Iraqi J Pharm Sci, Vol.25(1) 2016 Gestational diabetes mellitus and hormonal alteration 37 Gestational Diabetes Mellitus and Hormonal Alteration Sura A.Abdul Sattar *, 1 ,Amer H.Abdulla * and Aufaira Sh. Nsaif ** * Department of Chemistry, College of Science, AL-Mustansiriya University , Baghdad, Iraq. ** National Diabetes Center, AL-Mustansiriya, Baghdad, Iraq. Abstract Gestational Diabetes Mellitus is known as carbohydrate intolerance first detected during pregnancy. Pregnancy is periods of intense hormonal changes. The aim of the present study was to investigate a possible relation between the changes in serum hormones such as Luteinizing hormone (LH) , follicle stimulating hormone(FSH), Progesterone, and Prolactin with gestational diabetes mellitus. Thirty patients with gestational diabetes mellitus aged (22 -40) year attending the national center for treatment and research of diabetes/ AL-Mustansiriya University in Baghdad and 29 controls aged (20-39) year were participated. Hormonal tests including, FSH, LH, Progesterone, and Prolactin were detected by using Enzyme Linked Fluorescent Assay (ELFA) kits. The demographic characteristics of gestational diabetes mellitus indicated that the most commonly affected age at (20-29) year (50%) ,60% of patients had Body Mass Index(BMI) at ≥ 30kg/m 2+ , 76.6% of patients at first trimester of pregnancy, 23.3% had previous abortion,60% at the first pregnancy ,and 46.6% of patients had urine protein with one plus. A highly significant increase (p≤0.001) in Fasting serum glucose(FSG), LH, FSH, progesterone, and prolactin were observed in sera of gestational diabetes mellitus patients in comparison to that of control pregnancy group. A non-significant correlation of FSG with age, BMI, LH, FSH, and progesterone were demonstrated. While a significant positive correlation of FBS with prolactin was found. It is conclude that higher prolactin level in pregnancy possibly played a role in gestational diabetes mellitus partly by impairing the functions of insulin, and result in hyperglycemia. Keyword: Gestational diabetes, FSH, LH, Progesterone, Prolactin. داء السكري الحملي والتغيراث الهرمىويت سري احمد عبد الستار ،*1 عبد هللا امر حسه،ع * وصيف ة شاكرريو عف ** * فزع انكًٛٛاء،كهٛت انعهٕو ، انضايعت انًسخُصزٚت ، بغذاد ، انعزاق . ** .انًزكش انٕطُٙ نبحٕد انسكز٘ ، انضايعت انًسخُصزٚت ، بغذاد ، انعزاق الخالصة دٔرة يٍ انحًم انذ٘ ًٚزم فخزة خالل يزة ألٔل اكخشف انكزبْٕٛذراحٙ ْٕ يعزٔف بعذو انخحًم ٔكًا داء انسكز٘ انحًهٙ اٌ انٓزيٌٕ يزم انذو فٙ انٓزيَّٕٛ انخغٛزاث بٍٛ يحخًهت عاللت عٍ ٔصٕد انحانٛت انٗ انكشف انذراست حٓذف .انًكزفت انٓزيَٕٛت انخغٛزاث ضاث يٍ انًزٚ 03ْذِ انذراست ضًج. انحًهٙ انسكز٘ يزض يع ٔانبزٔالكخٍٛ انبزٔصسخزٌٔ، انٓزيٌٕ انًحذ نهضزٚب،، انهٕحُٛٙ ًزكش انٕطُٙ نعالس ٔابحاد انسكز٘ فٙ انضايعت انًسخُصزٚت ببغذاد بًذٖ انٔحضزٔا انحًهٙ انسكز٘ داء يٍ ٚعاٍَٛ انهٕاحٙ حضًُج سُت . ( 02-23) بٍٛ يٍ انحٕايم غٛز انًصاباث بانسكز٘ بًذٖ عًز٘ حزأط 22ٔ سُت( 03- 22) بٍٛ عًز٘ حزأط ٔانبزٔالكخٍٛ باسخخذاو عذة االنفا انبزٔصسخزٌٔ، انٓزيٌٕ انًحذ نهضزٚب،، انهٕحُٛٙانٓزيٌٕ انفحٕصاث انٓزيَٕٛت (ELFA)ٔكخهت ،٪(03) سُت( 22-23) سٍ حكٌٕ فٙ عادة حأرزا األكزز انحًهٙ أٌ نذاء نسكز٘ ًٕٚغزافٛت.اظٓزث َخائش انذراسّ انذ سابك، اصٓاض نذٚٓى٪ 20.0 انحًم، يٍ األٔنٗ انزالرت األشٓز ٍْ فٙ انًزٚضاث % ي50.00ٍٔ 03 ≥ انًزضٗ يٍ٪ 03 انضسى ل يعُٕٚت عانٛت ٔصٕد سٚادة بُٛج انُخائش . بمًٛت سائذ ٔاحذ انًزٚضاث يٍ٪ 00.0 ٔكاٌ بزٔحٍٛ انبٕل ل األٔل، ْٕ انحًم٪ 03 (p≤0.001) ٙفٙ ٔانبزٔالكخٍٛ انبزٔصسخزٌٔ، انٓزيٌٕ انًحذ نهضزٚب، انٓزيٌٕ انهٕحُٛٙ، يسخٕٖ كم يٍ سكز انذو انصٛايٙ ، ف حى ارباث َفسّ انٕلج فٙ. انحٕايم غٛز انًصاباث بذاء انسكز٘ نًضًٕعت حهك يع يمارَت انحٕايم انًصاباث بذاء انسكز٘ يصم دو حبٍٛ ٍحٛ فٙ انبزٔصسخزٌٔ ، انٓزيٌٕ انًحذ نهضزٚب،ٔ عذو ٔصٕد عاللت يعُّٕٚ نسكز انذو انصٛايٙ يع انعًز ، انٓزيٌٕ انهٕحُٛٙ، دٔر انٗ نّ انحًم فٙ انبزٔالكخٍٛ يسخٕٖ ارحفاع أٌ َسخُخش. انبزٔالكخٍٛ بٍٛ سكز انذو انصٛايٙ ْٔزيٌٕ عاللت يعُّٕٚ يٕصبت ٔصٕد .