INTRODUCTION:

The rate of Diabetes in Egypt has significantly increased, exceeding international rates. The International Diabetes Federation (IDF) listed Egypt among the world's top 10 countries in the number of patients with Diabetes. Gestational diabetes mellitus (GDM) is a common pregnancy complication in which spontaneous hyperglycemia develops during pregnancy.

According to the most recent IDF estimates, GDM affects approximately 14% of pregnancies worldwide, representing approximately 18 million births annually^1-3. Risk factors of GDM include overweight/obesity, westernized diet, micronutrient deficiencies, advanced maternal age, and family history of insulin resistance and/or Diabetes. While GDM usually resolves following delivery, it can have long-lasting health consequences, including increased risk of short and long-term complications for mother and child^4,5. The most frequent metabolic disease in pregnancy is Diabetes. Diabetes in pregnancy affects women in one of two ways: pregestational (which includes type 1 and type 2 diabetes) or gestational diabetes mellitus (which includes type 1 and type 2 diabetes) (GDM). According to the International Diabetes Federation, Diabetes affects one in every six (16.8%) pregnancies. Pregestational Diabetes affects 13.6 percent of these women, but GDM affects the majority (86.4 percent). This chapter analyses the problems of precisely quantifying disease patterns, especially in the case of GDM, and covers the prevalence and clinical features of women diagnosed with Diabetes during pregnancy^6-9.

For obese women (BMI >30kg/m²), a modest energy restriction to reduce weight gain can be achieved by restricting caloric intake by approximately 30 percent below the Dietary Reference Intakes (DRI) for pregnant women¹⁰. This can be achieved while meeting the Institute of Medicine (IOM) weight gain recommendations without causing ketosis. In the 2014 meta-analysis described above¹¹, energy restriction did not significantly reduce the cesarean delivery rate, frequency of Macrosomia, or rate of neonatal hypoglycemia, but data were limited to two small trials and were inconsistent.

Gestational diabetes mellitus has major fetal effects on birth weight and body composition: infants of diabetic mothers are at high risk of being large for gestational age. Macrosomia may not be prevented by dietary therapy alone¹². However, the variable quality of these studies and wide confidence intervals precluded a definitive conclusion about the value of dietary intervention. For example, the investigators did not consistently assess dietary compliance or postprandial glucose concentration in women prescribed a diet. In the two randomized trials in which diagnosis and treatment of mild gestational diabetes improved outcomes¹³, only 20 and 8 percent of women, respectively, required insulin, while 80 and 92 percent of women, respectively, were treated satisfactorily with diet. Medical, nutritional therapy for women who do not meet oral glucose tolerance test (GTT) criteria for Gestational Diabetes but have fasting blood glucose concentrations >90mg/dL [5 mmol/L]¹⁴, and abnormal glucose challenge test¹⁵ or one abnormal value on the three-hour 100g oral GTT. The rationale for this approach is that there appears to be a continuous relationship between glucose concentration and fetal growth/adverse fetal outcome, even in women who did not meet the former ADA criteria for diagnosis of diabetes¹⁶. This was best illustrated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, which included more than 23,000 pregnant¹⁷. After a two-hour 75g oral GTT, the risk of Macrosomia increased as much as fivefold as fasting plasma glucose concentration increased above 75mg/dL (4.2mmol/L), or one-hour glucose concentration increased above 105mg/dL (5.8mmol/L), or two-hour glucose concentration increased above 90mg/dL (5.0 mmol/L), and the risk increased continuously across the spectrum of glucose results. There was also a positive, but weaker, correlation between increasing glucose concentration and maternal complications (e.g., Preeclampsia) and neonatal metabolic morbidity (e.g., hypoglycemia, hyperbilirubinemia), but not intermediate-term childhood morbidity, such as obesity at age two years in a small subset of offspring¹⁸. Although, obesity does not manifest itself in the offspring of diabetic mothers until the age of 6 to 7 years. Of note, women with significant hyperglycemia were excluded from the HAPO analysis (exclusion criteria: fasting glucose concentration greater than 105mg/dL [5.8mmol/L], two-hour glucose concentration greater than 200mg/dL [11.1mmol/L], or a random glucose concentration later in gestation greater than 160mg/dL [8.9mmol/L]).

