DIABETES/METABOLISM RESEARCH AND REVIEWS RESEARCH Diabetes Metab Res Rev 2014; 30: 716–725. Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/dmrr.2540
ARTICLE
Early gestational weight gains within current recommendations result in increased risk of gestational diabetes mellitus among Korean women
Sunmin Park1 Min-Hyoung Kim2 Sung-Hoon Kim3* 1
Department of Food & Nutrition, Hoseo University, Asan, Korea
Abstract Background We prospectively assessed whether maternal weight gain at 24–28 weeks of gestation (MWG24) influences the risk of developing gestational complications, such as gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes, in pregnant Korean women.
2
Department of Obstetrics and Gynecology, Cheil General Hospital & Women’s Healthcare Center, College of Medicine, Kwandong University, Seoul, Korea
3
Division of Endocrinology & Metabolism, Department of Medicine, Cheil General Hospital & Women’s Healthcare Center, College of Medicine, Kwandong University, Seoul, Korea *Correspondence to: Sung-Hoon Kim, Division of Endocrinology & Metabolism, Department of Medicine, Cheil General Hospital & Women’s Healthcare Center, College of Medicine, Kwandong University, Seoul, Korea. E-mail: [email protected]
Received: 28 November 2013 Revised: 13 February 2014 Accepted: 3 March 2014
Copyright © 2014 John Wiley & Sons, Ltd.
Methods Maternal weight gain from self-reported pre-pregnancy weight until 24–28 weeks of gestation was measured in 731 pregnant women, and an expected MWG24 was determined using the Institute of Medicine 2009 guidelines. Glucose tolerance, insulin resistance, insulin secretory capacity, anthropometric measurements, lipid profiles, nutrient intakes and pregnancy outcomes were evaluated at 24–28 weeks of gestation. The adjusted odds ratios (ORs) for GDM, large-for-gestational-age infants, small-for-gestationalage infants and preterm delivery were determined according to maternal weight gain by logistic regression analysis after adjusting for covariates. Results Compared with a normal MWG24, an inadequate MWG24 reduced the OR (0.565) for GDM, but an excessive MWG24 did not affect the OR (0.854). However, ORs for preterm delivery were significantly higher in both inadequate and excessive MWG24 groups in comparison with the normal MWG24. There were no other adverse pregnancy outcomes due to the inadequate MWG24. MWG24 was not associated with a significant increase in ORs for delivering large-for-gestational-age or small-for-gestational-age infants or delivery by caesarean section. Although energy intake was less than the estimated energy requirement in all groups, MWG24 was linearly associated with energy intake such that energy balance was positive in the excessive MWG24 group. Conclusions This study suggests that both target weight gain and energy intake recommendations for early pregnancy may not be optimal for Korean women and that race-specific recommendations are needed to decrease the risk of GDM without increasing adverse pregnancy outcomes. Copyright © 2014 John Wiley & Sons, Ltd. Keywords gestational diabetes mellitus; early birthweight; pregnancy outcome; energy intake
gestational
weight
gain;
717
Early Maternal Weight Gain and GDM
Introduction Gestational diabetes mellitus (GDM) develops in the later stages of the second trimester because of increased insulin resistance and concomitantly decreased utilization of maternal glucose [1]. This decrease in maternal glucose utilization is necessary for the delivery of glucose to the fetus, but extreme changes can result in maternal hyperglycaemia and macrosomia [1,2]. Maternal body weight and early gestational weight gain are independent risk factors for the development of GDM later in pregnancy [3]. Excessive early gestational weight gain might be associated with an early increase in insulin resistance, which in turn results in the exhaustion of pancreatic βcells [4]. This decrease in β-cell function could reduce the capacity to compensate for enhanced insulin resistance during pregnancy and eventually lead to maternal hyperglycaemia and excessive fetal growth [4,5]. β-cell depletion can be prevented by increasing β-cell mass [6], and there is emerging evidence that improvements in lifestyle and dietary habits also mitigate the development of GDM. Lifestyle and dietary habits that result in gestational weight gain are crucial risk factors for GDM. Gestational diabetes mellitus