Novel adiponectin-resistin (AR) and insulin resistance (IRAR) indexes are useful integrated diagnostic biomarkers for insulin resistance, type 2 diabetes and metabolic syndrome: a case control study

Background

Adiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis. Meta-analyses showed that hypoadiponectinemia and hyperresistinemia are strongly associated with increased risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS) and cardiovascular disease. The aim of this study was to propose a novel adiponectin-resistin (AR) index by taking into account both adiponectin and resistin levels to povide a better indicator of the metabolic homeostasis and metabolic disorders. In addition, a novel insulin resistance (IR_AR) index was proposed by integration of the AR index into an existing insulin resistance index to provide an improved diagnostic biomarker of insulin sensitivity.

Methods

In this case control study, anthropometric clinical and metabolic parameters including fasting serum total adiponectin and resistin levels were determined in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40-70 years old. Significant differences in continuous variables among subject groups were confirmed by ANCOVA or MANCOVA test using 1,000 stratified bootstrap samples with bias corrected and accelerated (BCa) 95% CI. Spearman's rho rank correlation test was used to test the correlation between two variables.

Results

The AR index was formulated as 1+log₁₀(R₀)-log₁₀(A₀). The AR index was more strongly associated with increased risk of T2DM and MS than hypoadiponectinemia and hyperresistinemia alone. The AR index was more strongly correlated with the insulin resistance indexes and key metabolic endpoints of T2DM and MS than adiponectin and resistin levels alone. The AR index was also correlated with a higher number of MS components than adiponectin and resistin levels alone. The IR_AR index was formulated as log₁₀(I₀G₀)+log₁₀(I₀G₀)log₁₀(R₀/A₀). The normal reference range of the IR_AR index for insulin sensitive individuals was between 3.265 and 3.538. The minimum cut-off values of the IR_AR index for insulin resistance assessment were between 3.538 and 3.955.

Conclusions

The novel AR and IR_AR indexes are cost-effective, precise, reproducible and reliable integrated diagnostic biomarkers of insulin sensitivity for screening subjects with increased risk of future development of T2DM and MS.     

Both Fasting and Glucose-Stimulated Proinsulin Levels Predict Hyperglycemia and Incident Type 2 Diabetes: A Population-Based Study of 9,396 Finnish Men

Background

Hyperproinsulinemia is an indicator of β-cell dysfunction, and fasting proinsulin levels are elevated in patients with hyperglycemia. It is not known whether proinsulin levels after a glucose load are better predictors of hyperglycemia and type 2 diabetes than fasting proinsulin.

Methods

Participants were 9,396 Finnish men (mean±SD, age 57.3±7.1 years, BMI 27.0±4.0 kg/m²) of the population-based METabolic Syndrome In Men Study who were non-diabetic at the recruitment, and who participated in a 6-year follow-up study. Proinsulin and insulin levels were measured in the fasting state and 30 and 120 min after an oral glucose load. Area under the curve (AUC) and proinsulin to insulin ratios were calculated.

Results

Fasting proinsulin, proinsulin at 30 min and proinsulin AUC during the first 30 min of an oral glucose tolerance test significantly predicted both the worsening of hyperglycemia and type 2 diabetes after adjustment for confounding factors. Further adjustment for insulin sensitivity (Matsuda index) or insulin secretion (Disposition index) weakened these associations. Insulin sensitivity had a major impact on these associations.

Conclusion

Our results suggest that proinsulin in the fasting state and after an oral glucose load similarly predict the worsening of hyperglycemia and conversion to type 2 diabetes.     

Human liver-derived cells stably modified for regulated proinsulin secretion function as bioimplants in vivo

Background

Insulin deficiency is currently treated with pharmacological insulin secretagogues, insulin injections or islet transplants. Secondary failure of pharmacological agents is common; insulin injections often fail to achieve euglycemic control; and islet transplants are rare. Non‐β cells capable of regulated insulin secretion in vivo could be a functional cure for diabetes. Hepatocytes are good candidates, being naturally glucose‐responsive, protein‐secreting cells, while the liver is positioned to receive direct nutrient signals that regulate insulin production.

Methods

Human liver‐derived Chang cells were modified with a plasmid construct in which a bifunctional promoter comprising carbohydrate response elements and the human metallothionein IIA promoter controlled human proinsulin cDNA expression. Secretory responses of stable cell clones were characterized in vitro and in vivo by proinsulin radioimmunoassay.

