Obstetrics & Gynecology:
Maternal Weight Gain in Women Who Develop Gestational Diabetes Mellitus
Gibson, Kelly S. MD; Waters, Thaddeus P. MD; Catalano, Patrick M. MD
From MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Presented as a poster at the Society for Gynecologic Investigation 57th Annual Scientific Meeting, March 24–27, 2010, Orlando, Florida.
Corresponding author: Kelly S. Gibson, MD, Department of Obstetrics and Gynecology, MetroHealth Medical Center, 2500 Metrohealth Drive, Cleveland Ohio 44109; e-mail: firstname.lastname@example.org.
Financial Disclosure The authors did not report any potential conflicts of interest.
OBJECTIVE: To assess maternal weight gain before 24 weeks in women developing gestational diabetes mellitus (GDM) compared with controls with normal glucose tolerance.
METHODS: This was a retrospective cohort study of maternal weight gain. Women developing GDM were matched to three controls by self-reported prepregnancy body mass index (BMI), maternal age, race, and parity. Women without documented pregravid or 22- to 24-week weights and multiple gestations were excluded. The primary outcome was weight gain through 24 weeks of gestation.
RESULTS: Six hundred fifty-two women (163 in the GDM group and 489 controls) underwent chart review. There were no significant differences in race (36% compared with 36% African American, P=.99), age (28.7±6.3 years compared with 29.4±6.9 years, P=.26) or prepregnancy BMI (31.7±8.2 compared with 31.8±8.6, P=.88). Maternal weight gain was higher in the GDM group than in the control group (14.8 compared with 11.2 lb, P<.001). When controlling for prepregnancy BMI, overweight (18.6 compared with 12.9 lb, P<.004), and obese (12.6 compared with 8.8 lb, P<.008), GDM participants gained significantly more weight by 24 weeks. Both diet-controlled (A1) and insulin-requiring (A2) GDM had higher weight gain compared with controls (control compared with A1: 11.2 compared with 15.3 lb, P=.029; control compared with A2: 11.2 compared with 14.6 lb, P=.018. No difference was found between A1 and A2 patients (P=.942).
CONCLUSION: Women who develop GDM have higher gestational weight gain through 24 weeks. Gestational weight gain is a significant risk factor for GDM in the overweight or obese patient but not in patients who were underweight or had a normal BMI before pregnancy.
LEVEL OF EVIDENCE: II
Gestational diabetes mellitus (GDM), defined as carbohydrate intolerance diagnosed during pregnancy, is a common complication affecting 2–5% of all pregnancies in the United States.1,2 Specifically, GDM is a condition of maternal hyperglycemia that develops subsequent to increased insulin resistance and inadequate insulin response.3 In the third trimester, insulin resistance increases by 40–60% compared with prepregnancy measures.4,5 Maternal obesity significantly affects the development of GDM as obese women have a greater prepregnancy insulin resistance. The added effects of placental hormones and tumor necrosis factor alpha contribute to impaired post–insulin receptor signaling in skeletal muscle and decreased glucose transport in adipose tissue.6–8
Although it is well known that obese women have increased insulin resistance and are at risk of having clinically significant glucose intolerance during pregnancy, it is unclear how maternal weight gain contributes to developing GDM. Investigations to date have been mixed, with some failing to identify a relationship between gestational weight gain and GDM, whereas others have found both excess and low weight gain to be associated with GDM.9–11
Given the lack of consistency in the data and the recent national focus on gestational weight gain following the Institute of Medicine (IOM) guidelines,12 the aim of this investigation was to estimate the total early pregnancy weight gain, before 24 weeks of gestation, among women who develop GDM and compare gestational weight gain to a control group with normal glucose tolerance testing in pregnancy matched one-to-one for maternal age and prepregnancy body mass index (BMI).
