Higher Insulin Research Articles

Causal associations between insulin and Lp(a) levels in Caucasian population: a Mendelian randomization study

BackgroundNumerous observational studies have demonstrated that circulating lipoprotein(a) [Lp(a)] might be inversely related to the risk of type 2 diabetes (T2D). However, recent Mendelian randomization (MR) studies do not consistently support this association. The results of in vitro research suggest that high insulin concentrations can suppress Lp(a) levels by affecting apolipoprotein(a) [apo(a)] synthesis. This study aimed to identify the relationship between genetically predicted insulin concentrations and Lp(a) levels, which may partly explain the associations between low Lp(a) levels and increased risk of T2D.MethodsIndependent genetic variants strongly associated with fasting insulin levels were identified from meta-analyses of genome-wide association studies in European populations (GWASs) (N = 151,013). Summary level data for Lp(a) in the population of European ancestry were acquired from a GWAS in the UK Biobank (N = 361,194). The inverse-variance weighted (IVW) method approach was applied to perform two-sample summary-level MR. Robust methods for sensitivity analysis were utilized, such as MR‒Egger, the weighted median (WME) method, MR pleiotropy residual sum and outlier (MR-PRESSO), leave-one-out analysis, and MR Steiger.ResultsGenetically predicted fasting insulin levels were negatively associated with Lp(a) levels (β = − 0.15, SE = 0.05, P = 0.003). The sensitivity analysis revealed that WME (β = − 0.26, SE = 0.07, P = 0.0002), but not MR‒Egger (β = − 0.22, SE = 0.13, P = 0.11), supported a causal relationship between genetically predisposed insulin levels and Lp(a).ConclusionOur MR study provides robust evidence supporting the association between genetically predicted increased insulin concentrations and decreased concentrations of Lp(a). These findings suggest that hyperinsulinaemia, which typically accompanies T2D, can partially explain the inverse relationship between low Lp(a) concentrations and an increased risk of T2D.

Exploring Factors Influencing Stroke Risk: Insights From a Predictive Analysis.

Introduction Stroke is a serious medical condition characterized by the sudden interruption of blood flow to the brain, resulting in the death of brain cells. It is a leading cause of long-term disability and mortality worldwide. Stroke has some associated risk factors, both modifiable and non-modifiable ones.As for non-modifiable risk factors, these are age, gender (men are more vulnerable), and family history of stroke.The controllable or adjustable risk factors include hypertension (high blood pressure), diabetes, smoking, high cholesterol levels, obesity, and insulin resistance. Methods In our study, we collected data from 229 patients which were originally collected for clinical purposes and were retrospectively analyzed. These data contain features such assex and age, the presence of ischemic heart disease (IHD) or stroke history, and different blood sugar readings. These measurements include fasting blood sugar (FBS), postprandial blood sugar (PPBS), HbA1c%, and insulin levels (fasting and postprandial).Furthermore, cholesterol was also tested, such as total cholesterol, triglycerides (TGL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL). Surprisingly, stroke was observed in 24of the 205 patients. This contrast permits us to be concerned with the chance of the association between stroke and insulin levels. Given the imbalanced nature of our outcome variable (stroke occurrence), the primary analytical method will be logistic regression. Results In this cross-sectional study, we investigated the association between high insulin levels (both fasting and postprandial) and the occurrence of stroke within a dataset of 229 patients. Out of the 229 included cases, 102 individuals were female (44.5%) and 127 individuals were male (55.5%). Twenty-four cases have ischemic heart disease (10.5%). Among the analyzed cases, 24 individuals have a history of stroke. The average age of the sample is approximately 57 years ± 14.87. There was no significant difference between the males and females in most of the descriptive statistics. However, females experienced significantly higher levels of postprandial glucose level and significantly lower levels of postprandial insulin. According to our predictive model, we found that an increase in fasting insulin levels was linked to a lower risk of stroke occurrence. On the other hand, increasing insulin postprandial levels and age were associated with an increased risk of stroke. Conclusion Our study identified age, fasting insulin, and postprandial insulin as key factors influencing stroke risk. Higher fasting insulin levels were associated with reduced risk, while increased postprandial insulin and age were linked to higher risk. Blood glucose, cholesterol, and triglycerides had minor effects. Notably, higher total cholesterol and triglyceride levels were slightly associated with lower stroke occurrence. Further research with larger samples is needed for validation.

