PREGNANCY AND THE DIABETIC PATIENT

PRECONCEPIONAL COUNSELINGDr Mona Fouda

Neel MBBS,MRCP(UK),FRCPEConsultant Endocrinologist

Associate Professor of MedicineCollege of Medicine

King Saud University

Introduction:GESTATIONAL DIABETES MELLITUS

Gestational Diabetes Mellitus is carbohydrate intolerance with onset or first recognition during pregnancy,

It has been recognized for decades but the potential significance of the condition as well as criteria for screening and diagnosis remain controversial.

It affects up to 14% of the pregnant population.

The main pathogenic factor is insulin resistance, which occurs to some degree in all pregnancies, but those who are unable to compensate develop GDM.

 

Obese Older than 25 years Have a previous history of abnormal glucose metabolism Have prior poor obstetric outcome Have first-degree relatives with diabetes Are members of ethnic groups with high prevalence of DM

Women at greater risk of developing GDM are those who are:

At the fourth International Workshop Conference on Gestational Diabetes Mellitus sponsored by the ADA, the glucose concentrations considered diagnostic of GDM was lowered. 

•Members of ethnic groups with a low prevalence of GDM

•No known DM in first-degree relatives

•Those younger than 25 years

•Not obese before pregnancy

•No history of abnormal glucose metabolism

•No history of poor obstetric outcome

This was based on data suggesting that lower degrees of glucose intolerance were associated with increased risk of adverse perinatal outcome. The recommendation to test all pregnant women was changed and women who appear to be at a low risk of GDM will no longer be screened with a glucose load test

 

* In an identified low-risk group the risk of GDM is less than 2%.

Women within the high-risk group should undergo glucose testing as soon as feasible.

Women of average risk or found negative on initial screening should undergo the testing at 24-28 weeks of gestation.

A FBS > 7 mmo1 or causal plasma glucose > 11.1 meets the threshold for diagnosis of DM and if confirmed on a subsequent day there is no need to do any glucose challenge.

 

ON-STEP APPROACHAn OGTT is performed without prior screening. It is cost effective in high-risk patients or populations. TWO-STEP APPROACHAn initial screening test using 50gm glucose load and during 1hr blood sugar level and of higher than a certain threshold do OGTT. A glucose threshold value > 7.8 mmo1/L identifies approximately 80% of women with GMD and the yield is further increased to 90% if the threshold is lowered to 7.2.

 Table 1: Criteria for the Diagnosis of Gestational Diabetes Mellitus

 ______________________________________________________________________________________________________________________________________________

WHO

National American Impaired DiabetesDiabetes Data Diabetes GlucoseGroup Association Tolerance

______________________________________________________________________________________________________________________________________________

Glucose load for oral 100 100 + 75 75 75Glucose toleranceGlucose level fating 105 95 95 NA 140

 Time, h 1 190 180 180 NA NA

2 165 155 155 140 200

3 145 140 NA NA NA

_____________________________________________________________________________________________________________________________________________

Since many women do not recognize their pregnancies until they are will into the first trimester, and since it usually takes several weeks of effort to attain good glycaemic control, preconception control must be the goal for women with diabetes. In their reproductive years, they must be educated and impressed with the fact that they must plan their pregnancies and make concerted effort to maximize control before conception.  

Diabetes mellitus should be monitored carefully in pregnancy. If left untreated, whether it is pregnancy associated (Gestational Diabetes Mellitus) or pre-existing before pregnancy, increases the risk of material and fetal/neonatal mortality and morbidity. 

Maternal Complications In Diabetic Pregnancy

Hyperglycaemic ketoacidosis

Pregnancy induced hypertension

 Pyelonephritis and other infections

 Polyhydramnios

 Preterm labour

Worsening of chronic complications, e.g., Retinopathy Nephropathy, Neuropathy, Cardiac Diseases.

Before the era of insulin, maternal mortality was a high as 30% and perinatal mortality varied from 66-90%

Till the mid 1970s physicians were still advising diabetic women to avoid pregnancies.

