Homeostasis Model Assessment-insulin Resistance Index Research Articles

Iron Homeostasis-Related Parameters and Hepcidin/Ferritin Ratio: Emerging Sex-Specific Predictive Markers for Metabolic Syndrome.

Metabolic syndrome (MetS) is a worldwide public health challenge. Accumulating evidence implicates elevated serum ferritin and disruptions in iron metabolism as potential elements linked to an increased risk of MetS. This study investigates the relationship between iron homeostasis-including hepcidin levels, serum iron concentration, unsaturated iron-binding capacity (UIBC), and the hepcidin/ferritin (H/F) ratio-and MetS. In this descriptive cross-sectional study, 209 participants aged 24-70 were categorized into two groups: 103 with MetS and 106 without MetS. All participants underwent medical assessment, including anthropometric measures, indices of glycemic control, lipid profiles, and iron-related parameters. Participants were further stratified by the Homeostasis Model Assessment-Insulin Resistance index into three subgroups: insulin-sensitive (IS) (<1.9), early insulin resistance (EIR) (>1.9 to <2.9), and significant insulin resistance (SIR) (>2.9). Notable increments in serum ferritin and hepcidin were observed in the SIR group relative to the IS and EIR groups, with a significant association between metabolic parameters. The UIBC and serum ferritin emerged as significant predictors of MetS, particularly in men, with an area under the curve (AUC) of 0.753 and 0.792, respectively (p ≤ 0.001). In contrast, hepcidin was notably correlated with MetS in women, with an AUC of 0.655 (p = 0.007). The H/F ratio showed superior predictive capability for MetS across both sexes (at cutoff level = 0.67). Among women, this ratio had an AUC of 0.639 (p = 0.015), and for men, it had an AUC of 0.792 (p < 0.001). Hypertension proved an independent risk factor for MetS, affirming its role in metabolic dysregulation. The findings highlight a significant interconnection between iron homeostasis parameters and MetS, with sex-specific variations underscoring the importance of personalized diagnostic criteria. The crucial role of the H/F ratio and the UIBC as emerging predictive markers for MetS indicates their potential utility in identifying at-risk individuals. Further longitudinal research is essential to establish causality and explore the interplay between these biomarkers and MetS.

The correlation between HOMA-IR and cardiometabolic risk index among different metabolic adults: a cross-sectional study.

This study aimed to explore the correlation between homeostasis model assessment of insulin resistance(HOMA-IR)and cardiometabolic risk index(CMRI) among different metabolic adults to evaluate the value of HOMA-IR in predicting cardiometabolic risk. This cross-sectional study was conducted over 18 months (from August 1, 2020 to February 18, 2022) and included 1550 participants divided into non-metabolic syndrome (non-MetS) group (n = 628) and metabolic syndrome (MetS) group (n = 922) in three centers of China. Logistic regression analysis was employed to investigate the correlation between HOMA-IR, body fat percentage, BMI (body mass index), visceral fat index, waist-to-hip ratio, vitamin D, and CMRI. Further analysis was conducted to evaluate the ability of HOMA-IR in diagnosing high CMRI within different metabolic, gender, and age groups to predict the risk of cardiovascular disease (CVD). HOMA-IR was significantly higher in the MetS group compared with the non-MetS group (P < 0.05). CMRI was significantly higher in the MetS group compared to the non-MetS group (P < 0.05). According to ROC curve analysis, HOMA-IR can predict cardiovascular risk (CVR) in the general population, non-MetS individuals, and MetS people. Logistic regression analysis revealed that BMI, visceral fat index, waist-to-hip ratio, and HOMA-IR are independent risk indicators of high CVR, whereas vitamin D may exert a protective role. HOMA-IR was an independent risk factor for increased CVR in MetS patients. Moreover, HOMA-IR elevates the risk of CVD regardless of MetS and thus can be used for screening the general population. The study was registered at the Chinese Clinical Trial Registry (Registration Number: ChiCTR2100054654).

Evaluating antiretroviral therapy–induced insulin resistance syndrome using the homeostasis model assessment method: an important global clarion call for concern among people living with HIV-disease

