scholarly journals Placental Restriction of Fetal Growth Increases Insulin Action, Growth, and Adiposity in the Young Lamb

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1350-1358 ◽  
Author(s):  
Miles J. De Blasio ◽  
Kathryn L. Gatford ◽  
I. Caroline McMillen ◽  
Jeffrey S. Robinson ◽  
Julie A. Owens
Keyword(s):  
Insulin Sensitivity ◽  
Fetal Growth ◽  
Insulin Action ◽  
Visceral Obesity ◽  
Later Life ◽  
Anabolic Hormone ◽  
Increased Risk ◽  
Catch Up ◽  
Diabetes And Obesity

Most children who are short or light at birth due to intrauterine growth restriction (IUGR) exhibit accelerated growth in infancy, termed “catch-up” growth, which together with IUGR, predicts increased risk of type 2 diabetes and obesity later in life. Placental restriction (PR) in sheep reduces size at birth, and also causes catch-up growth and increased adiposity at 6 wk of age. The physiological mechanisms responsible for catch-up growth after IUGR and its links to these adverse sequelae are unknown. Because insulin is a major anabolic hormone of infancy and its actions are commonly perturbed in these related disorders, we hypothesized that restriction of fetal growth would alter insulin secretion and sensitivity in the juvenile sheep at 1 month, which would be related to their altered growth and adiposity. We show that PR impairs glucose-stimulated insulin production, but not fasting insulin abundance or production in the young sheep. However, PR increases insulin sensitivity of circulating free fatty acids (FFAs), and insulin disposition indices for glucose and FFAs. Catch-up growth is predicted by the insulin disposition indices for amino acids and FFAs, and adiposity by that for FFAs. This suggests that catch-up growth and early-onset visceral obesity after IUGR may have a common underlying cause, that of increased insulin action due primarily to enhanced insulin sensitivity, which could account in part for their links to adverse metabolic and related outcomes in later life.

FABP1 gene variant associated with risk of metabolic syndrome

2021 ◽  
Vol 24 ◽  
Author(s):  
Reza Zare-Feyzabadi ◽  
Majid Mozaffari ◽  
Majid Ghayour-Mobarhan ◽  
Mohsen Valizadeh
Keyword(s):  
Metabolic Syndrome ◽  
International Diabetes Federation ◽  
Amplification Refractory Mutation System ◽  
Study Cohort ◽  
Increased Risk ◽  
Mutation System ◽  
Polymerase Chain ◽  
The Relationship ◽  
Diabetes And Obesity

Background: Metabolic Syndrome (MetS) is defined by a clustering of metabolic abnormalities associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. There has been an increasing interest in the associations of genetic variants involved in diabetes and obesity in the FABP1 pathway. The relationship between the rs2241883 polymorphism of FABP1 and risk of MetS remains unclear. Objective: We aimed to examine the association between this genetic polymorphism and the presence of MetS and its constituent factors. Methods: A total of 942 participants were recruited as part of the Mashhad Stroke and Heart Atherosclerosis Disorders (MASHAD study) Cohort. Patients with MetS were identified using the International Diabetes Federation (IDF) criteria (n=406) and those without MetS (n=536) were also recruited. DNA was extracted from peripheral blood samples and used for genotyping of the FABP1 rs2241883T/C polymorphism using Tetra-Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-ARMS PCR). Genetic analysis was confirmed by gel electrophoresis and DNA sequencing. Results: Using both univariate and multivariate analyses after adjusting for age, sex and physical activity, carriers of C allele (CT/CC genotypes) in FABP1 variant were related to an increased risk of MetS, compared to non-carriers (OR: 1.38, 95%CI: 1.04,1.82, p=0.026). Conclusion: The present study shows that C allele in the FABP1 variant can be associated with an increased risk of MetS. The evaluation of these factors in a larger population may help further confirm these findings.

009. The effect of maternal asthma during pregnancy on placental function, fetal growth and childhood development

2005 ◽  
Vol 17 (9) ◽  
pp. 65 ◽  
Author(s):  
V. L. Clifton
Keyword(s):  
Fetal Growth ◽  
Later Life ◽  
Growth Patterns ◽  
Childhood Development ◽  
Antenatal Visit ◽  
Contributing Factors ◽  
Male Fetus ◽  
Female Fetus ◽  
Adult Disease ◽  
Increased Risk

