data modified from Erasmus, 1993

and oils


data modified from: \* Tanakol et al., 1999 [Black & Marmara Sea]; # Soriguer et al., 1997 [Atlantic Ocean & Mediterranean Sea]; \$Li et al., 2011 [East China Sea & Quiantang River]

Table 3. Fat content and fatty acid composition (g fatty acid/100 g fat) of selected sea fishes

#### **2.3 Fatty acids during pregnancy**

LCPUFAs play an important role in the maturation of the developing nervous system. AA and DHA are accreted in large amounts into the fetal nervous system: into the cortex and retinal cell membranes during the third trimester of pregnancy and in the first months of life (Farquharson et al., 1992; Martinez & Mougan, 1998). DHA can be predominantly found in the grey matter and retina (Horrocks & Yeo, 1999), while the highest AA content is in the amygdala (Brenna & Diau, 2007). In a primate study (Diau et al., 2005), the highest DHA content was found in globus pallidus (15.8%), while the lowest in the optic nerve (4.5%). AA content was the highest in the amygdale (13.7%) and the lowest in the optic tract (6.8%). Grey matter was richer is both AA and DHA, but there was a discontinuity between grey and white matter DHA concentration, while this great difference wasn't seen in AA concentrations.

The human body has the enzymes needed to synthesise LCPUFAs from their parent essential fatty acids, but the synthesis is a very slow, limited process. In vivo human studies showed that from ALA only a little part is metabolised into EPA and DHA: when supplementing ALA in low dose (<100 mg) only 1.5-7.0% EPA and max. 0.3% DHA were synthesised, while supplementing ALA in high dose (>100 mg) resulted in the synthesis of 0.2-9.0% EPA and 3.8- 10.4% DHA. Hence, rise of EPA by 20-100% can be seen in a dose-dependent manner after the administration of ALA. In contrast, the change in DHA values is rather negligible in healthy

Fatty Acid Supply in Pregnant Women with Type 1 Diabetes Mellitus 443

months (Bouwstra et al., 2006), 3.5 years (Williams et al., 2001) and 4 years (Helland et al., 2003), while other studies failed to corroborate these findings (Bakker et al., 2003; Ghys et al., 2002). Because of the beneficial fetal/neonatal effects of n-3 LCPUFAs, for pregnant and lactating women, at least 200 mg/day DHA intake is recommended (Koletzko et al., 2007b).

T1DM disturbs not only the carbohydrate, but also the lipid metabolism. The most extensively studied experimental animal model of T1DM is the alloxane or streptozotocininduced diabetic rat or mouse. The results of animal studies are quite unequivocal: in diabetic animals significantly higher LA contents were found in liver, renal cortex and heart lipids (Ramsammy et al., 1993), in liver microsomes and erythrocyte membranes (Shin et al., 1995) as well as in plasma, liver and skeletal muscle phospholipids (Mohan & Das, 2001), while its most important metabolite, AA was significantly decreased in diabetic animals. These results can be explained with the diminished activity of -5 (Ramsammy et al., 1993) and -6 desaturase enzymes in T1DM (Ramsammy et al., 1993; Shin et al., 1995). On the basis of these animal studies, insulin is considered as the most potent activator of both -5

Human studies are even less unambiguous than animal observations. Some studies found significantly higher LA values in diabetic patients (Decsi et al., 2002, 2007; Tilvis & Miettinen, 1985), while others found no significant differences (Ruiz-Gutierrez et al., 1993; Seigneur et al., 1994). On the other hand, most studies report significantly lower AA (Decsi et al., 2002; Ruiz-Gutierrez et al., 1993) and DHA values (Decsi et al., 2002; Ruiz-Gutierrez et al., 1993; Tilvis & Miettinen, 1985) in diabetic patients than in controls. In one study (Tilvis et al., 1986), diabetic patients treated with continuous insulin infusion therapy had significantly lower LA, and significantly higher AA and DHA values both in plasma and erythrocyte membrane lipids than patients with conventional insulin therapy. These results suggest that better diabetic control may improve the activity of -6 desaturase enzyme. After a longer period, hyperglycaemia and hypoinsulinemia may lead to several complications in diabetic patients. Several studies investigated the relationship between disturbed fatty acid status in diabetic patients and a number of complications, like diabetic neuropathy, nephropathy and retinopathy. These relationships and the potential role of n-3 fatty acid supplementation in diabetic patients are reviewed elsewhere (Szabó et al., 2010b).