انذو فٙ انسكز ارحفاع إنٗ يًا ٚؤد٘ األَسٕنٍٛ، ٔظائف يٍ خالل انخعطٛم فٙ انحًهٙ انسكز٘ حذ يا فٙ االصابت بذاء سكر الحمل ، الهرمىن المحث للجريب ،الهرمىن اللىتيىي ، البروجستيرون ، البروالكتيه.الكلماث المفتاحيت: Introduction Gestational Diabetes Mellitus (GDM) is known as carbohydrate intolerance first revealed during pregnancy (1) . It is the most public metabolic disturbance of pregnant women, involves between 2% and 5% of pregnant women (2) . Diabetes Mellitus type1 and type 2 could be diagnosed newly or secondary to metabolic changes related to pregnancy (3) .Gestational diabetes mellitus accounts for ninety percent of cases of diabetes 1 Corresponding author E-mail: sura742003@yahoo.com. Received: 10/1/2016 Accepted: 12/4/2016 mailto:sura742003@yahoo.com Iraqi J Pharm Sci, Vol.25(1) 2016 Gestational diabetes mellitus and hormonal alteration 38 mellitus in pregnancy, however eight percent of cases are preexisting type 2 (4) . GDM reveals usually between 24 and 28 weeks of gestation (5) .A large number of risk factors related to GDM increase have been fixed, including history of macrosomia, strong family history of diabetes, ethnicity, metabolic syndrome and obesity (2,6) .Pregnancy is periods of intense hormonal changes (1) . Women at risk for gestational diabetes have insulin resistance before conception. Insulin resistance during pregnancy stems from a variety of factors, including alterations in growth hormone and cortisol secretion , human placental lactogen secretion , and insulinase excretion which is produced by the placenta and facilitates metabolism of insulin (7) . Moreover, the steroid hormones such as progesterone and the estrogens have been shown to be involved in β-cell physiology and disturbance of the glucose insulin balance (8,9) . Luteinizing hormone (LH) and follicle- stimulating hormone (FSH) are omit gonadotropins are secreted from gonadotrophs cells in the anterior pituitary. Most gonadotrophs secrete only LH or FSH, but some time both hormones (10) . In female, LH stimulates secretion of sex steroids from the gonads progesterone and estradiol (10) . Progesterone is necessary for pregnancy reservation, and, in most mammals, LH is required for function and growth of corpora lutea (10) . LH levels will decrease if pregnancy occurs, and luteal function will instead be maintained by the action of human chorionic gonadotropin, which is similar to LH and secreted from the new placenta (11) . The prolactin(PRL), is major stimuli for the adaptation of the endocrine pancreas during gestation (12) . Prolactin is a polypeptide originally known as a pituitary hormone for its ability to promote lactation in response to the breast feeding (13) . Besides its well-known lactogenic properties, prolactin is also a highly versatile hormone whose functions are related to reproduction, growth and development, metabolism, immune regulation, brain function, and behavior (14,15) . Maternal prolactin increases synchronously to insulin during the second half pregnancy and stimulates β-cell proliferation, insulin production, and insulin secretion (16,17) . Moreover, it is known that the glucose metabolic regulation impact of prolactin is not close to the period of pregnancy (15,18,19) . The aim of the present study was to investigate a possible correlation between the changes in serum hormones such as LH, FSH, Progesterone, and Prolactin with gestational diabetes mellitus. Materials and Methods Case control study was used in the present where 30 women