Results

Transfected Chang cells secreted 5–8 pmol proinsulin/10⁶ cells per 24 h in continuous passage for at least a year in response to 5–25 mM glucose and 10–90 µM zinc in vitro. Glucose and zinc synergistically increased proinsulin production by up to 30‐fold. Non‐glucose secretagogues were also active. Glucose transporter 2 (GLUT2) and glucokinase cDNA co‐transfection enhanced glucose responsiveness. Intraperitoneally implanted Chang cells secreted proinsulin in scid and Balb/c mice. Serum proinsulin levels were further increased 1.3‐fold (p<0.05) after glucose and 1.4‐ to 1.6‐fold (p<0.005) after zinc administration in vivo.

Conclusions

These results are the first to demonstrate stable proinsulin production in a human liver‐derived cell line with activity in vitro and in vivo and provide a basis for engineering hepatocytes as in vivo bioimplants for future diabetes treatment. Copyright © 2002 John Wiley & Sons, Ltd.

     

Exenatide once weekly treatment maintained improvements in glycemic control and weight loss over 2 years

Background

Latinos in the United States have a higher prevalence of type 2 diabetes than non-Latino whites, even after controlling for adiposity. Decreased adiponectin is associated with insulin resistance and predicts T2DM, and therefore may mediate this ethnic difference. We compared total and high-molecular-weight (HMW) adiponectin in Latino versus white individuals, identified factors associated with adiponectin in each ethnic group, and measured the contribution of adiponectin to ethnic differences in insulin resistance.

Methods

We utilized cross-sectional data from subjects in the Latinos Using Cardio Health Actions to reduce Risk study. Participants were Latino (n = 119) and non-Latino white (n = 60) men and women with hypertension and at least one other risk factor for CVD (age 61 ± 10 yrs, 49% with T2DM), seen at an integrated community health and hospital system in Denver, Colorado. Total and HMW adiponectin was measured by RIA and ELISA respectively. Fasting glucose and insulin were used to calculate the homeostasis model insulin resistance index (HOMA-IR). Variables independently associated with adiponectin levels were identified by linear regression analyses. Adiponectin's contribution to ethnic differences in insulin resistance was assessed in multivariate linear regression models of Latino ethnicity, with logHOMA-IR as a dependent variable, adjusting for possible confounders including age, gender, adiposity, and renal function.

Results

Mean adiponectin levels were lower in Latino than white patients (beta estimates: -4.5 (-6.4, -2.5), p < 0.001 and -1.6 (-2.7, -0.5), p < 0.005 for total and HMW adiponectin), independent of age, gender, BMI/waist circumference, thiazolidinedione use, diabetes status, and renal function. An expected negative association between adiponectin and waist circumference was seen among women and non-Latino white men, but no relationship between these two variables was observed among Latino men. Ethnic differences in logHOMA-IR were no longer observed after controlling for adiponectin levels.

Conclusions

Among patients with CVD risk, total and HMW adiponectin is lower in Latinos, independent of adiposity and other known regulators of adiponectin. Ethnic differences in adiponectin regulation may exist and future research in this area is warranted. Adiponectin levels accounted for the observed variability in insulin resistance, suggesting a contribution of decreased adiponectin to insulin resistance in Latino populations.     

Elevated Plasma SPARC Levels Are Associated with Insulin Resistance,Dyslipidemia, and Inflammation in Gestational Diabetes Mellitus

Objective

Recent studies suggested that secreted protein acidic and rich in cysteine (SPARC), a novel adipokine, is a key player in the pathology of obesity and type 2 diabetes. We aimed to determine whether concentrations of SPARC were altered in patients with gestational diabetes mellitus (GDM) compared to normal glucose tolerance (NGT) controls and to investigate the relationships between SPARC and metabolic parameters in pregnant women.

Design/Methods

Cross-sectional study of 120 pregnant women with GDM and 60 controls with NGT, in a university hospital setting. Plasma levels of SPARC, adiponectin, fibroblast growth factor 21 (FGF21), insulin and proinsulin were determined by ELISA.

