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JAPI - DIPSI Guidelines
Gestational Diabetes Mellitus – Guidelines*
V Seshiah, AK Das, Balaji V, Shashank R Joshi, MN Parikh, Sunil Gupta
For Diabetes In Pregnancy Study Group (DIPSI)+
Abstract
The Diabetes In Pregnancy Study group India (DIPSI) is reporting practice guidelines for GDM in the Indian
environment. Due to high prevalence, screening is essential for all Indian pregnant women. DIPSI recommends that as a pregnant woman walks into the antenatal clinic in the fasting state, she has to be given a 75g oral glucose load and at 2 hrs a venous blood sample is collected for estimating plasma glucose. This one step procedure of challenging women with 75 gm glucose and diagnosing GDM is simple, economical and feasible.
Screening is recommended between 24 and 28 weeks of gestation and the diagnostic criteria of ADA are applicable. A team approach is ideal for managing women with GDM. The team would usually comprise an obstetrician, diabetes physician, a diabetes educator, dietitian, midwife and pediatrician. Intensive monitoring, diet and insulin is the corner stone of GDM management. Oral agents or analogues though used are still controversial. Until there is evidence to absolutely prove that ignoring maternal hyperglycemia when the fetal growth patterns appear normal on the ultrasonogram, it is prudent to achieve and maintain normoglycemia in every pregnancy complicated by gestational diabetes. The maternal health and fetal outcome depends upon the care by the committed team of diabetologists, obstetricians and neonatologists. A short term intensive care gives a long term pay off in the primary prevention of obesity, IGT and diabetes in the offspring, as the preventive medicine starts before birth. tuning of glycemic level during pregnancy is possible INTRODUCTION
due to the compensatory hyperinsulinaemia, as the normal pregnancy is characterized by insulin resistance.
The maternal metabolic adaptation is to maintain the mean fasting plasma glucose of 74.5 ± 11 mg/dl and A pregnant woman who is not able to increase her the post prandial peak of 108.7 ± 16.9mg/dl.1 This fine insulin secretion to overcome the insulin resistance that occurs even during normal pregnancy develops +DIPSI GDM Guidelines Committee
Chairman : Prof V Seshiah
(President : Diabetes In Pregnancy Study group India) The metabolic goals of pregnancy are 1) in early pregnancy Members : Dr A K Das, Dr Balaji V, Dr Shashank R Joshi, Dr
to develop anabolic stores to meet metabolic demands in late pregnancy and 2) in late pregnancy to provide fuels DIPSI National Meeting Experts: Dr Anil S Bhoraskar, Dr
Anjalakshi C, Dr Aparna Agarwal, Dr Balaraman V T, Dr for fetal growth and energy needs. Bharti Kalra, Dr Bhavatharini A, Dr Cynthia Alexander, Dr - Dr Patrick Catalano
Dorendra Singh I, Dr Hariharan R S, Dr Himangi Lubree, Dr Jitendra Singh, Dr Jothi S Parthasarathy, Dr Krishnaveni G V, Gestational Diabetes Mellitus (GDM) is defined as Dr Kumaravel V, Dr. Lakshminarayanan S, Dr Lilly John, Dr Madhini V, Dr Madhuri S Balaji, Dr Mala Chettri, Dr Marina ‘carbohydrate intolerance with recognition or onset during Packiaraj, Dr Mary John, Dr Mayur Patel, Dr Mirudhubashini pregnancy’, irrespective of the treatment with diet or G, Dr Mohan V, Dr Munichoodappa C, Dr Nalini Shah, Dr insulin. The importance of GDM is that two generations Panneerselvam A, Dr Paulose KP, Dr Padma Menon, Dr Pratiba are at risk of developing diabetes in the future. Women D, Dr Rajan S K, Dr Rajendran N, Dr Rakesh M Parikh, Dr Ramachandran A, Dr Rao PV, Dr Rastogi S S, Dr Sahay B K, with a history of GDM are at increased risk of future Dr Samar Banerjee, Dr Sanjay Kalra, Dr Saraswathy K, Dr diabetes, predominately type 2 diabetes, as are their Shailaja Kale, Dr Sharad Pendsey, Dr Shyam Mukundan, Dr Siddharth N Shah, Dr Smita P Bhavsar, Dr Sridhar C B, Dr Sundaram A, Dr Suresh S, Dr Vitull K Gupta, Dr Yajnik C S GDM occurs when the woman’s beta cell function is not International Faculty : Dr Alberto de Leiva, Dr Lois Jovanovic,
able to overcome the antagonism created by the anti-insulin hormones of pregnancy and the increased fuel consumption *Based on the deliberations of the First National Conference of Diabetes In Pregnancy Study Group India at Chennai, February required to provide for the growing fetomaternal unit. - Dr Alberto de Leiva
SCREENING
pregnant women without GDM is associated with a graded increase in adverse maternal and fetal outcomes9 The controversy concerning optimal strategy still implying that fetal morbidity starts at a lower maternal continues for the detection and diagnosis of GDM.
