study. Blood glucose level of 6.6 retool/1 or below was considered non-diabetic. As shown in line 3, maternal BMI increased with increasing age and was significantly different in the group of 36 years and over when compared **4th the 20-24 year age group (31.8 i 0.5 vs 28.8 ± 0.5). Gestadonal age in days (line 4) was higher in the group o f 36 years and over, but the difference was not significant. Birth weight and umbilical cord blood glucose showed slight increase ~Jth increasing age of diabetic women (lines 5, 6, 7 and 8). The ratios of maternal BMI vs birth weight were similar in all age groups of diabetics (tab. 1, line 9). The means ± SEM of variable parameters in different age groups of nondiabetic muttiparous Nigerian women are shown in tab, 2. The subjects were considered non-diabetic if the 2-h whole blood glucose was 6,6 mmol/1 or lower following th.e 75 g OGTT.
maternal age (?,ears) variable parameters
l
maternal body weight (kg)
2
maternal height (m)
3
rnateraN BM[
4
gestatloual age (days)
5
birth ~eight (kg)
20-24 (n=80)
25-35 (n=t25]
36-over (n=lCa0)
64,8 ± 0.8
65.7 z 0.9
66.9 ± 0.7
L59 --+ 0.9
1.62 +_ 0.6
1.57 ± 0.7
25.63 ± 0.5
25A8 ±: 0.6
27.14 ± 0.5
263.6
266.3
265.6
2.9 ± 0.4
3.2 -+ 0.5
3,7 ± 0.8 2,9t ± 0.8
6
cord blood glucose at fetal end (mrnol/1)
2.66 ± 0,9
2.72 ± 0.2
7
cord blood glucose at placental end (retool/l)
3~35 ± 0.7
3.56 ±: 0.6
3.74 z 0.5
8
maternM fasdng blood glucose (retool/l)
4.22 ± 0.8
4.63 ± L1
4.8t ± 0.9
9
maternaI BML"bbth weight
8.84
7.82
7.33
Tab. 2 - Variable parameters in differen~ age groups o f non-diabetic m u l d p a r o u s w o m e n in Nigeria.
97
B I R T H W E I G H T A N D MATEP~NAL B L O O D G L U C O S E A N D B M I I N D I A B E T E S
i I 0 J •
o
°iIl
mg
o
®
e m
®
45~ 4' 3
3.5
4
4.5
5
5.5
6
babv weight (kg)
Fig. 1 - Diagram of linear regression of maternal blood gtucose v s baby weight in pregnant diabetics. Each regression point on the graph represents 5-8 preg-nant diabetic women age 95 years or over. r = 0.90503.
2
2.5
3
3,5
4
4.5
baby weight (kg)
Fig. 2 - Diagram of linear regression o f maternal blood giucose v s baby weight in pregnant non-diabetics. Each regression point on the ~ a p h represents 5-10 pregnant non-diabetic women age 25 years or over, r = 0.15480.
As shown in line 3 the maternal BMI increased only slighdy but not significantly (p>0.5) at the age of 36 years or over in the non-diabetics (27.14 _+ 0.5). There was no difference in the maternal BMI between the 20-year and 35-}ear age groups (25.03 _+ 0.5; 25.63 +_ 0.6). There was also no significant difference (p>0.5) in the gestationat period between the various age groups of non-diabetics. However, birth weight appeared to increase with increasing maternal age. The umbilical cord blood glucose and maternal blood glucose levels were similar in all age groups. The ratio of maternal BMt v s birth weight did not decrease significantly (p>0.5) with increasing maternal age 8.84, 7.82, 7.33 for the corresponding age group 20-24, 25-35, and 36 and over, respectively (line 9). Figures 1 and 2 are graphs of linear regression analyses of maternal blood glucose v s baby weight in diabetic and non-diabetic muhiparous Nigerian women aged 25 years and over. The correlation coefficient (r) of the relationship between maternal blood glucose and baby weight in the diabetics was +0.905. The degree of correlation between maternal blood glucose and baby weight in the non-diabetics of similar age was +0.t55 indicating only a slight linear relationship. In both groups, however, baby weight reIated positively with maternal blood glucose, but the relationship was stronger in the diabetics as shown in fig. 1. Figures 3 and 4 show graphs of linear regression analyses of maternal BMI vs baby weight in diabetic and non-diabetic multiparous women aged 25 years 98
j, co, AKPAN
i
!
