Early Marker Of Insulin Resistance Research Articles

Fetuin-A as a Marker of Insulin Resistance

Abstract Fetuin-A is a glycoprotein which helps in the regulation of metabolism. It is an early marker of insulin resistance (IR). The aim of this study was to evaluate the role of Fetuin-A as a predictive biomarker in cases of newly detected type 2 diabetes (NDD). The study involved 60 NDD and 60 Normal Healthy Controls (NHC). All the demographics and anthropological characteristics were noted. Fasting blood samples were drawn and various biochemical parameters were analyzed. The homeostatic model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) score was calculated. Chisquare, student T-test and Mann Whitney U tests were employed to associate and compare the mean and median between the NDD and NHC groups. Pearson's and Spearman’s correlation analysis were employed to examine the relationship of Fetuin-A levels with parametric and nonparametric variables. The independent predictors of Fetuin-A was determined by employing multiple forward linear regression. Fetuin-A was significantly high in NDD compared to NHC (1323 vs. 306.98 mcg/mL; p<0.001). Majority of NDD patients demonstrated IR based on the HOMA-IR (88.33% vs. 66.67%) and QUICKI score (96.67% vs. 85%). The multiple linear regression analysis showed that systolic blood pressure, age and QUICKI score were independently associated with Fetuin-A (p value <0.01). Fetuin-A may be used as a biomarker to detect NDD. Therefore, early detection of Fetuin-A levels in NDD gives an opportunity for suitable patient management.

Acanthosis nigricans in the knuckles: An early, accessible, straightforward, and sensitive clinical tool to predict insulin resistance.

ABSTRACTAny clinical/biochemical marker revealing obesity or diabetes before their appearance is valuable. Insulin resistance (IR) is present in both disorders many years before occurrence. Accordingly, we determined whether acanthosis nigricans (AN) in the knuckles is associated to higher insulin and homeostasis model assessment for estimated insulin resistance (HOMA-IR) index values, and assessed the influence of body-mass index (BMI) and the diagnostic performance of AN in the knuckles to detect IR. In this cross-sectional controlled study, we included men or women, 18 to 23 years old, with or without AN in the knuckles. In 149 cases with AN in the knuckles and 145 controls, fasting insulin was higher in cases (13.45 µU/mL ± 7.8 vs. 8.59 µU/mL ± 3.63, P < .001, respectively). Mean HOMA-IR index was also higher (2.86 ± 1.68 vs. 1.78 ± 0.77, P < .001). A significant increase in fasting insulin and HOMA-IR values between and within BMI groups from normal through obese category was identified in controls and cases. By multivariate regression analysis, cases with normal BMI were significantly associated to a HOMA-IR ≥2.5 (OR = 3.09, CI95% = 1.75–5.48, P = .001). A model of AN in the knuckles, normal BMI, and increased waist circumference allowed identifying 2 out of 3 cases with HOMA-IR index ≥2.5. AN in the knuckles could be addressed with two aims: as an easy, accessible, and costless diagnostic tool suggesting hyperinsulinemia secondary to IR, and, an early marker of IR even in the absence of overweight or obesity.

Gestational Diabetes Mellitus Is Strongly Associated With Non-Alcoholic Fatty Liver Disease.

Insulin resistance is central to the development of non-alcoholic fatty liver disease (NAFLD), and gestational diabetes mellitus (GDM) is an early marker of insulin resistance. We hypothesized that a history of GDM would identify women at higher risk of NAFLD in middle age. Women from the multicenter Coronary Artery Risk Development in Young Adults (CARDIA) cohort study who delivered ≥1 birth, were free of diabetes prior to pregnancy(ies), and underwent CT quantification of hepatic steatosis 25 years following cohort entry (Y25: 2010-2011) were included (n=1,115). History of GDM by self-report, validated in a subsample by review of antenatal glucose testing, and metabolic risk factors were assessed prospectively. NAFLD was defined by liver attenuation (LA)≤40 Hounsfield Units on CT scan after exclusion of other causes of hepatic steatosis. Of 1,115 women meeting selection criteria (57% black, 43% white, median age 25 years at baseline), 124 (11%) reported a history of GDM and 75 (7%) met the CT definition for NAFLD at year 25. The crude risk of NAFLD at the 25-year visit was significantly higher in women with GDM compared to those without (14 vs. 5.8%, OR: 2.56, 95% CI: 1.44-4.55, P<0.01). History of GDM remained associated with NAFLD (OR: 2.29, 95% CI: 1.23-4.27, P=0.01) after adjustment for covariates in multivariable logistic regression. Addition of incident diabetes mellitus (DM) into the final model attenuated the association between GDM and NAFLD (OR: 1.48, 95% CI: 0.73-3.02, P=0.28). GDM is a risk marker for NAFLD and represents an opportunity to identify women at risk for NAFLD at a young age and may be mediated by the development of incident DM.

