Nutritional programming of insulin resistance: causes and consequences

doi:10.1016/j.tem.2013.05.006

Trends in Endocrinology & Metabolism

Volume 24, Issue 10, October 2013, Pages 525-535

https://doi.org/10.1016/j.tem.2013.05.006 Get rights and content

Highlights

•
Nutritional programming causes insulin resistance in offspring.
•
Effects of nutritional programming could be transmitted across generations.
•
Interventions are being explored to prevent the effects of nutritional programming.

Strong evidence indicates that adverse prenatal and early postnatal environments have a significant long-term influence on risk factors that result in insulin resistance, type 2 diabetes (T2D), and cardiovascular disease later in life. Here we discuss current knowledge of how maternal and neonatal nutrition influence early growth and the long-term risk of developing insulin resistance in different organs and at the whole-body level. Accumulating evidence supports a role for epigenetic mechanisms underlying this nutritional programming, consisting of heritable changes that regulate gene expression which in turn shapes the phenotype across generations. Deciphering these molecular mechanisms in key tissues and discovering key biological markers may provide valuable insight towards the development of effective intervention strategies.

Section snippets

Insulin resistance and nutritional programming

Insulin resistance is a well-recognized factor in the development and progression of metabolic syndrome (MetS), a constellation of disorders including obesity, T2D, hypertension, dyslipidemia, and cardiovascular disease [1]. In recent decades the prevalence of MetS has increased dramatically throughout the developed and developing world [2]. The primary function of insulin, a key anabolic hormone secreted by the pancreatic β cell, is to remove glucose from the circulation, when levels become

Pre- and postnatal nutritional environment and disease

The pre- and postnatal nutritional environment crucially shapes the ultimate phenotype of the organism. Nutritional programming during the perinatal period significantly influences risk factors that promote the development of insulin resistance and associated complications in the fetus 7, 8 (Box 2). This evidence comes from studies both in humans and in animal models using four main types of nutritional modulation, as outlined below.

Contribution of different organs and tissues to the process

To understand how nutritional programming causes insulin resistance in the offspring it is necessary to consider the key tissues that regulate fetal nutrient supply as well as those that respond to changes in circulating insulin (Figure 1).

The role of epigenetics

The term epigenetics refers to heritable changes in gene expression that are driven by extracellular stimuli and mechanisms that act on DNA but without changing the DNA sequence [100]. The main epigenetic mechanisms are DNA methylation, histone modification, and microRNAs [101]. Epigenetic regulation is crucial to the development and differentiation of various cell types, and offers organisms phenotypic plasticity to help them adapt their gene expression and function in response to the

Future directions and intervention strategies

Several reports suggest that insulin resistance plays central role in linking maternal nutrition to the development of several metabolic diseases [114]. Indeed, the development of insulin resistance and subsequent metabolic complications, such as increased glycemia, blood pressure, triglyceride, waist circumference, and decreased high-density cholesterol, doubles the risk of heart disease and increases fivefold the risk of T2D [115]. Targeting factors that increase risk of developing insulin

Concluding remarks

In summary, insulin resistance is an important factor contributing to nutritional programming of T2D and/or cardiovascular disease. Considering the explosive increase in these metabolic diseases in recent years, several types of interventions are being explored in an attempt to prevent the development of insulin resistance in the context of nutritional programming, although more studies are needed to prove their efficacy. Moreover, the involvement of epigenetic mechanisms in this nutritional

Acknowledgments

D.E.D.G. is a Science without Borders-CNPq (Brazil) Postdoctoral Fellow and S.E.O. is a British Heart Foundation Senior Fellow.

References (147)

A.J. Cameron
The metabolic syndrome: prevalence in worldwide populations
Endocrinol. Metab. Clin. North Am.
(2004)
A.M. Johnson et al.
The origins and drivers of insulin resistance
Cell
(2013)
L.M. Berends et al.
Early determinants of type-2 diabetes
Best Pract. Res. Clin. Endocrinol. Metab.
(2012)
K.L. Kind
Diet around conception and during pregnancy – effects on fetal and neonatal outcomes
Reprod. Biomed. Online
(2006)
C.G. Victora
Maternal and child undernutrition: consequences for adult health and human capital
Lancet
(2008)
T. Roseboom
The Dutch famine and its long-term consequences for adult health
Early Hum. Dev.
(2006)
M. Palou
Impaired insulin and leptin sensitivity in the offspring of moderate caloric-restricted dams during gestation is early programmed
J. Nutr. Biochem.
(2012)
M.Y. Jou
Maternal zinc deficiency in rats affects growth and glucose metabolism in the offspring by inducing insulin resistance postnatally
J. Nutr.
(2010)
K.A. Kumar
Maternal dietary folate and/or vitamin B12 restrictions alter body composition (adiposity) and lipid metabolism in Wistar rat offspring
J. Nutr. Biochem.
(2013)
C.P. Stewart
Low maternal vitamin B-12 status is associated with offspring insulin resistance regardless of antenatal micronutrient supplementation in rural Nepal
J. Nutr.
(2011)

