Markers Of Insulin Sensitivity Research Articles

RETRACTED ARTICLE: Different Aspects of Sartan + Calcium Antagonist Association Compared to the Single Therapy on Inflammation and Metabolic Parameters in Hypertensive Patients

This study aims to evaluate the effects of an angiotensin receptor blocker (ARB)/calcium channel blocker combination on blood pressure control, lipid profile, insulin sensitivity, and inflammation markers. We randomized 276 hypertensive patients to olmesartan 20 mg, amlodipine 10 mg, or a single pill containing an olmesartan/amlodipine combination 20/5 mg for 12 months. We evaluated the following: body weight, systolic and diastolic blood pressure, fasting plasma glucose, fasting plasma insulin (FPI), M value, lipid profile, adiponectin (ADN), high sensitivity C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor-1β (MIP-1β). Olmesartan/amlodipine combination better reduced blood pressure, FPI, homeostasis model assessment index, and increased M value and ADN compared to olmesartan and amlodipine monotherapies. Olmesartan/amlodipine significantly decreased Hs-CRP, MCP-1, and MIP-1β. In this multicenter, randomized, double-blind, clinical study, ARB/calcium antagonist combination resulted to be more effective than single monotherapies in reducing blood pressure, in improving insulin sensitivity, and in reducing inflammation parameters in patients with stage I essential hypertension.

Taurine‐induced insulin signalling improvement of obese malnourished mice is associated with redox balance and protein phosphatases activity modulation

Obese protein malnourished mice display liver insulin resistance and taurine (TAU) seems to attenuate this effect. The association between early-life malnutrition and hepatic redox balance in diet-induced insulin resistance is unknown. We investigated TAU supplementation effects upon liver redox state and insulin signalling in obese protein malnourished mice. Weaned male C57BL-6 mice were fed a control (14% protein - C) or a protein-restricted diet (6% protein - R) for 6 weeks. Afterwards, mice received a high-fat diet (34% fat - HFD) for 8 weeks (CH - RH). Half of the HFD-mice were supplemented with TAU (5%) throughout the treatment (CHT - RHT). Body and tissues' weight, respiratory quotient (RQ), glucose tolerance and insulin sensitivity, hepatic oxidant and antioxidant markers and insulin cascade proteins were assessed. Protein restriction leads to typical features whereas HFD was able to induce a catch-up growth in RH. HFD-groups showed higher energy intake and adiposity, lower energy expenditure and altered RQ. Glucose tolerance and insulin sensitivity were impaired in HFD-groups and TAU attenuated these effects. H2 O2 content was increased in CHT and RHT despite no differences in antioxidant enzymes and GSH concentration. AKT and PTEN phosphorylation were significantly increased in CHT but not in RHT. Our data provide evidence for an association between TAU-induced improved glycaemic control because of PTEN inactivation and higher AKT phosphorylation. These effects seem to be related with altered hepatic redox balance in obese mice, and this effect is impaired by protein malnutrition.

Serum IL-18 and hsCRP correlate with insulin resistance without effect of calcitriol treatment on type 2 diabetes.

Chronic low-grade systemic inflammation presented in Type 2 diabetes mellitus plays a major role in disease progression as well as development of micro- and macro-vascular complications of diabetes. Therefore, reducing inflammation can be beneficial in prevention of diabetes complications. To investigate the association between insulin resistance and inflammatory markers, and assessing the effects of oral Calcitriol on inflammatory cytokines in type 2 diabetic patients. In this double-blind randomized placebo-controlled trial, 70 participants with type-2 diabetes were randomly divided to two groups. One group received two capsules of Calcitriol (0.25 μg 1,25-dihydroxy cholecalciferol per each capsule) per day. The second group received placebo tablets. At the beginning of the study, we assessed insulin resistance and its relation to inflammatory profile. Serum high sensitive C-reactive protein (hs CRP), interleukin-6 and interleukin-18 were also measured at the beginning and the end of the 12-week supplementation trial. Mean calcium, phosphorus and vitamin D concentrations in the study participants were 8.98 ± 0.79 mg/dL, 3.86 ± 0.50 mg/dL and 40.91 ± 30.9 ng/mL, respectively. IL-18 and hsCRP had significant positive associations with insulin resistance markers and negative associations with insulin sensitivity markers. At the end of the 12-week supplementation trial, no significant difference was seen in serum levels of hsCRP, IL-6 and IL-18 between the two groups, while these values were adjusted for baseline values. Inflammation was associated with insulin resistance in diabetic patients. No anti-inflammatory effect of Calcitriol in terms of decreasing hsCRP, IL-6 and IL-18 detected.

