Insulin Resistance Homeostasis Model Research Articles

Detection of Independent Associations of Plasma Lipidomic Parameters with Insulin Sensitivity Indices Using Data Mining Methodology.

ObjectiveGlucolipotoxicity is a major pathophysiological mechanism in the development of insulin resistance and type 2 diabetes mellitus (T2D). We aimed to detect subtle changes in the circulating lipid profile by shotgun lipidomics analyses and to associate them with four different insulin sensitivity indices.MethodsThe cross-sectional study comprised 90 men with a broad range of insulin sensitivity including normal glucose tolerance (NGT, n = 33), impaired glucose tolerance (IGT, n = 32) and newly detected T2D (n = 25). Prior to oral glucose challenge plasma was obtained and quantitatively analyzed for 198 lipid molecular species from 13 different lipid classes including triacylglycerls (TAGs), phosphatidylcholine plasmalogen/ether (PC O-s), sphingomyelins (SMs), and lysophosphatidylcholines (LPCs). To identify a lipidomic signature of individual insulin sensitivity we applied three data mining approaches, namely least absolute shrinkage and selection operator (LASSO), Support Vector Regression (SVR) and Random Forests (RF) for the following insulin sensitivity indices: homeostasis model of insulin resistance (HOMA-IR), glucose insulin sensitivity index (GSI), insulin sensitivity index (ISI), and disposition index (DI). The LASSO procedure offers a high prediction accuracy and and an easier interpretability than SVR and RF.ResultsAfter LASSO selection, the plasma lipidome explained 3% (DI) to maximal 53% (HOMA-IR) variability of the sensitivity indexes. Among the lipid species with the highest positive LASSO regression coefficient were TAG 54:2 (HOMA-IR), PC O- 32:0 (GSI), and SM 40:3:1 (ISI). The highest negative regression coefficient was obtained for LPC 22:5 (HOMA-IR), TAG 51:1 (GSI), and TAG 58:6 (ISI).ConclusionAlthough a substantial part of lipid molecular species showed a significant correlation with insulin sensitivity indices we were able to identify a limited number of lipid metabolites of particular importance based on the LASSO approach. These few selected lipids with the closest connection to sensitivity indices may help to further improve disease risk prediction and disease and therapy monitoring.

Association of Intestinal Microbiota with Metabolic Markers and Dietary Habits in Patients with Type 2 Diabetes

Background/Aims: Evidence suggests that intestinal microbiota, along with factors such as diet and host genetics, contributes to obesity, metabolic dysfunction and diabetes. Therefore, we examined the relationship between gut microbiota, blood metabolic markers, dietary habits and fecal short-chain fatty acids (SCFAs) in patients with type 2 diabetes mellitus (T2DM). Methods: Dietary habits, blood and fecal samples from 59 T2DM patients were recruited, and the association of intestinal microbiota with metabolic markers and dietary habits was analyzed. Results: Total energy intake was 1,692 ± 380 kcal/day. Carbohydrate, fat and protein intakes were 57.5 ± 5.2, 23.2 ± 5.3 and 13.2 ± 2.2%, respectively. Dietary habits - high carbohydrate, fat, and protein intake - were associated with increased counts of Clostridium clusters IV and XI and decreased counts of Bifidobacterium spp., order Lactobacillales and Clostridium cluster IV. Protein intake was negatively correlated with fecal acetate and total SCFAs. Total SCFAs, propionate and acetate were negatively correlated with blood insulin levels and the homeostasis model of insulin resistance. Conclusion: Diets low in protein and carbohydrates favor a healthy gut microbiome and improve glucose tolerance in T2DM patients, although further elucidation of the role of the gut microbiome could lead to better therapies and prophylaxes.