develops because of an imbalance between insulin resistance and insulin secretion. The second half of pregnancy is characterized by progressive insulin resistance and simultaneous decreases in maternal glucose utilization [7,8], and maternal fat accumulation appears to accelerate the progression of subsequent maternal insulin resistance [8]. To maintain normoglycaemia, insulin secretion sufficient to compensate for insulin resistance is necessary. However, Asians have a limited insulin secretory capacity compared with other ethnic groups [6,9]. Asians are susceptible to GDM-like type 2 diabetes because of inherently low β-cell function and mass that impairs their ability to compensate for insulin resistance by increasing insulin secretion [9]; thus, this population is more likely to develop GDM at lower levels of insulin resistance than other populations. Pre-pregnancy obesity and excessive gestational weight gain during pregnancy are major risk factors for increases in insulin resistance and the development of GDM. However, these factors can be controlled by dietary and lifestyle modifications. In 2009, the American Institute of Medicine (IOM) established a set of guidelines with recommended weight gains throughout pregnancy, as well as weekly weight gain recommendations for the second and third trimesters of pregnancy that are based on pre-pregnancy body mass index (BMI) [10]. Maternal weight gain at 24– 28 weeks of gestation (MWG24) is thought to be associated with pregnancy complications, including GDM, because GDM typically develops at the end of the second trimester. Herring et al. [11] reported that a greater degree of gestational weight gain leads to a higher prevalence of abnormal Copyright © 2014 John Wiley & Sons, Ltd.
glucose tolerance in the third trimester of pregnancy [odds ratio (OR): 2.14, 95% confidence interval (CI): 1.04–4.42]. However, few studies have evaluated weight gain during early pregnancy based on pre-pregnancy BMI. It was hypothesized that MWG24 affects the development of adverse maternal and neonatal outcomes via alterations in insulin sensitivity. Thus, in the present study, we assessed whether optimal MWG24, based on pre-pregnancy BMI, can lower the risk for developing gestational complications such as GDM and other adverse pregnancy outcomes in a hospital-based prospective study.
Subjects and methods Subjects and screening for GDM This cohort study included 731 pregnant women who were first evaluated and then delivered their babies at Cheil General Hospital & Women’s Healthcare Center in Seoul, South Korea, between June 2006 and March 2009. Fifty-two women were dropped from the 783 pregnant women recruited during the study. When twins were delivered, the data were excluded from the study. In addition, the subjects with missing data values were excluded at the end of the study. During their first visit to the diabetes clinic, participants completed a short survey regarding pre-pregnancy body weight and medication use, measurements of body weight and blood glucose levels were taken, and each participant received a general education session regarding managing pregnancy, including food intake. The survey was monitored by a nurse and a dietician to eliminate missing values from the survey. Standard protocols for the screening and diagnosis of GDM were followed. All pregnant women without a previous diagnosis of glucose intolerance were screened for GDM between 24 and 28 weeks of gestation using the 50-g glucose challenge screening test. A 1-h glucose value ≥7.2 mM on the glucose challenge test, without regard for the time of day or time of last meal, was considered to be a positive screen. Women with a positive screen underwent a 3-h 100-g oral glucose tolerance test (OGTT) according to the criteria of Carpenter and Coustan [12]. Threshold glucose values were as follows: fasting: ≥5.3 mM, 1 h: ≥10.0 mM, 2 h: ≥8.6 mM and 3 h: ≥7.8 mM. GDM (n = 231) was confirmed by the presence of at least two abnormal OGTT values. Subjects with a twin pregnancy, medical conditions that could affect fetal growth or pregnancies in which gestational age could not be ascertained by early ultrasonography were excluded. All subjects provided written informed consent, and the study protocol was approved by the Ethics Committee of the Institutional Review Board of Cheil General Hospital. Diabetes Metab Res Rev 2014; 30: 716–725. DOI: 10.1002/dmrr
