The association between exposure to famine in early life and risks of diabetic complications in adult patients with type two diabetes.

Background: In this study, we aimed to assess the associations between early exposure to famine and the risks of diabetic complications in adult patients with type two diabetes. Methods: The participants in this study were selected from China National HbA1c Surveillance System (2009-13) and further stratified according to the birth year. The participants born between 1956-59, 1959-61, and 1962-64 were classified as foetal exposed group with 70 852, infant/toddler exposed group with 93 616, and unexposed group with 72 723 participants. The association between exposure to famine in early life and risks of diabetic complications were analysed by logistic regression. We assessed the attributing effects of the interaction between exposure to famine in early life and modifiable risk factors by the multiplicative and additive interactive models. Results: After adjustments for sex, famine severity, economic status in adulthood, body mass index, blood pressure, low-density lipoprotein cholesterol, glycated haemoglobin, diabetes duration, and the use of antidiabetic agents, the increased risks of coronary heart disease (odds ratio (OR) = 1.31; 95% CI (confidence interval) = 1.26, 1.36), cerebrovascular disease (OR = 1.32; 95% CI = 1.24, 1.41), and diabetic retinopathy (OR = 1.06; 95% CI = 1.02, 1.10) were observed in patients with early-life exposure to famine. The reduced risk of diabetic kidney disease (OR = 0.94; 95% CI = 0.90, 0.99) was observed in patients with early-life exposure to famine compared with those without famine exposure. The interaction analyses indicated that obesity might exacerbate the increased risk of coronary heart disease (OR = 1.26; 95% CI = 1.22, 1.30), cerebrovascular disease (OR = 1.26; 95% CI = 1.21, 1.32), and diabetic retinopathy associated with early-life exposure to famine (OR = 1.09; 95% CI = 1.06, 1.12) in patients with type two diabetes. Moreover, high economic status in adulthood might also exacerbate the increased risk of coronary heart disease (OR = 1.35; 95% CI = 1.30, 1.40) and cerebrovascular disease (OR = 1.33; 95% CI = 1.23, 1.43) associated with early-life exposure to famine in patients with type two diabetes. Conclusions: Early-life exposure to famine in patients with type two diabetes might be associated with increased risks of coronary heart disease, cerebrovascular disease, and diabetic retinopathy but a reduced risk of diabetic kidney disease in adulthood. Obesity and high economic status might further exacerbate the risk of diabetic complications associated with early-life exposure to famine. Improving early-life nutritional status may promote better risk prevention and management of diabetic complications in patients with type two diabetes.

Fetal exposure to the Ukraine famine of 1932-1933 and adult type 2 diabetes mellitus.

The short-term impact of famines on death and disease is well documented, but estimating their potential long-term impact is difficult. We used the setting of the man-made Ukrainian Holodomor famine of 1932-1933 to examine the relation between prenatal famine and adult type 2 diabetes mellitus (T2DM). This ecological study included 128,225 T2DM cases diagnosed from 2000 to 2008 among 10,186,016 male and female Ukrainians born from 1930 to 1938. Individuals who were born in the first half-year of 1934, and hence exposed in early gestation to the mid-1933 peak famine period, had a greater than twofold likelihood of T2DM compared with that of unexposed controls. There was a dose-response relationship between severity of famine exposure and increase in adult T2DM risk.

Individual and combined effects of famine exposure and obesity parameters on type 2 diabetes in middle-aged and older adults: A population-based cross-sectional study.

Malnutrition early in life may have adverse effects on health later in life. The relationship between malnutrition and obesity parameters (body mass index [BMI] and waist circumference [WC]) and type 2 diabetes is inconsistent. This study aimed to identify the effects of famine exposure and obesity parameters on type 2 diabetes individually or in combination among middle-aged and older adults in China. Data were extracted from the China Health and Retirement Longitudinal Study Wave1 in 2011. The sample involved 13,065 adults aged 45 to 90. The t- or F test was employed to compare age among groups. The chi-square test was utilized to compare baseline characteristics according to the categorical WC levels/BMI levels/famine exposure and examine between-group differences in type 2 diabetes (diabetes and non-diabetes). Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models to estimate the individual and combined associations of BMI/WC levels and famine exposure with the prevalence of type 2 diabetes. In this study, 1559 (11.93%) individuals were exposed to Chinese famine during their fetal stage, 5132 (39.28%) and 4428 (33.89%) in childhood and adolescence/adulthood, respectively. Among BMI measurements, 3780 (28.93%) were overweight, and 1487 (11.38%) were obese, whereas WC measurements showed that 5408 (41.39%) were obesity. In addition, 831 (45.48%) males and 996 (54.52%) females reported type 2 diabetes. In multivariable-adjusted regression models, obesity parameters and famine exposure were independently associated with type 2 diabetes prevalence among all participants (P < .001). In the interaction analysis, there existed a trend of higher odds for prevalence of type 2 diabetes across all groups compared to the combination of no-exposed and normal BMI/WC level group (the most increase in odds, adolescence/adulthood-exposed group with central obesity in WC levels: OR 4.51 (95% CI = 3.42-5.95); adolescence/adulthood-exposed group with obesity in BMI levels: OR 5.84 (95% CI = 4.11-8.30; P for interaction <.001). The findings for females exhibited similar to the overall participants, when by gender stratification. Our results suggest famine exposure and obesity parameters have positive combined effects on type 2 diabetes in middle-aged and older adults in China.