Potatoes Compared with Rice in Meals with either Animal or Plant Protein Reduce Postprandial Glycemia and Increase Satiety in Healthy Adults: A Randomized Crossover Study

BackgroundRice and pasta are recommended as healthier than potatoes on the basis of their glycemic index when eaten alone. ObjectivesThe study objective was to evaluate postprandial glycemia (PPG), appetite, and food intake (FI) at meals with potatoes or rice when consumed with either meatballs or their vegetarian substitute. MethodsIn a randomized, single-blinded, crossover design, 26 (13 males and 13 females) healthy adults (age: 18–45 y; body mass index [kg/m2]: 18.5–29.9) consumed isocaloric fixed amounts of either meatballs or vegetarian-substitute balls with ad libitum access to either baked French fries (BFF), instant mashed potatoes (IMPs), or rice (control). FI was measured at the meal and at an ad libitum pizza meal served 120 min later. Blood glucose (BG), appetite, and plasma insulin responses were measured within the meal (0–30 min), postmeal (30–120 min), within pizza meal (120–140 min), and post-pizza (140–170 min). Effects of protein source, carbohydrate (CHO) source, and sex and their interactions were analyzed using analysis of variance followed by Tukey’s post hoc test. ResultsParticipants consumed 23–25% less treatment meal energy (kcal), 32–34% less CHO energy (kcal), and 13–16% less total energy (kcal) after the BFF and IMP than rice meals (P < 0.0001). Postmeal BG was lower after IMP (6.76 ± 0.15; P < 0.0001) and rice (6.92 ± 0.15; P = 0.0012) compared with BFF (7.19 ± 0.15). Post-pizza BG was higher after rice (6.77 ± 0.09) than that after BFF (6.51 ± 0.09; P = 0.0012) and IMP (6.39 ± 0.09; P < 0.0001). Postmeal meaned insulin was higher after BFF (82.16 ± 8.58) and IMP (77.75 ± 8.60) compared with rice (56.44 ± 8.59; P < 0.002). Insulin during pizza meal was lower after BFF (17.14 ± 6.90) compared with both IMP (39.03 ± 6.90; P = 0.0060) and rice (34.21 ± 6.90; P = 0.0336). Meatballs led to lower BG (6.48 ± 0.09; P = 0.0076) and higher insulin (84.54 ± 5.87; P = 0.0406) post-pizza compared with their plant protein substitute (6.64 ± 0.09 and 73.18 ± 5.87, respectively). ConclusionsAdults consuming meatballs or plant-based substitute with ad libitum IMP had lower PPG post-treatment and at a later pizza meal compared with rice. Both IMP and BFF resulted in lower energy intake than after rice.This trial was registered at http://clinicaltrials.gov (https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000CKIJ&selectaction=Edit&uid=U0000IA4&ts=2&cx=-uf51kf) as NCT05610124. Protocol ID: 43406 (Postprandial Glycemia and Satiety of Meals with Potatoes, with and without Protein).

Targeting cancer stress-associated hyperinsulinemia and abnormal behavior mitigates lung carcinoma in postmenopausal mouse: Intervention function of peimine

Obesity stress and its associated metabolic disruption increase the likelihood and advancement of several forms of malignancies, such as postmenopausal lung cancer in humans. Also, the mechanism of lung cancer stress-related cognitive impairment and rhythm change are still unknown. Peimine (PE), an alkaloid derived from the Fritillaria genus, has the ability to mitigate the metabolic dysfunctions induced by obesity and inhibit tumor growth. The objective of this study was to investigate the regulatory impact of PE on obese mice with postmenopausal lung cancer generated by a high fat diet. Our initial findings indicate that PE can significantly reduce the metabolic dysfunction caused by a high-fat diet in mice. This is demonstrated by better glucose tolerance and insulin resistance, reduced accumulation of lipids in the liver, and improved histological alterations in the mammary fat pad. Subsequently, the treatment of PE suppressed the formation of lung tumors caused by a high-fat diet in mice models placed in their original location. In addition, PE effectively inhibited the formation of pre-existing lung tumors in a mouse model of postmenopausal women who were fed a high-fat diet. This treatment also reduced the severity of metabolic problems. Notably, laboratory studies demonstrated that insulin exposure increased the growth and movement of lung cancer cells, but this effect was significantly reduced when the cells were co-cultured with PE. Meanwhile, PE intervention can significantly alleviate cancer stress-related cognitive impairment and disturbed circadian rhythm changes and associated gene expression abnormalities in model animals. Analysis using bioinformatics and molecular biology techniques revealed that PE has the ability to decrease the expression levels of signal transducer and activator of transcription 3 (STAT3) in the liver, mammary fat pad, and tumor tissues of postmenopausal mice with obesity generated by a high-fat diet. The inhibitory effects of PE on the growth and movement of lung cancer cells induced by insulin were completely eliminated when STAT3 expression was removed. This suggests that the suppression of STAT3 expression is crucial for PE to exert its anti-cancer effects against lung cancer in the presence of high insulin levels. The findings of our study indicate that consuming PE is highly effective in preventing and treating lung cancer that is connected with obesity. This is achieved via regulating the signaling pathway of STAT3.