**3.1 Fatty acid supply during pregnancy in women with type 1 diabetes mellitus:** 

T1DM disturbs the fatty acid supply, therefore maternal LCPUFA stores may be compromised compared to healthy pregnant women. Disturbed fatty acid supply and metabolism may influence the course of pregnancy and delivery and may lead both to maternal and fetal complications. Nevertheless, we found only two human studies investigating the fatty acid supply during pregnancy in women with T1DM and four studies investigating fatty acid supply in cord blood lipids of newborns born from mothers with

Ghebremeskel et al. (Ghebremeskel et al., 2002) induced diabetes with streptozotocin in pregnant rats and investigated the liver fatty acid composition. They found significantly higher essential fatty acid values (ALA and LA) as well as n-3 and n-6 LCPUFA values (AA, EPA, DPA and DHA) in the TG and NEFA fractions. In an earlier study (Chen CH et al.,

**3. Effect of type 1 diabetes mellitus on fatty acid supply** 

and -6 desaturase enzymes (Brenner, 2003).

**Maternal effects** 

T1DM (Table 4).

adults. Similarly, LA supplementation has little effect on AA supply, only ~0.1% of dietary LA is converted to AA in healthy adults (Plourde & Cunnane, 2007).

As AA and DHA play a key role in the fetal and neonatal brain and visual development, several authors investigated whether the fetus and/or the infant is capable to synthesise AA and DHA from LA and ALA, respectively. In an experimental study (Salem et al., 1996), in vivo conversion of EFAs in newborns was investigated. After the administration of deuterium-labeled LA and ALA, deuterium-labeled AA, EPA and DHA appeared in the neonatal blood. However, this capacity can hardly cover the LCPUFA requirement of the developing brain. Two groups of infants with sudden and unexpected death were studied (at the age of 2 to 48 weeks) and significantly higher AA and DHA values were found in erythrocyte and brain cortex lipids in breastfed infants than in infants fed formula that contained only LA and ALA, and the accretion of DHA was correlated with the length of breastfeeding (Makrides et al., 1994).

Since LCPUFA synthesis in the human organism is limited, the most important source of AA and DHA is diet. During pregnancy maternal diet covers the fetal requirements of these fatty acids, while after delivery either maternal diet (breastfeeding) or the independent diet of the infant (formula feeding). In an animal study (Diau et al., 2005), baboon neonates were fed either breastmilk or formula with or without AA and DHA. DHA supplementation restored the DHA supply in the grey matter to breastfed levels, while dietary AA had little effect on brain AA content. In other words: AA seems to be less sensitive to dietary manipulation than DHA.

Maternal diet and metabolism as well as maternal stores are the sources of fetal fatty acid supply. As the ability of the fetus to synthesise LCPUFAs is limited, placenta plays an important role in transferring AA and DHA from mother to the fetus. Several research groups (Berghaus et al., 1998; Gil-Sanchez et al., 2010; Ortega-Senovilla et al., 2009) investigated the differences in maternal and fetal (newborn) blood fatty acid composition and found a higher proportion of LCPUFAs, while lower proportion of the EFAs in the fetal circulation than in the mothers. This phenomenon is called "biomagnification" and may be related to the ability of the placenta to selectively transport LCPUFAs to the fetus. In an in vivo study (Larqué et al., 2003), pregnant women undergoing elective caesarean section received 4 h before delivery an oral dose of 13C-labeled palmitic acid, oleic acid, LA and DHA. Venous blood was taken from the mothers every hour, and cord blood and placental tissues were also collected at delivery. All four fatty acids appeared in the placental tissues and cord blood triacylglycerol (TG) and non-esterified fatty acid (NEFA) lipids, and there was a preferential sequestration of DHA into the placenta. In a recent study (Gil-Sanchez et al., 2010), it was also shown that all labeled fatty acids were enriched in maternal plasma, as well as placental and cord blood lipids. This was the first study that showed a higher ratio of 13C-labeled DHA in cord to maternal plasma. Unesterified fatty acids are transferred to the fetal circulation by both passive diffusion and through a complex, saturable, proteinmediated transport (Koletzko et al., 2007a). There are several fatty acid transfer proteins in the placenta, like fatty acid binding protein (FABP), that preferentially binds LCPUFAs, fatty acid translocase (FAT) and fatty acid transporter protein (FATP) located on both sides of trophoblast cells transporting fatty acids bidirectionally (Cetin et al., 2009). The plasma membrane FABP is located exclusively on the maternal side of membranes and might be involved in the preferential uptake of LCPUFAs by these cells (Koletzko et al., 2007a).

