الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 167 |  |  |
| | | from | 167 | | |
Abstract
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The definition applies whether insulin or only diet modification is used for treatment and whether or not the condition persists after pregnancy.
Gestational diabetes mellitus should be diagnosed at any time during pregnancy based on any one of the following values: (1) Fasting plasma glucose = 5.1-6.9 mmol/L (92-125 mg/dL), (2) 1 h post 75 g oral glucose load ≥ 10.0 mmol/L (180 mg/dL), (3) 2 h ≥ 8.6 mmol/L (155 mg/dL) according to WHO criteria.
The infants of diabetic mothers (IDM) may have great risk for serious problems during pregnancy and at birth. Problems during pregnancy may include increased risk for birth defects and stillbirth. Also including problems with the formation of the brain, heart, lung, spinal cord, gastrointestinal system and urinary tract.
Glutathione (GSH) recently considered the body’s master antioxidant, it composed of three amino acids – glycine, cysteine and glutamate. It can be found in every cell of the human body, the highest concentration is in the liver making it critical in the body’s detoxification process.
Glutathione S-transferases are members of a multigene family of phase II metabolic enzymes which catalyze the detoxifying reaction of a wide variety of carcinogenic and toxic compounds by conjugating them to glutathione, thus protecting cells from oxidative damage, the GST family consists of three super families: the
Summary
125
mitochondrial ,cytosolic and microsomal also known as MAPEG-proteins.
The genes encoding the mu class of enzymes are organized in gene cluster on chromosome 1p13.3 also GST T class with gene located in chromosome 22q11.23.
GSTT1 null genotype can be considered as risk factor for development of (GDM) gestational diabetes mellitus also GSTM1 null genotype considered as risk factor for respiratory distress and low Apgar score at 1 minute in infants of diabetic mothers. The aim of this work is to study glutathione S-transferase genetic variants in pregnant mothers with gestational diabetes and their degree of glycemic control and possible impact on their infants.
Patient and methods: The present study was carried out on 80pregnant women 40 of them have gestational diabetes mellitus during third trimester of pregnancy and their infants attending the department of obstetrics and department of pediatrics, Faculty of Medicine, Menoufia University Hospital.
40 apparently healthy, pregnant women and their infants matched with diabetic mothers and their infants in the same age from our obstetrics and pediatric general clinic in Menoufia University Hospital as a control group.
The mothers with GDM:
Their ages ranged from 21-38 years with mean age (30.23±5.428).
Summary
126
The infants of diabetic mothers:
Included 31 males and 9 females,80% of them their weight were at gestational age.
All patients and controls were subjected to the following after taking informed written consent:
1. Detailed history taking.
2. Complete general examination of all body systems.
3. Laboratory investigations:
a. from mothers:
Estimation of Fasting plasma glucose level.
Estimation of 2hr Postprandial plasma glucose level.
Estimation of glycosylated hemoglobin (HbA1C).
Estimation of liver and renal function tests.
b. from infants of diabetic mothers:
Estimation of complete blood count (CBC) at 1hr and 24hr of age.
Estimation of random blood sugar (RBS) at 1,2 ,3, 6, 12, 24, 36, 48hrof age.
Estimation of calcium level.
4. Molecular study of GSTT1 and GSTM1 gene polymorphism by PCR.
5. Family counseling.
6. Data management and statistical analysis.
7. Statistical analysis.
Summary
127
This study revealed that:
Positive family history of DM in diabetic mothers was 55% and this was found to be statistically significant (p=0.001)
Systolic blood pressure of mothers with GDM ranging from (128.75±21.36) versus (118±21.15)in control group and this was found to be statistically significant (p=0.0001) also diastolic blood pressure ranging from (80. 25±11. 2) versus (77±12.03) in control group and this was found to be statistically significant (p=0.029) as 52.2% (21) of our cases were complained from gestational hypertension during pregnancy and on antihypertensive drugs.
Regarding to laboratory investigations of mothers with GDM (FBS, PBS) showing statistically significant (p=0,0001).
