Homeostatic Assessment Of Insulin Resistance Research Articles

Gut permeability is associated with lower insulin sensitivity in youth living with perinatally-acquired HIV.

The relationships between alterations in the intestinal barrier, and bacterial translocation with the development of metabolic complications in youth with perinatally-acquired HIV (YPHIV) have not been investigated. The PHACS Adolescent Master Protocol enrolled YPHIV across 15 U.S. sites, including Puerto Rico, from 2007-2009. For this analysis, we included YPHIV with HIV viral load ≤1000 c/mL, with at least one measurement of homeostatic assessment of insulin resistance (HOMA-IR) or non-high density lipoprotein (non-HDLc) between baseline and year 3 and plasma levels of intestinal fatty-acid binding protein (I-FABP), lipopolysaccharide binding protein (LBP), and zonulin levels at baseline. We fit linear regression models using generalized estimating equations to assess the association of baseline log10 gut markers with log10 HOMA-IR and non-HDLc at all timepoints. HOMA-IR or non-HDLc was measured in 237, 189, and 170 PHIV at baseline, Yr2, and Yr3, respectively. At baseline, median age (Q1, Q3) was 12 yrs (10, 14), CD4 count was 762 cells/mm3 (574, 984); 90% had HIV RNA <400 c/mL. For every 10-fold higher baseline I-FABP, HOMA-IR dropped 0.85-fold at baseline and Yr2. For a 10-fold higher baseline zonulin, there was a 1.35-fold increase in HOMA-IR at baseline, 1.23-fold increase in HOMA-IR at Yr2, and 1.20-fold increase in HOMA-IR at Yr3 in adjusted models. For a 10-fold higher baseline LBP, there was a 1.23-fold increase in HOMA-IR at baseline in the unadjusted model, but this was slightly attenuated in the adjusted model. Zonulin was associated with non-HDLc at baseline, but not for the other time points. Despite viral suppression, intestinal damage may influence downstream insulin sensitivity in YPHIV.

Serum Levels of Activin A: Predictor of Insulin Resistance and Atherosclerosis in Prediabetics.

Pathological effects of dysglycemia and insulin resistance on atherosclerosis and cardiac remodeling starts as early as in the prediabetic state before the onset of overt diabetes. Activin A is a molecule with multiple functions, including an important part in glucose homeostatic mechanisms as well as inflammatory processes and is therefore being researched as a useful novel biomarker for prompt recognition of the risk of cardiovascular disease (CVD) in prediabetic individuals, thereby helping in disease prognostication and early institution of therapeutic measuresObjective: The study aimed to measure serum levels of activin A in prediabetic patients and evaluate them in comparison to normoglycemic controls. The association of activin A with carotid intima media thickness (CIMT), left ventricular diastolic dysfunction (LVDD), and homeostatic assessment of insulin resistance (HOMA-IR) was also studiedMaterials and methods: A total of 60 prediabetic cases and 60 normoglycemic control subjects [matched as per age, gender, and body mass index (BMI)] were recruited. Measurement of serum glucose levels (fasting and postprandial) and fasting insulin levels and glycated hemoglobin (HbA1c) levels were done in all the subjects. The values of HOMA-IR were computed using established formulae. Enzyme-linked immunosorbent assay (ELISA) kits were used for the evaluation of serum levels of activin A in both groups. Parameters for the two groups were compared. In the cases, CIMT (using B-mode ultrasound) and LVDD (using two-dimensional (2D) echocardiography) were measured and correlated with activin A levelsResults: Serum fasting insulin (mIU/L) was considerably higher in cases than in the controls (p &lt; 0.001). HOMA-IR median [interquartile range (IQR)] was 4 (3.25-4.93) in some cases, and that in the control group was 1.2 (0.88-1.5) (p &lt; 0.001). Serum activin A levels in the cases group had a median (IQR) of 263.55 (227.1-279.5) ng/mL, which was substantially greater as compared to the control group 159.9 (150.7-178.7) ng/mL (p &lt; 0.001). A significant positive association of serum activin A levels with HOMA-IR (ρ = 0.75, p &lt; 0.001) and CIMT (ρ = 0.50, p &lt; 0.001) was found. In LVDD grade I and II groups, the serum levels of activin A were 257.86 (219.3-271.2) ng/mL and 269 (244.19-291.5) ng/mL, respectively (p = 0.12)Conclusion: A substantial proportion of morbidity and mortality related to dysglycemic states can be attributed to cardiovascular complications. Elevated levels of activin A in prediabetes can act as an indicator of subclinical CVD leading to early diagnosis and intervention.

