Development Of Metabolic Derangements Research Articles

Impact of Combined Antiretroviral Therapy on Metabolic Syndrome Components in Adult People Living with HIV: A Literature Review.

The development of metabolic derangements as a result of HIV treatment has been an important area of research since the introduction of zidovudine in the 1980’s. Antiretroviral therapy has intensely evolved in the last three decades, with new drugs gradually incorporated into everyday clinical practice. With the life expectancy of people living with HIV rapidly approaching that of their HIV-negative counterparts, the influence of these antiretrovirals on the development of the components of the metabolic syndrome remains of major interest to clinicians and their patients. In this review, we aimed to discuss the impact of cART on components of the metabolic syndrome, i.e., weight, plasma lipid levels, plasma glucose levels, and blood pressure, describing the influence of cART classes and of individual antiretrovirals. We also aimed to outline the limitations of the research conducted to date and the remaining knowledge gaps in this area.

The relationship between serum adiponectin levels, cardiometabolic indices and metabolic syndrome in schizophrenia.

Adiponectin is a hormone secreted by adipose tissues that is thought to influence lipid and glucose metabolism, and the development of metabolic derangements, including metabolic syndrome (MetS), in schizophrenia. We aim to determine the serum adiponectin levels in Chinese patients with schizophrenia, and explore the relationship between adiponectin levels and metabolic parameters, including MetS and its components. We hypothesized that serum adiponectin levels are similar in schizophrenia patients and controls, but decreased amongst patients on atypical antipsychotics. 81 patients and 81 controls were recruited. Anthropometric parameters and fasted blood samples for metabolic measurements were obtained. Serum adiponectin levels were measured using Bioplex assays. There was no difference in median adiponectin levels between schizophrenia patients and controls. Those taking typical antipsychotics alone had lower median adiponectin levels than those on mixed typical and atypical antipsychotics. Serum adiponectin level, controlled for age, gender and body mass index, was positively correlated with high-density lipoprotein cholesterol, and negatively correlated with diastolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels in schizophrenia patients. Patients with MetS had lower median adiponectin levels than those without MetS, and serum adiponectin levels decreased as the number of MetS components increased. After adjusting for variables thought to influence MetS, our logistic regression model did not reveal any significant association between adiponectin levels and MetS in schizophrenia patients. Our findings highlight the need for more studies focusing on serum adiponectin level and its relationship with MetS in schizophrenia, particularly in those taking typical antipsychotics.

Visceral fat does not contribute to metabolic disease in lipodystrophy.

SummaryObjectivesLipodystrophies are characterized by regional or generalized loss of adipose tissue and severe metabolic complications. The role of visceral adipose tissue (VAT) in the development of metabolic derangements in lipodystrophy is unknown. The study aim was to investigate VAT contribution to metabolic disease in lipodystrophy versus healthy controls.MethodsAnalysis of correlations between VAT volume and biomarkers of metabolic disease in 93 patients and 93 age/sex‐matched healthy controls.ResultsPatients with generalized lipodystrophy (n = 43) had lower VAT compared with matched controls, while those with partial lipodystrophy (n = 50) had higher VAT versus controls. Both groups with lipodystrophy had lower leg fat mass versus controls (p < 0.05 for all; unpaired t‐test). In both generalized and partial lipodystrophy, there was no correlation between VAT and glucose, triglycerides or high‐density lipoprotein cholesterol (p > 0.05 for all; Spearman correlation). In controls matched to patients with generalized or partial lipodystrophy, VAT correlated with glucose (R = 0.42 and 0.36), triglycerides (R = 0.36 and 0.60) and high‐density lipoprotein cholesterol (R = −0.34 and −0.64) (p < 0.05 for all; Spearman correlation).ConclusionsIn contrast to healthy controls, metabolic derangements in lipodystrophy did not correlate with VAT volume. These data suggest that, in lipodystrophy, impaired peripheral subcutaneous fat deposition may exert a larger effect than VAT accumulation on the development of metabolic complications. Interventions aimed at increasing functional subcutaneous adipose tissue may provide metabolic benefit.

