scholarly journals Superimposition of Postnatal Calorie Restriction Protects the Aging Male Intrauterine Growth- Restricted Offspring from Metabolic Maladaptations

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4216-4226 ◽  
Author(s):  
Yun Dai ◽  
Shanthie Thamotharan ◽  
Meena Garg ◽  
Bo-Chul Shin ◽  
Sherin U. Devaskar
Keyword(s):  
Physical Activity ◽  
Insulin Sensitivity ◽  
Postnatal Growth ◽  
Growth Restriction ◽  
Fine Tuning ◽  
Whole Body ◽  
Aging Male ◽  
Intrauterine Growth ◽  
Euglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp

Intrauterine growth restriction (IUGR) results in dysregulated glucose homeostasis and adiposity in the adult. We hypothesized that with aging, these perturbations will wane, and superimposition of postnatal growth restriction (PNGR) on IUGR [intrauterine and postnatal growth restriction (IPGR)] will reverse the residual IUGR phenotype. We therefore undertook hyperinsulinemic-euglycemic clamp, energy balance, and physical activity studies during fed, fasted, and refed states, in light and dark cycles, on postweaned chow diet-fed more than 17-month aging male IUGR, PNGR, and IPGR vs. control (CON) rat offspring. Hyperinsulinemic-euglycemic clamp revealed similar whole-body insulin sensitivity and physical activity in the nonobese IUGR vs. CON, despite reduced heat production and energy expenditure. Compared with CON and IUGR, IPGR mimicking PNGR was lean and growth restricted with increased physical activity, O2 consumption (VO2), energy intake, and expenditure. Although insulin sensitivity was no different in IPGR and PNGR, skeletal muscle insulin-induced glucose uptake was enhanced. This presentation proved protective against the chronologically earlier (5.5 months) development of obesity and dysregulated energy homeostasis after 19 wk on a postweaned high-fat diet. This protective role of PNGR on the metabolic IUGR phenotype needs future fine tuning aimed at minimizing unintended consequences.

Abstract 17025: Myeloid Rage Protects From Insulin Resistance in Mice Fed High Fat Diet

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Lakshmi Arivazhagan ◽  
Henry Ruiz ◽  
Robin Wilson ◽  
Laura Frye ◽  
Ravichandran Ramasamy ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
High Fat Diet ◽  
Whole Body ◽  
High Fat ◽  
Double Knockout ◽  
Euglycemic Clamp ◽  
Insulin Resistant ◽  
Hyperinsulinemic Euglycemic Clamp

Introduction: Obesity is a major global health problem, with over one third of adults in the US classified as obese. Obesity often leads to a state of insulin resistance (IR), type 2 diabetes (T2D) and its complications. We previously showed that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and IR, as whole body and adipocyte-specific Ager (gene encoding RAGE) deleted mice fed a high fat diet (HFD) were significantly protected from weight gain and IR. Here, we hypothesize that myeloid RAGE contributed to IR upon HFD feeding. Methods: We generated mice with myeloid-specific (MDR) LyzMCre(+/+).Ager flox/flox and adipocyte and myeloid-specific (Double Knockouts) AdipoQCre(-/+)LyzMCre(+/+).Ager flox/flox deletion of Ager and LysMCre mice were used as control. Mice were fed either standard chow (LFD) or HFD (60% kcal/fat) for 3 months starting at age 6 weeks. Mice were assessed for body mass and composition, glucose and insulin sensitivity and whole body glucose metabolism by hyperinsulinemic-euglycemic clamp studies. Results: After 3 months HFD, there were no significant differences in body mass, body composition, food intake, energy expenditure and physical activity of the MDR mice vs. controls. Similar findings were observed in mice fed LFD. However, surprisingly, in HFD-fed mice, insulin tolerance tests and hyperinsulinemic-euglycemic clamp studies showed decreased insulin sensitivity and insulin action in the MDR vs. control mice, indicating that the MDR mice were more insulin resistant. The Double Knockout (myeloid/adipocyte) Cre (+) mice were more glucose tolerant and insulin sensitive compared to MDR mice, showing that deletion of Ager in the adipocytes rescued the adverse effects of Ager deletion in myeloid cells. Conclusions: Myeloid Ager protects from IR in mice fed HFD. Furthermore, in MDR mice, concomitant adipocyte-specific deletion of Ager rescues these mice from IR and, at the same time, reduces HFD-induced adiposity. The mechanisms underlying these findings are under active investigation.

scholarly journals Lipid accumulation product (LAP) as a potential index to predict risk of insulin resistance in young, non-obese Asian Indian males from Southern India: observations from hyperinsulinemic-euglycemic clamp studies