with gestational diabetes mellitus aged (22 -40) years as case and 29 age-matched of pregnant women aged (20-39) years as control attending the national center for treatment and research of diabetes/ AL- Mustansiriya University in Baghdad. Exclusion criteria were: age <20 years, diabetes diagnosed before pregnancy, physical disability, medications like oral corticosteroids and metformin, and multiple pregnancies. Five milliliters of venous blood samples were collected from the gestational diabetes mellitus and the healthy pregnant as controls group then immediately transferred into plane tube and allowed to coagulate at room temperature then centrifuged at 3000 rpm for 5 min. The resulting serum was separated and stored at (-20°C) until use. BMI is being calculated directly as weight (in kilograms)/ height 2 (in meters). Hormonal tests including, FSH, LH, Progesterone, and Prolactin were detected by using Enzyme Linked Fluorescent Assay (ELFA) kits in Mini Vidas system and performed according to the manufacturer's instructions. Statistical Analysis The statistical software (SPSS v 15; Chicago, IL, USA) was used. The data were analyzed using unpaired t-test and person correlation coefficients. Differences were considered significant when P< 0.05. Results and Discussion Table 1 show the baseline characteristics of gestational diabetes mellitus where it was found that the most commonly affected age at (20-29) year(50%) ,60% of patients had BMI at ≥ 30kg/m 2+ , 76.6% of patients at first trimester of pregnancy, 23.3% had previous abortion,60% at the first pregnancy ,and 46.6% of patients had urine protein with one plus. https://en.wikipedia.org/wiki/Pregnancy https://en.wikipedia.org/wiki/Human_chorionic_gonadotropin https://en.wikipedia.org/wiki/Human_chorionic_gonadotropin http://care.diabetesjournals.org/content/36/7/1974.long#ref-1 http://care.diabetesjournals.org/content/36/7/1974.long#ref-2 http://care.diabetesjournals.org/content/36/7/1974.long#ref-3 http://care.diabetesjournals.org/content/36/7/1974.long#ref-4 http://care.diabetesjournals.org/content/36/7/1974.long#ref-5 http://care.diabetesjournals.org/content/36/7/1974.long#ref-3 http://care.diabetesjournals.org/content/36/7/1974.long#ref-6 http://care.diabetesjournals.org/content/36/7/1974.long#ref-7 Iraqi J Pharm Sci, Vol.25(1) 2016 Gestational diabetes mellitus and hormonal alteration 39 Table (1): Baseline characterization of gestational diabetes mellitus. Category Number (%) Age in year 20-29 30-39 40-49 15(50%) 14(46.6%) 1(3.33%) BMI ≤19 20-24 25-29 ≥30 0(0%) 1(3.33%) 11(36.66%) 18(60%) Trimester First Second Third 23(76.66%) 6(20%) 1(3.33%) Pregnancy history Previous abortion No abortion First pregnant 7(23.3%) 23(76.66%) 18(60%) Urine protein Trace + ++ +++ 5(16.66%) 14(46.66%) 9(30%) 2(6.66%) Meanwhile a highly significant increase of BMI values was observed in gestational diabetes mellitus patients in comparison to that of control group (p=0.00) as shown in Table 2. This result was in line with Torloni MR et.al who reported that the GDM is positively associated with prepregnancy BMI where for every 1 kg/ m 2 increase in BMI, the prevalence of GDM increased by 0.92% (20) . The results represented in Table 2 indicated highly significant increases (p=0.00) in FSG, LH, FSH, progesterone, and prolactin in sera of gestational diabetes mellitus patients in comparison to that of control pregnancy group.Insulin secretion in women with GDM is defective and, therefore, is unable to rise adequately to compensate for the insulin resistance; the result is hyperglycemia (21) . LH and FSH play central roles in the hypothalamic-pituitary-gonadal