The role of maternal gut hormones in normal pregnancy: fasting plasma active glucagon-like peptide 1...

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The role of maternal gut hormones in normal pregnancy: Fasting plasma active GLP-1 level is

a negative predictor of fetal abdomen circumference and maternal weight change

Georgios Valsamakis1, Alexandra Margeli

2, Nikolaos Vitoratos

1, Anastassios Boutsiadis¹, Evangelos

.G. Sakkas¹, George. Papadimitriou1, Nasser M. Al-Daghri

3, Dimitrios Botsis¹, Sudhesh Kumar

3,

Ioannis Papassotiriou2, George Creatsas

1 and George Mastorakos

1

1Endocrine Unit, 2

nd Department of Obstetrics and Gynecology, Aretaieion University Hospital,

Athens Medical School, Athens, Greece,

2Department of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, Athens, Greece,

3Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM),

University Hospital Coventry and Warwick Medical School, Coventry, UK

Running title: Fasting active GLP-1 in normal pregnancy

Word Count: 2971

Corresponding author

Ass Prof. George Mastorakos, MD, DSc

3, Neofytou Vamva

Athens 10674 Greece

Fax: 00302103636229, tel:00302103636230

Email: [email protected]

of 23 Accepted Preprint first posted on 1 March 2010 as Manuscript EJE-10-0047

Copyright © 2010 European Society of Endocrinology.

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Abstract

Objective: Maternal weight in pregnancy contributes to glycemic environment affecting fetal

growth. Gut peptides (GLP-1; GIP; ghrelin; PYY) have been related to insulin sensitivity and

secretion, weight control and adipose tissue metabolism. This study aimed at examining the

associations of gut hormones during pregnancy with maternal glucose homeostasis, maternal weight

and fetal growth.

Methods: 55 pregnant non-obese non-diabetic Caucasian women were examined during the

three trimesters of pregnancy and had anthropometric measurements, evaluation of fasting maternal

plasma GLP-1(active), ghrelin (active), total PYY, total GIP and a 75g oral glucose tolerance test.

Homeostasis model assessment (HOMA-R), insulin sensitivity index (ISI), and indices of insulin

secretion were calculated. Fetal growth was estimated by ultrasound.

Results: Fasting GLP-1 increased significantly from second to third trimester (p<0.05).

Fasting GLP-1 correlated positively with HDL-C (r=0.52, p=0.04). At second trimester fasting GLP-

1 levels correlated negatively with fetal abdomen circumference (r=-0.55, p=0.034), birthweight (r=-

0.50, p=0.040), HOMA-R (r=-0.65, p=0.001), insulin secretion and triglycerides. At first trimester

fasting ghrelin levels correlated negatively with HOMA-R and insulin secretion and positively with

ISI. By backwards multiple regression analysis, first trimester GLP-1 levels were the best negative

predictor of second trimester fetal abdomen circumference (beta=-0.96, p=0.009). By longitudinal

regression model, maternal fat and HOMA-R were positive and fasting GLP-1 levels negative

predictors of maternal weight change during pregnancy.

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Conclusions: During pregnancy, maternal GLP-1 might be involved in mechanisms

compensating for the pregnancy-related increase of glycemia and insulin resistance, suggesting a role

of this peptide in maternal metabolism and weight and fetal growth.

Key words: gut hormones, fasting active GLP-1, maternal weight, fetal abdomen

circumference

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Introduction

During pregnancy there is an increase of insulin resistance from second to third trimesters

(1). The prevalence of prepregnancy maternal obesity is also increasing. The negative role of excess

maternal weight gain on maternal carbohydrate metabolism during pregnancy as well as on fetal

growth is well established (2, 3, 4). Reports from Scandinavia (5) and North America (6) show an

increase of births of large for gestational age. Endometrial environment via its role on fetal growth is

important on programming of future metabolic diseases during adult life (7, 3).

