Dietary shifts and human health: cancer and cardiovascular disease in a sustainable world.

INTRODUCTION: Increasing evidence suggests that optimal food choice is critical for sizable prevention of western diseases such as cardiovascular disease and cancer. The Mediterranean diet is an important step in this direction. Moreover, substantially lower rates of Western disease, even compared to Mediterranean countries, have been observed among hunter-gatherers and other non-western populations (Lindeberg 2010). Observational studies and controlled trials support the notion that an evolutionary perspective is helpful when designing food models for optimal human health. DISCUSSION: However, sustainable health for the individual patient is not enough: environmental sustainability must also be considered. Are fish and fruit sustainable for everyone? Are starchy root vegetables a better option than cereal grains? Is locally produced meat an underestimated wholesome food? These and other questions need to be addressed in order to cut greenhouse gases and the consumption of (blue) water and nonrenewable energy.

ST depression at caesarean section and the relation to oxytocin dose. A randomised controlled trial.

OBJECTIVE: To investigate whether there is a difference in occurrence of electrocardiogram changes suggestive of myocardial ischaemia between two different doses of oxytocin. DESIGN: Double-blind randomised controlled trial. SETTING: University hospital in Sweden. POPULATION: A total of 103 healthy women undergoing elective caesarean section under spinal anaesthesia. METHODS: The participants were randomised to 5 or 10 units of oxytocin, given as an intravenous bolus. A Holter monitor was used to record electrocardiograms and non invasive blood pressure and heart rate (HR) was monitored. A blood sample was obtained 12-hour postoperatively. MAIN OUTCOME MEASURES: Depression of the ST segment. SECONDARY OUTCOMES: symptoms, Troponon I levels, mean arterial pressure (MAP), HR and blood loss. RESULTS: There was a significant difference in occurrence of ST depressions associated with oxytocin administration, 4 (7.7%) with 5 and 11 (21.6%) with 10 units, P < 0.05. The absolute risk reduction was 13.9% (95% confidence interval, 0.5-27.3). Decrease of mean MAP from baseline to 2 minutes differed, being 9 mmHg in the 5 unit group and 17 mmHg in the 10 unit group (P < 0.01). The increase in mean HR did not differ. Troponin I levels were increased in four subjects (3.9%). There were no differences in occurrence of symptoms, Troponin I levels, or estimated blood loss. CONCLUSION: ST depressions were associated with oxytocin administration significantly more often in subjects receiving 10 units compared with 5 units. Interventions to prevent hypotension during caesarean section may reduce the occurrence of ST depressions on electrocardiograms.

Metabolic acidosis at birth and suboptimal care--illustration of the gap between knowledge and clinical practice.

OBJECTIVE: To evaluate the occurrence and nature of suboptimal intrapartum care in cases with metabolic acidosis in the newborn, and to estimate the degree to which this may be prevented. DESIGN: Case-control study. Clinical audit. Setting Delivery units at two university hospitals in Sweden. POPULATION: Out of 28 486 deliveries, 161 neonates > or =34 weeks of gestational age were born with metabolic acidosis. METHODS: Cases (n = 161): umbilical artery pH < 7.05 and base deficit > or =12 mmol/l. Controls (n = 322): pH > or = 7.05 and Apgar score > or =7 at 5 minutes. Obstetric characteristics and oxytocin administration were recorded. The last 2 hours of electronic fetal monitoring before delivery were evaluated blinded to outcome. Intrapartum management was analysed for suboptimal care by using predefined criteria. MAIN OUTCOME MEASURE: Suboptimal intrapartum care. RESULTS: Case and control comparisons displayed an occurrence of suboptimal care in 49.1% versus 13.0% (P < 0.001), oxytocin misuse in 46.6% versus 13.0% (P < 0.001), a failure to respond to a pathological cardiotocographic pattern in 19.9% versus 1.2% (P < 0.001) and suboptimal care related to vacuum deliveries in 3.1% versus 0.3% (P < 0.01) respectively. CONCLUSION: Metabolic acidosis at birth is often associated with suboptimal intrapartum care. The high rate of suboptimal care with regard to oxytocin use and fetal surveillance illustrate a gap between guidelines and clinical practice. Metabolic acidosis and related neonatal morbidity could potentially be prevented in 40-50% of cases. The adherence to guidelines must be checked.

