Therapeutic Treatment for Gestational Diabetes Mellitus

Introduction
Gestational diabetes mellitus (GDM) has become a global concern and poses a great risk of
complications for both the mother and her fetus/newborn child.1,2 Some of the risks that GDM
pose are that the mother and infant are more likely to develop type 2 diabetes mellitus later in
life, preeclampsia, abnormal delivery, and the infant is likely to be obese later in life.2,3
Treatment and prevention of GDM is beneficial to both the mother and infant and can help
minimize the adverse effects of GDM.1 The topic of prevention and/or treatment of GDM is
controversial. This article aims to review and analyze different forms of treatment and/or
prevention of GDM to find the best treatment for women who have GDM or are likely to
develop GDM. The article will discuss the use of probiotics for the treatment of GDM, the use of
medications such as metformin and insulin to control GDM, and manipulation of lifestyle
factors that can effect GDM.2,3,4,5,6,7,8 It will also discuss the effects that the Dietary Approach to
Stop Hypertension (DASH) diet has on GDM, and the effects of the Mediterranean diet on
GDM.1,9,10
Probiotics
Neda Dolatkhah conducted a study at Alzahra University Hospital in Tabriz where they tested
the effects of probiotics on women with GDM.3 The study was an 8 week double-blind placebocontrolled randomized clinical trial. 64 women aged 18-45 participated in the study and were
randomly assigned by a computer to take a probiotic or a placebo. 29 participants received the
probiotic and 27 participants received the placebo. The probiotic contained 4 strands:

Lactobacillus acidophilus L-5, Bifidobacterium BB-12, Streptococcus thermophiles STY-31, and

Lactobacillus delbrukeckii blugaricus LBY-27.3 In coordination with the probiotic/placebo,
participants were given dietary advice.
To measure the effects of the probiotic taken, all participants had a blood sample taken before
and after the intervention. Every 2 weeks all participants had their blood pressure and weight
measured. To help participants with compliance in taking their probiotic/placebo, a phone call
was made every week to ask about any problems or concerns.
The study concluded that The probiotic supplement appeared to affect glucose metabolism
and weight gain among pregnant women with GDM.3 Both the participants that took the
probiotic and participants that took the placebo had an increase in insulin sensitivity. Weight
gain was similar for both groups for the first six weeks of the study, but during the last two
weeks of the study the group that took probiotics had a healthier weight gain that was
significantly less than those who took the placebo.3 Fasting blood sugars for participants taking
the probiotic had a significant decrease of 14.66% while those taking the placebo had a
decrease of 7.38%.3 Insulin resistance significantly decreased for the probiotic group by 6.74%
while for the placebo group there was a non-significant increase of 6.45%.3
Even though Neda Dolatkhahs study had positive results for participants taking probiotics, her
study pointed out that not all probiotic studies done on GDM have had the same result. Her
article discussed a recent double blind randomized clinical study of which 149 women were
given lactobacillus salivarius UCC118 or a placebo. After the study there wasnt a difference in
fasting blood sugar levels between the two groups.3 There are many factors that can be

explored with probiotics such as type and strains of probiotic. There other confounding factors
such as diet, exercise, BMI, and a family history of GDM that can affect the results of taking a
probiotic supplement.3
Although the field is not greatly researched, probiotics do show potential for reducing the risk
of and treatment of GDM. A meta-analysis in the PLOS ONE journal looked at factors that could
prevent GDM. One factor the meta-analysis focused on was nutritional manipulation. It was
found interventions that were mainly based on diet reduced the rates of GDM by 33%.2 While
the risk of GDM was reduced by 60% for probiotics (with diet) in comparison to standard
care.2
Oral Medications and Insulin
The article Metformin for gestational diabetes in routine clinical practice,4 found in the
Diabetic Medicine Journal, discusses the use of metformin, insulin, and diet as treatment for
GDM. This prospective randomized trial observed 1,269 women who had babies from January
2007 to December 2009 who were in the National Womens Health database.4 Of the 1,269
women, treatment was diet in 371, insulin in 399, and metformin in 465 (249 metformin
alone, 216 metformin and insulin).4 Women treated with diet alone had a significantly lower
BMIs and fasting blood glucose levels than women treated with either metformin or insulin.
From this study 34 women were excluded due to no treatment for the GDM, or being treated
with glibenclamide.4
The study found that women who took insulin to treat their GDM had the worst outcomes
when compared to both the metformin and diet treated women. Women who took insulin had