Great leap forward famine exposure and urban-rural migration convolute the modern prevalence of diabetes in China.

BACKGROUND: Although evidence from birth cohort analysis has indicated the metabolic risk of early-life exposure to the Great Leap Forward Famine (GLFF) in China, three confounding effects, including the exposure windows, aging, and geographical variations in famine severity, have been brought to debates for a decade. This study aimed to address these confounding effects and extensively examine how GLFF exposure is associated with diabetes risk in mid-to-late life and its interaction with urban-rural migration. METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed with age-stratification and stepped wedge approaches. Weighted prevalence and multivariable logistic regression were used to investigate the effects of GLFF exposure and urban-rural migration on mid-to-late life diabetes risk and the interaction between GLFF exposure and urban-rural migration. Birth provinces were controlled as a fixed effect to account for variations in famine severity across provinces. RESULTS: Compared to those who were never exposed to GLFF, fetal GLFF exposure was associated with a higher risk of adult-onset diabetes after controlling for provinces, demographics, and health statuses. Yet, after adding the proxy of childhood growth environments into the model, fetal exposure to GLFF was not significantly associated with adult-onset diabetes risk (OR = 1.22, p = 0.10), compared to those who were never exposed to GLFF. Across the three age-stratification groups, static urban residents, in general, had a higher risk of diabetes compared to static rural residents. Interaction effects between GLFF exposure and urban-rural migration were insignificant across all three age-stratification groups. CONCLUSION: Fetal exposure to GLFF might have a traceable effect on adult-onset diabetes risk. Yet, the growth environment and urban lifestyle outweigh and further confound the impact of GLFF exposure on adult-onset diabetes risk.

Vestiges of famine: Long-term mortality impacts of early-life exposure to the 1840s famine in Estonia.

The paper investigates whether exposure to a famine in the Russian Tsarist Province of Livland in 1844-1846 in early life negatively affected survival at later ages, using individual data from two rural parishes. We follow 18 birth cohorts born between 1834-1852 until age 75 and differentiate between timing and length of exposures. We find that relative to individuals born in pre- or post- crisis years, there were no significant differences in survival from age 21-75. Cohorts with longer exposure to famine conditions had increased mortality only in short term, up to age 20. Males were more vulnerable in younger ages than females. The negative effect of adverse early life exposure on survival in later life was constrained to lower social group - the landless, but for the better-off groups the effect was constrained to younger ages. The paper highlights the importance of accounting for sex and socio-economic differences in studies exploring the effects of early life conditions on later-life survival.

Severe prenatal shocks and adolescent health: Evidence from the Dutch Hunger Winter.

This paper investigates health impacts at the end of adolescence of prenatal exposure to multiple shocks, by exploiting the unique natural experiment of the Dutch Hunger Winter. At the end of World War II, a famine occurred abruptly in the Western Netherlands (November 1944-May 1945), pushing the previously and subsequently well-nourished Dutch population to the brink of starvation. We link high-quality military recruits data with objective health measurements for the cohorts born in the years surrounding WWII with newly digitised historical records on calories and nutrient composition of the war rations, daily temperature, and warfare deaths. Using difference-in-differences and triple differences research designs, we first show that the cohorts exposed to the Dutch Hunger Winter since early gestation have a higher Body Mass Index and an increased probability of being obese at age 18. We then find that this effect is partly moderated by warfare exposure and a reduction in energy-adjusted protein intake. Lastly, we account for selective mortality using a copula-based approach and newly-digitised data on survival rates, and find evidence of both selection and scarring effects. These results emphasise the complexity of the mechanisms at play in studying the consequences of early conditions.

Dairying, diseases and the evolution of lactase persistence in Europe.

In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years1. Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions2,3. Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectories than uniform selection since the Neolithic period. In the UK Biobank4,5 cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation-proxies for these drivers-provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.

Perinatal famine is associated with excess risk of proliferative retinopathy in patients with type 2 diabetes.