S.R. Crozier

Maternal vitamin D status in pregnancy is associated with adiposity in the offspring: findings from the Southampton Women's Survey

Am. J. Clin. Nutr.

(2012)

D.A. Lawlor

Does maternal weight gain in pregnancy have long-term effects on offspring adiposity?. A sibling study in a prospective cohort of 146,894 men from 136,050 families

Am. J. Clin. Nutr.

(2011)

D. Farley

Feto-placental adaptations to maternal obesity in the baboon

Placenta

(2009)

B.R. Carone

Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals

Cell

(2010)

A.C. Ferguson-Smith et al.

You are what your dad ate

Cell Metab.

(2011)

J.C. Challier

Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta

Placenta

(2008)

M.J. Zhu

Maternal obesity up-regulates inflammatory signaling pathways and enhances cytokine expression in the mid-gestation sheep placenta

Placenta

(2010)

M.C. Vogt et al.

CNS insulin signaling in the control of energy homeostasis and glucose metabolism – from embryo to old age

Trends Endocrinol. Metab.

(2013)

J.W. Hill

Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility

Cell Metab.

(2010)

K.L. Grove

Development of metabolic systems

Physiol. Behav.

(2005)

S.G. Bouret

Role of early hormonal and nutritional experiences in shaping feeding behavior and hypothalamic

J. Nut.

(2010)

D. Simar

Interaction between maternal obesity and post-natal over-nutrition on skeletal muscle metabolism

Nutr. Metab. Cardiovasc. Dis.

(2012)

N.G. Ashino

Maternal high-fat feeding through pregnancy and lactation predisposes mouse offspring to molecular insulin resistance and fatty liver

J. Nutr. Biochem.

(2012)

G.Y. Choi

Gender-specific programmed hepatic lipid dysregulation in intrauterine growth-restricted offspring

Am. J. Obstet. Gynecol.

(2007)

N. Theys

Maternal malnutrition programs pancreatic islet mitochondrial dysfunction in the adult offspring

J. Nutr. Biochem.

(2011)

J.C. Clemente

The impact of the gut microbiota on human health: an integrative view

Cell

(2012)

O. Koren

Host remodeling of the gut microbiome and metabolic changes during pregnancy

Cell

(2012)

E. Jimenez

Is meconium from healthy newborns actually sterile?

Res. Microbiol.

(2008)

M.C. Collado

Effect of mother's weight on infant's microbiota acquisition, composition, and activity during early infancy: a prospective follow-up study initiated in early pregnancy

Am. J. Clin. Nutr.

(2010)

R.A. DeFronzo

Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009

Diabetologia

(2010)

R.A. DeFronzo et al.

Regulation of hepatic glucose metabolism in humans

Diabetes Metab. Rev.

(1987)

M.E. Symonds

Nutritional programming of the metabolic syndrome

Nat. Rev. Endocrinol.

(2009)

G.C. Burdge et al.

Nutrition, epigenetics, and developmental plasticity: implications for understanding human disease

Annu. Rev. Nutr.

(2010)

C. Remacle

Developmental programming of adult obesity and cardiovascular disease in rodents by maternal nutrition imbalance

Am. J. Clin. Nutr.

(2011)

P.H. Whincup

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

JAMA

(2008)

C.N. Hales

Fetal and infant growth and impaired glucose tolerance at age 64

BMJ

(1991)

C.J. Petry

Diabetes in old male offspring of rat dams fed a reduced protein diet

Int. J. Exp. Diabetes Res.

(2001)

S.E. Ozanne

Low birth weight is associated with specific changes in muscle insulin-signalling protein expression

Diabetologia

(2005)

Y. Li

Exposure to the Chinese famine in early life and the risk of hyperglycemia and type 2 diabetes in adulthood

Diabetes

(2010)

S.A. Stanner

Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study

BMJ

(1997)

S.E. Ozanne et al.

