Randomized Controlled Trial

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The primary outcome of the Finnish Gestational Diabetes Prevention Study (RADIEL) was to examine the effect of combined moderate physical activity and diet intervention in high-risk women on the incidence of GDM in a randomized controlled study setting.

Eligible participants for the study were women aged 18 years or older, pregnant at less than 20 weeks of gestation, with a history of GDM or a pre-pregnancy BMI of at least 30kg/m².

• Type 1 or type 2 diabetes or GDM diagnosed before 20 weeks of gestation
• Use of medication that influences glucose metabolism, such as continuous therapy with oral corticosteroids or metformin
• Multiple pregnancy
• Physical disability
• Current substance abuse
• Severe psychiatric disorder
• Significant difficulty in cooperating (e.g., inadequate Finnish language skills).

Recruitment

• Participants were recruited from obese women, primarily in association with the first trimester screening ultrasound and women with prior GDM, by personal invitation letters sent out based on data in the hospital registry
• In addition, notices in newspapers, social media and antenatal clinics were used.

Design

• Randomization was done by permuted blocks stratified by risk factors (BMI at least 30kg/m², history of GDM)
• The randomization was performed by a study nurse and by dispensing the next sequentially numbered subject code and opening the corresponding code envelope, which included the intervention arm to be assigned to the subject.

Blinding Used
Study physicians were blinded to study groups when evaluating maternal and neonatal diagnoses.

Intervention

Study participants received lifestyle counseling from study nurses and dietitians who were specifically trained for their tasks. The participants visited the study nurse three times during pregnancy. These visits were structured, but the counseling was individualized according to the stage of the pregnancy. At the time of study enrollment, the participants attended one two-hour group counseling session led by a dietitian.

• The study visits took place at the following times:
  • Baseline visit was at 13.3 weeks of gestation [interquartile range (IQR), 12.0 weeks to 14.6 weeks of gestation]
  • Second visit at 23.1 weeks of gestation (IQR, 22.4 to 24.1 weeks of gestation)
  • Third visit at 35.1 weeks of gestation (IQR, 34.4 to 35.6 weeks of gestation).

In addition, the participants visited antenatal clinics according to standard national practice. For women with a pre-pregnancy BMI of at least 30kg/m², the recommendation was no weight gain during the first two trimesters. The dietary advice was based on contemporary Nordic Nutrition Recommendations (2004). The dietary counseling focused on optimizing participants’ consumption of vegetables, fruits and berries, whole-grain products rich in fiber, low-fat dairy products, vegetable fats high in unsaturated fatty acids, fish and low-fat meat products, and a lower intake of sugar-rich foods. A food frequency questionnaire designed for this study was filled in before each visit to the study nurse.

To measure the general adherence to the recommended diet, a dietary index was developed based on the food frequency questionnaire, with higher scores indicating better diet quality. The dietary index includes 11 components that represent each topic of the counseling and were scored based on reported intake frequency, as follows:

• Snacks (0–2 points)
• Sugar-sweetened beverages (0–1 point)
• Vegetables (0–2 points)
• Fruits and berries (0–1 point)
• Low-fat cheese (0–1 point)
• Cooking fat (0–1 point)
• Spread fat (0–2 points)
• Fast food (0–1 point)
• High-fiber bread and cereals (0–2 points)
• Fish (0–2 points)
• Low-fat milk (0–2 points).

The highest score (17 points) was set to reflect the highest adherence to the recommended intake of each score item. 

Regarding physical activity, the aim was to achieve a minimum of 150 minutes of moderate-intensity physical activity per week and to adopt an overall active lifestyle. The participants and the study nurses planned (and during the follow-up, they updated) an individual physical activity program. Participants had access, free of charge, to public swimming pools or guided exercise groups once a week, provided by the municipalities. Evaluation of leisure-time physical activity was based on the self-reported time spent weekly on physical activity that makes a participant at least slightly out of breath and sweaty. Pre-pregnancy physical activity was assessed at baseline in a similar way.

In the Control Group, participants received general information leaflets on diet and physical activity, usually provided by local antenatal clinics. Also, during pregnancy the Control Group participants visited the study nurse three times, to make measurements, obtain blood samples and to administer questionnaires, as well as antenatal clinics, according to standard practice.

Statistical Analysis

• The comparison between groups was made by using a T-test, X² test, or Mann-Whitney test
• When using adjusted models, ANCOVA, a logistic regression model or a median regression (least absolute-value) model was applied
• Repeated measures were analyzed using a generalized estimating equation (GEE) model with the unstructured correlation structure
• GEEs were developed as an extension of the general linear model to analyze longitudinal and other correlated data
• In the case of violation of the assumptions (e.g., non-normality), a bootstrap-type test was used (10,000 replications)
• The normality of the variables was tested by using the Shapiro-Wilk W-test
• All statistical analyses were performed unadjusted and adjusted for age, pre-pregnancy BMI, previous GDM status, weeks of gestation and baseline value.

Timing of Measurements
Participants underwent OGTT at study enrollment (20 weeks gestation) and at 24 to 28 weeks gestation.

