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Convergence in insulin resistance between very severely obese and lean women at the end of pregnancy.

Forbes S, Barr SM, Reynolds RM, Semple S, Gray C, Andrew R, Denison FC, Walker BR, Norman JE - Diabetologia (2015)

Bottom Line: Disrupted intermediary metabolism may contribute to the adverse pregnancy outcomes in women with very severe obesity.Pregnancies complicated by obesity demonstrate attenuation in weight gain and insulin resistance compared with pregnancies in lean women.When targeting maternal metabolism to treat adverse pregnancy outcomes, therapeutic intervention may be most effective applied early in pregnancy.

View Article: PubMed Central - PubMed

Affiliation: Tommy's Centre for Fetal and Maternal Health, MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK. Shareen.Forbes@ed.ac.uk.

ABSTRACT

Aims: Disrupted intermediary metabolism may contribute to the adverse pregnancy outcomes in women with very severe obesity. Our aim was to study metabolism in such pregnancies.

Methods: We recruited a longitudinal cohort of very severely obese (n = 190) and lean (n = 118) glucose-tolerant women for anthropometric and metabolic measurements at early, mid and late gestation and postpartum. In case-control studies of very severely obese and lean women we measured glucose and glycerol turnover during low- and high-dose hyperinsulinaemic-euglycaemic clamps (HEC) at early and late pregnancy and in non-pregnant women (each n = 6-9) and body fat distribution by MRI in late pregnancy (n = 10/group).

Results: Although greater glucose, insulin, NEFA and insulin resistance (HOMA-IR), and greater weight and % fat mass (FM) was observed in very severely obese vs lean participants, the degree of worsening was attenuated in the very severely obese individuals with advancing gestation, with no difference in triacylglycerol (TG) concentrations between very severely obese and lean women at term. Enhanced glycerol production was observed in early pregnancy only in very severely obese individuals, with similar intrahepatic FM in very severely obese vs lean women by late gestation. Offspring from obese mothers were heavier (p = 0.04).

Conclusions/interpretation: Pregnancies complicated by obesity demonstrate attenuation in weight gain and insulin resistance compared with pregnancies in lean women. Increased glycerol production is confined to obese women in early pregnancy and obese and lean individuals have similar intrahepatic FM by term. When targeting maternal metabolism to treat adverse pregnancy outcomes, therapeutic intervention may be most effective applied early in pregnancy.

No MeSH data available.


Related in: MedlinePlus

Infusion studies in obese and lean control pregnant and non-pregnant participants. (a) EGP (mg [kgFFM]−1 min−1) at baseline and low-dose insulin infusion; (b) M/I index is the stimulated glucose disposal rates with high-dose insulin infusion (mg [kgFFM]−1 min−1 divided by insulin concentrations at steady state [pmol/l × 10]); (c) glycerol turnover (mg [kgFFM]−1 min−1) at baseline, low-dose and high-dose insulin infusions. Two-way ANOVA analyses were performed on the variables to determine the independent effects of BMI and advancing gestation/non-pregnant state and their interaction. Obese (white bars); lean control (black bars); *p < 0.05, **p < 0.01, difference in obese vs lean at 19 weeks [w], 36 weeks and non-pregnant (NP). †p < 0.05 by two-way ANOVA for obese vs lean; ‡p < 0.05 by two-way ANOVA for gestational age vs non-pregnant status; §p < 0.05 for two-way ANOVA interaction between obese vs lean and gestational age vs non-pregnant status. See ESM Figs 2 and 3 and ESM Table 2
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Fig2: Infusion studies in obese and lean control pregnant and non-pregnant participants. (a) EGP (mg [kgFFM]−1 min−1) at baseline and low-dose insulin infusion; (b) M/I index is the stimulated glucose disposal rates with high-dose insulin infusion (mg [kgFFM]−1 min−1 divided by insulin concentrations at steady state [pmol/l × 10]); (c) glycerol turnover (mg [kgFFM]−1 min−1) at baseline, low-dose and high-dose insulin infusions. Two-way ANOVA analyses were performed on the variables to determine the independent effects of BMI and advancing gestation/non-pregnant state and their interaction. Obese (white bars); lean control (black bars); *p < 0.05, **p < 0.01, difference in obese vs lean at 19 weeks [w], 36 weeks and non-pregnant (NP). †p < 0.05 by two-way ANOVA for obese vs lean; ‡p < 0.05 by two-way ANOVA for gestational age vs non-pregnant status; §p < 0.05 for two-way ANOVA interaction between obese vs lean and gestational age vs non-pregnant status. See ESM Figs 2 and 3 and ESM Table 2

Mentions: The technical success of the HECs are shown (ESM Figs 2 and 3; ESM Table 2). At 19 weeks’ gestation, basal glucose and insulin concentrations (i.e. no insulin infusion) were greater in very severely obese vs lean women but were comparable otherwise (ESM Table 2). In the absence of insulin, EGP (derived from [2H2]glucose infusion) did not change during pregnancy in either lean or very severely obese women, and was not different in pregnancy compared with non-pregnant controls (Fig. 2). During low-dose insulin infusion, EGP was variable in non-pregnant women, and similar between groups; in pregnancy, EGP was suppressed in very severely obese but not lean women at 19 and 36 weeks’ gestation (Fig. 2), suggesting greater hepatic insulin sensitivity during pregnancy in obese women. During the high-dose HECs, insulin-stimulated glucose disposal (M/I) showed a marked diminution from early to late pregnancy in the lean group. Glucose disposal was lower in very severely obese vs lean women at 19 weeks’ gestation only with similar insulin-stimulated glucose disposal by 36 weeks’ gestation (Fig. 2).


