Effect of dietary and lifestyle factors on the risk of gestational diabetes: review of epidemiologic evidence^,

Abstract

Gestational diabetes mellitus (GDM), defined as glucose intolerance with onset or first recognition in pregnancy, is a common pregnancy complication and a growing health concern. GDM has been related to significant short-term and long-term adverse health outcomes for both mothers and offspring. Importantly, this number is increasing with the increasing burden of obesity among women of reproductive age. Collectively, these data highlight the significance of understanding risk factors, in particular modifiable factors, for GDM and of preventing GDM among high-risk populations. Research in the past decade has identified a few diet and lifestyle factors that are associated with GDM risk. This review provides an overview of emerging diet and lifestyle factors that may contribute to the prevention of GDM. It also discusses major methodologic concerns about the available epidemiologic studies of GDM risk factors.

INTRODUCTION

Gestational diabetes mellitus (GDM), defined as glucose intolerance with onset or first recognition in pregnancy, is a common pregnancy complication that affects ≈1–14% of all pregnancies and is a growing health concern (1). The incidence of GDM is increasing with the increasing burden of obesity among women of reproductive age (2). GDM has been related to substantial short-term and long-term adverse health outcomes for both mothers and offspring. Women with GDM have an increased risk of perinatal morbidity and a considerably increased risk of impaired glucose tolerance and type 2 diabetes in the years after pregnancy (1, 3–6). Children of women with GDM are more likely to be obese and have impaired glucose tolerance and diabetes in childhood and early adulthood (1, 7, 8). Collectively, these data highlight the importance of identifying risk factors, in particular modifiable factors, for this common pregnancy complication and of preventing GDM among high-risk populations (9).

RISK FACTORS BOTH BEFORE AND DURING PREGNANCY ARE RELEVANT

Normal pregnancy, especially the third trimester, is characterized by elevated metabolic stresses on maternal lipid and glucose homeostasis, which includes insulin resistance and hyperinsulinemia (10–12). Although the precise underlying mechanisms are yet to be identified, insulin resistance and inadequate insulin secretion to compensate for it play a central role in the pathophysiology of GDM (9, 10). Women who develop GDM are thought to have a compromised capacity to adapt to the increased insulin resistance characteristic of late pregnancy, primarily during the third trimester (10). Pregnancy-related metabolic challenges unmask a predisposition to glucose metabolic disorders in some women (10, 13, 14). The majority of women with GDM have β cell dysfunction against a background of chronic insulin resistance to which the insulin resistance of pregnancy is partially additive (10). Factors that contribute to insulin resistance or relative insulin deficiency both before and during pregnancy may have a deleterious effect during pregnancy and may be risk factors for GDM (9). Limited attention has been paid to pregravid risk factors for GDM.

OVERVIEW OF RISK FACTORS FOR GDM: EVIDENCE FROM EPIDEMIOLOGIC STUDIES

Epidemiologic studies on risk factors for GDM are relatively limited (15, 16). The diagnostic criteria and screening strategy for GDM and the measurements of risk factors vary significantly across study periods and study populations, which makes it difficult to compare findings across studies. Moreover, substantial heterogeneity exists in the approach of analyzing the association between risk factors and the risk of GDM. The majority of earlier studies on risk factors for GDM failed to address bias due to potential confounding by other risk factors. Furthermore, the actual number of GDM cases in the majority of studies is rather low, which hampers reaching solid conclusions. Despite these methodologic concerns, several GDM risk factors emerge consistently (9).

Well-recognized risk factors for GDM include excessive adiposity, advanced maternal age, a family history of type 2 diabetes, and a history of GDM (15–19). Among them, excessive adiposity is the most commonly investigated modifiable risk factor with consistent findings (20–22). The risk of GDM increases significantly and progressively in overweight, obese, and morbidly obese women. Cigarette smoking has not been consistently identified as a risk factor for GDM (15, 17, 19, 23–27). Available data suggest that the magnitude of possible association between maternal smoking (before and during pregnancy) and GDM may be modest. Asian, Hispanic, and Native American women, as compared with non-Hispanic white women, have an increased risk of GDM (15, 17, 19, 28). African American women have been reported to have an increased risk of GDM, as compared with non-Hispanic whites, by some (19, 29), although not all (17, 28), investigators. Other reported risk factors include, but are not limited to, short maternal stature (30–34), polycystic ovary disease, previous stillbirth, high blood pressure during pregnancy, and multiple pregnancies (9, 15).