axis, and, thus, conditions related to LH and FSH increases can be caused by pathology of either the hyperthalamus or pituitary (22) . LH increases almost always occurs in conjunction with follicle-stimulating hormone (FSH) increases because LH and FSH are secreted by the same pituitary gonadotrope cells. Table (2): Mean values of BMI, F.S.G, LH, FSH, Progesterone, and Prolactin levels in sera of patient and control groups. Parameters group Range (min-max) Mean SD P value BMI (kg/m 2 ) Control 19.00-28.40 23.5724 1.9063 0.00 Patients 21.90-35.50 29.8967 3.0337 FSG (mg/dl) Control 65.00-100.00 84.5172 32.6097 0.00 Patients 130.40-260.00 180.0900 32.6097 LH (pg/ml) Control 9.10-17.10 14.3966 1.8084 0.00 Patients 9.70-30.10 19.6633 4.6668 FSH(pg/ml) Control 8.80-18.70 15.8138 1.9913 0.00 Patients 10.10-34.20 20.1533 5.3723 Progesterone(pg/ml) Control 10.20-104.00 44.7276 19.7237 0.00 Patients 35.40-92.50 75.3533 12.7009 Prolactin(pg/ml) Control 13.70-42.10 27.2414 8.0499 0.00 Patients 38.00-80.10 52.9900 12.2372 Though a highly significant increase of progesterone level((p=0.00) was observed in the present study in sera of gestational diabetes mellitus in comparison to that level in control group (Table 2), we demonstrated a non- significant correlation ((p˃0.05) of progesterone with FBS as shown in Table 3. In previous studies of progesterone conflict data was reported where one of them has found association of progesterone with the development of gestational diabetes due to the enhancement of insulin resistance (23,24) , while another group did not find a correlation between progesterone level and an increasing risk of gestational diabetes mellitus (25) . In diabetes, the death of insulin-producing β-cells by apoptosis leads to insulin deficiency. The lower prevalence of diabetes in females suggests that female sex steroids protect from β-cell injury (26) . In addition Straub et al. suggested that the progesterone, might contribute to the poor adaptation of insulin secretion and action to the increased requirements during pregnancy (27). http://www.ncbi.nlm.nih.gov/pubmed/?term=Torloni%20MR%5BAuthor%5D&cauthor=true&cauthor_uid=19055539 http://joe.endocrinology-journals.org/content/221/2/273.long#ref-40 Iraqi J Pharm Sci, Vol.25(1) 2016 Gestational diabetes mellitus and hormonal alteration 40 Table (3): Correlations of FSG with age, BMI, and hormonal parameters. Parameters r value P value Age 0.302 0.105 BMI 0.252 0.179 LH -0.151 0.424 FSH -0.148 0.434 Progesterone 0.173 0.360 Prolactin 0.427 0.019 The present study indicated a highly significant increase in progesterone level in sera of gestational diabetes mellitus in compression to that of control group. This result was in agreement with Guyton & Hall who’s reported that no significant difference in plasma prolactin in normal or diabetic pregnant in fact it level might be lower in the pregnant with GDM (28) . While this result was in disagreement with the results of Milasinovic L. et.al who reported that there were no significant differences in the level of plasma prolactin in normal or diabetic pregnancies; in fact its level might be lower in the pregnancies with gestational diabetes mellitus and, prolactin might have no effect on glucose intolerance during pregnancy (29) . Arumugam R et al reported that PRL up-regulates β-cell glucose uptake and employment, whereas glucose increases islet PRL receptor expression and more effects of PRL on cell cycle gene expression and DNA synthesis (30) . The results presented in Table 3 indicated a non-significant correlation of FSG with age, BMI, LH, FSH, and progesterone. 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