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Exposure to severe famine in the prenatal or postnatal period and the development of diabetes in adulthood: an observational study

DOI:10.1007/s00125-016-4148-4
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Ningjian Wang at Shanghai Jiao Tong University
Ningjian Wang
Jing Cheng
Jing Cheng
Jing Cheng
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Bing Han at Shanghai Jiao Tong University
Bing Han
Qin Li
Qin Li
Qin Li
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Aims/hypothesis: Limited studies have compared the effect of prenatal or postnatal exposure to different severities of famine on the risk of developing diabetes. We aimed to measure the association between diabetes in adulthood and the exposure to different degrees of famine early in life (during the prenatal or postnatal period) during China's Great Famine (1959-1962). Methods: Data from 3967 individuals were included (a total of 2115 individuals from areas severely affected by famine, 1858 from moderately affected areas, 6 excluded due to missing data). A total of 2335 famine-exposed individuals were further divided into those exposed during the fetal stage, childhood or adolescence/young adulthood. We constructed a difference-in-differences model to compare HbA1c and fasting plasma glucose among the participants exposed to different degrees of famine intensity at different life stages. Logistic analyses were used as measures of the association between diabetes and the different levels of famine severity at different life stages. Results: Individuals who had been exposed to famine during the fetal period, childhood, and adolescence/adulthood and who had lived in a severely affected area had a 0.31%, 0.20% and 0.27% higher HbA1c, respectively, (all p < 0.01) compared with unexposed individuals. After adjusting for age, sex, smoking status, education level and waist circumference, participants exposed to severe famine during the fetal stage (OR 1.90, 95% CI 1.12, 3.21) and childhood (OR 1.44, 95% CI 1.06, 1.97) had significantly higher odds estimates. Unexposed participants living in severely and moderately affected areas had a comparable prevalence of diabetes (OR 1.22, 95% CI 0.80, 1.87). A significant interaction between famine exposure during the fetal and childhood periods and the level of severity in the area of exposure was found (p < 0.05). Conclusions/interpretation: Exposure to severe famine in the fetal or childhood period may predict a higher HbA1c and an increased diabetes risk in adulthood. These results from China indicate that both the prenatal and postnatal period may offer critical time windows for the determination of the risk of diabetes.
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ARTICLE
Exposure to severe famine in the prenatal or postnatal period
and the development of diabetes in adulthood: an observational
study
Ningjian Wang
1
&Jing Cheng
1
&Bing Han
1
&Qin Li
1
&Yi Chen
1
&Fangzhen Xia
1
&
Boren Jiang
1
&Michael D. Jensen
2
&Yingli Lu
1
Received: 19 July 2016 /Accepted: 3 October 2016 /Published online: 2 November 2016
#Springer-Verlag Berlin Heidelberg 2016
Abstract
Aims/hypothesis Limited studies have compared the effect of
prenatal or postnatal exposure to different severities of famine
on the risk of developing diabetes. We aimed to measure the
association between diabetes in adulthood and the exposure to
different degrees of famine early in life (during the prenatal or
postnatal period) during China’s Great Famine (1959–1962).
Methods Data from 3967 individuals were included (a total of
2115 individuals from areas severely affected by famine, 1858
from moderately affected areas, 6 excluded due to missing
data). A total of 2335 famine-exposed individuals were further
divided into those exposed during the fetal stage, childhood or
adolescence/young adulthood. We constructed a difference-
in-differences model to compare HbA
1c
and fasting plasma
glucose among the participants exposed to different degrees
of famine intensity at different life stages. Logistic analyses
were used as measures of the association between diabetes and
the different levels of famine severity at different life stages.
Results Individuals who had been exposed to famine during
the fetal period, childhood, and adolescence/adulthood and
who had lived in a severely affected area had a 0.31%,
0.20% and 0.27% higher HbA
1c
, respectively, (all p<0.01)
compared with unexposed individuals. After adjusting for
age, sex, smoking status, education level and waist circumfer-
ence, participants exposed to severe famine during the fetal
stage (OR 1.90, 95% CI 1.12, 3.21) and childhood (OR 1.44,
95% CI 1.06, 1.97) had significantly higher odds estimates.
Unexposed participants living in severely and moderately af-
fected areas had a comparable prevalence of diabetes (OR
1.22, 95% CI 0.80, 1.87). A significant interaction between
famine exposure during the fetal and childhood periods and
the level of severity in the area of exposure was found
(p<0.05).
Conclusions/interpretation Exposure to severe famine in the
fetal or childhood period may predict a higher HbA
1c
and an
increased diabetes risk in adulthood. These results from China
indicate that both the prenatal and postnatal period may offer
critical time windows for the determination of the risk of
diabetes.
Keywords Diabetes .Famine .Postnatal period .Prenatal
period .Severity
Abbreviations
DID Difference-in-differences
FPG Fasting plasma glucose
SPECT-
China
Survey on Prevalence in East China for
Metabolic Diseases and Risk Factors
Introduction
Diabetes is an important cause of mortality and morbidity
worldwide [1]. It has become pandemic in some developing
countries. According to data from 2008, individuals in China
Electronic supplementary material The online version of this article
(doi:10.1007/s00125-016-4148-4) contains peer-reviewed but unedited
supplementary material, which is available to authorised users.
*Michael D. Jensen
jensen@mayo.edu
*Yingli Lu
luyingli2008@126.com
1
Institute and Department of Endocrinology and Metabolism,
Shanghai Ninth People’s Hospital, Shanghai JiaoTong University
School of Medicine, Shanghai 200011, People’s Republic of China
2
Endocrine Research Unit, 5-194 Joseph, Mayo Clinic,
Rochester, MN 55905, USA
*Yingli Lu
luyingli2008@126.com
*Michael D. Jensen
jensen@mayo.edu
Diabetologia (2017) 60:262–269
DOI 10.1007/s00125-016-4148-4
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Previous famine studies conducted in Asia, Europe, and Africa contributed a substantial body of evidence on the association of prenatal exposure to famine and hyperglycemia and or development of diabetes mellitus in adulthood [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] . However, these reports indicated inconsistent findings where the majority reported higher risk of hyperglycemia and or diabetes with the exposure [19][20][21][22][23][24][25][26][27][28] . ...