Abstract Background Antiretroviral treatment advances have been accompanied by a new spectrum of adverse drug reactions that affect metabolism and body composition. Purpose This review was principally designed to focus on how to comprehensively evaluate for the occurrence of antiretroviral therapy-induced insulin resistance syndrome with associated impaired glucose metabolism disorder(s) among people living with HIV disease. Data sources and materials During the course of this present study, original peer-reviewed articles reported in English language that investigated antiretroviral therapy-induced insulin resistance were identified by exploring the Medline-Entrez-PubMed search, Web of Science database, Google Scholar search, and Science Direct database online facilities. Also, information was sourced from printed textbooks and the reports documented by some recognized medically inclined and health professional bodies. These published materials containing documented reports relating to the subject matter of focus in this review were accessed and adequately referenced. This study spanned for 12-month duration from March 2023 to February 2024. Study selection and manuscript preparation with limitations A total number of 92 published articles were reviewed, out of which 55 referenced articles were found to contain information pertinent to this present study; while those parts of the referenced articles inapt to this study were neglected. Antiretroviral therapy-induced insulin resistance syndrome can be broadly classified into mild, moderate, and severe categories; based on the severity grading reviews of homeostasis model assessment-insulin resistance index values. Conclusion The clinical assessment of antiretroviral therapy-induced insulin resistance syndrome should be given utmost importance in HIV-disease individuals with considerably high-risk factor(s) for its occurrence.

Insulin Resistance in Systemic Lupus Erythematosus

The objective: to analyze the frequency of insulin resistance (IR) in patients with systemic lupus erythematosus (SLE), study of traditional and rheumatic disease-related risk factors for the development of IR, assessment of the possibility of using of Finnish Type 2 Diabetes Risk Assessment Form (FINDRISC) to detect IR. Materials and methods. 58 patients with SLE (53 women and 5 men) without diabetes mellitus (DM) and hyperglycemia were included in the one-time study. The patients have received the inpatient treatment at the regional medical and diagnostic center of the communal enterprise “Poltava Regional Clinical Hospital named after M. V. Sklifosofsky PRC” in 2020-2023. The average age of patients was 38 [28; 43] years, the average duration of the disease is 4.0 [0.6; 6.0] years. 49 (85%) patients received glucocorticoids (GC), 20 (34%) – hydroxychloroquine, 26 (45%) – immunosuppressants, 2 (3%) persons received biological drugs. In all patients fasting glucose and insulin levels were determined, and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. The value of the HOMA-IR index ≥2.77 corresponded to the presence of IR. Traditional risk factors for type 2 DM and the risk of its development in the next 10 years in patients with SLE were assessed using the FINDRISC questionnaire. Results. IR was determined in 14 (24%) of 58 patients with SLE. The average value of the HOMA-IR index was 1.8 [1.3; 2,6]. The data of patients with and without IR were similar in terms of sex, age, duration and activity of SLE, therapy performed at the time of examination, frequency of traditional risk factors for type 2 DM. Body mass index (BMI), waist circumference (WC), and insulin concentration were higher in patients with IR. The HOMA-IR index was correlated with BMI (r=0.7; p&lt;0.001), WC (r=0.6; p&lt;0.001), risk categories for the development of type 2 diabetes according to FINDRISС (r=0.4; p=0.04), the SLEDAI-2K index (r=–0.3; p&lt;0.02), the serum concentration of C3 complement (r=0.4; p=0.035) and the duration of GC therapy (r=0.4; p=0.02). Conclusions. IR was diagnosed in 24% of patients with SLE without a history of DM and with a normal fasting venous blood glucose level. The HOMA-IR index increased as SLE activity decreased and the duration of GC treatment increased. However, the development of IR was statistically significantly associated only with an increase in BMI and WC. The use of the FINDRISC questionnaire, which allows to assess the risk of developing type 2 DM in the general population, did not help to detect IR in patients with SLE.

Evaluation of the Diagnostic Utility of Selected Serum Adipokines and Cytokines in Subjects with MASLD-A Pilot Study.

Excess adipose tissue, particularly of the visceral type, triggering chronic low-grade inflammation and altering its secretory profile, is a contributing factor to the initiation and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the levels of selected adipokines and cytokines in individuals with normal weight and obesity, assessing their potential for diagnosing MASLD and establishing a cutoff point for body fat content associated with hepatic steatosis development. The research involved 99 participants categorized by body mass index and MASLD presence, undergoing body composition analysis, liver elastography, biochemical tests, and evaluation of adipokines and cytokines in serum. The results indicated elevated IL-6 (interleukin 6) serum levels in individuals with obesity with MASLD compared to the normal-weight group without MASLD. The multivariate regression analysis demonstrated a connection between hepatic steatosis and total adipose tissue content, VAT (visceral adipose tissue), VAT/SAT (subcutaneous adipose tissue) ratio, HOMA-IR (homeostasis model assessment of insulin resistance), IL-6, Il-1β (interleukin 1β), and MMP-2 (matrix metalloproteinase 2). Among the adipokines and cytokines examined in this study, interleukin 6 was the strongest predictor of MASLD regardless of gender. In addition, an association between the development of hepatic steatosis and higher serum IL-1β levels and higher adipose tissue was observed in women. However, further studies on a larger group of patients are needed to consider the use of these cytokines as markers of MASLD. The HOMA-IR index demonstrated potential diagnostic utility in identifying hepatic steatosis.

