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Mark H. Vickers

Bio: Mark H. Vickers is an academic researcher from University of Auckland. The author has contributed to research in topics: Offspring & Pregnancy. The author has an hindex of 44, co-authored 212 publications receiving 8686 citations. Previous affiliations of Mark H. Vickers include Technische Universität München & Health Science University.


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Journal ArticleDOI
TL;DR: This study is the first to demonstrate that profound adult hyperphagia is a consequence of fetal programming and a key contributing factor in adult pathophysiology.
Abstract: Environmental factors and diet are generally believed to be accelerators of obesity and hypertension, but they are not the underlying cause Our animal model of obesity and hypertension is based on the observation that impaired fetal growth has long-term clinical consequences that are induced by fetal programming Using fetal undernutrition throughout pregnancy, we investigated whether the effects of fetal programming on adult obesity and hypertension are mediated by changes in insulin and leptin action and whether increased appetite may be a behavioral trigger of adult disease Virgin Wistar rats were time mated and randomly assigned to receive food either ad libitum (AD group) or at 30% of ad libitum intake, or undernutrition (UN group) Offspring from UN mothers were significantly smaller at birth than AD offspring At weaning, offspring were assigned to one of two diets [a control diet or a hypercaloric (30% fat) diet] Food intake in offspring from UN mothers was significantly elevated at an early postnatal age It increased further with advancing age and was amplified by hypercaloric nutrition UN offspring also showed elevated systolic blood pressure and markedly increased fasting plasma insulin and leptin concentrations This study is the first to demonstrate that profound adult hyperphagia is a consequence of fetal programming and a key contributing factor in adult pathophysiology We hypothesize that hyperinsulinism and hyperleptinemia play a key role in the etiology of hyperphagia, obesity, and hypertension as a consequence of altered fetal development

1,008 citations

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TL;DR: What is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration are discussed, are discussed.
Abstract: Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.

736 citations

Journal ArticleDOI
TL;DR: The complete normalization of the programmed phenotype by neonatal leptin treatment implies that leptin has effects that reverse the prenatal adaptations resulting from relative fetal undernutrition, and is potentially reversible by an intervention late in the phase of developmental plasticity.
Abstract: An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity and insulin resistance. Although the mechanisms are unclear, this programming has generally been considered an irreversible change in developmental trajectory. Adult offspring of rats subjected to undernutrition during pregnancy develop obesity, hyperinsulinemia, and hyperleptinemia, especially in the presence of a high-fat diet. Reduced locomotor activity and hyperphagia contribute to the increased fat mass. Using this model of maternal undernutrition, we investigated the effects of neonatal leptin treatment on the metabolic phenotype of adult female offspring. Leptin treatment (rec-rat leptin, 2.5 μg/g·d, sc) from postnatal d 3–13 resulted in a transient slowing of neonatal weight gain, particularly in programmed offspring, and normalized caloric intake, locomotor activity, body weight, fat mass, and fasting plasma glucose, insulin, and leptin concentrations in programmed offspring in adult life in contras...