1343. Body fat and metabolic complications in youth with perinatally-acquired HIV

Abstract Background The role of obesity on long-term metabolic complications remains poorly understood in youth living with perinatally-acquired HIV (YPHIV). Methods The PHACS Adolescent Master Protocol (AMP) study enrolled YPHIV from 2007-2009 across 15 U.S. sites, including Puerto Rico. We included YPHIV aged 7-19 yr with body composition data assessed by whole-body dual energy x-ray absorptiometry (DXA) at baseline and 2 years later. Metabolic outcomes included homeostatic assessment of insulin resistance (HOMA-IR) and non-high-density lipoprotein cholesterol (non-HDL-C). We fit linear regression models using generalized estimating equations to assess the association of % change in body and trunk fat over 2 yr with metabolic outcomes at years 2 and 3, adjusted for potential confounders (age, race: Black vs. non-Black, Tanner stage, sex, family history, CD4, viral load, and ART). Results 232 participants had a second DXA and either HOMA-IR or non-HDL-C measured at year 2. Participant characteristics at the first DXA were: median (Q1, Q3) age 12 yr (9, 14) 70% Black, CD4 count 714 cells/mm3; 70% with HIV RNA &amp;lt; 400 copies/mL; 72% on protease inhibitor-, 25% on non-nucleoside reserve transcriptase inhibitor-, and 3% on integrase strand transfer inhibitor-based ART. The median % increase from baseline in total body and trunk fat percentage at 2 yr was 5.41% and 4.47%, respectively. The figure shows distributions of HOMA-IR and non-HDL-C. In both unadjusted and adjusted analyses (Table), for every 1% increase in total body fat percentage from baseline to 2 years, we observed a 0.002 (95%CI -0.0, 0.005) higher log10 HOMA-IR at year 3, which equals ∼ a 0.5% higher HOMA-IR. For every 1% increase in total body and trunk fat percentage over 2 years, non-HDL-C (mg/dL) was 0.19 (95%CI 0.03, 0.35) higher and 0.65 (95%CI 0.12, 1.19) higher, respectively, in unadjusted models. Results were similar but slightly attenuated when we additionally adjusted for confounders including ART. Figure:HOMA-IR and non-HDL cholesterol at baseline, year 2, and year 3Table:Unadjusted and adjusted models assessing the association of percent change in body fat and trunk fat percentage with metabolic outcomes ¹Adjusted for age (years), sex (male vs female), race (Black vs non-Black), Tanner stage (2, 3, 4-5 vs 1), family history of diabetes or cardiovascular disease (yes, not known vs no), CD4 (≤350 vs &amp;gt;350 cells/mm³), and viral load (≥400 vs &amp;lt;400 copies/mL). ²Adjusted for age (years), sex (male vs female), race (Black vs non-Black), Tanner stage (2, 3, 4-5 vs 1), family history of diabetes or cardiovascular disease (yes, not known vs no), CD4 (≤350 vs &amp;gt;350 cells/mm³), viral load (≥400 vs &amp;lt;400 copies/mL), and ARV exposure (PI without NNRTI, NNRTI without PI vs other). Conclusion Increases in adiposity over time may lead to downstream decreased insulin sensitivity and dyslipidemia in YPHIV. This is clinically significant, as even small increases in HOMA-IR have been associated with all-cause mortality in non-diabetic HIV-uninfected adults. Long-term follow-up is warranted. Disclosures Mitchell E. Geffner, MD, Adrenas: Advisor/Consultant|Adrenas: Honoraria|Ascendis: Advisor/Consultant|Ascendis: Honoraria|Aventria: Honoraria|Eton: Advisor/Consultant|Eton: Honoraria|ICON Clinical Research, LLC/Aeterna Zentaris: Advisor/Consultant|ICON Clinical Research, LLC/Aeterna Zentaris: Honoraria|McGraw-Hill: Royalties|Neurocrine Biosciences: Grant/Research Support|Novo Nordisk: Grant/Research Support|Nutritional Growth Solutions Ltd: Advisor/Consultant|Nutritional Growth Solutions Ltd: Honoraria|Pfizer, Inc.: Advisor/Consultant|Pfizer, Inc.: Honoraria|Spruce Biosciences: Grant/Research Support|UpToDate: Royalties Grace A. McComsey, MD, Gilead, Merck, ViiV, Janssen, Theratechnologies: Advisor/Consultant.

A performance review of novel adiposity indices for assessing insulin resistance in a pediatric Latino population.

IntroductionBody mass index (BMI) percentile or BMI adjusted for age and sex is the most common anthropometric index to monitor and assess obesity in children. However, the ability of BMI to accurately predict insulin resistance (IR) in youth is debated. Determining the best method to noninvasively measure IR in the pediatric population is especially important due to the growing prevalence of type 2 diabetes mellitus (T2DM), which is more likely to develop in people with IR. Therefore, this study analyzed the performance of BMI against newer anthropometric indices in assessing IR in a pediatric Latino identifying sample.MethodsWe studied 127 pediatric Latino participants from the Arizona Insulin Resistance (AIR) registry and performed linear regression analyses between various measures of IR and adiposity indices, including body mass index (BMI), triponderal mass index (TMI), body adiposity index (BAI), pediatric body adiposity index (pBAI), a body shape index (ABSI), abdominal volume index (AVI), waist to height ratio (WtHR) and waist to hip ratio (WHR). Log transformations of each index adjusted for age and sex and IR were used for the linear regressions. Additionally, we generated receiver operating characteristics (ROC) from logistic regressions between HOMA-IR and HOMA2IR against the same indices.ResultsUsing the homeostatic assessment of insulin resistance (HOMA-IR), HOMA2IR, the quantitative insulin-sensitivity check index (QUICKI), fasting serum insulin, and FPG/FSI to measure IR, we showed that BMI adjusted for age and sex performs similarly to many of the newer indices in our sample. The correlation coefficients for pBAI [R2: 0.27, 95% confidence interval: 0.88–1.81, p < 0.001] and BMI [R2: 0.27, 95% confidence interval: 0.92–1.92, p < 0.001] were the highest for HOMA-IR. Similarly, pBAI [R2: 0.29, 95% confidence interval: 0.88–1.72, p < 0.001] and BMI [R2: 0.29, 95% confidence interval: 0.93–1.83, p < 0.001] were the highest for HOMA2IR. A similar trend was observed with QUICKI, FSI, and FPG/FSI. ABSI had the lowest R2 value for all measures of IR. Area under the curve (AUC) values for the receiver operating characteristics (ROC) for HOMA-IR and HOMA2IR support these conclusions.ConclusionsBMI adjusted for age and sex, despite its usage and simplicity, still stacks up well against newer indices in our Latino sample. Testing these indices across larger samples is necessary to generalize these findings and translate performance to adults.

