Food contaminants and programming of type 2 diabetes: recent findings from animal studies

It is now accepted that the way our health evolves with aging is intimately linked to the quality of our early life. The present review highlights the emerging data of Developmental Origins of Health and Disease field on developmental disruption by toxicants and their subsequent effect on type 2 diabetes. We report adverse neonatal effects of several food contaminants during pregnancy and lactation, among them bisphenol A, chlorpyrifos, perfluorinated chemicals on pancreas integrity and functionality in later life. The described alterations, in conjunction with disruption of β cell mass in early life, can lead to dysregulation of glucose metabolism, insulin synthesis, which facilitates the development of insulin resistance and progression of diabetes in the adult. Despite limited and often inconclusive epidemiologic and experimental data, more recent data clearly show that infants appear to be at increased risk of type 2 diabetes in later life. This may be a result of continued exposure to chemical food contaminants during the critical window of pancreas development. In societies already burdened with increased incidence of non-communicable chronic diseases, there is a clear need for information regarding the potential harmful effects of chemical food contaminants on adult health diseases.

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Maternal High-Fiber Diet Protects Offspring against Type 2 Diabetes

Nutrients ◽

10.3390/nu13010094 ◽

2020 ◽

Vol 13 (1) ◽

pp. 94

Author(s):

Huishi Toh ◽

James A. Thomson ◽

Peng Jiang

Keyword(s):

Type 2 Diabetes ◽

Early Life ◽

Maternal Diet ◽

Later Life ◽

High Fiber ◽

Early Life Environment ◽

Fiber Diet ◽

Increased Risk ◽

High Fiber Diet

Previous studies have reported that maternal malnutrition is linked to increased risk of developing type 2 diabetes in adulthood. Although several diabetic risk factors associated with early-life environment have been identified, protective factors remain elusive. Here, we conducted a longitudinal study with 671 Nile rats whereby we examined the interplay between early-life environment (maternal diet) and later-life environment (offspring diet) using opposing diets that induce or prevent diet-induced diabetes. Specifically, we modulated the early-life environment throughout oogenesis, pregnancy, and nursing by feeding Nile rat dams a lifelong high-fiber diet to investigate whether the offspring are protected from type 2 diabetes. We found that exposure to a high-fiber maternal diet prior to weaning significantly lowered the risk of diet-induced diabetes in the offspring. Interestingly, offspring consuming a high-fiber diet after weaning did not develop diet-induced diabetes, even when exposed to a diabetogenic maternal diet. Here, we provide the first evidence that the protective effect of a high-fiber diet can be transmitted to the offspring through the maternal diet, which has important implications in diabetes prevention.

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Maternal High Fiber Diet Protects Offspring Against Type 2 Diabetes

10.1101/2020.09.26.315069 ◽

2020 ◽

Author(s):

Huishi Toh ◽

James A. Thomson ◽

Peng Jiang

Keyword(s):

Type 2 Diabetes ◽

Early Life ◽

Maternal Diet ◽

Later Life ◽

High Fiber ◽

Early Life Environment ◽

Fiber Diet ◽

Increased Risk ◽

High Fiber Diet

AbstractPrevious studies have reported that maternal malnutrition is linked to increased risk of developing type 2 diabetes in adulthood. Although several diabetic risk factors associated with early life environment have been identified, protective factors remain elusive. Here, we modulate the early life environment using a maternal high fiber diet to investigate whether the offspring are protected from type 2 diabetes. We examined the interplay between early life environment (maternal diet) and later life environment (offspring diet) using a longitudinal study with 671 Nile rats. We found that exposure to a high fiber maternal diet prior to weaning significantly lowers the risk of diet-induced diabetes in the offspring. Interestingly, offspring consuming a high fiber diet after weaning do not get diet-induced diabetes, even when exposed to a diabetogenic maternal diet. Here, we provide the first evidence that the protective effect of high fiber can be transmitted to the offspring through a maternal diet, which has important implications in diabetes prevention.

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Killing Me Softly: The Fetal Origins Hypothesis

The Journal of Economic Perspectives ◽

10.1257/jep.25.3.153 ◽

2011 ◽

Vol 25 (3) ◽

pp. 153-172 ◽

Cited By ~ 539

Author(s):

Douglas Almond ◽

Janet Currie

Keyword(s):

Type 2 Diabetes ◽

Heart Disease ◽

Educational Attainment ◽

Test Scores ◽

Later Life ◽

Observational Evidence ◽

Adult Health ◽

Fetal Origins ◽

Fetal Origins Hypothesis

In the epidemiological literature, the fetal origins hypothesis associated with David J. Barker posits that chronic, degenerative conditions of adult health, including heart disease and type 2 diabetes, may be triggered by circumstances decades earlier, particularly, by in utero nutrition. Economists have expanded on this hypothesis, investigating a broader range of fetal shocks and circumstances and have found a wealth of later-life impacts on outcomes including test scores, educational attainment, and income, along with health. In the process, they have provided some of the most credible observational evidence in support of the hypothesis. The magnitude of the impacts is generally large. Thus, the fetal origins hypothesis has not only survived contact with economics, but has flourished.