There are two pharmacologic options in pregnant patients who require medical therapy to control blood glucose: insulin (and some insulin analogs) and selected oral antihyperglycemic agents. We consider insulin the treatment of choice.

SUBJECTS AND METHODS:

This prospective study was conducted on 90 pregnant females with normal menstrual cycles before pregnancy. The current study was conducted after ethics approval from the ethics committee at Misr University for Science and Technology.

At the time of initial recruitment, the purpose of the study was explained to the participants, and they were informed of the need for follow-up contact, and all the patients were asked to sign a written consent of their approval. The 90 patients were collected from the obstetrics and gynecology outpatient clinic in the memorial Souad Kafafi University hospital and Al- Kasr Al-Einy Teaching hospital with comparable demographic data. Subjects were divided into three groups, Group I is non-diabetic pregnant with a normal glycemic profile (control), Group II is pregnant patients with proven Diabetes during pregnancy (Gestational.

Diabetes), and Group III are pregnant women who became pregnant while diabetic.

(Pregestational Diabetes). A normal result for a 1-hour glucose screening test using 50g glucose is a blood sugar equal to or less than 140mg/dL (7.8mmol/L) 1 hour after drinking the glucose solution. A normal result means the absence of gestational diabetes.

Pregestational Diabetes is defined as Type I or Type II DM that existed before conception.

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy¹⁹. In the present study, all patients without a history of Diabetes mellitus on their visit at the 24^th week's gestation were screened for Gestational Diabetes by a 1hour postprandial glucose test using 50grams glucose. Patients with abnormal high reading > 140mg/dl were directed to perform the 3 hours modified OGTT (3 hr test) using 100grams glucose for further confirmation of gestational Diabetes, in addition to Ultrasound screening for polyhydramnios and any congenital anomalies. After performing the above screening tests, we obtained the 30 patients with confirmed gestational Diabetes, i.e., with at least two abnormal OGTT readings and those with Twenty patients diagnosed with gestational diabetes (group II) were advised to be on diet control. In comparison, the rest ten patients and all the thirty patients with pre-gestational Diabetes (Group III) received insulin individually. All their doses were accurately calculated concerning their trimester of pregnancy and the severity of their cases according to their glycemic profiles.

The current study explained the importance of self-monitoring of blood glucose, diet control, medication adherence if needed, and exercise to the patient. On each visit, the patient was monitored for the blood glucose values and the results from both the ophthalmological and laboratory examinations (e.g., renal functions, hemoglobin A1c, thyroid function, etc.). The patient was asked to take good care of the quality and quantity of her food (diet control), which was very important to her mother and fetus. The patient was directed to record the blood glucose readings before the three meals and the postprandial 2 hours in a copybook and was asked to bring these recorded readings with her each visit to check the efficacy of her insulin doses and if they needed further adjustment.

The target blood glucose values according to ACOG and the American Diabetes Association (ADA) 2021: Fasting ≤95mg/dL and 2-hr postprandial ≤120mg/dL

Eligibility criteria:

We included in our study women; Prim gravida or Multipara, Age of the mother between 15 - 55 years, Single intrauterine pregnancy with ultrasound screening at the thirteenth and the twentieth week's gestation, and with No history of a medical disorder such as thyroid dysfunction or hypertension.

We excluded:

Unwilling to participate in the study and Twin pregnancy/abnormal lie or other known complications.

All patients had undergone the following:

Demographics profiles like age, BMI, parity, family history of Diabetes and blood pressure will be evaluated, Full history taking including current or past illness, Drug history, present or past, Full clinical examination including; General examination and Abdominal examination. The following blood tests were performed: complete blood count, glycated hemoglobin, fasting blood glucose, and oral glucose tolerance test (OGTT) using Beckman Coulter AU 480 analyzer and Urine analysis performed using Beckman Coulter AU 480 analyzer was: urea, uric acid, creatinine clearance, Ultrasound studies were carried out using Mindray dp20 to determine intrauterine gestational sac, gestational age, and viability of the fetus as well as the presence of any congenital anomalies, Follow up of the patient until delivery was done and Pregnant diabetic women were prescribed insulin therapy and blood glucose (and other tests) were followed- up for the proper intervention.