Improvement in insulin sensitivity after switching from an integrase inhibitor-based regimen to doravirine/tenofovir disoproxil fumarate/lamivudine in people with significant weight gain.

We performed an observational, retrospective, cohort study to assess changes in insulin sensitivity after a switch from dolutegravir/lamivudine (DOL/3TC) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) to doravirine/tenofovir disoproxil fumarate/3TC (DOR/TDF/3TC) in virologically suppressed people living with HIV with recent significant weight gain. All non-diabetic patients with HIV treated with DOL/3TC or BIC/F/TAF for ≥12 months, with HIV RNA <20 copies/mL, and with a weight increase ≥3 kg in the last year, who underwent a switch to DOR/TDF/3TC were enrolled into the study. Serum levels of glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were evaluated every 6 months during a 12-month follow-up. Overall, 81 patients were enrolled: 41 were treated with DOL/3TC and 40 with BIC/F/TAF. At baseline, median HOMA-IR index was 3.18 and insulin resistance (HOMA-IR index >2.5) was present in 49 subjects (60%). At 12 months after the switch to DOR/TDF/3TC, change in mean serum glucose concentration was not significant, but the reduction in median concentration of insulin was significant (-3.54 mcrUI/L [interquartile range -4.22 to -2.87]; p = 0.012), associated with a significant reduction in mean HOMA-IR index (-0.54 [interquartile range -0.91 to -0.18]; p = 0.021). A significant reduction in total and low-density lipoprotein cholesterol was also reported, whereas decreases in mean body weight and mean body mass index were not significant. In our retrospective study in virologically suppressed people living with HIV treated with DOL/3TC or BIC/F/TAF and with recent weight gain, the switch to DOR/TDF/3TC led to a significant improvement in insulin sensitivity and plasma lipids, with a trend to decreased body weight.

Assessment of Serum Atherogenic Indices and Insulin Resistance in Retinal Vein Occlusion.

This study aimed to investigate serum atherogenic indices as novel cardiovascular risk factors associated with retinal vein occlusion (RVO). This retrospective case-control study included 57 patients with newly diagnosed RVO whose plasma lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and insulin resistance were examined. Serum atherogenic indices (LDL-C/HDL-C, TC/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios) and presence of insulin resistance were compared between the patients and 63 healthy subjects. Cut-off values were determined by receiver operating characteristic curve analysis. The mean age of the RVO patients was 63.7±9.4 years. Plasma levels of LDL-C, HDL-C, TC, and TG showed no significant difference between the patient and control groups (p>0.05). However, LDL-C/HDL-C, non-HDL-C/HDL-C, and TC/HDL-C ratios were higher in the RVO group compared to healthy subjects (p=0.015, p=0.036, and p=0.015, respectively). Fasting insulin concentrations, plasma insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were higher in the RVO patients compared to controls (p=0.003, p=0.001, and p=0.001, respectively). LDL-C/HDL-C, TC/HDL-C, and non-HDL-C/HDL-C ratios were found to be increased in RVO. Compared to the traditional plasma lipid profile, serum atherogenic indices were found to be superior predictors of RVO development. Measurement of HOMA-IR index should be taken into consideration in the evaluation of insulin resistance. High serum atherogenic indexes in RVO patients reveal the need to take precautions against the risk of cardiovascular disease and stroke.

Non-Insulin-Based Indices of Insulin Resistance for Predicting Incident Albuminuria: A Nationwide Population-Based Study.

Studies have shown that incident albuminuria is associated with insulin resistance (IR); however, an IR marker that best predicts the prevalence of albuminuria has not yet been established. This study explored the association between IR and incident albuminuria using various IR indices, including the homeostasis model assessment of IR (HOMA-IR), metabolic score for IR (METS-IR), and triglyceride-glucose (TyG) index, and compared their predictive abilities for the prevalence of albuminuria. A total of 4,982 Korean adults from the 2019 Korea National Health and Nutritional Examination Survey were analyzed. The odds of albuminuria were determined using the quartiles of the IR indices. Receiver operating characteristic (ROC) curves were used to calculate the area under the ROC curve and predictability. The cutoff values for albuminuria detection were also computed. An increase in the quartiles of all three IR indices was associated with incident albuminuria, even after full adjustment for covariates (HOMA-IR: odds ratio [OR], 1.906; 95% confidence interval [CI], 1.311-2.772; P=0.006; METS-IR: OR, 2.236; 95% CI, 1.353-3.694; P=0.002; TyG index: OR, 1.757; 95% CI, 1.213-2.544; P=0.003). The area under the ROC curve for incident albuminuria based on the HOMA-IR, METS-IR, and TyG indices was 0.594 (95% CI, 0.568-0.619), 0.633 (95% CI, 0.607-0.659), and 0.631 (95% CI, 0.606-0.656), respectively. The optimal cutoff values for predicting albuminuria were 2.38, 35.38, and 8.72 for the HOMA-IR, METS-IR, and TyG indices, respectively. The METS-IR and TyG indices outperformed HOMA-IR in predicting incident albuminuria.

