Normalizing Metabolism in Diabetic Pregnancy: Lipids
Normalizing Metabolism in Diabetic Pregnancy: Lipids
Many, but not all, studies examining lipids in women with preexisting diabetes or GDM in pregnancy report a deviation from the usual patterns of pregnancy-associated changes in maternal lipids. Changes in maternal lipoproteins or differences in the triglyceride, cholesterol, or apolipoprotein content of the maternal lipoproteins have been reported in pregnancies complicated by diabetes (Supplementary Table 1).
The most common finding in studies examining pregnant women with well-controlled type 1 diabetes is that the changes in lipoproteins are similar to women with uncomplicated pregnancy. However, the coexistence of other maternal factors, including maternal obesity, preexisting metabolic syndrome, poor glycemic control, renal disease, and the development of preeclampsia, has been associated with an exaggeration of the gestational change in maternal lipoproteins. Women with type 1 diabetes and coexistent metabolic syndrome have lower HDL cholesterol (HDL-C) and higher triglycerides in the first trimester, and although both women with and without metabolic syndrome showed an increase in cholesterol, HDL-C, LDL cholesterol (LDL-C), and triglycerides from the first to third trimester, the increase (in all except HDL-C) was nonsignificant in women with preexisting metabolic syndrome. Women with type 1 diabetes and renal disease (as defined by the presence of >0.05 g protein/24 h in urine) showed a greater increase in cholesterol and LDL-C but not triglycerides across gestation than those with no renal disease. Women with well-controlled type 1 diabetes (mean HbA1c 6.1%, 43 mmol/mol) had lipoprotein levels comparable to women with uncomplicated pregnancy, but those with poor control (HbA1c 8.3%, 67 mmol/mol) at the time of delivery had higher triglycerides and VLDL and lower HDL3 levels. Women with type 1 diabetes who go on to develop preeclampsia later in pregnancy have higher LDL-C and cholesterol than women with type 1 diabetes who do not develop preeclampsia.
Data on lipids in women with type 2 diabetes in pregnancy are scarce. Studies have shown higher free fatty acid levels compared with normal pregnancy and higher triglyceride and lower HDL-C levels in the first trimester when compared with women with type 1 diabetes in pregnancy, or no difference in any lipoprotein compared with either type 1 diabetes or GDM. However, <;80 women with type 2 diabetes were included in these reports.
In women with GDM, maternal triglycerides have been reported to be increased in all trimesters of pregnancy, although this is not a universal finding. Similarly, maternal cholesterol has been reported as increased or unchanged across gestation. Studies in women with GDM have shown no difference or a decline in LDL-C concentration but with increased levels of small, dense LDL and increased LDL oxidation.
Maternal obesity is associated with a range of adverse outcomes for mother and infant, including higher rates of preeclampsia, GDM, and macrosomia. Maternal obesity is associated with an increase in maternal lipid levels, higher triglycerides and VLDL, and lower HDL-C than observed in lean women. Obese women without GDM have been shown to have higher glucose profiles on continuous glucose monitoring performed during pregnancy than normal-weight women; the mean time spent with glucose >6.7 mmol/L is longer in obese than normal-weight women (209 ± 62 min vs. 33 ± 12 min, P = 0.001). In addition to changes in lipid and glucose metabolism, there is greater inflammation and more vascular endothelial dysfunction associated with obese pregnancy. Disentangling the effect of maternal obesity per se from that of maternal diabetes on maternal metabolism and pregnancy outcomes in the women with obesity and diabetes in pregnancy is almost impossible without very large cohorts with refined metabolic measures.
Maternal Lipids in Diabetic Pregnancy
Many, but not all, studies examining lipids in women with preexisting diabetes or GDM in pregnancy report a deviation from the usual patterns of pregnancy-associated changes in maternal lipids. Changes in maternal lipoproteins or differences in the triglyceride, cholesterol, or apolipoprotein content of the maternal lipoproteins have been reported in pregnancies complicated by diabetes (Supplementary Table 1).
Preexisting Type 1 Diabetes
The most common finding in studies examining pregnant women with well-controlled type 1 diabetes is that the changes in lipoproteins are similar to women with uncomplicated pregnancy. However, the coexistence of other maternal factors, including maternal obesity, preexisting metabolic syndrome, poor glycemic control, renal disease, and the development of preeclampsia, has been associated with an exaggeration of the gestational change in maternal lipoproteins. Women with type 1 diabetes and coexistent metabolic syndrome have lower HDL cholesterol (HDL-C) and higher triglycerides in the first trimester, and although both women with and without metabolic syndrome showed an increase in cholesterol, HDL-C, LDL cholesterol (LDL-C), and triglycerides from the first to third trimester, the increase (in all except HDL-C) was nonsignificant in women with preexisting metabolic syndrome. Women with type 1 diabetes and renal disease (as defined by the presence of >0.05 g protein/24 h in urine) showed a greater increase in cholesterol and LDL-C but not triglycerides across gestation than those with no renal disease. Women with well-controlled type 1 diabetes (mean HbA1c 6.1%, 43 mmol/mol) had lipoprotein levels comparable to women with uncomplicated pregnancy, but those with poor control (HbA1c 8.3%, 67 mmol/mol) at the time of delivery had higher triglycerides and VLDL and lower HDL3 levels. Women with type 1 diabetes who go on to develop preeclampsia later in pregnancy have higher LDL-C and cholesterol than women with type 1 diabetes who do not develop preeclampsia.
Preexisting Type 2 Diabetes
Data on lipids in women with type 2 diabetes in pregnancy are scarce. Studies have shown higher free fatty acid levels compared with normal pregnancy and higher triglyceride and lower HDL-C levels in the first trimester when compared with women with type 1 diabetes in pregnancy, or no difference in any lipoprotein compared with either type 1 diabetes or GDM. However, <;80 women with type 2 diabetes were included in these reports.
GDM
In women with GDM, maternal triglycerides have been reported to be increased in all trimesters of pregnancy, although this is not a universal finding. Similarly, maternal cholesterol has been reported as increased or unchanged across gestation. Studies in women with GDM have shown no difference or a decline in LDL-C concentration but with increased levels of small, dense LDL and increased LDL oxidation.
Maternal Obesity
Maternal obesity is associated with a range of adverse outcomes for mother and infant, including higher rates of preeclampsia, GDM, and macrosomia. Maternal obesity is associated with an increase in maternal lipid levels, higher triglycerides and VLDL, and lower HDL-C than observed in lean women. Obese women without GDM have been shown to have higher glucose profiles on continuous glucose monitoring performed during pregnancy than normal-weight women; the mean time spent with glucose >6.7 mmol/L is longer in obese than normal-weight women (209 ± 62 min vs. 33 ± 12 min, P = 0.001). In addition to changes in lipid and glucose metabolism, there is greater inflammation and more vascular endothelial dysfunction associated with obese pregnancy. Disentangling the effect of maternal obesity per se from that of maternal diabetes on maternal metabolism and pregnancy outcomes in the women with obesity and diabetes in pregnancy is almost impossible without very large cohorts with refined metabolic measures.
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