glycemic level (< 140 mg/dl). A number of prospective American Diabetes Association (ADA) recommends two and retrospective studies have substantiated the step procedures for screening and diagnosis of diabetes observation that the frequency of adverse fetal outcome and that too in selective (high risk) population.
increases with 2hr PG > 120mg/dl and taking care of Compared with selective screening, universal screening these women had resulted in a better fetal outcome.10-14 for GDM detects more cases and improves maternal and Thus, the data is robust and indicates that 2 hr > 120mg/ neonatal prognosis.3 In the Indian context, screening is essential in all pregnant women as the Indian women have 11 fold increased risk of developing glucose The term ‘Impaired Gestational Glucose Tolerance intolerance during pregnancy compared to Caucasian (IGGT)’ is used by few authors to indicate pregnant women.4 The recent data on the prevalence of GDM in women whose 2 hr PG is > 120mg/dl. It may be our country was 16.55% by WHO criteria of 2 hr PG ≥ appropriate to use the term ‘Decreased Gestational 140 mg/dl.5 As such Universal screening during glucose tolerance (DGGT)’ instead of impaired pregnancy has become important in our country. For gestational glucose tolerance. The use of the term this we need a simple procedure which is economical ‘Decreased’ is appropriate as it implies only ‘Low’ whereas the term ‘Impaired’ means both high and low.
Further, quiet frequently we come across, labeling any DIPSI Recommended Method
abnormal value in the OGTT not meeting the diagnostic As a pregnant woman walks into the antenatal clinic criteria of GDM as IGT.15 The use of this term ‘IGT’ during in the fasting state, she has to be given a 75g oral glucose pregnancy may be confusing, as this terminology is also load and at 2 hrs a venous blood sample is collected for being used in non pregnant adult with 2 hr PG > 140 estimating plasma glucose. This one step procedure of mg/dl. This level is also applied to diagnose GDM by challenging women with 75 gm glucose and diagnosing WHO criteria. Hence it may be prudent to label 2 hr plasma glucose value > 140 mg/dl as GDM and a 2 hr plasma glucose value > 120 mg/dl as ‘Decreased IAGNOSTIC CRITERIA
Gestational Glucose Tolerance’ (DGGT). The term IGT American Diabetes Association (Carpenter and should not be used to denote any abnormal value during Couston) recommends 3 hour 100 gm OGTT and pregnancy. The figures suggested below are easy to Gestational Diabetes Mellitus is diagnosed if any 2 values meet or exceed FPG > 95 mg/dl, 1 hr PG > 180 mg/dl, 2 hr PG > 155 mg/dl and 3 hr PG > 140 mg/dl.
This criteria was originally validated against the future risk of these women developing diabetes and not on the fetal outcome. Carpenter himself now recommends a 2 hour OGTT with 75 gm glucose. The reason for this is that “when a glucose tolerance test is administered to non-pregnant individuals, it is standard to use the 75-g, Gestational Weeks at Which Screening is
2-hour OGTT. Using a different glucose challenge in Recommended
pregnant versus non-pregnant patients leads to Practically all the pregnant women should undergo confusion in the laboratory and may result in errors in screening for glucose intolerance. The usual applying the proper diagnostic criteria. Further, the 75- recommendation for screening is between 24 and 28 g, 2-hour OGTT is in use during pregnancy in many weeks of gestation. The recent concept is to screen for countries around the world, typically using the same glucose intolerance in the first trimester itself as the fetal thresholds as in non-pregnant individuals”.7 To beta cell recognizes and responds to maternal glycemic standardize the diagnosis of GDM, the World Health level as early as 16th week of gestation.16 If found negative Organisation (WHO) proposed using a 2 hour 75 gm at this time, the screening test is to be performed again OGTT with a threshold plasma glucose concentration around 24th – 28th week and finally around 32nd – 34th of greater than 140 mg/dl at 2 hour, similar to that of IGT, outside pregnancy.8 Still all these recommendations (ADA and WHO) have not projected the influence of the MANAGEMENT OF GDM
A team approach is ideal for managing women with Clarity in Labelling The Different Magnitude of
GDM. The team would usually comprise an obstetrician, Abnormal Glucose Intolerance on Pregnancy
diabetes physician, a diabetes educator, dietitian, Increasing maternal carbohydrate intolerance in midwife and pediatrician. In practice, however, the team approach is not always possible due to limited resources.