DIETARY AND LIFESTYLE RISK FACTORS

Overview

In the past decades efforts to identify risk factors for GDM have increased, in part because of the escalating prevalence of diabetes and obesity worldwide (9). Subsequently, several potentially novel risk factors for GDM have been identified. A few studies have provided some suggestive evidence of dietary factors both before or during pregnancy that are related to GDM risk (35–46). Moreover, a series of studies have linked physical activity before and/or during pregnancy with a decreased GDM risk (47–54). This effect seems to increase with increasing intensity of, and time spent on, the physical activity (9).

Dietary factors and GDM

Substantial evidence has related diet to the development of glucose intolerance. An extensive body of literature has reported both protective and risk-enhancing associations between particular dietary factors and type 2 diabetes in adult men and nonpregnant women. These studies suggest that the quality of dietary carbohydrate and fat intake may be more relevant to type 2 diabetes risk than is the total amount of these nutrients (9). Specific types of carbohydrates may be protective [eg, whole grains (55–58)], and specific types of fats [eg, trans fat (59–63)] may be risk enhancing (64, 65). Dietary treatment/counseling has long been recommended for women who develop GDM. However, studies of the association between dietary factors and the risk of development of GDM have just emerged. A limited number of studies have examined diet before and/or during pregnancy in association with GDM risk (35–46, 66).

Dietary factors during pregnancy and GDM risk

Earlier studies on the effect of diet during pregnancy, many of which were cross-sectional or retrospective in design, suggested that macronutrient components of the diet in midpregnancy may predict incidence (37, 39, 40) or recurrence (43) of GDM (9). For instance, findings from some studies (37, 38), although not all (37, 38, 44), suggested that polyunsaturated fat intake may be protective against glucose intolerance in pregnancy, and high intake of saturated fat may be detrimental (39). Of note, these analyses did not adjust for or consider the effect of other types of fat, which is important because intake of different fat subtypes tends to be correlated and may have opposing effects (64). A recent prospective study that considered the correlation of nutrients showed that higher intake of fat and lower intake of carbohydrates may be associated with increased risk of GDM and impaired glucose tolerance (40). In addition, in a prospective study of pregnant women, lower plasma vitamin C (35) and vitamin D concentrations (67) in early pregnancy were significantly associated with increased GDM risk. Note that the number of GDM cases in the majority of studies of dietary factors during pregnancy is rather low. Inferences from the majority of available studies are further limited by cross-sectional or retrospective design. Thus far, no concrete conclusion can be drawn as to the role of dietary factors during pregnancy in the development of GDM (9).

Prepregnancy diet and GDM risk

A number of pregravid dietary factors were recently associated with the risk of glucose intolerance during pregnancy. These were based on data primarily from a large prospective study, the Nurses’ Health Study II (36, 41).

Western dietary pattern and red meat.

In the Nurses’ Health Study II, 2 dietary patterns, the Western pattern and the prudent pattern, were identified by factor analyses. Strong positive associations were observed between the Western dietary pattern score and GDM risk, whereas the prudent dietary pattern score was significantly and inversely associated with GDM risk, even after adjustment for major risk factors for GDM, such as family history of diabetes, prepregnancy body mass index (BMI), physical activity, parity, and so forth (41). The prudent dietary pattern was characterized by a high intake of fruit, green leafy vegetables, poultry, and fish, whereas the Western pattern was characterized by a high intake of red meat, processed meat, refined grain products, sweets, french fries, and pizza (9).