Regulation of Neuropeptide Y Receptor Gene Expression and Hormone Level in Obese Male Rats Receiving 6-Gingerol and L-Arginine Supplementation.

Obesity and its associated disorders, such as hyperlipidemia, have become a ‎global issue following the consumption of unhealthy, high-fat, and high-‎carbohydrate foods, which burdens the economies and the ‎health systems of human societies worldwide. This study aimed to evaluate ‎the effect of oral consumption of 6-gingerol and L-arginine supplements on obesity factors. Thirty rats in five groups were fed a diet specific to each ‎group for 12 weeks and then treated with the oral administration of L-arginine (200 mg/day) and 6-gingerol (100 mg/day) for 12 weeks. The food and water ‎intake and weight change, were then measured. In addition, plasma glucose, ‎triglyceride, cholesterol, high-density lipoprotein (HDL), very-low-density lipoprotein (VLDL)‎, low-density ‎lipoprotein (LDL), and serum hormone levels, including corticosterone, testosterone, and insulin, were measured, and NPY, Y1, and Y5 receptor gene expression were recorded using real-time PCR. Administration of 6-gingerol and L-arginine decreased food intake, ‎weight gain, glucose levels, insulin levels, and homeostasis model assessment-insulin resistance (HOMA-IR) index compared to ‎the HCD control group. In addition, corticosterone and testosterone levels in the ‎study groups showed a significant decrease (P<0.05) and increase (P<0.01) compared to the control groups, respectively. Triglyceride, total cholesterol, HDL, and VLDL levels in the groups treated with L-arginine and gingerol alone or combined significantly decreased compared to ‎the control group (P<0.01). This study confirms that 6-gingerol and L-arginine supplements prevent ‎HCD-induced hyperlipidemia by controlling hormones and neurotransmitters ‎involved in the general metabolism.‎.

Improving insulin resistance by sulforaphane via activating the Bacteroides and Lactobacillus SCFAs-GPR-GLP1 signal axis.

Background: Insulin resistance (IR) is closely associated with non-alcoholic fatty liver disease (NAFLD), and the gut microbiome contributes to the development of NAFLD. Sulforaphane (SFN) is a phytochemical in cruciferous vegetables that could improve lipid metabolism disorder. However, whether SFN can alleviate IR in NAFLD by regulating the intestinal flora remains unclear. Methods: SFN was administered to high fat diet (HFD)-fed Wistar rats for 10 weeks. Gut microbiota was analysed by 16S rRNA sequencing and the short chain fatty acids (SCFAs) by gas chromatography. The expression of tight junction protein and the numbers of Lactobacillus, Bacteroides and Bifidobacterium were determined by qPCR. The expression of G-protein-coupled receptor 41/43 (GPR41/43) was determined by western blot. A randomized controlled trial (RCT) was conducted in NAFLD patients with broccoli seed tablets (rich in SFN, 42 mg d-1) as intervention for 12 weeks. Thirty-six volunteers with abnormal glucose before the broccoli seed tablet treatment were selected in the intervention group to analyze their blood glucose, insulin, homeostasis model assessment-insulin resistance index (HOMA-IRI), homeostasis model assessment-insulin sensitivity index (HOMA-ISI) and glucagon-like peptide (GLP-1). Results: SFN reduced blood glucose and HOMA-IRI while increasing insulin sensitivity in HFD rats. SFN reduced glycogen synthase kinase 3 (GSK-3), phosphoenolpyruvate carboxykinase (PEPCK) activity, and phosphorylation of serine residues of IRS-2 induced by HFD. SFN reshaped the gut microbiota composition of HFD-induced rats and, especially, increased the content of Bacteroidaceae, Lactobacillaceae and Bifidobacteriaceae, which are related to the improvement from SFN of the blood glucose and HOMA-IRI. The increased numbers of Bacteroides and Lactobacillus were the targets of SFN to enhance the expression of tight junction proteins ZO-1 and occludin, thereby lowering lipopolysaccharide content to reduce inflammation, ultimately alleviating IR. Bacteroides and Lactobacillus produced SCFAs, which activated GPR41/43 to secrete GLP1. Moreover, it was also confirmed in RCT that SFN intervention increased the level of GLP1 in NAFLD patients, which was positively correlated with the reduction of blood glucose and HOMA-IR. Conclusions: SFN alleviated IR in NAFLD via the Bacteroides and Lactobacillus SCFAs-GPR41/43-GLP1 axis and protected the intestinal mucosal barrier to decrease inflammation.

