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Impaired insulin secretion after prenatal exposure to the Dutch famine.

OBJECTIVE: We previously reported that people prenatally exposed to famine during the Dutch Hunger Winter of 1944-1945 have higher 2-h glucose concentrations after an oral glucose tolerance test in later life. We aimed to determine whether this association is mediated through alterations in insulin secretion, insulin sensitivity, or a combination of both. RESEARCH DESIGN AND METHODS: We performed a 15-sample intravenous glucose tolerance test in a subsample of 94 normoglycemic men and women from the Dutch Famine Birth Cohort. We used the disposition index, derived as the product of insulin sensitivity and the first-phase insulin response to glucose as a measure of the activity of the beta-cells adjusted for insulin resistance. In all analyses, we adjusted for sex and BMI. RESULTS: Glucose tolerance was impaired in people who had been prenatally exposed to famine compared with people unexposed to famine (difference in intravenous glucose tolerance test K(g) value -21% [95% CI -41 to -4]). People exposed to famine during midgestation had a significantly lower disposition index (-53% [-126 to -3]) compared with people unexposed to famine. Prenatal exposure to famine during early gestation was also associated with a lower disposition index, but this difference did not reach statistical significance. CONCLUSIONS: Impaired glucose tolerance after exposure to famine during mid-gestation and early gestation seems to be mediated through an insulin secretion defect.

Blood Glucose↗

Fertility trends, excess mortality, and the Great Irish Famine.

This paper has developed estimates of the age-specific mortality rates prevailing during the Great Irish Famine and has analyzed fertility trends during the 25 years before the Famine. Our calculations confirm that 1 million Irish people perished as a result of this disaster. This figure does not include the deaths among the 1.3 million emigrants who left Ireland during the Famine period. The Famine produced a significant drop in the fertility rate, and we estimate that more than 300,000 births did not take place as a result of the Famine. The effects were especially severe on the very young and the very old, a result echoed in the findings of demographic analyses of other famines. Our procedure permits a reconstruction of the Irish population by age and sex during the period 1821-1841. In addition, it yields year-by-year estimates of the birth rate over this period. We estimate that the rate fell by about 14 percent, a result robust to our assumptions regarding emigration. Economic historians have debated this issue, and we hope that our evidence, although preliminary, will be of assistance. Our analysis also permits year-by-year reconstruction of Irish population totals for the period 1821-1851. Two years are of particular interest. Virtually all recent writers, with the notable exception of Lee (1981), have suggested that the 1831 census returns overestimated the actual population resident in Ireland at that date. Our reconstruction supports the validity of the 1831 census figure. We obtain a total of 7,847,000, which is in good agreement with the disputed census figure of 7,767,000. But perhaps the most interesting figure is the population total for the end of 1845, the highest ever achieved in Ireland. We estimate that the population on the eve of the Great Famine was 8,525,000. Throughout the paper we have tried to highlight those areas in which the data are unreliable, unavailable, or distorted. We have tried to devise cross-checks for consistency and to test the sensitivity of the results to a range of assumptions. A case in point concerns the age-sex profile and volume of emigration to England, Scotland, and Wales. Additional work at the micro level would be helpful here. More solid evidence on Famine births would also be helpful. The parish registers we have sampled certainly provide a clue to trends, but we have only made a start in that respect. A much more comprehensive survey is needed to convey the national picture.(ABSTRACT TRUNCATED AT 400 WORDS)

Birth Rate↗

The Dutch famine and schizophrenia spectrum disorders.