.°i
r
35t
35,
30'
I
=
®
J
25t
~25
E
1
-
"~ 201
2o1 ~= is
" "
:
:,,
== t5]
'°
E
' .
~oI
5 t 0
3.5
,~
45
5
s5
baby weight (kg}
Fig. 3 - Diagram of linear regression of matermd BMI vs baby weight in pregnant diabetics. Each regqession poine on the graph represents 5-8 pregnant diabetic women age 25 years or over. r = 0.91846
0!1.0
1.5
2
2.5
3
3.5
4
baby weight (kg)
Fig. 4 - D i a g r a m o f l i n e a r r e g r e s s i o n o f m a t e r -
hal BMI v s baby weight in pregnam non-diabetics. Each regression point on the graph represents 5-10 pregnant non-diabetic women aged 25 years or over. r = 0.t380.3
a n d over, respectively. M a t e r n a l B M I related positively a n d linearly with b a b y weight (r = +0.918) in the diabetics. I n the non-diabetics, however, the relationship b e t w e e n m a t e r n a l BMI a n d b a b y weight was r a t h e r w e a k with correlation coefficient (r) o f +0.t38, indicating that the n o r m a l m a t e r n a l physical stature in n o r m a l w o m e n (non-diabetic) h a s little or no i n f l u e n c e o n the size o f the b a b y (fig. 4). T h e c o r r e l a t i o n b e t w e e n lJae O G T T values in the first t r i m e s t e r o f p r e g n a n c y a n d b a b y weight at term in the diabetics was strong (r = 0.895). T h e r e was little or no c o r r e l a t i o n b e t w e e n O G T T values a n d b a b y weight in tim non-diabetics (r = 0.213). G r a p h s o f l i n e a r r e g r e s s i o n o f glycemic values o f the O G T T are not presented. DISCUSSION T h e f r e q u e n c y o f o c c u r r e n c e o f diabetes mellitus in Nigeria is often desc r i b e d as indefinite due to insufficient i n f o r m a t i o n ~. Variable m ~ e - m - f e m a t e sex rados in adult-onset diabetes in Nigeria as h i g h as 2:1 in s o m e groups (mostly in western Nigeria) have b e e n r e p o r t e d by OS~NTOKb..w a n d A ~ y KtrcBE 7. Inl:;ormation o n a caret\d a n d n o n - r e t r o s p e c t i v e study o f diabetes in p r e g n a n c y a n d the association o f parity with birth weight, etc., a m o n g Nigerian w o m e n is ve W scarce. I n this report, m a t e r n a l aald umbilical cord b t o o d glucose levels in diabetic a n d non-diabetic m u h i p a r o u s N i g e r i a n w o m e n were c o m p a r e d to b a b y weight 99
BIRTH WEIGHT AND MATERNAL BLOOD GLUCOSE AND BMI IN DL~BETES
and maternal BMI. Other parameters such as the gestational age and the ratio of maternal BMI vs baby weight of different age groups were also assessed in diabetics and non-diabetics. In the author's opinion, probably diabetes management during pregnancy in the cases observed in this study was not sufficiently effective and hence the data presented in this report may not reflect a well controlled diabetes during pregnancy. As sho~.~ in tab. 1, maternal BMt increased significantly with age particularly at 36 years and over in the diabetics whereas the maternal BMI only increased slightly but not significantly in the non-diabetics. Maternal BMI was determined by dividing maternal weight in kg by the square of maternal height in m. It is an index of obesity. In Western countries, BMI of 95 or more for women and 27 or more for men are classified as obese*. A standardized obesity index for Nigerians is not yet available. The greater adiposity of the diabetics and the resultant increase in fetal mass may account for the signifIcant increase in the calculated maternal BMI in the diabetics as shown in tab. 1. This because the BMI is the ratio of maternal body weight to the square of maternal height. This influence of adiposiV/is in agreement with reports by HORC.ER et al. ~ who demonstrated a strong association of maternal adiposi b" and birth weight. The increases observed in birth weight with increases in umbilical blood glucose, and maternal blood glucose are expected and are consistent with reports of similar studies of non-Negro diabetic populations 9.