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.

Erythrocyte sodium/lithium countertransport is associated with thrombotic and fibrinolytic factors in 58-year-old men

2004 ◽  
Vol 91 (06) ◽  
pp. 1152-1157
Author(s):  
Lena Bokemark ◽  
Björn Fagerberg ◽  
Hans Herlitz
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Fat ◽  
Plasma Insulin ◽  
Univariate Analysis ◽  
Serum Triglyceride ◽  
Separate Analysis ◽  
The Metabolic Syndrome ◽  
Erythrocyte Sodium ◽  
Old Men

SummaryThe metabolic syndrome, in which insulin resistance is the core feature, is associated both with dysregulation of thrombosis/ fibrinolysis and erythrocyte sodium/lithium countertransport (SLC).To investigate this further we designed a cross-sectional study to examine whether factors involved in coagulationand fibrinolysis systems were associated with SLC independently of insulin resistance in 93 58-year-old men. SLC was in univariate analysis positively correlated with PAI-1 activity (r = 0.35, p <0.01), tPA antigen (r = 0.38, p <0.01), von Willebrand factor (r = 0.25, p <0.05), protein S (r = 0.26, p <0.05), and C (r = 0.30, p <0.01), and negatively associated with tPA activity(r = −0.28, p <0.01). Since these correlations could be influenced by the components of the metabolic syndrome itself, a separate analysis with adjustment for glucose infusion rate (GIR), plasma insulin, body fat, sagittal diameter of the abdomen (SD) and log serum triglyceride concentration (TG) was conducted. Then SLC was associated with tPA antigen independent of GIR, plasma insulin, body fat, SD and TG. SLC was also associated with protein C independent of GIR, insulin, body fat and SD but not TG. In conclusion, we found a relationship between SLC and the fibrinolytic system that was not related to the metabolic syndrome.

Effects of pharmacological reversal of hyperuricemia on features of the metabolic syndrome in patients with gouty arthritis

2018 ◽  
Vol 66 (7) ◽  
pp. 1031-1036
Author(s):  
Mariana Marin ◽  
Naim M Maalouf
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Gouty Arthritis ◽  
Oxidase Inhibitor ◽  
Model Assessment ◽  
Urine Ph ◽  
Serum Triglycerides ◽  
Xanthine Oxidase Inhibitor ◽  
The Metabolic Syndrome

Hyperuricemia has been associated in epidemiological studies with the development of obesity, hypertension, insulin resistance and type 2 diabetes. Nevertheless, it remains unclear whether lowering of serum uric acid (UA) alters any of the features of the metabolic syndrome. In this prospective study (ClinicalTrials.gov identifier: NCT01654276), 24 patients with gouty arthritis and hyperuricemia were treated for 6 months with the xanthine oxidase inhibitor febuxostat to lower serum UA to <6 mg/dL. Measurements of 24 hours ambulatory blood pressure (ABP) and serum and urine markers of the metabolic syndrome were measured at baseline and at the end of 6 months of febuxostat. The study population consisted of 18 men and 6 women, 18 of which completed the baseline and 6 months visits. Serum UA decreased significantly from 8.7±1.5 mg/dL at baseline to 4.4±1.1 mg/dL at 6 months (P<0.0001). During that time frame, there was no significant change in body mass index, systolic or diastolic blood pressure measured by 24 hours ABP monitor, serum glucose, insulin or homeostatic model assessment for insulin resistance, serum total and high-density lipoprotein-cholesterol, serum triglycerides or urine pH (P>0.05 for all). There was no correlation between parameters of the metabolic syndrome and the decline in serum UA or serum UA achieved at study end. In conclusion, in patients with gouty arthritis, UA lowering with febuxostat below 6 mg/dL had no significant impact on features of the metabolic syndrome.

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.

Apoptosis in skeletal muscle myotubes is induced by ceramides and is positively related to insulin resistance

2006 ◽  
Vol 291 (6) ◽  
pp. E1341-E1350 ◽  
Author(s):  
Sarah M. Turpin ◽  
Graeme I. Lancaster ◽  
Ian Darby ◽  
Mark A. Febbraio ◽  
Matthew J. Watt
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Glucose Uptake ◽  
Protein Content ◽  
The Metabolic Syndrome ◽  
Effector Caspase ◽  
Induced Apoptosis ◽  
Ceramide Accumulation

Fatty acid-induced apoptosis occurs in pancreatic β-cells and contributes to the metabolic syndrome. Skeletal muscle insulin resistance is mediated by fatty acid oversupply, which also contributes to the metabolic syndrome. Therefore, we examined whether fatty acids induce apoptosis in skeletal muscle myotubes, the proapoptotic signaling involved, and the effects on insulin sensitivity. Exposure of L6 myotubes to palmitate induced apoptosis, as demonstrated by increased caspase-3 activation, phosphatidylserine exposure on the plasma membrane, and terminal deoxynucleotide transferase dUTP nick end labeling and DNA laddering, both markers of DNA fragmentation. Ceramide content was concomitantly increased, indicating a potential role for ceramides in palmitate-induced apoptosis. Supporting this notion, reducing stearoyl-CoA desaturase-1 (SCD-1) protein content with short interfering RNA resulted in ceramide accumulation and was associated with increased apoptosis in the absence of palmitate. Furthermore, the membrane-permeable C2-ceramide enhanced apoptosis in myotubes, whereas the ceramide synthase inhibitor, fumonisin B1, abrogated the proapoptotic effects of palmitate. Insulin-stimulated glucose uptake was inhibited by palmitate treatment, whereas the addition of effector caspase inhibitors [Ac-DEVD-aldehyde (DEVD-CHO), Z-DQMD-FMK] independently restored >80% of the insulin-stimulated glucose uptake. These effects were observed independently from changes in the protein content of insulin signaling proteins, suggesting that proteosomal degradation is not involved in this process. We conclude that lipoapoptosis occurs in skeletal muscle myotubes, at least partially via de novo ceramide accumulation, and that inhibiting downstream apoptotic signaling improves glucose uptake in vitro.