597 citations

Journal ArticleDOI
TL;DR: It is of interest that a lifetime of HF nutrition produced a similar offspring phenotype to HF nutrition restricted to pregnancy and lactation alone, thus suggesting that the postnatal sequelae of maternal HF nutrition occurs independent of preconceptional diet.
Abstract: Significant alterations in maternal nutrition may induce long-term metabolic consequences in offspring, in particular obesity and leptin and insulin resistance. Although maternal nutrient deprivation has been well characterized in this context, there is a relative paucity of data on how high fat (HF) nutrition impacts on the subsequent generation. The present study investigated the effects of maternal HF nutrition either throughout the mother's life up to and including pregnancy and lactation or HF nutrition restricted to pregnancy and lactation, on growth and metabolic parameters in male and female offspring. Virgin Wistar rats were assigned to one of three experimental groups: (1) controls (Cont): dams fed a standard chow diet throughout their life and throughout pregnancy and lactation; (2) maternal high fat (MHF) group: dams fed a HF diet from weaning up to and throughout pregnancy and lactation; and (3) pregnancy and lactation high fat (PLHF): dams fed a chow diet through their life until conception and then fed a HF diet throughout pregnancy and lactation. At weaning, all offspring were fed either a chow or HF diet for the remainder of the study (160 days). Litter size and sex ratios were not significantly different between the groups. MHF and PLHF offspring had significantly lower body weights and were hypoleptinaemic and hypoinsulinaemic at birth compared to Cont offspring. As adults however, chow-fed MHF and PLHF offspring were significantly more obese than Cont offspring (DEXA scanning at day 150, P < 0.001 for maternal HF diet). As expected a postweaning HF diet resulted in increased adiposity in all groups; MHF and PLHF offspring, however, always remained significantly more obese than Cont offspring. Increased adiposity in MHF and PLHF offspring was paralleled by hyperinsulinaemia and hyperleptinaemia (P < 0.001; MHF and PLHF versus Cont). It is of interest that a lifetime of HF nutrition produced a similar offspring phenotype to HF nutrition restricted to pregnancy and lactation alone, thus suggesting that the postnatal sequelae of maternal HF nutrition occurs independent of preconceptional diet. These data further reinforce the importance of maternal nutrition during these critical windows of development and show that maternal HF feeding can induce a markedly obese phenotype in male and female offspring completely independent of postnatal nutrition.

427 citations

Journal ArticleDOI
TL;DR: This work is the first to clearly separate prenatal from postnatal effects and shows that lifestyle choices themselves may have a prenatal origin, and predispositions to obesity, altered eating behavior, and sedentary activity are linked and occur independently of postnatal hypercaloric nutrition.
Abstract: The discovery of a link between in utero experience and later metabolic and cardiovascular disease is one of the most important advances in epidemiology research of recent years. There is now increasing evidence that alterations in the fetal environment have long-term consequences on metabolic and endocrine pathophysiology in adult life. This process has been termed "fetal programming," and we have shown that undernutrition of the mother during gestation leads to obesity, hypertension, hyperphagia, hyperinsulinemia, and hyperleptinemia in offspring. Using this model of maternal undernutrition throughout pregnancy, we investigated whether prenatal influences may lead to alterations in postnatal locomotor behavior, independent of postnatal nutrition. Virgin Wistar rats were time mated and randomly assigned to receive food either ad libitum (ad libitum group) or at 30% of ad libitum intake (undernourished group). Offspring from UN mothers were significantly smaller at birth than AD offspring. At weaning, offspring were assigned to one of two diets [control or hypercaloric (30% fat)]. At ages of 35 days, 145 days, and 420 days, voluntary locomotor activity was assessed. At all ages studied, offspring from undernourished mothers were significantly less active than offspring born of normal birth weight for all parameters measured, independent of postnatal nutrition. Sedentary behavior in programmed offspring was exacerbated by postnatal hypercaloric nutrition. This work is the first to clearly separate prenatal from postnatal effects and shows that lifestyle choices themselves may have a prenatal origin. We have shown that predispositions to obesity, altered eating behavior, and sedentary activity are linked and occur independently of postnatal hypercaloric nutrition. Moreover, the prenatal influence may be permanent as offspring of undernourished mothers were still significantly less active compared with normal offspring at an advanced adult age, even in the presence of a healthy diet throughout postnatal life.

360 citations


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[...]

08 Dec 2001-BMJ
TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

33,785 citations

01 Jan 2014
TL;DR: These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care.
Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

9,618 citations

01 Feb 2015
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

4,409 citations

Journal ArticleDOI
TL;DR: It is concluded that damage suffered in early life leads to permanent impairment, and might also affect future generations, as undernutrition is associated with lower human capital and its prevention will probably bring about important health, educational, and economic benefits.

3,341 citations

Journal ArticleDOI
TL;DR: Evidence from several disciplines is synthesized to support the contention that environmental factors acting during development should be accorded greater weight in models of disease causation.
Abstract: Many lines of evidence, including epidemiologic data and extensive clinical and experimental studies, indicate that early life events play a powerful role in influencing later susceptibility to certain chronic diseases. This review synthesizes evidence from several disciplines to support the contention that environmental factors acting during development should be accorded greater weight in models of disease causation.

3,290 citations