The role of a new class of gut-derived peptides such as glucagon-like peptide 1 (GLP-1),

glucose-dependent insulinotropic peptide (GIP), ghrelin and peptide YY (PYY) in insulin sensitivity

and secretion, weight control and adipose tissue metabolism has been recently stressed. Glucagon-

like peptide 1, an incretin, stimulates insulin and suppresses glucagon secretion, inhibits gastric

emptying and reduces appetite and food intake. In insulin resistance states (i.e. type 2 diabetes

(T2DM) and obesity) GLP-1 secretion is decreased (8, 9). The administration of GLP-1 receptor

agonists in T2DM improves glucose homeostasis while it is followed by a dose dependent weight

loss compared to placebo (10, 11, 12). Furthermore, GIP, another incretin, has been associated to

decrease of resting energy expenditure in healthy humans (13). Ghrelin, discovered as a natural

ligand of the growth hormone secretagogue receptor type 1a, is a gut-brain peptide with

somatotropic, food intake increasing and adipogenic effects. In subjects with T2DM as well as in

those with abdominal obesity and/or metabolic syndrome ghrelin levels are low (14, 15). The gut

hormone PYY reduces feeding in obese humans and shows Y2-receptor mediated anorectic effects,

modulating neuronal activity within hypothalamic, brainstem and brain regions involved in reward

processing. Fasting circulating PYY concentrations correlate negatively with BMI and waist

circumference in humans (16, 17). In morbidly obese individuals GLP-1 and PYY levels increase

while ghrelin levels decrease after Roux-en-Y gastric bypass surgery more than after laparoscopic

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adjustable gastric banding surgery. These changes have been associated to the importance of weight

loss and the improvement insulin sensitivity (18, 19).

The aim of this study was to examine the possible physiological associations of gut hormone

levels in the same cohort of non obese, non diabetic pregnant women during the three trimesters of

pregnancy with maternal glucose homeostasis and body weight as well as with fetal growth. The

exclusion of obese or diabetic pregnant women from this study aimed at eliminating obvious

confounding factors from the study of the direct interplay among fasting gut hormones, maternal

insulin resistance and fetal growth. Further studies targeting at these specific populations should be

undertaken.

Materials and Methods

Patients

Sixty healthy pregnant Caucasian women aged 29.5 ± 4.5 (mean±SD) years with body mass

index (BMI) 24.7 ± 2.2 kg/m2 before pregnancy, with no history of T2DM or other endocrine

disease, were recruited from the Obstetrics and Gynecology outpatient clinic of a university hospital

during the first trimester of pregnancy, after exclusion of women with BMI (before pregnancy) over

30. The study was approved from the local ethics committee. Written informed consent was obtained

from all subjects.

Protocol

The recruited pregnant women were seen in the outpatient clinic once during each of the

three trimesters of their pregnancy at 10 th

-12th

, 24 th

-26 th

and 34 th

-36 th

week, respectively. Five of

the above women developed gestational diabetes during pregnancy and were subsequently excluded.

At each visit they were submitted to anthropometric measurements, a blood sampling for

measurement of gut hormones (active GLP-1, total GIP, active ghrelin, total PYY) and lipids (total

cholesterol, HDL and LDL cholesterol, triglycerides) at fasting state and an oral glucose tolerance

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test (OGTT). An ultrasound of the fetus was performed during second (24th-26th

week) and third

trimesters (34-36th

week).

Anthropometric measurements: All measurements were carried out from a single observer.

Weight of all subjects without shoes and light clothing was measured in kilograms to the nearest 0.1

kg on a beam balance. Height in meters was measured to the nearest mm using a stadiometer and the

BMI in kilograms per square meter was calculated. Maximum hip circumference in centimeters was

taken in duplicate with a 6 mm wide flexible tape at the widest part of the trochanters at horizontal

position with feet kept 20-30 cm apart. Skinfold thicknesses were measured on the left part of the

body with Harpenden skinfold caliper (Assist creative resources Ltd, Wrexham, UK) in triplicate to

the nearest 0.2 mm. Biceps and triceps thicknesses were measured at the midpoint of the upper arm,

between the acromion process and the tip of the bent elbow. Subscapular skinfold thickness was

measured at the natural fold about 2-3 mm below the shoulder blade in an oblique angle.

Suprailiac skinfold was pinched at 2-3 cm above the iliac crest on the lateral side and mid-

axillary line. The sum of all four location skinfold measurements was estimated and percent body fat

was determined by charts interpolating for age based on the Durnin and Womersly data (20). Supine

blood pressure was recorded with a mercury sphygmomanometer using the mean of three

measurements.

Blood sampling for gut hormones collection: Blood samples for measurement gut hormones

were collected in tubes with EDTA as an anticoagulant. After blood collection, DPPIV inhibitor for

GLP-1 measurement and serine protease inhibitor for active ghrelin measurement were added. Tubes

were inverted several times to mix, then they were centrifuged and the plasma that was collected

after centrifugation was aliquoted and stored at –70° C until assay.

Oral glucose tolerance test: After an overnight fast, a 75 g OGTT was performed. Glucose

and insulin levels were determined in blood samples drawn at 0, 5, 15, 30, 60, 90 and 120 min time-

points. Blood samples were stored immediately at –70° C.

