Microvascular Dysfunction in Obesity: A Potential Mechanism in the Pathogenesis of Obesity-Associated Insulin Resistance and Hypertension

Physiology ◽  
2007 ◽  
Vol 22 (4) ◽  
pp. 252-260 ◽  
Author(s):  
Amy M. Jonk ◽  
Alfons J. H. M. Houben ◽  
Renate T. de Jongh ◽  
Erik H. Serné ◽  
Nicoloaas C. Schaper ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Microvascular Dysfunction ◽  
Important Risk Factor ◽  
Potential Mechanism ◽  
The Metabolic Syndrome ◽  
New Treatments ◽  
Insight Into

Obesity is an important risk factor for insulin resistance and hypertension and plays a central role in the metabolic syndrome. Insight into the pathophysiology of this syndrome may lead to new treatments. This paper has reviewed the evidence for an important role for the microcirculation as a possible link between obesity, insulin resistance and hypertension.

scholarly journals Association between proinsulin, insulin, proinsulin/insulin ratio, and insulin resistance status with the metabolic syndrome

2007 ◽  
Vol 51 (7) ◽  
pp. 1128-1133 ◽  
Author(s):  
Ivana Pivatto ◽  
Patricia Bustos ◽  
Hugo Amigo ◽  
Ana Maria Acosta ◽  
Antonio Arteaga
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Resistance Index ◽  
Cross Sectional Study ◽  
Blood Levels ◽  
Model Assessment ◽  
Cross Sectional ◽  
Predictive Values ◽  
The Metabolic Syndrome

The Metabolic Syndrome (MS) constitutes an independent risk factor of cardiovascular disease. There is evidence that proinsulin blood levels and the proinsulin/insulin ratio are associated to the MS. The purpose of this study was to compare proinsulin and insulin, insulin resistance index, and the proinsulin/insulin ratio as predictors of MS. This is a cross-sectional study involving 440 men and 556 women with a mean age of 24 years. Diagnosis of MS was made according to the National Cholesterol Education Program Adult Treatment Panel III. Blood levels of insulin and proinsulin were measured, and the insulin resistance status was estimated using the homeostatic model assessment (HOMA-IR). The prevalence of MS was 10.1%. HOMA-IR was the best MS risk factor for both women and men (OR = 2.04; 95% CI: 1.68-2.48 and 1.09; 95% CI: 1.05-1.13, respectively). HOMA-IR presented the best positive predictive value for MS: 22% and 36% for men and women, respectively, and was the best MS indicator. The proinsulin/insulin ratio did not show significant association with MS. HOMA-IR, proinsulin, and insulin presented good negative predictive values for both genders that could be used to identify an at-risk population.

IGF-I/IGFBP-3 ratio: a mechanistic insight into the metabolic syndrome

2009 ◽  
Vol 116 (6) ◽  
pp. 507-512 ◽  
Author(s):  
Justo Sierra-Johnson ◽  
Abel Romero-Corral ◽  
Virend K. Somers ◽  
Francisco Lopez-Jimenez ◽  
Anders Mälarstig ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Characteristic Curve ◽  
Model Assessment ◽  
Linear Regression Models ◽  
The Metabolic Syndrome ◽  
Igf I ◽  
Definition Of ◽  
Insight Into ◽  
Igfbp 3

Recent reports suggest that IGF (insulin-like growth factor)-I and IGFBP-3 (IGF-binding protein-3) have independent and opposing mechanistic effects on insulin. The aim of the present study was to assess the relationship between the IGF-I/IGFBP-3 ratio and the metabolic syndrome. We examined 3281 subjects (1463 men and 1818 women, aged 20–49 years), otherwise healthy adults, who participated in NHANES III (Third National Health and Nutrition Examination Survey), which has released measurements of IGF-I and IGFBP-3. Insulin resistance was estimated using the computer HOMA2 (homoeostatic model assessment 2) model. The updated ATP-III (Adult Treatment Panel III) definition of the metabolic syndrome was used. We applied adjusted logistic and linear regression models. After adjusting for age and race, men and women in the lowest quartile of the IGF-I/IGFBP-3 ratio were 3-fold more likely to meet the ATP-III definition of the metabolic syndrome and twice as likely to be insulin-resistant. Mean values of the IGF-I/IGFBP-3 ratio decreased significantly as the number of metabolic syndrome components increased (P<0.0001, as determined by ANOVA). The area under the ROC (receiver operating characteristic) curve for detecting insulin resistance using the IGF-I/IGFBP-3 ratio was 0.760, significantly improving upon either protein alone (P=0.01). In conclusion, the IGF-I/IGFBP-3 ratio is significantly associated with the metabolic syndrome. Calculating the ratio of these two proteins may provide insight into the metabolic syndrome clustering phenomenon.

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.

Microvascular dysfunction: causative role in the association between hypertension, insulin resistance and the metabolic syndrome?