... Previous famine studies conducted in Asia, Europe, and Africa contributed a substantial body of evidence on the association of prenatal exposure to famine and hyperglycemia and or development of diabetes mellitus in adulthood [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] . However, these reports indicated inconsistent findings where the majority reported higher risk of hyperglycemia and or diabetes with the exposure [19][20][21][22][23][24][25][26][27][28] . Conversely, there existed studies which revealed null findings [14][15][16][17][18] and an inverse association of early childhood famine exposure and impaired glucose metabolism during adulthood 19 . ...
... Corroborating our finding, many epidemiological surveys and studies involving children with low birthweight reported a link between early childhood nutrition deprivation and increased risk of diabetes [19][20][21][22][23][24][25][26][27][28] . Similarly, proxy to famine exposure, survivors of severe childhood malnutrition were also found to have reduced insulin sensitivity, or glucose intolerance [37][38][39][40] . ...
Impact of prenatal famine exposure on adulthood fasting blood glucose level
Article
Full-text available
  • Apr 2022
In the past decade, in low-income countries, there have been a rapid rise in prevalence of diabetes among adult population. Hence, understanding the context specific drivers of this change including the impacts of childhood nutrition adversaries on adult metabolic conditions is critical undertaking. This study investigates the potential effects of prenatal famine exposure to the Ethiopian great famine (1983–1985) on adulthood blood glucose level of survivors. A total of 441 adults (222 exposed and 219 controls) were included in the study. Self-reported place of birth and, date of birth and/or age were used to identify participants. A multivariable linear regression analysis was used to analyze the impact of prenatal famine exposure on the level of fasting blood glucose. In linear regression, unadjusted model (Model 1), fasting blood glucose level was increased by 4.13 (β = 4.13; 95% CI .41, 7.42) points in prenatal famine exposed groups, compared with non-exposed. Similarly, the positive association of prenatal famine exposure and fasting blood glucose level was maintained after adjusted for sex (Model 2) (β = . 4.08 95% CI .056, 7.50). Further adjusted for age, residence, educational status, wealth index and family size (Model 3) resulted in 4.10 (β = . 4.10 95% CI .45, 7.56) points increases in fasting blood glucose level. In model 4 adjusting for dietary pattern, physical activity level and family history of diabetes, alcohol and cigarette smoking resulted in 3.90 (β = 3.90, 95% CI 039, 7.52) points increase in fasting glucose level. In the he full adjusted model (Model 5) prenatal exposure to famine was resulted in 3.78 (β = 3.78, 95% CI .22, 7.34) increases in fasting blood glucose level after adjusted for BMI and waist to height ratio. There existed a positive association of prenatal famine exposure and adulthood blood glucose levels. In this population, establishing effective overweight/obesity prevention programs to minimize the co-impact of early famine exposure on blood glucose control are important.
... Because the Chinese Famine occurred from 1959 to 1962, consistent with previous Chinese famine studies (4,12,16,17), birth year was taken as the proxy variable of exposure to famine in this study. We defined those born between January 1, 1959, and December 31, 1962, as fetal exposure group, those born between January 1, 1949, and December 31, 1958, as childhood-exposed group, and those born between January 1, 1963, and December 31, 1974, as a nonexposed group. ...
... First, misclassification of famine exposure may exist, which might underestimate the effects of famine exposure. However, using the birth date of an individual to define famine exposure was the most common method in studies on the Great Chinese Famine (12,17). Second, the ideal diet calculated by the AHA Diet Score should be calculated on the basis of consumption of whole grains, fruits, vegetables, fish, sodium, sweets, and sugary beverages. ...
Ideal Cardiovascular Health Metrics Modify the Association Between Exposure to Chinese Famine in Fetal and Cardiovascular Disease: A Prospective Cohort Study
Article
Full-text available
  • Nov 2021
Background: No study has explored the modification effect of ideal cardiovascular health metrics (ICVHMs) on the association between famine exposure and risk of cardiovascular disease (CVD) so far. We aim to examine the effect of ICVHMs on the association between exposure to famine early in life and the risk of CVD in adulthood. Methods: A total of 61,527 participants free of CVD were included in this study from the Kailuan Study. All participants were divided into three groups, included nonexposed, fetal-exposed, and childhood-exposed groups. Cox regression was used to estimate the effect of famine exposure and ICVHMs on CVD risk. Results: After a median of 13.0 (12.7–13.2) years follow-up, 4,814 incident CVD cases were identified. Compared with nonexposed participants, the CVD risk increased in participants with fetal famine exposure (hazard ratio [HR]: 1.21; 95% CI: 1.07–1.37), but not in childhood famine-exposed participants. After stratifying by the number of ICVHMs, the increased CVD risk associated with fetal famine exposure was only observed in participants with less ICVHMs ( ≤ 2) (HR: 1.30; 95% CI: 1.11–1.52, P for interaction=0.008), but disappeared in those with three or more ICVHMs. The modified effect of ICVHMs was sex specific ( P for sex interaction = 0.031). Conclusions: Exposing to famine in the fetal period could increase the risk of CVD in late life; however, ICVHMs might modify the effect of famine exposure on CVD risk, especially in men.
... Erken yaşamdaki yetersiz beslenme koşulları ile yaşamın ilerleyen dönemlerinde olumsuz sağlık sonuçları arasında nedensel bir ilişki, hem deneysel hem de gözlemsel çalışmalarda tekrar tekrar gösterilmiştir (7,8). Bu çalışmalardan elde edilen bulgulara dayanarak, "Sağlık ve Hastalığın Gelişimsel Kökenleri" (Developmental Origins of Health and Disease, DOHaD) kavramı tanıtılmıştır. ...