S. Park et al.
718
Category of maternal weight gain at 24–28 weeks of gestation
Laboratory measurements and physiological indexes
Pre-pregnancy BMI was calculated as pre-pregnancy weight (kg)/height2 (m2). Weight gain during pregnancy was calculated as pre-pregnancy weight subtracted from weight before delivery. Unlike Caucasians, a mild degree of obesity is associated with obesity-related disease in Asians [1,2]. The definition for obesity in Asians differs from the definition put forth by the National Institutes of Health; the Korean Society for the Study of Obesity defines overweight and obesity as 23 ≤ BMI < 25 and BMI ≥ 25, respectively. Consistent with this definition of obesity, pregnant Korean women tend to develop adverse pregnancy outcomes even when their gestational weight gain is less than that of Caucasians. In this study, optimal MWG24 was defined according to the IOM guidelines because no specific guidelines for optimal weight gain during pregnancy for Koreans are available [10]. The data were stratified into three categories according to inadequate, normal and excessive MWG24: inadequate MWG24, 6.5 kg for normal weight participants.
Plasma glucose concentrations were measured by the glucose oxidase method using a YSI 2300 STAT (YSI; Yellow Springs, Ohio). Plasma insulin concentrations were measured using a human-specific radioimmunoassay kit (Linco Research, St. Charles, MO). Homeostatic model assessments for insulin resistance (HOMA-IR) and β-cell function (HOMA-B) were calculated using the equations developed by Matthews et al. [13]. HbA1c levels were determined at the initial diagnosis of GDM and prior to delivery by the Variant II HbA1c Program (BioRad; Hercules, CA). Plasma lipid profiles (total, HDL and LDL cholesterol, and triglyceride) were determined by enzymatic colorimetry. Plasma LDL cholesterol was calculated using the Friedewald equation. Gestational hypertension was diagnosed if blood pressure was ≥140 for systolic and 90 mmHg for diastolic in the absence of proteinuria. Questionnaires were used to obtain the following information: age, pre-pregnancy weight, obstetric history including gestational age and parity and family history of diabetes among first-degree relatives.
Management of blood glucose levels in all GDM women during a late pregnancy Women diagnosed with GDM were referred to a specialist team composed of obstetricians, a diabetologist, a nurse educator and dietitians. All GDM subjects were required to maintain blood glucose levels within a normal range using diet, physical activity and/or insulin treatment. Additionally, all GDM patients received dietary education and/or counselling on how to regulate their dietary intake and physical activity, and self-monitored blood glucose values and weight changes were obtained during biweekly clinic visits until the time of delivery. Treatment targets included blood glucose concentrations that did not exceed 5.3 mM at fasting and 6.7 mM at 2h postprandial. Insulin therapy was initiated if blood glucose levels remained above target levels, and insulin dosage was adjusted accordingly by the patients on the basis of a protocol using self-monitored blood glucose levels. Urine ketone levels were monitored to detect insufficient caloric or carbohydrate intakes in women treated with calorie restriction; all subjects maintained negative urinary ketones. Copyright © 2014 John Wiley & Sons, Ltd.
Nutritional assessment at 24–28 weeks of pregnancy Food intakes were determined by a skilled dietician using the 24-h recall method. Nutrient intakes were analysed from the food intakes using CAN-PRO (version 3; Korean Nutrient Society, Seoul, Korea), and some were calculated as the percentage of the Korean Dietary Reference Intake for pregnant women according to age. Activity was determined by activity recall, and daily energy expenditure was calculated by multiplying basal energy expenditure and activity levels [14]. Basal energy expenditure was calculated using body weight, height, age and pregnancy status according to the modified Harris–Benedict equation [14].