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Fetal ultrasound measurements: At each ultrasound visit fetal measurements (estimated

weight, abdomen circumference, femur length, head circumference, biparietal diameter) were carried

out from a single observer. Ultrasound was performed with employing a Phillips HD11

ultrasonographer.

Blood Chemistry and hormone assays

Blood chemistry included measurements of glucose, serum total cholesterol HDL-cholesterol,

LDL-cholesterol and triglycerides was performed the Siemens Advia 1800 Clinical Chemistry

system, while insulin was determined using the Medgenic immunoenzymetric assay (Biosource,

Nivelles, Belgium).

Active GLP-1, total GIP, active ghrelin and total PYY were measured in plasma

simultaneously by a multiplex assay kit manufactured by Millipore, the Human Gut Hormone

LINCOplex Kit purchased from LINCO Research Inc, Missouri, USA). Intraassay and interassay

coefficient of variation (CV) were less than 11 % and less than 19 %, respectively, according to the

manufacturer.

Mathematical transformations

Indices of carbohydrate metabolism: a) Carbohydrate metabolism index derived from fasting

values. Insulin resistance was estimated by the homeostasis model assessment (HOMA-R) [insulin at

baseline (pmol/L) x glucose at baseline (mmol/L)]/135 (21). b) Carbohydrate metabolism indices

derived from OGTT values. Insulin sensitivity was estimated by the insulin sensitivity index

(ISI)=0.226-[0.0032 x BMI]-[0.0000645 x insulin at 120 min (pmol/L)]-[0.00375 x glucose at 90

min (mmol/L)] (22). Beta cell secretion of insulin was estimated by the following indices (25-25):

Predicted index of first phase of insulin secretion (1st PHIS) = 1283+[1.289 x insulin at 30 min

(pmol/L)]-[138.7 x glucose at 30 min (mmol/L)] +[3.772 x insulin at baseline (pmol/L)] and

predicted index of second phase of insulin secretion (2nd

PHIS) =287 + [0.4164 x insulin at 30 min

(pmol/L)]- [26.07 x glucose at 30 min (mmol/L)] + [0.9226 x insulin at baseline (pmol/L)].

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Statistical analysis

Data are described as mean ± SD (median and interquartile range for data not normally

distributed). To test the change of each variable during pregnancy the one-way repeated measures

ANOVA test was used in case of normally distributed variables and the non parametric Friedman

ANOVA test in case of non normally distributed variables. To test whether changes between

different time points were different we performed paired t-test. To test the associations between

different variables and to test correlations between differences the Spearmann correlation analysis

was performed. Backwards regression analysis was undertaken to define early predictive variables of

the second trimester. To find predictors for the maternal weight during the whole study time we used

a longitudinal regression model. A p-value of <0.05 was considered to be significant. The SPSS

statistical software was used for statistical analysis (SPSS Inc., Chicago, IL, USA) (23).

Results

1. Changes of anthropometric variables, ultrasound measurements, hormones and

carbohydrate metabolism parameters during pregnancy (Table 1)

Maternal weight and percent of total body fat increased significantly in an incremental way

from the first to the second and to the third trimesters of pregnancy (p<0.05). Ultrasound fetal

measurements of estimated weight, abdomen circumference, head circumference, biparietal

diameter, and femur increased significantly from the second to the third trimester of pregnancy

(p<0.05).

Plasma GLP-1 increased significantly from the second to the third trimester (p<0.05). There

was no statistically significant change of plasma GIP total, ghrelin active and PYY total during

pregnancy (p>0.05).

Fasting insulin levels and HOMA-R index were significantly higher in the third as compared

to the first and the second trimesters (p<0.05) while the ISI index decreased significantly in the third

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as compared to the first and the second trimesters (p<0.05). At the second and the third trimesters 1 st

PHIS and 2 nd

PHIS were significantly higher than at the first trimester (p<0.05).

2. Correlations among anthropometric variables, ultrasound measurements, hormones and

carbohydrate and lipid metabolism parameters during pregnancy

2a) Anthropometric variables, ultrasound measurements and maternal hormones

At second trimester fasting plasma GLP-1 active correlated negatively with U/S measured

fetal abdomen circumference (p=0.034, r=-0.55) (Fig 1) and birthweight (p=0.040, r=-0.50) (Fig 2).

There was no other correlation observed among anthropometric variables, ultrasound measurements

and hormones.