PURPOSE: Intrauterine undernutrition is associated with increased risk of type 2 diabetes. Children born premature or small for gestational age were reported to have abnormal retinal vascularization. However, whether intrauterine famine act as a trigger for diabetes complications, including retinopathy, is unknown. The aim of the current study was to evaluate long-term effects of perinatal famine on the risk of proliferative diabetic retinopathy (PDR). METHODS: We studied the risk for PDR among type 2 diabetes patients exposed to perinatal famine in two independent cohorts: the Ukrainian National Diabetes Registry (UNDR) and the Hong Kong Diabetes Registry (HKDR). We analysed individuals born during the Great Famine (the Holodomor, 1932-1933) and the WWII (1941-1945) famine in 101 095 (3601 had PDR) UNDR participants. Among 3021 (251 had PDR) HKDR participants, we studied type 2 diabetes patients exposed to perinatal famine during the WWII Japanese invasion in 1942-1945. RESULTS: During the Holodomor and WWII, perinatal famine was associated with a 1.76-fold (p = 0.019) and 3.02-fold (p = 0.001) increased risk of severe PDR in the UNDR. The risk for PDR was 1.66-fold elevated among individuals born in 1942 in the HKDR (p < 0.05). The associations between perinatal famine and PDR remained statistically significant after corrections for HbA1c in available 18 507 UNDR (padditive interaction < 0.001) and in 3021 HKDR type 2 diabetes patients (p < 0.05). CONCLUSION: In conclusion, type 2 diabetes patients, exposed to perinatal famine, have increased risk of PDR compared to those without perinatal famine exposure. Further studies are needed to understand the underlying mechanisms and to extend this finding to other diabetes complications.

Early-Life Exposure to the Chinese Great Famine and Later Cardiovascular Diseases.

Objectives: This study aimed to examine the association between early life famine exposure and adulthood cardiovascular diseases (CVDs) risk. Methods: A total of 5,504 subjects were selected using their birthdate from national baseline data of the China Health and Retirement Longitudinal Survey to analyze the association between famine exposure in early life and CVDs risk in adulthood. CVDs was defined based on the self-reported doctor's diagnosis. Results: The prevalence of CVDs in the unexposed group, fetal-exposed, infant-exposed, and preschool-exposed groups was 15.0%, 18.0%, 21.0%, and 18.3%, respectively. Compared with the unexposed group, fetal-exposed, infant-exposed and preschool-exposed groups had higher CVDs risk in adulthood (p < 0.05). Compared with the age-matched control group, infancy exposed to famine had a significantly higher adulthood CVDs risk (OR = 1.52, 95% CI: 1.15, 2.01; p = 0.006). The association seems to be stronger among population with higher education level (P interaction = 0.043). Sensitivity analysis revealed consistent association between early-life famine exposure and adult CVDs risk. Conclusion: Early life exposed to the China great famine may elevate the risk of CVDs in adulthood.

Overweight and obesity at age 19 after pre-natal famine exposure.

BACKGROUND: Weight for height has been used in the past as an indicator of obesity to report that prenatal exposure to the Dutch famine of 1944-1945 determined subsequent obesity. Further evaluation is needed as unresolved questions remain about the possible impact of social class differences in fertility decline during the famine and because being overweight is now defined by a Body Mass Index (BMI: kg/m2) from 25 to <30 and obesity by a BMI of 30 or more. METHODS: We studied heights and weights of 371,100 men in the Netherlands born between 1943 and 1947 and examined for military service at age 19. This group includes men with and without prenatal exposure to the Dutch famine. RESULTS: There was a 1.3-fold increase in the risk of being overweight or obese in young adults at age 19 after prenatal famine exposure in early gestation. The increase was only seen in sons of manual workers born in the large cities of Western Netherlands and not among those born in smaller cities or rural areas in the West. Social class differentials in fertility decline during the famine did not bias study results. CONCLUSIONS: The long-term adverse impact of prenatal famine on later life type 2 diabetes and mortality through age 63 is already showing at age 19 in this population as a significant increase in overweight risk.

Exposure to the Great Famine in Early Life and the Risk of Obesity in Adulthood: A Report Based on the China Health and Nutrition Survey.

Intrauterine malnutrition has a long-term effect on human health. This study aimed to evaluate the associations between exposure to famine in early life and obesity in adulthood in Chinese adults. A total of 5033 participants (22,132 observations) of the China Health and Nutrition Survey (CHNS) in 1991-2015 were classified into three famine exposure groups according to their birth year: unexposed (1963-1966), fetal-exposed (1959-1962) and childhood-exposed (1955-1958). Compared with the unexposed group, the fetal-exposed group had higher levels of body-mass-index (BMI) and waist-circumference (WC), and higher prevalence of overweight and central obesity, whereas the childhood-exposed group had lower levels of the measurements. However, the positive associations of fetal exposure with BMI, WC and prevalence of overweight and central obesity were attenuated by additionally adjusting for age at survey. Stratified analysis showed that the adverse effect of fetal exposure to famine was only observed in subjects at several specific age-groups, and in men living in rural areas and in women living in more severe famine exposed areas (p for interaction < 0.05). Our results provide evidence for the weak effect of fetal exposure to famine on body measurements in adulthood, and suggest the importance of severity of famine exposure and timing of exposure.

