Insulin Resistance In Women Research Articles

Insulin Regulation of Lysine and α-Aminoadipic Acid Dynamics and Amino Metabolites in Women With and Without Insulin Resistance.

Insulin is a key regulator of amino acids (AAs) metabolism. Many plasma AAs, including lysine and its metabolite, α-aminoadipic acid (α-AA), a predictor for developing diabetes, are elevated in insulin resistance. In 18 insulin-resistant (IR) over-weight women with polycystic ovary syndrome compared to 12 lean controls, high physiological insulin during a euglycemic clamp failed to normalize many elevated AA metabolites, including branched-chain and aromatic AA, alphaamino- butyric acid, and lysine, but normalized α-AA. To understand the underpinning of differential responses of lysine and its metabolic product α-AA to high physiological insulin in IR compared to controls, we developed a kinetic model utilizing [α-15N1] lysine and [13C1] α-AA as tracers and measured the two tracers simultaneously in α-AA by innovative mass spectrometry. High insulin increased lysine conversion to α-AA in IR and controls but failed to normalize plasma lysine concentrations in IR due to a decrease in lysine metabolic clearance rate (MCR). In contrast, despite higher conversion rates of lysine to α-AA by high insulin, α-AA concentration decreased in IR because of the sustained greater MCR of α-AA. The abnormal AAs and metabolites, even while on high physiological insulin, could potentially explain many functional derangements in IR.

The effect of vitamin D supplementation on markers of insulin resistance in women with polycystic ovarian syndrome: a systematic review.

Insulin resistance (IR) is a common pathology in women with polycystic ovarian syndrome (PCOS) involved in increased rates of cardiometabolic disease such as diabetes and cardiovascular disease. Low serum vitamin D is often associated with insulin resistance but there is no consensus on whether vitamin D supplementation can ameliorate markers of IR in PCOS. We assessed evidence on the effects of vitamin D supplementation (≥ 1000 IU/day), without the use of additional supplements or other pharmacological treatments known to affect IR, on markers of IR and glycemic control in women with PCOS. A systematic search was conducted using PubMed, Medline and Web of Science databases from January 2000 up to November 2023. Randomized controlled trials that assessed the effects of vitamin D supplementation in women with PCOS, on fasting glucose, fasting insulin, glycated haemoglobin (HbA1c) or homeostatic model assessment for insulin resistance (HOMA-IR) were included. 9 studies were identified. Study populations ranged from 28 to 180 participants, with mean ages ranging from 22 to 30 years. Daily vitamin D doses ranged from 1714-12,000 IU. Of the included studies, 3 reported statistically significant reductions in fasting glucose, 2 reported reductions in fasting insulin, 2 reported reductions in HOMA-IR, none reported reductions in HbA1c and 5 reported no differences in any of the relevant outcomes. In conclusion, in RCTs of vitamin D supplementation in women with PCOS, the majority of studies do not report statistically significant improvements in fasting glucose, fasting insulin, HbA1c or HOMA-IR. However, as a minority of studies report some statistically significant results, further investigation may be warranted. PROSPERO ID: CRD42023486144.

Study of risk factors for insulin resistance in women with a burdened metabolic history

Insulin Resistance (IR) is a state of insufficient biological response of the body's cells to insulin, which leads to further disruption of carbohydrate metabolism and increased blood glucose levels. Early detection of IR risk factors improves the prognosis and prevention of severe metabolic syndrome, preservation and restoration of women's reproductive potential, and becomes the foundation for the health of the future generation. Aim of the study was the influence of potential risk factors on the development of latent IR manifestations 82 women of early reproductive age who signed an informed consent for the study were examined. A specially designed questionnaire was used for the study, and anthropometric parameters and laboratory data (including insulin, glucose tolerance test), and calculation of indices (HOMA-IR (Homeostasis Model Assessment of Insulin Resistance) and Matsuda). According to the results of the study, in accordance with the indicators of Relative Risk (RR) and Odds Ratio (OR), we consider the following potential factors to be developmental bad habits (tobacco smoking regardless of the amount, regular alcohol abuse) (RR=1.299; p=0.00321), burdened hereditary history of cardiovascular diseases (essential hypertension, heart attacks and strokes) (RR=1.313; p=0.0041), type I and type II diabetes mellitus (RR=1.340; p=0.0038), obesity (RR=1.641; p=0.0043), thyroid diseases (hypothyroidism, hyperthyroidism, hyperparathyroidism) (RR=1.565; RR=1.565; p=0.00284) and adrenal (Itzen-Cushing's syndrome, adrenal cortex insufficiency) (RR=1.348; p=0.0025). The manifestations of IR should be skin rashes (OR=3.542; p=0.0033) and unwanted hair growth (OR=3.670; p=0.0029). Keywords: overweight, obesity, metabolic syndrome, vaginal microbiome, ovulation, infertility.