2b) Hormones, carbohydrate metabolism parameters and lipids

At first trimester fasting plasma active ghrelin levels correlated negatively with HOMA-R

(p=0.027, r=-0.50), 1 st

PHIS (p=0.03, r=-0.49) and 2nd

PHIS (p=0.04, r=-0.41) and positively with

ISI (p=0.009, r=0.77). Fasting plasma GLP-1 correlated positively with HDL-C (p=0.04, r=0.52). At

second trimester fasting plasma GLP-1 active levels correlated negatively with 1st PHIS (p=0.03, r=-

0.54), 2nd

PHIS (p=0.04, r=-0.50) and HOMA-R (p=0.001, r=-0.65) and triglycerides (p=0.02, r=-

0.55). There was no other correlation between hormones with carbohydrate metabolism parameters

and lipids.

2c) Correlations among hormones

At first trimester fasting plasma active ghrelin levels correlated positively with fasting plasma

GIP total levels (p=0.02, r=0.52). At third trimester fasting plasma active ghrelin levels correlated

positively with fasting plasma active GLP-1 levels (p=0.028, r=0.68).

3. Correlations between changes (delta, ∆) of the measured variables among the three

trimesters of pregnancy

Between first and second trimester ∆ maternal weight correlated positively with ∆ 1st PHIS

(p=0.02, r=0.63), ∆ 2nd

PHIS (p=0.04, r=0.59) and ∆ percent maternal fat (p=0.008, r=0.51).

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Between second and third trimester fasting active ∆ GLP-1 correlated negatively and positively with

∆ maternal weight (p=0.001, r=-0.97) and fasting active ∆ ghrelin (p=0.02, r=0.69), respectively.

Delta maternal weight correlated positively with ∆ maternal fat change (p=0.04, r=0.45).

4. First trimester predictor of second trimester fetal abdomen circumference.

Backwards multiple regression analysis revealed that fasting active plasma GLP-1 levels of

the first trimester were the best negative predictor (p=0.009, beta=-0.96) of U/S measured fetal

abdomen circumference of the second trimester among maternal fat, plasma levels of active ghrelin,

total GIP and total PYY levels of the first trimester.

5. Predictors of maternal weight change during all trimesters of the pregnancy.

The longitudinal regression model revealed that the best predictors of maternal weight change

during the three trimesters of pregnancy were maternal fat (p=0.005, t-value=3.12) and HOMA-R

(p=0.013, t-value=2.79) as positive predictors and fasting active plasma GLP-1 levels (p=0.015, t-

value=-2.71) as negative predictor among PHIS-1, PHIS-2, plasma total GIP, active ghrelin, and

total PYY.

Discussion

We investigated the fasting circulating levels of maternal gut hormones (active GLP-1, active

ghrelin, total PYY, total GIP) during each of the three trimesters of normal pregnancy in the same

group of non-obese non diabetic women and their correlations with maternal weight, adipose tissue

(total percent fat), lipid and carbohydrate metabolism. The latter was evaluated on OGTT-based

mathematically derived indices (24). GLP1 affects mostly post-prandial glycemia and it presents in

two forms, the total reflecting secretion and the active reflecting potential action. Fasting active

GLP1 was measured in this study so that the description of its role in maternal physiology is not

confounded by insulin secretion induced from orally ingested glucose. Data exist showing that active

GLP-1 might affect blood glucose via actions other than stimulation of glucose dependent insulin

secretion (25, 26, 27) such as glucagon secretion, suppression of hepatic glucose output and decrease

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of gastric emptying rate (8, 27). We found that during the second trimester fasting active plasma

GLP-1 levels correlated negatively with HOMA-R. In the past Cypryk et al. have shown a positive

correlation of fasting total GLP-1 with HOMA-R in a mixed population of 13 controls and 13

pregnancies with GDM at second trimester (28). This discrepancy might be due to the facts that in

our study active GLP1 and not total was measured, and secondly, active GLP1 was measured in a

non-GDM population of women with normal pregnancies. In insulin resistance states such as type 2

diabetes GLP-1 levels are significantly decreased whereas in obesity there is attenuated GLP-1

secretion (8, 9). In addition, in this study, during the second trimester fasting active plasma GLP-1

levels correlated negatively with insulin secretion parameters. It is well accepted that most cases of

increased insulin resistance are followed by increased insulin secretion (29, 30). Furthermore, we

found that fasting active plasma GLP-1 increased significantly from second to third trimester. This

increase of fasting GLP-1 might be part of mechanisms involved in compensation of the pregnancy-

related increase of glycemia and the development of insulin resistance.