Associations of Alanine Aminotransferase/Aspartate Aminotransferase, a Marker of Hepatosteatosis, with Adipose Tissue Insulin Resistance Index and Leptin/Adiponectin Ratio in Japanese Women.

Objective: We assessed whether alanine aminotransferase/aspartate aminotransferase (ALT/AST), a marker of hepatic steatosis, may be associated with adipose tissue dysfunction more closely than hepatic and muscle insulin resistance (IR). Methods: Associations with adipose tissue IR index (AT-IR) calculated as a product of fasting insulin and free fatty acids, leptin/adiponectin ratio, a proxy of adipocyte dysfunction, homeostasis model assessment IR (HOMA-IR), hepatic and muscle IR inferred from plasma insulin kinetics during a 75 grams oral glucose tolerance test (OGTT) were studied in nondiabetic 307 young and 148 middle-aged Japanese women, whose body mass index averaged 20 and 22 kilograms/m2, respectively. Results: On multivariate linear regression analysis in young women, ALT/AST was associated with trunk/leg fat ratio (standardized β = 0.202, P = 0.007), a marker of abdominal fat accumulation, and AT-IR (standardized β = 0.185, P = 0.003) independently of HOMA-IR and Matsuda index (R2 = 0.07). In middle-aged women, leptin/adiponectin ratio (standardized β = 0.446, P < 0.001) and AT-IR (standardized β = 0.292, P = 0.009) emerged as determinants of ALT/AST independently of trunk/leg fat ratio, OGTT-derived hepatic IR, leptin, and adiponectin (R2 = 0.34). Conclusions: ALT/AST was associated with AT-IR and adipocyte dysfunction more closely than hepatic and muscle IR even in nondiabetic lean Japanese women.

Circulating mir-199-3p screens the onset of type 2 diabetes mellitus and the complication of coronary heart disease and predicts the occurrence of major adverse cardiovascular events

BackgroundCoronary heart disease (CHD) is a major complication of type 2 diabetes mellitus (T2DM), which causes an adverse prognosis. There is an urgent need to explore effective biomarkers to evaluate the patients’ adverse outcomes.ObjectiveThis study aimed to identify a novel indicator for screening T2DM and T2DM-CHD and predicting adverse prognosis.Materials and methodsThe study enrolled 52 healthy individuals, 85 T2DM patients, and 97 T2DM patients combined with CHD. Serum miR-199-3p levels in all study subjects were detected with PCR, and its diagnostic significance was evaluated by receiver operating curve (ROC) analysis. The involvement of miR-199-3p in disease development was assessed by the Chi-square test, and the logistic regression analysis was performed to estimate the risk factor for major adverse cardiovascular events (MACE) in T2DM-CHD patients.ResultsSignificant downregulation of miR-199-3p was observed in the serum of both T2DM and T2DM-CHD patients, which discriminated patients from healthy individuals and distinguished T2DM and T2DM-CHD patients. Reduced serum miR-199-3p was associated with the increasing blood glucose, glycated hemoglobin (HbA1c), and homeostasis model assessment-insulin resistance index (HOMA-IR) of T2DM patients and the increasing triglycerides (TG), low-density lipoprotein (LDL), fibrinogen, and total cholesterol (TC) and decreasing high-density lipoprotein (HDL) of T2DM-CHD patients. miR-199-3p was also identified as a biomarker predicting the occurrence of MACE.ConclusionDownregulated miR-199-3p could screen the onset of T2DM and its complication with CHD. Reduced serum miR-199-3p was associated with the severe development of T2DM and T2DM-CHD and predicted the adverse outcomes of T2DM-CHD patients.

Prediction and Validation of Metabolic Dysfunction-Associated Fatty Liver Disease Using Insulin Resistance-Related Indices in the Japanese Population.

