Continuous glucose profiles in obese and normal-weight pregnant women on a controlled diet: metabolic determinants of fetal growth

Abstract

Objective: We sought to define 24-h glycemia in normal-weight and obese pregnant women using continuous glucose monitoring (CGM) while they consumed a habitual and controlled diet both early and late in pregnancy.

Research design and methods: Glycemia was prospectively measured in early (15.7 ± 2.0 weeks' gestation) and late (27.7 ± 1.7 weeks' gestation) pregnancy in normal-weight (n = 22) and obese (n = 16) pregnant women on an ad libitum and controlled diet. Fasting glucose, triglycerides (early pregnancy only), nonesterified fatty acids (FFAs), and insulin also were measured.

Results: The 24-h glucose area under the curve was higher in obese women than in normal-weight women both early and late in pregnancy despite controlled diets. Nearly all fasting and postprandial glycemic parameters were higher in the obese women later in pregnancy, as were fasting insulin, triglycerides, and FFAs. Infants born to obese mothers had greater adiposity. Maternal BMI (r = 0.54, P = 0.01), late average daytime glucose (r = 0.48, P < 0.05), and late fasting insulin (r = 0.49, P < 0.05) correlated with infant percentage body fat. However, early fasting triglycerides (r = 0.67, P < 0.001) and late fasting FFAs (r = 0.54, P < 0.01) were even stronger correlates.

Conclusions: This is the first study to demonstrate that obese women without diabetes have higher daytime and nocturnal glucose profiles than normal-weight women despite a controlled diet both early and late in gestation. Body fat in infants, not birth weight, was related to maternal BMI, glucose, insulin, and FFAs, but triglycerides were the strongest predictor. These metabolic findings may explain higher rates of infant macrosomia in obese women, which might be targeted in trials to prevent excess fetal growth.

Figure 1

Blood glucose measurements recorded by CGMS in lean and obese women early (A, C, and E) and late (B, D, and F) in pregnancy. Mean values ± SEM are listed by each data point for lean (○) and obese (●) women throughout the day and night, as defined. Night (mean of values between 11:30 p.m. and 6:30 a.m.); Fast (mean of six consecutive values before breakfast); PRE-L (mean of three consecutive values directly before lunch); PRE-D (mean of three consecutive values directly before dinner); PPB (1hr), PPL (1hr), and PPD (1hr) (mean of three values, 1 h after each meal); PPB (2hr), PPL (2hr), and PPD (2hr) (mean of three values, 2 h after each meal). Significant differences are denoted (*P < 0.05; †P < 0.01; ‡P < 0.001). C and D: CGMS data (~6,000 and ~4,000 for lean [thin line] and obese [thick line], respectively) were sorted, and frequency, cumulative frequency, and percentage relative cumulative frequency were determined for lean and obese women early and late in pregnancy over the range of glucose values. Equations for the resulting curves were fitted (r > 0.99) to the following equation: Y = 100 × ^H/(EC50^H + X^H), where Y = percentage relative cumulative frequency curves, X = blood glucose, H = slope, and EC50 = 50th percentile value for glucose-utilizing curve-fitting software (NCSS 2007; Kaysville, UT, www.ncss.com), and are given for each curve. The mean glucose values at the 50% percentile were significantly different between lean and obese subjects, both early and late in pregnancy (P < 0.001). The 24-h AUC for glucose values were significantly greater for obese women than lean women in early (P = 0.037) (E) and late (P = 0.007) (F) in pregnancy. NW, normal weight.

Figure 2

Relationships between maternal glucose, other plasma measurements, and infant adiposity. Triceps, subscapular skinfolds, and abdominal circumference were measured in triplicate by a single trained observer within 48 h of birth. The sum of the two skinfold measurements and the sex of the child were used to estimate percentage body fat [BFat (%)] (–10) using the equations as follows: BFat (%) = 1.21 × (triceps + subscapular) – 0.008 × (triceps + subscapular)² – 1.7 (for male subjects); BFat (%) = 1.33 × (triceps + subscapular) – 0.013 × (triceps + subscapular)² – 2.5 (for female subjects). Linear regression analysis revealed significant relationships for daytime glucose (mean of all values between 6:30 a.m. and 11:30 p.m.) (A), plasma insulin (B), plasma FFA (C), plasma triglycerides (D), PPD-1hr (mean of three values, 1 h after dinner) (E), mean glucose (mean glucose of all values in a 24-h period) (F), and infant adiposity (percentage body fat). All maternal glucose and plasma measurements were measured late in pregnancy except for plasma triglycerides, which was only measured early in pregnancy. Equations, correlation coefficients, and P values are given for each relationship. ○, lean subjects; ●, obese subjects.