Gut Microbiota Composition in Prediabetes and Newly Diagnosed Type 2 Diabetes: A Systematic Review of Observational Studies.

Evidence of gut microbiota involvement in regulating glucose metabolism and type 2 diabetes mellitus (T2DM) progression is accumulating. The understanding of microbial dysbiosis and specific alterations of gut microbiota composition that occur during the early stages of glucose intolerance, unperturbed by anti-diabetic medications, is especially essential. Hence, this systematic review was conducted to summarise the existing evidence related to microbiota composition and diversity in individuals with prediabetes (preDM) and individuals newly diagnosed with T2DM (newDM) in comparison to individuals with normal glucose tolerance (nonDM). A systematic search of the PubMed, MEDLINE and CINAHL databases were conducted from inception to February 2021 supplemented with manual searches of the list of references. The primary keywords of “type 2 diabetes”, “prediabetes”, “newly-diagnosed” and “gut microbiota” were used. Observational studies that conducted analysis of the gut microbiota of respondents with preDM and newDM were included. The quality of the studies was assessed using the modified Newcastle-Ottawa scale by independent reviewers. A total of 18 studies (5,489 participants) were included. Low gut microbial diversity was generally observed in preDM and newDM when compared to nonDM. Differences in gut microbiota composition between the disease groups and nonDM were inconsistent across the included studies. Four out of the 18 studies found increased abundance of phylum Firmicutes along with decreased abundance of Bacteroidetes in newDM. At the genus/species levels, decreased abundance of Faecalibacterium prausnitzii, Roseburia, Dialister, Flavonifractor, Alistipes, Haemophilus and Akkermansia muciniphila and increased abundance of Lactobacillus, Streptococcus, Escherichia, Veillonella and Collinsella were observed in the disease groups in at least two studies. Lactobacillus was also found to positively correlate with fasting plasma glucose (FPG), HbA1c and/or homeostatic assessment of insulin resistance (HOMA-IR) in four studies. This renders a need for further investigations on the species/strain-specific role of endogenously present Lactobacillus in glucose regulation mechanism and T2DM disease progression. Differences in dietary intake caused significant variation in specific bacterial abundances. More studies are needed to establish more consistent associations, between clinical biomarkers or dietary intake and specific gut bacterial composition in prediabetes and early T2DM.

Timing of Meals and Exercise Affects Hormonal Control of Glucoregulation, Insulin Resistance, Substrate Metabolism, and Gastrointestinal Hormones, but Has Little Effect on Appetite in Postmenopausal Women.

The current prevalence of obesity in the US is strongly associated with excessive food intake and insufficient physical activity. This study examined whether changing the timing of exercise before or after two daily meals could alter human appetite for food. Fifty-four healthy postmenopausal women were matched by body weight and assigned to two groups: (1) two bouts of 2-h moderate-intensity exercise ending one hour before each weight-maintenance meal (XM, n = 23), (2) two-hour moderate-intensity exercise starting 1 h after each weight-maintenance meal (MX, n = 23), and one sedentary control (SED) arm (n = 8). Measurements included appetite ratings, circulating glucose, free fatty acids (FFAs), a ketone body D-ß-hydroxybutyrate (BHB), glucoregulatory hormones insulin and glucagon, and gastrointestinal hormones associated with food digestion and absorption and implicated in appetite sensations. XM group increased concentrations of FFAs and BHB during exercise and increased insulin and homeostatic assessment of insulin resistance (HOMA-IR) during postprandial periods. MX group reduced postprandial insulin and HOMA-IR by about 50% without a major change in plasma glucose. There was brief suppression of hunger and an increase in satiation in both exercise groups near the end of the first postprandial period. The time course of hunger was unrelated to the perturbations in fuel metabolism, depletion of liver glycogen, and not correlated with concentration changes in hunger-stimulating hormone ghrelin during XM exercise before meals. Similarly, there was no correlation between the time course of fullness during exercise after meals with the postprandial secretion of gastrointestinal hormones including cholecystokinin (CCK) that has been linked to satiation. Hunger and satiation appear to depend on oral intake and gastrointestinal processing of nutrients and are not affected by metabolic and hormonal consequences of the timing of exercise with respect to meals. Moderate-intensity exercise performed shortly after meals induces a rapid and highly effective lowering of insulin resistance.