MATERIALS AND METHODS
This is a retrospective case controlled cohort study of women whose pregnancies were complicated by GDM and who received prenatal care at MetroHealth Medical Center, a tertiary referral center affiliated with Case Western Reserve University in Cleveland, Ohio. The study was approved by the MetroHealth System Institutional Review Board. The primary outcome was total gestational weight gain through 24 weeks of gestation. Secondary outcomes included weight gain before 12 weeks of gestation and between 12 and 24 weeks of gestation, and in diet and exercise (A1) compared with insulin-requiring (A2) GDM patients. Gestational diabetes mellitus was diagnosed with either a 1-hour 50-g oral glucose screening result of more than 200 mg/dL or two or more abnormal results identified on a 3-hour 100-g oral glucose tolerance test according to the Carpenter-Coustan criteria.13
All patients diagnosed with GDM who received care at our institution from 2006 through 2009 were identified. Individual chart review of the electronic medical records was then performed to determine demographics, maternal comorbidities, prepregnancy weight, weight at 12 weeks (if available) and 24 weeks, glucose tolerance test results, and delivery outcomes. Exclusion criteria included fetal congenital anomalies, multifetal gestation, diagnosis of pre-existing diabetes, or failure to meet inclusion criteria. Total weight gain at 24 weeks was estimated as the difference between the recorded maternal weight at 24 weeks (±2 weeks) and the patient reported prepregnancy weight in the antenatal chart. The 12-week weight gain was estimated as the difference between the recorded maternal weight at 12 weeks (±2 weeks) and the patient reported prepregnancy weight. The weight gain between 12 and 24 weeks was calculated as the difference between the documented 12-week and the documented 24-week recorded maternal weights. The prepregnancy BMI was calculated using the patient self-reported prepregnancy weight (in kilograms) divided by the maternal height (in meters squared) recorded at the first prenatal visit. Each case patient with GDM was matched with three women who had normal glucose tolerance testing in pregnancy (defined as venous plasma glucose of less than 135 mg/dL obtained 60 minutes after a 50-g oral glucose tolerance screening load at 26–28 weeks of gestational age). Assignment was achieved using one-to-one assignment for the first three matching women delivering at this institution and listed in our perinatal database between 2000 and 2007, with the cohort sorted by race, age (±2 years), prepregnancy BMI (±2), and parity. For two women with extreme obesity (BMI more than 60), matching was done within BMI class to the closest available BMI. Controls were excluded if they had pre-existing diabetes mellitus, multiple gestations, no documented 1-hour glucose tolerance test, no recorded prepregnancy height and weight, or no recorded maternal weight recorded between 22 and 24 weeks. The first three controls meeting inclusion criteria for each case were selected. If a control participant did not meet inclusion criteria, the next eligible control was selected. When a control was selected for inclusion, that patient was removed from the list to ensure that the same control patient was not used more than once. A review of our records identified 257 GDM patients, consistent with our average incidence of 6.6% GDM. After excluding those with missing or ineligible data, a total of 163 patients were included. Eleven patients were erroneously included in the initial list because they actually had either type 1 or type 2 diabetes mellitus. A total of 83 patients were excluded for missing or unavailable data (51 screened after 28 weeks in pregnancy and had no 12- or 24-week weights, four had no listed prepregnancy weight, 24 were missing delivery variables, and four other [twins, still pregnant]). A 3:1 control-to-GDM patient ratio was chosen to enhance the power, given the limited number of available cases.
The mean difference between the 24-week recorded maternal weight and the self-reported prepregnancy weight was compared between women diagnosed with GDM and those with normal glucose tolerance. Patients then were classified by prepregnancy BMI categories as follows: underweight (less than 18.5), normal weight (18.5–24.9), overweight (25.0–29.9), and obese (30.0 or higher).12 Mean total 24-week weight gain was then compared between cases and controls within each BMI category. For the continuous variables, the data were analyzed using both parametric and nonparametric tests with the Student t test, Mann-Whitney U test, and Kruskal-Wallis test. The most appropriate test was dependent on the assessment of the kurtosis and skewness or distribution of the continuous data. For the categorical variables, χ2 or Fisher exact tests were used. A P<.05 was considered significant. All statistical analysis was done using Statview 5.01.