the highest rates of: Caesarean delivery, preterm delivery, large-for-gestational age, neonatal
admissions, and intravenous dextrose use when compared to those taking metformin or
women who just changed their diet. Results were fairly similar between women who took
metformin and women who changed their diet. Due to women having much higher BMIs and
fasting blood glucose levels in the metformin group and having similar results when compared
to the diet group, this paper firmly argues that metformin is a logical treatment for women
with gestation diabetes.4 However, as the results were very positive for participants taking
metformin this paper also acknowledged that baseline differences between treatment groups
may have contributed4 to the results.
Another study that looked at insulin in comparison to metformin took 104 women, age 18-45,
with GDM or type 2 diabetes mellitus at 20-30 weeks gestation where patients were
randomized to either receive insulin or metformin.5 When participants receiving metformin
alone couldnt achieve blood glucose targets, they were also given insulin. 94% of participants
with GDM completed the study while 76% of participants with type 2 diabetes mellitus
completed the study.5
The study concluded that metformin monotherapy is effective in achieving glycemic targets in
the management of diabetes in pregnancy. It is more effective than insulin in lowering the two
hour post prandial blood glucose level.5 There was not a significant difference between
participants taking metformin and insulin in respect to fasting blood glucose levels and one
hour post prandial blood glucose levels.5

Exercise and Diet

The journal Diabetes, Obesity and Metabolism took a look at the effects of diet and exercise on
gestational diabetes. They did this in their article Simple lifestyle recommendations and the
outcomes of gestational diabetes. 2x2 factorial randomized trial.6 This study looked at all
pregnant women who attended the SantAnna Hospital from July 2009 to February 2012.
Women who participated were aged 18-50 and gestation of 24-26 weeks. Women had to have
GDM which was based on a 75g oral glucose tolerance test.6 Women were excluded if their BMI
was greater than 40, had a disease, or had a contraindication, including medication, to
exercise.6
To test multiple aspects of diet and exercise women were broken into different groups. Groups
were: diet only, group D, diet and behavioral recommendations, group B, diet and exercise,
group E, Diet and behavioral recommendations and exercise group BE.6 Exercise consisted of
walking 20 minutes a day. Behavioral recommendations consisted of written instruction for
healthier diets such as lowering carbohydrate intake and correcting misinformation about diets
for pregnancy. Women were given individual diets which consisted of carbohydrates 48-50%,
proteins 18-20%, fats 30-35%, fiber 20-25 g/day, (and) no alcohol.6 Participants received
weekly phone calls and were visited every two weeks to check for adherence to the
intervention.6
Many aspects of diet had improved for all groups including: total energy intake, total fat,
saturated fat, and sodium decreased, alcohol was abolished, and protein and fiber intake

increased. Adherence to nutritional recommendations did not differ among groups. 6 Group E
had 68.6% compliance to exercise while group BE had 64% compliance to exercise.
In conclusion: exercise reduced maternal postprandial glucose, HbA1C, CRP and triglycerides
values and the incidence of any maternal/neonatal complications, but not fasting glucose in
GDM women.6 Fasting glucose levels did not change most likely due to levels being within
normal range at baseline.6 Behavioral recommendations failed to produce significant outcomes,
and those who had only changed their diet had a high rate of complications for both mother
and baby.6
Another study looked at weight-gain restriction to control the outcomes of GDM.7 Interventions
were diet compared to diet and exercise. The study was published in the journal: Applied
Physiology, Nutrition and Metabolism.7 The study took 96 women diagnosed with GDM, at 33
weeks gestation or less, and allowed them to choose to be in the diet only intervention group
or the diet and exercise intervention group. Only 39 women chose to be in the diet and exercise
group while 57 women chose to be in the diet intervention group, this was most likely due to
preference of not wanting to exercise.7
Caloric allowance for women depended on their BMI: 25 Kcal/kg for a BMI of 25-29.9, 20
Kcal/kg for a BMI of 30-39.9, and 15 Kcal/kg for a BMI of 40 or greater.7 Carbohydrates
consisted of 40-45% of Kcals consumed. Women in the diet and exercise intervention group
averaged exercising 153 minutes per week.7 For some women the intervention was not
effective enough to bring blood glucose levels into a normal range thus requiring insulin
therapy for those participants. During the study 13 (35.1%) of the exercise and diet group

participants required insulin while 22 (38.6%) of the diet intervention group required insulin to
maintain blood glucose levels.7 Blood glucose levels and insulin sensitivity were not outcomes
measured as a result of the interventions.
This study found that in both intervention groups women who gained weight had a higher
percentage of macrosomic infants than those who lost weight or had no weight change during
pregnancy.7 All other pregnancy outcomes were similar. One difference found when
comparing the 2 intervention groups was that women who changed their diet alone had
significantly more weight gain than women who exercised and changed their diet.
The study concluded women with GDM would benefit from caloric restriction and exercise
because it would help reduce the risk of macrosomic infants and have no adverse effects on
other pregnancy outcomes. In addition this study states: pregnancy is an ideal time for
behavior modification, and this intervention may also help promote long-term healthy lifestyle
changes. 7
A meta-analysis published in the Journal of Womens Health reviewed strategies to prevent
GDM, and or the symptoms of GDM.8 The review found that dietary counseling and exercising
programs had reduced the incidence of GDM more effectively than standard care. And that
instruction in special diets particularly a low glycemic diet would help reduce the adverse
effects of GDM such as macrosomia.8 The article clearly states that no interventions relating to
exercise and diet had an effect on fasting blood glucose levels.8