2006 ◽  
Vol 42 ◽  
pp. 163-176 ◽  
Author(s):  
Erik H. Serné ◽  
Renate T. de Jongh ◽  
Etto C. Eringa ◽  
Richard G. Ijzerman ◽  
Michiel P. de Boer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Microvascular Dysfunction ◽  
Metabolic Risk Factors ◽  
Causative Role ◽  
Metabolic Risk ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Potential Factor

The metabolic syndrome defines a clustering of metabolic risk factors that confers an increased risk for type 2 diabetes and cardiovascular disease. The metabolic syndrome seems to have multiple etiological factors and microvascular dysfunction may be one potential factor explaining the clustering of multiple metabolic risk factors including hypertension, obesity, insulin resistance and glucose intolerance. Microvascular dysfunction may increase not only peripheral vascular resistance and blood pressure, but may also decrease insulin-mediated glucose uptake in muscle. The present article summarizes some of the data concerning the role of microvascular dysfunction in the metabolic syndrome.

scholarly journals Metabolic Syndrome: An Important Risk Factor for Parkinson’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Pei Zhang ◽  
Bo Tian
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Parkinson’S Disease ◽  
Metabolic Syndrome ◽  
Parkinson's Disease ◽  
Risk Factor ◽  
Important Risk Factor ◽  
The Metabolic Syndrome ◽  
System Review ◽  
Clear Relation

Metabolic syndrome is becoming commoner due to a rise in obesity rates among adults. Generally speaking, a person with metabolic syndrome is twice as likely to develop cardiovascular disease and five times as likely to develop diabetes as someone without metabolic syndrome. Increasing oxidative stress in metabolic syndrome and Parkinson’s disease is mentioned in the comprehensive articles; however, the system review about clear relation between metabolic syndrome and Parkinson’s disease is deficient. In this review, we will focus on the analysis that the metabolic syndrome may be a risk factor for Parkinson’s disease and the preventions that reduce the incident of Parkinson’s disease by regulating the oxidative stress.

scholarly journals Peroxisome proliferator-activated receptor gamma and its coactivator-1 alpha may be associated with features of the metabolic syndrome in adolescents

2005 ◽  
Vol 35 (2) ◽  
pp. 373-380 ◽  
Author(s):  
S Sookoian ◽  
S I García ◽  
P I Porto ◽  
G Dieuzeide ◽  
C D González ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Peroxisome Proliferator ◽  
Model Assessment ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Metabolic Syndrome ◽  
Arterial Blood ◽  
Blood Pressures

Our objective was to search for differences in genotypes of peroxisome proliferator-activated receptor gamma (PPARγ) (Pro12 Ala) and its coactivator PGC-1α (Gly482 Ser) in adolescents harboring features of metabolic syndrome. In a population-based study, we determined medical history, anthropometric variables, biochemical measurements and arterial blood pressures of 934 high-school students of Caucasian origin. We selected 220 adolescents who had systolic or diastolic blood pressures more than the 80th or less than the 20th percentiles based on the previous single set of measurements. One hundred and seventy-five adolescents completed the study and underwent two additional blood pressure measurements on different days, as well as biochemical analysis and genotyping. We found no association between insulin resistance, body mass index (BMI) and leptin levels and PPARγ and PGC-1α genotypes. The 12 Ala PPARγ allele was associated with increased waist-to-hip ratio (WHR) and carriers seemed to have higher diastolic blood pressure and lower pulse pressure than non-carriers, particularly in the hypertensive and overweight group. Although Ser482 Ser PGC-1α homozygotes had lower WHRs than other PGC-1α genotypes, they were more frequent in the hypertensive group than in the normotensive (44.4 vs 24.5%, P<0.03), so the 482 Ser PGC-1 allele was in our population a risk factor for hypertension independently of WHR, homeostasis model assessment of insulin resistance, BMI and Pro12 Ala PPARγ variant (odds ratio=4.0, 95% confidence interval 1.5–10.6, P<0.01). Multiple regression analysis showed that age- and sex-adjusted systolic blood pressure correlated with the 482 Ser PGC-1 allele regardless of those covariates. In conclusion, the Gly482 Ser variant of the PGC-1α gene may be an independent genetic risk factor for young-onset hypertension.

scholarly journals Sleep and Diabetes

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Swetha Bopparaju ◽  
Salim Surani
Keyword(s):  
Myocardial Infarction ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Obstructive Sleep Apnea ◽  
Risk Factor ◽  
Sleep Apnea ◽  
Independent Risk Factor ◽  
The Metabolic Syndrome ◽  
Obstructive Sleep ◽  
Independent Association

Sleep apnea is clinically recognized as a heterogeneous group of disorders characterized by recurrent apnea and/or hypopnea. Its prevalence ranges from 4% to 24%. It has been implicated as an independent risk factor for several conditions such as hypertension, stroke, arrhythmia, and myocardial infarction. Recently data has been emerging which suggests an independent association of obstructive sleep apnea with several components of the metabolic syndrome, particularly insulin resistance and abnormalities in lipid metabolism. We hereby review the salient features of the association between sleep and diabetes.

Metabolic Syndrome During Menopause

2019 ◽  
Vol 17 (6) ◽  
pp. 595-603 ◽  
Author(s):  
Sezcan Mumusoglu ◽  
Bulent Okan Yildiz
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Central Obesity ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Natural Menopause ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Aging Women

The metabolic syndrome (MetS) comprises individual components including central obesity, insulin resistance, dyslipidaemia and hypertension and it is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The menopause per se increases the incidence of MetS in aging women. The effect(s) of menopause on individual components of MetS include: i) increasing central obesity with changes in the fat tissue distribution, ii) potential increase in insulin resistance, iii) changes in serum lipid concentrations, which seem to be associated with increasing weight rather than menopause itself, and, iv) an association between menopause and hypertension, although available data are inconclusive. With regard to the consequences of MetS during menopause, there is no consistent data supporting a causal relationship between menopause and CVD. However, concomitant MetS during menopause appears to increase the risk of CVD. Furthermore, despite the data supporting the association between early menopause and increased risk of T2DM, the association between natural menopause itself and risk of T2DM is not evident. However, the presence and the severity of MetS appears to be associated with an increased risk of T2DM. Although the mechanism is not clear, surgical menopause is strongly linked with a higher incidence of MetS. Interestingly, women with polycystic ovary syndrome (PCOS) have an increased risk of MetS during their reproductive years; however, with menopausal transition, the risk of MetS becomes similar to that of non-PCOS women.

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