The association with the Western pattern was largely explained by intake of red and processed meat products. Pregravid intake of red and processed meats were both significantly and positively associated with GDM risk, independent of known risk factors for type 2 diabetes and GDM. For instance, after the adjustment for major risk factors for GDM, which include prepregnancy BMI, physical activity, parity, and other dietary risk factors, those who consumed >6 servings of red meat/wk had a more than 1.7-fold increased risk of GDM compared with those women who consumed <1.5 servings of red meat/wk (relative risk: 1.74; 95% CI: 1.35, 2.26).

Although the precise molecular mechanisms are unclear, the observed associations of red and processed meat intakes with GDM risk are biologically plausible. First, they could be related to several possible biologically adverse effects of components in red and processed meats, such as saturated fat and cholesterol, on insulin sensitivity and β cell function that might be relevant to the pathophysiology of GDM (9). In the present study, the strong association of red meat and processed meat with GDM risk remained significant after further adjustment for these other dietary factors that included fatty acids and cholesterol, which indicates that components of red meat and processed meat other than these nutrients might also be relevant to the pathogenesis of GDM. For example, nitrites, frequently used as a preservative in processed meats, have been implicated in the development of diabetes. Nitrosamines can be formed by the interaction of amino compounds with nitrites present either in the stomach or within the food product (68). They have been linked to β cell toxicity (69). In addition, low doses of the nitrosamine streptozotocin were shown to induce type 2 diabetes in animal models (70). Another potential explanation is related to the toxic effects of advanced glycation end products (AGEs), which can be formed in meat and high-fat products through heating and processing (71). Animal models and human studies suggest that AGEs are involved in the progression of diabetes. The development of type 2 diabetes was decreased by treatment with aminoguanidine, an AGE inhibitor, in genetically diabetic mice (72), and improvement of various features of insulin resistance was shown in mice fed a diet low in AGEs (73). Heme iron in red meat might also contribute to the increased risk of GDM, because body iron overload has been postulated to promote insulin resistance and increase the risk of type 2 diabetes (74). More recently, iron supplements and increased iron stores in pregnant women without iron deficiency were related to an increased risk of GDM (75). However, the association between processed meat and GDM risk remained strong after adjustment for heme iron. Nevertheless, it is also plausible that other unidentified components in red meat and processed meat can contribute to the adverse effect on GDM related to them (9).

Dietary fiber and glycemic index.

Pregravid consumption of dietary fiber (ie, total, cereal, and fruit fiber) was significantly and inversely associated with GDM risk (36). In contrast, dietary glycemic load was positively associated with GDM risk. The glycemic index is a relative measure of the glycemic effect of the carbohydrates in different foods (76). Total glycemic load was calculated by first multiplying the carbohydrate content of each food by its glycemic index value, then multiplication of this value by the frequency of consumption, and the summation of the values from all food. Dietary glycemic load thus represents the quality and quantity of carbohydrate intake and the interaction between the 2. Each 10-g/d increment in total fiber intake was associated with a 26% (95% CI: 9%, 49%) decrease in risk; each 5-g/d increment in cereal or fruit fiber was associated with a 23% (9–36) or 26% (5–42) decrease, respectively. The combination of high glycemic load and a low-cereal-fiber diet was associated with a 2.15-fold (95% CI: 1.04-, 4.29-fold) increased risk of GDM compared with the reciprocal diet (9).

Sugar-sweetened beverages.

Sugar-sweetened beverages are the leading source of added sugars in Americans’ diets (77). In animal models and human studies, a high-sugar diet decreases insulin sensitivity (78, 79) and insulin secretion (80). In the Nurses’ Health Study II, after adjustment for age, parity, race, physical activity, smoking, alcohol intake, prepregnancy BMI, and Western dietary pattern, intake of sugar-sweetened cola was positively associated with the risk of GDM, whereas no significant association was shown for other sugar-sweetened beverages and diet beverages. Compared with women who consumed <1 serving/mo, those who consumed ≥5 servings/wk of sugar-sweetened cola had a 22% greater GDM risk (relative risk: 1.22; 95% CI: 1.01, 1.47).

In summary, epidemiologic studies on the role of dietary factors in the development of GDM are at their early stage. Although the observational design of this study does not prove causality, available data did provide evidence that supports the theory that dietary factors may play a role in the development of GDM. Large prospective studies on dietary factors both before and during pregnancy and the risk of GDM are warranted (9).