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Potential Perinatal Morbidity/Mortality in Infants of Diabetic Mothers______________________________________________________________________________________________________________________________________

-    Asphyxia Increased blood volume

-  Birth injury Intra uterine growth retardation

-   Cardiac hypertrophy Macrosomia

-   Congenital anomalies Neurological instability and irritability

-   Erythema and hyperviscosity Organomegally

-   Heart failure Respiratory distress syndrom

-   Hyperbilirubinaemia Small left colon

-   Hhypocalcaemia Still birth

-   Hypoglycaemia Transient haematuria

-   Hypomagnesaemia

______________________________________________________________________________________________________________________________________

In spite of all the advances achieved so far in the care of the pregnant diabetic woman, many problems remain.

High incidence of congenital anomalies and spontaneous abortion in infants of diabetic mothers (IDMs).

The true incidence of SAB in diabetic pregnancies is not known, but has been reported to be as high as 30%, double that of the general population.

The increased risk of congenital anomalies in IDMs ranges from 6-12%, a two-five-fold increase over the general population and accounts for around 40% of perinatal loss in IDMs

 

Table III:

Congenital Malformations in Infants of Diabetic Mother (IDMs)

Anomaly * Ratio

•        Caudal regression 252•         Spina bifida, hydrocephalus and others CNS defects

2•         Anencephalus

3•         Heart anomalies

4•    

The etiology of this increased incidence of congenital anomalies in IDMs is not yet clearly defined. Some have shown that hyperglycaemia and other metabolic abnormalities are teratogenic singly or in combination.

  Anal/Rectal Atresia 3   Renal anomalies 5 - Agenesis 6 - Cystic Kidney 4 - Ureter Duplex 23   Situs inversion

48Ratio of incidence is in comparison to the general population.

It is very important to understand that fetal organogenesis is largely completed by eight weeks after the last menstrual period (six weeks past conception) and therefore, poorly controlled diabetes during the early weeks of pregnancy, in many cases before the woman even know that she is pregnant, significantly increases the rise of a first trimester SAB or delivering an infant with a major anomaly.

The association between HbA1c, which expresses roughly the control of blood glucose over the preceding 4-6 weeks before its measurement, and increased risk of congenital anomalies of SABs has made it a useful tool in assessing the metabolic control in early pregnancy during the critical period of organogenesis (< 13 weeks) and therefore predicting such complications early on. Therefore, normalizing blood glucose levels before and during the early weeks of pregnancy can reduce dramatically the risk of major anomalies as well and the occurrence of SABs to almost near that of the non-diabetic population.

 

Care of the difficult patient who often presents late for antenatal care and/or is non compliant. 

Care of the woman with severe diabetic complications.

 Therefore, pre-pregnancy counseling has emerged as a vital component in the woman with diabetes. The major component of a pre-pregnancy counseling include:

 - Contraceptive advice.- Risks of pregnancy, maternal and fetal/neonatal.- Importance of maintaining normal blood glucose levels.- Genetics counseling.

- Personal commitment by the woman.

Goals of Pregnancy Planning Program

-         Assessment of patient’s fitness for pregnancy-         Obstetric evaluation-         Intensive education of patient and partner-         Attainment of optimum Diabetic control-         Timing and planning of pregnancy

A planned pregnancy is a major objective of a preconception counseling

 

 

The woman should understand fully the increased risk of complications both for her and for her diabetes is not properly controlled before and during the early weeks of pregnancy, but should also be reassured that with continual optimal glucose control throughout pregnancy, she can effectively reduce the reduce the risk of complications.She will also need to know that diabetic chronic complications can worsen during pregnancy, e.g. retinopathy and nephropathy, and preconception evaluations of such complication must be emphasized.

Blood glucose should be normalized as possible before and throughout pregnancy to reduce the risk of developing complications.

 

Deep, personal commitment can never be overemphasized. The woman has to understand that she will be seen frequently by her physician and may need to be hospitalized if problems arise. Personal involvement in maintaining normal blood glucose throughout pregnancy is mandatory and the pregnant woman has to understand the importance of such deep personal commitment on the outcome of her pregnancy.

