Susanne R. de Rooij

Birth weight and risk of type 2 diabetes: A systematic review

CONTEXT Low birth weight is implicated as a risk factor for type 2 diabetes. However, the strength, consistency, independence, and shape of the association have not been systematically examined. OBJECTIVE To conduct a quantitative systematic review examining published evidence on the association of birth weight and type 2 diabetes in adults. DATA SOURCES AND STUDY SELECTION Relevant studies published by June 2008 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1950), and Web of Science (from 1980), with a combination of text words and Medical Subject Headings. Studies with either quantitative or qualitative estimates of the association between birth weight and type 2 diabetes were included. DATA EXTRACTION Estimates of association (odds ratio [OR] per kilogram of increase in birth weight) were obtained from authors or from published reports in models that allowed the effects of adjustment (for body mass index and socioeconomic status) and the effects of exclusion (for macrosomia and maternal diabetes) to be examined. Estimates were pooled using random-effects models, allowing for the possibility that true associations differed between populations. DATA SYNTHESIS Of 327 reports identified, 31 were found to be relevant. Data were obtained from 30 of these reports (31 populations; 6090 diabetes cases; 152 084 individuals). Inverse birth weight-type 2 diabetes associations were observed in 23 populations (9 of which were statistically significant) and positive associations were found in 8 (2 of which were statistically significant). Appreciable heterogeneity between populations (I(2) = 66%; 95% confidence interval [CI], 51%-77%) was largely explained by positive associations in 2 native North American populations with high prevalences of maternal diabetes and in 1 other population of young adults. In the remaining 28 populations, the pooled OR of type 2 diabetes, adjusted for age and sex, was 0.75 (95% CI, 0.70-0.81) per kilogram. The shape of the birth weight-type 2 diabetes association was strongly graded, particularly at birth weights of 3 kg or less. Adjustment for current body mass index slightly strengthened the association (OR, 0.76 [95% CI, 0.70-0.82] before adjustment and 0.70 [95% CI, 0.65-0.76] after adjustment). Adjustment for socioeconomic status did not materially affect the association (OR, 0.77 [95% CI, 0.70-0.84] before adjustment and 0.78 [95% CI, 0.72-0.84] after adjustment). There was no strong evidence of publication or small study bias. CONCLUSION In most populations studied, birth weight was inversely related to type 2 diabetes risk.

Hungry in the womb: what are the consequences? Lessons from the Dutch famine.

An increasing body of evidence suggests that poor nutrition at the very beginning of life - even before birth - leads to large and long term negative consequences for both mental and physical health. This paper reviews the evidence from studies on the Dutch famine, which investigated the effects of prenatal undernutrition on later health. The effects of famine appeared to depend on its timing during gestation, and the organs and tissues undergoing critical periods of development at that time. Early gestation appeared to be the most vulnerable period. People who were conceived during the famine were at increased risk of schizophrenia and depression, they had a more atherogenic plasma lipid profile, were more responsive to stress and had a doubled rate of coronary heart disease. Also, they performed worse on cognitive tasks which may be a sign of accelerated ageing. People exposed during any period of gestation had more type 2 diabetes. Future investigation will expand on the finding that the effects of prenatal famine exposure may reach down across generations, possibly through epigenetic mechanisms. Recent evidence suggests that similar effects of prenatal undernutrition are found in Africa, where many are undernourished. Hunger is a major problem worldwide with one in seven inhabitants of this planet suffering from lack of food. Adequately feeding women before and during pregnancy may be a promising strategy in preventing chronic diseases worldwide.

Prenatal undernutrition and cognitive function in late adulthood

At the end of World War II, a severe 5-mo famine struck the cities in the western part of The Netherlands. At its peak, the rations dropped to as low as 400 calories per day. In 1972, cognitive performance in 19-y-old male conscripts was reported not to have been affected by exposure to the famine before birth. In the present study, we show that cognitive function in later life does seem affected by prenatal undernutrition. We found that at age 56 to 59, men and women exposed to famine during the early stage of gestation performed worse on a selective attention task, a cognitive ability that usually declines with increasing age. We hypothesize that this decline may be an early manifestation of an accelerated cognitive aging process.

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 β-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 Kg 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 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 offsprings 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.

Depression and anxiety: Associations with biological and perceived stress reactivity to a psychological stress protocol in a middle-aged population

BACKGROUND Depression and anxiety have been linked to higher as well as lower reactivity to stressful circumstances. Large, population-based studies investigating the association between depression and anxiety, perceived and physiological stress responses are lacking. METHODS We studied 725 men and women, aged 55-60 years, from a population-based cohort, who filled out the Hospital Anxiety and Depression Scale (HADS). We performed a standardized interview on medical history and lifestyle. We measured continuous blood pressure (BP) and heart rate (HR) reactivity, saliva cortisol reactivity and perceived stress during a psychological stress protocol. RESULTS Albeit not statistically significant in all groups, systolic BP (SBP), diastolic BP (DBP), HR and cortisol reactivity to the psychological stress protocol were lower in those with mild-to-severe depression or anxiety symptoms and those ever clinically diagnosed with depression or anxiety, while perceived levels of stress were higher compared to those without depression or anxiety symptomatology. Maximum SBP, HR and cortisol stress responses significantly decreased and perceived stress scores significantly increased with increasing scores on the HADS depression subscale (HADS-D) and HADS anxiety subscale (HADS-A) (all P<0.05). The same held for stress responses in relation to the total HADS score (all P<0.05) and, in this case, the maximum DBP stress response was also significantly lower with an increasing HADS score (P=0.05). In addition, the maximum DBP stress response was significantly lower for those ever clinically diagnosed with depression (P=0.04). Adjusting for sex, use of anti-hypertensive medication, anti-depressant and anxiolytic medication, smoking, alcohol consumption, socio-economic status (SES) and body mass index (BMI) did not attenuate the results. CONCLUSION The present study results suggest that the biological stress response of middle-aged men and women who experienced depressed and anxious feelings does not completely correspond with how stressed they feel at that moment. Although differences were not substantial in all cases, response to a psychological stress protocol seemed to be decreased in the groups with experience of depressed and anxious feelings, while the perception of stress seemed to be increased.