Insulin Resistance in Women Correlates with Chromatin Histone Lysine Acetylation, Inflammatory Signaling, and Accelerated Aging.

Epigenetic changes link medical, social, and environmental factors with cardiovascular and kidney disease and, more recently, with cancer. The mechanistic link between metabolic health and epigenetic changes is only starting to be investigated. In our in vitro and in vivo studies, we performed a broad analysis of the link between hyperinsulinemia and chromatin acetylation; our top "hit" was chromatin opening at H3K9ac. Building on our published preclinical studies, here, we performed a detailed analysis of the link between insulin resistance, chromatin acetylation, and inflammation using an initial test set of 28 women and validation sets of 245, 22, and 53 women. ChIP-seq identified chromatin acetylation and opening at the genes coding for TNFα and IL6 in insulin-resistant women. Pathway analysis identified inflammatory response genes, NFκB/TNFα-signaling, reactome cytokine signaling, innate immunity, and senescence. Consistent with this finding, flow cytometry identified increased senescent circulating peripheral T-cells. DNA methylation analysis identified evidence of accelerated aging in insulin-resistant vs. metabolically healthy women. This study shows that insulin-resistant women have increased chromatin acetylation/opening, inflammation, and, perhaps, accelerated aging. Given the role that inflammation plays in cancer initiation and progression, these studies provide a potential mechanistic link between insulin resistance and cancer.

Lower Serum ATG7 Levels Linked to Insulin Resistance in Women with Polycystic Ovary Syndrome.

BACKGROUND Previous studies have suggested that autophagy, a cellular process regulated by ATG7, plays a critical role in ovarian physiology and pathology. In this study, our objective was to examine ATG7 levels in women with and without polycystic ovary syndrome (PCOS) and to explore potential associations between serum ATG7 levels and PCOS. MATERIAL AND METHODS The study included 188 women diagnosed with PCOS, matched with an equal number of healthy women for comparison. Serum levels of ATG7 were determined using the ELISA technique, and the difference was assessed using an independent samples t test. The association between ATG7 serum levels and the risk of developing PCOS was evaluated by using a multivariable logistic regression model. Additionally, the potential of ATG7 to predict PCOS was investigated through logistic regression and receiver operating characteristic (ROC) analysis. RESULTS Our study found that women with PCOS had significantly lower serum ATG7 levels than their healthy counterparts. Lower ATG7 levels were associated with a higher risk of developing PCOS after adjusting for various confounding variables. The combination of ATG7 with HOMA-IR performed well in predicting PCOS, with an AUC of 92.3%, a sensitivity of 88.3%, and a specificity of 85.3%. CONCLUSIONS Our study found that serum ATG7 levels were significantly lower in women with PCOS and were associated with an increased risk of developing PCOS. This suggests that ATG7 could potentially serve as a biomarker for diagnosing and managing PCOS.

The Efficacy and Safety of DLBS3233, A Combined Bioactive Fraction of Cinnamomum burmanii and Lagerstroemia speciosa Plants on The Endocrine-Metabolic Profile of Women with Polycystic Ovary Syndrome: A Randomized Clinical Trial.

A bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa, DLBS3233, has recently been used for type-2-diabetes treatment due to its favorable effect on insulin sensitivity. The insulin resistance leading to metabolic syndrome is closely linked to hyperandrogenemia in polycystic ovary syndrome (PCOS). This study evaluated the metabolic and reproductive efficacy and safety of DLBS3233 in insulin-resistant PCOS women. This was a 2-arm, randomized, double-blind, controlled, noninferiority clinical study over a 6-month therapy with DLBS3233 100-mg daily in comparison to metformin-XR 750 mg twice daily, involving 124 PCOS women with insulin resistance. The primary efficacy endpoint was the improvement of Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). Secondary endpoints were improvements in other metabolic and reproductive parameters. Safety endpoints were based on blood pressure, heart rate, electrocardiogram findings, liver and renal function, and adverse events. After 6 months, HOMA-IR improvement in DLBS3233-treated group (-1.03 ± 0.50) and metformin-XR (-1.19 ± 0.50) were comparable, with a between-group difference fell within the pre-set non-inferiority margin (0.16; 95% confidence interval (CI): -1.24, 1.56; P=0.3168). The HOMA-IR in both groups were significantly improved from baseline. On all secondary endpoints, both groups showed comparable effects. Markedly fewer adverse events occurred in the DLBS3233 treated group than in the Metformin-XR-treated group and most were mild clinically and had been resolved by the end of the study. Treatment with DLBS3233 100-mg daily in PCOS women demonstrated comparable efficacy to metformin- XR 750-mg twice daily in improving insulin resistance. However, the non-inferiority of DLBS3233 to metformin- XR remains inconclusive. DLBS3233 was more tolerable than metformin-XR (registration number: NCT01733459).

Association of Adiposity indices with insulin resistance in women with polycystic ovary syndrome

Association of Adiposity indices with insulin resistance in women with polycystic ovary syndrome

High Fructose Diet (HFrD) Induced Hepatic Insulin Resistance Is Not Present in Liver Androgen Receptor Knockout (LivARKO) Male Mice

Background: Hyperandrogenism (HA), a common symptom of polycystic ovary syndrome (PCOS), involves action of the androgen receptor (AR) and can induce insulin resistance among 35-80% of PCOS women (PMID 35432749: Amisi 2022). The liver plays an essential role in the metabolism of insulin and androgen signaling. HA has been shown to increase insulin resistance in women and female mice. Previous studies have suggested that knocking out liver AR can lead to improvements in metabolic and reproductive functions of PCOS (PMID 34547140: Andrisse 2021). Hypothesis: We hypothesized that liver androgen receptor knockout (LivARKO) mice on a high fructose diet would exhibit increased insulin resistance compared to controls, as measured by expression of phospho-Akt (p-Akt) and phospho-FoxO1 (p-foxo1), proteins involved in insulin signaling. Methods: LivARKO mice were divided into groups based on an assigned diet (Control or High Fructose; Con, Research Diets Inc, RDI D12450J, Protein (20%), Carbs (70%, corn starch-50%, sucrose-maldextrin-20%, fructose-0%), Fat 10% (lard)) and High Fructose (HFrD, RDI D02022704, Protein (20%), Carbs (70%, corn starch-9%, sucrose-maldextrin-1%, fructose-60%), Fat 10% (lard)). The mice were sacrificed and liver tissue samples were extracted for western blotting analysis examining p-Akt S473 and p-foxo1 S256 levels. Results: LivARKO male mice fed the control diet for one month displayed a significant increase in p-AKT expression when stimulated with insulin compared to basal controls. Similarly, LivARKO male mice fed the high fructose diet for one month displayed a significant increase in p-AKT expression when stimulated with insulin compared to basal mice on the same diet. After one month, LivARKO male mice on a control diet stimulated with insulin displayed significantly decreased p-Foxo1 expression compared to non-stimulated basal control. A similar trend was seen between basal and insulin-stimulated groups in the LivARKO-HFrD male mice, though this trend was not significant. Discussion: These findings suggested that the HFrD did not induce hepatic insulin resistance in LivARKO male mice. Here, we observed a similar pattern of increased insulin stimulated p-AKT to what is seen in WT mice on a chow diet (PMCID PMC3296881: Lu 2012); and this suggested that LivARKO did not disrupt insulin signaling in the liver of male mice when fed a control diet, which was similar to what was seen previously (DOI: 10.1002/hep.22252, Lin 2008, insulin increased PI3K activity in chow diet LivARKO male mice). Our data suggested that the HFrD induced hepatic insulin resistance seen in some WT models (such as PMCID PMC3131094: Nagai 2009) is not present in LivARKO male mice.This also suggested that unlike HFD, HFrD did not cause insulin resistance in LivARKO male mice. These results illuminate LivARKO as a potential therapeutic target for insulin resistance. This project was supported by the following grants to Dr. Stanley Andrisse. (1) NIH 1R01DK126892; (2) NIH 1T34GM142610; and (3) NSF 1931045. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Association between serum levels of calcium, magnesium, iron and copper and insulin resistance in women with full blown and not-full blown phenotypes of polycystic ovary syndrome.