Erken Yaşamda Yetersiz Beslenmenin Tip 2 Diyabetes Mellitus Gelişim Riskine Etkisi
Article
Full-text available
  • Dec 2021
Tip 2 diyabetes mellitus (T2DM) genetik, epigenetik ve çevresel faktörlerin karmaşık bir etkileşimi olan çok faktörlü bir hastalıktır. Tip 2 diyabetes mellitusun küresel sağlık ve ekonomik yük üzerinde önemli etkileri vardır. Biriken kanıtlar doğrultusunda bu hastalığın dünya genelinde insidansındaki artışı sadece genetik veya yetişkin çevresel koşullardan değil aynı zamanda yaşamın erken dönemlerindeki olumsuz durumlardan etkilenebileceğini düşündürmektedir. Son yıllarda, hem hayvan deneyleri hem de kıtlık gibi doğal durumlardan elde edilen kanıtlar, erken yaşamda yetersiz besin alımını, yetişkin yaşamındaki T2DM riski ile ilişkilendirmiştir. İntrauterin yetersiz besin alımı ile ortaya çıkan büyüme kısıtlamasının, fetal gelişimi bozabileceği ve böylece fetal yağ dokusu ve pankreatik beta hücre disfonksiyonuna neden olabileceğine dair kanıtlar vardır. Bunun sonucunda insülin sekresyon kapasitesinde azalma ve insülin direnci de dâhil olmak üzere, glukoz-insülin metabolizmasında kalıcı adaptif değişiklikler meydana gelebilir. Bu değişiklikler artan bir yağ depolama kabiliyetine yol açabilir, böylece birey daha sonraki yaşamda T2DM gelişimine yatkın hâle gelebilir. Bu ilişkide DNA metilasyonu, histon modifikasyonu ve mikroRNA etkileşimleri gibi epigenetik mekanizmalar temel rol oynamaktadır. Bu derlemede, T2DM patogenezinde gelişimsel epigenetik varyasyonun rolünü gösteren temel mekanizmalar ve araştırma bulguları özetlenmiştir.
... Activation of the HPG axis through GnRH signaling at the onset of puberty stimulates the transition from juvenile to adult life in mammals (Parent et al., 2003). Juvenile metabolic stress caused by famine or low socioeconomic status perturbs HPG activity and thereby contributes to the pathogenesis of metabolic syndrome both within and across generations (Habtu et al., 1999;Painter et al., 2008;Jang et al., 2013;Wang et al., 2017). ...
The Glucagon-Like Adipokinetic Hormone in Drosophila melanogaster – Biosynthesis and Secretion
Article
Full-text available
  • Dec 2021
Metabolic homeostasis requires the precise regulation of circulating sugar titers. In mammals, homeostatic control of circulating sugar titers requires the coordinated secretion and systemic activities of glucagon and insulin. Metabolic homeostasis is similarly regulated in Drosophila melanogaster through the glucagon-like adipokinetic hormone (AKH) and the Drosophila insulin-like peptides (DILPs). In flies and mammals, glucagon and AKH are biosynthesized in and secreted from specialized endocrine cells. K ATP channels borne on these cells respond to fluctuations in circulating glucose titers and thereby regulate glucagon secretion. The influence of glucagon in the pathogenesis of type 2 diabetes mellitus is now recognized, and a crucial mechanism that regulates glucagon secretion was reported nearly a decade ago. Ongoing efforts to develop D. melanogaster models for metabolic syndrome must build upon this seminal work. These efforts make a critical review of AKH physiology timely. This review focuses on AKH biosynthesis and the regulation of glucose-responsive AKH secretion through changes in CC cell electrical activity. Future directions for AKH research in flies are discussed, including the development of models for hyperglucagonemia and epigenetic inheritance of acquired metabolic traits. Many avenues of AKH physiology remain to be explored and thus present great potential for improving the utility of D. melanogaster in metabolic research.
... Most of the previous studies meant exactly that famine exposure was at a higher risk for health outcomes in late adolescence and adulthood. Exposure to Chinese famine in early life was related to increased risk of metabolic syndrome [41,44,[53][54][55][56][57], weight gain [26][27][28][29][30][31], diabetes [58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73], hypertension [11,12,[14][15][16][17][18][19][20][21][22][23], cognitive decline [74][75][76][77][78][79][80], and depressive syndrome [42,76,81,82]. In addition, our study found that there were linear trends in the associations of BMI with hypertension which was consistent with our previous study [83]. ...