Major depletion of insulin sensitivity-associated taxa in the gut microbiome of persons living with HIV controlled by antiretroviral drugs

BackgroundPersons living with HIV (PWH) harbor an altered gut microbiome (higher abundance of Prevotella and lower abundance of Bacillota and Ruminococcus lineages) compared to non-infected individuals. Some of these alterations are linked to sexual preference and others to the HIV infection. The relationship between these lineages and metabolic alterations, often present in aging PWH, has been poorly investigated.MethodsIn this study, we compared fecal metagenomes of 25 antiretroviral-treatment (ART)-controlled PWH to three independent control groups of 25 non-infected matched individuals by means of univariate analyses and machine learning methods. Moreover, we used two external datasets to validate predictive models of PWH classification. Next, we searched for associations between clinical and biological metabolic parameters with taxonomic and functional microbiome profiles. Finally, we compare the gut microbiome in 7 PWH after a 17-week ART switch to raltegravir/maraviroc.ResultsThree major enterotypes (Prevotella, Bacteroides and Ruminococcaceae) were present in all groups. The first Prevotella enterotype was enriched in PWH, with several of characteristic lineages associated with poor metabolic profiles (low HDL and adiponectin, high insulin resistance (HOMA-IR)). Conversely butyrate-producing lineages were markedly depleted in PWH independently of sexual preference and were associated with a better metabolic profile (higher HDL and adiponectin and lower HOMA-IR). Accordingly with the worst metabolic status of PWH, butyrate production and amino-acid degradation modules were associated with high HDL and adiponectin and low HOMA-IR. Random Forest models trained to classify PWH vs. control on taxonomic abundances displayed high generalization performance on two external holdout datasets (ROC AUC of 80–82%). Finally, no significant alterations in microbiome composition were observed after switching to raltegravir/maraviroc.ConclusionHigh resolution metagenomic analyses revealed major differences in the gut microbiome of ART-controlled PWH when compared with three independent matched cohorts of controls. The observed marked insulin resistance could result both from enrichment in Prevotella lineages, and from the depletion in species producing butyrate and involved into amino-acid degradation, which depletion is linked with the HIV infection.

Cystic fibrosis-related diabetes develops from a combination of insulin secretion defects and insulin resistance.

The relative contributions of insulin secretory defects and possible additional contribution of insulin resistance for the development of cystic fibrosis (CF)-related diabetes (CFRD) are poorly understood. We aimed to (a) determine which indices of insulin resistance predict progression to CFRD, and (b) to model the relative contributions of insulin secretory function and insulin resistance to predict the risk of CFRD. Three hundred and three individuals living with CF underwent a 2-h oral glucose tolerance test with blood sampling every 30 min at 12-24-month intervals until they developed CFRD or until the end of follow-up (up to 15 years). Indices of insulin resistance (e.g. Stumvoll) and insulin secretion were calculated from oral glucose tolerance test glucose and insulin measurements. CFRD-free survival was assessed by survival analysis. Estimated insulin resistance showed associations with glucose homeostasis and risk of progression to CFRD. The CFRD-free survival was significantly different between quartiles of insulin resistance (p < 0.0001). When patients were subdivided according to both insulin resistance and insulin secretion (insulinogenic index), CFRD-free survival was significantly lower in those with combined lowest insulin secretion and highest insulin resistance (Stumvoll) indices (hazard ratio: 11.2; p < 0.0001). There was no significant difference when the same analysis was performed for the nine other indices. Insulin resistance is correlated with glucose homeostasis and the risk of progression to CFRD. Patients combining low insulin secretion and high insulin resistance had the greatest odds of developing CFRD over a 15-year period.