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 The degree of coronary atherosclerosis as a marker of insulin resistance in non-diabetics

2010 ◽  
Vol 138 (7-8) ◽  
pp. 436-443
Author(s):  
Biljana Parapid ◽  
Jovica Saponjski ◽  
Mladen Ostojic ◽  
Vladan Vukcevic ◽  
Sinisa Stojkovic ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Coronary Atherosclerosis ◽  
Diabetic Patients ◽  
Intravenous Glucose ◽  
Significant Stenosis ◽  
Vessel Disease ◽  
The Metabolic Syndrome ◽  
Lipid Panel ◽  
Significant Difference

Introduction. The metabolic syndrome and its influence on coronary artery disease development and progression remains in focus of international research debates, while insulin resistance, which represents its core, is the key component of hypertension, dyslipidaemias, glucose intolerance and obesity. Objective. The aim of this study was to establish relationship between basal glucose and insulin levels, insulin sensitivity and lipid panel and the degree of coronary atherosclerosis in nondiabetic patients. Methods. The coronary angiograms were evaluated for the presence of significant stenosis, insulin sensitivity was assessed using the intravenous glucose tolerance test with a minimal model according to Bergman, while baseline glucose (G0), insulin (I0) and lipid panel measurements (TC, HDL, LDL, TG) were taken after a 12-hour fasting. Results. The protocol encompassed 40 patients (19 men and 21 women) treated at the Institute for Cardiovascular Diseases of the Clinical Centre of Serbia, Belgrade. All were non-diabetics who were divided into 3 groups based on their angios: Group A (6 patients, 15%, with no significant stenosis), Group B (18 patients, 45%, with a single-vessel disease) and Group C (16 patients, 40%, with multi-vessel disease). Presence of lower insulin sensitivity, higher I0 and TC in the group of patients with a more severe degree of coronary atherosclerosis (insulin sensitivity: F=4.279, p=0.023, A vs. C p=0.012, B vs. C p=0.038; I0: F=3.461 p=0.042, A vs. B p=0.045, A vs. C p=0.013; TC: F=2.572, p=0.09), while no significant difference was found for G0, LDL, HDL and TG. Conclusion. Baseline insulinaemia, more precisely, fasting hyperinsulinaemia could be a good predictor of significant coronary atherosclerosis in non-diabetic patients, which enables a more elegant cardiometabolic risk assessment in the setting of everyday clinical practice.

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

scholarly journals Endothelium-dependent flow-mediated vasodilatation, insulin resistance and the metabolic syndrome in 60-year-old men

2002 ◽  
Vol 252 (4) ◽  
pp. 305-313 ◽  
Author(s):  
I. Wendelhag ◽  
B. Fagerberg ◽  
J. Hulthe ◽  
L. Bokemark ◽  
J. Wikstrand
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
The Metabolic Syndrome ◽  
Dependent Flow ◽  
Old Men

scholarly journals Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: the RISC study

2009 ◽  
Vol 161 (2) ◽  
pp. 223-230 ◽  
Author(s):  
Susanne R de Rooij ◽  
Jacqueline M Dekker ◽  
Michaela Kozakova ◽  
Asimina Mitrakou ◽  
Olle Melander ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Odds Ratio ◽  
Cardiometabolic Risk ◽  
Oral Glucose ◽  
Fasting Insulin ◽  
Men And Women ◽  
The Metabolic Syndrome ◽  
Preclinical Atherosclerosis

ObjectiveFasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis.Design and methodsThe Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) cohort consists of 1326 European non-diabetic, overall healthy men and women aged 30–60 years. We performed standard oral glucose tolerance tests and hyperinsulinemic euglycemic clamps. As a general measure of cardiovascular risk, we assessed the prevalence of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis.ResultsFasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds ratio for the metabolic syndrome of those in the highest quartile of fasting insulin compared with those in the lower quartiles was 5.4 (95% confidence interval (CI) 2.8–10.3, adjusted for insulin sensitivity) in men and 5.1 (2.6–9.9) in women. The odds ratio for metabolic syndrome of those with insulin sensitivity in the lowest quartile of the cohort compared with those in the higher quartiles was 2.4 (95% CI 1.3–4.7, adjusted for fasting insulin) in men and 1.6 (0.8–3.1) in women. Carotid IMT was only statistically significantly associated with fasting insulin in both men and women.ConclusionsFasting insulin, a simple and practical measure, may be a stronger and independent contributor to cardiometabolic risk and atherosclerosis in a healthy population than hyperinsulinemic euglycemic clamp-derived insulin sensitivity.

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