Fetal growth and neonatal birth weight are significant contributing factors to the development of adult disease states in later life. In human pregnancy, we have identified sexually dimorphic differences in fetal growth with the female fetus reducing growth in response to maternal asthma and the male fetus continuing to grow at a normal rate but being at an increased risk of in utero death. The physiological mechanisms that confer sex-specific differences in the fetal response to maternal asthma are unknown. However our research has identified differences in mechanisms associated with fetal glucocorticoid regulation, which are also associated with changes in childhood growth patterns. Asthmatic and control pregnant women were recruited at their first antenatal visit and followed through to delivery. Subjects were assessed for severity of asthma and their use of medication, including glucocorticoid therapy, was recorded. In addition to routine antenatal care, fetal growth was determined using Doppler ultrasound. Following delivery placentas and cord blood were collected. The children of the women followed during the study were examined by a paediatrician at 6 months of age and every 12 months after that initial visit. Our data shows that in response to maternal asthma, the female fetus has an increase in cortisol, which downregulates placental GR expression, immune and hypothalamic-pituitary-adrenal function and is associated with decreased growth. The male fetus responds to increased cortisol with an increase in GR expression and no change in HPA or immune function or growth. These data indicate that the male and female fetus have different strategies to control growth and in their response to a maternal stress, such as asthma.

scholarly journals Metabolic signature of obesity-associated insulin resistance and type 2 diabetes

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Haya Al-Sulaiti ◽  
Ilhame Diboun ◽  
Maha V. Agha ◽  
Fatima F. S. Mohamed ◽  
Stephen Atkin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Serum Samples ◽  
Metabolic Markers ◽  
Insulin Resistant ◽  
Increased Risk ◽  
Novel Biomarkers ◽  
Prospective Cohorts

Abstract Background Obesity is associated with an increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). However, some obese individuals maintain their insulin sensitivity and exhibit a lower risk of associated comorbidities. The underlying metabolic pathways differentiating obese insulin sensitive (OIS) and obese insulin resistant (OIR) individuals remain unclear. Methods In this study, 107 subjects underwent untargeted metabolomics of serum samples using the Metabolon platform. Thirty-two subjects were lean controls whilst 75 subjects were obese including 20 OIS, 41 OIR, and 14 T2DM individuals. Results Our results showed that phospholipid metabolites including choline, glycerophosphoethanolamine and glycerophosphorylcholine were significantly altered from OIS when compared with OIR and T2DM individuals. Furthermore, our data confirmed changes in metabolic markers of liver disease, vascular disease and T2DM, such as 3-hydroxymyristate, dimethylarginine and 1,5-anhydroglucitol, respectively. Conclusion This pilot data has identified phospholipid metabolites as potential novel biomarkers of obesity-associated insulin sensitivity and confirmed the association of known metabolites with increased risk of obesity-associated insulin resistance, with possible diagnostic and therapeutic applications. Further studies are warranted to confirm these associations in prospective cohorts and to investigate their functionality.

scholarly journals Developmental origin of polycystic ovary syndrome - a hypothesis

2002 ◽  
Vol 174 (1) ◽  
pp. 1-5 ◽  
Author(s):  
DH Abbott ◽  
DA Dumesic ◽  
S Franks
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Regulatory Region ◽  
Later Life ◽  
Ovary Syndrome ◽  
Increased Risk ◽  
Genetically Determined ◽  
Lh Secretion

Polycystic ovary syndrome (PCOS) is a common but complex endocrine disorder and is a major cause of anovulation and consequent subfertility. It is also associated with a metabolic disturbance, characterized by hyperinsulinaemia and insulin resistance that carries an increased risk of type 2 diabetes in later life. Despite its prevalence little is known about its aetiology, but there is increasing evidence for an important genetic involvement. On the basis of experimental observations in the prenatally androgenized sheep and rhesus monkey, and supported by data from human studies, we propose that the clinical and biochemical features of PCOS can arise as a consequence of genetically determined hypersecretion of androgens by the ovary during, or very likely long before, puberty. The resulting hyperandrogenism results in 'programming' of the hypothalamic-pituitary unit to favour excess LH secretion, and encourages preferential abdominal adiposity that predisposes to insulin resistance. The severity of hyperinsulinaemia and insulin resistance (which has a profound influence on the phenotype of PCOS) is further influenced by both genetic factors (such as polymorphism in the insulin gene regulatory region) and environmental factors, notably obesity. This hypothesis therefore suggests a unifying, 'linear' model to explain the aetiology of the heterogeneous phenotype.

