scholarly journals Rare Mutations of Peroxisome Proliferator-Activated Receptor Gamma: Frequencies and Relationship with Insulin Resistance and Diabetes Risk in the Mixed Ancestry Population from South Africa

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Z. Vergotine ◽  
A. P. Kengne ◽  
R. T. Erasmus ◽  
Y. Y. Yako ◽  
T. E. Matsha
Keyword(s):  
Insulin Resistance ◽  
Resistance Index ◽  
Population Group ◽  
Diabetes Risk ◽  
Peroxisome Proliferator ◽  
Model Assessment ◽  
Mixed Ancestry ◽  
Cross Sectional ◽  
Peroxisome Proliferator Activated Receptor ◽  
Diabetes Status

Background. Genetic variants in the nuclear transcription receptor, PPARG, are associated with cardiometabolic traits, but reports remain conflicting. We determined the frequency and the clinical relevance of PPARG SNPs in an African mixed ancestry population.Methods. In a cross-sectional study, 820 participants were genotyped for rs1800571, rs72551362, rs72551363, rs72551364, and rs3856806, using allele-specific TaqMan technology. The homeostatic model assessment of insulin (HOMA-IR),β-cells function (HOMA-B%), fasting insulin resistance index (FIRI), and the quantitative insulin-sensitivity check index (QUICKI) were calculated.Results. No sequence variants were found except for the rs3856806. The frequency of the PPARG-His447His variant was 23.8% in the overall population group, with no difference by diabetes status (P=0.215). The His447His allele T was associated with none of the markers of insulin resistance overall and by diabetes status. In models adjusted for 2-hour insulin, the T allele was associated with lower prevalent diabetes risk (odds ratio 0.56 (95% CI 0.31–0.95)).Conclusion. Our study confirms the almost zero occurrences of known rare PPARG SNPs and has shown for the first time in an African population that one of the common SNPs, His447His, may be protective against type 2 diabetes.

Impact of α-lipoic acid on liver peroxisome proliferator-activated receptor-α, vascular remodeling, and oxidative stress in insulin-resistant rats

2011 ◽  
Vol 89 (10) ◽  
pp. 743-751 ◽  
Author(s):  
Adil El Midaoui ◽  
Calin Lungu ◽  
Hui Wang ◽  
Lingyun Wu ◽  
Caroline Robillard ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipoic Acid ◽  
Tap Water ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Cross Sectional ◽  
Peroxisome Proliferator Activated Receptor ◽  
Insulin Resistant ◽  
Plasma Ffa ◽  
The Impact

This study sought to determine the impact of α-lipoic acid (LA) on superoxide anion (O2•–) production and peroxisome proliferator-activated receptor-α (PPARα) expression in liver tissue, plasma free fatty acids (FFA), and aortic remodeling in a rat model of insulin resistance. Sprague–Dawley rats (50–75 g) were given either tap water or a drinking solution containing 10% D-glucose for 14 weeks, combined with a diet with or without LA supplement. O2•– production was measured by lucigenin chemiluminescence, and PPAR-α expression by Western blotting. Cross-sectional area (CSA) of the aortic media and lumen and number of smooth muscle cells (SMC) were determined histologically. Glucose increased systolic blood pressure (SBP), plasma levels of glucose and insulin, and insulin resistance (HOMA index). All of these effects were attenuated by LA. Whereas glucose had no effect on liver PPAR-α protein level, it decreased plasma FFA. LA decreased the aortic and liver O2•– production, body weight, and plasma FFA levels in control and glucose-treated rats. Liver PPAR-α protein levels were increased by LA, and negatively correlated with plasma FFA. Medial CSA was reduced in all glucose-treated rats, and positively correlated with plasma FFA but not with SBP or aortic O2•– production. Glucose also reduced aortic lumen area, so that the media-to-lumen ratio remained unchanged. The ability of LA to lower plasma FFA appears to be mediated, in part, by increased hepatic PPAR-α expression, which may positively affect insulin resistance. Glucose-fed rats may serve as a unique model of aortic atrophic remodeling in hypertension and early metabolic syndrome.

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.

