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. 2023 Mar 3;13(3):470.
doi: 10.3390/biom13030470.

Insulin Resistance Is Associated with an Unfavorable Serum Lipoprotein Lipid Profile in Women with Newly Diagnosed Gestational Diabetes

Mikael Huhtala  1   2 , Tapani Rönnemaa  3   4 , Kristiina Tertti  1   2
Affiliations

Insulin Resistance Is Associated with an Unfavorable Serum Lipoprotein Lipid Profile in Women with Newly Diagnosed Gestational Diabetes

Mikael Huhtala et al. Biomolecules. .

Abstract

Background: Gestational diabetes (GDM) is associated with various degrees of insulin resistance-a feature related to increased risk of adverse perinatal outcomes. We aimed to determine the previously poorly investigated associations between maternal insulin resistance and serum fasting metabolome at the time of GDM diagnosis.

Methods: Serum lipoprotein and amino acid profile was analyzed in 300 subjects with newly diagnosed GDM using a validated nuclear magnetic resonance spectroscopy protocol. Associations between insulin resistance (homeostasis model assessment of insulin resistance, HOMA2-IR) and serum metabolites were examined with linear regression.

Results: We found insulin resistance to be associated with a distinct lipid pattern: increased concentration of VLDL triglycerides and phospholipids and total triglycerides. VLDL size was positively related and LDL and HDL sizes were inversely related to insulin resistance. Of fatty acids, increased total fatty acids, relative increase in saturated and monounsaturated fatty acids, and relative decrease in polyunsaturated and omega fatty acids were related to maternal insulin resistance.

Conclusions: In newly diagnosed GDM, the association between maternal insulin resistance and serum lipoprotein profile was largely as described in type 2 diabetes. Lifestyle interventions aiming to decrease insulin resistance from early pregnancy could benefit pregnancy outcomes via more advantageous lipid metabolism.

Keywords: GDM; gestational diabetes; insulin resistance; metabolome; metabolomics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Associations between insulin resistance and serum metabolites. Regression β-estimates with 95% confidence intervals are given for each association adjusted for BMI class and gestational age at sampling. Filled circles denote significant (p < 0.01) and open circles nonsignificant associations. BCAA: branched-chain amino acids, FA: fatty acids, MUFA: monounsaturated FAs, PUFA: polyunsaturated FAs, SFA: saturated FAs.
Figure 2
Figure 2
Associations between insulin resistance and lipoprotein lipids. Regression β-estimates with 95% confidence intervals are given for each association adjusted for BMI class and gestational age at sampling. Filled circles denote significant (p < 0.01) and open circles nonsignificant associations. S/M/L: small/medium/large, XS: very small, XL: very large, XXL: extremely large.
Figure 3
Figure 3
Associations between insulin resistance and average lipoprotein particle size. Insulin resistance, as estimated by log-HOMA2-IR, versus mean particle diameter (nm). Trend line depicts regression beta coefficient with the respective p-values.
Figure 4
Figure 4
Lipoprotein metabolism and associations between insulin resistance and lipids in lipoprotein subfractions. Very-low-density lipoproteins (VLDLs) are synthesized in the liver. Lipoprotein lipase (LPL) hydrolyzes triglycerides (TGs) in VLDLs to glycerol and free fatty acids (FFAs) to be stored in adipose tissue. VLDLs are transformed into intermediate density lipoproteins (IDLs) and subsequently into low-density lipoproteins (LDLs), which are metabolized in the liver. High-density lipoproteins (HDLs) transport cholesterol (C) from other tissues to liver. Cholesterol ester transfer protein (CETP) exchanges C and TG between LDL, HDL, and VLDL. Hepatic lipase (HL) hydrolyzes TG and phospholipids (PLs) in IDL, LDL, and HDL, hence promoting formation of smaller LDL and HDL particles. The associations between insulin resistance (HOMA2-IR) and particle concentration, C, and TG in different lipoprotein subfractions (XS–XXL) are shown as standardized regression coefficients with 95% confidence intervals. Regression coefficients were adjusted for gestational age at sampling and maternal BMI class.
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