In the Dutch Hunger Winter at the end of World War II a combination of circumstances created the conditions of a natural experiment. Unlike other famines, the Dutch famine struck at a precisely circumscribed time and place, and in a society able to document the timing and severity of the nutritional deprivation as well as the effects on fertility and health. Because the Dutch maintained comprehensive military and health records, it was possible to compare the incidence of neurodevelopmental disorders in adulthood for birth cohorts exposed versus those unexposed to prenatal famine. We have conducted several studies guided by the hypothesis that prenatal micronutrient deficiencies can cause neurodevelopmental schizophrenia or related personality disorders. In this paper we shall summarize our previous work and combine the outcome data of the different studies. Early prenatal famine was found to be specifically and robustly associated with each of three conditions: (1) congenital anomalies of the central nervous system, (2) schizophrenia, and (3) schizophrenia spectrum personality disorders. We found that the greatest increase in the risk of schizophrenia spectrum disorder- schizophrenia plus spectrum personality disorder- occurred among males born in the famine cities in December 1945 (relative risk = 2.7; 95% confidence interval = 1.5-5.1). Persons born in December 1945 were generally conceived at the absolute peak of the famine (March-April 1945). In the hope that the associations we have found may offer clues to the aetiology of schizophrenia, we are currently tracing and examining the cases of schizophrenia after prenatal exposure to famine.

Adult↗

Reduced intima media thickness in adults after prenatal exposure to the Dutch famine.

BACKGROUND: Restricted prenatal growth is associated with an increased risk of coronary heart disease morbidity and mortality. We studied the effects of exposure to famine during gestation on intima media thickness (IMT) in later life. METHODS AND RESULTS: We studied 730 people aged 58 years who were born as term singletons around the time of the 1944-45 Dutch famine. Persons exposed to famine during gestation (n=293) had reduced carotid artery IMT compared to people who had not been exposed to famine in utero (n=437) (mean 0.71 mm, S.D. 0.16 mm compared to 0.75 mm, S.D. 0.15 mm, sex adjusted p=0.001). Femoral artery IMT was also thinner among people exposed to famine during gestation compared to people unexposed in utero (mean 0.64 mm, S.D. 0.20mm, compared to 0.68 mm, S.D. 0.24), although the difference did not achieve statistical significance. CONCLUSION: Exposure to famine in utero may reduce IMT. However, it does not reduce the risk of coronary heart disease among famine exposed people.

Blood Vessels↗

Glucose tolerance in adults after prenatal exposure to famine.

BACKGROUND: Reduced growth in utero is associated with type 2 (non-insulin-dependent) diabetes and impaired glucose tolerance in adult life. There is no direct evidence in human beings that maternal nutrition during gestation affects insulin-glucose metabolism. We investigated glucose tolerance in people born around the time of famine in the Netherlands during 1944-45. METHODS: We included 702 people born between Nov 1, 1943, and Feb 28, 1947, in Amsterdam, for whom we had detailed prenatal and birth records. We compared glucose and insulin responses to a standard oral glucose load in participants exposed to famine at any stage during gestation (exposed participants) with those who were born in the year before or conceived in the year after the famine (non-exposed participants). FINDINGS: Glucose concentrations were increased 2 h after a standard glucose load among exposed participants (p = 0.006), and were highest in men and women exposed during mid and late gestation. Mean 2 h glucose concentration among non-exposed participants was 5.8 mmol/L; concentrations were 0.5 mmol/L (95% CI 0.1-0.9) higher among participants exposed during late gestation, 0.4 mmol/L (0-0.8) higher among those exposed during mid gestation, and 0.1 mmol/L (-0.4 to 0.6) among those exposed during early gestation. Participants born as thin babies to mothers with low bodyweights had the highest concentrations and concentrations were especially high among people exposed to famine who became obese as adults. Prenatal exposure to famine was related to increased fasting proinsulin (p = 0.05) and 2 h insulin concentrations (p = 0.04), which suggests an association with insulin resistance. INTERPRETATION: Prenatal exposure to famine, especially during late gestation, is linked to decreased glucose tolerance in adults. Poor nutrition in utero may lead to permanent changes in insulin-glucose metabolism, even if the effect on fetal growth is small. This effect of famine on glucose tolerance is especially important in people who become obese.

Birth Weight↗

Obesity at the age of 50 y in men and women exposed to famine prenatally.