The long term consequences of intra-uterine protein malnutrition on glucose metabolism

Proc. Nutr. Soc.

(1999)

D.S. Fernandez-Twinn

Maternal protein restriction leads to hyperinsulinemia and reduced insulin signaling protein expression in 21-mo-old female rat offspring

Am. J. Physiol. Regul. Integr. Comp. Physiol.

(2005)

N. Theys

Maternal low-protein diet alters pancreatic islet mitochondrial function in a sex-specific manner in the adult rat

Am. J. Physiol. Regul. Integr. Comp. Physiol.

(2009)

T.X. Vo

LXR mediates enhanced hepatic gluconeogenic gene expression in adult male rat MPR offspring

J. Endocrinol.

(2013)

S. Mayeur

Maternal calorie restriction modulates placental mitochondrial biogenesis and bioenergetic efficiency: putative involvement in fetoplacental growth defects in rats

Am. J. Physiol. Endocrinol. Metab.

(2013)

A. Swali

Processes underlying the nutritional programming of embryonic development by iron deficiency in the rat

PLoS ONE

(2012)

I.H. Rosenberg

Metabolic programming of offspring by vitamin B12/folate imbalance during pregnancy

Diabetologia

(2008)

V. Jain et al.

Catch up growth in low birth weight infants: striking a healthy balance

Rev. Endocr. Metab. Disord.

(2012)

L.M. Berends

Catch-up growth following intra-uterine growth-restriction programmes an insulin-resistant phenotype in adipose tissue

Int. J. Obes. (Lond.)

(2012)

J. Eriksson

Size at birth, fat-free mass and resting metabolic rate in adult life

Horm. Metab. Res.

(2002)

Cited by (111)