A Correlational Study of Hepatic Steatosis (Fatty Liver Disease) and Liver Enzymes (ALT, AST, GGT) In The Scenario of Insulin Resistance Among Young Medicos.

Background and Objectives In the last few decades,Nonalcoholic Fatty Liver Disease (NAFLD) has become a common health issue that leads to serious complications like cirrhosis, cardiovascular disease, etc. Insulin resistance (IR) is the key pathogenic factor for NAFLD. The young medicos being habituated in stressful and sedentary lifestyle and representative of the youth as well can fully justify their selection as study population and help to build social awareness by emphasizing the importance of early lifestyle modifications in preventing or delaying the severe complications of NAFLD. This study is aiming to find out if there is any correlation of hepatic steatosis with IR, Alanine Transaminases (ALT), Aspartate Transaminases (AST) or Gama Glutamyl Transferases (GGT) and also to identify if one enzyme is better correlating with hepatic steatosis than others in the scenario of Insulin Resistance among young medicos. METHODS: 132 medical students of North Bengal Medical College, aged between 18-25 years were included in this institution based observational cross-sectional study. Their Fasting Insulin, glucose, ALT, AST, GGT were measured, and IR was calculated by the Homeostatic Assessment of Insulin Resistance (HOMA-IR) calculator. Sonography was done to assess Hepatic steatosis. RESULTS: Among 132 subjects normal, grade 1 and grade 2 fatty changes have been found in 67.4%, 25%, and 7.6% of the study population respectively. The Grouping was done using the cut-off value of IR (i.e. subjects with IR&lt;1.525 vs. IR≥1.525). Significant differences were found in the mean values of ALT, AST, GGT between groups. Significant positive concordances were found between enzymes ALT, GGT, and hepatic steatosis in subjects having IR ≥ 1.525.Regression analysis showed that higher GGT values have a stronger positive correlation with hepatic steatosis than ALT among the same. Interpretation and Conclusion From this study, we can interpret that subjects having higher GGT values are better associated with steatosis than those having higher ALT values and can lead us to the conclusion that GGT might be an important independent marker for NAFLD associated with IR. Furthermore, such observations may suggest considering GGT as a marker for assessing the severity of fatty liver irrespective of etiopathogenesis, though the population-based vivid evaluation is highly recommended.

Evaluation of Changes in Levels of Hyperandrogenism, Hirsutism and Menstrual Regulation After a Period of Aquatic High Intensity Interval Training in Women with Polycystic Ovary Syndrome.

Background:Polycystic ovary syndrome (PCOS) is a polygenic endocrine disorder in women of reproductive ages which will lead to infertility. This study is aimed to determine changes in levels of hyperandrogenism, hirsutism and menstrual regulation after a period of aquatic high intensity interval training (AHIIT) in women with PCOS.Methods:Thirty patients with PCOS having age between 20 and 35 and body mass index (BMI) ≥30 kg/m2 in obstetrics and gynaecology clinics in Isfahan were selected based on Rotterdam Diagnostic Criteria. They were randomly divided into experimental (AHIIT + metformin, N = 15) and control groups (metformin, N = 15). The exercises were done for 12 weeks, three sessions of 20 minutes. Metformin (1500 mg) was taken daily for 3 consecutive days for 12 weeks. Kolmogorov–Smirnov test, t-test, Covariance and Wilcoxon were applied (P value < 0.05).Results:After 12 weeks, no significant difference was observed in waist-to-hip ratio (WHR), but in AHIIT, the BMI and fat mass significantly decreased and levels of follicle-stimulating hormone (FSH), free testosterone (FT) and sex hormone binding globulin (SHBG) increased compared to control group (P < 0.05). While levels of improvement of total testosterone (TT), dehydroepiandrosterone sulphate (DHEAS), FT, luteinising hormone (LH) and free androgen index (FAI) were not significant between the two groups (P > 0.05). Furthermore, there was a significant decrease in homeostatic assessment of insulin resistance (HOMA-IR) and hirsutism severity in experimental group (P < 0.05). In both groups, the order of menstrual cycles improved significantly (P < 0.05).Conclusions:Doing AHIIT besides drug therapy can be effective for PCOS patients.

Sleep Timing, Stability, and BP in the Sueño Ancillary Study of the Hispanic Community Health Study/Study of Latinos

Timing and stability of the sleep-wake cycle are potential modifiable risk factors for cardiometabolic disease. The aim of this study was to evaluate the relationship between objective measures of sleep-wake timing and stability with cardiometabolic disease risk. In this multicenter, cross-sectional, population-based study, actigraphy data were obtained from the 2,156 adults, aged 18 to 64 years, recruited from the Sueño ancillary study of the Hispanic Community Health Study/Study of Latinos (2010-2013). These data were correlated with measures of cardiometabolic disease risk, including systolic and diastolic BPs, homeostatic assessment of insulin resistance, glycosylated hemoglobin, BMI, and hypertension and diabetes status. Each 10%decrease in interdaily stability was associated with a 3.0%absolute increase in the prevalence of hypertension (95%CI, 0.6-5.3; P< .05), an increase in systolic BP by 0.78mmHg (95%CI, 0.12-1.45; P< .05) and an increase in diastolic BP by 0.80mmHg (95%CI, 0.28-1.32; P< .05). In addition, delaying the midpoint of sleep by 1h was associated with an increase in systolic BP by 0.73mmHg (95%CI, 0.30-1.16; P< .01) and diastolic BP by 0.53mmHg (95%CI, 0.17-0.90; P< .01). These associations were not significant after adjusting for shift work status. No association was found between interdaily stability or sleep timing and diabetes, BMI, or insulin resistance. These results suggest that beyond sleep duration, the timing and regularity of sleep-wake schedules are related to hypertension prevalence and BP.

