Interventions to reduce maternal inflammation and insulin resistance

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Studies in non-pregnant obese individuals provided evidence that changes in lifestyle (weight reduction, changes in dietary fat and fiber, and increased physical activity) reduced the risks of type 2 diabetes mellitus in obese individuals.31 Weight loss is a very effective way to reduce circulating cytokine levels and fasting insulin concentrations in obese women32 but weight loss is not indicated for pregnant women. However, modest reductions in the total amounts gained by obese women are appropriate. The Institute of Medicine recommends that obese women gain at least 15 lb during gestation; normal weight women are advised to gain 25 to 35 lb.33

Physical activity is an effective intervention for reducing the risk of type 2 diabetes and associated metabolic anomalies such as insulin resistance, oxidative stress, and dyslipidemia.34 Physical activity activates the AMP-activated protein kinase (AMPK) enzyme, which increases glucose transport into the muscle, enhances fat oxidation, and reduces insulin resistance.7. Exercise, even intermittently, reduces the risk of GDM among obese women with BMIs >33 by nearly two-fold.35 Women who exercise throughout pregnancy (i.e., perform endurance exercises >4 times/week) gain significantly less fat and had significantly lower increases in TNF-a and leptin during gestation.36 The changes in leptin, but not TNF-a, were correlated with reduced fat mass in physically active women. Possibly, the differences in TNF-a levels reflect the exercise-induced reductions in insulin resistance whereas the leptin changes are more closely linked to fat accretion. Nevertheless, moderate physical activity during pregnancy may be an effective way to reduce subclinical inflammation and insulin resistance during pregnancy.

Changes in the types of dietary fat and carbohydrates consumed may be other ways to reduce maternal inflammation and insulin resistance. Decreases in total fat and saturated fat intakes and increases in dietary fiber are recommended for reducing the risk of type 2 diabetes mellitus in non-pregnant adults.37 Results from the limited number of studies of pregnant women suggest that similar changes in dietary fats and carbohydrates also effectively reduced the risks of glucose intolerance. Clapp randomized 12 pregnant women to a low or high glycemic index diet prior to conception.38 The amounts of carbohydrate consumed were similar in the two groups: 56% of the total energy.

During pregnancy, the women on the low glycemic diet showed no significant changes in their glycemic responses to mixed meals whereas the women on the high glycemic diet experienced 190% increases in their responses compared to pre-pregnancy values. These findings are similar to those reported by Fraser et al.39 who showed that a high fiber diet reduced the post-prandial response to a meal in comparison to low fiber intake. Bronstein and co-workers have also shown that reducing the glycemic index of a test meal lowered post-prandial glucose and insulin responses in both lean and obese women studied in the third trimester40 (Figure 6.3). These findings suggest that the maternal insulin-resistant state and

Oxidative Stress and Inflammatory Mechanisms Insulin Area Under Curve

Oxidative Stress and Inflammatory Mechanisms Insulin Area Under Curve

High GL

Lower GL

High GL

Lower GL

Glucose Area Under Curve

Glucose Area Under Curve

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FIGURE 6.3 Serum insulin and glucose responses to lower glycemic test meals in lean and obese pregnant women. The areas under the curve for serum insulin and glucose were measured over a 2-hour period in 6 lean and 8 obese pregnant women studied at 32 to 36 weeks of gestation.40

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Lower GL

FIGURE 6.3 Serum insulin and glucose responses to lower glycemic test meals in lean and obese pregnant women. The areas under the curve for serum insulin and glucose were measured over a 2-hour period in 6 lean and 8 obese pregnant women studied at 32 to 36 weeks of gestation.40

hyperglycemic responses to meals reflect the intake of a Westernized, low fiber, high glycemic diet rather than a typical metabolic response to pregnancy.

Studies of non-pregnant, obese individuals also suggest that increasing the ratio of polyunsaturated to saturated fats in the diet may reduce the risk of developing metabolic syndrome and its complications as early as adolescence.41 Similar findings have been reported for pregnant women. In a study of 171 pregnant Chinese women with or without impaired glucose tolerance, the type of dietary fat predicted impaired glucose tolerance and GDM.42 In a logistic regression analysis, increased body weight, decreased polyunsaturated fat intake, and a low dietary polyunsaturated-to-saturated fat ratio independently predicted glucose intolerance. Bo and co-workers also found that glucose intolerance in pregnant women without conventional risk factors (i.e., family history, age, and

BMI) was related to the percent of saturated and polyunsaturated fats in the diet with high intakes of saturated fat increasing the risk and high intakes of polyunsaturated fat decreasing the risk.43

The conventional dietary treatment of women with GDM is to reduce the amount of dietary carbohydrate and increase slightly the amount of fat. The preliminary data reviewed here suggest that it is more important to consider the types of carbohydrates and fats rather than the amounts. Increasing dietary fiber (or lowering the glycemic index) and the proportion of polyunsaturated fatty acids may be effective interventions for reducing inflammation and insulin resistance in pregnancy.

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