Earlier or delayed seasonal broodstock spawning changes nutritional status and metabolic programming of growth for next-generation Atlantic salmon
2022, Aquaculture
Atlantic salmon (Salmo salar) breeding companies depend on changing light, temperature and feeding regimes to achieve new generations outside the natural spawning season. However, there have been few conducted trials reported that have studied whether this shift affects important traits. We test whether an induced shift of two months earlier or two months later than normal spawning season affects the nutritional status (folate, methionine, vitamin B12, vitamin B6, free amino acids, N-metabolites and lipids) in broodstock liver and muscle and whether this affects the levels of the same nutrients in the offspring. The results showed significant seasonal differences in the Cahill cycle (glucose-alanine cycle), 1C metabolism and for free amino acids catabolized in the citric acid cycle all which are important for embryonic growth The broodstock nutritional status was reflected in the eggs. Nutritional status of broodstock liver and muscle and newly fertilized eggs showed two general scenarios: Advanced spawning period did not obtain optimal deposition of nutrients in the eggs. Delayed spawning broodstock displayed a metabolic profile which indicated that it had enhanced catabolization of muscle protein which led to accumulation of aminogroups from muscle breakdown to such a degree that these amino groups were increased in the eggs. The total body weight at start-feeding stage revealed best growth for both the normal and late spawning compared to early spawning. We show here that environmental alterations in broodstock husbandry influence the nutrient status of the next generation via nutritional and metabolic programming. This is an important concept which needs more careful awareness as the metabolism compensate and regulate the energy between catabolism and anabolism through the early stages of cell divisions which give rise to changes in permanent traits for the next generation.
Does nutritional history impact on future performance and utilization of plant based diet in common carp?
2022, Aquaculture
This study investigated the possibility to improve the use of plant based feed in common carp (Cyprinus carpio), via feeding plant based diet from the early life stage. Fry, obtained from larvae produced by common carp broodstock fed with either of two diets viz. fish based diet (F diet) or plant based diet (P diet), were stocked into six earthen ponds in triplicate. Fry obtained from the F- and P- group were also fed with isoproteic (37% crude protein) and isolipidic (6.5% crude lipid) F- and P- diet respectively, for four months to attain juvenile stage. This early feeding period referred as ‘nutritional history F or P', and fish from the respective nutritional histories were denoted as ‘F- or P- fish’. After four months, a crossover experiment was initiated with random distribution of F- and P- fish into twelve cages fixed in the pond. Fish in triplicate cages per treatment group were either fed with their original diets or respective complementary diet for six weeks (C- phase). After six weeks, fish reared with complementary diets were switched to their original diet for another six weeks (O- phase). Growth performance, nutrient utilization, gene expression profile (IGF-1, GH and GHR) and protein metabolism enzyme activity were analysed at the end of both C- and O- phase. During C- phase, higher growth performance and improved nutrient utilization in P- fish and F- fish were recorded when they were fed with their original diet (P/F) compared to the complementary diet (F/P). The decreased growth performance and nutrient utilization of F- fish fed with P diet during the C- phase increased again during the O- phase and resumed to a similar growth performance with F- fish fed with F diet; however P- fish could not resume the same growth performance in the O- phase. Expression patterns of IGF-1 and GHR genes in the liver were concomitant with the growth performance. The present study confirms that nutritional history has a significant impact on nutrient utilization during latter life stages, and nutritional programming at early stage may be the strategy for complete replacement of fish based diet with plant based diet in common carp without compromising the growth performance and nutrient utilization. Conclusively, the findings revealed the profound effect of feeding common carp according to their nutritional history on the later performance of the progeny, as well as effective utilization of the plant based diet.
Placental superoxide dismutase 3 mediates benefits of maternal exercise on offspring health
2021, Cell Metabolism
Poor maternal diet increases the risk of obesity and type 2 diabetes in offspring, adding to the ever-increasing prevalence of these diseases. In contrast, we find that maternal exercise improves the metabolic health of offspring, and here, we demonstrate that this occurs through a vitamin D receptor-mediated increase in placental superoxide dismutase 3 (SOD3) expression and secretion. SOD3 activates an AMPK/TET signaling axis in fetal offspring liver, resulting in DNA demethylation at the promoters of glucose metabolic genes, enhancing liver function, and improving glucose tolerance. In humans, SOD3 is upregulated in serum and placenta from physically active pregnant women. The discovery of maternal exercise-induced cross talk between placenta-derived SOD3 and offspring liver provides a central mechanism for improved offspring metabolic health. These findings may lead to novel therapeutic approaches to limit the transmission of metabolic disease to the next generation.
Increasing preweaning milk replacer supply affects postweaning energy metabolism of Holstein male calves
2021, Animal
Citation Excerpt :
This major difference between experiments may explain the different outcomes. In addition to the type of diet, the timing of the intervention may also play a critical role on long-term metabolism modulation (Kenéz et al., 2018) and development of insulin resistance (Duque-Guimarães and Ozanne, 2013). By starting the nutritional interventions at 21 d of age, a crucial period for metabolism configuration was missed.