Hyperinsulinemia and insulin resistance in children

Obesity during childhood is a risk factor for developing cardiovascular diseases during adulthood. To measure insulin and glucose levels and parameters of insulin resistance in obese, overweight and normal weight Mexican children. Comparative study of 21 obese children with a body mass index (BMI) over percentile 95, aged 10 ± 1 years (10 males), 14 children aged 10 ± 2 (7 males) with a BMI between percentiles 85 and 94 and 16 children aged 9 ± 2 years (3 males) with a body mass index between percentiles 10 and 84. Body weight, blood pressure and waist circumference were measured and a blood sample was obtained to measure fasting glucose and insulin levels. Homeostasis model of insulin resistance (HOMA) and quantitative insulin sensitivity check index (QUICKI) were calculated. Among obese, overweight and normal weight children, insulin levels were 14.9 (95% CI 10.90-18.99), 7.20 (CI 5.12-9.28) and 4.73 (CI 95% 1.92-7.53) uU/ml, respectively. The figures for HOMA were 3.16 (95% CI 2.20-4.12), 1.49 (95% CI 1.03-1.94) and 0.97 (95% CI 0.35-1.60), respectively. The figures for QUICKI were 0.331 (95% CI 0.319-0.343), 0.371 (95% CI 0.349-0.393) and 0.419 (95% CI 0.391-0.446), respectively. Compared to their normal weight counterparts, the risk of obese children and those with a waist circumference over percentile 90 of having a HOMA over 3.16 was 17 and 10 times higher, respectively. BMI correlated better than waist circumference with insulin levels. Obese children have higher levels of insulin resistance than their normal weight counterparts.

Validation of different measures of insulin sensitivity of glucose metabolism in dairy cows using the hyperinsulinemic euglycemic clamp test as the gold standard

The aim of the present research was to compare different measures of insulin sensitivity in dairy cows at the end of the dry period. To do so, 10 clinically healthy dairy cows with a varying body condition score were selected. By performing hyperinsulinemic euglycemic clamp (HEC) tests, we previously demonstrated a negative association between the insulin sensitivity and insulin responsiveness of glucose metabolism and the body condition score of these animals. In the same animals, other measures of insulin sensitivity were determined and the correlation with the HEC test, which is considered as the gold standard, was calculated. Measures derived from the intravenous glucose tolerance test (IVGTT) are based on the disappearance of glucose after an intravenous glucose bolus. Glucose concentrations during the IVGTT were used to calculate the area under the curve of glucose and the clearance rate of glucose. In addition, glucose and insulin data from the IVGTT were fitted in the minimal model to derive the insulin sensitivity parameter, Si. Based on blood samples taken before the start of the IVGTT, basal concentrations of glucose, insulin, NEFA, and β-hydroxybutyrate were determined and used to calculate surrogate indices for insulin sensitivity, such as the homeostasis model of insulin resistance, the quantitative insulin sensitivity check index, the revised quantitative insulin sensitivity check index and the revised quantitative insulin sensitivity check index including β-hydroxybutyrate. Correlation analysis revealed no association between the results obtained by the HEC test and any of the surrogate indices for insulin sensitivity. For the measures derived from the IVGTT, the area under the curve for the first 60 min of the test and the Si derived from the minimal model demonstrated good correlation with the gold standard.

Insulin resistance-associated decreases in left ventricular diastolic function are strongly modified by the extent of concentric remodeling in a community sample

BackgroundWhether excess adiposity, associated metabolic abnormalities or alternative risk factors for left ventricular (LV) diastolic function are modified rather than mediated by geometric LV remodeling, is uncertain. MethodsEchocardiographic LV mass index (LVMI), relative wall thickness (RWT) and diastolic function (lateral and septal wall myocardial tissue lengthening at the level of the mitral annulus [e′] [n=430], ratio of early-to-late transmitral blood flow velocity (E/A), and E/e′ [n=430]) were determined in 737 randomly recruited participants of a community-based study (43% obese). ResultsIndependent of LVMI and confounders, indexes of adiposity and the homeostasis model of insulin resistance (HOMA-IR) were independently associated with LV diastolic function (p<0.05). In addition, RWT was independently associated with LV diastolic function (p<0.002). Importantly, an independent interaction between HOMA-IR and RWT, but not between blood pressure or age and RWT, was related to LV diastolic function (p<0.05). This translated into an independent relationship between HOMA-IR and lateral e′ (partial r=−0.17, p<0.02), septal e′ (partial r=−0.14, p=0.05), E/A (partial r=−0.17, p<0.005) and E/e′ (partial r=0.19, p<0.01) in those with RWT above, but a lack of relationship between HOMA-IR and LV diastolic function (p>0.59) in those with RWT below the median for the sample. Similarly, HOMA-IR was independently associated with LV diastolic dysfunction in those with RWT above (p<0.05) but not below (p>0.19) the median for the sample. ConclusionsThe relationship between insulin resistance, but not alternative risk factors and LV diastolic function is markedly modified by the presence of a more concentrically remodeled LV.