DASH Diet
The European Journal of Clinical Nutrition recognized that multiple strategies have been used to
reduce the adverse effects of GDM.9 Diet has been a factor tested many times. For example
there have been benefits for those with GDM from diets that are low in glycemic index. 9 As the
DASH diet was originally designed to manage hypertension it also has shown to be beneficial to
type II diabetics partially because it is naturally low in glycemic index. Due to this, the European
Journal of Clinical Nutrition studied the effects of the DASH diet on GDM.
52 women 18-40 years old, 24-28 weeks gestation, diagnosed with GDM participated in a
randomized controlled clinical trial that lasted for 4 weeks. 26 participants were given a control
diet designed to contain 45-55% carbohydrates, 15-20% protein, and 25-30% total fat.9 At the
same time 26 other participants were assigned to the DASH diet. The DASH diet was rich in
fruit, vegetables, whole grains and low-fat dairy products, and contained lower amounts of
saturated fats, cholesterol and refined grains with a total of 2400 mg/day sodium.9
Women who used the DASH diet had significantly better results than women who took the
control diet. Of the 2 groups 46.2% of women who were on the DASH diet needed a cesarean
section while 80.8% of women on the control diet needed a caesarean section.9 Women who
were on the DASH diet also had lower rates of insulin therapy post intervention in comparison
to women who were on the control diet 23% and 73% respectively.9 Effects of the DASH diet
were also beneficial for the infants. Birth weight along with head circumference and ponderal
index was significantly lower than in the control group.9 In conclusion this study found that

consumption of (the) DASH diet for 4 weeks among pregnant women with GDM resulted in
improved pregnancy outcomes.9
Another study published in the journal Nutrition found similar results for the DASH diet.10 A
small study of 32 women diagnosed with GDM gestation 24-28 weeks participated in a
randomized controlled clinical trial for 4 weeks.10 The study focused on fasting blood glucose
levels, plasma antioxidant capacity, serum insulin, glutathione levels, and C-reactive protein.10
Women were randomly assigned either the control diet or DASH diet. The DASH diet was rich
in fruits, vegetables, whole grains, and low-fat dairy products and was low in saturated fats,
total fats, cholesterol, refined grans, and sweets, with a total of 2400 mg/day of sodium.10 The
control diet was 40-55% carbohydrates, 10-20% protein, and 25-30% total fat.10 To measure the
effects of the diets, fasting blood was drawn at baseline and after the 4 week intervention.10
The study found that participants who were on the DASH diet benefited greatly. Fasting blood
glucose, serum insulin/resistance, plasma antioxidant capacity, and glutathione levels
improved.10 There wasnt a difference seen in C-reactive protein levels.10
Mediterranean Diet
A non-interventional, prospective, observational study titled: Relation of the Mediterranean
diet with the incidence of gestation diabetes was published in the European Journal of Clinical
Nutrition.1 This study aimed to find the benefits of adherence to the Mediterranean diet on
GDM. This study looked at 10 Mediterranean countries. 1,076 women diagnosed with GDM at

24-32 weeks gestation were evaluated. If women previously had type I or II diabetes they were
excluded from the study.1
Women in this study were given a validated questionnaire to measure their Mediterranean Diet
Index (MDI).1 A higher MDI score indicates better adherence to the Mediterranean diet. When
comparing the participants adjustments were made for age, BMI, family history, weight gain,
energy intake, and multiple comparions.1
By observation it was found that adherence to a Mediterranean diet pattern of eating is
associated with lower incidence of GDM and a better degree of glucose tolerance, even in
women without GDM.1 Although this was a published study it was observational, and based
off of participants honesty and ability to recall their diet.
Conclusion
There are multiple prevention strategies and treatments for GDM. All treatments and prevention
strategies are not created equal, some provide greater benefits for the mother and child than others.
Difficulty of intervention implementation for women with GDM greatly varies between different types of
treatments. Difficulty ranges from simply taking metformin to changing your lifestyle by exercising and
changing your dietary patterns.
Healthcare providers vary in their perceived role of care for women with GDM. The majority of
healthcare providers, 60-70%, also report that lifestyle modification programs and corresponding
reimbursement would better support them to provide improved care11 to women with GDM. The
majority of healthcare providers also agree that there is a need for more local nutrition specialists and

patient education materials.11 Education materials and nutrition specialists would help women provide
self-care.
Based on the findings of this research article I suggest that women at risk/with GDM implement an
exercise regimen as simple as walking 20 minutes a day and follow the DASH diet. The DASH diet has
shown to provide the greatest benefits to both mother and baby. Implementing both exercise and diet
changes will not only be beneficial to treat/prevent GDM but it will also be beneficial for overall health
in the long run. If glycemic control is not obtained by adherence to exercise and the DASH diet then
women ought to take metformin. If there still isnt glycemic control with metformin then as a last result
women should use insulin.

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