Pregnancy outcomes Preterm delivery was defined as delivery before 37 weeks of gestation, and macrosomia was considered to be a birthweight of 4000 g or greater. LGA was defined as a birthweight ≥90th percentile based on a Korean reference population. The Apgar score was defined as low if a score of
ARTICLE
Early gestational weight gains within current recommendations result in increased risk of gestational diabetes mellitus among Korean women
Sunmin Park1 Min-Hyoung Kim2 Sung-Hoon Kim3* 1
Department of Food & Nutrition, Hoseo University, Asan, Korea
Abstract Background We prospectively assessed whether maternal weight gain at 24–28 weeks of gestation (MWG24) influences the risk of developing gestational complications, such as gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes, in pregnant Korean women.
2
Department of Obstetrics and Gynecology, Cheil General Hospital & Women’s Healthcare Center, College of Medicine, Kwandong University, Seoul, Korea
3
Division of Endocrinology & Metabolism, Department of Medicine, Cheil General Hospital & Women’s Healthcare Center, College of Medicine, Kwandong University, Seoul, Korea *Correspondence to: Sung-Hoon Kim, Division of Endocrinology & Metabolism, Department of Medicine, Cheil General Hospital & Women’s Healthcare Center, College of Medicine, Kwandong University, Seoul, Korea. E-mail: [email protected]
Received: 28 November 2013 Revised: 13 February 2014 Accepted: 3 March 2014
Copyright © 2014 John Wiley & Sons, Ltd.
Methods Maternal weight gain from self-reported pre-pregnancy weight until 24–28 weeks of gestation was measured in 731 pregnant women, and an expected MWG24 was determined using the Institute of Medicine 2009 guidelines. Glucose tolerance, insulin resistance, insulin secretory capacity, anthropometric measurements, lipid profiles, nutrient intakes and pregnancy outcomes were evaluated at 24–28 weeks of gestation. The adjusted odds ratios (ORs) for GDM, large-for-gestational-age infants, small-for-gestationalage infants and preterm delivery were determined according to maternal weight gain by logistic regression analysis after adjusting for covariates. Results Compared with a normal MWG24, an inadequate MWG24 reduced the OR (0.565) for GDM, but an excessive MWG24 did not affect the OR (0.854). However, ORs for preterm delivery were significantly higher in both inadequate and excessive MWG24 groups in comparison with the normal MWG24. There were no other adverse pregnancy outcomes due to the inadequate MWG24. MWG24 was not associated with a significant increase in ORs for delivering large-for-gestational-age or small-for-gestational-age infants or delivery by caesarean section. Although energy intake was less than the estimated energy requirement in all groups, MWG24 was linearly associated with energy intake such that energy balance was positive in the excessive MWG24 group. Conclusions This study suggests that both target weight gain and energy intake recommendations for early pregnancy may not be optimal for Korean women and that race-specific recommendations are needed to decrease the risk of GDM without increasing adverse pregnancy outcomes. Copyright © 2014 John Wiley & Sons, Ltd. Keywords gestational diabetes mellitus; early birthweight; pregnancy outcome; energy intake
gestational
weight
gain;
717
Early Maternal Weight Gain and GDM
Introduction Gestational diabetes mellitus (GDM) develops in the later stages of the second trimester because of increased insulin resistance and concomitantly decreased utilization of maternal glucose [1]. This decrease in maternal glucose utilization is necessary for the delivery of glucose to the fetus, but extreme changes can result in maternal hyperglycaemia and macrosomia [1,2]. Maternal body weight and early gestational weight gain are independent risk factors for the development of GDM later in pregnancy [3]. Excessive early gestational weight gain might be associated with an early increase in insulin resistance, which in turn results in the exhaustion of pancreatic βcells [4]. This decrease in β-cell function could reduce the capacity to compensate for enhanced insulin resistance during pregnancy and eventually lead to maternal hyperglycaemia and excessive fetal growth [4,5]. β-cell depletion can be prevented by increasing β-cell mass [6], and there is emerging evidence that improvements in lifestyle and dietary habits also mitigate the development of GDM. Lifestyle and dietary habits that result in gestational