scholarly journals Relation of cholesterol metabolism and non-cholesterol sterols to insulin resistance

2007 ◽  
pp. 749-755
Author(s):  
A Šmahelová ◽  
R Hyšpler ◽  
T Haas
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Insulin Level ◽  
Cholesterol Absorption ◽  
Tolerance Test ◽  
Sex Hormone Binding Globulin ◽  
The Metabolic Syndrome

Using non-cholesterol sterols investigation several authors postulated a hypothesis that in the metabolic syndrome cholesterol endogenous synthesis is increased and its absorption decreased. Our study is the first attempt to evaluate the direct relation of cholesterol metabolism to the principal pathogenetic phenomenon of the metabolic syndrome--namely to insulin resistance. We have measured insulin sensitivity by two methods--Quicki (Quantitative Sensitivity Check Index) and intravenous insulin tolerance test (Kitt) and 3 indirect markers--fasting insulin level, fasting C-peptide level and SHBG (sex hormone binding globulin). The investigation was performed in three groups of subjects with a different prevalence of insulin resistance: 72 non-diabetics with ischemic heart disease, 117 young blood donors and 63 type 2 diabetics on diet therapy only. Analyzing altogether 60 relationships--between four sterols (lathosterol, squalene, sitosterol and campesterol) and five markers of insulin resistance in three groups of subjects--we have found only six significant relations between cholesterol synthesis and absorption and insulin resistance in all groups of patients. Our results indicate that there exists a significant relationship between insulin sensitivity and indices of either increased cholesterol synthesis or decreased cholesterol absorption. Insulin resistance explains only a part of both abnormalities mentioned above.

Analysis of candidate genes in Polish families with obesity

2004 ◽  
Vol 42 (5) ◽  
Author(s):  
Malgorzata Malczewska-Malec ◽  
Iwona Wybranska ◽  
Iwona Leszczynska-Golabek ◽  
Lukasz Partyka ◽  
Jadwiga Hartwich ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Tolerance Test ◽  
Whole Body ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
The Metabolic Syndrome

AbstractThis study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-γThe 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated.The single gene mutations such as CWe conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.

scholarly journals Muscle capillarization, their morphology and pathogenesis of metabolic syndrome

1996 ◽  
Vol 42 (4) ◽  
pp. 42-46
Author(s):  
M. Krotkiewski
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Blood Supply ◽  
Early Stage ◽  
Morphological Changes ◽  
Muscle Fibers ◽  
Sex Hormone Binding Globulin ◽  
Main Role ◽  
The Metabolic Syndrome ◽  
Further Development

Morphological changes in muscles associated with a decrease in the number of fast, oxidizing muscle fibers of type IIA and an increase in the number of fast, glycolytic muscle fibers of type IIB, as well as a violation of the blood supply to muscle tissue, were considered by us in many pathological conditions associated with insulin resistance. Violation of tissue blood supply, closely associated with a decrease in sensitivity to insulin and the degree of hypertension, occurs at a relatively early stage, while an increase in the number of muscle fibers of type IIB occurs later and is associated with an increase in the concentration of atherogenic factors and hyperlipidemia. Type IIB muscle fibers (MF) are the most insulin-insensitive type MF and are not adapted to fat oxidation during muscle work. This contributes to the further development of insulin resistance and obesity; while the excess of fatty acids is sent to the liver, again violating its function. Excessive insulin also inhibits the liver. Hyperinsulinemia leads to inhibition of the synthesis of specific proteins such as the protein transporting testosterone (a sex hormone-binding globulin). As a result, an increased concentration of free testosterone leads to virilization of women and the further development of insulin insensitivity. In contrast to the previously existing concept, which assigned the main role to intra-abdominal adipose tissue, muscles and liver should also be considered as organs involved in the pathogenesis and development of the metabolic syndrome.

scholarly journals The biochemical assessment of insulin resistance

2007 ◽  
Vol 44 (4) ◽  
pp. 324-342 ◽  
Author(s):  
Anwar Borai ◽  
Callum Livingstone ◽  
Gordon A A Ferns
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Model Assessment ◽  
Intravenous Glucose ◽  
Gold Standard Method ◽  
The Metabolic Syndrome ◽  
Increased Risk