Vitamin D and Insulin Action and Secretion –An Overview of Current Understanding and Future Perspectives

2010 ◽  
Vol 6 (2) ◽  
pp. 13 ◽  
Author(s):  
Hanne L Gulseth ◽  
Cecilie Wium ◽  
Kåre I Birkeland ◽  
◽  
◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin D ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Current Knowledge ◽  
Vitamin D Status ◽  
Cross Sectional ◽  
Indirect Measures

Impaired vitamin D status has been linked to the development of type 2 diabetes. This review summarises the current knowledge of the effects of vitamin D on insulin action and secretion. Animal andin vitrostudies suggest an effect of vitamin D on insulin action and secretion. The effects of vitamin D status in humans are not as clear, however, and cross-sectional data on insulin sensitivity and secretion are inconclusive. Intervention studies are few and often suffer from inadequate design including short duration, low sample power, low dose of vitamin D or use of indirect measures of insulin sensitivity and secretion. Despite some plausible biological mechanisms for an effect of vitamin D on both insulin secretion and action, more evidence is needed to decide whether vitamin D plays an important role in the pathophysiology of type 2 diabetes.

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

2016 ◽  
Vol 7 (5) ◽  
pp. 505-512 ◽  
Author(s):  
S. Firmin ◽  
N. Bahi-Jaber ◽  
L. Abdennebi-Najar
Keyword(s):  
Type 2 Diabetes ◽  
Early Life ◽  
Animal Studies ◽  
Cell Mass ◽  
Later Life ◽  
Adult Health ◽  
Food Contaminants ◽  
Insulin Synthesis ◽  
Increased Risk

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.

scholarly journals Microbiota-related metabolites and the risk of type 2 diabetes

2020 ◽  
Author(s):  
Jagadish Vangipurapu ◽  
Lilian Fernandes Silva ◽  
Teemu Kuulasmaa ◽  
Ulf Smith ◽  
Markku Laakso
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Oral Glucose ◽  
Microbial Metabolites ◽  
Cross Sectional ◽  
Metabolomics Data ◽  
Incident Type ◽  
Increased Risk

<b>OBJECTIVE: </b>Recent studies have highlighted the significance of microbiome in human health and disease. Changes in the metabolites produced by microbiota have been implicated in several diseases. Our objective was to identify microbiome metabolites that are associated with type 2 diabetes. <p> </p> <p><b>RESEARCH DESIGN AND METHODS: </b>5,181 participants from the cross-sectional METabolic Syndrome In Men (METSIM) study that included Finnish men (age 57 ± 7 years, body mass index 26.5 ± 3.5 kg/m<sup>2</sup>) having metabolomics data available were included in our study. Metabolomics analysis was performed based on fasting plasma samples. Based on an oral glucose tolerance test, Matsuda ISI and Disposition index were calculated as markers of insulin sensitivity and insulin secretion. A total of 4,851 participants had a 7.4-year follow-up visit and 522 participants developed type 2 diabetes.</p> <p><b> </b></p> <p><b>RESULTS: </b>Creatine, 1-palmitoleoylglycerol(16:1), urate, 2-hydroxybutyrate/2-hydroxyisobutyrate, xanthine, xanthurenate, kynurenate, 3-(4-hydroxyphenyl)lactate, 1-oleoylglycerol(18:1), 1-myristoylglycerol(14:0), dimethylglycine and 2-hydroxyhippurate(salicylurate) were significantly associated with an increased risk of type 2 diabetes. These metabolites were associated with decreased insulin secretion or insulin sensitivity or both. Among the metabolites that were associated with a decreased risk of type 2 diabetes, 1-linoleoyl-glycerophosphocholine (18:2) significantly reduced the risk of type 2 diabetes.</p> <p><b> </b></p> <p><b>CONCLUSIONS: </b>Several novel and previously reported microbial metabolites related to gut microbiota were associated with an increased risk of incident type 2 diabetes, and they were also associated with decreased insulin secretion and insulin sensitivity. Microbial metabolites are important biomarkers for the risk of type 2 diabetes. </p>

scholarly journals Outcome of COVID-19: Diabetes and Obesity

2021 ◽  
pp. 248-255
Author(s):  
Rithika Gunta
Keyword(s):  
Vascular Inflammation ◽  
Diabetic Patients ◽  
Vulnerable Group ◽  
Glucose Levels ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Lipid Aldehydes ◽  
Diabetes And Obesity ◽  
Corona Viruses

Today the world is facing one of the biggest crisis, due to a new beta-corona virus emerged from Wuhan in China, on December 2019. WHO declared ‘acute respiratory syndrome COVID-19 (SARS Co-2)’as a pandemic on March 12, 2020. Corona viruses are enveloped positive single stranded RNA viruses, causing severe acute respiratory syndrome in the infected individuals. The risk of getting infected by covid-19 is similar in all the individuals across the nation. But the outcome of the infection varies from one individual to another, depending on the comorbidities present in them. The most vulnerable group of patients in respect to severity of outcome of the infection are the once with unbalanced heath conditions like age (>65 years), immune-compromised, hypertension, type 2 diabetes, increased insulin resistance, cardiovascular diseases, chronic kidney disease, chronic liver disease, vasculitis(vascular inflammation)and obesity. It is now a public knowledge that diabetes and obesity are a risk factor for any individual as these conditions can exacerbate the manifestations of COVID-19 infections thus increasing the severity of the condition, that may require hospitalization of the patient, later may even require intensive care unit or/and mechanical ventilation, with increased risk of mortality rates. In diabetic patients it is mainly due to failure in controlling the glucose levels and the risk of ketoacidosis. In patients with obesity lipid peroxidase creates reactive lipid aldehydes leading to poor prognosis.