2021 ◽  
Vol 9 (1) ◽  
pp. e002414
Author(s):  
Shajith Anoop S ◽  
Riddhi Dasgupta ◽  
Grace Rebekah ◽  
Arun Jose ◽  
Mercy Prem Inbakumari ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Asian Indian ◽  
Lipid Accumulation ◽  
Predictive Accuracy ◽  
Southern India ◽  
Whole Body ◽  
Lipid Accumulation Product ◽  
Euglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp

IntroductionWe aimed to compare the predictive accuracy of surrogate indices namely the lipid accumulation product (LAP) index, homeostatic model of assessment of insulin resistance (HOMA-IR), fasting glucose-insulin ratio (FG-IR) and the quantitative-insulin sensitivity check index (QUICKI), against the M value of hyperinsulinemic-euglycemic clamp (HEC), and to determine a cut-off value for the LAP index to predict risk of insulin resistance in non-obese (body mass index <21 kg/m2), normoglycemic, Asian Indian males from Southern India.Research design and methodsData of HEC studies performed in 108 non-obese, normoglycemic, Asian Indian males was obtained retrospectively and the M value (a measure of whole-body insulin sensitivity) was calculated. The M value is the rate of whole-body glucose metabolism at the hyperinsulinemic plateau (a measure of insulin sensitivity) and is calculated between 60 and 120 min after the start of the insulin infusion in the HEC procedure. The LAP index, the HOMA-IR, FG-IR and QUICKI were calculated. Spearman’s correlation and logistic regression analysis were performed. Cut-off value for the LAP index was obtained using receiver operating characteristics with area under curve (AUC) analysis at 95% CI. P value <0.05 was considered to be statistically significant.ResultsSignificant negative correlation was observed for the M value with LAP index (r=−0.39, p<0.001) while significant positive correlation was noted with FG-IR (r=0.25; p<0.01) and QUICKI (r=0.22; p<0.01). The LAP index cut-off value ≥33.4 showed 75% sensitivity and 75% specificity with AUC (0.72) to predict risk of insulin resistance in this cohort.ConclusionThe LAP index showed higher predictive accuracy for the risk of insulin resistance as compared with HOMA-IR, QUICKI and FG-IR in non-obese, normoglycemic Asian Indian males from Southern India.

scholarly journals The influence of reduced insulin sensitivity via short-term reductions in physical activity on cardiac baroreflex sensitivity during acute hyperglycemia

2015 ◽  
Vol 119 (12) ◽  
pp. 1383-1392 ◽  
Author(s):  
S. W. Holwerda ◽  
L. J. Reynolds ◽  
R. M. Restaino ◽  
D. P. Credeur ◽  
H. J. Leidy ◽  
...  
Keyword(s):  
Physical Activity ◽  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Baroreflex Sensitivity ◽  
Glucose Consumption ◽  
Oral Glucose ◽  
Short Term ◽  
Acute Hyperglycemia ◽  
Euglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp

Reduced insulin sensitivity and impaired glycemic control are among the consequences of physical inactivity and have been associated with reduced cardiac baroreflex sensitivity (BRS). However, the effect of reduced insulin sensitivity and acute hyperglycemia following glucose consumption on cardiac BRS in young, healthy subjects has not been well characterized. We hypothesized that a reduction in insulin sensitivity via reductions in physical activity would reduce cardiac BRS at rest and following an oral glucose tolerance test (OGTT). Nine recreationally active men (23 ± 1 yr; >10,000 steps/day) underwent 5 days of reduced daily physical activity (RA5) by refraining from planned exercise and reducing daily steps (<5,000 steps/day). Spontaneous cardiac BRS (sequence technique) was compared at rest and for 120 min following an OGTT at baseline and after RA5. A substudy ( n = 8) was also performed to independently investigate the influence of elevated insulin alone on cardiac BRS using a 120-min hyperinsulinemic-euglycemic clamp. Insulin sensitivity (Matsuda index) was significantly reduced following RA5 (BL 9.2 ± 1.3 vs. RA5 6.4 ± 1.1, P < 0.001). Resting cardiac BRS was unaffected by RA5 and significantly reduced during the OGTT similarly at baseline and RA5 (baseline 0 min, 28 ± 4 vs. 120 min, 18 ± 4; RA5 0 min, 28 ± 4 vs. 120 min, 21 ± 3 ms/mmHg). Spontaneous cardiac BRS was also reduced during the hyperinsulinemic-euglycemic clamp ( P < 0.05). Collectively, these data demonstrate that acute elevations in plasma glucose and insulin can impair spontaneous cardiac BRS in young, healthy subjects, and that reductions in cardiac BRS following acute hyperglycemia are unaffected by reduced insulin sensitivity via short-term reductions in physical activity.

