THE ROLE OF MATERNAL PHYSICAL ACTIVITY TO TREAT OR PREVENT GESTATIONAL DIABETES.

Physical inactivity is a risk factor for obesity and type 2 diabetes, both of which are reaching epidemic proportions. Obesity and gestational diabetes mellitus (GDM) are closely linked. The prevalence of GDM in obese women is 17%, and overweight women have a 1.8-6.5 times greater risk of developing GDM than normal weight women. In addition, women with GDM are at increased risk for type 2 diabetes later in life. Sedentary lifestyle is a risk factor for developing GDM and thus, the common link between obesity and GDM is physical inactivity, with both obesity and GDM as risk factors for type 2 diabetes.

Definition of GDM

GDM is defined as a form of diabetes first diagnosed during pregnancy. During a normal pregnancy, a series of hormonal events contributes to insulin resistance at the muscle level. An increase in insulin resistance decreases maternal blood glucose uptake by the muscles, ensuring an adequate glucose supply for fetal growth and development. If risk factors for GDM are present, pregnancy may tip the balance and abnormally high maternal blood glucose and insulin concentrations may result. The cause of GDM is unknown, but may be a combination of genetics and lifestyle, perhaps the cumulative effects of unmodifiable and modifiable risk factors.

Risk Factors for Developing GDM

Unmodifiable risk factors include a history of diabetes in the immediate family, ethnicity, and maternal age. Modifiable risk factors for GDM include physical inactivity, obesity/overweight, previous GDM, and a history of macrosomic (more than 4000 g) babies.

Up to 60% of women with GDM will develop type 2 diabetes within 4 years after delivery. Risk of developing type 2 diabetes is a function of the number of GDM pregnancies a woman has. In addition, there is increased health risk for offspring born to GDM women. These babies are more likely to develop type 1 or 2 diabetes later in life. Large babies are at greater risk for obesity, which is a risk factor for diabetes.

Effects of GDM on the Fetus

High blood glucose concentration in women diagnosed with GDM is available to the fetus for excessive growth and birth weight, which may result in difficult labor and delivery. The increase in body size usually consists of excessive body fat and the baby is born lethargic. In addition, baby growth is disproportional in that the shoulders grow bigger than the head, leading to difficult delivery through the birth canal, often resulting in a cesarean section delivery. Babies born to women with GDM may also be delivered with very low blood sugars due to high fetal insulin concentrations produced in response to excess maternal glucose diffusing into fetal blood. Once the umbilical cord is cut, the high maternal blood glucose supply is cut off, while the fetal pancreas continues to deliver high concentrations of insulin into the fetal circulation. This results in hypoglycemia at birth, requiring intravenous glucose supply.

Diagnosis of GDM

Most pregnant women in the US and Canada are screened for GDM between 24 and 28 weeks gestation. Screening is a random test in which the woman is given a 50 g glucose load to drink. A blood sample is analyzed one h after glucose ingestion. If blood glucose concentration is more than or equal to 7.8 mmol·L-1, a fasted oral glucose tolerance test is warranted. If the concentration is more than or equal to 10.3 mmol·L-1, GDM is diagnosed. In Canada, the oral glucose tolerance test (OGTT) is two hours and utilizes a drink containing 75 g of glucose. In the United States, the glucose drink is 100 g and the test is 3 h in length. If two of the blood glucose values are met or exceeded, GDM is diagnosed.

GDM-Conventional Management

GDM is managed primarily through energy intake control. The goals are to achieve normal blood glucose levels through good food choices, and to provide sufficient energy and nutrients to meet pregnancy needs. Dietary plans usually include smaller, more frequent meals, reducing simple and increasing more complex carbohydrates. Management of women with GDM encompasses self-glucose monitoring up to seven times per day. After two weeks of dietary intervention, failure to control capillary glucose concentrations may result in a need for blood glucose management through insulin injections. It is imperative that maternal blood glucose be maintained below target values, either through dietary intervention or diet plus insulin injections. The course of insulin injections depends on how well maternal blood glucose is controlled throughout the day. The type and amount of insulin injected is beyond the scope of this paper but depends on medical intervention and management.

Exercise as an Adjunctive Therapy for GDM

Many health professionals who counsel women with GDM recommend clients increase their physical activity. The Canadian Diabetes Association suggests that, "physical activity should be encouraged, with the frequency, type, duration and intensity tailored to individual obstetric risk". The American Diabetes Association suggests, "women without medical or obstetrical contraindications be encouraged to start or continue a program of moderate exercise as part of treatment for GDM". ACOG suggests that, "women with GDM who lead an active lifestyle should be encouraged to continue a program of exercise approved for pregnancy".

In fact, research has shown that the most physically active women have the lowest prevalence of GDM. However, frequency, intensity, time and type of activity leading to the best possible outcomes for women with GDM have yet to be determined. Thus, exercise remains an adjunctive therapy. When exercise has been evaluated for controlling blood glucose concentrations, or, for delaying or preventing insulin therapy, results have been inconclusive. Mixed results could be due to nonrandomization of the subject pool, small sample sizes, not well-controlled or reported exercise intensity, no evaluation of chronic physical activity, difference in exercise modalities, or exercise program compliance issues.

Studies Showing Improvement in Glucose Excursion

Jovanovic-Peterson et al. found a 6-wk arm ergometry exercise program to be successful in normalizing fasted plasma glucose concentrations and glycosylated hemoglobin (A1c) in GDM women randomized to diet therapy plus exercise, compared to diet therapy alone. The exercise program consisted of 20 min of arm ergometry, three times per week, at an intensity less than or equal to 50% O2max. Bung et al. randomized GDM women into a group with diet and insulin therapy or diet and exercise. The exercise program consisted of stationary cycle ergometry (50% O2max) for 45 min (three fifteen minute bouts with two rests), three times per week. Because no differences were found between groups, the authors suggested that exercise might be sufficient therapy for many patients due to an increase in insulin sensitivity.