Combined Effect of Famine Exposure and Obesity Parameters on Hypertension in the Midaged and Older Adult: A Population-Based Cross-Sectional Study
Article
Full-text available
Objectives: Undernutrition early in life may increase the incidence of adverse effects on adult health. The relations between undernutrition and obesity parameters (body mass index (BMI) and WC (waist circle)) and hypertension were often contradictory. Our study is aimed at identifying the combined effects of famine exposure and obesity parameters on hypertension in middle-aged and older Chinese. Design: A population-based cross-sectional study. Setting. Data were selected from the China Health and Retirement Longitudinal Study Wave2011 (CHARLS Wave2011). Participants. The sample included 12945 individuals aged 45 to 96. Main Outcome Measurements. The study analyzed data from 12945 middle-aged and older Chinese selected from CHARLS Wave2011. Differences between baseline characteristics and famine exposure/BMI levels/WC levels were evaluated using the t-, Chi-square- (χ 2-), and F-test. Then, the difference in the prevalence of hypertension between baseline characteristics was estimated by the t- and χ 2-test. Finally, multivariable-adjusted logistic regression models were used to explore the associations of famine exposure and obesity parameters with odds of prevalence of hypertension. Results: Among the 12945 participants, 1548 (11.96%) participants had been exposed to the Chinese famine during the fetal group, whereas 5101 (39.41%) participants and 4362 (33.70%) participants had been exposed to the famine during childhood and adolescence/adult group, respectively. Regarding the participants with BMI levels, 3746 (28.94%) were overweight, and 1465 (11.32%) were obese, whereas 5345 (41.29%) of the participants with WC levels were obese, respectively. Furthermore, 1920 (31.17%) had hypertension in males and 2233 (32.91%) in females. In multivariable-adjusted models, famine exposure and obesity parameters were related with prevalence of hypertension independently in total populations ((1) model threec, famine exposure with prevalence of hypertension: the fatal-exposed vs. no-exposed group (OR1.27; 95% CI 1.08, 1.49); childhood-exposed vs. no-exposed group (OR1.64; 95% CI 1.44, 1.87); the adolescence/adult-exposed vs. no-exposed group (OR3.06; 95% CI 2.68, 3.50); P for trend < 0.001; (2) model threee, famine exposure with prevalence of hypertension: the fatal-exposed vs. no-exposed group (OR1.25; 95% CI 1.06, 1.47); childhood-exposed vs. no-exposed group (OR1.52; 95% CI 1.34, 1.73); the adolescence/adult-exposed vs. no-exposed group (OR2.66; 95% CI 2.33, 3.03); P for trend < 0.001; (3) model threeg, BMI levels with prevalence of hypertension: overweight vs. normal (OR1.75; 95% CI 1.60, 1.91); obesity vs. normal (OR2.79; 95% CI 2.48, 3.15); P for trend < 0.001; (4) WC levels with prevalence of hypertension: overweight vs. normal (OR1.42; 95% CI 1.36, 1.48)). When stratified by sex, results in both males and females were mostly similar to those in the total population. In general, interaction analysis in the multivariable-adjusted model, compared with the combination of normal BMI/WC levels and no-exposed famine group, all groups trended towards higher odds of prevalence of hypertension (the greatest increase in odds, adolescence/adult-exposed group with obesity in BMI levels: (OR8.13; 95% CI 6.18, 10.71); adolescence/adult-exposed group with obesity in WC levels: (OR6.36; 95% CI 5.22, 7.75); P for interaction < 0.001). When stratified by sex, the results in both males and females were also similar to those in the total population. Conclusion: Our data support a strongly positive combined effect of famine exposure and obesity parameters on hypertension in middle-aged and elderly Chinese.
... 6 China's Great Famine from 1959 to 1962 spread throughout China and is regarded as one of the largest and most severe famines in the 20th century. 7 Studies have shown that prenatal and/or early postnatal exposure to China's Great Famine was associated with metabolic disturbances, including diabetes, non-alcoholic fatty liver diseases, metabolic syndrome and visceral adipose dysfunction, [8][9][10][11][12] ...
Metabolites in the association between early-life famine exposure and type 2 diabetes in adulthood over a 5-year follow-up period
Article
Full-text available
  • Apr 2021
Introduction: Exposure to malnutrition in early life has been found to significantly elevate type 2 diabetes risk in adulthood. However, the changes in metabolites resulting from malnutrition in early life have not been studied. The aim of this study was to identify metabolites with levels associated with type 2 diabetes resulting from exposure to China's Great Famine (1959-1962). Research design and methods: Participants were from SPECT-China 2014 and SPECT-China2 2019, two cross-sectional studies performed at the same site. In total, 2171 subjects participated in SPECT-China and SPECT-China2 simultaneously. The sample size of fetal-exposed (1959-1962) versus non-exposed (1963-1974) individuals was 82 vs 79 in 2014 and 97 vs 94 in 2019. Metabolomic profiling was performed between famine-exposed and non-exposed groups. Results: Among the different famine exposure groups, the fetal-exposed group (1959-1962) had the greatest incidence rate (12.5%), with an OR of 2.11 (95% CI 1.01 to 4.44), compared with the non-exposed group (1963-1974). Moreover, compared with those in the non-exposed group (1963-1974), four metabolites (indole-3-carbinol (I3C), phosphatidylcholine (PC) (22:6(4Z,7Z,10Z,13Z,16Z,19Z)/16:1(9Z)), pyrimidine, and PC(16:1(9Z)/22:5(4Z,7Z,10Z,13Z,16Z))) showed significantly lower relative intensities in the famine and diabetes groups both in 2014 and 2019. Pyrimidine significantly mediated the association of famine exposure with diabetes, and I3C marginally mediated this association. Conclusions: Famine exposure in the fetal period could increase type 2 diabetes risk in adults, even those in their 60s. I3C and pyrimidine are potential mediators of the effects of famine exposure on diabetes development.
... The sample size was calculated by applying two population proportion assuming a prevalence of type two diabetes mellitus as proxy risk factor for CKD in fetal exposed group (22.6%) and non-exposed group (9.8%) [25]. Accordingly, the total sample size was 456 (228 exposed and 228 non-exposed). ...