Dependent Variables

• GDM diagnosis: Decined as one or more pathological glucose values in a 75-gram, two-hour oral glucose tolerance test (OGTT; run by a central laboratory) with the following diagnostic thresholds:
  • Fasting plasma glucose at least 5.3mmol per L
  • One-hour value at least 10.0mmol per L
  • Two-hour value at least 8.6mmol per L.
• Maternal outcomes: Pregnancy-induced hypertension, pre-eclampsia, Cesarean section
• Neonatal outcomes: Birthweight over 4,500g, crown-heel length, gestational age at birth, respiratory distress.

Independent Variables

• Individualized counseling on diet, physical activity and weight control from trained study nurses
• One group meeting with a dietitan.

Control Variables
Pregnancy.

Initial N

• Intervention Group: 155
• Control Group: 138.

Attrition

• Intervention Group: 144
• Control Group: 125.

Age

• Intervention Group: 32.3 years
• Control Group: 32.6 years (NS).

Ethnicity
Caucasian Finnish women.

Other Relevant Demographics

• Anthropometrics: No signficant differences between groups in body weight, gestational age at baseline, prior GDM percentage, smoking, dietary index or physical activity index at baseline
• Location: Helsinki Finland and Lappeernata, Finland.

GDM Diagnosis

• GDM was diagnosed in 20 participants [13.9% (95% CI, 8.7% to 20.6%)] in the Intervention Group and in 27 participants [21.6% (95% CI, 14.7% to 29.8%)] in the Control Group (P=0.097 unadjusted; P=0.044 after adjustment for age, pre-pregnancy BMI, previous GDM status and number of weeks of gestation at the time of the diagnostic OGTT). The crude relative risk for GDM was 0.64 (95% CI, 0.38 to 1.09) in the Intervention Group.
• Women belonging to the Intervention Group had a crude reduction in fasting plasma glucose concentration of 20.18mmol per L (95% CI, 20.24mmol to 20.12mmol per L) from baseline to the third trimester, compared with 20.07mmol per L (95% CI, 20.13mmol to 20.02mmol per L) in the Control Group (P=0.026 unadjusted; P=0.011 after adjustment for age, pre-pregnancy BMI, previous GDM status, the number of weeks of gestation and baseline glucose concentration).
• In the Intervention Group, the two-hour glucose value increased from baseline to second trimester by 0.54mmol per L (95% CI, 0.35mmol to 0.72mmol per L) and in the Control Group by 0.55mmol per L [(95% CI, 0.33mmol to 0.78mmol per L) P=0.92 unadjusted; P=0.42 after adjustment for age, pre-pregnancy BMI, previous GDM status, number of weeks of gestation and baseline glucose concentration].

Gestational Weight Gain
There was a difference in gestational weight gain between the Intervention Group [2.5kg (95% CI, 2.1 to 3.0]) and the control group [3.1 kg (95% CI, 2.7 to 3.5)] from baseline to the second trimester (at the time of the OGTT at Week 23.4, on average) and the mean difference was 20.5kg [(95% CI, 21.1 to 0.05) P=0.072 unadjusted; P=0.039 after adjustment for age, previous GDM status, the number of weeks of gestation, and baseline weight]. The gestational weight gain was 7.6kg (95% CI, 6.7kg to 8.3kg) in the Intervention Group and 7.7kg (95% CI, 7.1kg to 8.4kg) in the Control Group from baseline to the third trimester and the mean difference was 20.2kg [(95% CI, 21.1 to 0.8) P=0.74 unadjusted; P=0.37 after adjustment for age, previous GDM status, the number of weeks of gestation and baseline weight)].

Dietary Index Score
The dietary index score improved more among women in the Intervention Group [0.7 (95% CI, 0.3 to 1.1)], compared with those in the Control Group [0.3 (95% CI, 20.1 to 0.7)] and the mean difference was 0.4 [(95% CI, 20.1 to 1.0) P=0.16 unadjusted; P=0.037 after adjustment for age, pre-pregnancy BMI, previous GDM status, the number of weeks of gestation and baseline values).

Physical Activity
Women in the Intervention Group increased their median weekly leisure time physical activity by 15 minutes (95% CI, one to 29 minutes), while the physical activities of women in the Control Group remained unchanged (P=0.17 unadjusted; P=0.029 after adjustment for age, pre-pregnancy BMI, previous GDM status, number of weeks of gestation and baseline values).

Maternal and Neonatal Outcomes
There were no differences in the other maternal pregnancy or birth outcomes assessed between the Intervention and Control Groups.

• GDM can be prevented in a high-risk population by simple, easily applicable lifestyle interventions
• Our findings suggest that individualized lifestyle intervention should be initiated in early pregnancy in high-risk women and continued throughout pregnancy
• These results are unique and highly promising. Preventing GDM may have major short- and long-term health consequences for both the mother and the child.

Government:

The Finnish Foundation for Cardiovascular Disease, The Finish Diabetes Research Foundation, State Provincial Office of Southern Finland, Social Insurance Institution of Finland

Well thought out study,