________________________________________________________________________________________

Pregnancy Assessment for Diabetic Women_______________________________________________________________________________________

_

-         Gynaecological evaluation-         Laboratory evaluation      • HbA1c level        • Urinalysis and culture      • 24-h Urine for creatinine clearance and total protein-       Thyroid panel (Type I Diabetic Women)-        Special studies

ECG or treadmill-         Neuropathy testing if indicated _______________________________________________________________________________________

POTENTIAL CONTRAINDICATIONS TO PREGNANCY

1.  Ischaemic heart diseases

2.  Active proliferative retinopathy, untreated3.  Renal insufficiency: Cr. C1 < 50 m1/min or serum

creatinine > 2mg/d1 or heavy protein > 2g/24hr orhypertension (BP > 140/90 despite treatment)

4.  Severe gastroneuropathy: nausea, vomiting, and diarrhea PRE-PREGNACY MANAGEMENT  

Once the woman has undergone the pre-pregnancy counseling and found fit to get pregnant, then a plan should

be outlined for pre-pregnancy management, with the goal of normalizing the blood glucose level before

conception and maintaining of euglycaemia throughout the

pregnancy

 

Ideally, the Diabetes care team should include:-  The primary care physician or an endocrinologist-  The obstetrician-  A nurse educator (preferably a certified Diabetes educator)-  A registered dietitian-  A paediatrician or neonatologist Then she can be placed on an intensive human insulin regimen with adequate coverage of premeal insulin as well as basal insulin need. She could be taught self-monitoring of blood glucose and she should do it frequently before and after meals.

Preconception goals for premeal glucose levels should be 70-90 mg/d1 (3.8-5 mmo1/L) and the 1-2 hours postmeal blood glucose levels should fall at or below 130mg/d1 (7.2 mmol/L).

Adjustment in insulin doses according to blood glucose levels can then be done by the patient\s team, or of she is quite motivated and apt, she can do it herself at home. She should also be warned about the symptoms and signs of hypoglycaemia and taught how to mange it. Her partner or a relative should also be instructed in the use of glucagons. 

Serial HbAlc can be drawn monthly to confirm normalization of blood glucose level in the preconceptional period to affirm the safety of pursuing pregnancy form the metabolic standpoint.

When maternal glucose levels are used, insulin therapy is recommended when MNT fails to maintain self-monitored glucose at the following levels: 

Fasting whole blood glucose 95mg/d1 (5.3 mmo1)

Fasting plasma glucose 105mg/d1 (5.8 mmo1/L/1)

or 1-h postprandial whole blood glucose

140mg/d1 (7.8 mmo1/L1)1-h postprandial plasma level 155mg/d1 (7.2 mmo1/1)

 

The most important tool in reducing perinatal morbidity and mortality owing to major malformation attributed to uncontrolled diabetes mellitus remains prevention. Glycaemic control in the first trimester is not only relevant it is critical. 

2-h postprandial whole blood glucose 120mg/d1 (6.7 nni1/1) 2-h postprandial plasma level

130mg/d1 (7.2 mmo1/1

PREGNANCY AND THE DIABETIC PATIENT

MONITORING AND CLINIC VISITSThe cornerstone of management of Diabetes in pregnancy is a team approach with frequent visits to the clinic by the pregnant woman as well as the daily home blood glucose monitoring.

 

SMBG reduces hospital admissions and hospital stay in days if required and it has been the single most important advance in the management of diabetes in pregnancy in the last decade because of its ability to provide intensive management of diabetes without the need for frequent admissions.

 

Achieving euglycaemia in pregnancy can promise an outcome that shows no deleterious effect of diabetes. Pre-existing diabetes has its own complications, which should be carefully monitored during pregnancy. “Controlled Diabetes is essential to fetal welfare”.This statement made by Dr. Priscilla White in 1928 is as pertinent now as it was then.

*The major diabetogenic hormones of placenta are human placental lactogen hPL, estrogen and progesterone. Also serum cortisol is increased during pregnancy and prolactin being elevated during gestation has a diabetogenic effect as well.

*Degradation of insulin is increased during pregnancy because of certain placental enzymes comparable to liver insulinases, and the function of the placental membrane, which has an insulin degrading activity.

The normal pancreas compensate by increasing insulin secretion. If the pancreas doesn’t respond adequately to these changes or of the clearance of glucose is defective then gestational diabetes occurs.