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Nutritional modulation of the epigenome and its implication for future health

Proceedings of The Nutrition Society ◽

10.1017/s0029665119000016 ◽

2019 ◽

Vol 78 (3) ◽

pp. 305-312 ◽

Cited By ~ 3

Author(s):

Mark A. Burton ◽

Karen A. Lillycrop

Keyword(s):

Gene Expression ◽

Early Life ◽

Animal Studies ◽

Disease Risk ◽

Regulation Of Gene Expression ◽

Later Life ◽

Future Health ◽

Level Of Activity ◽

Epigenetic Processes

Non-communicable diseases (NCD) such as type-2 diabetes and CVD are now highly prevalent in both developed and developing countries. Evidence from both human and animal studies shows that early-life nutrition is an important determinant of NCD risk in later life. The mechanism by which the early-life environment influences future disease risk has been suggested to include the altered epigenetic regulation of gene expression. Epigenetic processes regulate the accessibility of genes to the cellular proteins that control gene transcription, determining where and when a gene is switched on and its level of activity. Epigenetic processes not only play a central role in regulating gene expression but also allow an organism to adapt to the environment. In this review, we will focus on how both maternal and paternal nutrition can alter the epigenome and the evidence that these changes are causally involved in determining future disease risk.

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Gestational Diabetes Mellitus (GDM): Current concept and a short Review

Bangladesh Journal of Pathology ◽

10.3329/bjpath.v24i1.2877 ◽

1970 ◽

Vol 24 (1) ◽

pp. 16-20 ◽

Cited By ~ 1

Author(s):

MT Rahman ◽

T Tahmin ◽

S Ferdousi ◽

SN Bela

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Later Life ◽

Short Review ◽

Current Concept ◽

Increased Risk ◽

Develop Type

Gestational Diabetes Mellitus (GDM) is a very common and important disease occurring during pregnancy and has detrimental effect on both the mother and the baby. The mother is at increased risk of developing obstetric complications like prolonged labour, prone to develop type 2 diabetes in future and the baby is born with overweight, cause of childhood obesity and later life development of type 2 diabetes. A short review and current concept of GDM is discussed. Key words: GDM, Type 2 diabetes, Obesity, Macrosomia, Complications doi: 10.3329/bjpath.v24i1.2877 Bangladesh J Pathol 24 (1) : 16-20

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Magnesium deficiency associated with diabetic retinopathy in type 2 diabetes mellitus: A meta-analysis

International Journal of Public Health Science (IJPHS) ◽

10.11591/ijphs.v10i3.20916 ◽

2021 ◽

Vol 10 (3) ◽

pp. 565

Author(s):

Ronald Pratama Adiwinoto ◽

Robert Dwitama Adiwinoto ◽

Jongky Hendro Prajitno

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Diabetic Retinopathy ◽

Animal Studies ◽

Magnesium Deficiency ◽

Meta Analysis ◽

Serum Magnesium ◽

Increased Risk

Diabetic retinopathy (DR) is the major cause of visual impairment in the working-age population with type 2 diabetes mellitus (T2DM). Magnesium (Mg) is involved in various metabolic processes and in experimental animal studies; Mg has shown essential roles in physiological eye function. Magnesium deficiency is common in T2DM; therefore we analyzed the association between serum Mg status and the presence of DR in T2DM patients. Systematic literature searching in several databases, from 1988 to September 2020, was performed using search terms: “serum magnesium” or “hypomagnesemia” and “diabetic retinopathy” or “retinopathy”. A total of 3,227 patients from 17 studies were included in this meta-analysis. Hypomagnesemia was associated with increased risk of developing DR (OR 4.52 [2.08, 9.81], p=0.0001) in T2DM patients. Serum Mg levels also lower in patients with DR than those without DR (MD –0.30 mg/dL [–0.44, –0.15], p<0.0001). Additionally, serum Mg levels were lower in patients with proliferative DR (PDR) than those with non-proliferative DR (NPDR) (MD-0.21 mg/dL [–0.34, –0.09], p=0.0009). Leave-one-out sensitivity analysis did not change the overall effect. Hypomagnesemia or low serum Mg levels in T2DM patients increased the risk of developing DR.