Consequences of exposure to prenatal famine on estimated glomerular filtration rate and risk of chronic kidney disease among survivors of the great Ethiopian famine (1983–85): a historical cohort study
Article
Full-text available
Background The impact of an adverse prenatal environment such as famine exposure on the development of adulthood non-communicable chronic illnesses, including diabetes and hypertension has been well articulated in the recent past and supported by evidence. However, there exist few longitudinal studies conducted on the long term consequences of prenatal famine exposure on adulthood kidney function. Hence, we set out to examine whether prenatal exposure to the Ethiopian Great Famine (1983–1985) was associated with changes in estimated glomerular filtration rate (eGFR) and the risk of developing chronic kidney disease (CKD) later in adult life. Methods The study was conducted in 219 famine exposed and 222 non exposed cohorts in Raya Kobo district, North Wollo Zone, Northern Ethiopia. Estimated GFR was computed from standardized serum creatinine using the CKD Epidemiology Collaboration (CKD-EPI) equation. The definition of CKD includes those with an eGFR of less than 60 ml/min/1.73 m2 on at least in two occasions of 90 days apart (with or without markers of kidney damage). Linear and logistic regression analyses were employed to examine the independent effect of prenatal famine exposure on eGFR and CKD respectively. Results The mean (SD) serum creatinine of exposed and non-exposed groups were 0.78 (0.2) and 0.75 (0.2) respectively. The mean (SD) eGFR of exposed groups was 107.95 (27.49) while the non-exposed 114.48 (24.81) ml/min. In linear regression, the unadjusted model to examine the association between famine exposure and eGFR resulted in a significant negative beta coefficient (β = − 0.124: 95% CI: − 11.43, − 1.64). Adjusting the exposure for outstanding covariates of kidney health, including systolic blood pressure, fasting blood sugar and blood glucose did not alter the inverse relationship (β = −.114 95% CI: − 10.84, − 1.17). In the unadjusted bivariate logistic regression model, famine exposure resulted in nearly 2.7 times higher odds of developing CKD (OR: 2.68, 95% CI: 1.16, 6.2). The odds remained equivalent after adjusting for systolic blood pressure, fasting blood glucose and body mass index (OR = 2.61: 95% CI: 1.120, 6.09). Conclusion In the study setting, prenatal exposure to the Great Ethiopian Famine was associated with decreased eGFR and higher risk of developing CKD among survivors. These findings may imply that famine in early life may play a significant role in the development of kidney dysfunction in adulthood.
Moderation effect of economic status in the association between early‐life famine exposure and MAFLD in adulthood
Article
  • Oct 2021
Background & aims: The double burden of malnutrition (DBM) in China resulted in high prevalence of diet-related non-communicable diseases. The aim of this study was to analyze the moderation of economic conditions on the association between early famine exposure and metabolic dysfunction associated fatty liver disease (MAFLD) in adulthood. Methods: 10190 participants in the SPECT-China study enrolled from 2014 to 2016 were included in this study. Participants with fetal famine exposure (birth year 1959-1962) or early-childhood famine exposure (birth year 1955-1958) formed the exposure group. The associations with MAFLD were assessed via regression analyses. Results: In men, economic status could not moderate the association between early-life famine and MAFLD after adjusting for age, excess alcohol drinking, current smokers, famine severity, waist circumference, diabetes, hypertension, and dyslipidemia (P for interaction=0.52). However, in women and in the total population, economic status could moderate the association between early-life famine and MAFLD after adjusting for the above confounders (P for interaction=0.01). In the total population and in women, early life famine exposure was associated with MAFLD in both low economic status and high economic status. However, in men, early-life famine exposure was not associated with MAFLD in low economic status, while in high economic status, early-childhood famine-exposure was associated with MAFLD. Conclusions: Economic status could moderate the association between early-life famine exposure and MAFLD in total population and in women.
Individual and Combined Effect of Famine Exposure and Obesity Parameters on Dyslipidemia in Mid-Aged and Older Adult: A Population-Based Cross-Sectional Study
Preprint
Full-text available
  • Jul 2021
Background: Undernutrition in early life may have a lifelong effect on adult health. The associations between undernutrition and obesity parameters and dyslipidemia were inconsistent. The present study aimed to investigate the individual and combined effects of famine exposure and obesity parameters on dyslipidemia in middle-aged and older Chinese. Method: Data were selected from the China Health and Retirement Longitudinal Study Wave2011. The analytic sample included 9427 subjects aged 45 to 90. The present study analyzed data from 9427 middle-aged and older Chinese selected from the China Health and Retirement Longitudinal Study (CHARLS Wave2011). Differences between baseline characteristics and famine exposure/BMI levels/WC levels were evaluated using the Chi-square test, t-test, and F-test. Then, the difference in the prevalence of dyslipidemia between characteristic groups was also estimated by the Chi-square and t-test. Finally, multivariable-adjusted logistic regression models examined associations of famine exposure and obesity parameters with odds of prevalence of dyslipidemia. Results: Among the 9427 participants, 1097(11.64%) participants had been exposed to the Chinese famine during the fetal stage, whereas 3763(39.92%) participants and 3251(34.49%) participants had been exposed to the famine during childhood and adolescence/adult stage, respectively. Regarding the participants with BMI measurements,2771(29.39%) were overweight and 1105(11.72%) were obese, whereas 3955(41.95%) of the participants with WC measurements were obese, respectively. Furthermore, 1899(43.23%) reported having dyslipidemia in males and 1860(36.95%) in females. In multivariable-adjusted model, famine exposure and obesity parameters were associated with prevalence of dyslipidemia independently in total populations[(1) Model three c, famine exposure with prevalence of dyslipidemia: the fatal exposed vs no exposed group, 1.32 (95% CI 1.12, 1.56); childhood-exposed vs no exposed group, 1.49 (95% CI 1.30, 1.70); the adolescence/adult-exposed vs no exposed group, 1.49 (95%CI 1.30, 1.71) ; P for trend=0.000; (2) Model three e, famine exposure with prevalence of dyslipidemia: the fatal exposed vs no exposed group, 1.29 (95% CI 1 .09, 1.52); childhood-exposed vs no exposed group, 1.39 (95% CI 1.22, 1.59); the adolescence/adult-exposed vs no exposed group, 1.27 (95%CI 1.11, 1.46) ; P for trend=0.002; (3) Model three g, BMI levels with prevalence of dyslipidemia: overweight vs normal, 2.06 (95%CI 1.86, 2.27); obesity vs normal, 2.82(95% CI 2.42, 3.27); P for trend=0.000; (4) WC levels with prevalence of dyslipidemia: overweight vs normal, 2.24 (95% CI 2.05, 2.45)]. When stratified by sex, the results in females were mostly similar to those in the total population. In a multivariable logistic regression model three c, associations between famine exposure and dyslipidemia were not observed [fatal exposed group vs non-exposed group: 0.98 (95% CI 0.75, 1.28); childhood-exposed group vs non-exposed group: 0.96 (95% CI 0.78, 1.19); adolescence/adult exposed group vs non-exposed group: 0.86 (95% CI 0.69, 1.07)] independently of BMI only (P for trend =0.110). However, in a multivariable logistic regression model three e, associations between famine exposure and dyslipidemia in male were partly observed [fatal exposed group vs non-exposed group: 0.97 (95% CI 0.74, 1.26); childhood-exposed group vs non-exposed group: 0.91 (95% CI 0.74, 1.13); adolescence/adult exposed group vs non-exposed group: 0.73 (95% CI 0.59, 0.91)] independently of BMI only (P for trend =0.001). In general, the significant synergism between famine exposure and obesity parameters in lowering the prevalence of dyslipidemia was observed in males while the significant synergism in increasing prevalence of dyslipidemia was observed in females (P-interaction =0.000). Conclusion: Individual and combined associations of obesity parameters and famine exposure with the prevalence of dyslipidemia were observed in middle-aged and elderly Chinese.