The association of maternal chronic hypertension with perinatal death in male and female offspring: a record linkage study of 866,188 women.

OBJECTIVE: The purpose of this study was to determine whether there is a difference, by gender, in perinatal mortality in chronically hypertensive women compared with normotensive women. DESIGN: Population-based prospective cohort study. SETTING: Sweden. POPULATION: A total of 866,188 women with singleton pregnancies registered in the Swedish Medical Birth Registry 1992-2004, of which 4749 were diagnosed with chronic hypertension. METHODS: Multivariate logistic regression analysis was performed. In a first step, we adjusted for maternal characteristics and in a second step for mild and severe pre-eclampsia, gestational diabetes, placental abruption and small for gestational age. An effect modification by gender was included in the model. MAIN OUTCOME MEASURES: Odds ratios (OR) for intrauterine death, neonatal death and post-neonatal death with respect to gender of offspring. RESULTS: The unadjusted OR of intrauterine death was 4.12 (95% CI: 2.84-5.96) and 1.29 (95% CI: 0.67-2.48) for male and female offspring, respectively, and of neonatal death, it was 3.45 (95% CI: 2.13-5.59) and 2.17 (95% CI: 1.08-4.35) for male and female offspring, respectively. After multivariate analysis, the OR of intrauterine death was 3.07 (95% CI: 2.12-4.46) and neonatal death was 2.99 (95% CI: 1.84-4.85) for male offspring. For female offspring, the OR of intrauterine death was 0.98 (95% CI: 0.51-1.89) and neonatal death was 1.88 (95% CI: 0.93-3.79). CONCLUSION: Mothers with chronic hypertension have an increased risk of perinatal mortality of their male offspring.

The role of taste and appetite regulation in the understanding of overweight and obesity. Proceedings of the 16th Aschauer Soiree, 26th April 2008.

Overweight and obesity have developed into major illnesses in most Western societies and significantly contribute to the financial burden of modern public health systems. Almost daily, new therapeutic proposals are published in the lay press, and also the scientific literature has increased dramatically in recent years. E.g., when searching MEDLINE (1966 - May 2008 (1)), the key word "obesity" meanwhile appears in more than 108,000 articles. Primary focus however, is put upon aspects of treatment, neglecting the role of taste and appetite regulation. Combining keywords like "obesity + treatment" results in over 50.000 citations, "obesity + diet" in over 23.000, "obesity + energy + expenditure" in over 13.000 citations (even "obesity + gastric + bypass" still evoke 2.600 citations), whereas "obesity + appetite + regulation" result in some 3.000, "obesity + NPY" - neuropeptid Y being one of the major chemical stimulators of appetite - evoke some 500 and "obesity + Arc + nucleus" - the arcuate nucleus being the anatomical centre of appetite regulation - no more than 370 scientific publications. The apparent scarcity of literature about taste and appetite regulation and the amazing lack of interest in neuronal information processing in overweight and obesity, has prompted the authors to brainstorm new aspects of the world-wide derailment of weight control.

A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease.

AIMS/HYPOTHESIS: Most studies of diet in glucose intolerance and type 2 diabetes have focused on intakes of fat, carbohydrate, fibre, fruits and vegetables. Instead, we aimed to compare diets that were available during human evolution with more recently introduced ones. METHODS: Twenty-nine patients with ischaemic heart disease plus either glucose intolerance or type 2 diabetes were randomised to receive (1) a Palaeolithic ('Old Stone Age') diet (n = 14), based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; or (2) a Consensus (Mediterranean-like) diet (n = 15), based on whole grains, low-fat dairy products, vegetables, fruits, fish, oils and margarines. Primary outcome variables were changes in weight, waist circumference and plasma glucose AUC (AUC Glucose(0-120)) and plasma insulin AUC (AUC Insulin(0-120)) in OGTTs. RESULTS: Over 12 weeks, there was a 26% decrease of AUC Glucose(0-120) (p = 0.0001) in the Palaeolithic group and a 7% decrease (p = 0.08) in the Consensus group. The larger (p = 0.001) improvement in the Palaeolithic group was independent (p = 0.0008) of change in waist circumference (-5.6 cm in the Palaeolithic group, -2.9 cm in the Consensus group; p = 0.03). In the study population as a whole, there was no relationship between change in AUC Glucose(0-120) and changes in weight (r = -0.06, p = 0.9) or waist circumference (r = 0.01, p = 1.0). There was a tendency for a larger decrease of AUC Insulin(0-120) in the Palaeolithic group, but because of the strong association between change in AUC Insulin(0-120) and change in waist circumference (r = 0.64, p = 0.0003), this did not remain after multivariate analysis. CONCLUSIONS/INTERPRETATION: A Palaeolithic diet may improve glucose tolerance independently of decreased waist circumference.