Exposure to severe wartime conditions in early life is associated with an increased risk of irritable bowel syndrome: a population-based cohort study.

OBJECTIVES:Stressful events during early life have been suggested to play an important role in the development of the irritable bowel syndrome (IBS). In this study, we evaluate whether an exposure to severe wartime conditions during gestation and in early life are associated with an increased prevalence of IBS.METHODS:We assessed the prevalence of IBS using the Rome II questionnaire among 816 men and women (aged 58±1 years) who were born as term singletons in Wilhelmina Gasthuis, Amsterdam, The Netherlands around the time of World War II.RESULTS:Of a total of 816 participants, 9.6% (n=78, 52F) met the criteria for IBS. Exposure to severe wartime conditions in utero was not associated with the prevalence of IBS in adulthood (8.3%). Early-life exposure to severe wartime conditions was associated with an increased prevalence of IBS. The prevalence of IBS among individuals exposed up to 0.5 years of age, 1 year of age, and 1.5 years of age was 8.1%, 12.5%, and 15.3%, respectively. The increased IBS prevalence was not associated with an increased stress response.CONCLUSIONS:Our data indicate that exposure to severe wartime conditions in early life is associated with an increased risk of developing IBS. To what extent this is attributable to the stressful environment of war, to severe undernutrition, or to the increased prevalence of infectious diseases is, however, unclear.

Increased reproductive success of women after prenatal undernutrition

BACKGROUND Prenatal exposure to the Dutch famine is associated with an increased risk of chronic degenerative disease. We now investigate whether prenatal famine exposure affected reproductive success. METHODS We assessed reproductive success (number of children, number of twins, age at delivery, childlessness) of men and women born around the time of the Dutch famine of 1944–1945 in the Wilhelmina Gasthuis, Amsterdam, whose birth records have been kept. RESULTS Women who were exposed to the Dutch famine of 1944–1945 in utero are more reproductively successful than women who were not exposed to famine during their fetal development; they have more offspring, have more twins, are less likely to remain childless and start reproducing at a younger age. The increased reproductive success of these women is unlikely to be explained by genes which favor fertility and are passed from mothers to their daughters. In utero exposure to famine did not affect the reproductive success of males. CONCLUSIONS These findings suggest that poor nutrition during fetal development, followed by improved nutrition after birth can give rise to a female phenotype characterized by greater reproductive success.

Survival effects of prenatal famine exposure

BACKGROUND Adverse intrauterine conditions are known to be associated with an increased risk of chronic diseases in adult life. Previously, we showed that prenatal famine exposure increased the incidence of cardiovascular and metabolic disease in adulthood. OBJECTIVE We examined the association between prenatal famine exposure and adult mortality. DESIGN We studied adult mortality among 1991 term singletons from the Dutch Famine Birth Cohort. We compared overall and cause-specific adult mortality among people exposed to famine in late, mid, and early gestation with those unexposed to famine in utero by using Cox proportional hazard models. RESULTS A total of 206 persons (10%) had died by the end of follow-up. Compared with unexposed women, women exposed to famine in early gestation had a significantly higher risk of overall adult mortality (HR: 1.9; 95% CI: 1.1, 3.4), cardiovascular mortality (HR: 4.6; 95% CI: 1.2, 17.7), cancer mortality (HR: 2.3; 95% CI: 1.1, 4.7), and breast cancer mortality (HR: 8.3; 95% CI: 1.1, 63.0). In men exposed to famine in early gestation, these associations were as follows compared with unexposed men: overall adult mortality (HR: 0.4; 95% CI: 0.2, 1.1), cardiovascular mortality (HR: 0.9; 95% CI: 0.3, 3.1), and cancer mortality (HR: 0.3; 95% CI: 0.0, 1.9). CONCLUSIONS Women exposed to famine in early gestation had a higher overall adult, cardiovascular, cancer, and breast cancer mortality risk than did women not exposed to famine. No such effects were observed in men exposed to famine in early gestation.

Personality and physiological reactions to acute psychological stress

Stable personality traits have long been presumed to have biological substrates, although the evidence relating personality to biological stress reactivity is inconclusive. The present study examined, in a large middle aged cohort (N=352), the relationship between key personality traits and both cortisol and cardiovascular reactions to acute psychological stress. Salivary cortisol and cardiovascular activity were measured at rest and in response to a psychological stress protocol comprising 5min each of a Stroop task, mirror tracing, and a speech task. Participants subsequently completed the Big Five Inventory to assess neuroticism, agreeableness, openness to experience, extraversion, and conscientiousness. Those with higher neuroticism scores exhibited smaller cortisol and cardiovascular stress reactions, whereas participants who were less agreeable and less open had smaller cortisol and cardiac reactions to stress. These associations remained statistically significant following adjustment for a range of potential confounding variables. Thus, a negative personality disposition would appear to be linked to diminished stress reactivity. These findings further support a growing body of evidence which suggests that blunted stress reactivity may be maladaptive.