Effect of Maternal Diabetes on Pre- and Post-Natal Redox Status of F1 Rat Offspring

Background: The oxidative stress and disturbed redox signaling during gestation my play an important role in the fetal programming of adult diabetes. Objective: The study aimed to investigate the effects of maternal diabetes on pre- and post-natal pancreatic and peripheral tissues redox and oxidative status in order to clarify their role in the diabetogenic programming of F1 offspring. Methods: Two groups of female Wistar rats were used (diabetic and control); diabetes was neonatally induced by STZ injection to 5-day old rats. 10 pregnancies of each group were terminated at GD 17 to obtain placentas and fetal pancreas, liver, muscle and adipose tissues for prenatal measurements. The rest of pregnancies were completed to term and the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks 10 male rats were sacrificed and serum and tissues were obtained for assessment of fasting blood glucose, tissues content of 8-oxo-dG, TBARS, GSH, GSSG, antioxidant enzymes and caspase-3. Results: The results indicated that, prenatally redox status of the foetuses of diabetic mothers is shifted toward more oxidizing environment which results from elevated oxidative stress and impaired antioxidants as indicated by elevated fetal tissues content of 8-oxo-dG, TBARS and GSSG and decreased GSH and GSH/GSSG ratio. All of these induce the apoptotic pathway in fetal pancreas. Postnatally, impaired glucose tolerance in the offspring of diabetic mothers is detected at 15th week of age and no hyperglycemia was detected until age of 30 weeks in the offspring under CD while some of offspring under HCD at age 25 weeks and most of them at 30 weeks have developed hyperglycemia. The pancreas of the offspring of diabetic mothers suffers from oxidative stress from the 5th week of age as indicated by elevated levels of nuclear and mitochondrial 8-oxo-dG contents and TBARS. Also, GSH level showed depletion with age and the activity of glutathione reductase was lower in the β-cell and hepatic tissues of the offspring of diabetic mothers. The prenatal shift of redox status persists postnatal and exaggerates with age which may explain the significant induction of the apoptotic pathway in the pancreatic β-cell. Conclusion: Maternal diabetes can crucially affect the redox status in fetal tissues prenatally and these effects can persist postnatal which may play an important role in the programming of the metabolic state of the offspring. Postnatal diet play important role in accelerating development of metabolic derangements and aggravates oxidative stress in the tissues of F1 offspring.

Age-Dependent Development of Metabolic Derangement and Effects of Intervention with Pioglitazone in Zucker Diabetic Fatty Rats

Zucker diabetic fatty (ZDF) rats are a standard animal model for the study of type 2 diabetes and for pharmacological characterization of insulin-sensitizing drugs. To analyze the age-dependent development of their metabolic derangements and the associated changes in their responses to treatment with the insulin sensitizer pioglitazone, groups of 7, 10.5, or 15.5-week-old ZDF rats were treated orally with vehicle or pioglitazone (12 mg/kg/day). Metabolic parameters including circulating concentrations of glucose, insulin, lipids, and adiponectin as well as body weight, tissue glycogen content, and the activity of p70S6 kinase in skeletal muscle were determined. Blood glucose of ZDF rats rose steeply from 5.9 +/- 0.4 to 23.7 +/- 0.5 mM between 7 and 13 weeks of age and then reached a new steady state, which was associated with increased tissue glycogen content (in 15-week-old ZDF rats versus lean littermates: skeletal muscle, 18.0 +/- 0.9 versus 10.5 +/- 1.4 micromol/g; liver, 181 +/- 6 versus 109 +/- 14 micromol/g; both p < 0.001). Early intervention with pioglitazone at 7 weeks of age fully prevented the development of hyperglycemia (blood glucose, 6.4 +/- 0.4 versus 18.7 +/- 1.5 mM after 5.5 weeks of treatment), which was accompanied by a 40% (p = 0.01) reduction of the activity of p70S6 kinase in skeletal muscles. These beneficial effects of pioglitazone were progressively lost, if treatment was initiated at later stages of disease development. Thus, ZDF rats are suitable for preclinical characterization of insulin-sensitizing thiazolidinediones in many aspects, but several important differences versus human type 2 diabetes exist and are to be considered in the use of this animal model.