Insulin resistance is a common condition, recognized to be a central feature of the metabolic syndrome, and strongly associated with an increased risk of cardiovascular disease and diabetes. The quantitative assessment of insulin sensitivity is not used for routine clinical purposes, but the emerging importance of insulin resistance has led to its wider application to research studies that have examined its pathogenesis, aetiology and consequences. The gold standard method for the determination of insulin sensitivity is the euglycaemic hyperinsulinaemic clamp from which indices of insulin sensitivity can be derived. The clamp technique is both expensive and complex to undertake and has prompted the use of surrogate methods, notably the insulin tolerance test and frequently sampled intravenous glucose tolerance test. Indices may be derived from these methods and correlate well with those derived from clamp studies. Indices can also be derived from measurements made during a standard oral glucose tolerance test and from one-off fasting specimens (e.g. homeostasis model assessment and quantitative insulin sensitivity check index). These indices lend themselves for use in large population studies where a relatively simple, inexpensive assessment is necessary. However, these tests all suffer from important limitations, including poor precision. Insulin resistance is increasingly being assessed in clinical situations, where relatively simple markers are required. Insulin-like growth factor binding protein-1 is an emerging marker which may be useful in this context.

scholarly journals Decreased insulin sensitivity in small for gestational age males treated with GH and preterm untreated males: a study in young adults.

2008 ◽  
Vol 158 (6) ◽  
pp. 899-904 ◽  
Author(s):  
J Rotteveel ◽  
M M van Weissenbruch ◽  
H A Delemarre-Van de Waal
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Birth Weight ◽  
Insulin Sensitivity ◽  
Low Birth Weight ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Gh Therapy ◽  
The Metabolic Syndrome ◽  
Preterm Born

BackgroundLow birth weight and preterm birth are associated with growth delay as well as the development of insulin resistance. Insulin resistance is especially seen in subjects with catch-up growth. GH therapy induces growth in short subjects with low birth weight at term, but little is known about the long-term effects on insulin sensitivity. GH therapy is now also proposed for preterms that remain short.MethodsWe investigated insulin sensitivity using the gold standard hyperinsulinemic-euglycemic clamp technique in 10 young adult males born small for gestational age (SGA) who had been treated with GH during childhood (GH) in comparison with 15 males born preterm AGA (premAGA), 13 males born preterm SGA (premSGA), and 15 males born at term with normal birth weight (CON). Furthermore, we investigated the presence of the metabolic syndrome.ResultsInsulin sensitivity was decreased in premAGA, premSGA, and GH subjects compared with CON males. The metabolic syndrome was not present in any of the groups.ConclusionInsulin sensitivity is decreased in GH-treated SGA born males as well as in preterm born males. With respect to the SGA subjects, whether the difference results from perinatal-, postnatal-, or GH therapy-related factors are not known. With respect to the preterm born subjects, close surveillance is needed when commencing GH therapy.

Sodium/lithium countertransport, insulin resistance, insulin peptides and microalbuminuria in clinically healthy 58-year-old men

2001 ◽  
Vol 100 (4) ◽  
pp. 443-449 ◽  
Author(s):  
Hans HERLITZ ◽  
Lena BOKEMARK ◽  
Eva-Lena ALENHAG ◽  
John WIKSTRAND ◽  
Björn FAGERBERG
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Univariate Analysis ◽  
Serum Triglycerides ◽  
The Metabolic Syndrome ◽  
Significant Difference ◽  
N 93 ◽  
Old Men

The activity of the erythrocyte transport system, sodium/lithium countertransport (SLC), has been linked to the metabolic syndrome characterized by insulin resistance and compensatory hyperinsulinaemia. We measured SLC and insulin sensitivity with the euglycaemic hyperinsulinaemic clamp method in a patient sample (n = 93) randomly selected from a large clinically healthy group of 58-year-old men (n = 818). The lipid profile, blood pressure, body mass index (BMI) and insulin were also analysed. There was a significant difference (P < 0.001) in SLC between subjects with the metabolic syndrome (n = 19) and subjects without any components of this syndrome (n = 20). There was a highly significant correlation between SLC and BMI, waist/hip ratio, total body fat mass, serum triglycerides, plasma insulin, proinsulin split products and C-peptide in a univariate analysis. There was also a significant correlation between SLC and insulin sensitivity measured as insulin-mediated glucose uptake (P < 0.01). In multiple regression analysis, only two of the variables showing univariate significance were independently correlated to SLC, i.e. serum triglycerides (P < 0.001) and BMI (P < 0.01). The subjects with a SLC value in the highest tertile had a 6-fold higher prevalence of insulin resistance (low-insulin-mediated glucose uptake) as compared with those with a SLC value in the lowest tertile. We conclude that, in clinically healthy 58-year-old men from the general population, erythrocyte SLC is closely linked to metabolic syndrome, in particular to obesity, triglycerides and insulin resistance.