Liver enzymes but not free fatty acid levels predict markers of insulin sensitivity in overweight and obese, nondiabetic adults

Although obesity is a key predisposing risk factor in the development of insulin resistance (IR) and type 2 diabetes mellitus, not all obese individuals develop IR. This study aimed to identify key anthropometric and biochemical parameters that predict insulin sensitivity in overweight and obese adults. Based on previous literature, we hypothesized that markers of insulin sensitivity would be negatively correlated with plasma concentrations of free fatty acids and liver enzymes. Forty nondiabetic adult participants (body mass index ≥25.0kg/m2) were recruited. Data collection included anthropometric measurements and fasting plasma samples for the quantification of liver enzymes (alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase), blood lipid profile, and markers of insulin sensitivity. Questionnaires relating to dietary intake, physical activity, and fatigue were also completed. Insulin and Homeostasis Model of Assessment (HOMA) scores were significantly correlated with indirect measures of central obesity (P < .05). Glycosylated hemoglobin, insulin, and HOMA scores for IR were all positively correlated with selected liver function markers (P < .05). Scores of HOMA-IR were significantly positively correlated with plasma phospholipid levels of n-3 fatty acids (P = .04) and ratio of n-3/n-6 fatty acids (P < .05) and negatively correlated with n-6 fatty acids (P = .03). No significant correlations were found between markers of insulin sensitivity and cholesterol levels, physical activity, or self-reported fatigue. These results have reinforced the integral role of liver function in the development of IR. Despite previous data linking elevations in free fatty acid to the development of IR, we found no relationship between these variables in this study.

Validation of HOMA2S in acute phase of myocardial infarction, based on euglycemic-hyperinsulinemic clamp

Introduction: Insulin sensitivity (IS) has an important role in endothelial function, thrombogenesis and therefore the risk of further cardiovascular events in stress situations such as myocardial infarction (MI). The Homeostasis Modeling Assessment (HOMA2S) allows to measure the IS of more practical compared to the euglycemic-hyperinsulinemic clamp - considered the gold standard method in the evaluation of SI. But the HOMA2S has been validated only for situations of metabolic stability, but not for stress situations. Objectives: The study aims to validate the HOMA2S to situations of metabolic instability such as the acute phase of MI. Methods: We performed hyperinsulinemic-euglycemic clamps in 40 nondiabetic patients from the prospective cohort Brazilian Heart Study (BHS), admitted within the first 24 hours of symptoms of ST-segment elevation MI. The clamps were performed at the second (D2) (n = 40) and sixth day (D6) (n = 16) after MI. In addition, basal (12 hour-fasting) blood samples on D2 and D6 were used to evaluated blood glucose levels, insulinaemia and subsequently calculate HOMA2S. Statistical analysis: For the comparative analysis between HOMA2S and IS determined by clamp (ISclamp), linear regressions and ROC curve were performed. Furthermore, we used Bland-Altman analysis to determine whether there was systematic errors. Results: Linear regressions showed statistical significance between ISclamp and HOMA2S in D2 (R = 0.47, p = 0.004), HOMA2S in D6 (R = 0.54, p = 0.003) and the combined HOMA2S in D2 and D6 (R = 0.52, p <0.001). The Bland-Altman graph showed no significant systematic bias. In the ROC curves for discrimination of ISclamp in D2 and D6 above the 66th percentile, we obtained an area under the curve of 0.80 (95% CI 0.68 to 0.92, p <0.001). In the best cutoff point of the ROC curve, for a sensitivity of 75% we obtained a specificity of 83%. Conclusion: Based on the comparison with the euglycemic-hyperinsulinemic clamp, the HOMA2S can also be used in the acute phase of MI as a reliable marker of IS.

Filter paper blood spot enzyme linked immunoassay for adiponectin and application in the evaluation of determinants of child insulin sensitivity.