weight gain are crucial risk factors for GDM. Gestational diabetes mellitus develops because of an imbalance between insulin resistance and insulin secretion. The second half of pregnancy is characterized by progressive insulin resistance and simultaneous decreases in maternal glucose utilization [7,8], and maternal fat accumulation appears to accelerate the progression of subsequent maternal insulin resistance [8]. To maintain normoglycaemia, insulin secretion sufficient to compensate for insulin resistance is necessary. However, Asians have a limited insulin secretory capacity compared with other ethnic groups [6,9]. Asians are susceptible to GDM-like type 2 diabetes because of inherently low β-cell function and mass that impairs their ability to compensate for insulin resistance by increasing insulin secretion [9]; thus, this population is more likely to develop GDM at lower levels of insulin resistance than other populations. Pre-pregnancy obesity and excessive gestational weight gain during pregnancy are major risk factors for increases in insulin resistance and the development of GDM. However, these factors can be controlled by dietary and lifestyle modifications. In 2009, the American Institute of Medicine (IOM) established a set of guidelines with recommended weight gains throughout pregnancy, as well as weekly weight gain recommendations for the second and third trimesters of pregnancy that are based on pre-pregnancy body mass index (BMI) [10]. Maternal weight gain at 24– 28 weeks of gestation (MWG24) is thought to be associated with pregnancy complications, including GDM, because GDM typically develops at the end of the second trimester. Herring et al. [11] reported that a greater degree of gestational weight gain leads to a higher prevalence of abnormal Copyright © 2014 John Wiley & Sons, Ltd.
glucose tolerance in the third trimester of pregnancy [odds ratio (OR): 2.14, 95% confidence interval (CI): 1.04–4.42]. However, few studies have evaluated weight gain during early pregnancy based on pre-pregnancy BMI. It was hypothesized that MWG24 affects the development of adverse maternal and neonatal outcomes via alterations in insulin sensitivity. Thus, in the present study, we assessed whether optimal MWG24, based on pre-pregnancy BMI, can lower the risk for developing gestational complications such as GDM and other adverse pregnancy outcomes in a hospital-based prospective study.
Subjects and methods Subjects and screening for GDM This cohort study included 731 pregnant women who were first evaluated and then delivered their babies at Cheil General Hospital & Women’s Healthcare Center in Seoul, South Korea, between June 2006 and March 2009. Fifty-two women were dropped from the 783 pregnant women recruited during the study. When twins were delivered, the data were excluded from the study. In addition, the subjects with missing data values were excluded at the end of the study. During their first visit to the diabetes clinic, participants completed a short survey regarding pre-pregnancy body weight and medication use, measurements of body weight and blood glucose levels were taken, and each participant received a general education session regarding managing pregnancy, including food intake. The survey was monitored by a nurse and a dietician to eliminate missing values from the survey. Standard protocols for the screening and diagnosis of GDM were followed. All pregnant women without a previous diagnosis of glucose intolerance were screened for GDM between 24 and 28 weeks of gestation using the 50-g glucose challenge screening test. A 1-h glucose value ≥7.2 mM on the glucose challenge test, without regard for the time of day or time of last meal, was considered to be a positive screen. Women with a positive screen underwent a 3-h 100-g oral glucose tolerance test (OGTT) according to the criteria of Carpenter and Coustan [12]. Threshold glucose values were as follows: fasting: ≥5.3 mM, 1 h: ≥10.0 mM, 2 h: ≥8.6 mM and 3 h: ≥7.8 mM. GDM (n = 231) was confirmed by the presence of at least two abnormal OGTT values. Subjects with a twin pregnancy, medical conditions that could affect fetal growth or pregnancies in which gestational age could not be ascertained by early ultrasonography were excluded. All subjects provided written informed consent, and the study protocol was approved by the Ethics Committee of the Institutional Review Board of Cheil General Hospital. Diabetes Metab Res Rev 2014; 30: 716–725. DOI: 10.1002/dmrr