Insulin-based or non-insulin-based insulin resistance indicators and risk of long-term cardiovascular and all-cause mortality in the general population: A 25-year cohort study

ObjectiveAlthough insulin resistance (IR) has been recognized to be a causal component in various diseases, current information on the relationship between IR and long-term mortality in the general population is limited and conclusions varied among different IR indicators and different populations. We aimed to assess associations between different measurements of IR with long-term all-cause mortality and cardiovascular mortality risk for the general population. Research design and methodsWe included 13,909 individuals from the Third National Health and Nutrition Examination Survey. Mortality was identified via National Death Index information until December 31, 2019. IR was measured using fasting insulin, homeostasis model assessment of IR (HOMA-IR), homeostasis model assessment of β-cell function, quantitative insulin sensitivity check index (QUICKI), insulin-to-glucose ratio (IGR), triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and hypertriglyceridemic-waist phenotype. ResultsDuring median 25-year follow-up, 5,306 all-cause mortality events occurred. After multivariate adjustment, variables significantly associated with elevated all-cause mortality risk were (hazard ratio [95 % confidence interval]): higher insulin (1.07 [1.02;1.13]); HOMA-IR (1.08 [1.03;1.13]); IGR (1.05 [1.00;1.11]); TyG (1.07 [1.00;1.14]); TyG-BMI (1.24 [1.02;1.51]); lower QUICKI (0.91 [0.86–0.96]). After stratification by diabetes status, higher insulin, HOMA-IR, TyG-BMI and lower QUICKI were significantly associated with increased risk of all-cause mortality in both diabetes and non-diabetes populations (all P for interaction > 0.05). Higher TyG (adjusted HR 1.17 [1.09;1.26], P for interaction = 0.018) and hypertriglyceridemic-waist phenotype (adjusted HR 1.26 [1.08;1.46], P for interaction = 0.047) were significantly associated with increased risk of all-cause mortality in patients with diabetes, however, these associations could not be seen in people without diabetes. Similar results were observed between the above-mentioned IR indicators and cardiovascular death. ConclusionsFasting insulin, HOMA-IR, TyG-BMI, and QUICKI may indicate mortality risk in diabetes and non-diabetes populations, with TyG and the hypertriglyceridemic-waist phenotype showing particular relevance for individuals with diabetes. Further studies are needed to validate these findings and determine their broader applicability.

Insulin sensitivity, disposition index and insulin clearance in cystic fibrosis: a cross-sectional study

Aims/hypothesisThe aim of this study was to investigate insulin secretion, insulin sensitivity, disposition index and insulin clearance by glucose tolerance status in individuals with cystic fibrosis (CF) and exocrine pancreatic insufficiency.MethodsIn a cross-sectional study, we conducted an extended (ten samples) OGTT in individuals with pancreatic-insufficient CF (PI-CF). Participants were divided into normal glucose tolerance (NGT), early glucose intolerance (EGI), impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) groups. We used three different oral minimal models to assess insulin secretion, insulin sensitivity and insulin clearance during the OGTT. We evaluated insulin secretion using total secretion (Φ total), first-phase secretion (Φ dynamic) and second-phase secretion (Φ static) from the model, and we estimated the disposition index by multiplying Φ total and insulin sensitivity.ResultsAmong 61 participants (NGT 21%, EGI 33%, IGT 16%, CFRD 30%), insulin secretion indices (Φ total, dynamic and static) were significantly lower in the CFRD group compared with the other groups. Insulin sensitivity declined with worsening in glucose tolerance (p value for trend <0.001) and the disposition index declined between NGT and EGI and between IGT and CFRD. Those with CFRD had elevated insulin clearance compared with NGT (p=0.019) and low insulin secretion (Φ total) was also associated with high insulin clearance (p<0.001).Conclusions/interpretationIn individuals with PI-CF, disposition index declined with incremental impairment in glucose tolerance due to a reduction in both insulin secretion and insulin sensitivity. Moreover in CF, reduced insulin secretion was associated with higher insulin clearance.Graphical

Sleep Duration Alters Overfeeding-mediated Reduction in Insulin Sensitivity.