~0. The increase in birth weight in proportion to maternal age in both diabetics and non-diabetics is partly due to the increase of adiposity- with age previously alluded to 3, and to glycemia. This is in agreement with the concept of an age gradient in blood glucose levels reported by O'Sbq2,IvAN6. There is no ready explanation for the observed slight increase in the gestational age at 36 years and over particularly in the diabetics. Baby weight showed a strong positive correlation with maternal blood glucose only in the diabetics with a correlation coefficient (r) of +0.90503. There was little or no correlation between baby weight and maternal blood glucose in the non-diabetics (r = +0.1548, figs 1 and 2 respectively). In a study of 20 healthy pregnant Nigerian women who attended the ante-natal clinic of the UniversiW College Hospital, Ibadan, Nigeria, F.c.,~,tn-~wa et al. 2 reported lower levels of 2-h blood gtucose following 75 g O G T T in the second and third trimesters. Although such observations were at variance with experiences in Caucasian women in whom the O G T T patterns in pregnancy either remained unchanged or became worse in the course of gestation, it is possible to attribute the ]~ck of correlation between baby weight and maternal blood glucose in the pregnant non-diabetic women observed in this stud}" to normoglycemia. Maternal h~?erglycemia is considered the most likely explanation for the large babies of women with diabetes mellims ~. Therefore the strong correlation between birth weight and maternal blood glucose among the diabetic muttiparous Nigerian women observed in this report is consistent ~ith similar studies of non-Negro women. O n the other hand, the lack of a similar correlation among the non-diabetics shown in fig. 9 could indicate that normal blood glucose (individual high variation notvdthstanding) does not significantly affect birth weighL The maternal physical stature (under normal physiological considerations) does not significantly affect the birth weight. However, in poorly controlled diabetes mellims, there is a strong positive correlation between 100
j. o. A ~ . ~ b i r t h w e i g h t a n d m a t e r n a l B M I (figs 3 a n d 4). T h e s t r o n g c o r r e l a t i o n b e t w e e n birth weight and materna! stature in the diabetics could again be attribumd to g r e a t e r a d i p o s i t y a n d h } r p e r g l y c e m i a w h i c h a r e a s s o c i a t e d w i t h d i a b e t e s metlims. E ~ 4 d e n c e is p r e s e n t e d i n t h i s s t u d y t o s h o w t h a t t h e i n c r e a s e i n b i r t h w e i g h t i n N i g e r i a n d i a b e t i c w o m e n is t h e r e s u l t o f t h e m a t e r n a l h ? , p e r g l y c e m i a and adiposity, and that matmqqat physical stature does not significantly influence the size of the baby in the non-diabetics.
SUMMARY Maternal and cord blood glucose levels in diabedc multiparous Nigerian women were compared in reiation to variable parameters such as birth weight, maternal body mass index ~'BMI), age and number of births, in order to ascertain the effect of diabetes on p a r i g among womert of pure N e r o race. Pregnant women of pure Negro orig~n who were native to Nigeria or other African cotmtries were selected for the sin@. The subjects were age-matched into three age groups of 20-24, 25-35, and 36 or over years, respectively and then ,,ere further di~dded into diabetics and non-diabetics folio,Mug a 75 g OGTT. Umbilical cord blood and maternal blood samples were collected immediately after each delivery. The amount of glucose in blood was determined by means of Dextrosdx reagent strips read in a glucometer, girth weight, umbilical cord blood glucose and maternal blood glucose increased slightly with increasing age in the diabetics. There was no effect of age on umbilical cord and maternal blood glucose levels in non-diabedcs. MaternN BMI also increased with age in the diabetics whereas it increased only slighdy but not significantly at the age of 38 years and over in the non-diabetics. However, there was a slight increase in birth weight w-ith increasing age among the non-diabetics. The correlation coefficients (r) of the relationship between maternal blood glucose and baby weight were +0.905 for the diabede and ~-0.155 for non-diabetic groups. The correlation coefficients(r) of the relationship between maternal BMI and baby weight were +0.918 in the diabetics and +0.138 in the non-diabetics, ~espectivety. The correlation coefficient of the reladonship between the OGTT results were ÷0.095 for diabetic and +0.213 for non-diabetic groups. It is concluded that the increase in the baby weight in the diabetic mukiparous women in Nigeria is the result of maternal hyperglycemia and adiposi~, and that maternal physical stature in normal (non-diabetic) women does not significantly influence the size of the baby in non-diabetics.