Severe malnutrition or famine exposure in childhood and cardiometabolic non-communicable disease later in life : A systematic review
Article
Full-text available
  • Mar 2021
Introduction Child malnutrition (undernutrition) and adult non-communicable diseases (NCDs) are major global public health problems. While convincing evidence links prenatal malnutrition with increased risk of NCDs, less is known about the long-term sequelae of malnutrition in childhood. We therefore examined evidence of associations between postnatal malnutrition, encompassing documented severe childhood malnutrition in low/middle-income countries (LMICs) or famine exposure, and later-life cardiometabolic NCDs. Methods Our peer-reviewed search strategy focused on ‘severe childhood malnutrition’, ‘LMICs’, ‘famine’, and ‘cardiometabolic NCDs’ to identify studies in Medline, Embase, Global Health, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. We synthesised results narratively and assessed study quality with the UK National Institute for Health and Care Excellence checklist. Results We identified 57 studies of cardiometabolic NCD outcomes in survivors of documented severe childhood malnutrition in LMICs (n=14) and historical famines (n=43). Exposure to severe malnutrition or famine in childhood was consistently associated with increased risk of cardiovascular disease (7/8 studies), hypertension (8/11), impaired glucose metabolism (15/24) and metabolic syndrome (6/6) in later life. Evidence for effects on lipid metabolism (6/11 null, 5/11 mixed findings), obesity (3/13 null, 5/13 increased risk, 5/13 decreased risk) and other outcomes was less consistent. Sex-specific differences were observed in some cohorts, with women consistently at higher risk of glucose metabolism disorders and metabolic syndrome. Conclusion Severe malnutrition or famine during childhood is associated with increased risk of cardiometabolic NCDs, suggesting that developmental plasticity extends beyond prenatal life. Severe malnutrition in childhood thus has serious implications not only for acute morbidity and mortality but also for survivors’ long-term health. Heterogeneity across studies, confounding by prenatal malnutrition, and age effects in famine studies preclude firm conclusions on causality. Research to improve understanding of mechanisms linking postnatal malnutrition and NCDs is needed to inform policy and programming to improve the lifelong health of severe malnutrition survivors.
Exposure to Famine in Early Life and Nonalcoholic Fatty Liver Disease in Adulthood
Article
Full-text available
  • Mar 2016
Context: Epidemiologic studies have indicated that early-life nutrition influences later risk of obesity, type 2 diabetes and metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is also considered a metabolic disease. Objective: The aim was to explore the association between adult NAFLD and fetal or childhood exposure to Great Chinese Famine between 1959 and 1962 during fetal and childhood period. Design and setting: In total, 5306 subjects from the SPECT-China study were divided into a fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/young adult-exposed (1921-1948) and non-exposed (1963-1974, reference) group. Main outcome measure: The degrees of steatosis of NAFLD were determined by ultrasonography. Results: The prevalences of NAFLD in the non-exposed (1963-1974), fetal and childhood-exposed participants were 55.9%, 55.8% and 55.4% in men and 33.0%, 46.3% and 51.7% in women, respectively. Compared with those non-exposed, fetal- and childhood-exposed women but not men had a significantly higher prevalence of moderate-severe steatosis (P <0.05). A significant association existed in women between increased alanine aminotransferase and both fetal and childhood exposure to famine, after adjusting for age, rural/urban residence, economic status, BMI, diabetes, dyslipidemia and hypertension (both P <0.05). Famine exposure during the fetal period (OR 1.77, 95% CI 1.22, 2.57) and childhood (OR 1.82, 95% CI 1.35, 2.46) was associated with an increased prevalence of moderate-severe NAFLD in women in the above fully adjusted model. Conclusions: Exposure to the Great Famine in early life had sex-specific association with moderate-severe NAFLD. This indicates that malnutrition in early life may influence the development of adult NAFLD; thus pregnant women and their infants and children may require the highest priority in obtaining nutritional relief.
The famine exposure in early life and metabolic syndrome in adulthood
Article
Full-text available
Background & aims: Epidemiologic studies have revealed that early-life conditions influence later risk of chronic diseases. We aimed to explore whether exposure to Chinese famine between 1959 and 1962 during fetal and childhood period was related with metabolic syndrome (MS) in adulthood. Methods: 6445 subjects from SPECT-China study were divided into fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/young adult-exposed (1921-1948), non-exposed (1963-1974) and non-exposed (after 1975). MS was defined by the International Diabetes Federation criteria. Results: The prevalences of MS in the non-exposed (1963-1974), fetal and childhood-exposed were 16.4%, 20.1% and 19.1% in men and 13.5%, 23.7% and 33.5% in women, respectively. After adjustment for age, compared with non-exposed (1963-1974), fetal and childhood-exposed women had significantly higher prevalences of MS (P < 0.05), but not in men. Famine exposure during the fetal period (OR 1.47, 95% CI 1.05, 2.07) and childhood (OR 1.80, 95% CI 1.22, 2.67) was associated with higher risk of MS in women after adjusting for age (both P < 0.05). Further adjustments for age, smoking, rural/urban residence and economic status did not significantly attenuate this association. Conclusions: Exposure to famine in early life had sex-specific association with MS. It also suggests the adverse effects of malnutrition might extend beyond the 'first 1000 days' and last 9 years.