The Swedish Blood Pass project.

Manipulation of the blood's oxygen carrying capacity (CaO(2)) through reinfusion of red blood cells, injections of recombinant erythropoietin or by other means results in an increased maximal oxygen uptake and concomitantly enhanced endurance performance. Therefore, there is a need to establish a system--"A Blood Pass"--through which such illegal and unethical methods can be detected. Venous blood samples were taken under standardized conditions from 47 male and female Swedish national and international elite endurance athletes four times during the athletic year of the individual sport (beginning and end of the preparation period and at the beginning and during peak performance in the competition period). In these samples, different hematological values were determined. ON(hes) and OFF(hre) values were calculated according to the formula of Gore et al. A questionnaire regarding training at altitude, alcohol use and other important factors for hematological status was answered by the athletes. There were some individual variations comparing hematological values obtained at different times of the athletic year or at the same time in the athletic year but in different years. However, the median values of all individual hematological, ON(hes) and OFF(hre), values taken at the beginning and the end of the preparation or at the beginning and the end of the competition period, respectively, as well as median values for the preparation and competition periods in the respective sport, were all within the 95% confidence limit (CI) of each comparison. It must be mentioned that there was no gender difference in this respect. This study shows that even if there are some individual variations in different hematological values between different sampling times in the athletic year, median values of important hematological factors are stable over time. It must be emphasized that for each blood sample, the 95% CI in each athlete will be increasingly narrower. The conclusion is that there is a physiological basis for establishing an individual-based "Blood Pass" system, mainly for athletes competing at the international level. On indications of manipulations of hemoglobin concentration and red cell mass by deviations from established "Blood Pass" data, more specific methods can be applied.

Being born small for gestational age increases the risk of severe pre-eclampsia.

OBJECTIVE: The first aim of this study was to investigate the risk of pre-eclampsia, both mild and severe, in women born small for gestational age (SGA). The second aim was to investigate whether the risk is modified by pre-eclampsia in the previous generation. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: A population of 118 634 women registered both as newborns and as mothers in the Swedish Medical Birth Register of 1973-2003. Of these, 6883 had been born SGA. Only primiparas and singletons were included. METHODS: The pregnancies that the women were born out of were analysed with regard to presence of pre-eclampsia, while their own pregnancies were analysed regarding age at delivery, smoking, body mass index and incidence of mild or severe pre-eclampsia. Multiple logistic regression analysis was used. In a first step, we adjusted for maternal characteristics, and in a second step, for pre-eclampsia in the previous generation. MAIN OUTCOME MEASURES: Odds ratio for mild and severe pre-eclampsia. RESULTS: In women born SGA, the adjusted odds ratio (first step) for mild pre-eclampsia was 1.19 (95% CI 1.03-1.38), while for severe pre-eclampsia it was 1.69 (95% CI 1.40-2.02) compared with those not born SGA. After the second-step adjustment, the odds ratio for mild pre-eclampsia was 1.16 (95% CI 1.00-1.35) and for severe pre-eclampsia was 1.62 (95% CI 1.35-1.95). No statistically significant effect modification from pre-eclampsia in the previous generation was shown. CONCLUSIONS: Women born SGA suffer a markedly increased risk of severe pre-eclampsia. Exposure to pre-eclampsia during a woman's own fetal development significantly increases her risk of pre-eclampsia but does not modify the SGA effect.