Physical activity and GDM

Available data from epidemiologic and clinical studies among nonpregnant individuals support the thesis that physical activity can influence glucose homeostasis through its direct or indirect effects on insulin sensitivity and secretion (9). By increasing insulin sensitivity and improving glucose tolerance via several mechanisms, physical activity has a beneficial effect on many aspects of insulin resistance syndromes (81–83). After an episode of physical activity, insulin sensitivity was improved for up to 48 h by increasing cellular sensitivity to circulating insulin (84). In addition to this acute effect, longer-term, even relatively modest, increases in habitual physical activity induce adaptations that can profoundly affect glucose tolerance (82) and potentially decrease GDM risk. Long-term improvement in glucose tolerance and increased insulin sensitivity may also result from physical activity–induced decreases in fat mass and increases in lean muscle mass (9, 85, 86).

Studies on the effect of physical activity on pregnant women are limited. The definitions used to classify intensity, amount, and type of physical activity vary considerably, which makes comparisons between studies difficult. Furthermore, the actual number of GDM cases in the majority of studies is rather low, which hampers reaching solid conclusions (9). Despite these limitations, several studies have linked physical activity before and/or during pregnancy to a decreased risk of GDM (47–54). This effect seems to increase as the intensity of, and time spent on, the physical activity increases (9). For instance, in a prospective study of 21,765 women who reported at least one singleton pregnancy in the Nurses’ Health Study II, women in the highest quintile of habitual recreational physical activity before pregnancy (specifically, vigorous activity, which is equivalent to ≈30 min/d of brisk walking) had a ≈20% risk decrease for the development of GDM (54). Similarly, physical activity before pregnancy (particularly vigorous activity) was associated with a decreased risk of either GDM or any antepartum glucose intolerance (risk reductions of 44% and 24%, respectively) in another study of pregnant women (52). In both a prospective study and a case-control study, Dempsey et al (48, 49) showed that leisure-time physical activity (ie, nonoccupational activity) in the year before pregnancy was associated with a significantly lower risk of GDM. A recent meta-analysis of findings from the above studies among 34,929 women, which included 2,813 cases of GDM, gave a pooled odds ratio of 0.45 (95% CI: 0.28, 0.75) when the highest and lowest categories were compared (87).

Accumulative evidence has suggested that physical activity during pregnancy may be related to GDM risk as well. One study reported a significant protective effect (48), whereas others observed an association, but not at statistically significant levels (47, 49, 50, 52, 88). In a case-control study, participation in any recreational activities during the first 20 wk of pregnancy was related to a 48% decreased GDM risk (48). In 2 prospective cohort studies (49, 52), physical activity during early pregnancy appeared to be associated with a lower risk of developing GDM; however, the findings were not statistically significant. Dye et al (50) observed that women who exercised weekly for ≥30 min at some time during pregnancy had a lower risk of GDM, although this result was shown for only morbidly obese women (BMI > 33). In addition, data that were nationally representative of women with live births indicated that those who began physical activity during pregnancy had less risk of development of GDM than did those who were inactive during pregnancy (51). In the same study, women with activity levels above the median had a 67% lower risk of GDM than those who performed less physical activity (9). In a recent meta-analysis of 4401 women, which included 361 GDM cases, exercise in early pregnancy was related to a 24% decreased risk of GDM (odds ratio: 0.76; 95% CI: 0.70, 0.83) (87).

CONCLUSIONS

The spreading of epidemics of obesity and diabetes worldwide, the increase in the incidence of GDM during recent years, and the short-term and long-term adverse health outcomes for both women and offspring associated with GDM highlight the significance of preventing GDM among women at high risk. Accumulating evidence from observational studies suggest that several modifiable factors, in particular pregravid body adiposity, recreational physical activity before and during pregnancy, and pregravid dietary patterns, may be related to GDM risk. Collectively, these data suggest an additional potential benefit of the adoption or continuation of a healthy diet and active lifestyle for women of reproductive age.