BACKGROUND: It was shown that men who were conceived during the Dutch famine of 1944-1945 had higher rates of obesity at age 19 y than those conceived before or after it. OBJECTIVE: Our objective was to study the effects of prenatal exposure to the Dutch famine on obesity in women and men at age 50 y. DESIGN: We measured the body size of 741 people born at term between November 1943 and February 1947 in Amsterdam. We compared people exposed to famine in late, mid, or early gestation (exposed participants) with those born before or conceived after the famine period (nonexposed participants). RESULTS: The body mass index (BMI; in kg/m(2)) of 50-y-old women exposed to famine in early gestation was significantly higher by 7. 4% (95% CI: 0.7%, 14.5%) than that of nonexposed women. BMI did not differ significantly in women exposed in mid gestation (-2.1%; -7.0%, 3.1%) or in late gestation (-1.3%; -6.3%, 3.9%). In 50-y-old men, BMI was not significantly affected by exposure to famine during any stage of gestation: BMI differed by 0.4% (-3.5%, 4.5%) in men exposed to famine in late gestation, by -1.2% (-5.5%, 3.3%) in those exposed in mid gestation, and by 0.5% (-4.6%, 6.0%) in those exposed in early gestation compared with nonexposed men. CONCLUSIONS: Maternal malnutrition during early gestation was associated with higher BMI and waist circumference in 50-y-old women but not in men. These findings suggest that pertubations of central endocrine regulatory systems established in early gestation may contribute to the development of abdominal obesity in later life.

Birth Weight↗

Famine: a perspective for the nutrition community.

Famine is a nasty turn of events that intrudes on the world's consciousness from time to time. Pictures of starving people and acutely malnourished children, rampant disease, a rising death toll, and massive suffering in some far-off land move many among us to contribute to famine relief, shocked by the paradox of famine in a world "awash in grain". Those who think about it appreciate that famine is related to poverty, that it is often triggered by climatic instability, and that it is both an instrument and tragic by-product of political conflict. But few know very much about famine beyond such fleeting insights. Even fewer are aware that the collective response to famine is woefully deficient. Just as we in the nutrition community had to fight long and hard to get malnutrition onto the development agenda as an explicit concern of public policy, so we and others like us are going to have to labor hard again to do the same for famine. This paper is an attempt to crystallize the issues involved.

Africa↗

Mortality estimates of the 1984-85. Ethiopian famine.

A brief summary of famine and drought from a historical perspective is given. In an attempt to estimate the magnitude of deaths due to the 1984-85 famine in Ethiopia, a survey was conducted among the resettled famine victims. The results show that the expected life at birth among the male and female famine victims was 6.2 and 5.7 years, respectively. When compared with the highest mortality rates ever recorded (that is Coale-Demeny, West Model Life Table level 1), the Ethiopian famine induced rate seems to be considerably higher. Regional variations between the two famine affected regions show that mortality in Tigrai was slightly higher than that of Wello. Also prefamine socio-economic differentials between households did not seem to have an effect on mortality. The results suggest that as much as 700,000 excess deaths might have occurred during the 1984-85 famine period in Ethiopia.

Disasters↗

Sociodemographic differentials in mortality during the 1974-75 famine in a rural area of Bangladesh.

This study investigates the socio-demographic differentials in mortality during the 1974-75 famine in a rural area of Bangladesh. It is based on household socioeconomic information collected in the 1974 census and registration data on births, deaths and migrations for the period 1974-79 from the Demographic Surveillance System of the International Centre for Diarrhoeal Disease Research, Bangladesh. Ownership of selected household items was considered in the analysis as an indicator of household socioeconomic status. Mortality was 62% higher during the famine period and 31% higher during the post-famine period compared to the non-famine period. The mortality of both the poor and the rich increased during the famine period, by 117% and 28% respectively compared to the non-famine period. The poor suffered significantly in all age groups except 5-14 years, while the rich suffered only for ages 65 and over. Poor males suffered more than poor females except for ages 65 and over, while rich females suffered more than rich males except for ages under 1 year.