scholarly journals Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification

2010 ◽  
Vol 40 (3) ◽  
pp. 195-207 ◽  
Author(s):  
Ryan S. Friese ◽  
Jiaur R. Gayen ◽  
Nitish R. Mahapatra ◽  
Geert W. Schmid-Schönbein ◽  
Daniel T. O'Connor ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Chromogranin A ◽  
Secretory Granules ◽  
Cholesterol Biosynthesis ◽  
Hepatic Cholesterol ◽  
The Metabolic Syndrome ◽  
Insight Into

Chromogranin A (CHGA) has a crucial role in formation of regulated secretory granules in neuroendocrine tissues and is also a prohormone that is proteolytically processed into peptides with diverse and complex actions. CHGA and several of its peptide products, including catestatin and pancreastatin, are implicated in pathogenesis of essential hypertension, insulin resistance, and the metabolic syndrome. The Chga knockout mouse (Chga KO) displays severe hypertension coupled with reduction in size, number, and density of regulated secretory granules. We performed genome-wide transcriptome profiling in Chga KO adrenal gland and liver for insight into biochemical and physiological systems altered in this monogenic mouse model of hypertension. Adrenal gene expression pathway prediction of enhanced insulin sensitivity ( P = 0.03) in Chga KO was confirmed with glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) measurements: blood glucose was normal in Chga KO, blood insulin was reduced 4.5-fold ( P < 0.0001), and HOMA-IR was decreased 3.8-fold ( P < 0.002). Remarkably, such observations conclusively dissociate fundamental features of the metabolic syndrome in this monogenic hypertension model. Exogenous pancreastatin treatment restored insulin sensitivity in the Chga KO to near-normal levels. Gene expression predictions of decreased adrenal cholesterol biosynthesis ( P < 0.001) and increased hepatic cholesterol biosynthesis ( P < 0.001) were verified with tissue total cholesterol assays: Chga KO adrenal cholesterol decreased 1.8-fold ( P = 0.039) and hepatic cholesterol increased 1.8-fold ( P = 0.018). Transcriptional regulatory network prediction identified sets of transcription factors that may provide insight into the unclear mechanistic links among CHGA, cholesterol, insulin sensitivity, and the metabolic syndrome. These experiments demonstrate, for the first time, that genetic variation at the CHGA locus impacts insulin sensitivity and tissue cholesterol levels in an intact, living organism. The Chga KO may constitute a unique model for studying the relationship between the CHGA locus and disease phenotypes of the metabolic syndrome.

scholarly journals Surrogate Measures of Insulin Resistance in Middle-aged Non-diabetic Subjects

2013 ◽  
Vol 59 (6) ◽  
pp. 279-284
Author(s):  
Csép Katalin
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Fasting Insulin ◽  
Middle Aged ◽  
Insulin Levels ◽  
The Metabolic Syndrome ◽  
Sensitivity Indices ◽  
Increased Risk ◽  
Surrogate Measures

Abstract Objective: Insulin resistance has been shown to be a risk factor for type 2 diabetes and cardiovascular disease. The assessment of insulin sensitivity in the clinical practice, however, faces several difficulties. The study proposes to analyze surrogate measures of insulin resistance based on fasting insulin levels in central Romania, and check whether the diagnosis of the metabolic syndrome is an adequate strategy to identify middle-aged persons with reduced insulin sensitivity. Methods: Anthropometric measurements, metabolic profile, and surrogates measures of insulin sensitivity (GIR, HOMA, QUICKI, FIRI, Belfiore, Bennett, Raynaud, McAuley index) based on fasting insulin levels were assessed in 233 non-diabetic middle aged subjects. Results: Cutoff values, determined as the lowest quartile of insulin sensitivity for fasting insulin, HOMA, IRI (1/QUICKI), FIRI and Belfiore's, Bennett's, Raynaud's and McAuley's insulin sensitivity indices were 10.49 mU/L, 2.1, 3.01, 2.32, and 0.03, 1.34, 3.81, 6.29, 5.82. Components of the metabolic syndrome showed moderate but significant correlations with the surrogate measures of insulin resistance (r = 0.22-0.56, p <0.05). HOMA-IR and McAuley indices were the best predictors of clustered cardiometabolic risk factors (AUC - 0.83, 0.81 and 0.82). The metabolic syndrome diagnosis performed well in identifying patients with reduced insulin sensitivity (McAuley 2: sensitivity - 0.78, specificity - 0.84). Conclusion: Fasting insulin derived insulin sensitivity indices may help the recognittion of insulin resistant states predicting cardiometabolic disorders. Actively looking for insulin resistance by these simple indices, or by diagnosing the metabolic syndrome, those at increased risk can be recognized

