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Insulin resistance is closely associated with metabolic diseases such as type 2 diabetes and cardiovascular disease, and the resting heart rate (RHR) is an important marker of the autonomic nervous system’s status. This study aimed to investigate the association between the RHR and the homeostatic model assessment of insulin resistance (HOMA-IR) in Korean adults. Using data from the 2019 Korea National Health and Nutrition Examination Survey (KNHANES 2019), we analyzed 6118 adults and classified the participants into four groups based on their RHR (≤67, 68–71, 72–79, and ≥80 beats/min [bpm]). Logistic regression analysis considering demographic, lifestyle, and biochemical factors revealed that the odds of having a HOMA-IR of 2.5 or higher were significantly increased in the higher RHR groups. Specifically, compared to the ≤67 bpm group, the 68–71, 72–79, and ≥80 bpm groups had increased odds of 1.277, 1.599, and 1.919 times, respectively. These results are expected to contribute to the development of strategies for the early diagnosis and management of metabolic diseases through the RHR, and further research is needed to deepen the understanding of the physiological mechanisms of this relationship, including the management of the RHR through lifestyle modification and regular exercise and the effect of reducing insulin resistance.

Prosthechea karwinskii is an endemic orchid of Mexico with cultural significance for its ornamental, food, religious, and medicinal uses. In traditional medicine, diabetic patients use the leaves of this plant to lower glucose levels. The present study evaluated the effect of P. karwinskii leaves extract on the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in a model of obese rats with insulin resistance for its nutraceutical potential to reduce insulin resistance and oxidative stress. Obesity and insulin resistance were induced with 40% sucrose in water for 20 weeks. Four groups (control rats, obese rats, obese rats administered the extract, and obese rats administered metformin) were evaluated. Extract compounds were identified by UHPLC-ESI-qTOF-MS/MS. Glucose, insulin, triglyceride, and insulin resistance indices (HOMA-IR and TyG), as well as the activity of the antioxidant enzymes, increased in rats in the obese group. Administration of P. karwinskii extract and metformin reduced glucose, insulin, triglyceride, and insulin resistance indices and antioxidant enzyme activity to values similar to those of the control group. Therefore, this study shows the nutraceutical potential of P. karwinskii extract as an ingredient in the formulation of dietary supplements or functional foods to help treat diseases whose pathophysiology is related to oxidative stress and insulin resistance.

Metabolic dysfunctions are among the best documented hallmarks of ageing. Cardiovascular disease, Alzheimer’s disease, cancer, type 2 diabetes mellitus, metabolic-dysfunction-associated steatosis liver disease, and fragility fractures are diseases of hyperinsulinaemia that reduce life and healthspan. We studied the effect of suppressing ketosis in 10 lean (BMI 20.5 kg/m2 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9 years) maintaining nutritional ketosis (NK) for an average of 3.9 years (± 2.3) who underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Ketosis suppression significantly increased insulin, 1.83-fold (p = 0.0006); glucose, 1.17-fold (p = 0.0088); homeostasis model assessment for insulin resistance (HOMA-IR), 2.13-fold (p = 0.0008); leptin, 3.35-fold (p = 0.0010); total osteocalcin, 1.63-fold (p = 0.0138); and uncarboxylated osteocalcin, 1.98-fold (p = 0.0417) and significantly decreased beta-hydroxybutyrate, 13.50-fold (p = 0.0012) and glucagon-like peptide-1 (GLP-1), 2.40-fold (p = 0.0209). Sustained NK showed no adverse health effects and may mitigate hyperinsulinemia. All biomarkers returned to basal P1 levels after removing the intervention for SuK, indicating that metabolic flexibility was maintained with long-term euketonaemia.

