Insulin-Like Growth Factor Axis and Gestational Diabetes Mellitus: A Longitudinal Study in a Multiracial Cohort
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Figures
- Figure 1
Plasma mean concentrations of IGF-I (A), IGFBP-2 (B), and IGFBP-3 (C) and molar ratio of IGF-I to IGFBP-3 (D) among women with GDM and their matched control subjects at gestational weeks 10–14 and 15–26. P values for case-control comparisons were obtained by mixed-effect linear regression models accounting for matched case-control pairs at gestational weeks 10–14 and 15–26, respectively. GW, gestational weeks.
- Figure 2
Mean concentration (±SEM) of IGF-I (A), IGFBP-2 (B), and IGFBP-3 (C) and molar ratio of IGF-I to IGFBP-3 (D) according to gestational age intervals among women with GDM (squares, solid line) and their matched control subjects (circles, dashed line). *P < 0.05; **P < 0.01; ***P < 0.001 for case-control comparisons obtained by mixed-effect linear regression models accounting for matched case-control pairs at each gestational age interval.
Tables
- Table 1
Participant characteristics among women with GDM and their matched control subjects, the NICHD Fetal Growth Study–Singletons cohort
Case subjects with GDM (n = 107) Control subjects (n = 214) P* Age (years) 30.5 ± 5.7 30.4 ± 5.4 Race/ethnicity Non-Hispanic white 25 (23.4) 50 (23.4) Non-Hispanic black 15 (14.0) 30 (14.0) Hispanic 41 (38.3) 82 (38.3) Asian/Pacific Islander 26 (24.3) 52 (24.3) Education 0.18 Less than high school 17 (15.9) 26 (12.1) High school graduate or equivalent 15 (14.0) 23 (10.7) More than high school 75 (70.1) 165 (77.1) Insurance 0.43 Private or managed care 68 (63.5) 143 (66.8) Medicaid, other 39 (36.5) 69 (32.2) Self-pay 0 2 (0.9) Marital status 0.12 Never married 11 (10.3) 35 (16.4) Married/living with a partner 92 (86.0) 167 (78.0) Divorced/separated 4 (3.7) 12 (5.6) Nulliparity 48 (44.9) 96 (44.9) 1 Family history of diabetes 40 (37.4) 48 (22.4) 0.003 Prepregnancy BMI (kg/m2) <0.001 <25.0 37 (34.6) 123 (57.5) 25.0–29.9 35 (32.7) 56 (26.2) 30.0–34.9 20 (18.7) 17 (7.9) 35.0–44.9 15 (14.0) 16 (7.5) Unknown/missing 0 2 (0.9) Smoking 6 months before pregnancy 4 (3.7) 1 (0.5) 0.06 Alcoholic beverage consumption 3 months before pregnancy 61 (57.0) 137 (64.0) 0.22 Data are presented as n (%) for categorical variables and mean (SD) for continuous variables.
*P values for differences between case and control subjects were obtained by mixed-effect linear regression models for continuous variables and binomial/multinomial logistic regression with generalized estimating equations for binary/multilevel categorical variables, accounting for matched case-control pairs. P values are not shown for matching variables (age and race/ethnicity).
- Table 2
Adjusted odds ratio (95% CI) for the associations of GDM risk with quartiles of IGF-I, IGFBP-2, and IGFBP-3 concentrations and molar ratio of IGF-I to IGFBP-3 at gestational weeks 10–14 and 15–26, the NICHD Fetal Growth Study–Singletons cohort