Weight gain and sleep restriction both reduce insulin sensitivity. However, it is not known if sleep duration alters glucose metabolism in response to overfeeding. To examine the effect of sleep duration on overfeeding-mediated alterations in carbohydrate metabolism and insulin sensitivity. Retrospective exploratory analysis of a longitudinal overfeeding study in healthy participants (n = 28, age: 26.9 ± 5.5 years, body mass index: 25.74 ± 2.45 kg/m2). After providing baseline study measures, participants were overfed 40% above weight maintenance calorie requirements for 8 weeks. Insulin sensitivity was determined by a 2-step hyperinsulinemic-euglycemic clamp. Baseline habitual sleep duration was estimated by accelerometry, and sleep groups were created based on median sleep duration (5.2 hours/night). Overfeeding led to an average body weight gain of 7.3 ± .4 kg. Habitual sleep duration did not alter overfeeding-mediated body weight gain, fat gain, and fat distribution (all P > .15). Compared to participants with more sleep, fasting insulin (P = .01) and homeostatic model assessment for insulin resistance (P = .02) increased while fasting glucose remained unchanged (P = .68) with overfeeding in participants with shorter sleep duration. Glucose infusion rate during high insulin dose was reduced with overfeeding in participants with short sleep duration but not in participants with more sleep (P < .01). Overfeeding mediated weight gain reduced liver, adipose, and whole-body insulin sensitivity prominently in individuals with short sleep duration but not in individuals with longer sleep duration. This suggests that promoting adequate sleep during short periods of overeating may prevent detrimental effects on glucose metabolism.

دور داء السكري في متلازمة تكيس المبايض PCOS

The study focused on the insulin and its relationship with the Polycystic Ovary Syndrome (PCOS) in women. Where was it collected 44 samples of PCOS women and 46 samples as a control group. The results showed a significant decrease in progesterone at (P = 0.001), in women with PCOS. The findings in this study revealed the presence of a link between high insulin levels and polycystic ovarian syndrome, the statistical results demonstrate a positive significant association between insulin and estrogen at (p=0.001), and also found a significant negative correlation between other clinical parameter with insulin at, for those with the syndrome, due to the high level of insulin in their blood and the inability of female hormones and Insulin Antibody (AIA), to play their role in controlling the insulin and blood sugar level. Finally, the study showed that there is a new strong relationship between diabetes on PCOS and abortion.

Optimized Magnetically Docked Ingestible Capsules for Non‐Invasive Refilling of Implantable Devices

Automated drug delivery systems (ADDS) improve chronic disease management by enhancing adherence and reducing patient burden, particularly in conditions like type 1 diabetes, through intraperitoneal insulin delivery. However, periodic invasive refilling of the reservoir is needed in such a class of implantable devices. In previous work, an implantable ADDS with a capsule docking system is introduced for non‐invasive reservoir refilling. Yet, it encounters reliability issues in manufacturing, sealing, and docking design and lacks evidence on intestinal tissue compression effects and chronic in vivo data. This work proposes an optimization of the different components featuring this ADDS. The ingestible capsule is designed, developed, and tested following ISO 13485, exhibiting high insulin stability and optimal sealing for six days in harsh gastrointestinal‐like conditions. A magnetic docking system is optimized, ensuring reliable and stable capsule docking at a clinically relevant distance of 5.92 mm. Histological tests on human intestinal tissues confirm safe capsule compression during docking. Bench tests demonstrate that the integrated mechatronic system effectively docks capsules at various peristalsis‐mimicking velocities. A six‐week in vivo test on porcine models demonstrates chronic safety and provides hints on fibrotic reactions. These results pave the way for the further evolution of implantable ADDS.

Cynomorium songaricum: UHPLC/ESI-LTQ-Orbitrap-MS analysis and mechanistic study on insulin sensitivity of a flavonoid-enriched fraction