ACt~NOWLEDGEMENTS The author Mshes to acknowledge the clinical advice of Prof. A. Sogbanmu and Dr. A. Ekanem. Grateful acknowledgements also go to several nurses and technicians at the H e N ~ Centers and Hospitals where data for this study were collected. The author is highly indebted to the staff and management of the University of Ilorin Teaching Hospital, and those of General Hospitals located at Ikot Ekpene, and Diamond Hills Health Center for their assistance during this study. "This study was supported in part by Upjobn Company, Kalamazoo/MI, U.S.A. and by Senate Research Grant, Uriiversitv of Itorin Nigeria.
R~IFERENCES I. BENNET'r P. H.: Recommendations on the standardization of methods and reporting of tests for diabetes and its microvascular complications in epidemiolo~c studies - DidDeL Care 2. 98, 1979. 2. F,~,~L~T~VAO. O., , ~ ' ; R. A., Aoa~_.VS~B, O.: Oral glucose tolerance test in healthy pregnant Nigerian v,romen - Diabeu Care H, 412, t988. 3. HoaGea E. C., MILER M. C., CON~E~ E. D.: Relation of large birthweight to maternal diabetes mel!itus - Obstetr. GynecoL 45, 150. 1975. 101
B I R T H ~,~,JdllGHT AND M A T E R N A L B L O O D G L U C O S E duND B M [ [ N DIeYP,E T E S
4, JAICRETTR. J., IZXEN I1, Ha~:ow'mx C.: "Instant" blood glucose m e a s u r e m e n t using Dextrosdx a n d a reflectance-meter - Diabetes 19, 724, 1970, 5. O'SuLL~Va~'VJ. B.: Gestadonal diabetes, unsuspected asymptomadc diabetes in pregnancy New-Engl. J. Med. 264, t082, 1961. };. O'SULLIVANJ. B.: Age u a d i e n ~ in blood glucose levels. Magnitude a n d clinical implications Diabetes 23, 713, 1974. 7. OSUXTOK~UNB. O., AI¢IZqk~CE~:F. M, FRaN'C~S t. I., P,aEDD¥ S., OSUNTOKUN O , TAYLOR G. O. L.: Diabetes mellims in Nigerians. A study of 832 padencs - West Afr. reed. J. 20, 295, 197I. 8. PzoEt~sa-@, PEDERSEN L. M,,JoRoENSEX K. R.: Insulin a n d gtucose in the plasma from umbilicN vein a n d heel blood of newborn infants of diabe6c women - Acta endocrinol. (Kbh.) 53, 310, t966. 9. t~HP~SON S. L.: A study of the reladonship between some prediabetic sti~nas, glucose tolerance in la~e pregnancy and the birthweight of the children - Acta obstem gynecol, scand. (Suppl. 33), I07, 1974. t0. Vv~TZ R , Laaox Z,: Height and weight of children b o r n to mothers with diabeLes mellims IsraelJ. reed. Sci. 12, 195, 1976, 11. WES't K. M.: Epidemiotogy of diabetes and its ~asctflar [esions. Elsevier, New Y~rk, 1978; Chapter 7, p. i91.
P~ests for r@rims sho-uM be addressed to: JONES O. A~AN
D~art~tent o1"Pharmacology College of Medical Scie%ces University of Calabar Cal,abar- N~eria
102