The aim of present study was to investigate the association between serum calcium, iron, magnesium, copper levels and insulin resistance in women with full blown phenotype of polycystic ovary syndrome (PCOS) compared to women with not-full blown phenotype. 104 women, aged 18-39, in the first phase of menstrual cycle, diagnosed with PCOS based on the Rotterdam Criteria, were qualified for the study. Patients were divided into two groups: group I contained women with full blown PCOS (phenotype A) and group II contained women with not-full blown PCOS (phenotypes B, C and D). Whole study population was divided on group X containing women with proper insulin sensitivity and group Y containing women with insulin resistance. The study found that women with full blown PCOS had lower level of magnesium compared with not-full blown phenotypes. Also, the level of copper was lower in group with proper insulin sensitivity compared to group with insulin resistance. Serum cooper content showed a negative correlation with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in group with full blown phenotype. Magnesium level showed positive correlation with level of calcium and cooper in group with proper insulin sensitivity. Level of iron content showed a negative correlation with sex hormone binding globulin (SHBG) and HOMA-IR showed a positive correlation with age and body mass index (BMI) in group with insulin resistance. Either level of calcium showed positive correlation with iron and cooper in group with insulin resistance.

Evaluation of serum adiponectin as a marker of insulin resistance in women with polycystic ovarian syndrome: a comparative cross-sectional study

BackgroundInsulin resistance (IR) is known to be prevalent amongst women with polycystic ovarian syndrome (PCOS). Its presence has been linked to chronic anovulation and marked long term complications in women. Hence, identification and treatment of IR in women with PCOS is required to prevent the metabolic and reproductive complications of the disease. The aim of this study is to determine if serum adiponectin could be used as a surrogate marker for insulin resistance among women with PCOS.Materials and methodsA total number of 148 consenting women with PCOS diagnosed using the Rotterdam criteria were recruited for this study. Fifty-two of these women had insulin resistance were compared with 96 of the women who did not have insulin resistance. The serum Adiponectin levels, fasting blood glucose and fasting insulin levels were assayed in all study participants. Insulin resistance was assessed in all the study participants using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Data were analyzed using relevant inferential statistics at 95% confidence interval and p value of < 0.05.ResultsThe prevalence of insulin resistance among the study participants was 35.1%. Majority of the women (83.1%) had a high body mass index (BMI). More than half (68.2%) of the participants were in the age range of 21-30years and 76.4% (113) were nulliparous. There was no statistically significant difference in the median adiponectin level among insulin resistant (3.735 ug/ml) and non-insulin resistant participants vs. (3.705 ug/ml) (p = 0.6762). Both univariate and multivariate regression analysis did not show a statistically significant relationship between adiponectin and insulin resistance in PCOS.ConclusionThe prevalence of insulin resistance in women with PCOS is high and serum adiponectin is not a suitable surrogate marker of insulin resistance in women with PCOS.

A Cross-Sectional Study of Protein Changes Associated with Dementia in Non-Obese Weight Matched Women with and without Polycystic Ovary Syndrome.