Statistical methods:

IBM SPSS statistics (Statistical Package for Social Sciences) software version 22.0, IBM Corp., Chicago, USA, 2013 and Microsoft Office Excel 2007 were used to code, tabulate, and statistically analyze the obtained data. For quantitative normally distributed data, descriptive statistics were calculated as the lowest and maximum of the range and the mean and SD (standard deviation), whereas qualitative data was calculated as number and percentage. For quantitative variables, inferential analyses were conducted using the Shapiro-Wilk test for normality testing, an independent t-test in the case of two independent groups with normally distributed data, and an ANOVA test with post hoc Bonferroni test of more than two independent groups with normally distributed data. Inferential analysis for independent variables was performed on qualitative data using the Chi-square test for proportional differences with a post hoc Bonferroni test. If the P-value is less than 0.050, the result is significant; otherwise, it is non-significant.

Table (1): Demographic characteristics among the studied groups

Variables	Measures	Control (N=30)	Gestational (N=30)	Pregestational (N=30)	Groups comparis on	Adjusted p-values
Age (years) N (%)	20.0−	17 (56.7%)	12 (40.0%)	13 (43.3%)	F=1.875 P=0.392	I/II=0.589 I/III=0.905 II/III=0.629
Age (years) N (%)	30.0−40.0	13 (43.3%)	18 (60.0%)	17 (56.7%)	F=1.875 P=0.392	I/II=0.589 I/III=0.905 II/III=0.629
Socioeconomic class N (%)	Low	9 (30.0%)	14 (46.7%)	8 (26.7%)	F=4.884 P=0.299	I/II=0.999 I/III=0.999 II/III=0.999
	Middle	17 (56.7%)	12 (40.0%)	14 (46.7%)
	High	4 (13.3%)	4 (13.3%)	8 (26.7%)
	Below uni.	9 (30.0%)	12 (40.0%)	6 (20.0%)	F=3.575	I/II=0.999
EducationN (%)	University	17 (56.7%)	14 (46.7%)	17 (56.7%)	P=0.467	I/III=0.999 II/III=0.999
EducationN (%)	Postgraduate	4 (13.3%)	4 (13.3%)	7 (23.3%)	P=0.467	I/III=0.999 II/III=0.999
Work N (%)	Nor working	11 (36.7%)	10 (33.3%)	11 (36.7%)	F=0.649 P=0.958	I/II=0.999 I/III=0.999 II/III=0.869
	Desk work	15 (50.0%)	15 (50.0%)	13 (43.3%)
	Active work	4 (13.3%)	5 (16.7%)	6 (20.0%)

The table shows that:

No significant difference between the studied groups regarding demographic characteristics.

Table 2: outcome from study

Findings	Control (N=30)	Gestational (N=30)	Pregestational (N=30)	p-value
Family history N (%)	3 (10.0%)	5 (16.7%)	13 (43.3%)	0.005
Pregnancy induced hypertension N (%)	1 (3.3%)	8 (26.7%)	13 (43.3%)	0.001
Preeclampsia N (%)	0 (0.0%)	3 (10.0%)	6 (20.0%)	0.037
Polyhydramnios N (%)	0 (0.0%)	1 (3.3%)	3 (10.0%)	0.160
Proteinuria N (%)	1 (3.3%)	6 (20.0%)	12 (40.0%)	0.002
Cesarean delivery N (%)	4 (13.3%)	11 (36.7%)	16 (53.3%)	0.005
Vaginaldelivery N (%)	26 (86.7%)	19 (63.3%)	14 (46.7%)	0.005
Preterm delivery N (%)	1 (3.3%)	3 (10.0%)	10 (33.3%)	0.003
Birth weight (kg) mean±SD	3.1±0.3	3.3±0.4	3.6±0.5	0.001
Macrosomia N (%)	0 (0.0%)	2 (6.7%)	6 (20.0%)	0.021
Low birth weight N (%)	1 (3.3%)	0 (0.0%)	0 (0.0%)	0.364
Fetal anomalies N (%)	0 (0.0%)	1 (3.3%)	2 (6.7%)	0.355
APGAR-5 score <7.0 N (%)	1 (3.3%)	5 (16.7%)	12 (40.0%)	0.002
Neonatal respiratory distress N (%)	0 (0.0%)	1 (3.3%)	4 (13.3%)	0.064
Fetal and neonatal death N (%)	0	0	0	----

Our study showed that it was not statistically significant in terms of Polyhydramnios, Low birth weight, fetal anomalies, and Neonatal respiratory distress. At the same time, there was statistically significant in terms of Family history, Pregnancy-induced hypertension, Preeclampsia, Proteinuria, Cesarean delivery, Vaginaldelivery, Preterm delivery, Birth weight (kg), Macrosomia, and APGAR-5 score <7.0 <0.001.