Autoimmune polyglandular syndrome type 3 (APS-3) among patients with premature ovarian insufficiency (POI)

ObjectivesAutoimmune polyglandular syndrome type 3 – (APS-3), is defined as the coexistence of autoimmune thyroiditis with other non-ovarian autoimmune diseases without primary adrenal insufficiency. Additionally the definition of APS-3 also includes primary ovarian insufficiency (POI) coexistence with autoimmune thyroiditis.The main goal of that study is to assess the prevalence of APS-3 defined as coexistence of autoimmune thyroiditis with POI in population of 46 XX karyotype women with primary ovarian insufficiency (POI).The second goal is to investigate hormonal profile and insulin sensitivity in women with POI and subgroups of women with APS-3 – POI/APS-3(+) and without APS 3 – POI/APS-3(−). Materials and methodsAnthropometric measurements, coexistence of autoimmune diseases, androgens, fasting glucose and insulin, glucose and insulin at 60′ and 120′ of oral glucose tolerance test (OGTT) and homeostasis model for insulin resistance (HOMA-IR), were determine in 98 patients aged between 18 and 39 with spontaneous 46 XX primary ovarian insufficiency (POI), in 33 POI/APS-3(+), 65 POI/APS-3(−), and 75 healthy controls. ResultsContinuous data were summarized by the mean±standard deviation (SD), and categorical data by number (percentages). Data were checked for normality using Shapiro–Wilk test, the comparison between groups were performed using non-parametric Mann–Whitney or Kruskall–Wallis test. Pearson's correlation coefficient was used to assess the relationships between parameters. Statistical significance was defined as p values <0.05.Autoimmune thyroid disease (ATD) was presented in 33/98 (33.7%) patients with POI. The groups did not differ significantly in respect to age and body mass index (BMI). Women with POI, POI/APS-3(+) and POI/APS-3(−) showed significantly lower serum androgens in comparison to controls. Additionally women with POI/APS-3(+) showed hyperinsulinemia after 1h of OGTT; No significant differences in serum fasting glucose, insulin and during 2h OGTT between groups were observed. ConclusionsThe prevalence of APS-3 is 33.7% in patients with spontaneous 46 XX primary ovarian insufficiency. Women with POI, POI/APS-3(+) and POI/APS-3(−) feature lower testosterone, androstendione, dehydroepiandrostendione sulphate in comparison to controls. Women with POI/APS-3(+) could have hyperinsulinemia and should be carefully evaluated for metabolic disorders.

Changes in profile of lipids and adipokines in patients with newly diagnosed hypothyroidism and hyperthyroidism.

Changes in profile of lipids and adipokines have been reported in patients with thyroid dysfunction. But the evidence is controversial. The present study aimed to explore the relationships between thyroid function and the profile of lipids and adipokines. A cross-sectional study was conducted in 197 newly diagnosed hypothyroid patients, 230 newly diagnosed hyperthyroid patients and 355 control subjects. Hypothyroid patients presented with significantly higher serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDLC), fasting insulin, resistin and leptin than control (p < 0.05). Hyperthyroid patients presented with significantly lower serum levels of high-density lipoprotein cholesterol, LDLC and leptin, as well as higher levels of fasting insulin, resistin, adiponectin and homeostasis model insulin resistance index (HOMA-IR) than control (p < 0.05). Nonlinear regression and multivariable linear regression models all showed significant associations of resistin or adiponectin with free thyroxine and association of leptin with thyroid-stimulating hormone (p < 0.001). Furthermore, significant correlation between resistin and HOMA-IR was observed in the patients (p < 0.001). Thus, thyroid dysfunction affects the profile of lipids and adipokines. Resistin may serve as a link between thyroid dysfunction and insulin resistance.

Hypertension among HIV patients: prevalence and relationships to insulin resistance and metabolic syndrome.