Delta fasting active plasma GLP-1 levels from the second to the third trimester correlated

negatively with ∆ maternal weight. Treatment of non pregnant diabetic or obese subjects with GLP-1

receptor agonists resulted to weight loss (11, 31). An anorexigenic effect has been attributed to GLP-

1 exerted possibly via direct and/or indirect activation of CNS (32). In addition, in this study fasting

plasma active GLP-1 levels were negative predictors of maternal weight change in the longitudinal

regression model applied from the first to the third trimester whereas maternal total percent fat and

HOMA-R were positive predictors. Maternal total percent fat measured by using the sum of skinfold

caliper measurements is an approximation of the maternal fat content and does not reflect central fat

deposition. It is the only ethically available method that can be used for maternal fat content

estimation during pregnancy. It is possible that GLP-1 might play an important role in keeping

maternal weight within normalcy during pregnancy limiting, thus, in an indirect way the

development of insulin resistance.

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Moreover maternal fasting active GLP-1 levels at first trimester were the best negative

predictors of fetal abdomen circumference at second trimester. Early in pregnancy, the most

important contributor for fetal growth is the genetic potential. Maternal metabolic response to

alterations of the equilibrium is also based on the maternal genetic potential which, in part, is

inherited to the fetus. For example, in the past we have shown that the mothers of babies with

intrauterine growth restriction share a common metabolic feature with their offsprings ie. increased

circulating leptin levels as compared to mothers of babies of normal growth (40).

At the second trimester maternal fasting active GLP-1 levels correlated negatively with fetal

abdomen circumference as well as with birthweight. These anthropometric indices are positively

associated with the development of hyperglycemia during pregnancy (7). During pregnancy maternal

glucose, amino acids, lipids and vitamins cross the placenta and are employed to sustain fetal growth.

Glucose is quantitatively the most important nutrient. The fetus does not synthesize glucose and

employs maternal glucose as its primary energy source for maintenance of its basal metabolism

energy requirements for growth and storage. A maternal-fetal glucose gradient facilitates glucose

placental transfer and its rate is related to maternal glucose levels (33). The concentration of most

amino acids in fetus is higher than that found in the mother. Thus, placental transfer of amino acids

is carried out by an active process using selective transporters and energy (34). Lipids cross the

placenta with difficulty taken up by placental receptors or as fatty acids. Long-chain polyunsaturated

fatty acids are needed for fetal growth and development (35) Micronutrient (iron, iodine, calcium,

zinc etc), vitamin (ie vitamin A, C, E) and folate deficiencies are known to contribute to abnormal

prenatal development. (36, 37, 38, 39).

Furthermore, in this paper, maternal fasting plasma active GLP-1 levels correlated positively

and negatively with HDL cholesterol during the first and triglycerides during the second trimester of

pregnancy, respectively. This is in accordance with its negative correlation with maternal weight.

Studies in ob/ob mice showed that GLP-1 or combination of a DPP-4 inhibitor and pioglitasone

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improves lipid profile (41, 42). The origin and regulation of the maternal fasting GLP-1 secretion

during pregnancy remain to be unraveled.

Maternal fasting total GIP, fasting active ghrelin and total PYY levels did not change

throughout pregnancy and they did not correlate with maternal weight and total percent fat in this

non obese non diabetic pregnant population. In the past, basal acylated ghrelin and PYY 3-36 were

found increased and decreased, respectively, only in morbidly obese pregnant women as compared to

overweight or lean pregnant women (43). Others have reported that acylated ghrelin decreases

markedly during pregnancy in mothers with and without gestational diabetes (44). In addition,

ghrelin levels have been reported low in obesity, hyperinsulinemic and insulin resistant states (45,

46). Interestingly, in this study, ∆ fasting active ghrelin correlated positively with ∆ fasting active

GLP-1 from second to third trimester and fasting active ghrelin levels correlated positively with

fasting active GLP-1 levels at the third trimester suggesting a possible parallelism of their secretion

during normal pregnancy. During the first trimester, active ghrelin correlated negatively with

HOMA-R as well as insulin secretion parameters and positively with ISI. These correlations

disappeared during the second and third trimesters of pregnancy indicating that the maternal active

ghrelin involvement on maternal carbohydrate metabolism at this point might be less significant.