 

Deleterious effect of sustained or intermittent hyperglycaemia on the fetus: 1. During orgaqnogenesis (weeks 2-8), an increased risk of malformation2. Premature stimulation of fetal insulin secretion leads to;-         macrosomia -         inhibition of pulmonary surfactant maturation leading to fetal respiratory distress-         neonatal hypoglycaemia leading to permanent neurological damage 

Achieving optimal control of diabetes requires balancing the meal, insulin dosage, an activity level with strong commitment form all those involved in the care of the diabetic pregnant woman, with the pregnant woman herself being the most important member of the team. Working with the pregnant population is a rewarding experience as they are strongly motivated in the care of their disease. The best chance for success comes when the pregnancy is planned, as good metabolic control is desired before conception.

GOALS IN THE DIABETIC PREGNANCY

The target range for blood glucose during pregnancy is patterned after maternal plasma glucose levels in normal pregnancies.

Mean plasma glucose level is about 20% lower in pregnancy then pre-pregnancy level and the HbA1c follows suit.

Risk factors for developing GDM e.g. family history, obesity, and poor obstetric history identify only 50% of women at risk.

Blood Glucose Goals In Diabetic Pregnancy

-       Fasting 60 – 90mg/dl (3.3 – 5.0 mmol)-         Pre-meal 60 – 105mg/dl (3.3 – 5.8 mmol)-    1 hr post prandial 110 – 130mg/dl (6.1 – 7.3 mmol)-    2 hr post prandial 90 – 120mg/dl (5.0 –6.7 mmol)-    02.00 – 06.00 AM 60 – 120mG/dl (3.3 – 6.7 mmol)

To achieve this, frequent SMBG readings are necessary. Ideally, eight tests should be done; one before each meal and one 1-2 hours after each meal; one at bedtime and one in the middle of the night.

*Pre-meal tests assess presence of asymptomatic hypoglycaemic and establish the pre-meal short-acting insulin doses.

*Post-meal tests are used to evaluate the effect of the particular meal and insulin doses on the blood glucose.

*Bedtime testing is necessary to rule out any hypo or hyperglycaemia, which requires attention before retiring to bed and also determines the quantity and quality of the bedtime snack.

*03:00 testing is important in detecting hypoglycaemia if nocturnal hypoglycaemia is suspected.

These tests provide feedback about the match between food and insulin and the effect of dietary changes.

Although eight tests per day is ideal, this can be impractical for many patients and some centers recommend four tests each day –fasting 1-2 hours after each meal.

Patients on more than two injections per day or receiving continuous subcutaneous insulin injection therapy will need to perform at least seven tests a day-before each meal, after each meal, and at bedtime.

SMBG is one of the most important tools for maintaining euglycaemia during pregnancy. It provides day-to-day information on which treatment recommendations can be based, but it has the inherent potential for gross inaccuracies and therefore education and periodic reevaluation and reeducation are vitally important for its success.

Results should be recorded in an organized manner so that the glycaemic pattern is recognized and steps made appropriately, according to blood glucose levels.

HOME MONITORINGBlood glucose should be maintained in the normal range throughout the day, throughout pregnancy. This can only be achieved by self-monitoring of blood glucose be the patient at home. It should be taught at the initial visit to the clinic to allow for immediate monitoring on a daily basis.There are two methods currently available for SWMBG:i. visual comparison of reacted reagent stripsii.The use of reflectance or enzyme electrode blood glucose meters.Both methods depend on a glucose oxidase reactionThe members of the health care team looking after the pregnant diabetic mother should verify that the patient is monitoring her blood glucose accurately by frequent check-ups in the clinics. 

PROBLEMS WITH SMBG

i.Objectivity

Errors in judgment, especially when patients are highly motivated to keep their blood glucose readings in the normal range, is not uncommon, especially with the visually read strips. The meters are less likely to invite errors in judgment.

ii.AccuracyImproper technique can lead to variability in results and this can be minimized if patients are adequately trained and carefully monitored. Some systems are more dependent upon user skills than others.

Others factors affecting accuracy include defective strips, instrument malfunction, severe hypo or hyperglycaemia, and haematocrite value. With current systems, SMBG measurements should be within 15% of the results of a reference measurement using the same blood sample.