Abstract MP01: NMR Metabolomic Insulin Resistance Multimarkers Are Associated With Incident Diabetes: The CARDIA Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Amena Keshawarz ◽  
David R Jacobs ◽  
James D Otvos ◽  
Daniel A Duprez ◽  
Jamal S Rana ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Inflammatory Marker ◽  
Resistance Index ◽  
Cox Proportional Hazards ◽  
Diabetes Risk ◽  
Incident Diabetes ◽  
Categorical Variables ◽  
Lipoprotein Subclass ◽  
Diabetes Status ◽  
Lipid Panel

Introduction: Standard lipid panel measures (e.g., low HDL cholesterol and high triglyceride levels) are associated with developing diabetes. Lipoprotein and metabolomics profiles measured by nuclear magnetic resonance (NMR) carry additional information and may add to knowledge of future diabetes risk. Hypothesis: We assessed the hypothesis that two multimarkers of insulin resistance derived from NMR LipoProfile ® analysis, LP-IR (lipoprotein insulin resistance index) and IRDRF (insulin resistance diabetes risk factor index), are associated with incident diabetes independent of traditional risk factors in non-diabetic, apparently healthy subjects. Methods: LP-IR and IRDRF were measured at LipoScience/LabCorp for 3,564 non-diabetic participants (mean age 32±4 years, 46% [n=1,646] male) in the Coronary Artery Risk Development in Young Adults (CARDIA) study. LP-IR was calculated from 6 lipoprotein subclass and size parameters. IRDRF was calculated by combining LP-IR with levels of branched-chain amino acids, the inflammatory marker GlycA, and 2 additional lipoprotein subclasses. Diabetes status was ascertained by fasting glucose levels, hemoglobin A1c, and diabetes medications. We used Cox proportional hazards to model the relationship between LP-IR and IRDRF with incident diabetes. Participants were followed for a mean time of 21±5 years. We considered 4 models that examined LP-IR and IRDRF both as continuous and categorical variables and adjusted for various traditional predictors of diabetes. Results: Model 3, which adjusted for components of metabolic syndrome, had the best model fit in all cases ( Table 1 ). LP-IR and IRDRF had a significant linear relationship with incident diabetes. Participants who had LP-IR and IRDRF scores in Q4 were significantly more likely to develop diabetes than those with scores in Q1. Conclusions: In conclusion, LP-IR and IRDRF can be derived from a clinically-available NMR LipoProfile test, and both were associated with incident diabetes independent of traditional predictors.

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 Dynamic relationships between depressive symptoms and insulin resistance over 20 years of adulthood

2021 ◽  
pp. 1-10
Author(s):  
Che-Yuan Wu ◽  
Hugo Cogo-Moreira ◽  
Bradley J. MacIntosh ◽  
Jodi D. Edwards ◽  
Saffire H. Krance ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Depressive Symptoms ◽  
Latent Variables ◽  
Population Group ◽  
Population Based ◽  
Model Assessment ◽  
State Variables ◽  
Cross Sectional ◽  
Longitudinal Dynamics ◽  
Dynamic Relationships

Abstract Background Bidirectional longitudinal relationships between depression and diabetes have been observed, but the dominant direction of their temporal relationships remains controversial. Methods The random-intercept cross-lagged panel model decomposes observed variables into a latent intercept representing the traits, and occasion-specific latent ‘state’ variables. This permits correlations to be assessed between the traits, while longitudinal ‘cross-lagged’ associations and cross-sectional correlations can be assessed between occasion-specific latent variables. We examined dynamic relationships between depressive symptoms and insulin resistance across five visits over 20 years of adulthood in the population-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Possible differences based on population group (Black v. White participants), sex and years of education were tested. Depressive symptoms and insulin resistance were quantified using the Center for Epidemiologic Studies Depression (CES-D) scale and the homeostatic model assessment for insulin resistance (HOMA-IR), respectively. Results Among 4044 participants (baseline mean age 34.9 ± 3.7 years, 53% women, 51% Black participants), HOMA-IR and CES-D traits were weakly correlated (r = 0.081, p = 0.002). Some occasion-specific correlations, but no cross-lagged associations were observed overall. Longitudinal dynamics of these relationships differed by population groups such that HOMA-IR at age 50 was associated with CES-D score at age 55 (β = 0.076, p = 0.038) in White participants only. Longitudinal dynamics were consistent between sexes and based on education. Conclusions The relationship between depressive symptoms and insulin resistance was best characterized by weak correlations between occasion-specific states and enduring traits, with weak evidence that insulin resistance might be temporally associated with subsequent depressive symptoms among White participants later in adulthood.