Abstract 1127: Natural-Killer T Cells are Involved in the Development of Glucose Intolerance and Microalbuminuria in Diet-Induced Obese Mice

Introduction: Natural killer T (NKT) cells are a unique subset of T lymphocytes, which recognize glycolipids and integrate inflammation producing pro-inflammatory cytokines on activation. We have demonstrated that NKT cells are present in atherosclerotic lesions and play a pivotal role in atherogenesis. NKT cells also reside in visceral adipose tissues, however, their pathogenic role has not been studied in metabolic derangements. Methods and Results: To determine whether NKT cells are involved in the development of metabolic phenotypes, male β 2 microglobulin knockout (KO) mice, which lack T cells and NKT cells, and C57BL/6J (WT) mice were fed an western diet (WD) containing 21% fat and 0.15% cholesterol or a chow diet for 13 weeks. In both KO (n=14) and WT (n=10) mice fed WD, visceral adipose-tissue weight, adipose cell size, and plasma leptin and non-HDL cholesterol levels were significantly increased compared to those fed a chow ( p&lt; 0.05) but did not differ between KO and WT mice. However, in KO mice fed WD, impaired glucose tolerance (plasma glucose 15 minutes after intraperitoneal glucose injection, 228±7 vs 343±31 mg/dl, p&lt; 0.001) and microalbuminuria (urine albumin/creatinin ratio, 10±1 vs 24±2 μg/mg, p&lt; 0.0001) were significantly ameliorated, but not in WT mice. Plasma TNF-α was significantly lower in KO mice than in WT mice (29±6 vs 85±40 pg/ml, p&lt; 0.05). Immunohistochemical staining of visceral adipose tissues revealed that F4/80 (+) macrophages in KO mice were markedly reduced to 34% of those in WT mice ( p&lt; 0.0001). To further confirm that NKT cells can aggravate metabolic derangements, WT mice received α-galactosylceramide (0.1μg/g), which specifically activates NKT cells, (αgC, n=5) or saline (PBS, n=5) injection after 13 weeks of feeding WD. In αgC mice, impaired glucose tolerance (347±9 vs 308±13 mg/dl, p&lt; 0.05) and microalbuminuria (35±8 vs 17±1 μg/mg, p&lt; 0.05) were significantly exacerbated as compared to PBS mice. Conclusions: NKT cells enhance chronic inflammation in visceral adipose tissues and contribute to the development of metabolic derangements in diet-induced obese mice. NKT cells may be novel therapeutic targets in the prevention of metabolic syndrome.

The Adipokine Visfatin is Markedly Elevated in Obese Children

The insulin-mimetic adipocytokine visfatin has been linked to adiposity and the metabolic syndrome. Cross-sectional study. Eighty-three nondiabetic obese children and 40 healthy controls. We analyzed plasma visfatin concentrations to assess whether this adipokine is associated with adiposity. Plasma visfatin concentrations were nearly 2-fold higher in obese children (mean, 1.1 ng/mL; 95% CI, 0.2-6.6) than in controls (0.6 ng/mL, 95% CI, 0.6 to 0.6; P < 0.001). No relationship was detectable between visfatin and other subject characteristics, hsCRP or the lipid profile. Visfatin may be involved in the development of metabolic derangements in obese children.

Metabolic effects of theophylline in preterm infants

A loading dose of theophylline produces significant metabolic changes, including increase of plasma glucose concentration and an early rise in serum insulin in some infants. The chronic effects of theophylline on plasma glucose, serum insulin, and glucagon are not known at this time. The potential for development of metabolic derangements must be kept in mind when theophylline is used for protracted periods in premature infants.

Very early changes in circulating T3 and rT3 during development of metabolic derangement in diabetic patients.

Alterations in circulating iodothyronines were studied in 15 juvenile type diabetic patients during the development of metabolic derangement after withdrawal of insulin. By means of measurements of circulating C peptide, one group of patients with and one without residual beta-cell function had been selected. In both groups there was a gradual decrease in serum T3 during the 12-hour period studied after withdrawal of insulin, while an increase in serum rT3 was observed after 4-6 hours. The alterations in serum T3 and the metabolic derangement were significantly more pronounced in patients without than with residual beta-cell function.