Results

GDM women had higher SPARC and lower adiponectin than NGT subjects; no difference was found in FGF21. SPARC levels were the lowest in subjects in the third tertile of insulin sensitivity index (ISI_OGTT) and correlated positively with pre-pregnant BMI, insulin and 3 h glucose during 100-g OGTT, HOMA-IR, fasting proinsulin, hsCRP and white blood cells count, and negatively with ISI_OGTT, when adjusting for gestational age. Triglyceride (TG), Apolipoprotein A1, apolipoprotein B and lipoprotein (a) correlated with SPARC in partial Pearson correlation. Correlations between SPARC with adiponectin, systolic blood pressure and TG were marginally significant in partial Spearman correlation analysis. In multivariate regression analysis, SPARC was an independent negative indicator of ISI_OGTT.

Conclusions

SPARC levels are correlated significantly with inflammation and may also be correlated with dyslipidemia and represent an independent determinant of insulin resistance in late pregnancy, indicating a potential role of SPARC in the pathophysiology of GDM.     

Plasma levels of leptin, omentin, collagenous repeat-containing sequence of 26-kDa protein (CORS-26) and adiponectin before and after oral glucose uptake in slim adults

Background

Immigrant women from the Middle East have elevated risk of cardiovascular disease. Sagittal abdominal diameter (SAD), a simple marker of intra-abdominal fat, predicts insulin resistance and cardiovascular mortality in men. Its usefulness in immigrant women is however unknown. To investigate the predictive role of SAD compared to other anthropometric measures, we examined a random sample of native-Swedes and immigrant women from the Middle East living in Sweden.

Methods

157 women participated in the study; 107 immigrants and 50 natives. Anthropometric measurements (SAD, body mass index [BMI], waist circumference [WC] and waist-to-hip ratio [WHR]; all measured in supine position) and cardiovascular risk factors (C-reactive protein [CRP], insulin, glucose, insulin resistance [HOMA-IR], blood pressure and serum lipids) were assessed. The anthropometric measures were compared in their relation to cardiovascular risk factors using linear regression analyses.

Results

Overall, SAD showed a slightly higher correlation with most cardiovascular risk factors, especially insulin resistance, insulin, CRP, apolipoprotein B and triglycerides (all P-values < 0.01) than other anthropometric measures. BMI was however a better predictor of HDL cholesterol. SAD explained a greater proportion of the variation of insulin resistance and CRP levels, even independently of the other anthropometric measures.

Conclusion

SAD identifies insulin resistance, subclinical inflammation or raised serum lipids in a Swedish population with a large proportion of immigrant women from the Middle East. If these results could be confirmed in a larger population, SAD could be a more clinically useful risk marker than other anthropometric measures in women at high risk of cardiovascular disease.     

Canalization effect in the coagulation cascade and the interindividual variability of oral anticoagulant response. a simulation Study

Background

The aim of the study was to find a simple intravenous glucose tolerance test (IVGTT) that can be used to estimate insulin sensitivity.

Methods

In 20 healthy volunteers aged between 18 and 51 years (mean, 28) comparisons were made between kinetic parameters derived from a 12-sample, 75-min IVGTT and the M_bw (glucose uptake) obtained during a hyperinsulinemic euglycemic glucose clamp. Plasma glucose was used to calculate the volume of distribution (V _d) and the clearance (CL) of the injected glucose bolus. The plasma insulin response was quantified by the area under the curve (AUC_ins). Uptake of glucose during the clamp was corrected for body weight (M_bw).

Results

There was a 7-fold variation in M_bw. Algorithms based on the slope of the glucose-elimination curve (CL/V _d) in combination with AUC_ins obtained during the IVGTT showed statistically significant correlations with M_bw, the linearity being r² = 0.63-0.83. The best algorithms were associated with a 25-75^th prediction error ranging from -10% to +10%. Sampling could be shortened to 30-40 min without loss of linearity or precision.

Conclusion

Simple measures of glucose and insulin kinetics during an IVGTT can predict between 2/3 and 4/5 of the insulin sensitivity.     

Metabolic effect of telmisartan and losartan in hypertensive patients with metabolic syndrome

Background

Metabolic syndrome is a cluster of common cardiovascular risk factors that includes hypertension and insulin resistance. Hypertension and diabetes mellitus are frequent comorbidities and, like metabolic syndrome, increase the risk of cardiovascular events. Telmisartan, an antihypertensive agent with evidence of partial peroxisome proliferator-activated receptor activity-gamma (PPARγ) activity, may improve insulin sensitivity and lipid profile in patients with metabolic syndrome.