BackgroundType 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, posing a significant global health concern due to its increasing prevalence. Insulin resistance (IR) plays a major role in the development of T2DM and is often linked to factors such as obesity, physical inactivity, and a sedentary lifestyle. Recently, there has been growing interest in exploring the potential of natural products for improving insulin sensitivity and glucose metabolism. Among these, Cynomorium songaricum Rupr., an edible parasitic plant, has shown promising antidiabetic effects. However, research on its beneficial effects on IR is still nascent. Therefore, this study aims to investigate the application of a Cynomorium songaricum flavonoid-enriched fraction (CSF) in the treatment of IR in T2DM, along with elucidating the chemical and biochemical mechanisms involved. MethodFirst, UHPLC/ESI-LTQ-Orbitrap-MS was utilized to perform a chemical profiling of CSF. Subsequently, glycogen synthesis, gluconeogenesis and glucose consumption assays were conducted on HepG2 cells with a high glucose high insulin-induced IR model to illustrate the favorable impacts of CSF on IR. Then, an innovative network pharmacology analysis was executed to predict the potential chemical components and hub genes contributing to CSF's protective effect against IR. To further elucidate molecular interactions, molecular docking studies were performed, focusing on the binding interactions between active constituents of CSF and crucial targets. Additionally, an RNA-sequencing assay was employed to uncover the underlying biochemical signaling pathway responsible for CSF's beneficial effects. To validate these findings, western blot and qPCR assays were employed to verify the pathways related to IR and the potential signaling cascades leading to the amelioration of IR. ResultsThe UHPLC/ESI-LTQ-Orbitrap-MS analysis successfully identified a total of thirty-six flavonoids derived from CSF. Moreover, CSF was shown to significantly improve glycogen synthesis and glucose consumption as well as inhibit gluconeogenesis in HepG2 cells of IR. An innovative network pharmacology analysis unveiled key hub genes—AKT1 and PI3K—integral to metabolic syndrome-related signaling pathways, which contributed to the favorable impact of CSF against IR. Noteworthy active ingredients including quercetin, ellagic acid and naringenin were identified as potential contributors to these effects. The results of western blot and qPCR assays provided compelling evidence that CSF improved insulin sensitivity by modulating the PI3K-Akt signaling pathway. Subsequent RNA-sequencing analysis, in tandem with western blot assays, delved deeper into the potential mechanisms underlying CSF's advantageous effects against IR, potentially associated with the enhancement of endoplasmic reticulum (ER) proteostasis. ConclusionCSF exhibited a remarkable ability to enhance insulin sensitivity in the IR model of HepG2 cells. This was evident through enhancements in glycogen synthesis and glucose consumption, along with its inhibitory impact on gluconeogenesis. Furthermore, CSF demonstrated an improvement in the insulin-mediated PI3K-Akt signaling pathway. The potential active constituents were identified as quercetin, ellagic acid and naringenin. The underlying biochemical mechanisms responsible for CSF's beneficial effects against IR were closely linked to its capacity to mitigate ER stress, thereby offering a comprehensive understanding of its protective action.

Associations between different triglyceride glucose index-related obesity indices and periodontitis: results from NHANES 2009–2014

BackgroundThis study aimed to explore the associations between triglyceride glucose (TyG) index-related obesity indices and periodontitis within the American population.MethodsThis cross-sectional investigation utilized data from the National Health and Nutrition Examination Survey (NHANES) for 2009–2014. The association between the TyG–waist-to-height ratio (TyG-WHtR), TyG–weight-adjusted-waist index (TyG-WWI), TyG–waist circumference (TyG-WC), or TyG–body mass index (TyG-BMI) and periodontitis was investigated utilizing multivariable logistic regression model, subgroup, and dose-response curve analyses.ResultsThis study enrolled 4,808 adult participants. Except for TyG-BMI, which did not exhibit a relationship with periodontitis, TyG-WHtR, [odds ratio (OR) (95% confidence interval (CI))] = 2.83 [1.58–5.10], P = 0.002], TyG-WWI [OR (95% CI) = 7.50 (3.06–18.34), P < 0.001], and TyG-WC [OR (95% CI) = 2.12 (1.23–3.64), P = 0.011] were all associated with periodontitis. Participants in the highest quartile displayed an elevated risk of periodontitis relative to their counterparts in the lowest quartile, as evidenced for TyG-WWI [OR (95% CI) = 1.72 (1.26–2.33), P = 0.001] and TyG-WC [OR (95% CI) = 1.50 (1.13–1.99), P = 0.009] in the full adjustment model. Subgroup analyses suggested more pronounced positive associations between these indices and periodontitis in participants who were < 60 years old, had a BMI ≥ 25, and did not have diabetes. The dose-response curve indicated linear responses in these associations.ConclusionsThis investigation identified a significant and stable association between TyG-WHtR, TyG-WWI, or TyG-WC and periodontitis, which implies a robust correlation between high insulin resistance and susceptibility to periodontitis in the American population.

Study of the Relationship between Insulin Resistance, Iron Status Markers and Body Weight in a Sample of Egyptian Population