The effect of a prenatal lifestyle intervention on glucose metabolism: results of the Norwegian Fit for Delivery randomized controlled trial

BackgroundThe effectiveness of prenatal lifestyle intervention to prevent gestational diabetes and improve maternal glucose metabolism remains to be established. The Norwegian Fit for Delivery (NFFD) randomized, controlled trial studied the effect of a combined lifestyle intervention provided to a general population, and found significantly lower gestational weight gain among intervention participants but no improvement in obstetrical outcomes or the proportion of large infants. The aim of the present study is to examine the effect of the NFFD intervention on glucose metabolism, including an assessment of the subgroups of normal-weight and overweight/obese participants.MethodsHealthy, non-diabetic women expecting their first child, with pre-pregnancy body mass index (BMI) ≥19 kg/m2, age ≥ 18 years and a singleton pregnancy of ≤20 gestational-weeks were enrolled from healthcare clinics in southern Norway. Gestational weight gain was the primary endpoint. Participants (n = 606) were individually randomized to intervention (two dietary consultations and access to twice-weekly exercise groups) or control group (routine prenatal care). The effect of intervention on glucose metabolism was a secondary endpoint, measuring glucose (fasting and 2-h following 75-g glucose load), insulin, homeostatic assessment of insulin resistance (HOMA-IR) and leptin levels at gestational-week 30.ResultsBlood samples from 557 (91.9%) women were analyzed. For the total group, intervention resulted in reduced insulin (adj. Mean diff −0.91 mU/l, p = 0.045) and leptin levels (adj. Mean diff -207 pmol/l, p = 0.021) compared to routine care, while glucose levels were unchanged. However, the effect of intervention on both fasting and 2-h glucose was modified by pre-pregnancy BMI (interaction p = 0.030 and p = 0.039, respectively). For overweight/obese women (n = 158), intervention was associated with increased risk of at least one glucose measurement exceeding International Association of Pregnancy and Diabetes Study Group thresholds (33.7% vs. 13.9%, adj. OR 3.89, p = 0.004).ConclusionsThe Norwegian Fit for Delivery intervention lowered neither glucose levels nor GDM incidence, despite reductions in insulin and leptin. Prenatal combined lifestyle interventions designed for a general population may be unsuited to reduce GDM risk, particularly among overweight/obese women, who may require earlier and more targeted interventions.Trial registrationClinicalTrials.gov ID NCT01001689, registered July 2, 2009, confirmed completed October 26, 2009 (retrospectively registered).

Effects of High Intensity Interval Training and Strength Training on Metabolic, Cardiovascular and Hormonal Outcomes in Women with Polycystic Ovary Syndrome: A Pilot Study.

BackgroundPolycystic ovary syndrome is a common endocrinopathy in reproductive-age women, and associates with insulin resistance. Exercise is advocated in this disorder, but little knowledge exists on the optimal exercise regimes. We assessed the effects of high intensity interval training and strength training on metabolic, cardiovascular, and hormonal outcomes in women with polycystic ovary syndrome.Materials and MethodsThree-arm parallel randomized controlled trial. Thirty-one women with polycystic ovary syndrome (age 27.2 ± 5.5 years; body mass index 26.7 ± 6.0 kg/m2) were randomly assigned to high intensity interval training, strength training, or a control group. The exercise groups exercised three times weekly for 10 weeks.ResultsThe main outcome measure was change in homeostatic assessment of insulin resistance (HOMA-IR). HOMA-IR improved significantly only after high intensity interval training, by -0.83 (95% confidence interval [CI], -1.45, -0.20), equal to 17%, with between-group difference (p = 0.014). After high intensity interval training, high-density lipoprotein cholesterol increased by 0.2 (95% CI, 0.02, 0.5) mmol/L, with between group difference (p = 0.04). Endothelial function, measured as flow-mediated dilatation of the brachial artery, increased significantly after high intensity interval training, by 2.0 (95% CI, 0.1, 4.0) %, between-group difference (p = 0.08). Fat percentage decreased significantly after both exercise regimes, without changes in body weight. After strength training, anti-Müllarian hormone was significantly reduced, by -14.8 (95% CI, -21.2, -8.4) pmol/L, between-group difference (p = 0.04). There were no significant changes in high-sensitivity C-reactive protein, adiponectin or leptin in any group.ConclusionsHigh intensity interval training for ten weeks improved insulin resistance, without weight loss, in women with polycystic ovary syndrome. Body composition improved significantly after both strength training and high intensity interval training. This pilot study indicates that exercise training can improve the cardiometabolic profile in polycystic ovary syndrome in the absence of weight loss.Trial RegistrationClinicalTrial.gov NCT01919281