BackgroundAdiponectin is an adipocyte-derived hormone that acts as a marker of insulin sensitivity. Bloodspot sampling by fingerstick onto filter paper may increase the feasibility of large-scale studies of the determinants of insulin sensitivity. We first describe the validation of an enzyme-linked immunoassay (ELISA) for quantifying adiponectin from dried blood spots and then demonstrate its application in a large trial (PROBIT).MethodsWe quantified adiponectin from 3-mm diameter discs (≈3 µL of blood) punched from dried blood spots obtained from: i) whole blood standards (validation); and ii) PROBIT trial samples (application) in which paediatricians collected blood spots from 13,879 children aged 11.5 years from 31 sites across Belarus. We examined the distribution of bloodspot adiponectin by demographic and anthropometric factors, fasting insulin and glucose.ResultsIn the validation study, mean intra-assay coefficients of variation (n = 162) were 15%, 13% and 10% for ‘low’ (6.78 µg/ml), ‘medium’ (18.18 µg/ml) and 'high’ (33.13 µg/ml) internal quality control (IQC) samples, respectively; the respective inter-assay values (n = 40) were 23%, 21% and 14%. The correlation coefficient between 50 paired whole bloodspot versus plasma samples, collected simultaneously, was 0.87 (95% CI: 0.78 to 0.93). Recovery of known quantities of adiponectin (between 4.5 to 36 µg/ml) was 100.3–133%. Bloodspot adiponectin was stable for at least 30 months at −80°C. In PROBIT, we successfully quantified fasting adiponectin from dried blood spots in 13,329 of 13,879 (96%) children. Mean adiponectin (standard deviation) concentrations were 17.34 µg/ml (7.54) in boys and 18.41 µg/ml (7.92) in girls and were inversely associated with body mass index, fat mass, triceps and subscapular skin-fold thickness, waist circumference, height and fasting glucose.ConclusionsBloodspot ELISA is suitable for measuring adiponectin in very small volumes of blood collected on filter paper and can be applied to large-scale studies.

Racial/Ethnic differences in clinical and biochemical type 2 diabetes mellitus risk factors in children

ObjectiveTo examine whether peri-adolescent children demonstrate the significant racial/ethnic differences in body fatness relative to BMI and in the prevalence and relationship of body composition to risk factors for type 2 diabetes (T2DM) as in adults.Design and MethodsWe examined family history of obesity and T2DM, anthropometry, insulin sensitivity and secretory capacity, lipids, and cytokines (IL-6, CRP, TNF-α, and adiponectin) in a cohort of 994 middle school students (47% male, 53%, female; 12% African American, 14% East Asian, 13% South Asian, 9% Caucasian, 44% Hispanic, and 8% other).ResultsFractional body fat content was significantly greater at any BMI among South Asians. There were racial/ethnic specific differences in lipid profiles, insulin secretory capacity, insulin sensitivity, and inflammatory markers corrected for body fatness that are similar to those seen in adults. Family history of T2DM was associated with lower insulin secretory capacity while family history of obesity was more associated with insulin resistance.ConclusionChildren show some of the same racial/ethnic differences in risk factors for adiposity-related co-morbidities as adults. BMI and waist circumference cutoffs to identify children at-risk for adiposity-related co-morbidities should be adjusted by racial/ethnic group as well as other variables such as birthweight and family history.

Evaluation of safety and efficacy of a fixed olmesartan/amlodipine combination therapy compared to single monotherapies

Background: Hypertension is known to be one of the main risk factors for cardiovascular disease.Objectives: To evaluate the safety and efficacy of a fixed olmesartan/amlodipine (Olme/Amlo) combination in improving blood pressure control, lipid profile, insulin sensitivity and some inflammatory and insulin resistance markers.Two hundred and seventy-six hypertensive patients were randomly assigned to olmesartan 20 mg, amlodipine 10 mg or a single pill containing an Olme/Amlo combination 20/5 mg for 12 months. We evaluated after 6 and 12 months: body weight, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP, respectively), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, vaspin, visfatin, interleukins 8 and 10 (IL-8 and IL-10, respectively). Patients also underwent an euglycemic, hyperinsulinemic clamp.Results: Olme/Amlo combination was more effective in decreasing SBP, and DPB compared to single monotherapies after 12 months. Olme/Amlo combination, but not amlodipine, decreased FPG after 12 months. FPI and HOMA index were decreased, and M value increased by Olme/Amlo combination compared to olmesartan monotherapy, and to amlodipine monotherapy. Olme/Amlo significantly decreased IL-8 and IL-10 better than each monotherapy.Conclusions: Olme/Amlo single pill combination can be a safe and effective option to reduce blood pressure, improve insulin sensitivity and decrease inflammatory markers.