Table (3): Oral glucose tolerance test (mg/dL) among the diabetic groups

Hour	Measures	Gestational (N=30)	Presentational (N=30)	Groups comparison
Week 24
Fasting	Mean±SD	102.9±13.4	109.8±9.3	P=0.024*
Hour-1	Mean±SD	188.4±9.2	193.1±6.3	P=0.024*
Hour-2	Mean±SD	159.3±5.1	166.8±9.0	P<0.001*
Hour-3	Mean±SD	142.6±6.6	158.2±8.8	P<0.001*

Table (3)show that: Oral glucose tolerance test at different hours was significantly higher in the pregestational Group than in the gestational Group.

Table (4): HbA1c (%) among the diabetic groups

Measures	Gestational (N=30)	Pregestational (N=30)	Groups comparison
Week 24
Mean±SD	6.5±0.3	6.9±0.3	P<0.001*
Range	6.1–7.0	6.5–7.5	P<0.001*

Independent t-test. *Significant

Table (4) show that: HbA1c at weeks 24 was significantly higher in the pregestational Group than in the gestational Group.

DISCUSSION:

The rate of Diabetes in Egypt has significantly increased, exceeding international rates. The International Diabetes Federation (IDF) listed Egypt among the world's top 10 countries in patients with diabetes²⁰. GDM affects approximately 14% of pregnancies worldwide, representing approximately 18 million births annually.

In the present study, the presence of a DM family history was more common in the PGDM group, followed by the GDM Group; however, the differences were only significant between the Control and GDM groups, and this agrees with Shefali et al., 2006²¹Also, with Eltoony et al., 2021²²found that family history of Diabetes and GDM were the major risk factors for GDM in Recent study aimed at estimating the prevalence of GDM in Aswan Governorate in Egypt and determining the risk factors associated with GDM. Regarding maternal-related comorbidities, the current study found that pregnancy-induced hypertension and Preeclampsia and proteinuria, and pyuria were most Prevalent in the PGDM group. This study also found that the PGDM group had higher polyhydramnios and Oligohydramnios than the GDM group.

Our findings supported those of Fong et al., 2014²³, as Several clinical comorbidities were found to be significantly Higher in PGDM when compared to GDM after controlling for Covariates. Chronic disease conditions such as chronic hypertension were more common in subjects with PGDM, and Battarbee et al., 2020²⁴ study concluded that PGDM had More comorbidities than GDM. In the current study, the PGDM group performed Significantly better on the oral glucose tolerance test at different Hours than the GDM group. Also, the PGDM group had significantly higher hba1c levels at 24 and 28 weeks than the GDM group. These findings agreed with those of Shefali et al., 2006²⁵ and Middleton et al., 2016²⁶, who investigated the Relationship between glycemic control and pregnancy outcomes and discovered higher HbA1c in type 1 and type 2 diabetes when compared to GDM. According to a systematic review and meta-analysis, Preconception diabetes care for T1DM and T2DM effectively reduces diabetes-related congenital malformations, preterm delivery, and maternal hyperglycemia in the first trimester of pregnancy²⁷. This systematic review concluded that preconception Care effectively reduces congenital malformations, preterm delivery, and perinatal mortality, as well as lowers HbA1c by an average of 2.43 percent in the first trimester of pregnancy²⁸.