Convergence in insulin resistance between very severely obese and lean women at the end of pregnancy.

Forbes S, Barr SM, Reynolds RM, Semple S, Gray C, Andrew R, Denison FC, Walker BR, Norman JE - Diabetologia (2015)

Infusion studies in obese and lean control pregnant and non-pregnant participants. (a) EGP (mg [kgFFM]−1 min−1) at baseline and low-dose insulin infusion; (b) M/I index is the stimulated glucose disposal rates with high-dose insulin infusion (mg [kgFFM]−1 min−1 divided by insulin concentrations at steady state [pmol/l × 10]); (c) glycerol turnover (mg [kgFFM]−1 min−1) at baseline, low-dose and high-dose insulin infusions. Two-way ANOVA analyses were performed on the variables to determine the independent effects of BMI and advancing gestation/non-pregnant state and their interaction. Obese (white bars); lean control (black bars); *p < 0.05, **p < 0.01, difference in obese vs lean at 19 weeks [w], 36 weeks and non-pregnant (NP). †p < 0.05 by two-way ANOVA for obese vs lean; ‡p < 0.05 by two-way ANOVA for gestational age vs non-pregnant status; §p < 0.05 for two-way ANOVA interaction between obese vs lean and gestational age vs non-pregnant status. See ESM Figs 2 and 3 and ESM Table 2
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig2: Infusion studies in obese and lean control pregnant and non-pregnant participants. (a) EGP (mg [kgFFM]−1 min−1) at baseline and low-dose insulin infusion; (b) M/I index is the stimulated glucose disposal rates with high-dose insulin infusion (mg [kgFFM]−1 min−1 divided by insulin concentrations at steady state [pmol/l × 10]); (c) glycerol turnover (mg [kgFFM]−1 min−1) at baseline, low-dose and high-dose insulin infusions. Two-way ANOVA analyses were performed on the variables to determine the independent effects of BMI and advancing gestation/non-pregnant state and their interaction. Obese (white bars); lean control (black bars); *p < 0.05, **p < 0.01, difference in obese vs lean at 19 weeks [w], 36 weeks and non-pregnant (NP). †p < 0.05 by two-way ANOVA for obese vs lean; ‡p < 0.05 by two-way ANOVA for gestational age vs non-pregnant status; §p < 0.05 for two-way ANOVA interaction between obese vs lean and gestational age vs non-pregnant status. See ESM Figs 2 and 3 and ESM Table 2
Mentions: The technical success of the HECs are shown (ESM Figs 2 and 3; ESM Table 2). At 19 weeks’ gestation, basal glucose and insulin concentrations (i.e. no insulin infusion) were greater in very severely obese vs lean women but were comparable otherwise (ESM Table 2). In the absence of insulin, EGP (derived from [2H2]glucose infusion) did not change during pregnancy in either lean or very severely obese women, and was not different in pregnancy compared with non-pregnant controls (Fig. 2). During low-dose insulin infusion, EGP was variable in non-pregnant women, and similar between groups; in pregnancy, EGP was suppressed in very severely obese but not lean women at 19 and 36 weeks’ gestation (Fig. 2), suggesting greater hepatic insulin sensitivity during pregnancy in obese women. During the high-dose HECs, insulin-stimulated glucose disposal (M/I) showed a marked diminution from early to late pregnancy in the lean group. Glucose disposal was lower in very severely obese vs lean women at 19 weeks’ gestation only with similar insulin-stimulated glucose disposal by 36 weeks’ gestation (Fig. 2).

Bottom Line: Disrupted intermediary metabolism may contribute to the adverse pregnancy outcomes in women with very severe obesity.Pregnancies complicated by obesity demonstrate attenuation in weight gain and insulin resistance compared with pregnancies in lean women.When targeting maternal metabolism to treat adverse pregnancy outcomes, therapeutic intervention may be most effective applied early in pregnancy.

View Article: PubMed Central - PubMed

Affiliation: Tommy's Centre for Fetal and Maternal Health, MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK. Shareen.Forbes@ed.ac.uk.

ABSTRACT

Aims: Disrupted intermediary metabolism may contribute to the adverse pregnancy outcomes in women with very severe obesity. Our aim was to study metabolism in such pregnancies.

Methods: We recruited a longitudinal cohort of very severely obese (n = 190) and lean (n = 118) glucose-tolerant women for anthropometric and metabolic measurements at early, mid and late gestation and postpartum. In case-control studies of very severely obese and lean women we measured glucose and glycerol turnover during low- and high-dose hyperinsulinaemic-euglycaemic clamps (HEC) at early and late pregnancy and in non-pregnant women (each n = 6-9) and body fat distribution by MRI in late pregnancy (n = 10/group).

Results: Although greater glucose, insulin, NEFA and insulin resistance (HOMA-IR), and greater weight and % fat mass (FM) was observed in very severely obese vs lean participants, the degree of worsening was attenuated in the very severely obese individuals with advancing gestation, with no difference in triacylglycerol (TG) concentrations between very severely obese and lean women at term. Enhanced glycerol production was observed in early pregnancy only in very severely obese individuals, with similar intrahepatic FM in very severely obese vs lean women by late gestation. Offspring from obese mothers were heavier (p = 0.04).

Conclusions/interpretation: Pregnancies complicated by obesity demonstrate attenuation in weight gain and insulin resistance compared with pregnancies in lean women. Increased glycerol production is confined to obese women in early pregnancy and obese and lean individuals have similar intrahepatic FM by term. When targeting maternal metabolism to treat adverse pregnancy outcomes, therapeutic intervention may be most effective applied early in pregnancy.

No MeSH data available.


Related in: MedlinePlus