Adolescent↗

Glucose tolerance at age 58 and the decline of glucose tolerance in comparison with age 50 in people prenatally exposed to the Dutch famine.

AIMS/HYPOTHESIS: People who were small at birth have an increased risk of type 2 diabetes in later life. People who were in utero during the Dutch famine had decreased glucose tolerance and raised insulin concentrations at age 50. We aimed to evaluate whether prenatal famine exposure leads to more rapid progression of impaired glucose/insulin homeostasis with increasing age. METHODS: We performed an OGTT in 702 men and women at age 50 and in 699 men and women at age 58, all born as term singletons immediately before, during or after the 1944-1945 Dutch famine. RESULTS: People who had been exposed to famine in utero had significantly higher 120-min glucose concentrations at age 58 compared with people who had not been exposed to famine (difference=0.4 mmol/l, 95% CI 0.1 to 0.7, adjusted for sex and BMI). Glucose tolerance deteriorated between the age of 50 and 58. The unadjusted 120-min glucose concentrations rose by 0.2 mmol/l (95% CI 0.0 to 0.4), while 120-min insulin concentrations had increased by 64 pmol/l (95% CI 48 to 82). There were no differences in the rates of glucose and insulin level increase between the famine-exposed group and the unexposed group (p=0.28 for the difference in increase in glucose concentrations and p=0.09 for insulin concentrations). CONCLUSIONS/INTERPRETATION: Although we confirmed that undernutrition during gestation is linked to decreased glucose tolerance, the effect does not seem to become more pronounced at age 58 as compared with age 50.

Adult↗

The Dutch famine and its long-term consequences for adult health.

Small size at birth is linked with an increased risk of chronic diseases in later life. Poor maternal nutrition during gestation may contribute to restricted fetal growth, leading to increased disease susceptibility in later life. Animal studies have shown that undernutrition during gestation is associated with reduced life span and increased disease susceptibility. The Dutch famine is a unique counterpart for animal models that study the effects of restricted maternal nutrition during different stages of gestation. This paper describes the findings from a cohort study of 2414 people born around the time of the Dutch famine. Exposure to famine during any stage of gestation was associated with glucose intolerance. We found more coronary heart disease, a more atherogenic lipid profile, disturbed blood coagulation, increased stress responsiveness and more obesity among those exposed to famine in early gestation. Women exposed to famine in early gestation also had an increased risk of breast cancer. People exposed to famine in mid gestation had more microalbuminuria and obstructive airways disease. These findings show that maternal undernutrition during gestation has important effects on health in later life, but that the effects on health depend on its timing during gestation. Especially early gestation seems to be a vulnerable period. Adequate dietary advice to women before and during pregnancy seems a promising strategy in preventing chronic diseases in future generations.

Birth Certificates↗

Blood pressure response to psychological stressors in adults after prenatal exposure to the Dutch famine.

OBJECTIVE: There is increasing evidence that restricted prenatal growth is associated with exaggerated blood pressure responses to stress. We investigated the effect of maternal undernutrition on the adult offspring's stress response. DESIGN: A historical cohort study. METHODS: We performed continuous blood pressure and heart rate measurements during a battery of three 5-min physiological stress tests (Stroop test, mirror-drawing test and a public speech task) in 721 men and women, aged 58 years, born as term singletons in Amsterdam at about the time of the Dutch 1944-1945 famine. RESULTS: During the stress tests, the systolic blood pressure (SBP) rose from baseline by 20 mmHg during the Stroop test, by 30 mmHg during the mirror-drawing test and by 47 mmHg during the public speech task. The SBP and diastolic blood pressure increase during stress was highest among individuals exposed to famine in early gestation compared with unexposed subjects (4 mmHg extra systolic increase, P = 0.04; 1 mmHg diastolic increase, P = 0.1, both adjusted for sex). Exposure during mid and late gestation was not associated with a stress-related increment of blood pressure (P adjusted for sex > 0.6). Correcting for confounders in a multivariable model did not attenuate the association between famine exposure in early gestation and the SBP increment. The heart rate increment was not related to famine exposure during any part of gestation. CONCLUSION: We found a greater blood pressure increase during stress among individuals exposed to famine in early gestation. Increased stress responsiveness may underlie the known association between coronary heart disease and exposure to famine in early gestation.