Correlation between eosinophils and glucose and lipid metabolism disorder in obese children

Objective To investigate the association of eosinophils with glucose and lipid metabolism disorder in obese children. Methods A total of 180 subjects, 102 boys and 78 girls, aged 7 to 14 years were enrolled in General Hospital, Tianjin Medical University.The subjects were divided into 3 quartiles according to eosinophil percentage.E1(0 to<37% of eosinophils), E2(37% to<73% of eosinophils), and E3(73% to 100% of eosinophils). Forty-six children were selected as control group with matched age and sex (26 boys and 20 girls). The body weight, height, waist circumference, blood pressure, blood routine examination, fasting plasma glucose (FPG), fasting insulin (FINS), and blood lipid in 4 groups were measured.The values of glucose and lipid metabolism and the indexes of physical examination were compared among each group. Results The values of eosinophil percentage, body mass index (BMI), trigly-ceride, total cholesterol, low-density lipoprotein cholesterol, FINS, FPG, homeostasis model assessment of insulin resistance(HOMA-IR) and waist circumference in E1, E2, E3 group were significantly higher than those in control group, and the value of high-density lipoprotein cholesterol was significantly lower than that in control group, and there were significant differences (all P<0.05). The blood pressure was significantly higher in E1 groups than that in other 3 groups (all P<0.05). The values of BMI and HOMA-IR in E1 group were higher than those of E3 group(all P<0.05). Eosinophil percentage was positively correlated with FINS (r=0.190, P=0.01), and negatively correlated with BMI and HOMA-IR(r=-0.259, -0.190 respectively, all P<0.05). Conclusions Obese children have emerged glucose and lipid metabolism disorders.Peripheral eosinophil percentage may be an early marker of insulin resistance. Key words: Obese; Insulin resistance; Lipids; Blood glucose; Eosinophils; Child

Echocardiographic Epicardial Adipose Tissue Thickness as a Marker of Insulin Resistance

Objective. The main objective of this study is to determine if epicardial fat thickness can be an early marker of insulin resistance. The specific objectives are to determine the specific thickness of epicardial fat that will correlate with insulin resistance and to correlate epicardial fat thickness with co-morbidities, anthropometric measurements and other clinical variables. Methodology. Patients were enrolled into the study by purposive sampling. Insulin assay, fasting blood sugar (FBS) and 2D echocardiogram measuring the epicardial fat were requested. HOMA-IR was computed and correlated with epicardial fat thickness. SPSS version 19 and Epi info v3.5.1 were used for statistical analysis. Linear regression analysis was performed on all variables to identify correlates with epicardial fat thickness. Results. A total of 22 subjects were included in the study. Insulin resistance determined using HOMA-IR, as well as BMI and fasting insulin level showed significant correlation with epicardial fat thickness (p-value <0.01). Based on the analysis, 9.5 mm was found to be the most sensitive and specific measurement for epicardial fat thickness that is correlated to insulin resistance with sensitivity of 100% and specificity of 86%. Conclusions. Epicardial fat thickness through routine 2D echocardiogram is significantly directly correlated with insulin resistance and 9.5 mm is the cut–off value for predicting insulin resistance.