Altered body composition and cytokine production due to SARS-CoV-2 antigens may affect homeostasis model assessment for insulin resistance (HOMA-IR) after SARS-CoV-2 infection. To elucidate this phenomenon, we conducted a longitudinal study involving 47 COVID-19 patients, who were followed up for 12 months. During recruitment, body composition and glucose indices were measured, and heparin blood samples were collected for measuring cytokine production. HOMA-IR was considered an elevated or non-elevated group based on the ratio between HOMA-IR at 12 months and 1 month of convalescence. Those with elevated HOMA-IR had a significantly higher body mass index, body fat percentage, and visceral fat rating and had a lower lean mass and lean/fat mass ratio than their counterparts. During the convalescent period, the elevated HOMA-IR group had lower TNFα, IFNγ, IL-2, IL-10, and granzyme B expression levels but had higher TNFα/IL-10, IFNγ/IL-10, IL-2/IL-10, and granzyme B/IL-10 ratios than the other group. The reduced cytokine production and pro-/anti-inflammatory imbalance in patients with elevated HOMA-IR may suggest immune cell dysfunction toward SARS-CoV-2. Patients with elevated HOMA-IR after SARS-CoV-2 infection may experience an increase in BMI and body fat percentage, leading to increased immune dysfunction and chronic inflammatory condition. A nutritional approach and promotion of physical activity may help reduce HOMA-IR and ameliorate glucose indices in these patients.

Metabolic syndrome (MetS) is a condition defined by a cluster of symptoms, including excessive adipose tissue, impaired glucose homeostasis, dyslipidemia, and high blood pressure (BP). We aimed to evaluate the correlation between the MetS criteria (IDF) and fasting glucose-insulin-C-peptide-derived indices in a cohort of 128 healthy young adults who were 20–35 years old at the time of this study. We measured fasting serum glucose, insulin, C-peptide (CP), HDL-cholesterol, triglycerides, and hsCRP; HOMA-IR INS, HOMA-IR CP1, HOMA-IR CP2, HOMA-BETA, HOMA-BETA CP, QUICKI, disposition index (DI), CP index (CPI), and 20/C-peptide*glucose. Significant correlations were found between BMI and all HOMA indices, QUICKI, and CPI; waist circumferences and HOMA-IR INS, HOMA-BETA, and QUICKI (for both sexes); glucose and HOMA-IR INS/CP1/CP2, HOMA-BETA CP, DI, and QUICKI; HDL-cholesterol and HOMA-IR INS, HOMA-BETA, and QUICKI for males and females only with QUICKI; triglycerides and HOMA-IR INS, HOMA-BETA, and QUICKI; systolic BP and HOMA-IR INS, HOMA-BETA; diastolic BP and DI. The cut-off values for HOMA-IR INS, HOMA-BETA, and QUICKI in the combined group (females + males) were 1.855, 82.250, 0.355; 2.115, 106.370, 0.345 for males; 1.805, 71.305, 0.355 for females. A stronger correlation was found between males’ indices and hsCRP. In conclusion, CP-derived indices do not add significant information, and the male sex is more predisposed to MetS.

Prenatal stress (PNS), which alters the hypothalamic-pituitary-adrenal axis function in the offspring, predisposes to insulin resistance (IR) in later life and is associated with numerous disorders, including cognitive and memory impairments. At present, our main goal is to assess the effects of chronic piromelatine (Pir) administration, a melatonin analogue, on PNS-provoked IR in the periphery and the hippocampus in male and female offspring. Pregnant Sprague–Dawley rats were exposed to chronic stress (one short-term stressor on a daily basis and one long-term stressor on a nightly basis) from the first gestation week until birth. Vehicle or Pir 20 mg/kg were administered intraperitoneally for 21 days. Plasma glucose, serum insulin levels, and the homeostasis model assessment of insulin resistance (HOMA-IR) were determined as markers of peripheral IR. For the hippocampal IR assessment, insulin receptors (IRs) and glucose transporter 4 (GLUT4) were examined. Prenatally stressed offspring of both sexes indicated enhanced plasma glucose and serum insulin concentrations, increased HOMA-IR, and decreased hippocampal GLUT4 only in male rats. The PNS-induced changes were corrected by chronic treatment with Pir. The present results suggest that the melatoninergic compound Pir exerts beneficial effects on altered glucose/insulin homeostasis in PNS-exposed offspring.