Birth Weight↗

Malnutrition and poverty in the early stages of famine: North Darfur, 1988-90.

In this article we report findings on the relationship between malnutrition and poverty during a period of acute food insecurity in Darfur, Sudan. Children of rich and poor families were equally likely to be malnourished, which is explained in terms of people's responses to the threat of famine. This finding has important implications for targeting interventions in the early stages of famine. Appropriate interventions at the early stages of famine are livelihood and income support to the most vulnerable. The entitlement theory of famine causation assumes that the poor are most vulnerable, and become malnourished and die during famines. In this article we show that this assumption does not hold. Even though poverty is the root cause of malnutrition, it does not follow that anthropometric status can be used to target individual poor families, or even that targeting the poor is appropriate in famine situations.

Chi-Square Distribution↗

Atopy, lung function, and obstructive airways disease after prenatal exposure to famine.

BACKGROUND: Associations have been found between a large head size at birth and atopy, and between low birth weight and obstructive airways disease. A study was undertaken of people born around the time of the Dutch famine in 1944-5 to determine the effects of maternal malnutrition during specific periods of gestation on the prevalence of obstructive airways disease and atopy. METHODS: Nine hundred and twelve people aged about 50, born at term between November 1943 and February 1947 in Amsterdam, were asked about their medical history. Lung function was measured in 733 and serum concentrations of total IgE and specific IgE against mite, pollen and cat were measured in 726. Those exposed in late, mid, and early gestation (exposed participants) were compared with those born before or conceived after the famine (non-exposed participants). RESULTS: Exposure to famine during gestation affected neither the concentrations of total or specific IgE nor lung function values. The prevalence of obstructive airways disease was increased in people exposed to famine in mid gestation (odds ratio adjusted for sex 1.7, 95% confidence interval (CI) 1.1 to 2.6) and tended to be higher in those exposed in early gestation (odds ratio 1.5, 95% CI 0. 9 to 2.6). CONCLUSIONS: The observed increase in the prevalence of obstructive airways disease in people exposed to famine in mid and early gestation was not parallelled by effects on IgE concentrations or lung function. The link between exposure to famine in mid and early gestation and obstructive airways disease in adulthood suggests that fetal lungs can be permanently affected by nutritional challenges during periods of rapid growth.

Birth Weight↗

The political economy of famine.

This paper explores some of the reasons why the well-laid plans of the 1970's failed to be an effective bulwark against hunger. It is reflective rather than critical because we are faced with the certainty that just as surely as the famines of the 1980's followed the famines of the 1970's, the 1990's will again see drought, crop failure and, unless things change a great deal, famine as well. The analysis of the causes of hunger current in the 1970's can be summarized somewhat brutally as follows. Either there is not enough to eat, or what is available is poor in nutritional quality. Poor nutrition is synergistic with disease. Together they result in increasing debility and finally death. Famine is an unusual event, precipitated by this same triad of factors, on a catastrophic scale. The strategies which emerged from this analysis can be placed similarly under three broad headings. The first is that food production must be increased so that there is more available for everyone. The second is that national food security strategies should be developed and implemented. The third is that nutritional quality of people's diets should be improved. These are three major goals which have dominated international thinking for a decade. This paper argues that this analysis is at the very least incomplete and that the strategies based upon it have failed to make a marked impact on the risk vulnerable households face to famine. It goes on to suggest that, irrespective of the quantity and quality of food generally available, the households, poorer communities and poorer countries are able to lay claim to a share of what is available. These claims are mediated by a hierarchy of relationships--households within communities, communities within countries and countries in the world at large--and the nature of the relationships constitutes the 'political economy' within which famines arise and must be analysed.