Corrigendum: DNA methylation signatures link prenatal famine exposure to growth and metabolism
Article
Full-text available
  • Nov 2014
Periconceptional diet may persistently influence DNA methylation levels with phenotypic consequences. However, a comprehensive assessment of the characteristics of prenatal malnutrition-associated differentially methylated regions (P-DMRs) is lacking in humans. Here we report on a genome-scale analysis of differential DNA methylation in whole blood after periconceptional exposure to famine during the Dutch Hunger Winter. We show that P-DMRs preferentially occur at regulatory regions, are characterized by intermediate levels of DNA methylation and map to genes enriched for differential expression during early development. Validation and further exploratory analysis of six P-DMRs highlight the critical role of gestational timing. Interestingly, differential methylation of the P-DMRs extends along pathways related to growth and metabolism. P-DMRs located in INSR and CPT1A have enhancer activity in vitro and differential methylation is associated with birth weight and serum LDL cholesterol. Epigenetic modulation of pathways by prenatal malnutrition may promote an adverse metabolic phenotype in later life.
Prevalence and Control of Diabetes in Chinese Adults
Article
Full-text available
Noncommunicable chronic diseases have become the leading causes of mortality and disease burden worldwide. To investigate the prevalence of diabetes and glycemic control in the Chinese adult population. Using a complex, multistage, probability sampling design, we conducted a cross-sectional survey in a nationally representative sample of 98,658 Chinese adults in 2010. Plasma glucose and hemoglobin A1c levels were measured after at least a 10-hour overnight fast among all study participants, and a 2-hour oral glucose tolerance test was conducted among participants without a self-reported history of diagnosed diabetes. Diabetes and prediabetes were defined according to the 2010 American Diabetes Association criteria; whereas, a hemoglobin A1c level of <7.0% was considered adequate glycemic control. The overall prevalence of diabetes was estimated to be 11.6% (95% CI, 11.3%-11.8%) in the Chinese adult population. The prevalence among men was 12.1% (95% CI, 11.7%-12.5%) and among women was 11.0% (95% CI, 10.7%-11.4%). The prevalence of previously diagnosed diabetes was estimated to be 3.5% (95% CI, 3.4%-3.6%) in the Chinese population: 3.6% (95% CI, 3.4%-3.8%) in men and 3.4% (95% CI, 3.2%-3.5%) in women. The prevalence of undiagnosed diabetes was 8.1% (95% CI, 7.9%-8.3%) in the Chinese population: 8.5% (95% CI, 8.2%-8.8%) in men and 7.7% (95% CI, 7.4%-8.0%) in women. In addition, the prevalence of prediabetes was estimated to be 50.1% (95% CI, 49.7%-50.6%) in Chinese adults: 52.1% (95% CI, 51.5%-52.7%) in men and 48.1% (95% CI, 47.6%-48.7%) in women. The prevalence of diabetes was higher in older age groups, in urban residents, and in persons living in economically developed regions. Among patients with diabetes, only 25.8% (95% CI, 24.9%-26.8%) received treatment for diabetes, and only 39.7% (95% CI, 37.6%-41.8%) of those treated had adequate glycemic control. The estimated prevalence of diabetes among a representative sample of Chinese adults was 11.6% and the prevalence of prediabetes was 50.1%. Projections based on sample weighting suggest this may represent up to 113.9 million Chinese adults with diabetes and 493.4 million with prediabetes. These findings indicate the importance of diabetes as a public health problem in China.
Nutritional manipulations in the perinatal period program adipose tissue in offspring
Article
Full-text available
Epidemiological studies initially demonstrated that maternal undernutrition results in low birth weight with increased risk for long-lasting energy balance disorders. Maternal obesity and diabetes associated with high birth weight, excessive nutrition in neonates and rapid catch-up growth also increase the risk of adult-onset obesity. As stated by the Developmental Origin of Health and Disease concept, nutrient supply perturbations in the fetus or neonate result in long-term programming of individual body weight set-point. Adipose tissue is a key fuel storage unit mainly involved in the maintenance of energy homeostasis. Studies in numerous animal models have demonstrated that the adipose tissue is the focus of developmental programming events in a gender- and depot-specific manner. In rodents, adipose tissue development is particularly active during the perinatal period, especially during the last week of gestation and during early postnatal life. In contrast to rodents, this process essentially takes place before birth in bigger mammals. Despite these different developmental time windows, altricial and precocial species share several mechanisms of adipose tissue programming. Offspring from malnourished dams present adipose tissue with series of alterations: impaired glucose uptake, insulin and leptin resistance, low-grade inflammation, modified sympathetic activity with reduced noradrenergic innervations and thermogenesis. These modifications reprogram adipose tissue metabolism by changing fat distribution and composition, and by enhancing adipogenesis predisposing the offspring to fat accumulation. Subtle adipose tissue circadian rhythm changes are also observed. Inappropriate hormone levels, modified tissue sensitivity (especially glucocorticoid system) and epigenetic mechanisms are key factors for adipose tissue programming during the perinatal period.