Diabetes mellitus (DM) is a major risk and prognostic factor for heart failure (HF). Insulin resistance (IR) is an important component of DM, but the relationship between IR and HF prognosis has not yet been established across a wide variety of HF populations. We retrospectively evaluated the relationship between IR and clinical outcomes of HF patients at our hospital between 2017 and 2021. IR was defined as a homeostatic model assessment of IR (HOMA-IR) index ≥ 2.5, calculated from fasting blood glucose and insulin concentrations. The primary outcome was a composite of all-cause death and hospitalisation for HF (HHF). Among 682 patients included in the analyses, 337 (49.4%) had IR. The median age was 70 [interquartile range (IQR): 59–77] years old, and 66% of the patients were men. Among the patients, 41% had a left ventricular ejection fraction below 40%, and 32% had DM. The median follow-up period was 16.5 [IQR: 4.4–37.3] months. IR was independently associated with the primary outcome (HR: 1.91, 95% CI: 1.39–2.62, p < 0.0001), death (hazard ratio [HR]: 1.86, 95% confidence interval [CI]: 1.28–2.83, p < 0.01), and HHF (HR: 1.91, 95% CI: 1.28–2.83, p < 0.01). HOMA-IR is an independent prognostic factor of HF in a wide variety of HF populations.

Background: Obesity is a chronic inflammatory disorder that increases the risk of cardiovascular diseases (CVDs). Given the high CVD mortality rate among individuals with obesity, early screening should be considered. Plasminogen activator inhibitor (PAI-1), a cytokine that links obesity and CVDs, represents a promising biomarker. However, PAI-1 is not part of the clinical routine due to its high cost. Therefore, it is necessary to find good predictors that would allow an indirect assessment of PAI-1. Methods: This study enrolled 47 women with severe obesity (SO). The obtained anthropometric measurements included weight, height, neck (NC), waist (WC), and hip circumference (HC). Blood samples were collected to analyse glucose and lipid profiles, C-reactive protein, liver markers, adiponectin, and PAI-1 (determined by ELISA immunoassay). Homeostasis model assessment-adiponectin (HOMA-AD), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), triglyceride–glucose index (TyG), and atherogenic index of plasma (AIP) were calculated. The women were grouped according to PAI-1 levels. The data were analysed using IBM SPSS Statistics, version 21. The significance level for the analysis was set at 5%. Results: Women with SO who have higher levels of PAI-1 have lower values of high-density lipoprotein cholesterol (HDL) (p = 0.037) and QUICKI (0.020) and higher values of HOMA-AD (0.046) and HOMA-IR (0.037). HOMA-IR was demonstrated to be a good predictor of PAI-1 in this sample (B = 0.2791; p = 0.017). Conclusions: HOMA-IR could be used as a predictor of PAI-1 levels, pointing out the relevance of assessing glycaemic parameters for the prevention of CVDs in women with SO.

Psoriasis is a chronic inflammatory disease with specific cutaneous and nail lesions. Recent data has emphasized its systemic nature, highlighting metabolic conditions found in patients. Insulin resistance was identified in adult psoriasis, sometimes related to psoriasis severity. Data regarding this relationship in children are limited. Consequently, we tested the association between the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Psoriasis Area and Severity Index (PASI) using a retrospective dataset of 43 children with various types of psoriasis. First, we attempted to replicate the relationship between the HOMA-IR and PASI. Second, we explored potential associations between these variables and others in the dataset. The results illustrated no association between HOMA-IR and PASI (p-value = 0.512). The exploratory findings hinted at a connection between nail pitting and insulin resistance (p-value = 0.038), yet Bonferroni adjustments suggested the risk of a false-positive finding. Noteworthy associations were found between the HOMA-IR and body mass index (BMI) (p-value = 0.001), the PASI and quality of life impairment (p-value = 0.005), and psoriasis severity and type (p-value = 0.001). The null hypothesis that insulin resistance in children is not positively associated with psoriasis severity cannot be rejected. Pilot estimates of variables and covariates of interest are provided for further confirmatory studies assessing this hypothesis.