Fish or fish oil intake during pregnancy and lactation improves maternal fatty acid supply and, hence, may enhance fetal DHA concentrations. The increased DHA intake during pregnancy resulted in better visual and neural development in infants at the age of 18

adults. Similarly, LA supplementation has little effect on AA supply, only ~0.1% of dietary LA

As AA and DHA play a key role in the fetal and neonatal brain and visual development, several authors investigated whether the fetus and/or the infant is capable to synthesise AA and DHA from LA and ALA, respectively. In an experimental study (Salem et al., 1996), in vivo conversion of EFAs in newborns was investigated. After the administration of deuterium-labeled LA and ALA, deuterium-labeled AA, EPA and DHA appeared in the neonatal blood. However, this capacity can hardly cover the LCPUFA requirement of the developing brain. Two groups of infants with sudden and unexpected death were studied (at the age of 2 to 48 weeks) and significantly higher AA and DHA values were found in erythrocyte and brain cortex lipids in breastfed infants than in infants fed formula that contained only LA and ALA, and the accretion of DHA was correlated with the length of

Since LCPUFA synthesis in the human organism is limited, the most important source of AA and DHA is diet. During pregnancy maternal diet covers the fetal requirements of these fatty acids, while after delivery either maternal diet (breastfeeding) or the independent diet of the infant (formula feeding). In an animal study (Diau et al., 2005), baboon neonates were fed either breastmilk or formula with or without AA and DHA. DHA supplementation restored the DHA supply in the grey matter to breastfed levels, while dietary AA had little effect on brain AA content. In other words: AA seems to be less sensitive to dietary

Maternal diet and metabolism as well as maternal stores are the sources of fetal fatty acid supply. As the ability of the fetus to synthesise LCPUFAs is limited, placenta plays an important role in transferring AA and DHA from mother to the fetus. Several research groups (Berghaus et al., 1998; Gil-Sanchez et al., 2010; Ortega-Senovilla et al., 2009) investigated the differences in maternal and fetal (newborn) blood fatty acid composition and found a higher proportion of LCPUFAs, while lower proportion of the EFAs in the fetal circulation than in the mothers. This phenomenon is called "biomagnification" and may be related to the ability of the placenta to selectively transport LCPUFAs to the fetus. In an in vivo study (Larqué et al., 2003), pregnant women undergoing elective caesarean section received 4 h before delivery an oral dose of 13C-labeled palmitic acid, oleic acid, LA and DHA. Venous blood was taken from the mothers every hour, and cord blood and placental tissues were also collected at delivery. All four fatty acids appeared in the placental tissues and cord blood triacylglycerol (TG) and non-esterified fatty acid (NEFA) lipids, and there was a preferential sequestration of DHA into the placenta. In a recent study (Gil-Sanchez et al., 2010), it was also shown that all labeled fatty acids were enriched in maternal plasma, as well as placental and cord blood lipids. This was the first study that showed a higher ratio of 13C-labeled DHA in cord to maternal plasma. Unesterified fatty acids are transferred to the fetal circulation by both passive diffusion and through a complex, saturable, proteinmediated transport (Koletzko et al., 2007a). There are several fatty acid transfer proteins in the placenta, like fatty acid binding protein (FABP), that preferentially binds LCPUFAs, fatty acid translocase (FAT) and fatty acid transporter protein (FATP) located on both sides of trophoblast cells transporting fatty acids bidirectionally (Cetin et al., 2009). The plasma membrane FABP is located exclusively on the maternal side of membranes and might be involved in the preferential uptake of LCPUFAs by these cells (Koletzko et al., 2007a). Fish or fish oil intake during pregnancy and lactation improves maternal fatty acid supply and, hence, may enhance fetal DHA concentrations. The increased DHA intake during pregnancy resulted in better visual and neural development in infants at the age of 18

is converted to AA in healthy adults (Plourde & Cunnane, 2007).

breastfeeding (Makrides et al., 1994).

manipulation than DHA.

months (Bouwstra et al., 2006), 3.5 years (Williams et al., 2001) and 4 years (Helland et al., 2003), while other studies failed to corroborate these findings (Bakker et al., 2003; Ghys et al., 2002). Because of the beneficial fetal/neonatal effects of n-3 LCPUFAs, for pregnant and lactating women, at least 200 mg/day DHA intake is recommended (Koletzko et al., 2007b).