HbA1c MEASUREMENT IN PREGNANCY

I.Pre-existing Diabetes It is useful in evaluation of the degree of diabetic control over the period of 4-6 weeks before its measured and it is therefore very useful in the critical early weeks of pregnancy.Its level has been directly correlated with the increased incidence of congenital malformation in infants of diabetic mothers. The risks of congenital anomalies when the HbA1c is higher than the man value of the non-diabetic women in the first 8 weeks of gestation reached 28%. Therefore, it is important to measure the HbA1c level when the diabetic woman first presents with plans for pregnancy. This should be advised to be as early as possible and continue with serial measurements every 4-6 weeks until the pre-pregnancy goal of near normal HbA1c value is achieved.

Once pregnant, the HbA1c should be checked every 4-6 weeks to assess the degree of glycaemic control throughout the pregnancy and should be maintained within or near the non-diabetic range.

II.Gestational Diabetes Mellitus

An initial HbAlc measurement is helpful

i. If it is in the non-diabetic range, which is usually the case. It reassures the woman the GDM was diagnosed at the appropriate time and was probably not present earlier in gestation.

ii. If is elevated: then it warns that glucose intolerance or even overt DM may have been present earlier in the pregnancy or even predated the pregnancy. iii. It serves as a baseline value in pregnancyIt should be measured every 4-6 weeks to monitor the control and help in adjustment of the insulin doses.

URINARY KETONE TESTING

Ketonaemia during pregnancy has been associated with changes in the developing nervous system of the fetus and with decreased intelligence. It may also signal development of maternal ketoacidosis, which is associated with 50-90% mortality rate in the fetus.Starvation ketosis commonly occurs after an overnight fast; so it is best to test for urinary ketones in a first monitoring urine sample.

If ketonuria occurs despite good glucose control and is repeatedly seen at a particular tome of the day, then the patient may need the addition of a snack before that particular time. Urinary ketones need also to be checked if a meal is delayed or missed, with any illness, and with any blood glucose > 200mg/dl. Persistent ketonuria not responding to dietary change will require adjustment in the insulin doses.

In pregnant women with pre-existing diabetes, certain tests may be required in addition:

-  Thyroid function test (type IDDM).

-  A clear catch dipstick urine analysis should be evaluated for protein, ketones and WBC each visits to R/O occult UTI or incipient toxamia.

- A finger stick blood glucose measurement should be done each visit to verify self-testing results.

- Serial HbAlc levels every 4-6 weeks to assess overall glycaemic control 

Surveillance of diabetes related complications are also vital:-  A 24-hour urinary sample for creatinine clearance and protein should be collected each trimester with referral to a nephrologist if nephropathy is present.-  A baseline retinal examination done by an opthalogist with the necessary follow up examinations.-  Careful attention to cardiac status with referral to a cardiologist

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Frequency of Testing Maternal Status During Pregnancy for

Women with Pr-existing Diabetes_______________________________________________________________________________

Test Frequency

 

HbAlc Every 4-6 weeksGlucose During weekly or bi-weekly visits in the clinic SMBG 4-8 times dailyFastin ketones DailyUrinalysis During weekly or bi-weekly clinic visitsKidney function Each trimesterThyroid function Baseline & repeated as needed Eye status First trimester and repeated as necessary ________________________________________________________________________________

FOLLOW UP VISITS

The pregnant woman with diabetes should be seen every 1-2 week with fasting and/or random blood glucose collected at each visit to document control and assess how this value compares with SMBG at home.MSU analysis and HbAlc should be followed up as stated in the above table.

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Pregnancy Diet Calculation________________________________________________________________________________________________________________

Determination of desirable body weight:100 lbs for first 5 ft of height + 5 lb/inch for each l inch over 5 ft ±10% for large/small frame.

Determination of daily calorie requirement:30 kcal/kg (2.2 lb) current body weight for active woman25 kcal/kg (2.2 lb) current body weight for sedentary, obese womento lose l lb/week, subtract 500 kcal from daily requirement or increase exercise.