S. Park et al.
718
Category of maternal weight gain at 24–28 weeks of gestation
Laboratory measurements and physiological indexes
Pre-pregnancy BMI was calculated as pre-pregnancy weight (kg)/height2 (m2). Weight gain during pregnancy was calculated as pre-pregnancy weight subtracted from weight before delivery. Unlike Caucasians, a mild degree of obesity is associated with obesity-related disease in Asians [1,2]. The definition for obesity in Asians differs from the definition put forth by the National Institutes of Health; the Korean Society for the Study of Obesity defines overweight and obesity as 23 ≤ BMI < 25 and BMI ≥ 25, respectively. Consistent with this definition of obesity, pregnant Korean women tend to develop adverse pregnancy outcomes even when their gestational weight gain is less than that of Caucasians. In this study, optimal MWG24 was defined according to the IOM guidelines because no specific guidelines for optimal weight gain during pregnancy for Koreans are available [10]. The data were stratified into three categories according to inadequate, normal and excessive MWG24: inadequate MWG24, 6.5 kg for normal weight participants.
Plasma glucose concentrations were measured by the glucose oxidase method using a YSI 2300 STAT (YSI; Yellow Springs, Ohio). Plasma insulin concentrations were measured using a human-specific radioimmunoassay kit (Linco Research, St. Charles, MO). Homeostatic model assessments for insulin resistance (HOMA-IR) and β-cell function (HOMA-B) were calculated using the equations developed by Matthews et al. [13]. HbA1c levels were determined at the initial diagnosis of GDM and prior to delivery by the Variant II HbA1c Program (BioRad; Hercules, CA). Plasma lipid profiles (total, HDL and LDL cholesterol, and triglyceride) were determined by enzymatic colorimetry. Plasma LDL cholesterol was calculated using the Friedewald equation. Gestational hypertension was diagnosed if blood pressure was ≥140 for systolic and 90 mmHg for diastolic in the absence of proteinuria. Questionnaires were used to obtain the following information: age, pre-pregnancy weight, obstetric history including gestational age and parity and family history of diabetes among first-degree relatives.
Management of blood glucose levels in all GDM women during a late pregnancy Women diagnosed with GDM were referred to a specialist team composed of obstetricians, a diabetologist, a nurse educator and dietitians. All GDM subjects were required to maintain blood glucose levels within a normal range using diet, physical activity and/or insulin treatment. Additionally, all GDM patients received dietary education and/or counselling on how to regulate their dietary intake and physical activity, and self-monitored blood glucose values and weight changes were obtained during biweekly clinic visits until the time of delivery. Treatment targets included blood glucose concentrations that did not exceed 5.3 mM at fasting and 6.7 mM at 2h postprandial. Insulin therapy was initiated if blood glucose levels remained above target levels, and insulin dosage was adjusted accordingly by the patients on the basis of a protocol using self-monitored blood glucose levels. Urine ketone levels were monitored to detect insufficient caloric or carbohydrate intakes in women treated with calorie restriction; all subjects maintained negative urinary ketones. Copyright © 2014 John Wiley & Sons, Ltd.
Nutritional assessment at 24–28 weeks of pregnancy Food intakes were determined by a skilled dietician using the 24-h recall method. Nutrient intakes were analysed from the food intakes using CAN-PRO (version 3; Korean Nutrient Society, Seoul, Korea), and some were calculated as the percentage of the Korean Dietary Reference Intake for pregnant women according to age. Activity was determined by activity recall, and daily energy expenditure was calculated by multiplying basal energy expenditure and activity levels [14]. Basal energy expenditure was calculated using body weight, height, age and pregnancy status according to the modified Harris–Benedict equation [14].
Pregnancy outcomes Preterm delivery was defined as delivery before 37 weeks of gestation, and macrosomia was considered to be a birthweight of 4000 g or greater. LGA was defined as a birthweight ≥90th percentile based on a Korean reference population. The Apgar score was defined as low if a score of