Background: Recently, metabolic dysfunction-associated fatty liver disease (MAFLD), which is based on evidence of hepatic steatosis and any of the following three conditions: overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation, has been proposed. It is uncertain how indices that predict insulin resistance (IR) are associated with MAFLD. Methods: Among subjects who had undergone health examinations at our hospital, 1,257 (787 men and 474 women) who underwent fatty liver evaluation, were included in this cross-sectional study. The discriminatory ability of each index for MAFLD was tested using a receiver operating characteristic curve analysis. The associations between the homeostasis model assessment-IR (HOMA-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride-glucose (TyG) index, and MAFLD were investigated using multiple logistic regression analysis. Results: The mean age and body mass index of MAFLD subjects were 58.1 years and 26.0 kg/m2 in men and 63.0 years and 26.1 kg/m2 in women, respectively. The cutoff values of HOMA-IR, TG/HDL-C ratio, and TyG index in men and women were 1.40 (area under the curve [AUC]: 0.81) and 1.90 (AUC: 0.88); 1.56 (AUC: 0.75) and 1.06 (AUC: 0.78); and 8.62 (AUC: 0.75) and 8.45 (AUC: 0.80), respectively. All indices were significantly higher in both men and women with MAFLD. In the multivariate models, the odds of MAFLD were higher among both men and women in the highest tertile than those in the lowest tertile. When subjects were divided by sex, presence of MAFLD, and alanine aminotransferase (ALT) values, all indices were significantly higher in both men and women with high ALT levels who were diagnosed with MAFLD. Conclusion: IR strongly correlated with MAFLD, particularly in subjects with high ALT levels.

ASSOCIATION OF HBA1C, SERUM VASCULAR ENDOTHELIAL GROWTH FACTOR, INSULIN RESISTANCE IN PREDIABETES, DIABETES, AND DIABETIC RETINOPATHY PATIENTS

Background: In the micro- and macrovascular pathophysiology of diabetes mellitus, vascular endothelial growth factor (VEGF) is crucial. It has become recognized as a critical element contributing to the emergence of diabetes-related retinopathy and as a critical prognostic marker for the illness. Aims: The aim of this study is to assess the level of glycated hemoglobin (HbA1c), serum VEGF, insulin resistance (IR) in prediabetes, type-2 diabetic patients without microvascular complications, and diabetic retinopathy patients Methods: Values for serum VEGF, HbA1c, and IR were evaluated. Spearman coefficient correlation was used to perform the correlation. Results: Our results demonstrate that fasting insulin levels were almost completely correlated with homeostasis model assessment index of IR (HOMA-IR) (r=0.99) and highly correlated with homeostasis model assessment of β-cell function (r= −0.84). We also looked at if there was any relationship between blood VEGF levels and biochemical results (HbA1c, total cholesterol, triglycerides, low-density lipoprotein). According to a study, IR and serum levels of VEGF were considerably greater in diabetic patients than in controls. Conclusion: Both prediabetes and type 2 diabetes mellitus (T2DM) patients had elevated serum VEGF levels, and these individuals also had favorable relationships with their HOMA-IR scores. In comparison to controls, prediabetes and T2DM patients may have higher VEGF levels due to increased IR.

One-year efficacy of a lifestyle behavioural intervention on physical and mental health in people with severe mental disorders: results from a randomized controlled trial

This multicentric randomized controlled trial (RCT), carried out in six Italian University mental health sites, aims to test the efficacy of a six-month psychosocial intervention (LYFESTYLE) on Body Mass Index (BMI), body weight, waist circumference, fasting glucose, triglycerides, cholesterol, Framingham and HOmeostasis Model Assessment of insulin resistance (HOMA-IR) indexes in patients with schizophrenia, bipolar disorder, and major depression. Moreover, the efficacy of the intervention has also been tested on several other physical and mental health domains. Patients were randomly allocated to receive the six-month experimental intervention (LIFESTYLE) or a behavioural control intervention. All enrolled patients were assessed at baseline and after one year. We recruited 401 patients (206 in the experimental and 195 in the control group) with a diagnosis of schizophrenia or other psychotic disorder (29.9%), bipolar disorder (43.3%), or major depression (26.9%). At one year, patients receiving the experimental intervention reported an improvement in body mass index, body weight, waist circumference, HOMA-IR index, anxiety and depressive symptoms and in quality of life. Our findings confirm the efficacy of the LIFESTYLE intervention in improving physical and mental health-related outcomes in patients with severe mental illnesses after one year.

Effects of Endurance Exercise and Vitamin D Supplementation on Insulin Resistance and Plasma Lipidome in Middle-Aged Adults with Type 2 Diabetes.