Case subjects (n) Control subjects (n) Crude model Multivariable model* Gestational weeks 10–14† IGF-I (ng/mL) Q1: 60.0–125.8‡ 15 54 1.00 1.00 Q2: 126.0–156.5 29 53 2.10 (0.96, 4.59) 1.94 (0.77, 4.84) Q3: 156.6–194.5 24 54 1.74 (0.80, 3.78) 2.20 (0.92, 5.28) Q4: 194.6–378.3 36 53 2.87 (1.28, 6.42) 2.93 (1.18, 7.30) P for trend 0.018 0.023 Per SD increment 1.37 (1.04, 1.81) 1.37 (1.01, 1.86) IGFBP-2 (ng/mL) Q1: 37.3–82.5 58 54 1.00 1.00 Q2: 82.6–105.2 20 53 0.24 (0.11, 0.51) 0.22 (0.09, 0.55) Q3: 105.8–145.8 19 54 0.21 (0.09, 0.46) 0.14 (0.05, 0.38) Q4: 146.0–311.7 7 53 0.05 (0.02, 0.16) 0.04 (0.01, 0.16) P for trend <0.001 <0.001 Per SD increment 0.40 (0.26, 0.60) 0.42 (0.26, 0.67) IGFBP-3 (ng/mL) Q1: 2,729.0–3,876.4 19 54 1.00 1.00 Q2: 3,876.5–4,422.7 23 53 1.29 (0.62, 2.68) 1.06 (0.46, 2.42) Q3: 4,434.2–4,970.1 34 54 1.93 (0.94, 3.94) 1.91 (0.84, 4.37) Q4: 4,974.8–7,426.5 28 53 1.76 (0.72, 4.26) 1.66 (0.61, 4.52) P for trend 0.122 0.158 Per SD increment 1.31 (0.93, 1.84) 1.35 (0.94, 1.95) Molar ratio of IGF-I to IGFBP-3 Q1: 0.035–0.112 13 54 1.00 1.00 Q2: 0.113–0.141 32 53 2.85 (1.27, 6.42) 3.26 (1.26, 8.45) Q3: 0.143–0.175 28 54 2.72 (1.12, 6.58) 2.69 (0.97, 7.46) Q4: 0.178–0.355 31 53 3.44 (1.33, 8.88) 3.31 (1.10, 9.98) P for trend 0.02 0.067 Per SD increment 1.27 (0.94, 1.72) 1.24 (0.88, 1.75) Gestational weeks 15–26† IGF-I (ng/mL) Q1: 8.0–134.4 11 54 1.00 1.00 Q2: 135.7–169.6 19 53 1.88 (0.80, 4.46) 2.19 (0.85, 5.63) Q3: 169.8–216.0 27 54 3.06 (1.27, 7.38) 4.35 (1.55, 12.2) Q4: 218.6–428.7 37 53 5.39 (2.13, 13.6) 5.53 (1.94, 15.8) P for trend <0.001 0.001 Per SD increment 1.99 (1.41, 2.82) 2.19 (1.48, 3.23) IGFBP-2 (ng/mL) Q1: 37.9–71.6 39 54 1.00 1.00 Q2: 73.0–96.2 26 53 0.61 (0.31, 1.23) 0.55 (0.23, 1.32) Q3: 96.4–127.5 25 54 0.54 (0.26, 1.11) 0.64 (0.27, 1.56) Q4: 128.1–288.7 4 53 0.07 (0.02, 0.25) 0.03 (0.001, 0.23) P for trend <0.001 <0.001 Per SD increment 0.40 (0.26, 0.60) 0.34 (0.20, 0.59) IGFBP-3 (ng/mL) Q1: 2,575.7–3,977.1 18 54 1.00 1.00 Q2: 3,981.2–4,451.1 19 53 1.15 (0.54, 2.47) 1.11 (0.47, 2.61) Q3: 4,468.8–5,006.0 29 54 1.89 (0.88, 4.05) 2.05 (0.84, 4.99) Q4: 5,031.5–7,854.6 28 53 2.24 (0.94, 5.33) 2.27 (0.86, 6.00) P for trend 0.050 0.067 Per SD increment 1.26 (0.89, 1.79) 1.34 (0.90, 1.99) Molar ratio of IGF-I to IGFBP-3 Q1: 0.007–0.120 11 54 1.00 1.00 Q2: 0.120–0.154 22 53 2.63 (1.10, 6.24) 3.27 (1.22, 8.74) Q3: 0.155–0.193 24 54 3.48 (1.32, 9.15) 3.61 (1.25, 10.4) Q4: 0.194–0.427 37 53 8.31 (2.90, 23.8) 10.5 (3.26, 34.1) P for trend <0.001 <0.001 Per SD increment 2.23 (1.49, 3.33) 2.33 (1.51, 3.60) Q, quartile.
*Adjusted for maternal age (years), gestational age at blood collection (weeks), family history of diabetes (yes/no), and prepregnancy BMI (<24.9, 25.0–25.9, 30.0–34.9, or 35.0–44.9 kg/m2).
†Timing of blood sample collection all preceded the diagnosis of GDM.
‡Range of biomarker concentrations within each quartile among control subjects without GDM.
- Table 3
Partial Spearman correlation coefficients of IGF-I, IGFBP-2, and IGFBP-3 concentrations and molar ratio of IGF-I to IGFBP-3 at gestational weeks 10–14 with subsequent fasting plasma biomarkers at gestational weeks 15–26 among case subjects with GDM and control subjects without GDM*
HOMA-IR Glucose Insulin CRP Case subjects IGF-I 0.24† 0.12 0.25† −0.22† IGFBP-2 −0.34‡ −0.25† −0.33§ −0.05 IGFBP-3 −0.12 −0.02 −0.13 −0.14 Molar ratio of IGF-I to IGFBP-3 0.36‡ 0.13 0.37‡ −0.21† Control subjects IGF-I 0.17† 0.002 0.18† −0.07 IGFBP-2 −0.27‡ −0.02 −0.28‡ −0.11 IGFBP-3 0.04 0.04 0.04 0.04 Molar ratio of IGF-I to IGFBP-3 0.15† −0.05 0.17† −0.13 *P values were adjusted for age, gestational age at blood collection, family history of diabetes, and prepregnancy BMI.
†P < 0.05.
‡P < 0.001.
§P < 0.01.
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