Distribution of calories:55-60% of carbohydrate (preferably unrefined carbohydrate with fiber)12-20% protein< 30% fat (composed of up to 10% polyunsaturated fats, < 10% saturated fats,and remainder from monounsaturated fats).__________________________________________________________________________________________________________________

 Table IX:-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Sample Pregnancy Daily Insulin Therapy_________________________________________________________________________________________________________________________________

Goals for therapyFasting, premeal blood glucose < 150mg/dl (< 8.3-5.5 mM)1-2 h postmeal blood glucose < 150mg/dl (8.3 mM)HbAlc should be < 6.1%

Human insulin regimentsCombination of short-acting insulin with intermediate-acting orLong-acting insulin in 1 2 to 4-injection routine

 

0.5-1.0 Ukg –1 day –1 (0.2-0.4 Ulb–1 day) -⅔ total dose in A.N,⅓ total dose in P.M

 

ExamplesShort-and intermediate-acting insulin prebreakfast and predinner*Short-acting insulin before each meal + intermediate or long-acting insulin at bedtimeShort-intermediate-action insulin before lunch

___________________________________________________________________________________________________________________________________

* Most intensive insulin regimes will consist of > 2 injections/day to maintatin euglycemia  __________________________________________________________________________________________________________________________________

 Table IX:-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Sample Algorithms for PregnancyInsulin Adjustment___________________________________________________________________________________________________________________________________

Adjustments for unexplained hyperglycemia: check for deviations in diet and/or illness, then:

If prebreakfast blood glucose BG > 100mg/dl (5.5 mM) for 2-3 day, increase P.M intermediate-acting insulin by 2U or long-acting insulin by

1-2U. 

If prelunch BG > 100mg/dl (5.5 mM) for 2-3 day, increase prebreakfast short-acting insulin by 2U or prelunch short-acting

insulin by 1-2U. 

If predinner BG > 100mg/dl (5.5 mM) for 2-3 days, increase prebreakfast intermediate-acting insulin by 2U or prelunch shout-

acting insulin by 1-2U

 

If bedtime BG > 120mg/dl (6.6 mM) for 2-3 days, increase predinner shot-acting insulin by 1-2U.

_________________________________________________________________________________________________________________________________________

 

 

Adjustments for unexplained hyperglycemia: review meal plan, then:

If breakfast BG > 70mg/dl (3.8mM) twice during a week of is symptoms of low BG overnight.

decrease evening intermediate-acting insulin by 2U or long acting-insulin by 1-2U.

If predinner BG > 70mg/dl (3.8mM) or reaction occurs between breakfast and lunch,

decrease prebreakfast shot-acting insulin by 1-2U

If predinner BG > 70mg/dl (3.8mM) or reaction occurs between lunch and dinner,

decrease prebreakfast intermediate-acting insulin by 2U or prelunch short-acting insulin by 1-2U. 

If prebedtime BP< 70mg/dl (3.8mM) or reaction occurs between dinner and bedtime,

Decrease predinner short-acting insulin by 1-2U.___________________________________________________________________________

 

Labour and Delivery: 

Patients with documented good blood glucose control do not need early delivery but if a fetus with documented poor pulmonary maturity as assessed by aminiocentesis and poor results on fetal surveillance protocols (heart rate, kicks count etc….) then immediate delivery is advised.

Maternal insulin requirements usually drop quickly postpartum and gestational diabetic mother will require no further insulin. Pre-gestational diabetic mother will require resumption of insulin treatment but the requirement will be less for 48-96 hours post operatively.

 

Almost 98% of gestational diabetic women revert to normoglycaemia postpartum. An OGTT test should be performed 6 weeks postpartum. Diabetes Mellitus will recur in each subsequent pregnancy in 90% of cases. If they remain overweight 60% will have overt DM within 20 years.

REFERENCES:

Medical Management of Pregnancy complicated by diabetes.

American Diabetes Association Clinical Education Series, June 1993.

 

Diabetes Complicating Pregnancy. The Joslin Clinic Method, editor John W. Hare, MD. Allan T. Liss, Inc. New York, 1989.

 

Endocrinology and Metabolism Clinics of North America Diabetes Mellitus, Perspectives on Therapy, June 1992.

 

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