Dysregulated Alzheimer's disease (AD)-associated protein expression is reported in polycystic ovary syndrome (PCOS), paralleling the expression reported in type 2 diabetes (T2D). We hypothesized, however, that these proteins would not differ between women with non-obese and non-insulin resistant PCOS compared to matched control subjects. We measured plasma amyloid-related proteins levels (Amyloid-precursor protein (APP), alpha-synuclein (SNCA), amyloid P-component (APCS), Pappalysin (PAPPA), Microtubule-associated protein tau (MAPT), apolipoprotein E (apoE), apoE2, apoE3, apoE4, Serum amyloid A (SAA), Noggin (NOG) and apoA1) in weight and aged-matched non-obese PCOS (n = 24) and control (n = 24) women. Dementia-related proteins fibronectin (FN), FN1.3, FN1.4, Von Willebrand factor (VWF) and extracellular matrix protein 1 (ECM1) were also measured. Protein levels were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. Only APCS differed between groups, being elevated in non-obese PCOS women (p = 0.03) relative to the non-obese control women. This differed markedly from the elevated APP, APCS, ApoE, FN, FN1.3, FN1.4 and VWF reported in obese women with PCOS. Non-obese, non-insulin resistant PCOS subjects have a lower AD-associated protein pattern risk profile versus obese insulin resistant PCOS women, and are not dissimilar to non-obese controls, indicating that lifestyle management to maintain optimal body weight could be beneficial to reduce the long-term AD-risk in women with PCOS.

Silymarin Reduced Insulin Resistance in Non-Diabetic Women with Obesity.

Silymarin has ameliorated obesity, type 2 diabetes (T2DM), and insulin resistance (IR) in combination with standard therapy, diet, or exercise in recent studies. Obesity and IR are the main risk factors for developing T2DM and other metabolic disorders. Today, there is a need for new strategies to target IR in patients with these metabolic diseases. In the present longitudinal study, a group of non-diabetic insulin-resistant women with type 1 and type 2 obesity were given silymarin for 12 weeks, with no change in habitual diet and physical activity. We used the Homeostatic Model Assessment for Insulin Resistance Index (HOMA-IR) to determine IR at baseline and after silymarin treatment (t = 12 weeks). We obtained five timepoint oral glucose tolerance tests, and other biochemical and clinical parameters were analyzed before and after treatment. Treatment with silymarin alone significantly reduced mean fasting plasma glucose (FPG) and HOMA-IR levels at 12 weeks compared to baseline values (p < 0.05). Mean fasting plasma insulin (FPI), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (Tg), indirect bilirubin, and C-reactive protein (CRP) levels decreased compared to baseline values, although changes were non-significant. The overall results suggest that silymarin may offer a therapeutic alternative to improve IR in non-diabetic individuals with obesity. Further clinical trials are needed in this type of patient to strengthen the results of this study.

Effect of resveratrol on insulin action in primary myotubes from lean individuals and individuals with severe obesity.

Resveratrol, a natural polyphenol compound contained in numerous plants, has been proposed as a treatment for obesity-related disease processes such as insulin resistance. However, in humans there are conflicting results concerning the efficacy of resveratrol in improving insulin action; the purpose of the present study was to determine whether obesity status (lean, severely obese) affects the response to resveratrol in human skeletal muscle. Primary skeletal muscle cells were derived from biopsies obtained from age-matched lean and insulin-resistant women with severe obesity and incubated with resveratrol (1 µM) for 24 h. Insulin-stimulated glucose oxidation and incorporation into glycogen, insulin signal transduction, and energy-sensitive protein targets [AMP-activated protein kinase (AMPK), Sirt1, and PGC1α] were analyzed. Insulin-stimulated glycogen synthesis, glucose oxidation, and AMPK phosphorylation increased with resveratrol incubation compared with the nonresveratrol conditions (main treatment effect for resveratrol). Resveratrol further increased IRS1, Akt, and TBC1D4 insulin-stimulated phosphorylation and SIRT1 content in myotubes from lean women, but not in women with severe obesity. Resveratrol improves insulin action in primary human skeletal myotubes derived from lean women and women with severe obesity. In women with obesity, these improvements may be associated with enhanced AMPK phosphorylation with resveratrol treatment.NEW & NOTEWORTHY A physiologically relevant dose of resveratrol increases insulin-stimulated glucose oxidation and glycogen synthesis in myotubes from individuals with severe obesity. Furthermore, resveratrol improved insulin signal transduction in myotubes from lean individuals but not from individuals with obesity. Activation of AMPK plays a role in resveratrol-induced improvements in glucose metabolism in individuals with severe obesity.