Abstract Background Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels. Aim of the Work The aim of this study is to investigate the relationship between insulin Resistance, iron Status Markers and body Weight in a sample of Egyptian population. Patients and Methods Our study was case control study conducted on 90 subjects their age was ranging form18 to 70 from diabetes outpatient clinic, and they were divided into 3 groups: Group (1): Non-obese non-diabetic as a control group, Group (2): Obese non diabetic and group (3): Obese diabetic. Results In our study, there was no statistical significant difference found between the three studied groups regarding iron study, Also our study showed that there was statistically non significant correlation between (ferritin level and TIBC), and (ferritin level, HOMA IR), but there was statistical significant positive correlation found between TIBC and FBS (p- value 0.045),Similarly, we did not observe either abnormally high or low ferritin values in our study on subjects with obesity. We found no association between this marker and body weight, in contrast with others. In our study, the higher insulin and HOMA-IR values observed in the subjects with TSAT&amp;lt;20% = 4.2(1.4-11.6) than those with TSAT &amp;gt;20% =2.4 (1.15-6.95), but statistically non significant p- value. The present study also showed that There was statistical significant positive correlation between (T.SAT, serum ferritin), (T.SAT, S.iron) and (T.SAT,SBP) (with p-value 0.03). Our study also showed that there was no statistical significant difference found between patients with T.sat ≤ 20% and those with T.sat &amp;gt; 20% regarding all the studied parameters except ferritin level and iron level was found higher in patients with T.sat &amp;gt;20% than those with T. sat ≤20% with p-value &amp;lt;0.001 and &amp;lt;0.001 respectively. Conclusion Characteristics of iron deficiency or iron overload were not observed in subjects with overweight/obesity and diabetic patients. Our results suggest a complex metabolic dysregulation.

O-059 ART in PCOS

Abstract Polycystic Ovarian Syndrome affects an estimated 8 – 13% of women of reproductive age (WHO). It is the commonest cause of anovulation and infertility. The high AMH, LH, Insulin resistance and hyperandrogenism seen in PCOS women contributes to infertility along with poor oocyte quality and reduced endometrial receptivity. ART procedures are recommended as the third line of treatment after ovulation induction, IUI or ovarian drilling. Prior to IVF, metabolic assessment and lifestyle adjustments with weight management must be done. Adjuvant agents such as metformin melatonin, myoinositol and Vitamin-D have been tried to improve IVF outcomes. Mild stimulation is an option in patients as high risk for ovarian hyperstimulation syndrome (OHSS). Conventional stimulation with low dose FSH, GnRH antagonist down regulation, agonist trigger with freezing of all embryos, significantly reduces risk of OHSS without compromising cumulative live birth rates. Adjustments for stimulation protocols may need to be made for BMI, insulin resistance and AMH. In vitro maturation can be considered in patients with prior severe OHSS, though the results may be inferior. ART in PCOS patients is challenging and even after pregnancy is achieved, there may be a higher risk of adverse obstetric outcomes.

Therapeutic Insulin Analogue Concentrations at Infusion Sites Enhanced the Pro-Inflammatory Response and Apoptosis in an In Vitro Macrophage-Material Interaction Model.

Continuous subcutaneous insulin infusion for Type 1 diabetes relies upon insulin infusion sets (IIS) to reliably deliver insulin to a subcutaneous depot, where it is absorbed into systemic circulation. However, IIS are plagued by short wear times and high failure rates, due in part to inconsistent insulin absorption that can arise over time. While emerging evidence suggests that the local inflammatory response to the IIS cannula may impact both wear times and unreliable insulin adsorption, the mechanisms are poorly understood. Here, we investigated the effects of local infused insulin concentrations on the biomaterial host response to better understand the underlying factors that limit the IIS performance. We first modeled the insulin concentration for a constant basal infusion rate to select a relevant insulin concentration range of 0.1-10 U/mL within the infusion site. We then examined the influence of a commercial insulin analogue (Humulin-N) using an in vitro macrophage-material model, which uses adsorbed fibroblast lysate (containing damage-associated molecular patterns) to activate macrophages and recapitulates macrophage responses on implanted biomaterials. RAW-Blue macrophages cultured on lysate-adsorbed surfaces had increased nuclear factor-κB (NF-κB) and activating protein 1 (AP-1) activity and intracellular reactive oxygen species (ROS) accumulation compared to control surfaces. Humulin-N concentration (0.5-10 U/mL) enhanced the NF-κB/AP-1 activity and ROS accumulation in macrophages on lysate-adsorbed surfaces. However, Humulin-N had no effect on NF-κB/AP-1 or ROS in the absence of the inflammatory stimulus. Additionally, high insulin concentrations arising from therapeutic doses induced macrophage apoptosis with and without adsorbed lysate. This study contributes to emerging evidence that infused insulin affects the tissue response to IIS.

Insulin Blood Levels in Gestational Diabetes Mellitus in Relation to Ethnicity and Age in the Kingdom of Bahrain: A Cross-Sectional Study.