(1) Background: We investigated the effects of a 12-week exercise intervention with or without vitamin D supplementation on insulin resistance and the plasma lipidome of participants with type 2 diabetes. We further explored whether the effects of the intervention on glycemic parameters could be associated with the baseline lipidome. (2) Methods: Sixty-one participants were randomly allocated to control (Con), exercise (EX), vitamin D (VD), and EX + VD groups. Multiple glycemic and anthropometric parameters were evaluated before and after intervention. The homeostasis model assessment of insulin resistance (HOMA-IR) was the primary outcome. The plasma lipidome was analyzed before, after, and at an additional 12-week follow-up. Machine learning was applied to establish prediction models for responsiveness of glycemic control. (3) Results: Our interventions failed to improve the HOMA-IR index while fasting glucose was reduced in the EX + VD group (change%, -11.9%; effect size, 0.65; p < 0.05). Both EX and VD interventions altered the plasma lipidome, with EX + VD intervention considerably affecting levels of lyso-phosphatidylcholines and triglycerols containing long-chain unsaturated fatty acids. Such effects could last until 12 weeks after intervention. Notably, there was high inter-individual variability in glycemic parameters including HOMA-IR in response to the interventions, which could be predicted with great accuracy using an optimal panel of baseline lipid predictors alone or in combination with clinical indices, as assessed by an area under the receiver operating characteristic curve value of over 0.9. (4) Conclusions: Although substantial alterations were observed in the plasma lipidome related to glycemic control, our intervention failed to improve HOMA-IR scores, which may have been predominately due to the large inter-individual variability in responses. Basal plasma lipid levels could potentially predict an individual's response to intervention, highlighting the necessity of personalized nutrition.

Effect of zinc supplementation on blood sugar control in the overweight and obese population: A systematic review and meta-analysis of randomized controlled trials

BackgroundAlthough overweight and obese people have a higher risk of type 2 diabetes incidence than normal-weight individuals, the efficacy of zinc supplementation in blood sugar control in overweight and obese people remained unknown. This meta-analysis attempted to address this issue. MethodsDatabases including PubMed, Embase, and the Cochrane Library were searched from inception until May 2022 to identify randomized controlled trials (RCTs) investigating the effects of zinc supplementation among participants who were overweight or obese without language restriction. It is a random-effect meta-analysis that analyzed the impact of zinc supplementation on fasting glucose (FG) (i.e., primary outcome) and other variables including fasting insulin (FI), homeostasis model assessment-insulin resistance index (HOMA-IR), glycated hemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), and 2-hour postprandial glucose (2 h- PG). ResultsAnalysis of 12 eligible RCTs involving 651 overweight/obese participants demonstrated that zinc supplementation significantly improves FG (weighted mean difference [WMD]: −8.57 mg/dL; 95% confidence interval [CI]: −14.04 to −3.09 mg/dL, p = 0.002), HOMA-IR (WMD: −0.54; 95% CI: −0.78 to −0.30, p < 0.001), HbA1c (WMD: −0.25%; 95% CI: −0.43% to −0.07%, p = 0.006), and 2 h-PG (WMD: −18.42 mg/dL; 95% CI: −25.04 to −11.79 mg/dL, p < 0.001) compared to those in the control group. After conducting subgroup analyses, we found that the primary outcome, FG, showed more significant results in the subgroups with Asia, Zinc supplementation alone, higher dose (≥30 mg) and patients with diabetes. ConclusionOur meta-analysis indicated that zinc supplementation benefits blood sugar control in overweight and obese populations, with an especially significant reduction in FG.

Risk factors for insulin resistance related to polycystic ovarian syndrome in Iranian population

Polycystic ovary syndrome (PCOS) has significant metabolic sequelae linked to insulin resistance. This study aimed to compare clinical, metabolic, and hormonal characteristics of PCOS women with and without insulin resistance. The second aim was to compare the clinico-biochemical profiles of the various PCOS phenotypes. In this cross-sectional secondary analysis, we combined the baseline data from two separate randomized controlled trials (RCTs) in women diagnosed with PCOS. PCOS patients were categorized into the four Rotterdam PCOS phenotypes according to the presence of at least two criteria of oligomenorrhea/anovulation (O), hyperandrogenism (H), and polycystic ovary morphology (P): O–H–P, H–P, O–H, and O–P. Participants were categorized into two groups according to the homeostasis model assessment index of insulin resistance (HOMA-IR) levels: < 3.46, and ≥ 3.46. The correlation between the HOMA-IR and biometric, clinical, and biochemical variables was assessed in normal weight (BMI < 25) and overweight/obese (BMI ≥ 25) PCOS women. Then, the association between PCOS phenotypes and insulin resistance was investigated using logistic regression analysis. A total of 125 PCOS patients aged 18–40 years were included in the present study. Based on our results, the HOMA-IR index was positively correlated with diastolic blood pressure, free androgen index, and triglycerides levels; and negatively correlated with sex hormone-binding globulin in overweight/obese PCOS women. In addition, the HOMA-IR index was found to be positively correlated with alanine transaminase and negatively correlated with diastolic blood pressure in normal weight PCOS women. Moreover, individuals with O–H–P phenotype (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.02–6.24) had about two-fold increased risk of insulin resistance. In conclusion, the full-blown PCOS (O–H–P) phenotype has an increased risk of insulin resistance. Accordingly, phenotype division may help physicians to predict adverse metabolic outcomes.