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Famine Exposure in Early Life and Risk of Type 2 Diabetes in Adulthood: Findings From Prospective Cohort Studies in China

10.21203/rs.3.rs-672030/v1 ◽

2021 ◽

Author(s):

Feng Ning ◽

Jing Zhao ◽

Yanlei Zhang ◽

Lei Zhang ◽

Xin Song ◽

...

Keyword(s):

Type 2 Diabetes ◽

Rural Areas ◽

Early Life ◽

Critical Time ◽

Diabetes Incidence ◽

Family History Of Diabetes ◽

Child Exposure ◽

Increased Risk ◽

Famine Exposure

Abstract Background: This study will investigate effect of famine exposure in early life associated with the risk of type 2 diabetes in adulthood during the Chinese Famine.Methods: A total of 3,418 individuals aged 35-74 years free of diabetes in 2006 and in 2009 study surveys, were prospectively followed up to 2009 and 2012, respectively. Individuals were grouped into non-exposed (1962-1978), fetal-exposed (1959-1961), childhood-exposed (1949-1958) and adolescence/adult-exposed cohorts (1931-1948). Logistic regression model was employed to assess effect of famine exposure on diabetes incidence, adjusting for potential covariates.Results: During a mean follow up of 3 years, the age-adjusted cumulative incidences of type 2 diabetes were 6.3%, 13.0% 11.0% and 13.8% in non-exposed, fetal, child and adolescence/adult-exposed cohorts, respectively (P=0.026). Compared with non-exposed individuals, relative risks (95% confidence intervals) for diabetes incidence were 2.15(1.29-3.60), 1.53(0.93-2.51), and 1.65(0.75-3.63) in those exposure in fetal, child and adolescence/adult, controlling for covariates. The interactions between famine exposure and obesity, education, family history of diabetes were not observed, except for famine exposure and residential areas. Individuals lived in rural areas increased risk for type 2 diabetes in fetal and child exposure, with an incidence relative risk (95% confidence interval) of 8.79(1.82-42.54) and 2.33(1.17-4.65), respectively.Conclusions: Our findings indicate that famine exposure in early life is an independent predictor on type 2 diabetes, particularly in women. The identification and intervention on critical time can prevent residents from diabetes in later life.The clinical trial was registered, more detail linked in https://clinicaltrials.gov/ct2/home, as registration no. NCT01053195.

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Changes in the expression of the type 2 diabetes-associated gene VPS13C in the β-cell are associated with glucose intolerance in humans and mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00074.2016 ◽

2016 ◽

Vol 311 (2) ◽

pp. E488-E507 ◽

Cited By ~ 13

Author(s):

Zenobia B. Mehta ◽

Nicholas Fine ◽

Timothy J. Pullen ◽

Matthew C. Cane ◽

Ming Hu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cell Function ◽

Disease Risk ◽

Cell Mass ◽

Eqtl Analysis ◽

Β Cell ◽

Enhancer Activity ◽

Increased Risk

Single nucleotide polymorphisms (SNPs) close to the VPS13C, C2CD4A and C2CD4B genes on chromosome 15q are associated with impaired fasting glucose and increased risk of type 2 diabetes. eQTL analysis revealed an association between possession of risk (C) alleles at a previously implicated causal SNP, rs7163757, and lowered VPS13C and C2CD4A levels in islets from female ( n = 40, P < 0.041) but not from male subjects. Explored using promoter-reporter assays in β-cells and other cell lines, the risk variant at rs7163757 lowered enhancer activity. Mice deleted for Vps13c selectively in the β-cell were generated by crossing animals bearing a floxed allele at exon 1 to mice expressing Cre recombinase under Ins1 promoter control (Ins1Cre). Whereas Vps13cfl/fl:Ins1Cre (βVps13cKO) mice displayed normal weight gain compared with control littermates, deletion of Vps13c had little effect on glucose tolerance. Pancreatic histology revealed no significant change in β-cell mass in KO mice vs. controls, and glucose-stimulated insulin secretion from isolated islets was not altered in vitro between control and βVps13cKO mice. However, a tendency was observed in female null mice for lower insulin levels and β-cell function (HOMA-B) in vivo. Furthermore, glucose-stimulated increases in intracellular free Ca2+ were significantly increased in islets from female KO mice, suggesting impaired Ca2+ sensitivity of the secretory machinery. The present data thus provide evidence for a limited role for changes in VPS13C expression in conferring altered disease risk at this locus, particularly in females, and suggest that C2CD4A may also be involved.