Elevated Serum Oxychlordane is Associated with Increased Risk of Metabolic Syndrome: Results from the National Health and Nutrition Examination Survey 1999‐2004

Obesity, diet, and physical inactivity are risk factors commonly associated with metabolic syndrome (MetS). However, exposure to chlordane, a persistent organic pesticide that has been banned in the US since 1983, has been associated with metabolic risk. Chlordane continues to be found in indoor air of homes treated for termites as well as in foods. The objective of this research was to use the most recent non‐pooled NHANES data on chlordane exposure (1999‐2004) and its effect on metabolic syndrome risk. Data from NHANES were used to calculate odds ratios for metabolic syndrome, each of its five risk component measures, and related health markers in relationship with subjects' plasma oxychlordane concentrations. The logistic regression model used was adjusted for the influence of age, gender, ethnicity, BMI, and poverty income ratio. A total of 3465 adult subjects were used in this study. A significant relationship was found between plasma oxychlordane concentration (OR of highest quartile compared to the lowest quartile, 95% CI) and the prevalence of MetS (2.58, 1.80‐3.71), hypertriglyceridemia (3.26, 1.92‐5.46), elevated waist circumference (2.24, 1.34‐3.76), elevated blood pressure (2.58, 1.96‐3.38), and hyperglycemia (2.05, 1.23‐3.42). Additional post hoc analyses showed that high oxychlordane concentrations were also significantly related to elevated glycosylated hemoglobin, C‐reactive protein, and the homeostatic assessment of insulin resistance (HOMA‐IR). In conclusion, despite a nearly 20 year ban on its use, a significant association between plasma oxychlordane concentration and risk for metabolic syndrome exists.

Insulin resistance and medial prefrontal gyrus metabolism in women receiving hormone therapy

Insulin resistance (IR) is a putative risk factor for cognitive decline and dementia, and has been shown to impede neuronal glucose metabolism in animal models. This post hoc study focused on metabolic changes in the medial prefrontal region, a brain region exhibiting decline years before documented cognitive changes, relative to high or low IR status in a cohort of postmenopausal women at risk for dementia who were randomized to continue or discontinue existing stable hormone therapy (HT) for 2 years. Subjects were dichotomized into high and low IR groups based on the homeostatic model assessment of insulin resistance, which was within clinically normal limits for the group as a whole at both baseline and 2-year follow-up. Results showed that high and low IR groups showed significant differences in metabolic decline of the medial prefrontal gyrus, regardless of HT randomization group. However, HT randomization was predictive of metabolic decline only in women with low HOMA (homeostatic assessment of insulin resistance). Performance in working memory was consistent with observed metabolic changes. These results suggest IR may be an independent moderator of regional metabolic changes, while protective metabolic effects of HT are most apparent in those at low-end range of IR. If replicated in future studies, these findings will help to better understand the interaction between putative risk and protective factors, and further delineate cohort postmenopausal women who may benefit from HT.

Soluble receptor for advanced glycation end products independently predicts cardiometabolic syndrome in Latino youth

The soluble receptor for advanced glycation end products (sRAGE) has anti-atherogenic properties in adults, however, little is known about the relationship between sRAGE and cardiometabolic disease risk in pediatric populations. Therefore, the purpose of this investigation is to examine the relationship between sRAGE and cardiometabolic risk factors in Latino youth. Data from 133 Latino youth (58% female; age 16.3 ± 2.8 yr) enrolled in the Arizona Insulin Resistance Registry were analyzed. Cardiometabolic syndrome was determined using a continuous risk score normalized to the population. Components included waist circumference, high-density lipoprotein cholesterol (HDL-c), triglycerides, mean arterial pressure (MAP), and homeostatic assessment of insulin resistance (HOMA-IR). sRAGE levels were determined from fasting serum using an enzyme-linked immunosorbent assay. In univariate analysis, sRAGE was inversely associated with waist circumference (r = -0.22, p = 0.01), MAP (r = -0.15, p = 0.09), and HOMA-IR (r = -0.29, p < 0.01) and positively associated with HDL-c (r = 0.19, p < 0.05). In multiple regression analysis with age, sex, and BMI, sRAGE remained an independent predictor of cardiometabolic syndrome risk score (R(2) = 0.55, p < 0.001). These data suggest that sRAGE may be an early independent biomarker of cardiometabolic disease risk in youth. Prospective studies are needed to establish the predictive utility of sRAGE for long-term disease outcomes.