Increased GPC4 and clusterin associated with insulin resistance in patients with PCOS.

The aim of the study was to investigate the changes in serum glypican 4 (GPC4) and clusterin (CLU) levels in patients with polycystic ovary syndrome (PCOS) as well as their correlation with sex hormones and metabolic parameters. A total of 40 PCOS patients and 40 age-matched healthy women were selected. Serum GPC4 and CLU levels were compared between the PCOS and control groups, and binary logistic regression was used to analyze the relative risk of PCOS at different tertiles of serum GPC4 and CLU concentrations. Stepwise linear regression was used to identify the factors influencing serum GPC4 and CLU levels in PCOS patients. Serum GPC4 (1.82 ± 0.49 vs 1.30 ± 0.61 ng/mL, P < 0.001) and CLU (468.79 ± 92.85 vs 228.59 ± 82.42 µg/mL, P < 0.001) were significantly higher in PCOS patients than in healthy women after adjustment for body mass index (BMI). In the PCOS group, serum GPC4 was positively correlated with follicle-stimulating hormone, fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride, and CLU (P < 0.05), whereas serum CLU was positively correlated with BMI, FPG, FINS, and HOMA-IR (P < 0.05). Multiple stepwise linear regression analysis showed that HOMA-IR was independently associated with serum GPC4, and BMI and HOMA-IR were independently associated with CLU (P < 0.05). Serum GPC4 and CLU levels were significantly higher in PCOS patients than in healthy women, suggesting that GPC4 and CLU may be markers associated with insulin resistance in women with PCOS.

Revisiting the predictability of follicular fluid leptin and related adiposity measures for live birth in women scheduled for ICSI cycles: a prospective cohort study

BackgroundOur research question is could follicular fluid (FF) leptin solely or contemporaneously with other clinical, biochemical, and sonographic adiposity measures predict the probability of having a live birth during ICSI cycles? This is a prospective cohort study that enrolled infertile women without polycystic ovary syndrome scheduled for ICSI. At baseline, women had an assessment of obesity using different metrics: clinical, serum biochemical, and sonographic. Clinical measures encompassed waist circumference and body mass index. Biochemical evaluation comprised an assessment of the homeostasis model for insulin resistance, visceral adiposity index, and lipid accumulation product. Preperitoneal and subcutaneous abdominal fat were measured using ultrasound and body fat index was calculated. On the day of oocyte retrieval, pooled FF was sampled to assess FF leptin. Our primary outcome was live birth after one fresh embryo transfer cycle.ResultsOut of 91 women analyzed in this study, 28 have a live birth (30.8%). No difference in FF leptin concentration was found between women with and without live birth (mean ± SD; 20336 ± 8006 vs 18493 ± 6655 pg/ml; P = 0.2). None of the assessed adiposity markers was a predictor for live birth. Substantially, follicular fluid leptin was positively correlated with insulin resistance in women with and without live birth (r = 0.21, P = 0.04). In logistic regression analysis, the outcome of the prior cycle, the ability to have cryopreserved embryos, and the oocyte maturation index were the predictors for live birth in our study.ConclusionsThe present work could not find evidence that follicular fluid leptin, preperitoneal fat, and other evaluated adiposity measures could impact live births after ICSI cycles.

