Gestational Weight Gain and Maternal Glucose Metabolism

In This Article

Abstract and Introduction

Abstract

Context: Efforts to decrease the risk of developing metabolic complications of pregnancy such as gestational diabetes (GDM) through lifestyle intervention (decreasing excessive gestational weight gain (GWG)) during pregnancy have met with limited success.

Objective: The purpose of this study was to determine the relationship between the longitudinal changes in weight/body composition and insulin sensitivity and response in women with normal glucose tolerance (NGT) and those who developed GDM.

Design: We conducted a secondary analysis of a prospective cohort developed before conception and again at 34 to 36 weeks gestation. A total of 29 NGT and 17 GDM women were evaluated for longitudinal changes in insulin sensitivity/response using the hyperinsulinemic-euglycemic clamp and an IV-glucose tolerance test. Body composition was estimated using hydrodensitometry. Both absolute change (Δ) and relative change (%Δ) between these 2 time points were calculated. We performed simple and multiple linear regression analysis to assess the relationship between GWG and measures of glucose metabolism, ie, insulin sensitivity and response.

Results: Based on the primary study design there was no significant difference in clinical characteristics between women with NGT and those developing GDM. Prior to pregnancy, women who developed GDM had lower insulin sensitivity levels (P = 0.01) compared with NGT women. Absolute change and %Δ in insulin sensitivity/insulin response and body weight/body composition were not significantly different between NGT and GDM women. Changes in body weight contributed to only 9% of the Δ in insulin sensitivity both in women developing GDM and NGT women.

Conclusions: These data suggest that other factors—such as maternal pre-pregnancy insulin sensitivity and placental derived factors affecting insulin sensitivity—rather than maternal GWG account for the changes in glucose metabolism during human pregnancy.

Introduction

Gestational diabetes (GDM) is a common metabolic disorder of pregnancy affecting from 5% to 20% of pregnant women, depending on factors such as (but not limited to) the criteria used for diagnosis, ethnicity, family history of type 2 diabetes or past history of GDM, and prevalence of obesity in the population.^[1] In addition to adverse maternal and neonatal pregnancy outcomes, GDM increases the risk of maternal impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes 5 to 10 years postpartum.^[2] Further, GDM is a risk factor for childhood metabolic dysfunction and obesity.^[3]

Gestational weight gain (GWG) is a physiologic and fundamental adaptation for maternal fetal well-being.^[4] GWG outside of the Institute of Medicine guidelines are associated with adverse outcomes, not only for the mother but for her offspring.^[5,6] Studies indicate that 45% to 65% of women who begin pregnancy overweight or obese exceed Institute of Medicine GWG recommendations,^[5,6] increasing the risk of postpartum weight retention and beginning subsequent pregnancies with higher weight and adiposity. Increased GWG early during pregnancy has been associated with the development of GDM,^[7,8] but the role of excess GWG in the development of GDM is still unclear.

In nonpregnant individuals, significant weight gain has been associated with increased insulin resistance, and conversely, lifestyle interventions with goals of 5% to 7% weight loss have significantly improved metabolic function.^[9] However, efforts to decrease the risk of GDM and other metabolic dysfunction through lifestyle interventions—primarily healthy eating and increased physical activity during pregnancy with the goal of avoiding excessive GWG—have met with limited success.^[10–13]

In late gestation, women developing GDM have both increased insulin resistance and inadequate pancreatic beta-cell insulin response to maintain normoglycemia compared with a control group.^[14] The underlying rationale for many of these clinical trials has been that by decreasing excessive GWG, lifestyle interventions decrease the progression of insulin resistance. The relationship between GWG and changes in maternal insulin resistance are not well described, and few studies have baseline measures before pregnancy.^[15,16]

Hence, the purpose of this secondary analysis was to examine the relationship between the longitudinal changes in weight/body composition and insulin sensitivity/response and to estimate its impact in women with normal glucose tolerance (NGT) and those who developed GDM.

Table 1. Pre-Gravid Maternal Characteristics
	NGT (n = 29)	GDM (n = 17)	P value
Maternal age (years)	31.6 ± 4	32 ± 4	0.69
Parity	0.9 ± 0.6	1.0 ± 0.4	0.32
Weight (kg)	63 ± 13	68 ± 15	0.22
Fat mass (kg)	19 ± 10	21 ± 12	0.44
Body fat (%)	28 ± 8	30 ± 9	0.54
Fat-free mass (kg)	44 ± 5	46 ± 4	0.09
Risk factors for GDM (n)
1. Family history DM	11	14	0.005
2. Previous GDM	0	12	<0.0001
*Insulin sensitivity (mg/kgFFM/min)100*	13 ± 4	9 ± 6	0.01
Insulin response (first-phase)	235 ± 136	246 ± 132	0.80
Disposition index (IS × IR)	28 ± 12	20 ± 18	0.19

Values are mean ± SD. P value was calculated using Student t test. Frequency data were analyzed by Chi-square test.
Abbreviations: GDM, gestational diabetes mellitus; IS, insulin sensitivity; IR, insulin response; NGT, normal glucose tolerance.