We identified 163 women diagnosed with GDM and 489 controls who met the inclusion criteria for our investigation. Table 1 presents the maternal characteristics for the cohorts. Because of matching, no significant differences were noted in maternal race, age, parity, or prepregnancy BMI between women diagnosed with GDM and control patients. As expected, women diagnosed with GDM had a significantly elevated mean result of the 1-hour 50-g glucose screen (173.5 compared with 104.5 mg/dL, P<.001). In addition, women diagnosed with GDM delivered at an earlier gestational age (37.8 compared with 39.3 weeks, P<.001) and more often by cesarean (39.1% compared with 28.0%, P=.008). Only 20.9% of patients were either underweight or had normal BMIs before pregnancy, with the majority being classified as overweight or obese on the basis of the self-reported prepregnancy weight.
The primary outcome data are presented in Table 2. The maternal gestational weight gain by 24 weeks of gestation was significantly greater in the GDM group compared with the control group (14.8 compared with 11.2 lb, P=.001). In addition, for the 132 individuals with a recorded 12–gestational week weight gain, weight gain was also greater for the GDM participants compared with controls (4.0 compared with 2.8 lb, P=.048). No difference in gestational weight gain was found when we evaluated documented weight gain between 12 and 24 weeks of gestation. Individual comparison of weight gain by 24 weeks of gestation within each BMI group is presented in Figure 1. Significant differences in total gestational weight gain were found between GDM and control participants who were overweight (P=.004) or obese (P=.008) before pregnancy, with patients diagnosed with GDM having the greater weight gain. No significant difference was found in weight gain between GDM and control participants for those classified as underweight or of normal BMI before pregnancy.
To examine whether there was a difference in weight gain by the severity of GDM, we evaluated maternal weight gain by 24 weeks of gestation in individuals requiring insulin therapy (A2 GDM) compared with those who were diet- or exercise-controlled or both (A1 GDM). There were no significant differences in age, race, or parity among the individuals classified as A1 compared with A2 GDM and controls. Participants in the A1 GDM group had significantly lower prepregnancy BMI compared with those in the A2 GDM group (28.8 compared with 33.6) but had no difference in 1-hour glucose tolerance test or gestational age at delivery. Weight gain at 24 weeks in A1 GDM, A2 GDM, and control groups is presented in Figure 2. Compared with controls, both diet- and insulin-requiring GDM participants had significantly greater mean weight gain at 24 weeks of gestation (A1 GDM compared with controls, P<.027; A2 GDM compared with controls, P<.019). However, no difference was found in mean weight gain when comparing participants classified as A1 GDM compared with A2 GDM (P=.942) or when comparing A1 GDM and A2 GDM individuals based on prepregnancy BMI.
Because some women will lose weight over the course of early pregnancy, we compared the GDM and control groups according to different gestational weight gain categories. We categorized total maternal gestational weight gain achieved by 24 weeks of gestation into four groups: those who lost weight and those who gained 0–10 lb, 11–20 lb, and more than 20 lb. Figure 3 presents the frequency of cases and controls for each weight gain category. A relatively greater percentage of normal glucose tolerance patients lost weight or gained less than 10 lb (P=.029) in the first two trimesters. We found the GDM patients had more often gained 11–20 lb or more than 20 lb (P=.006). Among the weight gain categories, there were significant differences in race (P=.047), maternal age (P<.001), and prepregnancy BMI (P<.001), with African Americans, older patients, and those with a lower prepregnancy BMI tending to gain more by 24 weeks of gestation. There was no difference in parity, delivery type, or gestational age at delivery. When comparing the frequency of patients with either A1 GDM or A2 GDM by using our different maternal weight gain categories, we found no differences in the percentage who lost weight or gained 0–10, 11–20, or more than 20 lb.
Last, we examined whether remaining in the recent IOM guidelines for gestational weight gain was related to the development of GDM. The IOM recommended gaining 1.1–4.4 lb in the first trimester and 10.4–13 lb for normal-weight, 6.5–9.1 for overweight, and 5.2–7.8 lb for obese women in the second trimester.14 We found no significant difference among the controls and GDM patients who remained within the guidelines or gained outside the recommendations.
We found a significant difference between GDM and controls in gestational weight gain at 24 weeks of gestation. When examined by BMI category, this difference was significant only for overweight and obese patients. Additionally, both A1 and A2 GDM patients had higher gestational weight gain compared with controls.