Metabolic syndrome is a cluster of risk factors, such as central obesity, dyslipidemia, glucose intolerance, hypertension, related to insulin resistance. In HIV patients insulin resistance and several metabolic abnormalities of the metabolic syndrome have been described, but few and conflicting studies have investigated the behaviour of blood pressure. The aims of the present study were to evaluate the prevalence of hypertension in a large group of HIV-patients on highly active antiretroviral therapy (HAART) and to investigate the relationship between hypertension, metabolic syndrome and insulin resistance. Case control study. We enrolled 287 HIV-positive patients on HAART (mean age 41.1 +/- 7.5 years) and 287 age- and sex-matched controls. Insulin resistance was estimated by the homeostasis model insulin resistance assessment (HOMA) index. Metabolic syndrome was defined according to the European Group for the Study of Insulin Resistance. HIV patients showed a prevalence of subjects with hypertension (34.2 versus 11.9%; P < 0.0001) and metabolic syndrome (33.1 versus 2.4%; P < 0.0001) higher than controls. HOMA was higher in HIV-patients than controls (3.3 +/- 1.2 versus 2.0 +/- 0.9; P < 0.0001). HOMA (3.7 +/- 1.0 versus 3.1 +/- 1.2; P < 0.001) and the prevalence of subjects with the metabolic syndrome (64.3 versus 16.9%; P < 0.0001) were greater in HIV-patients with than in those without hypertension. Multiple logistic regression analysis showed that family history of hypertension (odds ratio [(OR): 8.73; 95% confidence interval (CI): 4.31-17.70; P < 0.0001], metabolic syndrome (OR: 6.79; 95% CI: 3.27-14.10; P < 0.0001), lipodystrophy (OR: 4.80; 95% CI: 2.43-9.85; P < 0.0001) and HOMA (OR: 4.13; 95% CI: 1.14-14.91; P < 0.05) were predictors of hypertension in HIV-patients. The present study shows that hypertension is frequent in HIV patients on HAART and that hypertension appears to be linked to insulin resistance; in particular, hypertension seems to be a part of the metabolic syndrome.

Impact of obstructive sleep apnoea on insulin resistance in nonobese and obese children.

Obstructive sleep apnoea (OSA) has been inconsistently associated with insulin resistance and adverse metabolic states. We aimed to assess independent contributions of OSA to insulin resistance and dyslipidaemia in a large paediatric cohort.Habitually snoring children underwent overnight polysomnography, anthropometric measurements and fasting laboratory evaluations. Primary outcome measures included insulin, glucose, homeostasis model of insulin resistance, lipoproteins and sleep disturbance measures.Among 459 children aged 5-12 years, obesity was the primary driver of most associations between OSA and metabolic measures, but sleep duration was inversely associated with glucose levels, with N3 and rapid eye movement (REM) sleep being negatively associated and sleep fragmentation positively associated with insulin resistance measures. In children with mild OSA, the presence of obesity increased the odds for insulin resistance, while higher apnoea/hypopnoea index values emerged among obese children who were more insulin-resistant.The exclusive presence of interactions between OSA and obesity in the degree of insulin resistance is coupled with synergistic contributions by sleep fragmentation to insulin resistance in the context of obesity. Insufficient N3 or REM sleep may also contribute to higher glycaemia independently of obesity. Studies are needed to better delineate the roles of puberty and sleep fragmentation in insulin resistance and the metabolic syndrome.

Circulating resistin concentrations are independently associated with aortic pulse wave velocity in a community sample.

The role of the adipokine, resistin in mediating increases in aortic stiffness is uncertain. We aimed to determine independent relations between circulating resistin concentrations and aortic pulse wave velocity (PWV) and wave reflection in a community-based sample with a high prevalence of untreated hypertension and obesity. Plasma resistin, adiponectin, and C-reactive protein concentrations (ELISA); carotid-femoral (aortic) PWV and the aortic reflected wave index (applanation tonometry and SphygmoCor software) were determined in 683 randomly selected participants of African ancestry from SOWETO, South Africa who had never received antihypertensive therapy. Resistin concentrations were not independently associated with office or 24-h (n = 492) blood pressure (BP). In a stepwise regression model with BMI included in the model, age (P < 0.0001), mean arterial pressure (P < 0.0001), plasma resistin concentrations (P < 0.005), female sex (P = 0.01), and creatinine concentrations (P < 0.01) contributed independently to variations in PWV. Independent relations between resistin concentrations and PWV persisted with further adjustments for C-reactive protein concentrations (P < 0.005), and the homeostasis model of insulin resistance (P < 0.02). Similar relations were noted with waist circumference rather than BMI in the model. Resistin concentrations were not independently associated with aortic reflected wave index or aortic BP. Resistin is independently and directly associated with aortic stiffness and these effects occur beyond BP, insulin resistance, and general inflammation.