Male Holstein calves commonly receive minimal quantities of milk replacer (MR) to speed up weaning and reduce costs. Studies with Holstein female calves show that early life feed restriction affects energy metabolism later in life. Aiming to test this hypothesis, 120 Holstein bull calves (48.4 ± 2.2 kg of BW and 20 ± 3.2 d of age) housed in 24 pens were blocked and randomized to two treatments: A low calf MR allowance (LP) (two daily doses of 2 l each, 582 g/d of DM), or a high MR allowance (HP) (two daily meals of 4 l each, 1 164 g/d of DM). Calves were weaned at day 49 of the study and slaughtered at 32.8 ± 0.5 weeks of age. Throughout the study, animals had ad libitum access to a common compound feed, straw, and water. Twenty-four animals were randomly selected for an intravenous glucose tolerance test (IVGTT). The IVGTT was performed at week 6 and 12 of the study and consisted of an intravenous glucose infusion and sequential blood sampling up to 90 min after glucose infusions. Calves were heavier for HP until week 12, after which the difference disappeared. By design, the MR intake was higher in the HP group resulting in a higher energy intake and a higher average daily gain in the preweaning phase. Blood glucose curves were not different at week 6, but at week 12, 5 min after the infusion, glucose was higher in HP calves. Insulin curves were not different at week 6. Nevertheless, in week 12, a higher insulin concentration was observed for HP 5, 10, 15, 20, 30, 35, and 45 min’ postinfusion, indicating a higher requirement of insulin to control glycemia. Differences between HP and LP calves were also observed for the quantitative insulin sensitivity check index, maximum insulin concentration, and insulin delta at week 12. Blood glucose reached maximum concentration within 5–10 min of the IVGTT test, and the concentration was, on average, 8.58 and 10.80 mmol/l at weeks 6 and 12, respectively. Insulin reached maximum concentration within 10–15 min of the IVGTT, and concentrations were, on average, 33.32 and 32.61 μUI/ml at weeks 6 and 12, respectively. Doubling MR supply improved animal growth up to weaning, but these differences disappeared by the end of the feeding period. Despite similar responses to glucose infusions preweaning, higher milk supply seemed to decrease insulin sensitivity after weaning.
Moderate over-feeding of different sources of metabolizable energy and protein improved gestational insulin resistance markers and maternal metabolic status of sheep around lambing
2021, Theriogenology
The objective of this study was to determine the effect of moderate over-nutrition of energy (using flaxseed as a source of n-3 fatty acids) and protein (using rumen-protected lysine and methionine) around parturition on prepartal insulin resistance (IR) and periparturient metabolic status and performance of ewes. For this purpose, 32 apparently healthy ewes (2.5 ± 1 years old, 42.19 ± 1.65 kg body weight (BW)) were randomly selected out of 200 pregnant Zell ewes on d 50 before the expected lambing. After receiving a ten-day adaptation diet, eight ewes were randomly allocated to one of the following four dietary treatments: 1) the adaptation diet that meets the metabolizable energy (ME) and protein (MP) requirements of ewes during late pregnancy as recommended by National Research Council = NRC (2007) (Control = CON). 2) A diet with 10% higher levels of ME than NRC (2007) recommendations using corn grain as a source of extra ME (HEC). 3) A diet with 10% higher levels of ME compared to NRC (2007) recommendations using flaxseed for additional ME (HEF). 4) A diet with a 10% higher level of MP than NRC (2007) recommendations using rumen-protected lysine and methionine as a source of extra MP (PRO). While the dietary treatments did not affect animals’ dry matter intake (DMI), the CON ewes lost more BW starting from d 10 to d 30 relative to parturition compared to others (P < 0.05). Milk protein and fat yield (g/d) were significantly higher for PRO and HEF compared to HEC and CON ewes (P < 0.05). Moderately over-fed ewes with MP and ME had an improved insulin sensitivity (IS) compared to CON ones. The source of additional ME also impacted IR indices because HEC showed an enhancement in IS than HEF animals (P < 0.05). A lower IS in CON ewes was parallel with higher concentrations of plasma urea at prepartum (P < 0.01), lower levels of plasma cholesterol, triglyceride (P < 0.01) and glucose post-partum (P < 0.05), and a tendency for higher levels of beta-hydroxybutyrate (BHB) and non-esterified fatty acids (NEFA) in CON ewes during both pre- and post-partum periods. There were negative correlations between plasma urea, BHB, and NEFA with IR markers on d 7 prepartum in line with these results. Comparing data, we could not find a significant change in metabolic status among ewes fed with either PRO or HEF/HEC. In conclusion, the inclusion of 10% extra MP and ME could improve late gestation maternal IS and the metabolic status of dams around lambing.
Out-of-season spawning affects the nutritional status and gene expression in both Atlantic salmon female broodstock and their offspring
2020, Comparative Biochemistry and Physiology -Part A : Molecular and Integrative Physiology
Citation Excerpt :
Vertebrates show a great developmental plasticity during embryogenesis, a period which is sensitive to nutritional stimuli. Nutritional stimuli can give long term metabolic consequences that persist even after the nutritional exposure terminates, a concept known as nutritional programming (Agosti et al., 2017; Duque-Guimaraes and Ozanne, 2013). In addition, embryonic development in fish accomplish a range of coordinates events consisting of intrinsic factors like nutrients accumulated during oocyte maturation, external environmental stimuli like temperature and toxicants and parental genetic material and gene regulation (Izquierdo et al., 2001; Izquierdo et al., 2015; Palace and Werner, 2006; Pelegri, 2003).
The Atlantic salmon aquaculture industry relies on adjustments of female broodstock spawning season to meet the demand for delivery of embryos outside the natural spawning season. Earlier results from zebrafish have shown that parental micronutrient status program offspring metabolism. Therefore, the main hypothesis of this study was to investigate if out-of-season (off-season) broodstock (spawning in June, in land-based recirculation systems) and their offspring deviate in micronutrient status when compared to broodstock and offspring from normal spawning season. Both seasons of female Atlantic salmon broodstock were fed the same diet and starved for approximately the same time interval prior to spawning. We compared nutrients related to the 1C metabolism (vitamin B12, folate, vitamin B6, methionine), free amino acids (FAAs) and lipid classes in broodstock muscle and liver tissues, and during offspring ontogeny. In general, the off-season broodstock showed higher levels of folate, vitamin B6 and selected FAAs in muscle tissue, and higher levels of folate and lipids (cholesterol and sphingomyelin) in liver tissue compared to normal-season. Furthermore, embryos from off-season had reduced amounts of all the measured lipid classes, like cholesterol and sphingomyelin, and lower levels of one type of folate and changes in FAAs and N-metabolites. We discovered significant differences between the seasons in mRNA levels of genes controlling fatty acid synthesis and 1C metabolism in both broodstock liver and offspring. Moreover, for genes controlling the methylation of DNA; both maintenance and de novo DNA methyltransferases (DNMTs) were expressed at higher levels in off-season compared to normal-season offspring. Our results show, in general that normal spawning season broodstock allocated more nutrients to eggs than off-season. Our results indicate a potential for improved maturation for off-season group to obtain a higher offspring growth potential, and this argues for a reassessment of the nutritional influence from broodstock to offspring and the consequences through nutritional programming.

