Gestational Diabetes Not Found To Alter The Metabolic Processes In
Obese Pregnant Women

An increase in fat oxidation may be related to increased maternal serum leptin

(June 22, 2004) -  Bethesda, MD - Gestational diabetes is a type of diabetes, or high blood sugar, that only pregnant women get. If a woman is found to have high blood sugar when she's pregnant, but she never had high blood sugar before, she has gestational diabetes. Nearly 135,000 pregnant women get the condition every year, making it one of the top health concerns related to pregnancy.

The energy cost of pregnancy and amount of increased fat during pregnancy vary among women in different cultures.  Consequently, recommendations for nutritional intake in pregnancy are diverse and depend on the study population, thereby making the development of general nutritional guidelines difficult.

Past studies have focused on long-term changes in energy expenditure and increase in fat in lean women (body fat less than 25 percent) with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM) relative to the alterations in carbohydrate metabolism during gestation. However, similar data in obese women have not been reported.  This is important to American women because the prevalence of obesity (defined as body mass index greater than 30) now approaches 20 percent in adolescents and adults, reaching epidemic proportions. Given the strong association of obesity with decreased insulin sensitivity, researchers prospectively evaluated changes, over an extended time period, in energy expenditure and increase in fat in a cohort of women with NGT and GDM, relative to the alterations in insulin sensitivity during gestation.

A New Study

A team of researchers has hypothesized that women with decreased pre-pregnancy insulin sensitivity, i.e. the GDM subjects, have a decrease in energy expenditure and an increase in fat accretion as compared with a matched NGT group. Additionally, because the role of the increased maternal serum leptin (a helical protein secreted by adipose tissue and acting on a receptor site in the ventromedial nucleus of the hypothalamus to curb appetite and increase energy expenditure as body fat stores increase) concentrations in pregnancy has not yet been fully explained, the research team examined the relationship of maternal serum leptin changes in nutrient metabolism.

The authors of the study, “Longitudinal Changes in Energy Expenditure and Body Composition in Obese Women with Normal and Impaired Glucose Tolerance,” are Ndubueze C. Okereke, Larraine Huston-Presley, Saeid B. Amini, Satish Kalhan, and Patrick M. Catalano, all from Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH.   Their findings appear in the online edition of the American Journal of Physiology—Endocrinology and Metabolism. The journal is one of 14 published each month by the American Physiological Society (www.the-aps.org).

Methodology

Fifteen healthy obese women (defined as pre-pregnancy percent body fat greater than 25 percent) were recruited before a planned pregnancy to participate in this study. None of the subjects were breast-feeding or using hormonal contraception, tobacco, or other medications that might affect carbohydrate metabolism or energy expenditure. None of the study subjects had diabetes mellitus before conception; seven of the women were at high risk of developing GDM, based on a history of GDM in a previous pregnancy (n=4), a strong family history of type 2 diabetes in a first-degree relative (n=2), or an impaired glucose tolerance test before conception plus a first-degree relative with type 2 diabetes (n=1). Other than GDM, the pregnancies were uncomplicated. Eight other women were recruited, none of whom had a history of abnormal glucose tolerance either before or during a previous pregnancy (i.e., the NGT group). All subjects were planning to conceive as soon as the baseline pre-pregnancy studies were completed.

Each subject was evaluated before conception (P), in early (E) gestation (12-14 weeks) and again in late (L) gestation (34-36 weeks). Twelve of the 15 subjects were evaluated in the follicular phase of the menstrual cycle and three were evaluated in the luteal phase. Each subject was instructed in a standard dietary regimen two weeks before each study period.  The dietary regimen was designed to standardize nutritional intake for each subject, in order to maintain weight before conception and allow appropriate increase in weight during pregnancy. The regimen was identical to the diet employed in the treatment of gestational diabetes. 

All were evaluated prior to conception (P) at 12-14 weeks (E) and 34-36 weeks (L). Energy expenditure and glucose and fat metabolism were measured using indirect calorimetry. Basal hepatic glucose production was measured using [6,6 2 H2] glucose and insulin.