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy. It may be attributed to certain placental hormones during pregnancy which render insulin less effective. Our study aimed to focus on the levels of insulin in gestational diabetic women in the Kingdom of Bahrain as compared with non-diabetic pregnant women. Furthermore, we studied the correlation between insulin levels by ethnicity and age of the pregnant women. Methods: A cross-sectional study was conducted on 75 pregnant participants: 41 with GDM (test group) and 34 without GDM (control group). Insulin levels were determined in patients with GDM and compared to non-diabetic pregnant women. A comparison between Bahraini and non-Bahraini women was carried out in two different age groups: below and above 30 years of age. P values < 0.05 were considered significant. The results showed higher mean values of fasting blood glucose (FBG), random blood glucose (RBG), and insulin levels in the test group when compared to the control group. There was no significant difference in FBG, RBG, and insulin levels among Bahraini women with GDM and non-Bahraini women (Indian, Pakistani. Bengali, and Filipino) with GDM. Age, less than 30 vs more than 30 years, had no significant effect on women with GDM. Insulin levels were higher in pregnant women with GDM irrespective of their ethnicity or age. The lack of blood glucose control in GDM even in the presence of high insulin secretion may suggest loss of insulin effectiveness due to other factors such as stress and lactogenic placental hormones.

Myo-inositol rescued insulin resistance and dyslipidemia in db/db mice.

Myo-inositol (MI), present in a variety of foods, is essential in several important processes of cell physiology. In this study, we explored the protective effects of MI against hyperglycemia and dyslipidemia in db/db mice, a typical animal model of type 2 diabetes mellitus (T2DM). MI supplement effectively suppressed the high plasma glucose and insulin levels and markedly relieved the insulin resistance (IR) in the db/db mice, comparable to metformin's effects. In MIN6 pancreatic β cells, MI also restrained the upsurge of insulin secretion stimulated by high-concentration glucose but had no impact on the promoted cell proliferation. Moreover, MI abated the enhanced plasma triglyceride and total cholesterol levels in the db/db mice. Notably, the lipid droplet formation of mesenchymal stem cells (MSCs) from db/db mice was significantly diminished after the treatment of MI, indicating that MI could effectively inhibit the differentiation of db/db mouse MSCs into adipocytes. However, MI regretfully failed to control obesity in db/db mice. This work proved that MI significantly helped db/db mice's metabolic disorders, indicating that MI has potential as an effective adjunctive treatment for hyperglycemia and dyslipidemia in T2DM patients.

Clinical and pathological characteristics of gestational diabetes mellitus with different insulin resistance

AimsTo elucidate the clinical and pathological characteristics of gestational diabetes mellitus (GDM) with high and low insulin resistance. MethodsIn total, 1393 GDM and 1001 non-GDM singleton deliveries were included in this study. Insulin resistance subtypes were classified according to the HOMA2-IR value. Clinical data were analyzed using SPSS 26.0. Placenta samples were collected for pathological analysis. ResultsMaternal age and fasting glucose were identified as independent risk factors for GDM with high insulin resistance (p < 0.01), while fasting glucose was the sole risk factor for GDM with low insulin resistance (p < 0.001). Fetal distress was associated with both of GDM subtypes (both p < 0.01), while anemia, fetal growth restriction, large for gestational age and intrahepatic cholestasis in pregnancy were related to specific GDM insulin resistance subtype. In addition, GDM with high insulin resistance showed an increase of syncytial knots with down-regulation of PI3K/AKT signaling, while GDM with low insulin resistance showed normal syncytial knot counts and up-regulation of PI3K/AKT signaling. ConclusionsOur findings provide novel perspectives to the clinical and pathological comprehensions of GDM with high and low insulin resistance, which might facilitate the mechanism study of GDM and its precision pregnancy management.

Alpha-lipoic acid induced insulin autoimmune antibody syndrome

BackgroundInsulin autoimmune antibody syndrome is an uncommon cause of hypoglycemia in non-diabetic individuals. We report a case of alpha-lipoic acid-induced insulin autoimmune antibody syndrome.Case reportA 40-year-old non-diabetic female presented with unresponsiveness due to severe hypoglycemia. Investigations revealed high fasting insulin levels, elevated C-peptide, and positive anti-insulin antibodies. Further history revealed recent ingestion of alpha-lipoic acid supplements. She was diagnosed with alpha-lipoic acid-induced insulin autoimmune antibody syndrome and managed with symptomatic measures and steroids.ConclusionsThis case highlights the importance of recognizing drug-induced insulin autoimmune antibody syndrome as a potential cause of hypoglycemia in non-diabetic individuals, especially in the context of recent supplement or medication use.