Methods

In a double-blind, parallel-group, randomized study, patients with World Health Organization criteria for metabolic syndrome received once-daily doses of telmisartan (80 mg, n = 20) or losartan (50 mg, n = 20) for 3 months. At baseline and end of treatment, fasting and postprandial plasma glucose, insulin sensitivity, glycosylated haemoglobin (HBA_1c) and 24-hour mean systolic and diastolic blood pressures were determined.

Results

Telmisartan, but not losartan, significantly (p < 0.05) reduced free plasma glucose, free plasma insulin, homeostasis model assessment of insulin resistance and HbA_ic. Following treatment, plasma glucose and insulin were reduced during the oral glucose tolerance test by telmisartan, but not by losartan. Telmisartan also significantly reduced 24-hour mean systolic blood pressure (p < 0.05) and diastolic blood pressure (p < 0.05) compared with losartan.

Conclusion

As well as providing superior 24-hour blood pressure control, telmisartan, unlike losartan, displayed insulin-sensitizing activity, which may be explained by its partial PPARγ activity.     

Serum Proteome Pool Changes in Type 2 Diabetic Patients Treated with Anakinra

Introduction

High glucose concentrations induce the production of IL-1β in human pancreatic beta cells leading to impaired insulin secretion, decreased cell proliferation and apoptosis. Blockade of IL-1 signalling with the recombinant human IL-1 receptor antagonist anakinra reduces HbA_1c in patients with type 2 diabetes. The aims of the present study were to identify: (1) candidate surrogates for improved glycemia in type 2 diabetic patients following treatment with anakinra, (2) proteins that change serum concentration because of anakinra treatment and (3) candidate biomarkers that may predict improved glycemia in type 2 diabetic subjects treated with anakinra.

Methods

Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry was used to analyse serum from 67 type 2 diabetic patients who had received either placebo or anakinra for 13 weeks. Immunodepletion with magnetic protein G bead-coupled antibodies were used to identify three proteins and Western blotting confirmed the biomarker concentration pattern of four proteins.

Results

Twelve proteins, including transthyretin (TTR) and transferrin (Tf), were identified as candidate surrogates for improved glycemia. Six proteins, including retinol-binding protein 4 (RPB4) and a protein tentatively identified as modified apolipoprotein-A1 (apo-AI), increased expression as a consequence of anakinra treatment and four proteins were candidate biomarkers that may predict improved glycemia following anakinra treatment. Furthermore, we found increased RBP4 to be associated with improved beta cell secretory function and increased TTR, RBP4 and modified apo-AI (peak at 28,601 Da) to be associated with decreased inflammation.

Conclusions

Anakinra-induced changes in the serum proteome pool associated with a decreased cardiovascular disease risk, reduced inflammation and improved beta cell secretory function.     

Comparison of secondary structures of insulin and proinsulin by FTIR

Although the structure of insulin is known in great detail, that of proinsulin has been little investigated, except for a few CD and NMR studies. The secondary structures of human proinsulin are now compared with those of insulin by Fourier Transformed Infrared (FTIR) studies. The deconvolved and second derivative spectra of proinsulin and insulin in the amide I' band region are closely similar with peaks corresponding to -helix, irregular helix, and 3₁₀ helix at nearly identical positions. For both proteins, the relative contents of the above structures as calculated from the peak areas are in good agreement with the values obtained from the known structure of crystalline porcine insulin. However, compared with insulin, proinsulin has markedly more unordered structures as indicated by the area under the peak at 1643.4 cm^–1. In addition, both peak positions and relative areas for turn structure of the prohormone are different from those for insulin. It appears from the above that the A-and B-chain segments of proinsulin and insulin are similar in their secondary structures, especially in helices. The C-chain segment is largely unordered except in a few -turns.     