Our findings supported those of Wahabi et al., 2017³² and Battarbee et al., 2020³³, who found an increased risk of large for gestational age and preterm birth in PGDM compared to GDM, as well as³⁴^,35studies that Discovered diabetic pregnant women, in general, had an Increased Risk for this complication. When screening for fetal anomalies in the current study, We revealed that it was most common in the pregestational Group, (6.7 %) showing fetal anomalies, compared to only (3.3%). In comparison, there were no fetal anomalies in the Control group. The differences between the three groups studied Were not statistically significant (P> 0.05). Unfortunately, it will be difficult to link congenital Anomalies detected in the postnatal period to any maternal Condition due to the lack of a national registry for congenital anomalies and the difficulty of following a cohort of children with the Frequent change of address and healthcare provider³⁶. Our findings illustrated that the PGDM group suffered From neonatal respiratory distress followed by the gestational Group with only 1 woman and were least frequent in the control group, which showed no occurrence of neonatal respiratory distress. The differences between the three studied groups were Non-significant. (P>0.05), in agreement with³⁷.

Our findings supported^36,37 that PGDM increases the risk of adverse pregnancy outcomes, including a nearly fourfold increase in the risk of stillbirth and fetal distress and a more than twofold increase in the risk of preterm birth and admission to the NICU. This can be explained by the fetus being exposed to a more and severe hyperglycemic environment for a longer time than in the GDM. Similar studies established a linear relationship between the degree of hyperglycemia and the development of certain maternal and neonatal complications.^41,42.

The present study agreed with the findings of Battarbee et al., 2020⁴³. PGDM was linked to an increased risk of respiratory distress syndrome and mechanical ventilation; however, gestational Diabetes was not linked to neonatal respiratory morbidity. Neither pregnancies nor gestations were linked to neonatal mortality.

Many factors could have influenced the outcomes of these two conditions, including the fetus's prolonged exposure to maternal hyperglycemia in the case of PGDM, which resulted in prolonged fetal hyperinsulinemia and increased C peptide levels, and thus more severe effects on fetal weight gain, Macrosomia, and related complications like CS delivery ⁴¹. Furthermore, persistent hyperglycemia in PGDM might damage the placental vascular bed, increasing the risk of stillbirth, prenatal and intrapartum hypoxia, and therefore the poor APGAR scores at delivery seen in our research. If there had been adequate data available to study the influence of PGDM time on birth weight, such a discovery might have been substantiated further⁴⁴.

CONCLUSION:

This study concluded that mothers with PGDM had worse pregnancy outcomes than those with GDM. They were more likely to be delivered by CS, had babies on average heavier than those born to GDM mothers, and were more likely to be macrosomic. Newborns of mothers with PGDM were at increased risk of having low APGAR scores at birth, respiratory distress, preterm, or being born as stillbirth.Adjustment of insulin dose, restrictive follow-up, diet control, and medication adherence are important parameters that minimize the diabetic risk and complications for diabetic pregnant females and their infants.

REFERENCE:

1. Knowler W, Drews K, Redman L et al. (2018): Changing Glucose Tolerance during Pregnancy— Implications for Diagnosis of Gestational Diabetes Mellitus (GDM). https://diabetes.diabetesjournals. org/content/67/Supplement_1/119-OR

2. Namba B, Namara A, Nyirenda M (2019): Burden, risk factors and maternal and offspring outcomes of gestational diabetes mellitus (GDM) in sub-Saharan Africa (SSA): a systematic review and meta-analysis. BMC Pregnancy and Childbirth, 19 (1): 450-5.

3. Januvia T, Zeitlin J, Egorova N, Balbierz A, Howell EA: The role of obesity in the risk of gestational diabetes among immigrant and U.S.-born women in New York City. Ann Epidemiol 2018;28:242–248.

4. American Diabetes Association. Gestational diabetes mellitus. Diabetes Care 2004; 27 Suppl 1:S88.

5. Viana LV, Gross JL, Azevedo MJ. Dietary intervention in patients with gestational diabetes mellitus: a systematic review and meta-analysis of randomized clinical trials on maternal and newborn outcomes. Diabetes Care 2014; 37:3345.

6. Walkinshaw SA. Dietary regulation for 'gestational diabetes'. Cochrane Database Syst Rev 2000; :CD000070.

7. Singh B. Lohan S. Sandhu PS. Jain A. Mehta SK. Functionalized carbon nanotubes and their promising applications in therapeutics and diagnostics. In Nanobiomaterials in Medical Imaging 2016; 455-478, William Andrew Publishing. https://doi.org/10.1021/nn700040t.