Physiological effects beyond the significant gain in muscle mass in sarcopenic elderly men: evidence from a randomized clinical trial using a protein-rich food

BackgroundSarcopenia is strongly associated with an inadequate intake of dietary protein. Dietary protein supplementation boosts muscle-protein synthesis and increases muscle mass in the elderly. This study tested whether adding a protein-rich food, ricotta cheese, to the habitual diet increased total appendicular skeletal muscle mass and strength in elderly people.MethodsParticipants (n = 40), were sarcopenic elderly men and women over 60 years of age. Two comparison groups were formed at random and followed for 3 months: the intervention group received 210 g/day of ricotta cheese plus the habitual diet, while the control group followed the habitual diet with no additional intervention. Total appendicular skeletal muscle (TASM) was assessed by dual-energy X-ray absorptiometry, while strength was measured using a handheld dynamometer at baseline and after the intervention period. The primary outcomes were the percentage of relative change in TASM and strength.ResultsThe percentage of relative change in TASM was not significant between the groups after the intervention period. Muscle strength improved in the intervention group, but showed only a tendency towards significance (P = 0.06). Secondary analysis showed that the men in the intervention group gained 270 g in TASM compared to those in the control group, and improved their fasting insulin levels (P = 0.05), muscle strength, lean body mass in the arms, and body weight variables.ConclusionThe results of this study indicate that a nutritional intervention using a high-quality protein food, specifically ricotta cheese, in order to increase the amount of protein intake might not be regarded as fully promising in elderly men and women with sarcopenia. However, the gender effects on muscle strength, lean tissue in the arms, homeostatic assessment of insulin resistance, and body weight detected in this study suggest that additional research is needed on elderly male subjects with sarcopenia.

Targeting Curcusomes to Inflammatory Dendritic Cells Inhibits NF-κB and Improves Insulin Resistance in Obese Mice

OBJECTIVETo determine whether and by what mechanism systemic delivery of curcumin-containing liposomes improves insulin resistance in the leptin deficient (ob/ob) mouse model of insulin resistance.RESEARCH DESIGN AND METHODSInsulin resistant ob/ob mice with steatosis were injected intraperitoneally with liposome nanoparticles, entrapping the nuclear factor-κB (NF-κB) inhibitor curcumin (curcusomes), and uptake in liver and adipose tissue was determined by flow cytometry. The effects of curcusomes on macrophage NF-κB activation and cytokine production were assessed. Transfer experiments determined the role of hepatic tumor necrosis factor (TNF)/inducible nitric oxide synthase-producing dendritic cells (Tip-DCs) and adipose tissue macrophages (ATMs) in inflammation-induced insulin resistance, determined by homeostatic assessment of insulin resistance.RESULTSPhagocytic myeloid cells infiltrating the liver in ob/ob mice had the phenotypic characteristics of Tip-DCs that arise from monocyte precursors in the liver and spleen after infection. Targeting Tip-DCs and ATMs with curcusomes in ob/ob mice reduced NF-κB/RelA DNA binding activity, reduced TNF, and enhanced interleukin-4 production. Curcusomes improved peripheral insulin resistance.CONCLUSIONSBoth hepatic Tip-DCs and ATMs contribute to insulin resistance in ob/ob mice. Curcusome nanoparticles inhibit proinflammatory pathways in hepatic Tip-DCs and ATMs and reverse insulin resistance. Targeting inflammatory DCs is a novel approach for type 2 diabetes treatment.

ALANINE AMINOTRANSFERASE AS A PREDICTOR OF METABOLIC SYNDROME IN KOREANS: PP.34.428

Aims: Alanine aminotransferase (ALT) is associated with insulin resistance, and is independent of the general metabolic measures. Method: A total of 1203 Koreans who visited the Institute of Health in Pusan National University Hospital were enrolled in this cross-sectional study. Their median age was 51 years old, and the prevalence of metabolic syndrome was 16.4% (n = 197). Results: For all the patients in the metabolic syndrome group, the median homeostatic assessment of insulin resistance (HOMA-IR), the waist circumference, the fasting blood glucose level, the systolic and diastolic blood pressure were all associated with the ALT level (P < 0.05). For the nonmetabolic syndrome group, all the metabolic risk factors were associated with the ALT level (P < 0.05). On logistic regression analysis, after correction for age, alcohol intake, HOMA-IR and body mass index, the logALT maintained a highly predictive value for metabolic syndrome, and this was better than the logGGT [odds ratio (OR) of logALT: 18.489, odds ratio of logGGT: 2.024] (P < 0.001). The risk of developing metabolic syndrome was significantly higher in the above 50 percentile and the above 75 percentile of ALT than in the lowest quartile. [for men: 3.6; 95% confidence interval (CI), 2.2–5.9; OR: 6.9; 95% CI: 4.3–10.9] [for women: 2.7; 95% CI: 1.5–4.7;OR: 6.5; 95% CI: 3.8–11] (P < 0.001). The cut-off value of ALT by the ROC curve was 24 IU/L for men (sensitivity: 64.3%, specificity: 66%, negative predictive value: 99.5%) and 20 IU/L for women (sensitivity: 78.9%, specificity: 61.4%, negative predictive value: 84.9%). Conclusions: Even although patients can have an ALT level that's included within the upper normal level, we may consider the probability that these patients will have metabolic syndrome. Furthermore, in our analysis, the ALT level is a better predictor of metabolic syndrome than the GGT level.