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GLP1 and cancer: friend or foe?

Endocrine Related Cancer ◽

10.1530/erc-12-0111 ◽

2012 ◽

Vol 19 (5) ◽

pp. F77-F88 ◽

Cited By ~ 30

Author(s):

Roman Vangoitsenhoven ◽

Chantal Mathieu ◽

Bart Van der Schueren

Keyword(s):

Type 2 Diabetes ◽

Animal Studies ◽

Cell Mass ◽

The United States ◽

Premalignant Lesions ◽

Dipeptidyl Peptidase 4 ◽

Receptor Agonists ◽

Beneficial Effects ◽

Dpp4 Inhibitors

The new incretin-based therapies, dipeptidyl peptidase-4 (DPP4) inhibitors and glucagon like peptide 1 (GLP1) receptor agonists are widely used for the treatment of type 2 diabetes because of their glucose-lowering capacity with low risk of hypoglycemia. As they are weight neutral or induce weight loss in this mostly overweight population, they are popular among clinicians and patients alike. Nonetheless, concerns have been raised about GLP1's trophic effects. While increased β cell mass observed in rodents sounds appealing for treatment of diabetes, there was also an increased incidence of medullary thyroid cancer (MTC) in some species. We reviewed literature available in the Medline database until March 2012. Safety signals have emerged for MTC and pancreatic carcinoma from adverse event databases in the United States and Europe. Considering the relatively short duration of these studies, it is more likely that premalignant lesions are stimulated in presence of GLP1, rather than new neoplasms induced. Moreover, interpreting results of animal studies is difficult because of species-specific differences in presence and density of GLP1 receptors. Furthermore, data are emerging suggesting beneficial effects of GLP1 on colon and breast cancer. In conclusion, presently, the benefits of using DPP4 inhibitors or GLP1 receptor agonists for treatment of type 2 diabetes outweigh the risks. Nonetheless, their safety profile should be monitored and their indications should be widened cautiously. At present they remain contra-indicated in patients with a personal or family history of MTC or multiple endocrine neoplasia type 2.

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Early-Life Exposure to Famine and Risk of MetabolicAssociated Fatty Liver Disease in Chinese Adults

Nutrients ◽

10.3390/nu13114063 ◽

2021 ◽

Vol 13 (11) ◽

pp. 4063

Author(s):

Jing Liu ◽

Guimin Wang ◽

Yiling Wu ◽

Ying Guan ◽

Zhen Luo ◽

...

Keyword(s):

Type 2 Diabetes ◽

Liver Disease ◽

Fatty Liver ◽

Early Life ◽

Fatty Liver Disease ◽

Chinese Adults ◽

Early Life Exposure ◽

Increased Risk ◽

Famine Exposure

Background: Early-life exposure to the Chinese famine has been related to the risk of obesity, type 2 diabetes, and nonalcoholic fatty liver disease later in life. Nevertheless, the long-term impact of famine exposure on metabolic associated fatty liver disease (MAFLD), a recently proposed term to describe liver disease associated with known metabolic dysfunction, remains unknown. The aim of our study was to explore the relationship between early famine exposure and MAFLD in adulthood. Methods: A total of 26,821 participants (10,994 men, 15,827 women) were recruited from a cohort study of Chinese adults in Shanghai. We categorized participants into four famine exposure subgroups based on the birth year as nonexposed (1963–1967), fetal-exposed (1959–1962), childhood-exposed (1949–1958), and adolescence-exposed (1941–1948). MAFLD was defined as liver steatosis detected by ultrasound plus one of the following three criteria: overweight/obesity, type 2 diabetes, or evidence of metabolic dysregulation. Multivariable logistic regression models were performed to examine the association between famine exposure and MAFLD. Results: The mean ± standard deviation age of the participants was 60.8 ± 6.8 years. The age-adjusted prevalence of MAFLD was 38.3, 40.8, 40.1, and 36.5% for the nonexposed, fetal-exposed, childhood-exposed, and adolescence-exposed subgroups, respectively. Compared with nonexposed participants, fetal-exposed participants showed an increased risk of adulthood MAFLD (OR = 1.10, 95% CI 1.00–1.21). The significant association between fetal famine exposure and MAFLD was observed in women (OR = 1.22, 95% CI 1.08–1.37), but not in men (OR = 0.88, 95% CI 0.75–1.03). In age-balanced analyses combining pre-famine and post-famine births as the reference, women exposed to famine in the fetal stage still had an increased risk of MAFLD (OR = 1.15, 95% CI 1.05–1.26). Conclusions: Prenatal exposure to famine showed a sex-specific association with the risk of MAFLD in adulthood.

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