Changes in biomarkers and DNA methylation in breast cancer survivors enrolled in the ENERGY weight loss trial: A pilot study.

181 Background: In 2014, an ASPO position statement was released calling for action regarding cancer survivors’ needs for weight management. Reduction of body weight is hypothesized to affect several cancer-related biological pathways. Methods: The Exercise and Nutrition to Enhance Recovery and Good health for You (ENERGY) trial is the largest weight loss trial completed to date among breast cancer survivors. In it, 692 stage Ic-IIIc breast cancer survivors were randomized to an intensive, group-based weight loss intervention with 26 contacts over one year or to a non-intensive intervention with two contacts over the same time period. Results recently reported in JCO showed significantly greater weight loss in the intensive intervention arm compared to the non-intensive arm. A pilot study exploring baseline to 6-month changes in gene methylation and expressed biomarkers was undertaken in 30 chemo-naïve, post-menopausal, non-Hispanic white women who participated in this study. Results: Several significant differences in mean change scores (standard error) between the intensive vs. non-intensive groups were noted, i.e., insulin: -4.19(0.80) vs. 0.42 (1.01)/p = 0.0016; c-peptide: -0.49(0.14) vs. 0.40(0.19)/p = 0.0009; leptin: -15.73(1.79) vs. 2.53(1.78)/p &lt; 0.0001; adiponectin:leptin ratio: 0.67(0.15) vs. 0.010(0.064)/p = 0.0007; homeostasis model of insulin resistance (HOMA-IR): 20.00(4.65) vs. 9.57(5.00)/p = 0.0003; sex hormone binding globulin 20.45(4.61) vs. 8.65(8.00)/p = 0.023; and Follistatin-Related Protein-3 (FSTL3): 0.48(0.19) vs. -0.88(0.55)/p = 0.0497. While effects were in the direction hypothesized for c-reactive protein, interleukin-6, vascular endothelial growth factor, and tumor necrosis factor no significant differences were noted. Significant differences in DNA methylation also were noted for genes encoding for Follistatin Related Protein (corresponds to FSTL3), and those on hormonal/growth pathways (e.g., AMOTL1, ESR, EGR3), inflammatory pathways (e.g., TNFRS10A/TRAIL-R1, C14orf106), and metabolic pathways (e.g., ZBED3, GABRA). Conclusions: While results are based on a small sample and not corrected for multiple testing, they provide evidence that weight loss affects several biomarkers and pathways that impact cancer and which warrant further investigation. Clinical trial information: NCT01112839.

Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis.

Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P < 0.001) increase in glycosylated hemoglobin, glucose, homeostasis model of insulin resistance, and pro-inflammatory cytokines. Serum insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly (P < 0.001) decreased in diabetic rats. Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P < 0.001) down-regulated in testes of diabetic rats, an effect which was significantly increased after administration of taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis.

Short-term moderate sleep restriction decreases insulin sensitivity in young healthy adults

Context and purposeThe literature suggests that severe sleep loss of more than a few hours a night decreases glucose tolerance and insulin sensitivity. The aim of this study was to determine whether moderate sleep restriction had similar effects. MethodsFifteen healthy non-obese (body mass index = 24.5 ± 3.4 kg/m2) young adults (20.6 ± 1.3 years) completed two 2-hour oral glucose tolerance tests (OGTTs): one was after 3 days of time-in-bed restriction by 1 to 3 hours each night, and the other was after 3 days of ad libitum sleep. Glucose and insulin concentrations during OGTT and fasting glucagon and cortisol concentrations were determined. The homeostasis model of insulin resistance, Matsuda index, and the quantitative insulin sensitivity check index were calculated. ResultsThe total time-in-bed during the sleep restriction and the ad libitum phase was 5.98 ± 0.76 and 7.98 ± 0.54 hours/day, and total sleep time was 5.16 ± 0.49 and 6.65 ± 0.64 hours/day, respectively. Glucose concentrations before and 30, 60, 90, and 120 minutes after consumption of glucose and area under the curve were not different for the 2 OGTTs (P > .10 for all). Insulin concentration at fasting and area under the curve during the OGTT were significantly higher (P = .034 and .038, respectively) after restricted sleep than after ad libitum sleep. Fasting glucagon concentration was also higher (P = .003). The homeostasis model of insulin resistance, Matsuda index, and quantitative insulin sensitivity check index all suggested decreased insulin sensitivity after restricted sleep. ConclusionShort-term moderate sleep restriction reduced insulin sensitivity compared to ad libitum sleep in this group of healthy young adults.