Fleeing mass starvation: what we (do not) know about the famine-migration nexus.

The relationship between famine and migration has not been studied adequately to date. A systematic review of scholarship centred on famine and its demographic, political, and socioeconomic effects demonstrates the paucity of academic attention to the issue. This paper surveys the dominant hypotheses and findings regarding the connection between famine and migration. It delineates key questions that an interdisciplinary and case-based exploration of the subject should address, highlighting gaps in the literature with respect to population-level analyses. Primary observations about the literature reviewed include tenuous generalisations about the linkage between famine and migration and partial examination of the role of politics in enabling or prohibiting mobility during hunger-related crises. In addition, disciplinary silos influence which particular aspects of a famine are scrutinised and which are not appraised. In view of these concerns, international legal and humanitarian norms governing migration also need to pay closer attention to its association with famine.

Association between famine exposure in early life with insulin resistance and beta cell dysfunction in adulthood.

OBJECTIVES: Famine exposure in early life was associated with type 2 diabetes, non-alcoholic fatty liver disease and metabolic syndrome, etc. But evidence in early famine exposure and insulin resistance and beta cell dysfunction were limited. We aimed to investigate whether the association existed between famine exposure in early life and beta cell dysfunction and insulin resistance in adulthood. METHODS: In all, 7912 non-diabetic participants were included in this study, based on SPECT-China study. Participants with fetal or childhood famine exposure (birth year 1949-1962) were exposure group. Insulin resistance was estimated by the homeostasis model assessment index of insulin resistance (HOMA-IR). Beta cell function, represented by insulin secretion, was estimated by the disposition index. The associations of famine exposure with HOMA-IR and disposition index were assessed via linear regression. RESULTS: In men, we did not observe a significant association between early life famine exposure and ln(HOMA-IR) in all three models (P > 0.05 for all). However, in women, early life famine exposure were found to have significant association with ln(HOMA-IR) after adjustments for urbanization, severity of famine exposure, current smoker, waist circumference, hypertension, and dyslipidemia (unstandardized coefficients 0.055, 95% confidence interval 0.021, 0.088, P = 0.001). Early life famine exposure was observed to be negatively associated with ln(disposition index) after adjustments for the above potential confounders, both in men (model 3: unstandardized coefficients -0.042, 95% confidence interval -0.072,-0.012, P = 0.006) and women (model 3: unstandardized coefficients -0.033, 95% confidence interval -0.058,-0.009, P = 0.008). CONCLUSIONS: In conclusion, exposure to famine in fetal- and childhood- life period is associated with beta cell dysfunction in males and females without diabetes, but early life famine exposure was only associated with insulin resistance in non-diabetic females. These results indicate that malnutrition in early life period may offer a modifiable factor for type 2 diabetes development.

Early Life Famine Exposure, Ideal Cardiovascular Health Metrics, and Risk of Incident Diabetes: Findings From the 4C Study.

OBJECTIVE: We aim to investigate the impact of ideal cardiovascular health metrics (ICVHMs) on the association between famine exposure and adulthood diabetes risk. RESEARCH DESIGN AND METHODS: This study included 77,925 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study who were born around the time of the Chinese Great Famine and free of diabetes at baseline. They were divided into three famine exposure groups according to the birth year, including nonexposed (1963-1974), fetal exposed (1959-1962), and childhood exposed (1949-1958). Relative risk regression was used to examine the associations between famine exposure and ICVHMs on diabetes. RESULTS: During a mean follow-up of 3.6 years, the cumulative incidence of diabetes was 4.2%, 6.0%, and 7.5% in nonexposed, fetal-exposed, and childhood-exposed participants, respectively. Compared with nonexposed participants, fetal-exposed but not childhood-exposed participants had increased risks of diabetes, with multivariable-adjusted risk ratios (RRs) (95% CIs) of 1.17 (1.05-1.31) and 1.12 (0.96-1.30), respectively. Increased diabetes risks were observed in fetal-exposed individuals with nonideal dietary habits, nonideal physical activity, BMI ≥24.0 kg/m2, or blood pressure ≥120/80 mmHg, whereas significant interaction was detected only in BMI strata (P for interaction = 0.0018). Significant interactions have been detected between number of ICVHMs and famine exposure on the risk of diabetes (P for interaction = 0.0005). The increased risk was observed in fetal-exposed participants with one or fewer ICVHMs (RR 1.59 [95% CI 1.24-2.04]), but not in those with two or more ICVHMs. CONCLUSIONS: The increased risk of diabetes associated with famine exposure appears to be modified by the presence of ICVHMs.