In such circumstances, management by an obstetrician This advice has scientific basis as the peaking of and physician, with the assistance of an appropriately plasma glucose is high with breakfast (due to Dawn skilled dietitian, diabetes educator, is acceptable.
phenomenon) than with lunch and dinner. Further in a A) Patient Education
normal person, insulin secretion is also high with The importance of educating women with GDM (and breakfast than with lunch or dinner.17 GDM mothers have their partners) about the condition and its management deficiency in first phase insulin secretion and to match this insulin deficiency the challenge of quantity of food The compliance with the treatment plan depends on Insulin Therapy
The implications of GDM for her baby and herself Insulin is essential if medical nutrition therapy fails to achieve euglycemia. Various criteria have been proposed for the initiation of insulin therapy. Fourth International Workshop on GDM recommended Self administration of insulin and adjustment of lowering capillary blood glucose concentration to 140 mg/dl at 1 hour and 120 mg/dl at 2 hours,18 whereas Identification and treatment of hypoglycemia ADA recommended the option of measuring 1 hour post meal values with cut off of 120mg/dl.19 These recommendations are based on one single determination, which reflects a “snap shot” of glucose evaluation rather Development of techniques to reduce stress and cope than a “video” of continuous glucose profile.20 The continuous glucose monitoring system has established Care should be taken to minimise the anxiety of the that in normal pregnancy, peak plasma glucose occurs at 60 minutes and the value was 108.7 ± 16.9 mg/dl.1 In B) Medical Nutrition Therapy (MNT)
a woman with GDM, the peak occurs between 70 – 110 minutes (at approximately 90 minutes) and with a good a) General Principles : All women with GDM should glycemic control the value was 103 ± 26 mg/dl.20 receive nutritional counseling. The meal pattern should However, being interstitial fluid glucose it has its own provide adequate calories and nutrients to meet the needs of pregnancy. The expected weight gain during pregnancy is 300 to 400 gm/week and total weight gain If the FPG concentration on the OGTT is >120mg/dl, is 10 to 12 kg by term. Hence the meal plan aims to then the patient is started on insulin immediately along provide sufficient calories to sustain adequate nutrition with meal plan. Other GDM women are seen within 3 for the mother and fetus and to avoid excess weight gain days and are also taught self monitoring of blood glucose and post prandial hyperglycemia. Calorie requirement (SMBG). SMBG is to be performed in fasting and 1 ½ depends on age, activity, pre pregnancy weight and stage hours after each meal. GDM women usually have high of pregnancy. Approximately 30 to 40 Kcal/kg ideal body post breakfast plasma glucose level compared to post weight or an increment of 300 kcal/day above the basal lunch and post dinner. A few GDM women do have requirement is needed. Pregnancy is not the ideal time post dinner plasma glucose also high. Insulin is started for obesity correction. Underweight subjects or those within 1 to 2 weeks, if the majority (i.e., at least four of not gaining weight as expected, particularly in the third seven per week) of fasting values exceed 90 mg/dl.
trimester, require admission to ensure adequate nutrition Similarly, if the majority of post prandial values after a to prevent low birth weight infants.
particular meal exceed 120 mg/dl, insulin is started.21 Pen injectors are very useful and the patient’s acceptance b) Calorie Counting : As a part of the medical nutrition therapy, pregnant diabetic woman are advised to wisely distribute their calorie consumption especially the The initial dose of NPH insulin could be as low as 4 breakfast. This implies splitting the usual breakfast into units and the dose of insulin can be adjusted on follow two equal halves and consuming the portions with a up. A few GDM patients may require combination of two hour gap in between. By this the undue peak in short acting insulin and intermediate acting insulin in plasma glucose levels after ingestion of the total quantity of breakfast at one time is avoided. For example if 4 idlis If a patient has elevated prelunch blood sugar, / chappathi / slices of bread (applies to all type of regular insulin is usually necessary in the morning breakfast menu) is taken for breakfast at 8 am and two to handle the post breakfast hyperglycemia, as there hours plasma glucose at 10 am is 140mg: the same is a lag period before the intermediate-acting insulin quantity divided into two equal portions i.e., one portion begins to work. The above regimen of regular and at 8 am and remaining after 10 am, the two hours post intermediate-acting insulin in the morning controls prandial plasma glucose at 10.00 am falls by 20 – 30 mg.