Starving in childhood and diabetes mellitus in elderly age
Article
  • Jan 2008
The long-term consequences of the protracted starvation or inadequate nutrition of children is a problem in which considerable interest has been shown in recent decades. Between June 1941 and January 1944 the civilian population of Leningrad was besieged for two and a half years. The non-combatant population of this large European city lived through lengthy periods of starvation or malnutrition against a background of additional complex stress factors (including cold, bombing, death of relatives and acquaintances, and lack of means of transport and communication). It may be assumed that the health in adulthood of those who were children and young people in Leningrad during the siege differed from that of people of the same age who were spared those extreme conditions. Impact of starvation in childhood on prevalence rate of diabetes mellitus in elderly age, time of onset, clinical features of the disease course were studied. The results confirm that insulin-independent diabetes without obesity develops more often and earlier in women who got through the Siege of Leningrad in their childhood. Health status of elderly people who underwent continuous starvation in their childhood is the actual problem, because health status of young people in this country who got through 90's, when one of three children in the age of 2 years starved, suggests developing of medical and social problems because of forthcoming changes in the illness patterns of the population in modern Russia.
Is Exposure to Famine in Childhood and Economic Development in Adulthood Associated With Diabetes?
Article
Context: The Chinese were afflicted by great famine between 1959 and 1962. These people then experienced rapid economic development where the GDP per capita increased from $28 in 1978 to $6807 in 2013. We hypothesize that these two events are associated with the booming rate of diabetes in China. Objective: We aimed to explore whether exposure to famine in early life and high economic status in adulthood was associated with diabetes in later life. Design and setting: Our data of 6897 adults were from a cross-sectional SPECT-China study in 2014. Among them, 3844 adults experienced famine during different life stages, and then lived in areas with different economic statuses in adulthood. Main outcome measure: Diabetes was considered as fasting plasma glucose ≥7.0mmol/L, HbA1c ≥6.5% and/or a previous diagnosis by health care professionals. Results: Compared with non-exposed subjects, famine exposure during the fetal period (OR 1.53, 95% CI 1.09, 2.14) and childhood (OR 1.82, 95% CI 1.21, 2.73) was associated with diabetes after adjusting for age and gender. Further adjustments for adiposity, height, the lipid profile and blood pressure did not significantly attenuate this association. Subjects living in areas with high economic status had a greater diabetes risk in adulthood (OR 1.46, 95% CI, 1.20, 1.78). In gender-specific analyses, fetal-exposed men (OR 1.64, 95% CI, 1.04, 2.59) and childhood-exposed women (OR 2.81, 95% CI, 1.59, 4.97) had significantly greater risk of diabetes. Conclusions: The rapid increase in the prevalence of diabetes in middle-aged and elderly people in China is associated with the combination of exposure to famine during the fetal stage and childhood and high economic status in adulthood. Our findings may partly explain the booming diabetes phenomenon in China.
Association between type 2 diabetes and prenatal exposure to the Ukraine famine of 1932-33: A retrospective cohort study
Article
  • Sep 2015
The effect of fetal and early childhood living conditions on adult health has long been debated, but empirical assessment in human beings remains a challenge. We used data from during the man-made Ukrainian famine of 1932-33 to examine the association between restricted nutrition in early gestation and type 2 diabetes in offspring in later life. We included all patients with type 2 diabetes diagnosed at age 40 years or older in the Ukraine national diabetes register 2000-08, and used all individuals born between 1930 and 1938 from the 2001 Ukraine national census as the reference population. This study population includes individuals born before and after the famine period as controls, and those from regions that experienced extreme, severe, or no famine. We used prevalence odds ratios (ORs) as the measure of association between type 2 diabetes and early famine exposure, with stratification by region, date of birth, and sex for comparisons of diabetes prevalence in specific subgroups. Using these two datasets, we compared the odds of type 2 diabetes by date and region of birth in 43 150 patients with diabetes and 1 421 024 individuals born between 1930 and 1938. With adjustment for season of birth, the OR for developing type 2 diabetes was 1·47 (95% CI 1·37-1·58) in individuals born in the first half of 1934 in regions with extreme famine, 1·26 (1·14-1·39) in individuals born in regions with severe famine, and there was no increase (OR 1·00, 0·91-1·09) in individuals born in regions with no famine, compared with births in other time periods. Multivariable analyses confirmed these results. The associations between type 2 diabetes and famine around the time of birth were similar in men and women. These results show a dose-response relation between famine severity during prenatal development and odds of type 2 diabetes in later life. Our findings suggest that early gestation is a critical time window of development; therefore, further studies of biological mechanisms should include this period. Ukraine State Diabetes Mellitus Program, US National Institutes of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.
Incidence of type 2 diabetes and number of events attributable to abdominal obesity in China: A cohort study
Article
  • Jan 2015
We aimed to estimate incidence of type 2 diabetes (T2D) and the number of diabetes events attributable to abdominal obesity in China. We conducted a cohort study in a sample of 24 996 Chinese adults aged 35-74 years, with 19.9% of subjects lost to follow-up. Waist circumference (WC) was measured at baseline in 1998 and 2000-2001, and abdominal obesity was defined as WC≥ 90 cm/80 cm (men/women). Information on incident diabetes was collected during follow-up in 2007-2008. We estimated the number of T2D events attributed to abdominal obesity using confounder-adjusted population-attributable risk, incidence of diabetes and the population size of China in 2010. After a mean follow-up of 8.0 years, age-standardized incidence of T2D was 9.6 and 9.2 per 1 000 person-years in men and women, respectively. Abdominal obesity accounted for 28.1% (95% confidence interval [CI]: 14.8%, 40.5%) of incident diabetes among men and 41.2% (28.3%, 52.6%) among women using the diagnosing criteria of abdominal obesity recommended by the International Diabetes Federation. We estimated that in 2010, 2.4 (1.5, 3.2) million diabetes events were attributable to abdominal obesity: 1.0 (0.5, 1.4) million in men and 1.4 (1.0, 1.8) million in women. Abdominal obesity is a major risk factor for T2D. Strengthening programs and initiatives for preventing and controlling obesity focusing on lifestyle changes should be a priority in the national strategy to reduce diabetes burden in China. This article is protected by copyright. All rights reserved.
Long-Term Health and Socioeconomic Consequences of Early-Life Exposure to the 1959-61 Chinese Famine
Article
  • Nov 2014