Hyperinsulinemia is associated with the loss of appendicular skeletal muscle mass at 4.6 year follow-up in older men and women

Homeostasis model assessment as a marker of insulin resistance has been associated with the pronounced loss of appendicular skeletal muscle mass in older adults. In the present study, we hypothesized that hyperinsulinemia as an early predictor of insulin resistance may be associated with the loss of appendicular skeletal muscle mass (ASM). This is a cohort study that included 147 well-functioning older men and women subjects who were followed for a period of 4.6 ± 1.8 years. Lean tissue in arm and legs, or ASM, was derived from dual-energy X-ray absorptiometry at baseline with follow-up measurements to obtain the relative change. Hyperinsulinemia was defined empirically at the 75th percentile. The relative change in ASM was negative and significant throughout the quartiles of fasting insulin levels (p ≤ 0.05); however, the loss of ASM was more pronounced in the later quartiles (-0.7 kg) compared with the relative change in Q1 and Q2 (-0.5 kg and -0.3 kg). The unadjusted analysis indicates a significant association between hyperinsulinemia and the loss of ASM (β = -0.28, 95% CI-0.57-0.009, p = 0.05), an association that remained significant after adjusting for several covariates. Hyperinsulinemia as an early marker of insulin resistance was associated with the loss of ASM in a cohort study of community-dwelling older men and women subjects without other chronic health conditions. The use of fasting insulin levels >8.4 μU/mL may help clinicians identify individuals in the geriatric population who are at a high risk of loss of appendicular skeletal muscle mass.

Lower serum apelin levels in women with polycystic ovary syndrome

We tested differences in serum apelin levels between women with polycystic ovary syndrome (PCOS) and those with a healthy regular menstrual cycle, finding that apelin levels were higher in normal women and that apelin was positively correlated with apolipoprotein A levels.

Retinol-binding protein 4 in neonates born small for gestational age

Retinol-binding protein 4 (RBP4) is an adipocyte-derived 'signal' that may contribute to the pathogenesis of insulin resistance and Type 2 diabetes. The relationship of RBP4 with insulin resistance and metabolic risk in human beings has been the subject of several studies. Subjects born small for gestational age (SGA) are at risk of insulin resistance and Type 2 diabetes. Though RBP4 could represent an early marker of insulin resistance, to date, none have determined RBP4 in SGA children. Our aim was to measure RBP4 concentrations in cord blood of SGA newborns compared with those in children born with a birth weight appropriate for gestational age (AGA) and to determine whether serum RBP4 levels at birth correlate with insulin sensitivity markers. Sixty-four newborns, 17 born SGA (mean gestational age: 36.4+/-2.1 weeks), and 47 born AGA (mean gestational age: 37.0+/-3.6 weeks) were studied. The main outcome measures included anthropometry, lipid profile, insulin, homeostasis model assessment, quantitative insulin-sensitivity check index, adiponectin, and RBP4. RBP4 concentrations were significantly reduced in SGA newborns (p<0.002). No relationship was found between RBP4 and insulin sensitivity parameters. Stepwise regression analysis revealed that birth weight was the major predictor of RBP4 serum concentrations (p<0.001). RBP4 is reduced in SGA newborns, birth weight representing the major determinant of RBP4 concentrations, and is not related to insulin sensitivity. No significant difference in adiponectin levels and insulin sensitivity markers was found between SGA and AGA neonates.

Soluble CD36 (sCD36) Clusters with Markers of Insulin Resistance, and High sCD36 Is Associated with Increased Type 2 Diabetes Risk

