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Objectives. The Pregnancy, Nutrition & Diabetes (PND) study aimed to evaluate the dietary status of urban Black pregnant women attending the Antenatal Clinic at the Charlotte Maxeke (Johannesburg General) Hospital. In addition, the study investigated the effects of maternal dietary intake and hormonal levels during pregnancy on fetal growth, birth size and the early postnatal development of risk factors for future Type 2 diabetes. The study analysis precedes a detailed description of the study population, including its comparison with other populations. Methods. 126 women were enrolled in the study before 24 weeks of gestation. Twice during pregnancy (weeks 20-24 and 30-36, visits V1 and V2) and approximately six months after the delivery (visit V3), volunteers participated in a standard 75 g oral glucose tolerance test (OGTT). Blood pressure, anthropometric and socio-demographic data were taken and a food frequency questionnaire was administered at each visit. The daily maternal intakes of total energy and macronutrients expressed as a % of total energy intake (%E) were calculated and further evaluated. A comparison with the crude nutrients intakes was also performed. During both pregnancy visits, an ultrasound examination was carried out to obtain estimates of fetal biometry and fetal well-being and the postnatal anthropometric parameters were also measured. Blood samples were collected at fasting, 30min, 60min and 120min of the OGTT for the measurements of maternal glucose (GLC), insulin (INS), C-peptide (C-PEP) and proinsulin (PI) and fasting samples for the determination of placental lactogen (HPL), insulinlike growth factor 1 (IGF-1), insulin-like growth factor binding protein 1 (IGF-BP1), free thyroxin (FT4), cortisol (CORT) and leptin (LEPT). Infant fasting blood samples were used for the analysis of the GLC, INS, PI, IGF-BP3 and LEPT. The plasma glucose samples were analysed on the Beckman Glucose Analyser 2, whilst all the other analytes were measured by an immunoassay method on 96-well plates. Results – DESCRIPTIVE DATA. Study participants. The majority of the study participants had completed high school education, however were unemployed and of low and very poor socio-economic levels. In comparison with another study from the developing world, the Pune study in India, the women from the current study were older, heavier with greater body mass index (BMI) and they were also taller. They had higher head and arm circumference. Birth outcomes. The birth size of African babies in the current study, although smaller in all parameters, was still relatively closer to the size of the Caucasian babies seen within the Southampton (Godfrey et al. 1996) or Helsinki (Forsén et al. 1997) studies than to the birth size of the babies from Trivandrum (Jaya et al. 1995) or Pune (Rao et al. 2001) in India. These relatively smaller African babies have comparable (or even larger) maternal placental sizes in relation to the mothers of both European studies. However, in comparison with the small Indian babies, the major difference noted was a substantially smaller placental size of the Pune mothers. Compared to z-scores from the World Health Organization (WHO) child growth standards (WHO Anthropo 2010), the PND study babies were born lighter and shorter with a larger head circumference (HC). A growth delay observed near the neonatal visit was followed by catch up growth in weight for age, however no catch-up growth was observed for length for age by the second postnatal visit. Dietary intakes. The PND study women had pregnancy energy intakes slightly below the national level intakes (Steyn et al. 2006), except for the energy intake at V3, which exceeded the national level. The lower energy intake during pregnancy is attributable to a lower intake of dietary protein and total carbohydrate. The fat intake was substantially higher in the PND study, with levels almost double at the second postnatal visit. This discrepancy may be due to differences between investigated populations or due to increased requirements of energy during lactation. In comparison with the Recommended Dietary Allowances (RDA), during the pregnancy period women in the current study had lesser crude protein and higher carbohydrate intake. Intake of the crude protein after delivery was low in comparison to the RDA for lactating women. Total carbohydrate intake exceeded the RDA. The relation between the intake of macronutrients expressed as a percentage of total energy (%E) and RDA was similar. The current study participants had a lower intake of energy, especially during the pregnancy period, when compared to populations in the developed world. They had a lower intake of protein at all visits in comparison with the national average for women or with that found in the Southampton study or when compared to the usual American diet. The energyadjusted intake of fat and carbohydrate were comparable with the Southampton and American data. This population in our study was therefore more comparable to that of Pune than to American or Southampton populations. However, despite similar total energy intakes as the Pune Study, total protein and fat intakes were higher in the African mothers, which may explain their higher weights and birthweights of their babies. Results – ANALYTICAL DATA Dietary intakes. Maternal dietary intakes showed significant effects on the fetal biometrical measurements, mainly involving the fetal head, femur length and the size of abdomen. The outcomes also show a significant relationship between maternal protein intake and baby’s birth weight. Associations were also found for maternal dietary intakes and the neonatal length and BMI and the markers of the infant β-cell function. Intakes of the plant protein and polyunsaturated fat supported the linear growth. There was no correlation between maternal dietary intake and the fetal growth rate. Effects of the total energy intake and carbohydrate seemed to be direct, while the effect of protein and fat may be delayed, possibly involving metabolic adaptation of the mother and the partitioning of nutrients between the mother, placenta and fetus. (See Table: Associations between the maternal dietary intake and the neonatal INSF1 levels, Pg. xiv). Maternal hormones. The data of the current study show significant relationships between maternal pregnancy hormones and fetal growth rate and the postnatal growth rate, although maternal anthropometry and fetal gender and BMI are also significantly involved. The maternal thyroid hormones seem to play an important role in fetal and postnatal growth and insulin metabolism (N=76, p=0.002, ß=-0.343; AR2=0.106) in the association with the neonatal fasting insulin. Discussion. The outcomes of the current study show that the African pregnant women in the study had lower energy intakes attributable to a lower intake of dietary protein and total carbohydrate. Maternal dietary intakes showed significant effects on the fetal biometrical parameters. Protein dietary intake was positively associated with baby’s birth weight and was shown to be statistically significant. Associations were also found for maternal dietary intakes and the infant postnatal BMI and the markers of the infant β-cell function. Quality of the protein and fat has different effects on fetal/infant growth. Maternal hormones showed correlations with fetal growth rate and the outcomes of the current study also show that maternal hormones can affect neonatal and early postnatal infant glucose levels and β-cell function. They are also linked to the programming of early obesity. The maternal thyroid hormones seem to play an important role. The maternal low energy, protein (especially plant protein) and PUFA intakes during gestation may be the reasons for the lower z-score birth parameters of the infants in comparison with the World Health Organization (WHO) child growth standards (WHO Anthro 2010). The disproportionally larger head of the newborn may be an outcome of the brain sparing effect. A suggestion for an increased maternal dietary intake of energy, protein and PUFA has been made.