Table 2. Study Variables; Absolute and Relative Change Difference Between NGT and GDM Women
Variables	Absolute (Δ)			Relative (%Δ)
Variables	NGT (n = 29)	GDM (n = 17)	P value	NGT (n = 29)	GDM (n = 17)	P value
Weight (kg)	13 ± 5	12 ± 4	0.27	22 ± 7.7	18 ± 7.4	0.14
Fat mass (kg)	5 ± 3	3 ± 4	0.06	32 ± 26	20 ± 21	0.06
Body fat (%)	2 ± 4	-0.4 ± 4	0.07	9 ± 16	0.8 ± 12	0.07
Fat-free mass (kg)	8 ± 3	9 ± 3	0.55	18 ± 7	19 ± 6	0.90
Insulin sensitivity	-5 ± 2	-4 ± 4	0.35	-29 ± 17	-33 ± 23	0.56
Insulin response	209 ± 122	168 ± 232	0.54	102 ± 84	90 ± 112	0.73
Disposition index	5 ± 7	3 ± 10	0.44	25 ± 40	12 ± 70	0.56

Values are mean ± SD. Absolute and relative change between values at 34–36 weeks and the pre-pregnancy period. P value was calculated by Student t test and it shows the difference between NGT and GDM women.
Abbreviations: GDM, gestational diabetes mellitus; NGT, normal glucose tolerance.

Table 3. Relationship Between Absolute Changes of Glucose Metabolism Parameters and Absolute Change in Body Composition
Δ Absolute^a	Insulin sensitivity				Insulin response				Disposition index
Δ Absolute^a	β	SE	P value	R²	β	SE	P value	R²	β	SE	P value	R²
Body weight
ALL ^b	-0.44	0.13	0.001	0.20	-0.01	0.18	0.94	0.00	-0.32	0.17	0.06	0.10
NGT	-0.38	0.12	0.002	0.24	0.23	0.21	0.27	0.07	-0.07	0.20	0.70	0.01
GDM	-0.49	0.28	0.08	0.15	-0.30	0.27	0.26	0.07	-0.61	0.25	0.01	0.26
Fat mass
ALL ^b	-0.36	0.13	0.008	0.13	0.03	0.18	0.86	0.00	-0.28	0.18	0.12	0.07
NGT	-0.25	0.14	0.07	0.10	0.18	0.26	0.48	0.04	-0.16	0.23	0.47	0.04
GDM	-0.44	0.28	0.11	0.13	-0.13	0.26	0.61	0.02	-0.43	0.26	0.09	0.14
Body fat (%)
ALL ^b	-0.24	0.14	0.08	0.06	0.03	0.17	0.83	0.00	-0.12	0.17	0.48	0.01
NGT	-0.17	0.13	0.20	0.05	0.13	0.19	0.49	0.02	-0.10	0.17	0.55	0.02
GDM	-0.27	0.33	0.41	0.04	0.13	0.29	0.53	0.02	-0.24	0.31	0.44	0.02
Fat-free mass
ALL ^b	-0.24	0.14	0.09	0.05	-0.05	0.18	0.76	0.00	-0.17	0.17	0.31	0.03
NGT	-0.26	0.12	0.02	0.14	0.13	0.18	0.47	0.02	0.01	0.16	0.93	0.00
GDM	-0.24	0.36	0.50	0.03	-0.41	0.33	0.22	0.09	-0.55	0.34	0.11	0.14

Abbreviations: β, beta coefficient; GDM, gestational diabetes mellitus; NGT, normal glucose tolerance.
^aAbsolute change, individual difference between values at 34–36 weeks and the pre-pregnancy period.
^bData were analyzed with both NGT and GDM women together. A positive coefficient implies an increase in absolute change. P value was calculated using simple linear regression.

Table 4. Multilinear Regression Analysis for Factors That Affect Absolute Change in Insulin Sensitivity, Insulin Response, and Disposition Index
	Adjusted R square	Δ R square (ΔR²)	P value
Insulin sensitivity (Δ)
Maternal Age (years)	0.2		0.11
Gestational age (weeks)	0.18	0.16	0.03
Maternal PP weight	0.22	0.04	0.20
Parity	0.23	0.01	0.13
Body weight (Δ)	0.32	0.09	0.02
Group (NGT)	0.33	0.01	0.27
Insulin response (Δ)
Maternal age (years)	0.8		0.05
Maternal PP weight	0.12	0.04	0.21
Group (NGT)	0.13	0.01	0.26
Disposition index (Δ)
Maternal age (years)	0.03		0.15
Body weight (Δ)	0.09	0.06	0.05
Group (NGT)	0.13	0.04	0.12

Absolute (Δ) changes between values at 34–36 weeks and the pre-pregnancy period. P value was calculated using multiple linear regression model. Abbreviations: NGT, normal glucose tolerance; PP, pre-pregnancy.