Soluble CD36 (sCD36) may be an early marker of insulin resistance and atherosclerosis. The objective of this prospective study was to evaluate sCD36 as a predictor of type 2 diabetes and to study its relationship with components of the metabolic syndrome (MetSy). DESIGN, SETTING, PARTICIPANTS, AND OUTCOME MEASURES: We conducted a case-referent study nested within a population-based health survey. Baseline variables included sCD36, body mass index, blood pressure, blood lipids, adipokines, inflammatory markers, and beta-cell function. A total of 173 initially nondiabetic cohort members who developed type 2 diabetes during 10 yr of follow-up were matched (1:2) with referents. Exploratory factor analysis was applied to hypothesize affiliation of sCD36 to the MetSy components. Doubling of baseline sCD36 increases the odds ratio for diabetes development by 1.24 in the general study population and by 1.45 in the female population (P < 0.025). Comparing upper sCD36 quartiles with lower, odds ratio for diabetes was 4.6 in women (P = 0.001), 3.15 in men (P = 0.011), and 2.6 in obese individuals (P < 0.025). Multivariate analysis shows that sCD36 does not predict diabetes independent of fasting plasma glucose and insulin. Factor analysis of 15 variables generates a six-factor model explaining 66-69% of total variance, where sCD36, body mass index, insulin, proinsulin, and leptin were assigned to the obesity/insulin resistance cluster. Upper quartile sCD36 is associated with elevated diabetes risk independent of age, gender, and obesity. Baseline sCD36 does not, however, predict diabetes independent of fasting glucose and insulin. sCD36 clusters with important markers of insulin resistance and MetSy that are key predictors of type 2 diabetes.

Response: The Relationship between Lung Function and Metabolic Syndrome in Obese and Non-Obese Korean Adult Males (Korean Diabetes J 2010;34:253-60)

We appreciate the comments on our study The Relationship between Lung Function and Metabolic Syndrome in Obese and Non-Obese Korean Adult Males, which was published in Korean Diabetes J 2010;34:253-260. We reported that insulin resistance, and other metabolic risk factors appear to be related to forced vital capacity (FVC), irrespective of obesity in Korean males. The age, height, and disease were the major determinants of ventilatory function [1]. In our study, there was a significant difference of age between metabolic syndrome (MetS) and non-MetS. So, we studied the relationship between MetS and FVC after adjusting for age. After adjusting age, there was still a significant difference in FVC between MetS and non-MetS groups (93.1 ± 12.1 vs. 97.0 ± 11.5, P < 0.05). Furthermore, insulin resistance and other metabolic components such as waist circumference were independently associated with FVC in a multi-linear regression analysis after adjusting for age and height, the major determinants of ventilatory function, and this was consistent with previous studies [2-5]. It has been reported that lung function is affected by several factors such as body composition and fat distribution, physical activity level, handgrip strength and respiratory muscle power [6-9]. Our study was performed on a limited cross-section of the population, so we could not control the potential biases due to differences in physical activity or respiratory muscle power. However, several studies have reported that insulin resistance is independently associated with lung function [3,10]. These studies reported that the lung function is still inversely associated with insulin resistance after adjusting for compounding factors such as age, height, smoking, and physical activity. Furthermore, Lazarus et al. [11,12] reported that skeletal muscle weakness served as a marker for future risk of insulin resistance, and that impaired lung function can aid in the prediction of development of insulin resistance. They suggested that some metabolic change that eventually leads to insulin resistance may initially induce diminished muscle strength and diminished ventilatory function [12]. So diminished muscle strength may be not confounding factor, but an early marker of insulin resistance. Several reports have suggested that impaired lung function is associated with glucose intolerance, hypertension, and cardiovascular disease, and that lung function is a reliable long-term predictor of mortality in the general population. We suggested that decreased FVC is associated with increased metabolic risk and insulin resistance in Korean males. Further prospective study to elucidate the relationship between lung function and metabolic risk is needed.