IL-12 serum levels in patients with type 2 diabetes treated with sulphonylureas

Interleukin-12 (IL-12) has been identified as a pro-inflammatory cytokine which is thought to contribute to the development of atherosclerosis. However, to date, the various associations between factors related to the course of type 2 diabetes, like metabolic compensation, beta cell secretory dysfunction, insulin resistance and IL-12 serum levels, remain unclear. Our study involved 41 patients with type 2 diabetes, 19 patients with coronary artery disease (CAD), and 19 healthy controls. We measured serum levels of fasting glucose, HbA₁c, 1,5-anhydro-d-glucitol, and lipids. In addition, serum levels of C-peptide, insulin, proinsulin and IL-12 were assayed. HOMA_IR score was calculated. The serum concentrations of IL-12 were higher in diabetics than in either patients with CAD or healthy controls, and were correlated with BMI, C-peptide, insulin, HOMA_IR, proinsulin and HDL serum levels. Multiple regression analysis revealed that the IL-12 serum level in type 2 diabetics primarily is dependent upon fasting proinsulin concentration. Our results demonstrate that elevated IL-12 serum levels in type 2 diabetics treated with sulphonylureas are induced especially by peripheral insulin resistance and beta cells dysfunction, as expressed by fasting serum proinsulin levels. This finding gives us hope that treatment to decrease peripheral insulin resistance and to avoid excessive proinsulin secretion might be successful in the prevention of IL-12-induced atherosclerosis.     

Early limited nitrosamine exposures exacerbate high fat diet-mediated type 2 diabetes and neurodegeneration

Background

Type 2 diabetes mellitus (T2DM) and several types of neurodegeneration, including Alzheimer's, are linked to insulin-resistance, and chronic high dietary fat intake causes T2DM with mild neurodegeneration. Intra-cerebral Streptozotocin, a nitrosamine-related compound, causes neurodegeneration, whereas peripheral treatment causes DM.

Hypothesis

Limited early exposures to nitrosamines that are widely present in the environment, enhance the deleterious effects of high fat intake in promoting T2DM and neurodegeneration.

Methods

Long Evans rat pups were treated with N-nitrosodiethylamine (NDEA) by i.p. injection, and upon weaning, they were fed with high fat (60%; HFD) or low fat (5%; LFD) chow for 8 weeks. Cerebella were harvested to assess gene expression, and insulin and insulin-like growth factor (IGF) deficiency and resistance in the context of neurodegeneration.

Results

HFD ± NDEA caused T2DM, neurodegeneration with impairments in brain insulin, insulin receptor, IGF-2 receptor, or insulin receptor substrate gene expression, and reduced expression of tau and choline acetyltransferase (ChAT), which are regulated by insulin and IGF-1. In addition, increased levels of 4-hydroxynonenal and nitrotyrosine were measured in cerebella of HFD ± NDEA treated rats, and overall, NDEA+HFD treatment reduced brain levels of Tau, phospho-GSK-3β (reflecting increased GSK-3β activity), glial fibrillary acidic protein, and ChAT to greater degrees than either treatment alone. Finally, pro-ceramide genes, examined because ceramides cause insulin resistance, oxidative stress, and neurodegeneration, were significantly up-regulated by HFD and/or NDEA exposure, but the highest levels were generally present in brains of HFD+NDEA treated rats.

Conclusions

Early limited exposure to nitrosamines exacerbates the adverse effects of later chronic high dietary fat intake in promoting T2DM and neurodegeneration. The mechanism involves increased generation of ceramides and probably other toxic lipids in brain.     

The impact of individualised cardiovascular disease (CVD) risk estimates and lifestyle advice on physical activity in individuals at high risk of CVD: a pilot 2 × 2 factorial understanding risk trial

Background

Epidemiological studies have revealed a relationship between early growth restriction and the subsequent development of insulin resistance and type 2 diabetes. Ligation of the uterine arteries in rats mimics uteroplacental insufficiency and serves as a model of intrauterine growth restriction (IUGR) and subsequent developmental programming of impaired glucose tolerance, hyperinsulinemia and adiposity in the offspring. The objective of this study was to investigate the effects of uterine artery ligation on the skeletal muscle expression of insulin receptor and key enzymes of LCFA metabolism.

Methods

Bilateral uterine artery ligation was performed on day 19 of gestation in Sprague-Dawley pregnant rats. Muscle of the posterior limb was dissected at birth and processed by real-time RT-PCR to analyze the expression of insulin receptor, ACCα, ACCβ (acetyl-CoA carboxylase alpha and beta subunits), ACS (acyl-CoA synthase), AMPK (AMP-activated protein kinase, alpha2 catalytic subunit), CPT1B (carnitine palmitoyltransferase-1 beta subunit), MCD (malonyl-CoA decarboxylase) in 14 sham and 8 IUGR pups. Muscle tissue was treated with lysis buffer and Western immunoblotting was performed to assay the protein content of insulin receptor and ACC.