If the post dinner blood sugar is high, a small dose of regular insulin is necessary before dinner in glibenclamide and metformin is interesting.
addition to the regular and intermediate acting MONITORING GLYCEMIC CONTROL
Combination of regular and intermediate acting The success of the treatment for a woman with GDM insulin before dinner may be necessary if fasting depends on the glycemic control maintained with meal blood sugar is high. This combination of short and plan or pharmacological intervention. To know the intermediate acting insulin in the morning and as effectiveness of treatment, monitoring of glycemic control well as in the evening is known as mixed and split dose of insulin regimen. In this regimen two-third Once diagnosis is made, medical nutritional therapy of the total daily dose of insulin is given in the (MNT) is advised initially for two weeks. If MNT morning and one third in the evening. For each fails to achieve control i.e., FPG ≥ 90mg/dl and/or combination one-third dose should be regular 1 ½ hr PPG ≥ 120mg/dl, insulin may be initiated.
insulin and two-third intermediate acting insulin.
Once target blood glucose is achieved, woman with With this regimen if the patient continues to have GDM till the 28th week of gestation require lab fasting hyperglycemia, the intermediate acting monitoring of both fasting and 1 ½ hr post breakfast insulin has to be given at bedtime instead of before once a month and at other time of the day as the dinner. Insulin dose is individualized.
Target Blood Glucose Levels
After the 28th week of gestation, the laboratory Maintenance of Mean Plasma Glucose (MPG) level ~ monitoring should be more frequent atleast once in 105 mg% is ideal for good fetal outcome.22 This is possible 2 weeks, if need be more frequently.
if FPG and post prandial peaks are around 90 mg/dl After 32 weeks of gestation, lab monitoring should and 120 mg/dl respectively (MPG should not be < 86 mg/dl as this may cause small for gestational age In high risk pregnancies, frequency of monitoring Species of Insulin
Continuous glucose monitoring devices are available It is ideal to use human insulins are least but these equipments need special training and are immunogenic. Though insulin does not cross the expensive. These devices may be useful in high risk placenta, the insulin antibodies due to animal source pregnancies to know the glycemic fluctuations and insulin can cross the placenta, and stress the fetal beta cell, increase insulin production and induce macrosomia. Rapid acting insulin analogues, Throughout the stages and phases of a diabetic woman, her (Novorapid/Humalog) have been found to be safe and health status is directly dependent on her nutritional status effective in achieving the targeted post prandial glucose and her blood glucose control. As a woman ages, to prevent value during pregnancy.23 Lyspro the first analogue to the increased risk of osteoporosis and cardiovascular disease get category B approval by US FDA and aspart has also of the diabetic woman, exercise and hormonal replacement therapy can minimize the ravages of diabetes per se on the Oral Antidiabetic Drugs
aging process. Normoglycemia throughout the lifecycle of Recently reports have shown good fetal outcome in a diabetic woman results in a lifecycle of health. GDM women who were on glyburide (micronised form - Dr Lois Jovanovic
of Glibenclamide). A randomized unblinded clinical trial compared the use of insulin and glyburide in women HbA c Levels
with GDM who were not able to meet glycemic goals on If the glucose intolerance is detected in the early meal plan. Treatment with either agent resulted in similar pregnancy, HbA1c level will be helpful to differentiate perinatal outcomes. All these patients were beyond the between a pre gestational diabetic and GDM. If the first trimester of pregnancy at the initiation of therapy.24 HbA c level is more than 6%, she is likely to be a pre More studies are required before routinely GDM. HbA c is useful in monitoring the glucose control recommending glibenclamide during pregnancy during pregnancy, but not for the day to day especially during the first trimester itself. Metformin has management. A c level may serve as a prognostic value.
been found to be useful in women with polycystic Estimation of fructosamine during pregnancy is less ovarian disease (PCOD) who failed to conceive.
Continuing this drug after conception is still a Measuring Other Parameters
controversy. But there are a few studies favouring The blood pressure has to be monitored during every continuation of metformin throughout pregnancy.25 visit. Examination of the fundus and estimation of Currently, oral agents are not routinely recommended microalbuminuria, every trimester is recommended.
e) Ultrasound Fetal Measurement : The management of receptor agonist to inhibit premature uterine contractions gestational diabetes, based on the foetal growth by are likely to induce adverse metabolic effects due to their ultrasonogram demands that the fetus at risk must first glycolytic, glycogenolytic and lipolytic effects. In this manifest overgrowth before treatment decisions are situation, extra insulin may be required to maintain made. Further, the cost of performing a number of euglycemia. Foetal demise can also occur due to ultrasonograms to monitor the foetal growth and preeclampsia, which can produce fetal hypoxia via recommending therapy has to be kept in mind. Until decreased uteroplacental perfusion. Some centres allow there is evidence to absolutely prove that ignoring women with uncomplicated diabetes to go into maternal hyperglycemia when the fetal growth patterns spontaneous labor irrespective of the gestational age, appear normal on the ultrasonogram, it is prudent to but most still advocate delivery at 38 weeks as perinatal achieve and maintain normoglycemia in every mortality and morbidity appear to increase after this pregnancy complicated by gestational diabetes.