Overfeeding in the early postnatal period aggravates inflammation and hepatic insulin sensitivity in the 5α-dihydrotestosterone-induced animal model of PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and is closely associated with chronic low-grade inflammation and insulin resistance. To clarify the contribution of prepubertal weight gain to the development of insulin resistance in PCOS, we investigated the effects of early postnatal overfeeding on inflammatory and energy-sensing pathways as well as on markers of insulin signaling in the liver of the PCOS rat model. Obesity induced by overfeeding was achieved by reducing litter size, while the PCOS-like condition was developed by treatment with 5α-dihydrotestosterone (DHT). Western blot and qPCR were used to analyze the expression of pro-inflammatory transcription factors and cytokines, as well as markers of the energy sensing and insulin signaling pathways. The results showed that hepatic insulin sensitivity was impaired only in DHT-treated rats raised in small litters, as evidenced by increased phosphorylation of IRS1 on Ser307 and decreased expression of total IRS1. Postnatal overfeeding stimulated JNK1 activation independent of hyperandrogenemia; nevertheless, the synergistic effect of both factors triggered NLRP3 activation and increased IL1β expression in the small litter DHT-treated group. This pro-inflammatory state was accompanied by decreased activatory phosphorylation of AMPK and reduced levels of its protein targets. Overfeeding in the early postnatal period leads to a decrease in hepatic insulin sensitivity in the rat model of PCOS, which is associated with decreased activation of AMPK and stimulation of the hepatic NLRP3-IL1β signaling pathway. Accordingly, the inhibition of NLRP3 activation could provide a basis for the development of new therapeutic strategies for the treatment of insulin resistance in women with PCOS.

Correlation of Vitamin D Levels with Insulin Resistance in women with PCOS

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder. Since PCOS impacts insulin metabolism and fertility, gene transcription and hormone regulation play a role in its development. The symptoms of PCOS, namely insulin resistance, ovulation, menstrual irregularities, infertility, hyperandrogenism, obesity, and an increase in the risk of cardiovascular disease can be worsen by decrement of 25(OH)D level. This study aimed to determine the phenotype distribution of PCOS; to know the levels of Vitamin D in women with PCOS; to know the picture of insulin resistance in women with PCOS with excess body weight; to analyze the relationship of Vitamin D with insulin resistance in women with PCOS. This study used analytical test with randomization on PCOS patients. The phenotypes of the study samples were phenotype 1 (6 patients = 30%) and phenotype 4 (14 patients = 70%), phenotypes 2 and 3 were not found; There was no relationship between vitamin D and insulin (12.635±4.2721 vs 11.407±4.2721; p= 0,068);There was no relationship between vitamin D and glucose (12.635 ±4.2721 vs 102.75±10.015; p= 0,835); There is a relationship between vitamin D and HOMA IR (12.635± 4.2721 vs 2.880±.4213; p = 0,026; r -0,497) with a negative correlation between the two variables and there is a relationship between BMI with HOMA-IR and vitamin D (p=0,001 and p= 0,003).There is a negative relationship between vitamin D and HOMA-IR, namely a decrease in vitamin D causes an increase in HOMA-IR (insulin resistance).

Increased OCT3 Expression in Adipose Tissue With Aging: Implications for Catecholamine and Lipid Turnover and Insulin Resistance in Women.

Catecholamine-stimulated lipolysis is reduced with aging, which may promote adiposity and insulin resistance. Organic cation transporter 3 (OCT3), which is inhibited by estradiol (E2), mediates catecholamine transport into adipocytes for degradation, thus decreasing lipolysis. In this study, we investigated the association of OCT3 mRNA levels in subcutaneous adipose tissue (SAT) with aging and markers of insulin resistance in women. SAT biopsies were obtained from 66 women with (19) or without (47) type 2 diabetes (age 22-76 years, 20.0-40.1 kg/m2). OCT3 mRNA and protein levels were measured for group comparisons and correlation analysis. SAT was incubated with E2 and OCT3 mRNA levels were measured. Associations between OCT3 single nucleotide polymorphisms (SNPs) and diabetes-associated traits were assessed. OCT3 mRNA and protein levels in SAT increased with aging. SAT from postmenopausal women had higher levels of OCT3 than premenopausal women, and there was a dose-dependent reduction in OCT3 mRNA levels in SAT treated with E2. OCT3 mRNA levels were negatively associated with markers of insulin resistance, and ex vivo lipolysis. OCT3 SNPs were associated with BMI, waist to hip ratio, and circulating lipids (eg, triglycerides). OCT3 mRNA and protein levels in SAT increased with aging, and mRNA levels were negatively associated with markers of insulin resistance. E2 incubation downregulated OCT3 mRNA levels, which may explain lower OCT3 mRNA in premenopausal vs postmenopausal women. High OCT3 protein levels in adipose tissue may result in increased catecholamine degradation, and this can contribute to the reduction in lipolysis observed in women with aging.