Regarding to HbA1C which ranged from (6.845±1.34)in mothers with GDM in relation to average ranges in control group (5.24±0.35)was found to be statistically significant (p=0.0001).
As regards to GST genetic variant in mothers with GDM, frequency of GST-M1-1 present genotype was (32.5% ) and GST-M1-0 null genotype was(67.5%) in comparison to control group that was (50.0%) for present and null genotype and this was found to be statistically insignificant (p=0.112) and OR(CI) 0.481 (0.194-1.192).
On the other hand frequency of GST-T1-1 present genotype was (10%) and GST-T1-0 null genotype was (90%) in mothers with GDM in comparison to control group that was (27.5%) for present genotype and (72.5%) for null genotype and this was found to be statistically significant (p=0.04) and OR (CI) 0.293(0.084-1.017).
Regarding to GST-T1 genotypes in relation to HbA1C ranging from (6.9±1.1%) in null genotype which was higher in comparison to
Summary
128
(5.63±1.9%) in present genotype and this was found to be statistically significant (p=0.04).
Frequency of GSTT1-0 null genotype in mothers with GDM who had positive family history of DM were 61.1%and 38.9 % respectively and this was found to be statistically significant (p=0.019).
Apgar score at 1 minute of infants of these diabetic mothers ranging from (7.275±1.18) also their respiratory rate(RR) showed higher level which ranging from (50±12.4 breath/minute) all of them in concordance evidence of statistically significant (p=0.0001).
Laboratory investigations of infants of diabetic mothers showed lower levels of RBS at 1st hr of age which ranging from 55.93±17.978 mg/dl, and RBS at 2nd hr of age which ranging from 68.30±15.73 mg/dl which were statistically significant (p= 0.0001).
Regarding GST genetic variant in infants of diabetic mothers, frequency of GST-M1-1 present genotype was(37.5% ) and GST-M1-0 null genotype was(62.5%) versus(60%) for present genotype and (40.0%) for null genotype in control group and this was found to be statistically significant (p=0.04) and OR(CI ) 0.400 (0.163-0.984).
On the other hand frequency of GST-T1-1 present genotype was (12.5%) and GST-T1-0 null genotype was (87.5%) in infant of diabetic mothers versus 10% for present genotype and 90% for null genotype in control group which found to be statistically insignificant (p=0.106) and OR (CI) 1.286(0.319-5.186).
The relation of GSTM1 genotypes and Apgar score of infants of diabetic mothers at 1 minute was significantly decreased in GSTM1-0 null genotype (7±1.15%) versus (7.7±1. 1%) in GSTM1-1
Summary
129
present genotype which was found to be statistically significant (p=0.043).
Also relation of GSTM1 genotypes and respiratory rate of infants of diabetic mothers was significantly increased in GSTM1-0 null genotype (55.44±11. 65breath /minute) versus (42.6 ±9.35 breath/minute ) in GSTM1-1present genotype which was found to be statistically significant (p=0.002),these data suggested the association of GSTM1 null genotype and complications present in infants of diabetic mother.
There were significant negative correlation between HbA1c, FBS of mothers with GDM and Apgar score at 1 minute of their infants.
There were significant positive correlation between 2hrPPBS, FBS of mothers with GDM and respiratory rate of their infants.
There were significant negative correlation between GSTT1-0 null genotype of mothers with GDM and the respiratory rate of their infants.
There were significant positive correlation between GSTM1-0 null genotype of infants of diabetic mothers and their Apgar score at 1 minute and negative correlation with their respiratory rate.
Conclusion and Recommendation:
GDM is a major health problem, based on the positive association between GSTT1-0 null genotype and the risk of the development of GDM and GSTM1-0 null genotype in IDM which was positively correlated with unfavorable presentation among affected newborn, carriers of this polymorphism as evidenced by low Apgar score at 1 minute and high level of respiratory rate. So we
Summary
130
recommended genomic study inspite of high coast in pregnant mothers with gestational diabetes mellitus.
Functional large studies are required to clarify the role of GSTT1 and GSTM1 gene polymorphism among Egyptian mothers and their infants to confirm our finding in this study.