Decreased maternal lipolysis in intrauterine growth restriction in the third trimester.

OBJECTIVE: Intrauterine growth restriction (IUGR) is a common complication of pregnancy. There are many possible aetiologic factors of maternal, placental and/or fetal origin. Often there is no known explanation. The aim of this study was to investigate whether a reduction in maternal energy substrate production could be one of the factors involved in IUGR. DESIGN: Measurement of maternal energy substrate production and glucoregulatory hormones in women with growth-restricted fetuses. SETTINGS: University Hospital, Uppsala, Sweden. POPULATION: Ten healthy pregnant women with IUGR were compared with eight recently reported healthy women with normal pregnancies. The women were studied at 35.4+/-1.6 weeks of gestation after an overnight fast. METHODS: Rates of glycerol and glucose production were analysed by gas chromatography/mass spectrometry following constant-rate infusion of [1,1,2,3,3-(2)H5]glycerol and [6,6-(2)H2]glucose. MAIN OUTCOME MEASURE: Third trimester glycerol and glucose production. RESULTS: Glycerol production, reflecting lipolysis, was lower in the women with IUGR than in those with normal pregnancies, 2.36+/-0.58 versus 3.06+/-0.66 micromol kg-1 minute-1 (P=0.033), whereas there was no difference in rate of glucose production (glucose production rate [GPR]), 12.1+/-1.5 versus 13.2+/-1.5 micromol kg-1 minute-1 (P=0.23). Plasma glycerol levels were increased in the women with IUGR (P=0.008). CONCLUSIONS: Lipolysis is lower in pregnancies complicated by IUGR as compared with normal pregnancies. Increased lipolysis during pregnancy provides substrate for maternal energy metabolism, which spares glucose for the fetus. A reduced maternal production of energy substrate could be one of several factors underlying IUGR. A lack of relationship between insulin levels and either lipolysis or GPR suggests defective regulation of energy substrate production in this group of pregnant women.

Placental dysfunction in Suramin-treated rats--a new model for pre-eclampsia.

Impaired placentation and oxidative stress are proposed to play major roles in the pathogenesis of placental dysfunction and pre-eclampsia. This study was carried out to evaluate if inhibited angiogenesis by Suramin injections in early pregnancy may cause a condition resembling pre-eclampsia in rats. Rats of two different Sprague-Dawley strains, U and H, were given intraperitoneal injections of Suramin or saline in early pregnancy. The outcome of pregnancy was evaluated on gestational day 20. Suramin injections caused increased blood pressure and decreased renal blood flow in the U rats. In both rat strains Suramin decreased the placental blood flow and caused fetal growth retardation. In both strains the placental concentration of the isoprostane 8-epi-PGF2alpha was increased, indicating oxidative stress. The serum concentration of Endothelin-1 was increased in the U rats. The U strain had a lower basal placental blood flow, and the effects of Suramin were more pronounced in this strain. We conclude, that Suramin injections to pregnant rats cause a state of placental insufficiency, which partly resembles human pre-eclampsia. The induction of this condition is at least partly mediated by oxidative stress, and is subject to varied genetic susceptibility.

Serum uric acid in traditional Pacific Islanders and in Swedes.

BACKGROUND: In some western populations, increased serum uric acid has been positively associated with cardiovascular disease, possibly because hyperuricaemia could be an untoward part of the insulin-resistant metabolic syndrome. However, there is evidence that uric acid is a free radical scavenger capable of inhibiting LDL oxidation. Amongst the traditional horticulturalists of Kitava, Trobriand Islands, Papua New Guinea, cardiovascular disease, hypertension, hyperinsulinaemia and abdominal obesity are absent or rare. In contrast, serum triglycerides are similar to Swedish levels. OBJECTIVE: To compare serum uric acid between nonwesternized and westernized populations. METHODS: Fasting levels of serum uric acid were measured cross-sectionally in 171 Kitavans aged 20-86 years and in 244 randomly selected Swedish subjects aged 20-80 years. RESULTS: There were small differences in serum uric acid between the two populations, although a slight increase with age was found only in Swedish males (r = 0.20; P = 0.03) and females (r = 0.36; P < 0.0001). Above 40 years of age, uric acid was approximately 10% lower in Kitavans, a difference which was statistically significant only in males, possibly because of the limited number of females. Regarding hyperuricaemia, two Kitavan males had uric acid above 450 micromol L-1 whilst none of the females was above 340 micromol L-1. Amongst the Swedish subjects, five of 117 males and 19 of 127 females had hyperuricaemia according to these definitions. CONCLUSION: The rather similar uric acid levels between Kitava and Sweden imply that uric acid is of minor importance to explain the apparent absence of cardiovascular disease in Kitava.