Insulin resistance and hippocampal volume in women at risk for Alzheimer's disease

Insulin resistance (IR) is the main pathological condition underlying vascular disorders, such as diabetes and cardiovascular disease, which are well established risk factors for cognitive decline and Alzheimer disease (AD). Hippocampal atrophy has been associated with cognitive decline, but little is known about the influence of IR on hippocampus integrity in non-diabetic, cognitively intact individuals. Herein, 50 women ages 50-65, current users of hormone therapy, underwent magnetic resonance imaging, cognitive testing, and homeostatic assessment of insulin resistance (HOMA-IR), as part of a longitudinal study examining brain structure and function in postmenopausal women at risk for AD. Results demonstrated a significant negative relationship between HOMA-IR and right and total hippocampal volume, overall cognitive performance, and selective tests of verbal and non-verbal memory. The main effect of HOMA-IR on brain structure and cognition was not altered by the presence of APOE-ε4 allele or by reproductive history, such as duration of endogenous and exogenous estrogen exposure. These results suggest that IR in middle-aged individuals at risk for AD may be biomarker for dementia risk.

Incidence of Type 2 Diabetes Mellitus and Glucose Abnormalities in Patients With Chronic Hepatitis C Infection by Response to Treatment: Results of a Cohort Study

Patients with chronic hepatitis C are at risk of developing type 2 diabetes mellitus (DM) and impaired fasting glucose (IFG), and this risk may increase among hepatitis C virus (HCV) patients not responding to an antiviral therapy. To compare the incidence of glucose abnormalities (IFG or DM) after an antiviral therapy between HCV+ patients with a long-term virological response (LTR) and nonresponders (NR; persistently positive HCV-RNA). All 202 HCV+ patients without the baseline glucose abnormalities enrolled by our center in investigational trials or routinely treated with interferon (IFN)/peginterferon (Peg-IFN) (+/- ribavirin) from 1988 to 2001, with the available baseline sera stored at -80 degrees C, were considered. The baseline data included age, sex, body mass index (BMI), viral load, genotype, liver histologic staging and steatosis, glucose, and cholesterol. The homeostatic assessment of insulin resistance (HOMA-IR) was calculated in the baseline serum. The incidence of IFG or DM at the end of follow-up was compared between patients with LTR and NR. After a median follow-up of 8.0 yr (range 5-16), the cumulative risk of DM (N = 7) or IFG (N = 33) among the 202 HCV+ included patients was 16.9% (95% confidence interval [CI] 11.3-22.5). The 8-yr risk was not significantly lower between LTRs (14.5%) compared to NRs (18.8%) (hazard ratio [HR] 0.60, CI 0.30-1.20, P= 0.16). The HR adjusted for the baseline risk factors for DM and the predictors of a poor response (age, sex, HOMA-IR, BMI, family history of diabetes, HCV genotype 1, high viral load, cirrhosis, and steatosis) was 0.88 (CI 0.38-2.02, P= 0.76). Among other factors, those more associated to IFG-DM were an increasing age (P= 0.017), a higher BMI (P= 0.054), and a family history of DM (P= 0.065). After adjustment for several baseline risk factors, the incidence of glucose abnormalities was not significantly different between LTRs and NRs. Our data suggest that HCV clearance does not significantly reduce the risk of glucose intolerance.

Alanine Aminotransferase as a Predictor of Metabolic Syndrome in Koreans

Aims: Alanine aminotransferase (ALT) is associated with insulin resistance, and is independent of the general metabolic measures. Gamma-glutamyltransferase (GGT) is regarded as a predictor of diabetes mellitus. We analyzed which of ALT or GGT is better tool to preestimate the development of metabolic syndrome. Method: A total of 1203 Koreans who visited the Institute of Health in Pusan National University Hospital from January 2005 to August 2006 were enrolled in this cross-sectional study. Their median age was 51 years old, and the prevalence of metabolic syndrome was 16.4% (n = 197). We excluded the subjects with diabetes mellitus, hypertension and viral hepatitis or those subjects with a level of alanine aminotransferase (ALT) or gamma-glutamyltransferase (r-GGT) > 80 IU/L. Results: For all the patients in the metabolic syndrome group, the median homeostatic assessment of insulin resistance (HOMA-IR), the waist circumference, the fasting blood glucose level, the systolic and diastolic blood pressure were all associated with the ALT level (P < 0.05). For the nonmetabolic syndrome group, all the metabolic risk factors were associated with the ALT level (P < 0.05). On logistic regression analysis, after correction for age, alcohol intake, HOMA-IR and body mass index, the logALT maintained a highly predictive value for metabolic syndrome, and this was better than the logGGT [odds ratio (OR) of logALT: 18.489, odds ratio of logGGT: 2.024] (P < 0.001). The risk of developing metabolic syndrome was significantly higher in the above 50 percentile and the above 75 percentile of ALT than in the lowest quartile. [for men – OR: 3.6; 95% confidence interval (CI), 2.2-5.9; OR: 6.9; 95% CI: 4.3-10.9] [for women – OR: 2.7; 95% CI: 1.5-4.7; OR: 6.5; 95% CI: 3.8-11] (P < 0.001). The cut-off value of ALT by the ROC curve was 24 IU/L for men (sensitivity: 64.3%, specificity: 66%, negative predictive value: 99.5%) and 20 IU/L for women (sensitivity: 78.9%, specificity: 61.4%, negative predictive value: 84.9%). Conclusions: Even although patients can have an ALT level that’s included within the upper normal level, we may consider the probability that these patients will have metabolic syndrome. Furthermore, in our analysis, the ALT level is a better predictor of metabolic syndrome than the GGT level. (J Korean Endocr