Fetal Programming of Adult Glucose Homeostasis in Mice

BackgroundEmerging evidence suggests that dietary soy and phytoestrogens can have beneficial effects on lipid and glucose metabolism. We have previously shown that male mice fed from conception to adulthood with a high soy-containing diet had reduced body weight, adiposity and a decrease in glucose intolerance, an early marker of insulin resistance and diabetes.ObjectivesThe purpose of this study was to identify the precise periods of exposure during which phytoestrogens and dietary soy improve lipid and glucose metabolism. Since intrauterine position (IUP) has been shown to alter sensitivity to endocrine disruptors, we also investigated whether the combination of IUP and fetal exposure to dietary phytoestrogens could potentially affect adult metabolic parameters.MethodsMale outbred mice (CD-1) were allowed ad libitum access to either a high soy-containing diet or a soy-free diet either during gestation, lactation or after weaning. Adiposity and bone mass density was assessed by dual x-ray absorptiometry. Glucose tolerance was assessed by a glucose tolerance test. Blood pressure was examined by the tail-cuff system.ResultsHere we show that metabolic improvements are dependent on precise windows of exposure during life. The beneficial effects of dietary soy and phytoestrogens on adiposity were apparent only in animals fed post-natally, while the improvements in glucose tolerance are restricted to animals with fetal exposure to soy. Interestingly, we observed that IUP influenced adult glucose tolerance, but not adiposity. Similar IUP trends were observed for other estrogen-related metabolic parameters such as blood pressure and bone mass density.ConclusionOur results suggest that IUP and fetal exposure to estrogenic environmental disrupting compounds, such as dietary phytoestrogens, could alter metabolic and cardiovascular parameters in adult individuals independently of adipose gain.

Retinol binding protein 4, low birth weight-related insulin resistance and hormonal contraception

It has been recently reported that increased serum levels of retinol binding protein 4 (RBP4), a molecule secreted by adipocytes and liver, could be an early marker of insulin resistance (IR). We determined whether serum RBP4 was increased in low birth weight (LBW)-young women as a model of early-onset IR, through a historical prospective study. The study-population included 35 LBW and 35 born at term appropriate for gestational age (term AGA) young women. Metabolic evaluations included the composite-insulin sensitivity index (composite ISI). Serum RBP4 was measured with a competitive enzyme-linked immunosorbent assay (ELISA). RBP4 levels were similar in LBW and term AGA women, while composite ISI was significantly lower in the former group. With multivariate logistic regression analysis hormonal contraception (HC) use but not birth weight, diabetes in either parents and body mass index was significantly associated with higher RBP4 levels: odds ratio = 10.6; 95% confidence interval (CI) = 2.4-76.6. In spite of higher RBP4 levels in women under HC, composite ISI was similar in women with or without HC. Women under HC also exhibited significantly higher levels of sex hormone binding globulin (SHBG), triglycerides, cholesterol, and C-reactive protein (CRP), and all of them, but not composite ISI, were significantly correlated with RBP4 levels. In conclusion, RBP4 serum level was not a marker of IR but, for the first time, it is documented a sustained increase of serum RBP4 under HC. Pathophysiological and clinical significance of this novel finding requires further investigations.

Impaired Postprandial Blood Flow in Adipose Tissue May Be an Early Marker of Insulin Resistance in Type 2 Diabetes

We investigated the changes in subcutaneous adipose tissue blood flow (ATBF) after a meal in the various stages of type 2 diabetes. Five groups were examined: healthy control subjects, first-degree relatives of subjects with type 2 diabetes, subjects with impaired glucose tolerance (IGT), subjects with type 2 diabetes and postprandial hyperglycemia but normal fasting plasma glucose levels (diabetes group A [DMA]), and subjects with type 2 diabetes with both postprandial and fasting hyperglycemia (diabetes group B [DMB]). ATBF was measured with (133)Xe. ATBF was higher in control subjects (1,507 +/- 103 ml/100 cm(3) tissue x min) versus relatives and IGT, DMA, and DMB subjects (845 +/- 123, 679 +/- 69, 765 +/- 60, and 757 +/- 69 ml/100 cm(3) tissue x min, respectively; P < 0.001). Insulin sensitivity index (ISI) in control subjects (82 +/- 3 mg x l(2)/mmol x mU x min) was higher versus that for relatives and IGT, DMA, and DMB subjects (60 +/- 3, 45 +/- 1, 40 +/- 6, and 29 +/- 4 mg x l(2)/mmol x mU x min, respectively; P < 0.0001). ISI was positively associated with peak-baseline ATBF (beta coefficient 0.029 +/- 0.013, P = 0.03). After meal ingestion, insulin-stimulated ATBF was decreased in relatives and and IGT, DMA, and DMB subjects. This defect could be an early marker of insulin resistance that precedes the development of type 2 diabetes.