#2937 INDIRECT INSULIN RESISTANCE INDICES AND THEIR CUT-OFF VALUES FOR POST-TRANSPLANTATION DIABETES MELLITUS IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Insulin resistance determination in kidney transplant recipients (KTRs) plays an important role to identify KTRs at risk of posttransplantation diabetes mellitus (PTDM) development. Current methods to measure insulin resistance include the hyperinsulinemic-euglycemic (HIEG) clamp technique, and minimal model approximation of the metabolism of glucose (MMAMG). These methods, however, require considerable time and are expense, complex, and invasive. As a result, indirect insulin resistance indices such as homeostasis model assessment-insulin resistance (HOMA-IR), visceral adiposity index (VAI), lipid accumulation product (LAP), or triglycerides-glucose (TyG) index, are used in epidemiological and clinical studies in the general population due to their simplicity and ease of use. However, it is unknown to what extent those indices may contribute to determine insulin resistance and PTDM development in KTRs. Therefore, this study aimed to investigate the role of indirect insulin resistance indices to determine insulin resistance and PTDM development in KTRs. Method We included 472 stable outpatient KTRs (with a functioning graft ≥1 year) without diabetes from a prospective cohort study. Crude and multivariable Cox proportional hazards regression analysis were performed to determine whether indirect insulin resistance indices (HOMA-IR, VAI, LAP, and TyG index) were prospectively associated with incident PTDM. We analyzed each measure using receiver operating characteristic (ROC) curve for the development of PTDM. The cut-off value was determined as the value with the highest Youden index score in the specificity dominant area. Results During a median 9.6 years [interquartile range (IQR) 6.6–10.2] of follow up, 68 (14%) KTRs developed PTDM. In Cox regression analyses, all indirect insulin resistance indices associated with incident PTDM, independent of potential confounders. ROC curve was 0.764 (95% CI,0.703-0.826) for HOMA-IR, 0.685 (95% CI,0.615-0.757) for VAI, 0.743 (95% CI,0.678-0.808) for LAP, and 0.698 (95% CI,0.629-0.766) for TyG index, with no significant difference between them (p = 0.05). The cut-off values with their corresponding sensitivity and specificity for each indices are presented in Table 1. To test this cut-off value, the association between the indices and incident PTDM was examined by using each index as a categorical variable (HOMA-IR&amp;lt;2.47 vs ≥2.47; VAI&amp;lt;4.01 vs ≥4.01; LAP&amp;lt;87.04 vs ≥87.04; TyG index&amp;lt;4.94 vs ≥4.94). Indirect insulin resistance indices as a categorical variable predicted incident PTDM independent of age, sex, smoking, time to transplantation, systolic blood pressure, eGFR, and medication. Conclusion Indirect insulin resistance indices could be used to predict incident PTDM in KTRs. In addition to HOMA-IR, insulin-free surrogates of insulin resistance might serve as useful methods to identify KTRs at risk for PTDM development.

Ganjiang Huangqin Huanglian Renshen Decoction improves insulin sensitivity by regulating intestinal flora in rats with Type 2 diabetes mellitus

Purpose: To study the effect of Ganjiang Huangqin Huanglian Renshen Decoction (GHHRD) on intestinal microflora and insulin resistance (IR) in type 2 diabetes mellitus (T2DM) rats. &#x0D; Methods: Streptozotocin (STZ) injection was used to establish a rat model of T2DM. The T2DM rats were divided into 5 groups: control, T2DM, T2DM + low-dose traditional Chinese medicine (TCM), T2DM + high-dose TCM, and T2DM + metformin groups. Total DNA kit was used for extraction of total DNA from fecal microorganisms from the T2DM model rats. High-throughput 16S rDNA sequencing was carried out to identify the intestinal flora of T2DM model rats. Fasting plasma glucose (FPG) and fasting serum insulin (FINS) levels were determined by a biochemical analyzer. &#x0D; Results: The 16S rDNA sequencing analysis showed that after GHHRD treatment, the levels of Ruminococcus, Prevotellaceae, Escherichia-Shigella and Bacteroidota in the intestinal tract of T2DM model rats exhibited significant changes. Furthermore, GHHRD decreased the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index and IR in T2DM model rats. &#x0D; Conclusion: GHHRD mitigates IR in T2DM model rats through alterations in the intestinal flora of the rats. This provides a theoretical basis for the potential use of GHHRD in the clinical management of T2DM.