Determinants of serum triglycerides and high-density lipoprotein cholesterol in traditional Trobriand Islanders: the Kitava Study.

OBJECTIVES: To analyse variables explaining the variation between serum triglycerides (TGs) and high density lipoprotein cholesterol (HDL-C) in a non-western population characterized by unfavourable TG and HDL-C levels despite marked leanness, low blood pressure and low fasting serum insulin. The study subjects included yraditional Pacific Islanders from Kitava, Trobriand Islands, Papua New Guinea and a population in Sweden. METHODS: The study was designed as a cross-sectional survey. Fasting serum lipoproteins and apolipoproteins, insulin, blood pressure and anthropometric measurements were analysed in 122 male and 47 female Kitavans aged 20-86 years and in a control population of 729 healthy men and women aged 20-66 from Uppsala. Main outcome measures were determinants of TG and HDL-C using a simple and multiple linear regression analysis. RESULTS: A negative association was found between TGs and HDL-C in Kitava (r = -0.38. p < 0.0001) and Sweden (r = -0.46, p < 0.0001), while TGs were positively associated with non-HDL-C and ApoB in both groups. In contrast to what was found in the Swedish subjects, TG and HDL-C levels were not associated with body mass index, waist circumference, glucose, insulin or systolic blood pressure in the Kitavans. CONCLUSION: Despite an apparent absence of cardiovascular disease and the metabolic syndrome in the Kitavans, the relationship between TGs and HDL-C was similar to that observed in Caucasians, while neither of the variables was associated with markers of insulin sensitivity in the Kitavans. Whether the findings can be explained by normal physiology or partially reflect the high intake of carbohydrates and saturated fat in Kitava is uncertain.

A high rate of epidural analgesia with bupivacaine-sufentanil is consistent with a low rate of caesarean section and instrumental deliveries.

OBJECTIVE: To prospectively evaluate if a high rate of epidural analgesia (EDA) with bupivacaine-sufentanil is consistent with a low rate of caesarean section, instrumental deliveries and dystocia and to evaluate maternal and fetal adverse effects of sufentanil. STUDY DESIGN: Populations-based prospective descriptive study. A change of EDA from bupivacaine to low dose bupivacaine-sufentanil at the delivery unit of the hospital during 1993 resulted in a marked increase in the rate of EDA. The outcome from the study period (1994-1995) was compared to the outcome during a reference period 1991-1992. RESULTS: There were no significant differences in the incidence of caesarean section and instrumental delivery for dystocia between the two periods (4.4 and 4.6%). The overall incidence of caesarean section, 9.6% and instrumental deliveries, 6.4% during the study period was lower than or comparable to the national background data (11.1 and 6.8%, respectively) while the EDA rate was markedly higher 37.8 versus 21.9%. CONCLUSION: A high rate of EDA, using low dose bupivacaine and sufentanil is consistent with a low rate of caesarean section and instrumental deliveries. No apparent negative effects on the neonates or mothers were observed.

Large differences in serum leptin levels between nonwesternized and westernized populations: the Kitava study.