Background: Repetitive episodes of apnea and hypopnea during sleep in patients with obstructive sleep apnea (OSA) are known to increase the risk of atherosclerosis. Underlying obesity and related disorders, such as insulin resistance, are indirectly related to the development of atherosclerosis. In addition, OSA is independently associated with insulin resistance; however, data regarding this relationship are scarce in Japanese populations. Methods: This study aimed to examine the relationship between the severity of OSA and insulin resistance in a Japanese population. We analyzed the data of consecutive patients who were referred for polysomnography under clinical suspicion of developing OSA and who did not have diabetes mellitus or any cardiovascular disease. Multiple regression analyses were performed to determine the relationship between the severity of OSA and insulin resistance. Results: The data from a total of 483 consecutive patients were analyzed. The median apnea-hypopnea index (AHI) was 40.9/h (interquartile range: 26.5, 59.1) and the median homeostasis model assessment for insulin resistance (HOMA-IR) was 2.00 (interquartile range: 1.25, 3.50). Multiple regression analyses revealed that the AHI, the lowest oxyhemoglobin saturation (SO2), and the percentage of time spent on SO2 < 90% were independently correlated with HOMA-IR (an adjusted R-squared value of 0.01278821, p = 0.014; an adjusted R-squared value of −0.01481952, p = 0.009; and an adjusted R-squared value of 0.018456581, p = 0.003, respectively). Conclusions: The severity of OSA is associated with insulin resistance assessed by HOMA-IR in a Japanese population.

The dysfunction of phospholipid metabolism enzymes and the change in membrane phospholipid composition are associated with insulin resistance, indicating that phospholipids play an important role in the regulation of insulin sensitivity. The reflection of phospholipid changes in blood might provide clues for both mechanism understanding and intervention. Using a targeted phospholipidomic approach, 199 phospholipid molecular species were identified and quantified in the plasma of 1053 middle-aged participants from a national investigation. The associations of the phospholipid matrix, clusters, and molecular species with insulin resistance were investigated. A significant association was confirmed between the phospholipid matrix and the homeostatic-model assessment of insulin resistance (HOMA-IR) by a distance-based linear model. Furthermore, three clustered phospholipid modules and 32 phospholipid molecular species were associated with HOMA-IR with the strict control of demographic and lifestyle parameters, family history of diabetes, BMI, WC, and blood lipid parameters. The overall decline in lysophosphatidylcholines (LPCs), the decrease in saturated lysophosphatidylethanolamines (LPEs), the decrease in polyunsaturated/plasmenyl phosphatidylcholines (PCs), and the increase in polyunsaturated phatidylethanolamines (PEs) were the prominent characters of plasma phospholipid perturbation associated with insulin resistance. This suggested that PC- and PE-related metabolic pathways were widely involved in the process of insulin resistance, especially the disorder of LPC acylation to diacyl-PC.

Background: Insulin resistance plays an important role in the development of post-transplantation diabetes mellitus (PTDM) in kidney transplant recipients (KTRs). Current methods for the direct determination of insulin resistance are complicated and invasive. Therefore, this study aimed to investigate the relevance of indirect insulin resistance indices in relation to the development of PTDM in KTRs. Methods: We included 472 stable outpatient KTRs without diabetes at baseline from a prospective cohort study. Four indirect insulin resistance indices, namely homeostasis model assessment–insulin resistance (HOMA-IR), visceral adiposity index (VAI), lipid accumulation product (LAP), and triglycerides–glucose (TyG) index, were assessed. We analyzed each measure using the receiver operating characteristic (ROC) curve for PTDM development. The optimal cut-off value for each parameter was determined using the Youden index. Results: After a median of 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 were 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 respective optimal cut-off values of 2.47, 4.01, 87.0, and 4.94. Conclusions: Indirect insulin resistance indices can 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 of PTDM, thus obviating the necessity to measure insulin.

The prevalence of people being overweight and obese has increased globally over the past decades. The use of omega-3 fatty acids—a compound usually primarily found in fish oil—has been known to improve the metabolic profile of obese patients. As the demand for eels increases, the number of waste products from the eels increases and creates environmental problems. This study was conducted to investigate the effect of a newly discovered Indonesian Shortfin eel by-product oil supplementation on the Homeostasis Model Assessment-Estimated Insulin Resistance (HOMA-IR) and lipid profiles of obese male (Lee index ≥ 0.3) Wistar rats (Rattus norvegicus). The oil was extracted from waste products (heads). Fifteen obese rats were divided into three groups and were administered NaCl (C), commercial fish oil (CO), and Indonesian shortfin eel by-product oil (EO). All groups had statistically significant differences in total cholesterol, LDL, and triglyceride levels (p < 0.05). The CO and EO group showed a significant decrease in total cholesterol, LDL, and triglyceride after treatment. However, no significant difference was found in HDL levels and HOMA-IR. The supplementation of Indonesian shortfin eel by-product oil significantly improved lipid profile while effectively mitigating environmental challenges.