Pre-Pubertal Children Born Post-Term Have Reduced Insulin Sensitivity and Other Markers of the Metabolic Syndrome

BackgroundThere are no data on the metabolic consequences of post-term birth (≥42 weeks gestation). We hypothesized that post-term birth would adversely affect insulin sensitivity, as well as other metabolic parameters and body composition in childhood.Methods77 healthy pre-pubertal children, born appropriate-for-gestational-age were studied in Auckland, New Zealand: 36 born post-term (18 boys) and 41 (27 boys) born at term (38–40 weeks gestation). Primary outcome was insulin sensitivity measured using intravenous glucose tolerance tests and Bergman’s minimal model. Other assessments included fasting hormone concentrations and lipid profiles, body composition from whole-body dual-energy X-ray absorptiometry, 24-hour ambulatory blood pressure monitoring, and inflammatory markers.ResultsInsulin sensitivity was 34% lower in post-term than in term children (7.7 vs. 11.6 x10-4·min-1·(mU/l); p<0.0001). There was a compensatory increase in acute insulin response among post-term children (418 vs 304 mU/l; p=0.037), who also displayed lower glucose effectiveness than those born at term (2.25 vs 3.11 x10-2·min-1; p=0.047). Post-term children not only had more body fat (p=0.014) and less fat-free mass (p=0.014), but also had increased central adiposity with more truncal fat (p=0.017) and greater android to gynoid fat ratio (p=0.007) compared to term controls. Further, post-term children displayed other markers of the metabolic syndrome: lower normal nocturnal systolic blood pressure dipping (p=0.027), lower adiponectin concentrations (p=0.005), as well as higher leptin (p=0.008) and uric acid (p=0.033) concentrations. Post-term boys (but not girls) also displayed a less favourable lipid profile, with higher total cholesterol (p=0.018) and LDL-C (p=0.006) concentrations, and total cholesterol to HDL-C ratio (p=0.048).ConclusionsPost-term children have reduced insulin sensitivity and display a number of early markers of the metabolic syndrome. These findings could have important implications for the management of prolonged pregnancies. Future studies need to examine potential impacts later in life, as well as possible underlying mechanisms.

Nutritional mismatch in postnatal life of low birth weight rat offspring leads to increased phosphorylation of hepatic eukaryotic initiation factor 2 α in adulthood

ObjectiveEpidemiological studies have established that low birth weight offspring, when faced with a nutritional mismatch in postnatal life, have an increased risk of developing the metabolic syndrome. Our laboratory and others have demonstrated that maternal protein restriction (MPR) leads to high cholesterol and insulin resistance in the offspring due to impaired liver function, though the underlying molecular mechanisms remain elusive. Recent in vitro studies have associated decreased phosphorylation of Akt1 (Serine 473), a marker of insulin sensitivity, with increased phosphorylation of eukaryotic initiation factor (eIF)-2α (Serine 51), a key regulator of protein translation attenuation. The main aim of the study was to determine whether nutritional mismatch in MPR offspring leads to elevated phospho-eIF2α (Ser51) levels in the liver. Materials/MethodsTo investigate if this occurs long-term in MPR offspring, pregnant Wistar rats were fed a control (20%) protein diet (control) or a low (8%) protein diet during pregnancy and postnatal life (LP1), or during pregnancy and lactation (LP2). ResultsAt postnatal day 130, LP2 offspring exhibited increases in hepatic phosphorylation of eIF2α (Ser51) concomitant with decreases in the phosphorylation of Akt1 (Ser473), while LP1 offspring exhibited the converse relationship. Interestingly, in embryonic day 19 livers derived from control or MPR pregnancy, no changes in eIF2α (Ser51) or Ak1 (Ser473) phosphorylation were observed. ConclusionCollectively, our data provide robust evidence that phosphorylation of eIF2α (Ser51) is inversely correlated with phosphorylated Akt1 (Ser473) in vivo. Moreover, this study demonstrates that this inverse relationship is adversely influenced in these MPR offspring by a mismatch in the postnatal nutritional environment.

Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis

The osteoblast-derived hormone osteocalcin promotes testosterone biosynthesis in the mouse testis by binding to GPRC6A in Leydig cells. Interestingly, Osteocalcin-deficient mice exhibit increased levels of luteinizing hormone (LH), a pituitary hormone that regulates sex steroid synthesis in the testes. These observations raise the question of whether LH regulates osteocalcin's reproductive effects. Additionally, there is growing evidence that osteocalcin levels are a reliable marker of insulin secretion and sensitivity and circulating levels of testosterone in humans, but the endocrine function of osteocalcin is unclear. Using mouse models, we found that osteocalcin and LH act in 2 parallel pathways and that osteocalcin-stimulated testosterone synthesis is positively regulated by bone resorption and insulin signaling in osteoblasts. To determine the importance of osteocalcin in humans, we analyzed a cohort of patients with primary testicular failure and identified 2 individuals harboring the same heterozygous missense variant in one of the transmembrane domains of GPRC6A, which prevented the receptor from localizing to the cell membrane. This study uncovers the existence of a second endocrine axis that is necessary for optimal male fertility in the mouse and suggests that osteocalcin modulates reproductive function in humans.

Effect of fish oil on circulating adiponectin: a systematic review and meta-analysis of randomized controlled trials.

Seafood long-chain polyunsaturated omega-3 fatty acids (n-3 PUFAs) improve insulin sensitivity in animal experiments, but findings remain inconsistent in humans. Adiponectin is a robust marker for insulin sensitivity and adipocyte function. Whether n-3 PUFAs affect adiponectin in humans is unknown. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the objective of the study was to perform a systematic review and meta-analysis of randomized, placebo-controlled clinical trials (RCTs) to determine the effect of n-3 PUFA consumption on circulating adiponectin in humans. MEDLINE, EMBASE, CABI (CAB abstracts), Cochrane Central Registry of Controlled Trials, ClinicalTrials.gov, SIGLE, and Faculty of 1000 were searched through to June 2012, supplemented with author contact and reference list searches. RCTs of either fish oil supplementation or isocaloric fish meal feeding that evaluated adiponectin as an outcome were selected for the study. Two investigators independently extracted the data. Effect estimates were pooled using inverse-variance weighted, random-effects meta-analysis. Heterogeneity was assessed by the I(2) and Q statistic. Prespecified sources of heterogeneity were investigated by meta-regression. Publication bias was assessed using funnel plots and Egger's test. Of 110 studies, 14 RCTs met inclusion criteria. Fourteen trial arms evaluated fish oil (fish oil, n = 682; placebo, n = 641). Fish oil increased adiponectin by 0.37 μg/mL [95% confidence interval (CI) 0.07; 0.67, P = .02]. Although effects in 11 of 14 trials were 0 or greater, statistical heterogeneity was evident (I(2) = 72.9%), unexplained by n-3 PUFA dose or duration, study quality score, study location, or baseline body mass index (meta-regression P > .05 each). The funnel plot was asymmetric in favor of smaller trials with greater effects (Egger's P = .11); the fill-and-trim method suggested a theoretical pooled effect of 0.18 μg/mL (95% CI -0.15; +0.52, P = .28). Only 2 trial arms evaluated fish feeding (n = 136 intervention and 68 control subjects), for which the pooled effect on adiponectin was not statistically significant (-0.01 μg/mL, 95% CI -0.65; 0.64, P = 0.99), although CIs were broad due to the small number of subjects. In placebo-controlled RCTs, fish oil moderately increases circulating adiponectin, although with unexplained heterogeneity as well as potential publication bias. These findings provide no evidence for harm and support possible benefits of n-3 PUFA consumption on insulin sensitivity and adipocyte function.