Africa↗

Hypothalamic-pituitary-adrenal axis activity in adults who were prenatally exposed to the Dutch famine.

OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be susceptible to fetal programming, the process by which an adverse fetal environment elicits permanent physiological and metabolic alterations predisposing to disease in later life. It is hypothesized that fetal exposure to poor circumstances alters the set point of the HPA axis, leading to increased HPA axis activity and subsequent increased cortisol concentrations. In this study, we tested the hypothesis that prenatal exposure to famine during different periods of gestation is associated with increased activity of the HPA axis. DESIGN AND METHODS: We assessed plasma cortisol concentrations after a dexamethasone suppression and an ACTH1-24 -stimulation test in a group of 98 men and women randomly sampled from the Dutch famine birth cohort. Cohort members were born as term singletons around the 1944-1945 Dutch famine. RESULTS: Cortisol profiles after dexamethasone suppression and ACTH1-24 stimulation were similar for participants exposed to famine during late, mid- or early gestation (P = 0.78). Cortisol concentrations after dexamethasone suppression test did not differ between those exposed and those unexposed to famine in utero (mean difference -2% (95% confidence interval (CI) -27 to 23)). Neither peak cortisol concentration (20 nmol/l (95% CI -27 to 66)), cortisol increment (-5 nmol/l (95% CI -56 to 47)) or cortisol area under the curve post-ACTH1-24 injection (4% (95% CI -4 to 12)) differed between exposed and unexposed participants. CONCLUSIONS: Prenatal famine exposure does not seem to affect HPA axis activity at adult age, at least not at the adrenal level. This does not exclude altered HPA axis activity at the levels of the hippocampus and hypothalamus.

Adult↗

The effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 gene on glucose/insulin metabolism interact with prenatal exposure to famine.

OBJECTIVE: An adverse fetal environment may permanently modify the effects of specific genes on glucose tolerance, insulin secretion, and insulin sensitivity. In the present study, we assessed a possible interaction of the peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala polymorphism with prenatal exposure to famine on glucose and insulin metabolism. RESEARCH DESIGN AND METHODS: We measured plasma glucose and insulin concentrations after an oral glucose tolerance test and determined the PPAR-gamma2 genotype among 675 term singletons born around the time of the 1944-1945 Dutch famine. RESULTS: A significant interaction effect between exposure to famine during midgestation and the PPAR-gamma2 Pro12Ala polymorphism was found on the prevalence of impaired glucose tolerance and type 2 diabetes. The Ala allele of the PPAR-gamma2 gene was associated with a higher prevalence of impaired glucose tolerance and type 2 diabetes but only in participants who had been prenatally exposed to famine during midgestation. Similar interactions were found for area under the curve for insulin and insulin increment ratio, which were lower for Ala carriers exposed to famine during midgestation. CONCLUSIONS: The effects of the PPAR-gamma2 Pro12Ala polymorphism on glucose and insulin metabolism may be modified by prenatal exposure to famine during midgestation. This is possibly due to a combined deficit in insulin secretion, as conferred by pancreatic beta-cell maldevelopment and carrier type of the Ala allele in the PPAR-gamma2 gene.

Aged↗

Demographic consequences of the 1984-1985 Ethiopian famine.

This article analyzes demographic responses to the 1984-1985 Ethiopian famine and compares them with Bongaarts and Cain's (1982) hypothesized responses. After briefly describing the data collection, I estimate the age distribution and the age-specific mortality and fertility rates of Ethiopian famine victims in a resettlement area and compare these with mortality estimates for the 1972-1973 Bangladesh famine and with fertility estimates from the 1981 Ethiopian demographic survey. The results show that the mortality rate among Ethiopian famine victims was about seven times higher than the rate among the Bangladesh victims and that the Ethiopian famine-related mortality was general and not a function of household socioeconomic variables. The data also show a 26 percent lower total fertility rate among famine victims.

Adolescent↗