scholarly journals Leptin as a Key Player in Insulin Resistance of Liver Cirrhosis? A Cross-Sectional Study in Liver Transplant Candidates

2020 ◽  
Vol 9 (2) ◽  
pp. 560 ◽  
Author(s):  
Iva Košuta ◽  
Anna Mrzljak ◽  
Branko Kolarić ◽  
Marijana Vučić Lovrenčić
Keyword(s):  
Insulin Resistance ◽  
Resistance Index ◽  
Cross Sectional Study ◽  
Model Assessment ◽  
Sectional Study ◽  
Cross Sectional ◽  
Risk Of Death ◽  
Increased Risk ◽  
Cirrhotic Patients ◽  
Transplant Candidates

Insulin resistance is associated with increased risk of death and liver transplantation in the cirrhotic population, independent of disease aetiology. However, factors accounting for insulin resistance in the context of cirrhosis are incompletely understood. This study aimed to investigate the association between adiponectin and leptin with insulin resistance in cirrhotic patients and to assess the influence of disease severity on insulin resistance and metabolic status. This cross-sectional study included 126 non-diabetic cirrhotic transplant candidates. The homeostasis model assessment 2 model was used to determine the insulin resistance index, and fasting adiponectin, leptin, insulin, c-peptide, glucose, HbA1c, and lipid profiles were analysed. Insulin resistance was detected in 83% of subjects and associated with increased leptin, fasting plasma glucose and body mass index, and lower triglyceride levels. Logistic regression analysis identified leptin and triglycerides as independent predictors of insulin resistance (OR 1.247, 95% CI 1.076–1.447, p = 0.003; OR 0.357, 95% CI 0.137–0.917, p = 0.032.). Leptin levels remained unchanged, whereas adiponectin levels increased (p < 0.001) with disease progression, and inversely correlated with HbA1c (ρ = −0.349, p < 0.001). Our results indicate that leptin resistance, as indicated by elevated leptin levels, can be regarded as a contributing factor to insulin resistance in cirrhotic patients, whereas triglycerides elicited a weak protective effect. Progressively increasing adiponectin levels elicited a positive effect on glucose homeostasis, but not insulin sensitivity across disease stages.

scholarly journals Acanthosis nigricans and insulin resistance in obese children

2010 ◽  
Vol 50 (5) ◽  
pp. 274 ◽  
Author(s):  
Kristellina Sangirta Tirtamulia ◽  
Adrian Umboh ◽  
Sarah Maria Warouw ◽  
Vivekenanda Pateda ◽  
Frecillia Regina
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Acanthosis Nigricans ◽  
Resistance Index ◽  
Skin Condition ◽  
Cross Sectional Study ◽  
Model Assessment ◽  
Obese Children ◽  
Cross Sectional

Background Acanthosis nigricans (AN) is a skin condition characterized by darkening and thickening of skin. AN has been reported to be linked to insulin resistance (IR), that associated with type 2 diabetes, in obese children in many country.Objective To determine the relation between acanthosis nigricans and insulin resistance in obese children.Methods We conducted a cross sectional study in Wenang District, Manado, from October 2009 until January 2010. We examined 54 obese children aged 10-14  years for insulin resistance using Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR). We analyzed the results byT-test and phi coefficient correlation. The value of P<O.05 was significant in statistical analysis.Results Acanthosis nigricans was positive in 33 children. Insulin resistance was found in 34 from 54 subjects, 28 of them has AN and 6has no AN. Obese children with AN had higher HOMA-IR than children without AN. Presence of AN was associated with IR (P<O.OOl, r=0.57).Conclusions There is a weak correlation between AN and IR in obese children. It is important to identify obese children with IR for early intervention and prevention of type  2 diabetes, but AN could not be a reliable marker of IR.

scholarly journals Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene on adiposity, insulin sensitivity and lipid profile in the Spanish population

2002 ◽  
pp. 495-501 ◽  
Author(s):  
JL Gonzalez Sanchez ◽  
M Serrano Rios ◽  
C Fernandez Perez ◽  
M Laakso ◽  
MT Martinez Larrad
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Ppar Gamma ◽  
Population Based ◽  
Peroxisome Proliferator ◽  
Model Assessment ◽  
Pro12ala Polymorphism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Sagittal Abdominal Diameter