Serum leptin was measured in duplicate by radioimmunoassay. This assay measures total (free and bound) and circulating leptin.  Total non-esterified free fatty acid (FFA) concentrations were measured in duplicate by an in vitro enzymatic calorimetric method.

Results

All subjects had normal results of routine renal, thyroid, and liver chemistries. Because of the study design there were no significant differences in any of the demographic characteristics, or body composition between the NGT and GDM groups. All subjects were, by definition, obese with greater than 25 percent body fat. There were no significant differences in caloric intake in study subjects across time or between groups. In addition there were no significant differences in percentages of protein, lipids or carbohydrates in their diets across time or between groups, as demonstrated by a three-day dietary record. Although physical activity decreased significantly (p=0.01) with advancing gestation, there was no significant difference between groups.  

Other key findings included:

• There was an approximately 30 percent increase in basal energy expenditure from pre-pregnancy to late pregnancy whether expressed as basal VO2 ml/min or kcal/day. The increase in energy expenditure was approximately 14 percent in the NGT and 21 percent in the GDM subjects. These differences did not reach statistical significance (p=0.3 to 0.5) because of the great inter-individual variability.
   

• There was a significant inverse correlation between the changes in basal endogenous glucose production and fat oxidation from time P to E. Although there was generally an increase in basal endogenous glucose production, half the subjects had increasing and the other half had decreasing fat oxidation. The researchers anticipated an increase in fat oxidation to be associated with an increase in basal endogenous glucose production, but serum concentrations were unchanged over the same time period.
   

• In obese subjects there was no change in either basal carbohydrate oxidation or non-oxidative carbohydrate metabolism over time. However, there was a significant 50-80 percent increase in basal fat oxidation. The increase was particularly evident from time E to L, when there was increased accretion of adipose tissue and decreasing insulin sensitivity. These data support the hypothesis that increased lipid rather than carbohydrate oxidation may represent an adaptive mechanism for the prevention of additional weight (adipose tissue) in situations where there was preexisting obesity and decreasing insulin sensitivity.
   

• The metabolic changes during insulin infusion in late gestation in obese women are similar to what was observed in lean women. There are progressive decreases in glucose and lipid insulin sensitivity, carbohydrate oxidation and non-oxidative metabolism but a significant 5-fold increase in fat oxidation with advancing gestation. These data support the concept that during fasting, pregnancy is a state of accelerated starvation with increased maternal reliance on lipids rather than carbohydrates for meeting energy needs. Carbohydrates and amino acids are thus made available for feto-placental energy requirements and growth.
   

• Although the source of leptin is well documented, the role of the increased maternal leptin concentrations during gestation has remained elusive. In addition to maternal adipose tissue, the placenta produces leptin and leptin concentrations fall within 48 hours of delivery.

Conclusions

The researchers found that during pregnancy of the obese women in this study, there are significant alterations in body composition and energy expenditure among individuals, but no difference between women with NGT and GDM. There are significant increases in fat mass, basal metabolic rate and an increased reliance on lipid metabolism both in the basal state and during insulin infusion. The increased reliance on fat metabolism is accompanied by a concomitant decrease in carbohydrate metabolism under conditions of hyperinsulinemia but not in the basal state.

The authors speculate that the pre-pregnancy metabolic status of the individual (and not whether or not the individual develops GDM) that provides the baseline upon which the alterations in pregnancy metabolism are mediated through placental hormones, cytokines and growth factors. 

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Source:  Online edition of the American Journal of Physiology—Endocrinology and Metabolism. The journal is one of 14 published each month by the American Physiological Society (www.the-aps.org).

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year. 

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Editor’s Note: A copy of the research article is available in pdf format to the press. Members of the press are invited to obtain a pdf copy of the study and to interview members of the research team. To do so, please contact Donna Krupa at 703.527.7357 (direct dial), 703.967.2751 (cell) or djkrupa1@aol.com.