Case presentation

A 32-year-old woman, 5’ 4” inches tall, weighing 57 kg, with a 3-year history of type 2 diabetes presented with a missed menstrual period and a positive pregnancy test. She was eight weeks pregnant and was on glyburide 10 mg twice daily. She had a positive family history of diabetes on the paternal side.

Her past obstetrical history revealed that she had five vaginal deliveries and six miscarriages. All occurred before diabetes was detected. She was not aware of any glucose problem during her pregnancies, and was unaware about the birth weights of her children. She was checking her blood glucose once daily in the morning with typical readings between 170 and 210 mg/dL on a glucometer. She had mild acanthosis nigricans and obesity with a body mass index (BMI) of 33 kg/m2. Her physical examination was otherwise normal. She had no retinopathy and no evidence of neuropathy. Her glycosylated hemoglobin (HbA1C) level was 9.2%.

Glyburide was stopped and she was started on insulin. She began monitoring her glucose before and after each meal, making daily adjustments in insulin dosage. She received nutrition education with an appropriate calorie intake plus an emphasis on frequent smaller meals and limited carbohydrate intake. Within one week, her plasma glucose values were in the target range for pregnancy.

The attending resident to the treating doctor raised the following questions:

Is there a relationship between her diabetes and the adverse obstetrical history?

What could have been done before her recent pregnancy to increase the odds of a favorable outcome?

What considerations affect the choice of therapy for her diabetes now?

Discussion

In the past, the trend was that most diabetic women who conceived had type 1 diabetes. But the recent trend is to have increasing number of women with type 2 diabetes. One reason may be the tendency for many women to delay pregnancy until a later age. However the main reason is the rising incidence and prevalence of diabetes in the community. 

The presence of diabetes in a woman of childbearing age is a challenge. Blood sugar control during the initial two months of pregnancy is critical for normal development of organs in the fetus. However, most women do not seek medical attention until after this period of early fetal development.

In well over half of the pregnancies, many women do not even realize that they are pregnant during this important period. Preconception counseling therefore must be an important aspect of management in all diabetic women of childbearing years, regardless of whether there is an expressed desire to conceive.2,3

Coming to the lady in question, though her diabetes was diagnosed three years ago, the fact that she is poorly controlled even on maximal sulfonylurea treatment suggests a longer duration of diabetes. This supports the hypothesis that her poor past obstetrical history may have been related to diabetes. There are reasons to believe that during her most recent pregnancy, she was poorly-controlled during the critical period of organ development, possibly leading to an anomaly incompatible with fetal viability.

Preconception counseling is always indicated for such patients. Oral diabetic medications are not safe during pregnancy. Any woman on oral medication and who wishes to conceive should be switched to insulin. All such patients if they plan pregnancy or if they are not actively using birth control, they need to resume insulin treatment. All diabetic patients even if their diabetes is well-controlled with diet and exercise alone are almost certain to require insulin during the later stages of gestation, when insulin resistance increases markedly. Before the pregnancy, as a part of preconception counseling, all such cases should be taught about insulin administration. This is also the ideal time to address any patient fears and misconceptions about insulin treatment.

Diabetic women of childbearing age who do not wish to become pregnant also require proper treatment. Insulin resistance is invariably present in type 2 diabetes and the same may be associated with reduced fertility, especially if associated with polycystic ovary syndrome. Oral diabetic medications such as metformin and thiazolidinediones that reduce insulin resistance  may also restore fertility. Thus, a previously infertile patient with type 2 diabetes may become unexpectedly pregnant after starting an insulin-sensitizing medication.

CONCLUSION

Compared to the Western population, we Indians develop diabetes at younger ages, at lower degrees of obesity, and at much higher rates given the same amount of weight gain. As a result we are seeing more and more women in childbearing years with diabetes, including those women who go on to have diabetes during pregnancy.5 Since, off-springs of mothers with pre-gestational diabetes are at risk of congenital malformation,  blood sugar control during the initial two months of pregnancy is critical. In well over half of the pregnancies, many women do not even realize that they are pregnant during this important period. Therefore,starting at puberty, preconception counselling should be incorporated in the routine diabetes clinic visit for all women of childbearing potential.5 In our patient, poorly controlled diabetes even on maximal sulfonylurea treatment , could be the cause of her poor past obstetrical history. Glyburide was therefore stopped and she was started on insulin.  Her glucose was monitored before and after each meal, making daily adjustments in insulin dosage. She received nutrition education with an appropriate calorie intake plus limited carbohydrate intake  and within one week, her plasma glucose values were in the target range for pregnancy. A team approach is thus ideal for managing women with GDM. The team should usually comprise an obstetrician, diabetologist, a diabetes educator,  and a pediatrician. 5

References

1. Rosenbloom AL, Joe JR, Young RS, et al. Emerging epidemic of type 2 diabetes in youth. Diabetes Care 22:345-54.
2. American Diabetes Association: Preconception care of women with diabetes (Position Statement). Diabetes Care 2002;23(Suppl 1):S65-68.
3. Kitzmiller JL, Buchanan TA, Kjos S, et al. Preconception care of diabetes, congenital malformations, and spontaneous abortions (Technical Review). Diabetes Care 1996;19:514-41.
4. Dunaif A, Scott D, Finegood D, et al. The insulin sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996:81:3299-306.
5.  Bajaj S, Jawad F, Islam N, et al. South Asian women with diabetes: Psychosocial challenges and management: Consensus statement. Indian Journal of Endocrinology and Metabolism. 2013;17(4):548-562.