OBJECTIVES: To compare serum leptin between nonwesternized and westernized populations. SETTING: (i) The tropical island of Kitava, Trobriand Islands, Papua New Guinea and (ii) the Northern Sweden MONICA study population. Design. Cross-sectional survey. METHODS: Fasting levels of serum leptin were analysed in 163 randomly selected Kitavans aged 20-86 years and in 224 Swedes aged 25-74. MAIN OUTCOME MEASURE: Mean and determinants of serum leptin. RESULTS: Geometric mean of serum leptin in Kitavan males and females were 1.5 and 4.0 vs. 4.9 and 13.8 ng mL-1 in Swedish male and females (P < 0.0001 for both sexes). In Kitavans, observed geometric mean were close to predicted levels (1.8 ng mL(-1) for males and 4.5 ng mL-1 for females) based on multiple linear regression equations including body mass index (BMI), triceps skinfolds (TSF) and age from the Swedish population-based sample. In Kitavans serum leptin was positively related to TSF amongst both sexes and, amongst females, to BMI. In Kitavans leptin was not related to fasting serum insulin. TSF explained 55% of the variation of leptin amongst females. There was a slight age-related increase of leptin amongst males. In Kitava leptin was not related to fasting serum insulin which was substantially lower than in Sweden. CONCLUSION: The low concentrations of serum leptin amongst Kitavans probably relates to the absence of overweight and hyperinsulinaemia. At a population level serum leptin can apparently be predicted from simple measures of adiposity.

Hypertension and factors associated with metabolic syndrome at follow-up at 15 years in women with hypertensive disease during first pregnancy.

OBJECTIVES: To study the possibility of identifiable factors at or close to pregnancy that could predict hypertension later in life. To evaluate if women with hypertensive disease in their first pregnancy and who later develop hypertension also have characteristics of the metabolic syndrome. METHODS: Case control study of a cohort of women with hypertension diagnosed in first pregnancy (n = 46) and controls without hypertension in pregnancy (n = 47), studied 15 years after the index pregnancy. Blood pressure, antihypertensive drug treatment, body parameters, blood glucose, serum insulin, and serum lipids were analyzed. RESULTS: In the study group, 43% had hypertension compared to 4% in the control group. Among the women in the study group with more than one pregnancy, there was a significantly higher prevalence of hypertension if pregnancy-induced hypertension was repeated in a later pregnancy. There were also significantly higher waist/hip ratios and fasting plasma levels of insulin in the study group. CONCLUSION: Hypertension in pregnancy is a strong predictor of hypertension later in life. Other factors related to hypertension and present at pregnancy are not useful in selecting a high-risk group. In a proportion of cases, the metabolic syndrome might be related to the hypertensive disease in pregnancy.

Low serum insulin in traditional Pacific Islanders--the Kitava Study.

Increased serum insulin is related to abdominal obesity and high blood pressure in affluent societies where insulin, weight, and blood pressure typically increase with age. The increased insulin level has been thought to reflect insulin resistance, a well-known associated factor in the metabolic syndrome. In most nonwesternized populations, body weight and blood pressure do not increase with age and abdominal obesity is absent. However, it is not known whether serum insulin likewise does not increase with age in nonwesternized societies. Fasting levels of serum insulin were measured cross-sectionally in 164 subsistence horticulturalists aged 20 to 86 years in the tropical island of Kitava, Trobriand Islands, Papua New Guinea, and in 472 randomly selected Swedish controls aged 25 to 74 years from the Northern Sweden WHO Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) Study. In Kitava, the intake of Western food is negligible and stroke and ischemic heart disease are absent or rare. The body mass index (BMI) and diastolic blood pressure are low in Kitavans. The main outcome measures in this study were the means, distributions, and age relations of serum insulin in males and females of the two populations. Serum fasting insulin levels were lower in Kitava than in Sweden for all ages (P < .001). For example, the mean insulin concentration in 50- to 74-year-old Kitavans was only 50% of that in Swedish subjects. Furthermore, serum insulin decreased with age in Kitava, while it increased in Sweden in subjects over 50 years of age. Moreover, the age, BMI, and, in females, waist circumference predicted Kitavan insulin levels at age 50 to 74 years remarkably well when applied to multiple linear regression equations defined to predict the levels in Sweden. The low serum insulin that decreases with age in Kitavans adds to the evidence that a Western lifestyle is a primary cause of insulin resistance. Low serum insulin may partly explain the low prevalence of cardiovascular disease in Kitavans and probably relates to their marked leanness.