This study shows the strong negative association of maternal fasting active GLP-1 levels,

among the rest of gut peptides studied, with maternal weight change throughout pregnancy and the

significance of its first trimester levels as an early negative predictor of fetal abdomen circumference

at the second trimester, a period where fetal growth and the development of maternal insulin

resistance accelerate. This is further supported by the negative correlation of maternal fasting active

GLP-1 levels with insulin resistance parameters during the second trimester, when active GLP-1

levels increase gradually till the third trimester. Thus, fasting active GLP-1 during pregnancy might

be involved in physiological mechanisms of compensation of the pregnancy-related hyperglycemia

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and insulin resistance, suggesting a role of this peptide in maternal metabolism, maternal weight gain

and fetal abdomen circumference. Further physiological and interventional studies are needed

involving obese and diabetic pregnancies to establish the role of active GLP-1 into maternal weight

in pregnancy and its effects into fetal growth.

DECLARATION OF INTEREST: Authors declare there is no conflict of interest that could

be perceived as prejudicing the impartiality of the research reported.

FUNDING SUPPORT: Funding was received from Athens University Medical School (to

G.M. and I.P.). The funding sources played no role in the study design; in the collection, analysis,

and interpretation of data; in the writing of the report; or in the decision to

submit the report for

publication.

FINANCIAL DISCLOSURES: None declared.

ACKNOWLEDGEMENTS: Non applicable.

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Legends to the Figures

Figure 1: Correlation between maternal fasting plasma active GLP-1 and Ultrasound measured fetal

abdomen circumference at second trimester (p=0.034, r=-0.55)

Figure 2: Correlation between maternal fasting plasma active GLP-1 at second trimester and

birthweight (p=0.040, r=-0.50)

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Table 1 Anthropometric variables, hormones and carbohydrate metabolism parameters of

non-obese non-diabetic pregnant women (n=55) before and during pregnancy [variables

expressed as mean (±SD) or median (25th

to 75th

interquartile range)]

PRE-PREGNANCY

BMI of (kg/m2) 24.7 (2.2)

PREGNANCY 1st trimester 2

nd trimester 3

rd trimester

Maternal weight (kg) 68.5 (13.1) 73 (12.7)* 77.9 (14.5)

* #

Maternal fat (%) 31.1 (5.3) 32.1 (4.6)* 33 (5.9)

*#

U/S fetal abdomen

circumference (mm)

189.1 (177-209.5) 298.3 (280.5-309.9) #

U/S fetal biparietal

diameter (mm)

60.6 (54.5-64.6) 86 (81.8-95.5)

#

U/S fetal head

circumference (mm)

208.4(193.1-228) 312.1 (300.6-319)

#

U/S fetal femur length (mm) 42.6 (37.8-46) 69.5 (63.6-89.2)

#

U/S fetal estimated weight

(gr)

607 (496-783) 2178.8 (1870-2443) #

Fasting active GLP-1

(pg/mL)

159.7 (89.8-209) 169.6 (127.5-203) 200.3 (166-234.5) *#

Fasting active Ghrelin

(pg/mL)

41.1 (29-58.3) 37.9 (29-50.9) 41.8 (36.7-44)

Fasting total PYY (pg/mL) 97.1 (69.4-129.6) 92.3 (73.8-137) 98 (89-113.9)

Fasting total GIP (pg/mL) 14 (9.5-22.4) 9.4 (6.2-14.8) 10.3 (8.6-14.7)

Fasting glucose (mmol/L) 4.3 (0.3) 4.4 (0.2) 4.5 (0.4)

Fasting insulin (pmol/L) 56.3 (42.5-73) 59 (49-119.3) 117 (88-147) * #

ISI 0.1 (0.07-0.1) 0.08 (0.05-0.1) * 0.04 (0.004-0.06)

* #

HOMA-R 1.7 (1.3-2.4) 1.9 (1.6-3.9) 3.9 (2.8-4.9)* #

1st PHIS 969 (812-1254) 1117 (886-1381)

* 1116.4 (673.5-1413)

*

2nd

PHIS 283 (213-375) 328 (257-436)* 339.4 (223.2-446.5)

*

POST-PREGNANCY

Birthweigt (gr) 3175 (2730-3512)

(*): statistically significant change of variable from 1st trimester

(#): statistically significant change of variable from 2nd

trimester

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Figure 1

100

120

140

160

180

200

220

240

100 120 140 160 180 200 220 240

Maternal fasting plasma GLP-1 active (pg/mL)

U/S

fet

al

ab

dom

en

circ

um

fere

nce

(mm

)

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Figure 2

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The role of maternal gut hormones in normal pregnancy: fasting plasma active glucagon-like peptide 1...

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