Nearly two thirds of adult women in the United States are currently overweight or obese.14 Although the IOM recently revised its pregnancy weight-gain recommendations,15 50–60% of women will have total pregnancy weight gain above these targets, placing themselves and their children at increased risk for complications during and after pregnancy.16
Our study suggests that increased maternal gestational weight gain in the first and second trimesters of pregnancy may affect glucose metabolism and GDM development in overweight and obese women. Gestational weight gain early in pregnancy is often related to increased plasma volume; however, accrual of adipose tissue begins around 12–14 weeks in overweight and obese women and potentially earlier in underweight and normal-weight women.17 Gestational diabetes mellitus develops when pancreatic beta cell function cannot compensate sufficiently to maintain normoglycemia in the face of increased insulin resistance. Because overweight and obese women have increased insulin resistance before conception, the increase in gestational weight gain by 24 weeks may “push them over the edge” toward GDM development. Among nonpregnant Pima Indians, insulin resistance was associated with lower rates of weight gain.18 Weight gain in early pregnancy has also been shown to be inversely proportional to changes in insulin sensitivity.19
Previous studies, all retrospective, reported an association between increased gestational weight gain and pregnancy complications including hypertensive disorders and GDM among normal-weight20 and overweight21 women, but not for morbidly obese patients.22 Two smaller investigations did not find associations between “excessive mid-trimester weight gain” and abnormal glucose tolerance test results.10,23 However, in a cohort of 5,131 women an increase in BMI category from normal weight to overweight or overweight to obese was associated with an increased risk of GDM.24 Several other studies have also found an association between gestational weight gain and an abnormal 50-g oral glucose tolerance test, especially in overweight and obese white, African American, and Hispanic women.11,25,26 Finally, a recent nested case-control study from California reported that first-trimester weight gain was associated with GDM development. When controlling for prepregnancy BMI in multivariate analysis, the overweight women who gained in the highest tertile were nearly twice as likely to develop GDM compared with those in the lowest tertile.27
These findings are of particular importance given the rising prevalence of overweight and obese women of childbearing age. Obesity itself is associated with a 3–5 times increased odds ratio of developing GDM.28 Interestingly, our data failed to identify a relationship between recommended compared with excessive weight gain on the basis of IOM recommendations15 and the diagnosis of GDM. Given the long-term health implications of GDM on future maternal and fetal cardiovascular health,28 identifying potential areas of prevention may have far-reaching benefits. To date there is no consensus regarding optimal lifestyle modification in obese patients showing consistently improved pregnancy outcomes, including incidence of GDM.29
Our study has several limitations. As a chart review, this study is open to ascertainment bias and is further limited by what data were available in the medical records. The entire cohort was drawn from over several years (2000–2007) to appropriately match 3:1 to GDM. Although the GDM definition and management protocols and the official recommendations for gestational weight gain in pregnancy did not change during that time, individual practice variations may have affected our outcomes. In addition, similar to many other studies, reliable pregravid weights were not available on the participants, so self-reported prepregnancy weights were used. On average patients tend to underestimate their weight, especially overweight and obese patients30–32; however, as the weights for both case and control groups were self-reported, this would bias the results only toward the null.33 To further reduce the bias, the documented weight gain between 12 and 24 weeks of gestational age was also compared between groups. Our study population was also nearly 80% overweight or obese with an increase in 0.74 m/kg2 of BMI over time,34 more than the national overweight and obesity rate but reflective of our typical GDM patient population. Importantly, our study has several strengths. As a matched case-control study, the influence of potential confounding variables such as prepregnancy BMI, race, age, and parity is reduced. Further, we examined gestational weight gain only until the time of diagnosis of GDM, thus avoiding the confounding effect of GDM treatment on gestational weight gain.
In summary, we examined gestational weight gain early in pregnancy in relation to developing GDM stratified by prepregnancy BMI. Gestational weight gain before 24 weeks of gestation was significantly higher among patients with GDM than in normal glucose tolerance control individuals, specifically in the overweight and obese patients.
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