OBJECTIVE: To investigate the role of the Pro12Ala peroxisome proliferator-activated receptor (PPAR) gamma-2 polymorphism in the susceptibility to the insulin resistance syndrome and its metabolic complications in a population-based nationwide multicenter study in Spain. DESIGN: 464 unrelated adults (45.3% men and 54.7% women) aged between 35 and 64 years were randomly chosen from a nationwide population-based survey of obesity and related conditions including insulin resistance and cardiovascular risk factors. METHODS: Anthropometric determinations included: body mass index (BMI), waist-to-hip ratio, sagittal abdominal diameter; biochemical determinations included: fasting plasma glucose concentration and concentration 2 h after an oral glucose tolerance test (OGTT), total cholesterol, high and low density lipoprotein-cholesterol, triglycerides, leptin and insulin. Systolic and diastolic blood pressure were also measured. Genotyping of the PPARgamma-2 Pro12Ala polymorphism was determined by polymerase chain reaction and single strand conformation polymorphism analysis. RESULTS: The Ala12 allele frequency was higher in obese men than in lean men (0.15 vs 0.08, P=0.03). Men carriers of the Ala12 allele had a higher BMI than non-carriers (38.9% vs 21.3%; adjusted odds ratio 2.36, 95% confidence interval 1.10-5.05, P=0.03). However, despite higher BMI obese men carriers of the Ala12 allele had lower sagittal abdominal diameter than Pro12 homozygotes (24.1+/-3.2 vs 26.3+/-2.5 cm, P=0.01). The Ala12 allele was associated with lower total triglycerides levels in the overall population and it was also associated with lower fasting insulin levels and a higher insulin sensitivity by homeostasis model assessment (HOMA) in women. CONCLUSIONS: Our results suggest that the Pro12Ala polymorphism of the PPARgamma-2 gene promotes peripheral deposition of adipose tissue and increased insulin sensitivity for a given BMI. The results in women might be due to their different adipose tissue distribution.

scholarly journals Insulin resistance associates with hepatic lobular inflammation in subjects with obesity

2019 ◽  
Vol 8 (9) ◽  
pp. 1294-1301 ◽  
Author(s):  
Frederique Van de Velde ◽  
Marlies Bekaert ◽  
Anja Geerts ◽  
Anne Hoorens ◽  
Arsène-Hélène Batens ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Positive Association ◽  
Model Assessment ◽  
Metabolic Disturbances ◽  
Cross Sectional ◽  
Nonalcoholic Fatty Liver ◽  
Insulin Levels ◽  
Diabetes Status ◽  
Obese Subjects ◽  
Lobular Inflammation

Purpose Obese subjects with nonalcoholic fatty liver disease (NAFLD) are more prone to develop additional metabolic disturbances such as systemic insulin resistance (IR) and type 2 diabetes. NAFLD is defined by hepatic steatosis, lobular inflammation, ballooning and stage of fibrosis, but it is unclear if and which components could contribute to IR. Objective To assess which histological components of NAFLD associate with IR in subjects with obesity, and if so, to what extent. Methods This cross-sectional study included 78 obese subjects (mean age 46 ± 11 years; BMI 42.2 ± 4.7 kg/m2). Glucose levels were analysed by hexokinase method and insulin levels with electrochemiluminescence. Homeostasis model assessment-estimated insulin resistance (HOMA-IR) was calculated. Liver biopsies were evaluated for histological components of NAFLD. Results A positive association between overall NAFLD Activity Score and HOMA-IR was found (r s = 0.259, P = 0.022). As per individual components, lobular inflammation and fibrosis stage were positively associated with HOMA-IR, glucose and insulin levels (P < 0.05), and HOMA-IR was higher in patients with more inflammatory foci or higher stage of fibrosis. These findings were independent of age, BMI, triglyceride levels, diabetes status and sex (all P < 0.043). In a combined model, lobular inflammation, but not fibrosis, remained associated with HOMA-IR. Conclusion In this group of obese subjects, a major contributing histological component of NAFLD to the relation between NAFLD severity and IR seems to be the grade of hepatic lobular inflammation. Although no causal relationship was assessed, preventing or mitigating this inflammatory response in obesity might be of importance in controlling obesity-related metabolic disturbances.

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