time. Induction at 38 weeks gestation may be slow or Until there is evidence to absolutely prove that ignoring unsuccessful due to unfavourable conditions of the maternal hyperglycemia when the fetal growth patterns cervix but this has to be balanced against the poorly appear normal on the ultrasonogram, it is prudent to defined and predictable risk of late intra uterine death, achieve and maintain normoglycemia in every pregnancy if pregnancy is allowed to continue more than 38 weeks.
complicated by gestational diabetes. Fetal health may deteriorate suddenly, hence obstetric - Dr Lois Jovanovic
management should not be rigid and each case needs individual care and attention. Having a neonatologist OBSTETRIC CONSIDERATIONS
support at the time of delivery is advisable.
Fetal Evaluation
Intra Partum Management
An ultrasound scan has to be performed around 18 – If labor is to be induced in GDM, the usual evening 20 weeks of gestation focusing on structures namely the insulin dose should be taken the night before, but spine, skull, kidney and heart. Fetal echocardiography no subcutaneous insulin is given the following has to be done around 20 – 24 weeks which allows to view all the four chambers of the heart. From 26th week Once labor begins, insulin is not necessary.
onwards, fetal growth and liquor volume has to be In a gestational diabetic the requirement of insulin monitored every 2-3 weeks. Fetal abdominal is likely to fall precipitously and no insulin may be circumference provides baseline for further serial required immediately after expulsion of placenta.
measurements which gives growth acceleration or restriction. Fetal movements are monitored from 20 weeks DELIVERY
onwards. Screening for chromosomal anomalies is A paediatrician experienced in resuscitation of ‘the necessary in pre GDM. Screening should be done for newborn should be present whether delivery is vaginal Down’s syndrome, alpha feto protein for neural defects or by caesarean section. As soon as the infant is born, and human chorionic gonadotrophin to identify any chromosomal abnormalities (16 – 20 weeks of gestation).
early clamping of the cord, i.e. within 20 seconds of The obese fetus of GDM mother is also hyperinsulinemic, thus interaction between leptin and insulin may be a link evaluate vital signs; Apgar scores at 1 and 5 minutes; between maternal diabetes and increased adiposity in the clear oropharynx and nose of mucus; later empty the stomach - be aware that stimulation of the - Dr Sylvie Hauguel-de Mouzon
pharynx with the catheter may lead to reflex GDM or severe obesity is superimposed to pregnancy, the resulting metabolic syndrome becomes detrimental for the avoid heat loss, keep neonate warm, transfer to fetus, evolving towards fetal overgrowth with increased adiposity at birth. This may be one major component for in perform a preliminary physical examination to utero programming of obesity later in life. detect major congenital malformations;monitor heart and respiratory rates, colour, and - Dr Sylvie Hauguel-de Mouzon
motor behaviour for at least the first 24 hours after Timing of Delivery
Sudden intrauterine fetal demise in the third trimester start early feeding, preferably breast milk, at 4-6 of diabetic pregnancy is not uncommon. To avoid this hours after delivery: aim at full caloric intake (125 risk, preterm delivery is recommended. But with this, kcal/kg/24 hours) at 5 days, divided into six to eight respiratory distress syndrome (RDS) is likely to occur.
Administering steroids for lung maturity or ß adreno promote early infant-parent relationship (bonding).
The neonate is usually best cared for, in a specialized the care by the committed team of diabetologists, neonatal unit. Interference with the infant should be obstetricians and neonatologists. A short term intensive minimal. The neonate should be observed closely after care gives a long term pay off in the primary prevention delivery for respiratory distress. Capillary blood glucose of obesity, IGT and diabetes in the offspring, as the should be monitored at 1 hour of age and before the first preventive medicine starts before birth.
four breast feedings (and for up to 24 hours in high- risk neonates). Amperometric blood glucose meters are REFERENCES
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JE. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab 22. Langer O, Levy J, Brustman L, Anyaegubunam A, Merkatz R, Divon MY: Glycemic control in gestational diabetes mellitus: how tight is tight enough: small for gestational age 26. Cornblath M, Ichord R. Hypoglycemia in the neonate. Semin versus large for gestational age? Am J Obstet Gynecol Announcement
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