Surrogate markers of insulin resistance in subjects with metabolic syndrome – data of the Berlin Aging Study II

Abstract Background: The metabolic syndrome (MetS) is a cluster of metabolic changes which is associated with insulin resistance (IR). Cutoff values for the homeostasis model of insulin resistance (HOMA-IR) – a surrogate marker of IR-to identify subjects with MetS are not established. Methods: Cross-sectional data of 446 younger (53% women, 28±3 years old) and 1271 elderly study participants (52% women, 68±4 years old) without diabetes were available for the current analysis. MetS was defined according to the IDF/AHA/NHLBI (International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute) criteria of 2009. Using receiving operating characteristics (ROC) analysis cutoff values for HOMA-IR were calculated above which participants with MetS could be identified with highest sensitivity and specificity. Finally, binary logistic regression models were calculated. Results: The prevalence of MetS was 6.7% in young and 28.3% in elderly subjects. HOMA-IR cutoff values for the detection of MetS were HOMA-IR &gt;1.88 (young subjects; sensitivity 80%, specificity 85.3%, positive predictive value 80%, negative predictive value 15%) and HOMAIR &gt;1.98 (elderly subjects; sensitivity 73.6%, specificity 72.9%, positive predictive value 74%, negative predictive value 27%). In adjusted regression models [age, body mass index (BMI), sex, physical activity and age groups] subjects above these cutoff-values had odds of 5.7 [95% confidence interval (CI): 4.1–7.9] in elderly and 22.2 (95% CI: 7.0–70.5) in younger study participants to have MetS. Conclusions: Cutoff values for HOMA-IR are not established in clinical practice; however, they could be used to identify subjects with MetS, even if a diagnosis of MetS cannot made based solely on HOMA-IR considering the negative predictive values.

Novel non-invasive biological predictive index for liver fibrosis in hepatitis C virus genotype 4 patients.

AIMTo investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy.METHODSA cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensin-converting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance (HOMA-IR).RESULTSFibrosis stages were distributed based on Metavir score as follows: F0 = 43, F1 = 136, F2 = 64, F3 = 45 and F4 = 44. Statistical analysis relied upon reclassification of fibrosis stages into mild fibrosis (F0-F) = 179, moderate fibrosis (F2) = 64, and advanced fibrosis (F3-F4) = 89. Univariate analysis indicated that age, log aspartate amino transaminase, log HOMA-IR and log platelet count were independent predictors of liver fibrosis stage (P < 0.0001). A stepwise multivariate discriminant functional analysis was used to drive a discriminative model for liver fibrosis. Our index used cut-off values of ≥ 0.86 and ≤ -0.31 to diagnose advanced and mild fibrosis, respectively, with receiving operating characteristics of 0.91 and 0.88, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were: 73%, 91%, 75%, 90% and 8.0 respectively for advanced fibrosis, and 67%, 88%, 84%, 70% and 4.9, respectively, for mild fibrosis.CONCLUSIONOur predictive model is easily available and reproducible, and predicted liver fibrosis with acceptable accuracy.

