Carbohydrate and lipid metabolisms in pregnant women with excessive gestational weight gain

Ivano-Frankivsk

Anthropometry was performed at the first prenatal visit (9.8±1.4 weeks (95 % CI 9.6-10.1)), at 22-24 weeks, and before the delivery. Patients were weighed with the electronic scale to the nearest 0.1 kg. Height was measured using a digital stadiometer with an accuracy of 1.0 cm. GWG was evaluated by the difference between the weight before delivery and pre-pregnancy. Pre-pregnancy weight status of patients was assessed with BMI (kilogram/meter²) calculated from pre-pregnancy weight and height. Information on the body weight of women before pregnancy was obtained by interviewing patients and medical records. The results were compared to the recommended weight gain according to the national recommendations [2].

Lipid profile was found on the basis of the laboratory determination of the concentration of triglycerides (TG) (Triglycerides SpL (SpinLab LLC, Ukraine)), total cholesterol (TC) (Cholesterol SPL (LLC SpinLab, Ukraine)), high-density lipoproteins, low-density lipoproteins and very low-density lipoproteins (HDL, LDL, VLDL) (“HDL-Cholesterol SPL” (LLC “SpinLab”, Ukraine)). Insulin concentration at baseline were measured by the immunoassay method (Insulin Test System-2425-300 (Monobind Inc., USA)). Insulin resistance index was calculated by the formula for the homeostasis model assessment (HOMO-IR): fasting glucose (mmol/l) x fasting insulin (pU/ml)/22.5. Biochemical analyses were performed in according to standard methods [1] in the centralized clinical and diagnostic laboratory of the Regional Perinatal Centre (Ivano-Frankivsk). Percentage of body fat mass was determined using spectral bioimpedansometry (with the use of “Diamant-aist” analyzer КМ-АР-01) connected to a computer [13].

Antenatal care with nutrition and physical activity recommendations was carried out in accordance with existing Ukrainian guidelines [2].

The results were statistically analyzed using Statistica 6.0 program pack (StatSoft Inc.,USA) and the Microsoft Excel statistical analysis package, parametric methods of analysis were used. The parameters are presented as mean arithmetic value, mean standard deviation (x±SD). To represent the accuracy of the calculated arithmetic mean odds ratio (OR), 95 % confidence interval (CI), and p-value were obtained. Pearson's correlation-regression analysis method (r) was used to determine the presence, strength, and direction of the relationship between the parameters. The differences between the selections were considered statistically reliable at p<0.05 (Tukey's test).

Results of the study and their discussion. Analysis of carbohydrate metabolism in the examined women has showed a significant positive association between the value of GWG and glucose level (r=0.44, p=0.000; r=0.67, p=0.000), insulin level (r=0.74, p=0.000; r=0.84, p=0.000) та HOMO-IR (r=0.72, p=0.000; r=0.81, p=0,000) respectively in the second and third trimesters of pregnancy. However, the dynamics of these indicators during the gestational period differed in groups (fig. 1 a-c).

Fig. 1 Dynamics of carbohydrate metabolism in recommended and excessive GWG groups of women: a - glucose concentration, mmol/l; b - insulin, мIU/ml; c - HOMO-IR; * - compared to the indices of the first trimester (p<0.05), # - compared to the indices of the recommended GWG group of women (p<0.05)

Thus, in recommended GWG group of women there was no significant dynamics of blood glucose level during pregnancy (р>0.05). We have seen elevation of insulin concentration in early pregnancy compared to the reference values of non-pregnant women (0.7-9.0 мIU/ml) and an increase until the end of pregnancy, but these changes were not statistically significant (p>0.05). Women in this group no significant dynamics of HOMO-IR during pregnancy were diagnosed. In excessive weight gain women insulin level and HOMOIR have been shown to increase gradually during pregnancy. In the third trimester, the insulin concentration 1.7-fold (p<0.05), HOMO-IR 1.9-fold (p<0.05) were higher than in the early terms. At the end of pregnancy HOMO-IR was 1.8-fold (p<0.05) significantly higher compared to normal GWG patients and exceeded the reference values (0-2.7) (p<0.05).

The results of the study of lipid metabolism have shown that the concentration of atherogenic lipoproteins increased during pregnancy, regardless of the category of GWG and reflected the body weight gain due to the fat component. Detailed analysis in the groups has showed a significant increase of TG levels 1.8-fold (p<0.05), LDL 1.3-fold (p<0.05) in the third trimester compared to early terms and the absence of significant changes in the levels of TC, HDL, VLDL during pregnancy in normal GWG women (p>0.05) (fig. 2 a - e).

Fig. 2 Dynamics of lipid metabolism in normal and excessive GWG groups of women: a - concentration of TG, mmol/l; b - TC, mmol/l; c - HDL, mmol/l; d - LDL, mmol/l; e - VLDL, mmol/l; * - compared to the indices of the first trimester (p<0.05), # - compared to the indices of recommended GWG group of women (p<0.05)

In excessive weight gain women, we have found a statistically significant increase in certain indicators in the second trimester and dyslipidemia at the end of pregnancy. Thus, the concentration of TG 2.0-fold (p<0.01), TC 1.3-fold (p<0.01), LDL 2.2-fold (p<0.05), VLDL 1.8-fold (p<0.05) were significantly higher in the second trimester and 2.3-fold (p<0.001), 1.2-fold (p<0.05), 1.4-fold (p<0.02) and 3.0-fold (p<0.001), respectively, in the third trimester compared to early pregnancy. It should be noted, that TG level at the end of pregnancy in excessive GWG women was significantly 1.4-fold (p<0.05) higher than in recommended weight gain women. TG are the main source of the mother's metabolic needs, and their excessive accumulation before delivery indicates a high risk of overweight in the postpartum period.