A Novel Use of the Hyperinsulinemic-Euglycemic Clamp Technique to Estimate Insulin Sensitivity of Systemic Lipolysis

2001 ◽  
Vol 33 (2) ◽  
pp. 89-95 ◽  
Author(s):  
M Stumvoll ◽  
H G Wahl ◽  
K Löblein ◽  
R Becker ◽  
A Volk ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Euglycemic Clamp ◽  
Clamp Technique ◽  
Hyperinsulinemic Euglycemic Clamp

scholarly journals Chronic kidney disease and obesity bias surrogate estimates of insulin sensitivity compared with the hyperinsulinemic euglycemic clamp

2017 ◽  
Vol 312 (3) ◽  
pp. E175-E182 ◽  
Author(s):  
Iram Ahmad ◽  
Leila R. Zelnick ◽  
Nicole R. Robinson ◽  
Adriana M. Hung ◽  
Bryan Kestenbaum ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Insulin Sensitivity ◽  
Kidney Disease ◽  
Oral Glucose ◽  
Cross Sectional ◽  
Euglycemic Clamp ◽  
Insulin Kinetics ◽  
Hyperinsulinemic Euglycemic Clamp ◽  
Sensitivity Indices ◽  
Organ Specific

Insulin sensitivity can be measured by procedures such as the hyperinsulinemic euglycemic clamp or by using surrogate indices. Chronic kidney disease (CKD) and obesity may differentially affect these measurements because of changes in insulin kinetics and organ-specific effects on insulin sensitivity. In a cross-sectional study of 59 subjects with nondiabetic CKD [estimated glomerular filtration rate: (GFR) <60 ml·min−1·1.73 m2] and 39 matched healthy controls, we quantified insulin sensitivity by clamp (SIclamp), oral glucose tolerance test, and fasting glucose and insulin. We compared surrogate insulin sensitivity indices to SIclamp using descriptive statistics, graphical analyses, correlation coefficients, and linear regression. Mean age was 62.6 yr; 48% of the participants were female, and 77% were Caucasian. Insulin sensitivity indices were 8–38% lower in participants with vs. without CKD and 13–59% lower in obese compared with nonobese participants. Correlations of surrogate indices with SIclamp did not differ significantly by CKD or obesity status. Adjusting for SIclamp in addition to demographic factors, Matsuda index was 15% lower in participants with vs. without CKD ( P = 0.09) and 36% lower in participants with vs. without obesity ( P = 0.0001), whereas 1/HOMA-IR was 23% lower in participants with vs. without CKD ( P = 0.02) and 46% lower in participants with vs. without obesity ( P < 0.0001). We conclude that CKD and obesity do not significantly alter correlations of surrogate insulin sensitivity indices with SIclamp, but they do bias surrogate measurements of insulin sensitivity toward lower values. This bias may be due to differences in insulin kinetics or organ-specific responses to insulin.

scholarly journals Physical activity during pregnancy and fetal outcomes: a case-control study

2010 ◽  
Vol 44 (1) ◽  
pp. 90-101 ◽  
Author(s):  
Monica Yuri Takito ◽  
Maria Helena D'Aquino Benício
Keyword(s):  
Physical Activity ◽  
Birth Weight ◽  
Preterm Birth ◽  
Low Birth Weight ◽  
Intrauterine Growth Restriction ◽  
Case Control Study ◽  
Growth Restriction ◽  
P Value ◽  
Intrauterine Growth ◽  
Control Study

OBJECTIVE: To investigate the relationship between physical activity during the second trimester pregnancy and low birth weight, preterm birth, and intrauterine growth restriction. METHODS: Case-control study including 273 low birth weight newborns and 546 controls carried out in the city of São Paulo, Southeastern Brazil, in 2005. Low birth weight cases were grouped into two subsamples: preterm birth (n=117) and intrauterine growth restriction (n=134), with their related controls. Information was collected by means of interviews with mothers shortly after birth and transcription of medical records. Data were analyzed using conditional multiple and hierarchical logistic regression. RESULTS: Light physical activity for over 7 hours per day was shown to be protective against low birth weight (adjusted OR=0.61; 95% CI 0.39-0.94) with a dose-response relationship (p-value for trend=0.026). A similar trend was found for intrauterine growth restriction (adjusted OR=0.51; 95% CI 0.26-0.97). Homemaking activities were associated as a protective factor for both low birth weight and preterm birth (p-value for trend=0.013 and 0.035, respectively). Leisure-time walking was found to be protective against preterm birth. CONCLUSIONS: Mild physical activity during the second trimester of pregnancy such as walking has an independent protective effect on low birth weight, preterm birth, and intrauterine growth restriction.