Lipid abnormalities in tissues of the KKAy mouse: effects of pioglitazone on malonyl-CoA and diacylglycerol

1994 ◽  
Vol 267 (1) ◽  
pp. E95-E101 ◽  
Author(s):  
A. K. Saha ◽  
T. G. Kurowski ◽  
J. R. Colca ◽  
N. B. Ruderman
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Control Group ◽  
Insulin Resistant ◽  
Kkay Mice ◽  
Malonyl Coa ◽  
Tissue Lipids ◽  
Lipid Abnormalities ◽  
Diabetes And Obesity

Insulin resistance is present in liver and muscle of subjects with type 2 diabetes and obesity. Recent studies suggest that such insulin resistance could be related to abnormalities in lipid-mediated signal transduction; however, the nature of these abnormalities is unclear. To examine this question further, tissue levels of diacylglycerol (DAG), malonyl-CoA, and triglyceride (TG) were determined in liver and soleus muscle of obese insulin-resistant KKAy mice and lean C57 BL control mice. In addition, the effects of treatment with pioglitazone, an antidiabetic agent that acts by increasing insulin sensitivity in muscle, liver, and other tissues, were assessed. The KKAy mice were hyperglycemic (407 vs. 138 mg/dl), hypertriglyceridemic (337 vs. 109 mg/dl), hyperinsulinemic (631 vs. 15 mU/ml), and weighed more (42 vs. 35 g) than the control mice. They also had 1.5- to 2.0-fold higher levels of malonyl-CoA in both liver and muscle, higher DAG (twofold) and TG (1.3-fold) levels in muscle, and higher TG (threefold), but not DAG, levels. Treatment of the KKAy mice with pioglitazone for 4 days decreased plasma glucose, TGs, and insulin by approximately 50% and restored hepatic and muscle malonyl-CoA levels to control values. In contrast, pioglitazone increased hepatic and muscle DAG levels two- or threefold. It has no effect on muscle or hepatic TG content, and it slightly increased hepatic TGs in the control group. The results indicate that abnormalities in tissue lipids occur in both liver and muscle of the KKAy mouse and that they are differentially altered when insulin sensitivity is enhanced by treatment with pioglitazone.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal regulation of postnatal growth from birth to age six months in Small-for-Gestational - Age children

2016 ◽  
Vol 7 (3) ◽  
pp. 104-110
Author(s):  
Kristina F Islamova ◽  
Dmitriy O Ivanov ◽  
Yuriy V Petrenko ◽  
Elizaveta A Kurzina
Keyword(s):  
Insulin Sensitivity ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Hormonal Regulation ◽  
Later Life ◽  
Postnatal Growth ◽  
Blood Levels ◽  
Model Assessment ◽  
Appropriate For Gestational Age ◽  
Catch Up

This article is devoted to the investigation hormonal mechanisms of postnatal growth from birth to age six months in small for gestational age children (SGA) with asymmetrical and asymmetrical IUGR. The IGF-1 and GH levels, insulin sensitivity (by homeostasis model assessment (HOMA-IR)) were measured blood at 3 and 6 months of age. The prospective study includes 40 SGA infants (group 1) - 24 - with asymmetrical (1a) and 16 with symmetrical IUGR babies (1b) and 17 appropriate for gestational age (AGA) infants (group 2). Most SGA infants showed rapid, or “catch-up” postnatal growth. Symmetrical IUGR infants with “catch-up” growth had higher IGF-1 and growth GH levels at 3 month of age than asymmetrical IUGR with “catch-up” growth (p < 0,05). From 3 to 6 months of age 77 % of infants with “catch-up” growth showed retardation of growth velocity. At 6 month of age SGA infants with “catch-up” growth had lower IGF-1, GH blood levels and HOMA-IR than at 3 months of age (p < 0,05). Infants without “catch-up” growth had similar hormone levels at 3 and 6 months of age. We suppose, that these changes of “GH - IGF-1” axis and insulin sensitivity at age 3 and 6 months in SGA infants are the mechanisms, which promote the postnatal growth. It can be assumed that the same mechanisms may underlie metabolic disorders in later life.

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