Fat-free mass index is a feasible predictor of insulin resistance in women with polycystic ovary syndrome: Evidence from a cross-sectional study.

Insulin resistance (IR) and adipose tissue amplify the metabolic and reproductive outcomes in women with polycystic ovary syndrome (PCOS). It has been widely discussed that body composition influences metabolic health. Still, limited studies were focused on the role of the fat-free mass index (FFMI) in assessing IR in PCOS women. We aimed to explore the associations between FFMI/fat mass index (FMI) and IR in women with PCOS and assess the role of FFMI in predicting IR in women with PCOS. In the current cross-sectional study, women with PCOS aged between 18 and 40 years were enrolled from October 2018 to July 2022. Baseline demographic information was obtained using standardized self-administered questionnaires. Anthropometric, biochemical, and hormonal information was measured and recorded by investigators. Pearson's correlation and multivariable logistical regression were used to analyze the associations of FFMI/FMI and IR. In addition, receiver operating characteristic (ROC) curves were implied to measure the predictive role of FFMI/FMI for IR in women with PCOS. A total of 371 women with PCOS, reproductive age (27.58 ± 4.89) were enrolled. PCOS women with IR have higher levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), homeostatic model assessment of insulin resistance (HOMA-IR), FMI, and FFMI than that without IR. FMI (r = 0.492, p < 0.001) and FFMI (r = 0.527, p < 0.001) were positively associated with IR. After adjusting for potential confounders, FMI and FFMI were significantly associated with IR in PCOS women, and the OR was 1.385 (95%CI: 1.212-1.583) and 2.306 (95%CI: 1.675-3.174), respectively. Additionally, the FFMI (0.847, 95%CI: 0.784-0.888) has a larger area of ROC (AUC) than the FMI (0.836, 95%CI: 0.799-0.896), while there is no difference in predicting IR (95%CI: -0.18-0.41, p = 0.456). These results indicated that FFMI and FMI could significantly increase the risk of IR, both of which could be feasible predictors of IR in PCOS women.

The association between triglyceride-glucose index and cognitive function in nondiabetic elderly: NHANES 2011–2014

BackgroundThe relationship between Insulin resistance (IR) evaluated through homeostasis model assessment insulin resistance (HOMA-IR) and cognitive function is controversial among nondiabetic individuals. No study so far has reported the association between the IR evaluated through triglyceride glucose (TyG) index and cognitive function among nondiabetics. This study aims to assess this association among US nondiabetic older elderly.MethodsData were obtained from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). Low cognitive function was evaluated using the Consortium to Establish a Registry for Alzheimer’s Disease Battery for immediate word list learning (CERAD-WL) and delayed recall (CERAD-DR) test, the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Logistic regression analyses were conducted to compute the odds ratio (OR) and 95% confidential interval (CI) to examine the association between the TyG index (continuous and quartiles) and low cognitive function.ResultsA total of 661 nondiabetic older adults were included with a mean age of 68.62 ± 6.49 years. Compared to the 1st quartile of the TyG index, participants in the TyG index 4th quartile were associated with low cognitive function evaluated through the CERAD test (CERAD-WL and CERAD-DR) [OR: 2.62; 95% CI (1.31, 5.23); P < 0.05]. Subgroup analyses showed that females (ORQ4 VS Q1: 3.07; 95% CI (1.04, 9.05); P < 0.05) and smokers (OR Q4 VS Q1: 2.70; 95% CI (1.01, 7.26); P < 0.05) categories were related with a higher risk of low cognitive function.ConclusionsA high TyG index was strongly correlated with low cognitive function evaluated through the CERAD test (CERAD-WL and CERAD-DR) among US nondiabetic older women. The management of IR in women might be beneficial to primarily prevent low cognitive function among nondiabetic older elderly.