8. Schrader HM, Jovanovic-Peterson L, Bevier WC, Peterson CM. Fasting plasma glucose and glycosylated plasma protein at 24 to 28 weeks of gestation predict Macrosomia in the general obstetric population. Am J Perinatol 1995; 12:247.

9. Scholl TO, Sowers M, Chen X, Lenders C. Maternal glucose concentration influences fetal growth, gestation, and pregnancy complications. Am J Epidemiol 2001; 154:514.

10. Jensen DM, Korsholm L, Ovesen P, et al. Adverse pregnancy outcome in women with mild glucose intolerance: is there a clinically meaningful threshold value for glucose?

a. Acta Obstet Gynecol Scand 2008; 87:59.

11. HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358:1991.

12. Pettitt DJ, McKenna S, McLaughlin C, et al. Maternal glucose at 28 weeks of gestation is not associated with obesity in 2-year-old offspring: the Belfast Hyperglycemia and Adverse Pregnancy Outcome (HAPO) family study. Diabetes Care 2010; 33:1219.

13. Schneider SH, Ruderman NB. Exercise and NIDDM. Diabetes Care 1993; 16:54.

14. Jovanovic-Peterson L, Durak EP, Peterson CM. Randomized trial of diet versus diet plus cardiovascular conditioning on glucose levels in gestational diabetes. Am J Obstet Gynecol 1989; 161:415.

15. Jovanovic-Peterson L, Durak EP, Peterson CM. Randomized trial of diet versus diet plus cardiovascular conditioning on glucose levels in gestational diabetes. Am J Obstet Gynecol 1989;161:415.

16. Barakat R, Pelaez M, Lopez C, et al. Exercise during pregnancy and gestational diabetes-related adverse effects: arandomized controlled trial. Br J Sports Med 2013; 47:630.16.Colberg SR, Sigal RJ, Fernhall B, et al. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care 2010; 33:e147.

17. American Diabetes Association. 13. Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes-2018. Diabetes Care 2021; 41:S137.

18. Ballesteros B. Tobias G. Shao L. Pellicer E. Nogués J. Mendoza E. Green ML et al Steam Purification for the Removal of Graphitic Shells Coating Catalytic Particles and the Shortening of Single-Walled Carbon Nanotubes. Small. 2008; 4(9):1501-6.doi.org/10.1021/ja061680u.

19. Chew EY, Mills JL, Metzger BE, et al. Metabolic control and progression ofretinopathy.TheDiabetesinEarly Pregnancy Study.NationalInstituteofChild Health and Human Development Diabetes in Early Pregnancy Study.DiabetesCare1995;18:631.

20. Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of intensive blood-glucosecontrolonlatecomplicationsoftypeIDiabetes.Lancet1993;341:1306.

21. EarlyworseningofdiabeticretinopathyintheDiabetesControlandComplications Trial. ArchOphthalmol 1998; 116:874.

22. KandaE,MatsudaY,MakinoY,MatsuiH.Riskfactorsassociatedwithaltered fetal growth in patients with pregestational diabetes mellitus. J MaternFetalNeonatalMed2012; 25:1390.

23. Langer O, Levy J, Brustman L, et al. Glycemic control in gestational diabetesmellitus--how tight is tight enough: small for gestational age versus large forgestationalage?AmJObstetGynecol1989;161:646.

24. Carl J, Christensen M, Mathiesen O. Human placental lactogen (hPL) modelforthenormal pregnancy.Placenta1991;12:289.

25. Glueck CJ, Goldenberg N, Pranikoff J, et al. Height, weight, and motor-socialdevelopment during the first 18 months of life in 126 infants born to 109mothers with polycystic ovary syndrome who conceived on and continuedmetforminthroughpregnancy.HumReprod 2004;19:1323.

26. Glueck CJ, Bornovali S, Pranikoff J, et al. Metformin, Preeclampsia, andpregnancy outcomes in women with polycystic ovary syndrome. Diabet Med2004; 21:829.