Results

A significant down regulation of insulin receptor protein (p < 0.05) and reduced expression of ACS and ACCα mRNA (p < 0.05) were observed in skeletal muscle of IUGR newborns. Immunoblotting showed no significant change in ACCα content.

Conclusion

Our data suggest that uteroplacental insufficiency may affect skeletal muscle metabolism down regulating insulin receptor and reducing the expression of key enzymes involved in LCFA formation and oxidation.     

Brief Intervention in Type 1 diabetes – Education for Self-efficacy (BITES): Protocol for a randomised control trial to assess biophysical and psychological effectiveness

Background

Studies have shown that metabolic syndrome and its consequent biochemical derangements in the various phases of diabetes may contribute to carcinogenesis. A part of this carcinogenic effect could be attributed to hyperinsulinism. High levels of insulin decrease the production of IGF-1 binding proteins and hence increase levels of free IGF-1. It is well established that bioactivity of free insulin growth factor 1 (IGF-1) increases tumor turnover rate. The objective is to investigate the role of insulin resistance/sensitivity in carcinogenesis by studying the relation between insulin resistance/sensitivity and IGF-1 levels in cancer patients. We postulate that hyperinsulinaemia which prevails during initial phases of insulin resistance (condition prior to overt diabetes) increases bioactivity of free IGF-1, which may contribute to process of carcinogenesis.

Methods/Design

Based on our pilot study results and power analysis of the same, we have designed a two group case-control study. 800 proven untreated cancer patients (solid epithelial cell tumors) under age of 50 shall be recruited with 200 healthy subjects serving as controls. Insulin resistance/sensitivity and free IGF-1 levels shall be determined in all subjects. Association between the two parameters shall be tested using suitable statistical methods.

Discussion

Well controlled studies in humans are essential to study the link between insulin resistance, hyperinsulinaemia, IGF-1 and carcinogenesis. This study could provide insights to the role of insulin, insulin resistance, IGF-1 in carcinogenesis although a precise role and the extent of influence cannot be determined. In future, cancer prevention and treatment strategies could revolve around insulin and insulin resistance.     

Estimating the absorptive root area in Norway spruce by using the common direct and indirect earth impedance methods

Aims

Estimates of root absorption magnitude are needed for the balanced management of forest ecosystems, but no methods able to work on the whole tree and stand level were available. Modified earth impedance method was developed recently and here it was tested, by comparing the results with those obtained by combination of several classical methods.

Methods

We used direct (soil cores, scanning and microscopy) and indirect (sap flow patterns and modified earth impedance) methods in an attempt to estimate the absorptive root area indexes (RAI) at two sites of about 25 and 40-years-old Norway spruce. We considered the geometric surfaces of all scanned fine roots to be equal to the fine root absorptive area (RAI _scan ). To estimate the potentially physically permeable area of fine roots, we microscopically evaluated the point of secondary xylem appearance and calculated the geometric area of root portions with primary structure (RAI _micro ). We termed the area of electrically conductive root surface as the active (ion) absorptive area (RAI _mei ) and measured its extent by the modified earth impedance (MEI) method.

Results

The highest values for absorptive root areas at the two experimental sites we obtained with the scanning method (RAI _scan was considered to be 100%), followed by the RAI _micro (51%) and RAI _mei (32%). RAImei reached about 2/3 of RAImicro. The surface area of the ectomycorrhizal hyphae was an order of magnitude larger than that of all fine roots, but the MEI did not measure such increase.

Conclusions

We showed that the absorptive root area, indirectly estimated by the MEI, provides consistent results that approach the values obtained for fine roots with a primary structure estimated by traditional direct methods. The similar range of the values for the absorptive root surface area obtained by microscopy and by the MEI method indicates that this method is feasible and that it could be used to determine the extent of active absorptive root surface areas in forests.     

Oxidation and reduction of sulfite contribute to susceptibility and detoxification of SO2 in Populus × canescens leaves

Key Message

The critical level for SO ₂ susceptibility of Populus × canescens is approximately 1.2 μL L ^?1 SO ₂ . Both sulfite oxidation and sulfite reduction and assimilation contribute to SO ₂ detoxification.