Two Weeks of Reduced Activity Decreases Leg Lean Mass and Induces “Anabolic Resistance” of Myofibrillar Protein Synthesis in Healthy Elderly

Alterations in muscle protein metabolism underlie age-related muscle atrophy. During periods of muscle disuse, muscle protein synthesis is blunted, and muscle atrophy occurs in young and old. The impact of a short reduction in physical activity on muscle protein metabolism in older adults is unknown. The aim of this study was to investigate the impact of 14 days of reduced daily steps on fasted and fed-state rates of myofibrillar protein synthesis (MPS) to provide insight into the mechanisms for changes in muscle mass and markers of metabolic health. Before and after 14 days of reduced daily step-count, 10 healthy older adults (age, 72 ± 1 y) underwent measures of insulin sensitivity, muscle strength, physical function, and body composition. Using a primed constant infusion of L-[ring-(13)C6]phenylalanine with serial muscle biopsies, basal, postabsorptive, and postprandial rates of MPS were determined before and after the 14-day intervention. Daily step-count was reduced by approximately 76% to 1413 ± 110 steps per day. Leg fat-free mass was reduced by approximately 3.9% (P < .001). Postabsorptive insulin resistance was increased by approximately 12%, and postprandial insulin sensitivity was reduced by approximately 43% after step reduction (P < .005). Concentrations of TNF-α and C-reactive protein were increased by approximately 12 and 25%, respectively, after step reduction (P < .05). Postprandial rates of MPS were reduced by approximately 26% after the intervention (P = .028), with no difference in postabsorptive rates. The present study demonstrates that 14 days of reduced steps in older adults induces small but measurable reductions in muscle mass that appear to be underpinned by reductions in postprandial MPS and are accompanied by impairments in insulin sensitivity and systemic inflammatory markers and postprandial MPS.

A Moderate‐Fat Diet with Pistachios Lowers Small‐Dense LDL and Improves Markers of Insulin Sensitivity in Subjects with Moderately‐Elevated Cholesterol Levels

We evaluated the dose‐response effects of pistachios over 4 weeks, on markers of insulin sensitivity in individuals (N=28) with moderately elevated LDL‐C (&gt;; 110 mg/dl). Three test diets (SFA ≈ 8%; cholesterol &lt; 300 mg/dl) were fed in this crossover study: control (25% total fat); 10% of energy from pistachios (1PD; 32–63 g; 30% total fat); or 20% of energy from pistachios (2PD; 63–126 g; 34% total fat). A Western run‐in diet (35% total fat, 11% SFA) was fed for 2 weeks; subjects had a mean BMI of 26.8 ± 0.7 kg/m2 and were weight stable while on the study. There was a significant diet effect on small‐dense LDL (sdLDL) levels (P = 0.001); sdLDL decreased on the 2PD versus the 1PD (P = 0.03) and the 2PD versus control (P = 0.001). There also was a significant diet effect for the TG/HDL‐C ratio (P = 0.041), with a significant reduction on the 2PD versus control (P = 0.036). Reductions in sdLDL levels were significantly correlated with reductions in TG levels (r = 0.424; P = 0.025); changes were calculated as the difference between baseline and post 2PD treatment. There were no significant diet effects for HDL‐C levels when comparing the pistachio diets to control, but there were trends for diet effects on increasing levels of functional α‐1 (P = 0.073) and α‐2 (P = 0.056) HDL particles. Pistachio inclusion in a moderate‐fat diet (≈ 35%) favorably affects insulin sensitivity and contributes to a beneficial cardio‐metabolic profile.Grant Funding Source: American Pistachio Growers

Polyphenol supplementation ameliorates PUFA benefits in metabolic and oxidative status in dogs

The effect of PUFA on obesity‐associated oxidant stress could be explained by the stimulation of endogenous antioxidant processes, or by their own ability to be oxidized. The adjunction of antioxidant to PUFA could help to elucidate their mechanism of action.Our aim was to check the effects of PUFA supplementation w/wo curcumin polyphenols on metabolic status, plasma lipids, and antioxidant status in dogs.Obese dogs were given for 2 consecutive periods of 6 w hyperenergetic diet supplemented with either n‐3 PUFA (Diet1) then n‐3 PUFA plus curcumin (Diet2). Before (T0) and at the end of each 6‐wk period, body composition, insulin sensitivity (IS), plasma lipid and oxidative status markers (total antioxidant status, TAS and glutathione peroxidise, GPx) were determined.At the end of both periods, body composition and IS were did not differ from T0 values. At the end of Diet1, plasma NEFA were lower and total cholesterol was higher than at T0; at the end of Diet2, TG levels were lower. The TAS was higher than at T0 at the end of Diet1, and even more at the end of Diet2. Compared to T0 GPx activity was unchanged at the end of each period.Our results show that polyphenols could have synergistic effects with PUFA. This suggests that PUFA would not act as oxidation substrates. Indeed their protection against oxidation would account for their action. Further experiments could be helpful for a better understanding of the mechanism of action.

Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: a randomized controlled trial

Obese adolescents are at a greater risk of vitamin D deficiency because vitamin D is thought to be sequestered by excess adipose tissue. Poor vitamin D status has been associated with a higher prevalence of the metabolic syndrome, type 2 diabetes, or both in adults and adolescents. The objective was to determine in obese adolescents the efficacy and safety of 4000 IU vitamin D3/d and whether subsequent increased circulating concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with improved markers of insulin sensitivity and resistance and reduced inflammation. Obese adolescent patients [n = 35; mean ± SD age: 14.1 ± 2.8 y; BMI (in kg/m(2)): 39.8 ± 6.1; 25(OH)D: 19.6 ± 7.1 ng/mL] were recruited from the University of Missouri Adolescent Diabetes and Obesity Clinic and were randomly assigned to receive either vitamin D3 (4000 IU/d) or placebo as part of their standard care. Anthropometric measurements, inflammatory markers (IL-6, TNF-α, C-reactive protein), adipokines (leptin, adiponectin), fasting glucose, fasting insulin, and HOMA-IR values were measured at baseline and at 2 follow-up visits (3 and 6 mo). After 6 mo, there were no significant differences in BMI, serum inflammatory markers, or plasma glucose concentrations between groups. Participants supplemented with vitamin D3 had increases in serum 25(OH)D concentrations (19.5 compared with 2.8 ng/mL for placebo; P < 0.001), fasting insulin (-6.5 compared with +1.2 μU/mL for placebo; P = 0.026), HOMA-IR (-1.363 compared with +0.27 for placebo; P = 0.033), and leptin-to-adiponectin ratio (-1.41 compared with +0.10 for placebo; P = 0.045). Inflammatory markers remained unchanged. The correction of poor vitamin D status through dietary supplementation may be an effective addition to the standard treatment of obesity and its associated insulin resistance. This trial was registered at clinicaltrials.gov as NCT00994396.

Commentary on: effect of vitamin D on insulin resistance and anthropometric parameters in type 2 diabetes; a randomized double-blind clinical trial

Dear Editor-in-Chief I read with interest the published article in the esteemed journal by Heshmat et al., entitled “effect of vitamin D on insulin resistance and anthropometric parameters in type 2 diabetes; a randomized double-blind clinical trial” [1]. The study has focused to investigate the effect of injection of vitamin D on insulin resistance and anthropometric parameters in type 2 diabetes mellitus (T2DM) [1]. Heshmat et al. studied 42 diabetic patients with similar baseline characteristics in two groups; intervention group with single intramuscular injection of 300,000 IU of vitamin D3 and the placebo group. They found that, 3 months after vitamin D injection, HbA1c, anthropometric factors and homeostasis model assessment (HOMA) index in intervention group stayed constant, however, serum 25- OHD3 was significantly increased. They suggested that, single injection of vitamin D was not accompanied by better diabetes control and improvement of insulin resistance [1]. Similar to this study, we conducted a double blind randomized clinical trial on 60 T2DM patients who were divided into 2 groups with 30 patients in each [2]. Group 1 were treated with oral Vitamin D, and group 2 were treated with placebo drug. After 3 months of treatment intervention, no significant difference of serum HbA1c and lipids between two groups was found. We concluded that, weekly vitamin D supplementation for 12 weeks had not significant decremented effect on HbA1c and lipid profiles [2]. Studies concerning the beneficial effects of vitamin D supplementation on improvement of diabetes or improvement of insulin sensitivity are limited and revealed different results. To find, whether receiving vitamin D3 (4000 IU/d) is associated with improved markers of insulin sensitivity and resistance, and also reduced inflammation in obese adolescents, Belenchia et al. studied participants who have supplemented with vitamin D3 for 6 months. They found a significant increase in serum 25-hydroxyvitamin D concentrations after this period. However, there were no significant differences in body mass index, serum inflammatory markers or plasma glucose concentrations in comparison to control group. Moreover, inflammatory markers remained unchanged [3]. Meanwhile, in the study conducted by Lim et al., on 1080 non-diabetic Korean subjects, it was found that 25(OH)D baseline is associated with the incidence of T2DM in high-risk subjects for up to 5 years of follow-up, independently of obesity, baseline insulin resistance, and β cell function [4]. Furthermore, to test the association of low plasma 25-hydroxyvitamin D with increased risk of T2DM in the general population, Afzal et al. measured 25-hydroxyvitamin D level in 9841 participants from the general population, of whom 810 developed type 2 diabetes during 29 years of follow-up. They found the association of low plasma 25-hydroxyvitamin D with increased risk of T2DM [5]. Prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide [6-11] and based on increasing evidence from animal and human studies, vitamin D deficiency is now regarded as a potential T2DM risk factor [12-18]. Hence, the present data is not convincing and further studies with large sample sizes are needed to show the definite effect of vitamin D supplementation on control of diabetes and its risk.

Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome – a randomized study (SYSDIET)

BackgroundDifferent healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome.MethodsWe conducted a randomized dietary study lasting for 18–24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m−2, 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids.ResultsBody weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (−0.18, mmol L−1 95% CI −0.35; −0.01, P = 0.04), LDL to HDL cholesterol (−0.15, −0.28; −0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (−0.04, −0.07; −0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference −84, −133; −37 ng L−1, P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, −0.23, −0.41; −0.05, P = 0.012) were associated with IL-1 Ra.ConclusionsHealthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.

Visceral fat resection in humans: Effect on insulin sensitivity, beta‐cell function, adipokines, and inflammatory markers

The visceral fat is linked to insulin resistance, the metabolic syndrome, type 2 diabetes and an increased cardiovascular risk, but it is not clear whether it has a causative role. Surgical resection of this fat depot is a research model to address this issue. Twenty premenopausal women with metabolic syndrome and grade III obesity were randomized to undergo Roux-en-Y gastric bypass (RYGBP) either alone or combined with omentectomy. Insulin sensitivity (IS; euglycemic-hyperinsulinemic clamp), acute insulin response to glucose (AIR; intravenous glucose tolerance test), disposition index (DI = AIR × IS measured by clamp), lipid profile, adipokine profile (leptin, adiponectin, resistin, visfatin, interleukin-6, TNF-α, MCP-1), ultra-sensitive C-reactive protein (CRP), body composition, and abdominal fat echography were assessed prior to surgery and 1, 6, and 12 months post-surgery. Omentectomy was associated with greater weight loss at all time points. IS improved similarly in both groups. Omentectomy was associated to lower CRP after 12 months, but it did not influence adipokines and other metabolic parameters. Among non-diabetic subjects, omentectomy was associated with a preservation of baseline AIR after 12 months (as opposed to deterioration in the control group) and a greater DI after 6 and 12 months. Although omentectomy did not enhance the effect of RYGBP on insulin sensitivity and adipokines, it was associated with a preservation of insulin secretion, a greater weight loss, and lower CRP.

Insulin sensitivity, androgens and isotretinoin therapy in women with severe acne

Background: Androgens appear to play a role in the development of acne, and presence of acne is a potential marker of hyperandrogenism. Objective: The authors evaluated androgens and insulin sensitivity markers before and after treatment with isotretinoin in women with post-adolescent severe acne who do not have hirsutism and/or ovulatory dysfunction. Methods: Androgens, lipids, glucose and insulin levels were measured in 26 patients and 21 controls during oral glucose tolerance test. Homeostasis model assessment for insulin resistance, area under curve (AUC)glucose and AUCinsulin were calculated. Twenty patients completed a minimum of 6-month isotretinoin treatment. Results: All studied parameters were similar in patients and controls at baseline. Isotretinoin therapy increased body mass index and triglyceride levels without any effect on androgens or insulin sensitivity. Conclusion: Severe acne itself is not associated with hyperandrogenemia and/or insulin resistance. Isotretinoin treatment does not alter serum androgens or insulin sensitivity, although it increases body weight and serum triglycerides.