An Okinawan-based Nordic diet improves anthropometry, metabolic control, and health-related quality of life in Scandinavian patients with type 2 diabetes: a pilot trial

BackgroundOur hypothesis was that a modified diet would improve blood glucose control with beneficial impact on weight management and overall health in established diabetes.ObjectiveThis prospective interventional study investigated the clinical effect of an Okinawan-based Nordic diet on anthropometry, metabolic control, and health-related quality of life (HRQoL) in Scandinavian type 2 diabetes patients.DesignFood was prepared and delivered to 30 type 2 diabetes patients. Clinical information along with data on HRQoL, blood samples, and urine samples were collected during 12 weeks of diet interventions, with follow-up 16 weeks after diet completion.ResultsAfter 12 weeks of dietary intervention, a reduction in body weight (7%) (p<0.001), body mass index (p<0.001), and waist circumference (7.0 cm) (p<0.001) was seen. Improved levels of proinsulin (p=0.005), insulin (p=0.011), and fasting plasma glucose (p<0.001) were found already after 2 weeks; these improved levels remained after 12 weeks when lowered levels of C-peptide (p=0.015), triglycerides (p=0.009), total cholesterol (p=0.001), and low-density lipoprotein-cholesterol (p=0.041) were also observed. Insulin resistance homeostasis model assessment for insulin resistance was lowered throughout the study, with a 20% reduction in hemoglobin A1c levels (p<0.001) at week 12, despite reduced anti-diabetes treatment. Lowered systolic blood pressure (9.6 mmHg) (p<0.001), diastolic blood pressure (2.7 mmHg) (p<0.001), and heart and respiratory rates (p<0.001) were accompanied by decreased cortisol levels (p=0.015) and improvement in HRQoL. At follow-up, increased levels of high-density lipoprotein-cholesterol were found (p=0.003).ConclusionThis interventional study demonstrates a considerable improvement of anthropometric and metabolic parameters and HRQoL in Scandinavian type 2 diabetes patients when introducing a modified Okinawan-based Nordic diet, independently of exercise or other interventions. Through these dietary changes, anti-diabetes treatment could be decreased or cancelled.

The Therapeutic Potential of Resistant Starch in Modulation of Insulin Resistance, Endotoxemia, Oxidative Stress and Antioxidant Biomarkers in Women with Type 2 Diabetes: A Randomized Controlled Clinical Trial

Aims: This trial aims to determine the effects of resistant starch (RS) subtype 2 (RS2) on glycemic status, metabolic endotoxemia and markers of oxidative stress. Methods: A randomized, controlled, parallel-group clinical trial group of 56 females with type 2 diabetes mellitus (T2DM) was divided to 2 groups. The intervention group (n = 28) and control group (n = 28) received 10 g/day RS2 or placebo for 8 weeks, respectively. Fasting blood samples were taken to determine glycemic status, endotoxin, high sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), total antioxidant capacity (TAC), antioxidant enzymes concentrations as well as uric acid at baseline and after the intervention. Results: After 8 weeks, RS2 caused a significant decrease in the levels of MDA (-34.10%), glycosylated hemoglobin (-9.40%), insulin (-29.36%), homeostasis model of insulin resistance (-32.85%) and endotoxin (-25.00%), a significant increase in TAC (18.10%) and glutathione peroxidase (11.60%) as compared with control. No significant changes were observed in fasting plasma glucose, quantitative insulin sensitivity check index, hs-CRP, superoxide dismutase, catalase and uric acid in the RS2 group as compared with the control group. Conclusion: Supplementation with RS2 may be improved glycemic status, endotoxemia and markers of oxidative stress in patients with T2DM.

Genetic and Non-Genetic Determinants of Circulating Levels of Adiponectin in a Cohort of Chilean Subjects.

Low adiponectin levels have been associated with obesity, diabetes, coronary disease and polymorphisms. The aim of this study was to assess the clinical and genetic factors related to adiponectin levels in a Chilean adult population. Four groups of 27 individuals, stratified by gender and abdominal obesity, were included in this cross-sectional study. Physical activity level, cardiovascular risk factors and therapy were assessed. Anthropometric measurements, adiponectin, glucose, insulin, hs-CRP, rs1501299, rs2241766, rs266729 and rs17300539 single nucleotide polymorphisms of the adiponectin gene were determined. Adiponectin levels were inversely correlated with waist circumference, waist-to-hip ratio, weight, body mass index, insulin levels, homeostasis model insulin resistance index (HOMA-IR) and physical activity. Mean adiponectin levels were lower in men (10.1 ± 3.6 vs 11.9 ± 2.9 μg/mL, p = 0.0051), obese (9.9 ± 3.2 vs 12.1 ± 3.3, p < 0.01), physically inactive (8.9 ± 3.2 vs 11.0 ± 2.8, p = 0.015) and insulin-resistant individuals (10.2 ± 3.1 vs 12.9 ± 3.9; p = 0.005). Adiponectin levels were lower in subjects with GG genotype (rs1501299) compared with those with TT or GT variants (6.9 ± 4.6 vs 12.2 ± 2.9 and 11.5 ± 3.4 μg/mL, p = 0.006) but were similar in the other polymorphisms studied. Lower adiponectin levels were related to gender, abdominal obesity, physical activity and insulin resistance and were less influenced by the polymorphisms studied.