Abstract

In the present study, uptake, susceptibility and metabolism of SO₂ were analyzed in the deciduous tree species poplar (Populus × canescens). A particular focus was on the significance of sulfite oxidase (SO) for sulfite detoxification, as SO has been characterized as a safety valve for SO₂ detoxification in herbaceous plants. For this purpose, poplar plants were exposed to different levels of SO₂ (0.65, 0.8, 1.0, 1.2 μL L^?1) and were characterized by visible injuries and at the physiological level. Gas exchange parameters (stomatal conductance for water vapor, CO₂ assimilation, SO₂ uptake) of the shoots were compared with metabolite levels (sulfate, thiols) and enzyme activities [SO, adenosine 5′-phosphosulfate reductase (APR)] in expanding leaves (80–90 % expanded). The critical dosage of SO₂ that confers injury to the leaves was 1.2 μL L^?1 SO₂. The observed increase in sulfur containing compounds (sulfate and thiols) in the expanding leaves strongly correlated with total SO₂ uptake of the plant shoot, whereas SO₂ uptake rate was strongly correlated with stomatal conductance for water vapor. Furthermore, exposure to high concentration of SO₂ revealed channeling of sulfite through assimilatory sulfate reduction that contributes in addition to SO-mediated sulfite oxidation to sulfite detoxification in expanding leaves of this woody plant species.     

Serum 25-hydroxyvitamin D is not related to cardiac natriuretic peptide in nulliparous and lactating women

Background

Visceral obesity is positively related to insulin resistance. The nature of the relationship between waist circumference and insulin resistance has not been known in Japanese populations. This study examined the relationship between waist circumference and insulin resistance and evaluated the optimal cutoff point for waist circumference in relation to insulin resistance in middle-aged Japanese men.

Methods

Study subjects included 4800 Japanese men aged 39 to 60 years. Insulin resistance was evaluated by the homeostasis model assessment of insulin resistance (HOMA-IR). The relationship of waist circumference with HOMA-IR was assessed by use of adjusted means of HOMA-IR and odds ratios of elevated HOMA-IR defined as the highest quintile (≥2.00). Receiver operating characteristics (ROC) curve analysis using Youden index and the area under curve (AUC) was employed to determine optimal cutoffs of waist circumference in relation to HOMA-IR.

Results

Adjusted geometric means of HOMA-IR and prevalence odds of elevated HOMA-IR were progressively higher with increasing levels of waist circumference. In the ROC curve analysis, the highest value of Youden index was obtained for a cutoff point of 85 cm in waist circumference across different values of HOMA-IR. Multiple logistic regression analysis also indicated that the AUC was consistently the largest for a waist circumference of 85 cm.

Conclusion

Waist circumference is linearly related to insulin resistance, and 85 cm in waist circumference is an optimal cutoff in predicting insulin resistance in middle-aged Japanese men.     

Sex-specific outcomes of diabetic patients with acute myocardial infarction who have undergone percutaneous coronary intervention: a register linkage study

Background

Chronic arterial stiffness contributes to the negative health effects of obesity and insulin resistance, which include hypertension, stroke, and increased cardiovascular and all-cause mortality. Weight loss and improved insulin sensitivity are individually associated with improved central arterial stiffness; however, their combined effects on arterial stiffness are poorly understood. The purpose of this study was to determine how insulin levels modify the improvements in arterial stiffness seen with weight loss in overweight and obese young adults.

Methods

To assess the effects of weight loss and decreased fasting insulin on vascular stiffness, we studied 339 participants in the Slow the Adverse Effects of Vascular Aging (SAVE) trial. At study entry, the participants were aged 20?C45, normotensive, non-diabetic, and had a body-mass index of 25?C39.9?kg/m². Measures of pulse wave velocity (PWV) in the central (carotid-femoral (cfPWV)), peripheral (femoral-ankle (faPWV)), and mixed (brachial-ankle (baPWV)) vascular beds were collected at baseline and 6?months. The effects of 6-month change in weight and insulin on measures of PWV were estimated using multivariate regression.

Results

After adjustment for baseline risk factors and change in systolic blood pressure, 6-month weight loss and 6-month change in fasting insulin independently predicted improvement in baPWV but not faPWV or cfPWV. There was a significant interaction between 6-month weight change and change in fasting insulin when predicting changes in baPWV (p?<?0.001). Individuals experiencing both weight loss and insulin reductions showed the greatest improvement in baPWV.

Conclusions

Young adults with excess weight who both lower their insulin levels and lose weight see the greatest improvement in vascular stiffness. This improvement in vascular stiffness with weight loss and insulin declines may occur throughout the vasculature and may not be limited to individual vascular beds.

Trial registration

NCT00366990