View all citing articles on Scopus

View full text

Trends in Endocrinology & Metabolism

ReviewFeature ReviewNutritional programming of insulin resistance: causes and consequences

Highlights

Section snippets

Insulin resistance and nutritional programming

Pre- and postnatal nutritional environment and disease

Contribution of different organs and tissues to the process

The role of epigenetics

Future directions and intervention strategies

Concluding remarks

Acknowledgments

Endocrinol. Metab. Clin. North Am.

Cell

Best Pract. Res. Clin. Endocrinol. Metab.

Reprod. Biomed. Online

Lancet

Early Hum. Dev.

J. Nutr. Biochem.

J. Nutr.

J. Nutr. Biochem.

J. Nutr.

Am. J. Clin. Nutr.

Am. J. Clin. Nutr.

Placenta

Cell

Cell Metab.

Placenta

Placenta

Trends Endocrinol. Metab.

Cell Metab.

Physiol. Behav.

J. Nut.

Nutr. Metab. Cardiovasc. Dis.

J. Nutr. Biochem.

Am. J. Obstet. Gynecol.

J. Nutr. Biochem.

Cell

Cell

Res. Microbiol.

Am. J. Clin. Nutr.

Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009

Diabetologia

Regulation of hepatic glucose metabolism in humans

Diabetes Metab. Rev.

Nutritional programming of the metabolic syndrome

Nat. Rev. Endocrinol.

Nutrition, epigenetics, and developmental plasticity: implications for understanding human disease

Annu. Rev. Nutr.

Developmental programming of adult obesity and cardiovascular disease in rodents by maternal nutrition imbalance

Am. J. Clin. Nutr.

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

JAMA

Fetal and infant growth and impaired glucose tolerance at age 64

BMJ

Diabetes in old male offspring of rat dams fed a reduced protein diet

Int. J. Exp. Diabetes Res.

Low birth weight is associated with specific changes in muscle insulin-signalling protein expression

Diabetologia

Exposure to the Chinese famine in early life and the risk of hyperglycemia and type 2 diabetes in adulthood

Diabetes

Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study

BMJ

The long term consequences of intra-uterine protein malnutrition on glucose metabolism

Proc. Nutr. Soc.

Maternal protein restriction leads to hyperinsulinemia and reduced insulin signaling protein expression in 21-mo-old female rat offspring

Am. J. Physiol. Regul. Integr. Comp. Physiol.

Maternal low-protein diet alters pancreatic islet mitochondrial function in a sex-specific manner in the adult rat

Am. J. Physiol. Regul. Integr. Comp. Physiol.

LXR mediates enhanced hepatic gluconeogenic gene expression in adult male rat MPR offspring

J. Endocrinol.

Maternal calorie restriction modulates placental mitochondrial biogenesis and bioenergetic efficiency: putative involvement in fetoplacental growth defects in rats

Am. J. Physiol. Endocrinol. Metab.

Processes underlying the nutritional programming of embryonic development by iron deficiency in the rat

PLoS ONE

Metabolic programming of offspring by vitamin B12/folate imbalance during pregnancy

Diabetologia

Catch up growth in low birth weight infants: striking a healthy balance

Rev. Endocr. Metab. Disord.

Catch-up growth following intra-uterine growth-restriction programmes an insulin-resistant phenotype in adipose tissue

Int. J. Obes. (Lond.)

Review
Feature Review
Nutritional programming of insulin resistance: causes and consequences