We've investigated that hyperlipoproteinemia was correlated with GWG: TG (r=0.19, p=0.016; r=0.59, p=0.000), VLDL (r=0.33, p=0.000; r=0.51, p=0.000) in the second and third trimesters, respectively, regardless of the final level of weight gain. At the end of pregnancy, there was a direct relationship between weight gain and levels of TG (r=0.47, p=0.000), LDL (r=0.34, p=0.000) and inverse with HDL (r=0.54, p=0.000). It was important to identify a significant association between high concentrations of TG (r=0.34, p=0.000), TC (r=0.51, p=0.000), HDL (r=0.20, p=0.011), LDL (r=0.35, p=0.000), VLDL (r=0.33, p=0.000) in mid-pregnancy and GWG in late pregnancy.

Analysis of the association between fat mass, the main component of pathological weight gain, with lipid profile levels indicated a significant correlation of high levels of atherogenic lipids in mid-pregnancy with an excessive increase in the percentage of body fat mass: TG (r=0.65, p=0.000; r=0.64, p=0.000), TC (r=0.46, p=0.000; r=0.61, p=0.000), HDL (r=0.32, p=0.0002; r=0.40, p=0.000), LDL (r=0.36, p=0.000; r=0.53, p=0.000), VLDL (r=0.79, p=0.000; r=0.84, p=0.000) in both the second and third trimesters, respectively. In the middle of pregnancy there was a positive relationship between the concentration of TG (r=0.74, p=0.000), TC (r=0.61, p=0.000), LDL (r=0.45, p=0.000), VLDL (r=0.75, p=0.000) and inverse correlation of HDL (r=0.26, p=0.001) with the percentage of body fat mass at the end of pregnancy. This may indicate that the excessive accumulation of fat mass in late pregnancy is a clinical manifestation of hyperlipoproteinemia at the earlier terms. According to modern knowledge, weight gain in non-pregnant women is associated with the development of obesity, insulin resistance and type 2 diabetes mellitus. It is considered, that such mechanisms of body weight is the basis of changes in glucose metabolism during pregnancy. Changes in carbohydrate and lipid metabolisms during normal pregnancy initiate the accumulation of maternal fat stores in the first half of pregnancy and increase mobilization in the late stages, regardless of pre-pregnancy body weight. We have proved in our work that recommended weight gain during pregnancy is accompanied with compensated hyperinsulinemia on the background of normal HOMO-IR, which indicates the activation of compensatory mechanisms of the body to maintain tissue sensitivity to insulin for adequate energy supply to cells.

In excessive GWG pregnant, we've found significant hyperinsulinemia and an increased HOMOIR in late pregnancy, which indicate the development of insulin resistance, which leads to impaired glucose uptake into insulin-dependent tissues: muscle, fat, liver. The studies of Kampmann U. et al. [8], Sonagra AD. et al. [12] also showed the state of hyperinsulinemia and insulin resistance during pregnancy, however, they did not take into account the difference in GWG, and compare the results with non-pregnant women. Moyce BL. et al. [9] and Powe CE. et al. [10] demonstrated an enhanced insulin response during a normal pregnancy, but suggested that excessive GWG, pre-pregnancy obesity, and genetic predisposition may cause beta-cell adaptation failure. In a current study (2020) Alvarado FL. et al. noted that the rate of insulin sensitivity before pregnancy is a strong determinant of changes in gestational glucose metabolism [4].

It is known, that the leading etiopathogenetic mechanisms of excessive weight are associated with energy imbalance - more energy intake from food against loss, which affects the synthesis of triglycerides and their increased deposition in fat depots [3]. Improper eating behavior of pregnant women with excessive amounts of calories, sedentary lifestyle, reduced physical activity lead to reduced energy consumption and play a leading role in the excessive GWG. Hypertriglyceridemia, hyperlipoproteinemia, inhibited glucose uptake into the tissues due to the progression of insulin resistance are observed in excessive GWG women, are the pathogenetic basis of energy deficiency that reduced adaptive capacity of the maternal organism to gestation.

Conclusion

During pregnancy the changers in carbohydrate and lipid metabolisms are determined by the level of gestational weight gain. Pathological pre-pregnancy body weight is an aggravating factor, but not significant. Excessive weight gain is associated with the development of pathological insulin resistance and dyslipidemia, regardless of weight before pregnancy. Pathological weight gain diagnosed in the second and third trimesters of pregnancy is a clinical manifestation of impaired carbohydrate and fat metabolisms at an earlier terms with progressing to the end of pregnancy. Consequently, excessive gestational weight gain can be considered as the marker of disruption of adaptive metabolic changes in conditions of increased energy demand, with the risk of weight retention, development of obesity and metabolic syndrome after delivery.

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