scholarly journals Postnatal Growth after Intrauterine Growth Restriction Alters Central Leptin Signal and Energy Homeostasis

PLoS ONE ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. e30616 ◽  
Author(s):  
Bérengère Coupé ◽  
Isabelle Grit ◽  
Philippe Hulin ◽  
Gwenaëlle Randuineau ◽  
Patricia Parnet
Keyword(s):  
Intrauterine Growth Restriction ◽  
Energy Homeostasis ◽  
Postnatal Growth ◽  
Growth Restriction ◽  
Intrauterine Growth

Improvement in Insulin Sensitivity and Dyslipidemia in Protease Inhibitor-Treated Adult Male Patients After Switch to Atazanavir/Ritonavir

2008 ◽  
Vol 56 (2) ◽  
pp. 539-544 ◽  
Author(s):  
Anthony J. Busti ◽  
Roger Bedimo ◽  
David M. Margolis ◽  
Dana S. Hardin
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Antiretroviral Therapy ◽  
Insulin Dose ◽  
Whole Body ◽  
Euglycemic Clamp ◽  
Viral Loads ◽  
Immunodeficiency Virus ◽  
Fat Redistribution ◽  
Male Patients

BackgroundTreatment of human immunodeficiency virus (HIV) with protease inhibitors (PIs) is associated with insulin resistance, triglyceride-rich dyslipidemia, and fat redistribution. Atazanavir (ATV), a potent once-daily PI, has been recognized for its convenience to patients, and some studies describe improved lipid metabolism. However, its effects on insulin sensitivity have not been elucidated. We conducted this study to test the hypothesis that ATV improves insulin resistance and dyslipidemia.MethodsWe prospectively studied 9 HIV-infected men with dyslipidemia (median age, 53 years; baseline triglyceride level, >200 mg/dL) on stable PI-containing antiretroviral therapy who elected to change PI therapy to ritonavir-boosted ATV therapy, dose of 300/100 mg. We measured insulin resistance at baseline and after 12 weeks of therapy using a hyperinsulinemic euglycemic clamp (insulin dose, 200 mU/m2 minute). Fasting lipid profiles and body composition (whole-body dual energy x-ray absorptiometry) were also measured at baseline and after 12 weeks.ResultsAll 9 patients completed the study and maintained undetectable viral loads (<50 copies/mL) and stable CD4 counts. After 12 weeks, insulin sensitivity significantly improved (+28%; P = 0.008) in all patients. Triglyceride levels also improved.ConclusionsUsing the gold-standard euglycemic clamp, ritonavir-boosted ATV therapy improved PI-induced insulin resistance among dyslipidemic HIV-infected men on PI-based antiretroviral therapy. These findings were not attributable to a change in body weight and provide further evidence for ATV's unique metabolic profile among the PIs.

scholarly journals Prenatal intrauterine growth restriction and risk of retinopathy of prematurity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alison Chu ◽  
Yasmeen Dhindsa ◽  
Myung Shin Sim ◽  
Marie Altendahl ◽  
Irena Tsui
Keyword(s):  
Gestational Age ◽  
Retinopathy Of Prematurity ◽  
Intrauterine Growth Restriction ◽  
Growth Failure ◽  
Postnatal Growth ◽  
Growth Patterns ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Prenatal Growth ◽  
Postnatal Growth Failure

Abstract Low birthweight and decreased postnatal weight gain are known predictors of worse retinopathy of prematurity (ROP) but the role of prenatal growth patterns in ROP remains inconclusive. To distinguish small for gestational age (SGA) from intrauterine growth restriction (IUGR) as independent predictors of ROP, we performed a retrospective cohort study of patients who received ROP screening examinations at a level IV neonatal intensive care unit over a 7-year period. Data on IUGR and SGA status, worst stage of and need for treatment for ROP, and postnatal growth was obtained. 343 infants were included for analysis (mean gestational age = 28.6 weeks and birth weight = 1138.2 g). IUGR infants were more likely to have a worse stage of ROP and treatment-requiring ROP (both p < 0.0001) compared to non-IUGR infants. IUGR infants were more likely to be older at worst stage of ROP (p < 0.0001) and to develop postnatal growth failure (p = 0.01) than non-IUGR infants. Independent of postnatal growth failure status, IUGR infants had a 4–5 × increased risk of needing ROP treatment (p < 0.001) compared to non-IUGR infants. SGA versus appropriate for gestational age infants did not demonstrate differences in retinopathy outcomes, age at worst ROP stage, or postnatal growth failure. These findings emphasize the importance of prenatal growth on ROP development.

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