Relationships between cholesterol homoeostasis and triacylglycerol-rich lipoprotein remnant metabolism in the metabolic syndrome

2003 ◽  
Vol 104 (4) ◽  
pp. 383-388 ◽  
Author(s):  
Dick C. CHAN ◽  
Gerald F. WATTS ◽  
P. Hugh R. BARRETT ◽  
Frans H. O'NEILL ◽  
Trevor G. REDGRAVE ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Cholesterol Metabolism ◽  
Visceral Obesity ◽  
Cholesterol Absorption ◽  
Dietary Energy ◽  
Lower Plasma ◽  
Apo B ◽  
The Metabolic Syndrome ◽  
Catabolic Rate ◽  
Plasma Markers

The dysmetabolic syndrome of insulin resistance and visceral obesity is characterized by elevated plasma concentration of triacylglycerol-rich lipoprotein (TRL) remnants that may be related to increased cardiovascular risk. Perturbed hepato-intestinal cholesterol metabolism may play a contributory role in this abnormality. We therefore investigated the association between plasma markers of cholesterol absorption and synthesis with TRL remnant metabolism in 35 men with the metabolic syndrome (MS). Plasma campesterol:cholesterol and lathosterol:cholesterol ratios were measured as estimates of cholesterol absorption and synthesis respectively. Remnant metabolism was assessed by measuring remnant-like particle-cholesterol (RLP-C), apolipoprotein (apo)B-48 and the fractional catabolic rate (FCR) of a labelled remnant-like emulsion. Compared with controls, subjects with the MS had significantly lower plasma campesterol:cholesterol ratio, but higher lathosterol:cholesterol ratio (P<0.05). Plasma RLP-C and apoB-48 concentrations were also higher (P<0.01) and the remnant-like emulsion FCR was lower (P<0.05). The plasma campesterol:cholesterol ratio was inversely correlated (P<0.05) with plasma triacylglycerols (r =-0.346), RLP-C (r =-0.443), apoB-48 (r =-0.427) and plasma lathosterol:cholesterol ratio (r =-0.366); the campesterol:cholesterol ratio was also positively correlated with the remnant-like emulsion FCR (r = 0.398, P<0.05). In multiple regression analysis, the significant correlations between plasma campesterol:cholesterol ratio and plasma triacylglycerols, RLP-C, apoB-48 and FCR of the remnant-like emulsion were independent of age, dietary energy and plasma lathosterol. Our findings suggest that in subjects with the MS alterations in cholesterol absorption and synthesis may be closely linked with the kinetic defects in TRL metabolism.

scholarly journals Insulin resistance and obesity in childhood

2008 ◽  
Vol 159 (suppl_1) ◽  
pp. S67-S74 ◽  
Author(s):  
Francesco Chiarelli ◽  
Maria Loredana Marcovecchio
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Childhood Obesity ◽  
Glucose Tolerance ◽  
Children And Adolescents ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
The Metabolic Syndrome

Childhood obesity is a significant health problem that has reached epidemic proportions around the world and is associated with several metabolic and cardiovascular complications. Insulin resistance is a common feature of childhood obesity and is considered to be an important link between adiposity and the associated risk of type 2 diabetes and cardiovascular disease. Insulin resistance is also a key component of the metabolic syndrome, and its prevalence in the paediatric population is increasing, particularly among obese children and adolescents. Several factors are implicated in the pathogenesis of obesity-related insulin resistance, such as increased free fatty acids and many hormones and cytokines released by adipose tissue.Valid and reliable methods are essential to assess the presence and the extent of insulin resistance, the associated risk factors and the effect of pharmacological and lifestyle interventions. The two most common tests to assess insulin resistance are the hyperinsulinemic euglycemic clamp and the frequently sampled i.v. glucose tolerance test utilizing the minimal model. However, both these tests are not easily accomplished, are time consuming, expensive and invasive. Simpler methods to assess insulin resistance based on surrogate markers derived from an oral glucose tolerance test or from fasting insulin and glucose levels have been validated in children and adolescents and widely used.Given the strong association between obesity, insulin resistance and the development of metabolic syndrome and cardiovascular disease, prevention and treatment of childhood obesity appear to be essential to prevent the development of insulin resistance and the associated complications.

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