27. GlueckCJ,GoldenbergN,WangP,etal.Metforminduringpregnancyreduces insulin, insulin resistance, insulin secretion, weight, testosterone anddevelopment of gestational diabetes: prospective longitudinal assessment ofwomenwithpolycysticovarysyndromefrompreconceptionthroughoutpregnancy.HumReprod 2004;19:510.

28. GlueckCJ,PranikoffJ,AregawiD,WangP.PreventionofGestationalDiabetes by metformin plus diet in patients with polycystic ovary syndrome.FertilSteril2008;89:625.

29. Kitzmiller JL, Block JM, Brown FM, et al. Managing preexisting Diabetes forpregnancy: summary of evidence and consensus recommendations for care.DiabetesCare2008;31:1060.

30. Institute of Medicine and National Research Council. Weight Gain DuringPregnancy: Reexamining the Guidelines, Rasmussen KM, Yaktine AL (Eds),NationalAcademiesPress, Washington,DC2009.

31. Hillier TA,PetulaKL,VescoKK,etal.Excessgestationalweightgain:modifyingfetalmacrosomiariskassociatedwithmaternalglucose.ObstetGynecol2008;112:1007.

32. Scifres CM, Feghali MN, Althouse AD, et al. Effect of excess gestationalweight gain on pregnancy outcomes in women with type 1 diabetes. ObstetGynecol2014;123:1295.

33. Stecher AL, Parellada CB, Ringholm L, et al. Higher gestational weight gain isassociatedwithincreasingoffspringbirthweightindependentofmaternalglycemiccontrolinwomenwithtype1diabetes.DiabetesCare2014;37:2677.

34. Franz MJ, Bantle JP, Beebe CA, et al. Evidence-based nutrition principles andrecommendationsfor the treatmentandprevention of diabetes andrelatedcomplications. DiabetesCare2003; 26 Suppl1:S51.

35. Harris JA, Benedict FG. A Biometric Study of Human Basal Metabolism. ProcNatl AcadSci U S A1918; 4:370.

36. Mifflin MD, St Jeor ST, Hill LA, et al. A new predictive equation for restingenergyexpenditurein healthy individuals.Am JClin Nutr1990; 51:241.

37. BertorelliAM.Nutritionalmanagement.In:DiabetesComplicatingPregnancy, 2nd ed, Brown FM, Hare JW (Eds), Wiley-Liss, New York 1995.p.88.

38. MestmanJH.OutcomeofDiabetesscreeninginpregnancyandperinatalmorbidity in infants of mothers with mild impairment in glucose tolerance.DiabetesCare1980;3:447.

39. American Diabetes Association. 3. Foundations of Care and ComprehensiveMedicalEvaluation.DiabetesCare2016; 39Suppl 1:S23.

40. Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrinesocietyclinicalpractice guideline.JClinEndocrinolMetab2013;98:4227.

41. Wilson RD, Genetics Committee, Wilson RD, et al. Pre-conception Folic Acidand Multivitamin Supplementation for the Primary and Secondary Preventionof Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies.JObstet GynaecolCan 2015; 37:534.

42. Jovanovic L, Knopp RH, Brown Z, et al. Declining insulin requirement in thelatefirsttrimester ofdiabetic pregnancy.DiabetesCare 2001;24:1130.

43. SteelJM,JohnstoneFD,HumeR,MaoJH.InsulinrequirementsduringpregnancyinwomenwithtypeIDiabetes.ObstetGynecol1994;83:253.

44. García-Patterson A, Gich I, Amini SB, et al. Insulin requirements throughoutpregnancy in women with type 1 diabetes mellitus: three changes of direction.Diabetologia2010;53:446.

45. HirschIB.Insulin analogues.NEnglJ Med2005;352:174.

46. Wyatt JW, Frias JL, Hoyme HE, et al. Congenital anomaly rate in offspring ofmothers with diabetes treated with insulin lispro during pregnancy.DiabetMed2005; 22:803.

47. Hod M, Damm P, Kaaja R, et al. Fetal and perinatal outcomes in type 1diabetes pregnancy: a randomized study comparing insulin aspart with humaninsulinin 322subjects.AmJObstet Gynecol2008; 198:186.e1.

Received on 07.04.2022 Modified on 14.07.2022

Research J. Pharm. and Tech 2023; 16(1):333-338.

DOI: 10.52711/0974-360X.2023.00059