IGF2, LEPR, POMC, PPARG, and PPARGC1 gene variants are associated with obesity-related risk phenotypes in Brazilian children and adolescents.

Association studies of genetic variants and obesity and/or obesity-related risk factors have yielded contradictory results. The aim of the present study was to determine the possible association of five single-nucleotide polymorphisms (SNPs) located in the IGF2, LEPR, POMC, PPARG, and PPARGC1genes with obesity or obesity-related risk phenotypes. This case-control study assessed overweight (n=192) and normal-weight (n=211) children and adolescents. The SNPs were analyzed using minisequencing assays, and variables and genotype distributions between the groups were compared using one-way analysis of variance and Pearson's chi-square or Fisher's exact tests. Logistic regression analysis adjusted for age and gender was used to calculate the odds ratios (ORs) for selected phenotype risks in each group. No difference in SNP distribution was observed between groups. In children, POMC rs28932472(C) was associated with lower diastolic blood pressure (P=0.001), higher low-density lipoprotein (LDL) cholesterol (P=0.014), and higher risk in overweight children of altered total cholesterol (OR=7.35, P=0.006). In adolescents, IGF2 rs680(A) was associated with higher glucose (P=0.012) and higher risk in overweight adolescents for altered insulin (OR=10.08, P=0.005) and homeostasis model of insulin resistance (HOMA-IR) (OR=6.34, P=0.010). PPARG rs1801282(G) conferred a higher risk of altered insulin (OR=12.31, P=0.003), and HOMA-IR (OR=7.47, P=0.005) in overweight adolescents. PARGC1 rs8192678(A) was associated with higher triacylglycerols (P=0.005), and LEPR rs1137101(A) was marginally associated with higher LDL cholesterol (P=0.017). LEPR rs1137101(A) conferred higher risk for altered insulin, and HOMA-IR in overweight adolescents. The associations observed in this population suggested increased risk for cardiovascular diseases and/or type 2 diabetes later in life for individuals carrying these alleles.

Independent associations between resistin and left ventricular mass and myocardial dysfunction in a community sample with prevalent obesity

BackgroundAlthough the adipokine resistin may play a role in heart failure, the mechanisms of this effect are uncertain. Relations with left ventricular mass (LVM) and function are uncertain. MethodsIn 739 randomly selected participants from a community sample (43.6% obese), we assessed relations between circulating resistin concentrations and LVM index (LVMI), LVM beyond that predicted by stroke work (inappropriate LVMI [LVMinappr]) and systolic and diastolic LV function (echocardiography). ResultsResistin concentrations were not independently associated with blood pressure (BP). However, resistin concentrations were associated with LVMI (partial r=0.12, p<0.0005), LVMinappr (partial r=0.18, p<0.0001) and LV hypertrophy (partial r=0.13, p<0.001) independent of BP, BMI, the homeostasis model of insulin resistance and additional confounders. Independent relations between resistin concentrations and LVMI and LVMinappr persisted with further adjustments for C-reactive protein concentrations. Resistin concentration (partial r=−0.12, p<0.002 in all and partial r=−0.15, p<0.0005 in untreated) was the only factor independently associated with LV midwall fractional shortening and these relations were enhanced at incremental concentrations of CRP. Resistin was not independently associated with transmitral and myocardial tissue Doppler indices of LV diastolic function. ConclusionsResistin in-part explains variations in LVM, hypertrophy and myocardial systolic dysfunction, and these effects are independent of insulin resistance and general inflammatory changes.