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Variants in the SIRT1 gene may affect diabetes risk in interaction with prenatal exposure to famine.

ABSTRACT: OBJECTIVE: To investigate whether SIRT1, a nutrient-sensing histone deacetylase, influences fetal programming during malnutrition. RESEARCH DESIGN AND METHODS: In 793 individuals of the Dutch Famine Birth Cohort, we analyzed the interaction between three SIRT1 single nucleotide polymorphisms (SNPs) and prenatal exposure to famine on type 2 diabetes risk. RESULTS: In the total population (exposed and unexposed), SIRT1 variants were not associated with type 2 diabetes. A significant interaction was found between two SIRT1 SNPs and exposure to famine in utero on type 2 diabetes risk (P = 0.03 for rs7895833; P = 0.01 for rs1467568). Minor alleles of these SNPs were associated with a lower prevalence of type 2 diabetes only in individuals who had been exposed to famine prenatally (odds ratio for rs7895833 0.50 [95% CI 0.24-1.03], P = 0.06; for rs1467568 0.48 [0.25-0.91], P = 0.02). CONCLUSIONS: SIRT1 may be an important genetic factor involved in fetal programming during malnutrition, influencing type 2 diabetes risk later in life.

SUBMITTER: Botden IP

PROVIDER: S-EPMC3263901 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Variants in the SIRT1 gene may affect diabetes risk in interaction with prenatal exposure to famine.

Botden Ilse P G IP Zillikens M Carola MC de Rooij Susanne R SR Langendonk Janneke G JG Danser A H Jan AH Sijbrands Eric J G EJ Roseboom Tessa J TJ

Diabetes care 20120106 2

<h4>Objective</h4>To investigate whether SIRT1, a nutrient-sensing histone deacetylase, influences fetal programming during malnutrition.<h4>Research design and methods</h4>In 793 individuals of the Dutch Famine Birth Cohort, we analyzed the interaction between three SIRT1 single nucleotide polymorphisms (SNPs) and prenatal exposure to famine on type 2 diabetes risk.<h4>Results</h4>In the total population (exposed and unexposed), SIRT1 variants were not associated with type 2 diabetes. A signifi ...[more]

PMID: 22228742

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Project description:BackgroundPrenatal exposure to famine and adulthood obesity have been independently related to the risk of type 2 diabetes; however, little is known about the joint effects of these risk factors at different stages of life on adulthood diabetes risk.MethodsThe analysis included 88 830 participants of the China Kadoorie Biobank, who were born around the time of the Chinese Great Famine and without diabetes, cardiovascular diseases, or cancer at baseline. We defined famine exposure subgroups as nonexposed (born between 1 October 1962 and 30 September 964), fetal-exposed (born between 1 October 1959 and 30 September 1961) and early-childhood exposed (born between 1 October 1956 and 30 September 1958). General obesity was assessed by body mass index (BMI: overweight ≥ 24.0, obesity ≥ 28.0) and abdominal obesity assessed by waist-to-hip ratio (WHR, men/women: moderate ≥ 0.90/0.85, high ≥ 0.95/0.90).ResultsDuring a median 7.3 years (642 552 person-years) of follow-up, we identified 1372 incident cases of type 2 diabetes. Compared with nonexposed and early-childhood exposed participants combined as a single comparison group, fetal-exposed participants showed an increased risk of diabetes in adulthood [hazard ratio (HR) = 1.25; 95% confidence interval (CI): 1.07-1.45]. The association between general obesity and diabetes was consistent across subgroups according to famine exposure (P for interaction > 0.05). A stronger association between abdominal obesity and diabetes was observed in the fetal-exposed subgroup than in other subgroups (P for interaction = 0.025 in the whole population). This interaction was more obvious in women (P = 0.013) but not in men (P = 0.699). Compared with normal-BMI and -WHR participants, those with both general (BMI ≥ 24.0) and abdominal (WHR ≥ 0.90/0.85) obesity in adulthood had 5.32 (95% CI: 3.81-7.43)-, 3.13 (2.48-3.94)- and 4.43 (3.45-5.68)-fold higher risks if these were carried during, before and after times of famine, respectively.ConclusionsCoexistence of prenatal experience of undernutrition and abdominal obesity in adulthood was associated with a higher risk of type 2 diabetes.

Project description:Background Early-life exposures during gestation may permanently alter thyroid physiology and health in adulthood. We investigated whether exposure to the Dutch Famine (1944-1945) in late, mid, or early gestation influences thyroid function (i.e., incidence of thyroid disease, thyroid autoantibodies, thyroid stimulating hormone (TSH), and free thyroxine (FT4) levels) in adulthood. We specifically assessed whether potential effects of famine differed for men and women. Methods This study includes 910 men and women born as term singletons in the Wilhelmina Gasthuis in Amsterdam, the Netherlands, shortly before, during, or after the Dutch Famine. We evaluated medical histories for previous diagnosis or current treatment for thyroid dysfunction. At age 50 blood samples were drawn from 728 individuals for tests of thyroid function. We studied the prevalence of overt hypo- and hyperthyroidism and thyroid autoimmunity using medical histories, and measurements of TSH, FT4, anti-TPO and anti-TG, comparing participants exposed to famine at different pregnancy trimesters or born before or conceived after the famine. Additionally, we studied associations of TSH and FT4 levels with in utero famine exposure in a subsample of men and women free of thyroid disease that were exposed in late, mid, or early gestation. Results There were no differences in thyroid dysfunction diagnosis or current treatment between participants at age 50 years who been exposed to famine during different periods of gestation and those born before or conceived after. There was no association between famine exposure and overt hypo- or hyperthyroidism or thyroid autoantibody positivity. Women who had been exposed to famine in mid gestation had slightly lower TSH levels than women who had not been exposed to famine prenatally (b=-0.06; 95%; CI=[-0.11,-0.02]; p<0.01). No differences in TSH levels were observed in men, and no differences in FT4 levels were observed in men or women. Conclusions There are no differences in adult thyroid disease at age 50 years according to prenatal famine exposure. However, the lower TSH levels in women exposed to famine in the second trimester suggest that there may be sex-specific effects of famine exposure during a critical period of thyroid development on hypothalamic-pituitary-thyroid axis regulation in adulthood.

Project description: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.

Project description:BackgroundThe 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.MethodsThe 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.ResultsThe 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).ConclusionIn 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.

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Variants in the SIRT1 gene may affect diabetes risk in interaction with prenatal exposure to famine.

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Variants in the SIRT1 gene may affect diabetes risk in interaction with prenatal exposure to famine.

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