Garcia-Patterson et al. also found a positive effect of physical activity on GDM women. Those who performed light postprandial walking at 2.25 km·h-1 showed decreased glucose excursion. More recently, Brankston et al. randomized GDM women to either diet alone or diet plus circuit-type resistance training groups. The number of women requiring insulin did not differ between groups. However, overweight women who exercised were less likely to need insulin compared to overweight women who had diet only interventions. Finally, Avery and Walker showed that, compared to rest, a single 30 min bout of cycle exercise at 35% or 55% of O2max improved glucose excursion.

Studies Showing No improvement in Glucose Excursion

Lesser et al. determined the effects of a single bout of stationary cycling for 30 min at 60% O2max, on six normal and five GDM gravidas. Eating a mixed meal 14 h postexercise did not result in improved glucose excursion in the GDM women. In another study, GDM women assigned to a partial home-based exercise program (70% of estimated heart rate max) were compared to GDM women with no structured exercise program. Although cardiorespiratory fitness improved in GDM women who exercised, glucose excursion did not differ between groups.

Preliminary Work

Since 2004, Davenport et al. have assessed conventional management of women diagnosed with GDM using retrospective chart review of patients from London, Canada. After conventional management performed for two weeks after diagnoses, 62% of these women required insulin therapy by 30 weeks gestation. Overweight women were 2.6 times more likely to require insulin therapy than normal weight women. Average prepregnancy BMI of women requiring insulin therapy was 30.6 ± 6.4 kg·m-2. This high incidence of insulin use in overweight women demonstrates the need for an alternative therapy. In a pilot study, only 50% of women diagnosed with GDM at 16-20 weeks gestation required insulin therapy if they followed a structured walking program (30% O2peak, 3-4 times per week) in addition to conventional management. Although these data are preliminary, it appears that early diagnoses in women at risk for GDM (especially overweight women) and the addition of structured physical activity, may have promising results.

Maternal Physical Activity to Prevent GDM

In high-risk groups, GDM is considered a significant initiating factor for type 2 diabetes, so prevention is crucial. Unfortunately, few prospective studies have been done in this area. Dyck et al. examined the feasibility of using first trimester exercise to prevent GDM in Aboriginal women. Despite incentives, compliance was minimal as the investigators recruited only eight women over two years. The exercise program may have been too strenuous as the women were required to exercise at 70% of age-predicted heart rate maximum. Due to small subject number, the authors were not able to determine whether the program truly prevented GDM, but it was nevertheless important to assess the feasibility of early GDM diagnosis and intervention.

Dempsey et al. studied women who participated in recreational activities using a self-reported questionnaire. The authors found that women who were most active within the first 20 weeks of pregnancy had a 48% reduction in GDM. In addition, women who were most active one year prior to pregnancy had a 51% reduction in GDM risk. When both variables were combined, overall GDM risk was reduced by 60%. The authors concluded that even though their physical activity measurement tool was imprecise, the relationship between physical activity and GDM risk reduction was robust. These data were confirmed later by the same authors using a prospective cohort design.

Preliminary Work

Mottola et al. investigated low-risk pregnant women and showed that mild (30% O2peak) cycling performed in late gestation was better than more intense (70% O2peak) exercise at promoting glucose tolerance in response to an oral glucose load. Vastus lateralis biopsies showed that GLUT4 (glucose transporters sensitive to insulin) was elevated in the mild compared to more intense exercisers, starting at 16-20 weeks gestation until delivery. In a subsequent study, nutritional intake was controlled during pregnancy to approximately 8350 kJ·day-1 and included 200 g of carbohydrate per day. This combination of nutritional control and mild exercise (30% O2peak on stair climber) was better than mild exercise alone in controlling blood glucose concentrations and preventing excessive weight gain during pregnancy. The blood glucose control remained at two months postpartum. These preliminary studies led to the development of a Nutrition, Exercise and Lifestyle Intervention Program (NELIP) which included mild walking (30% O2peak) combined with nutritional control (8350 kJ·d-1; 200 g carbohydrate per day) for women at risk for GDM.

Preliminary results are encouraging, as women at risk for GDM did not develop this disease while on NELIP (N = 23), excessive weight gain was prevented, and normal glucose tolerance remained at two months postpartum. In addition, high-risk women on NELIP maintained an insulin sensitivity index similar to those at low risk for GDM, and none developed the disease. Preliminary results suggest that overweight women at risk for GDM can enter a NELIP at 16 weeks gestation to help maintain their insulin sensitivity and glucose excursion, as well as prevent excessive weight gain and GDM. Assessment of glycosylated hemoglobin in these women also showed values well below the diabetic range. It may be that mild exercise, regardless of modality (e.g., bike, stair climber or walking), in combination with nutritional control, is key in helping women at risk for GDM regulate blood glucose concentrations and prevent excessive weight gain during pregnancy.

Summary

Researchers have not been able to determine a cost-effective, easily accessible evidence based program with guidelines for frequency, intensity, duration of exercise and type of activity that will produce optimal outcomes for women who are at risk for, or who develop GDM. Exercise is considered a valuable adjunctive therapy, and preliminary results are encouraging. However, until guidelines are available from well-controlled studies, the true effectiveness of a specific structured exercise program remains unknown. If modifiable GDM risk factors such as excessive weight gain and glucose intolerance can be improved by incorporating appropriate nutrition and physical activity intervention, we may help reduce diabetes and obesity epidemics in subsequent generations. Future studies should include the role of physical activity on subsequent type II diabetes incidence in women who were at risk for GDM during pregnancy.