Insulin resistance is the major metabolic defect in obesity and Type 2 diabetes. Increased lipid accumulation is strongly associated with insulin resistance. A significant component of insulin resistance is thought to be a reduced ability of insulin to activate the cascade of phosphorylation events that lead to the metabolic effects of this hormone. The broad aims of this thesis were to examine the effect of high-fat diets containing different fat subtypes on in vivo insulin signalling, under conditions normally used to detect whole body insulin resistance, and to compare the effects of acute and chronic lipid oversupply on insulin signalling in vivo. Time-course and dose-response effects of insulin stimulation on site-specific phosphorylation of key signalling proteins were studied in rat tissues in vivo, to establish an appropriate experimental system to examine the onset of activation of the insulin signalling pathway. It was determined that short insulin infusions with concurrent glucose infusion, similar to the beginning of a euglycaemic-hyperinsulinaemic clamp, significantly increased the phosphorylation of major intermediates of the insulin signalling pathway in important tissues of insulin action (skeletal muscle [RQ], liver [LIV] and white adipose tissue [EPI]). These experiments provided a platform to study insulin signalling under the same conditions used to study lipid-induced insulin resistance. The provision of diets enriched in polyunsaturated or saturated fatty acids (FA) resulted in the corresponding enrichment of these fat subtypes in rat plasma and tissues. However, the effects on insulin signalling were essentially the same. Both fat diets induced defects in sitespecific phosphorylation of insulin receptor substrate (IRS)-1 and protein kinase B (PKB) in RQ and LIV, but not EPI. This suggests that the amount of fat in the diet, rather than enrichment in a particular fat subtype, had a greater impact on the development of signalling defects and that the response to high-fat feeding was tissue-specific. A 3hr elevation of circulating FA (using a lipid/heparin infusion), to a level that is relevant in clinical Type 2 diabetes, impaired insulin-stimulated PKB phosphorylation with no significant effect on IRS-1 phosphorylation. This suggests that there may be differences in the way acute and chronic exposure to increased FA impair insulin signalling. The phosphorylation defects observed in both chronic and acute studies did not seem to be associated with activation of major stress signalling pathways (JNK and NFkB), which have been suggested to have a role in lipidinduced insulin resistance. In conclusion, these studies demonstrate that impaired IRS-1 and PKB phosphorylation do have a role in the reduced insulin action observed with lipid oversupply in vivo, because the changes were detected under similar conditions as those used to determine whole body insulin resistance.

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The independent effect of a high polyunsaturated:saturated fat (P:S) diet on glycemic control in humans has been poorly studied. We propose that a P:S $>$ 1.0 vs P:S 1.0 vs. P:S 1.0. HDL and IGFl were significantly lower with the P:S $>$ 1.0. Si was unaffected by the P:S difference, however, trends towards decreased Sg and increased insulin secretion were seen with P:S $>$ 1.0. The small sample size limits the making of firm conclusions, however, it suggests that glycemic control may be improved through increased insulin secretion a result of an increase in P:S.

Diss. Stockholm : Karol. inst.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.