Type 2 diabetes mellitus (T2DM) is a major global public health problem, as it is associated with increased morbidity, mortality, and healthcare costs. Insulin resistance (IR) is a condition characterized by disturbances in carbohydrate and lipid metabolism that precedes T2DM. The aim of the present study was to investigate the association between HDL and its subfraction profile and the progression of IR, as assessed by the Homeostatic Model Assessment for IR (HOMA-IR) index, and to define cut-off values to identify an increased risk of IR. Individuals with a HOMA-IR greater than 3.63 were considered to have IR. The HDL subfractions were separated using the Lipoprint system, which identifies ten subfractions (HDL-1-10) in three subclasses as large (HDL-L), intermediate (HDL-I) and small (HDL-S). Analyses were performed on samples from 240 individuals without IR and 137 with IR from the Hungarian general and Roma populations. The HDL-1 to -6 subfractions and the HDL-L and -I classes showed a significant negative association with the progression and existence of IR. Among them, HDL-2 (B = −40.37, p = 2.08 × 10−11) and HDL-L (B = −14.85, p = 9.52 × 10−10) showed the strongest correlation. The optimal threshold was found to be 0.264 mmol/L for HDL-L and 0.102 mmol/L and above for HDL-2. Individuals with HDL-L levels below the reference value had a 5.1-fold higher risk of IR (p = 2.2 × 10−7), while those with HDL-2 levels had a 4.2-fold higher risk (p = 3.0 × 10−6). This study demonstrates that the HDL subfraction profile (especially the decrease in HDL-2 and -L) may be a useful marker for the early detection and intervention of atherogenic dyslipidemia in subjects with impaired glucose and insulin metabolism.

Background: Childhood overweight and obesity have been described by the World Health Organization as noncommunicable diseases and among the greatest public health threats since they have reached epidemic proportions. A child with obesity risks becoming an adult with obesity and developing metabolic and hemostatic disorders which are the basis for the development of coronary heart diseases. Recently, a number of clinical reports have demonstrated that both an increase in plasminogen activator inhibitor-1 (PAI-1) and a deficiency in 25OH-vitamin D3 (VD) are associated with an increase in thrombotic episodes. Methods: PAI-1 and VD levels were measured in 259 clinically overweight and obese children aged between 2 and 18 years enrolled in the Nutritional Education Program of the Bambino Gesù Children’s Hospital and Research Institute of Rome (Italy) and 80 normal-weight subjects. Results: We observed increased HOMA-IR, PAI-1, and other inflammation indices associated with decreased VD levels when compared to normal-weight children. Conclusions: Our results demonstrated that overweight and obesity are correlated with higher levels of the inflammation index. Moreover, our patients show high PAI-1 and low VD levels, confirming the high thrombotic risk in our pediatric population.

Abdominal obesity is a common feature of women with polycystic ovary syndrome (PCOS), and it is known to exacerbate insulin resistance (IR). Improper dietary and physical activity patterns are crucial environmental factors involved in the development of obesity, and they can significantly influence the central deposition of adipose tissue. Therefore, in this cross-sectional study, we aimed to evaluate the relationship between abdominal adiposity (measured by VAT (visceral adipose tissue), SAT (subcutaneous adipose tissue), VAT/SAT ratio (visceral to subcutaneous fat ratio), and WHR (waist-to-hip ratio)) and the prevalence and odds ratios of IR (measured by the homeostatic model assessment of insulin resistance (HOMA-IR), the homeostatic model assessment-adiponectin (HOMA-AD) and leptin to adiponectin ratio (L/A ratio)) in 56 PCOS women. Furthermore, we investigated the relationship between these abdominal obesity indices and diet and physical activity. An original food frequency questionnaire and Actigraph GT3X-BT were used to assess adherence to the diet recommended in IR and the level of physical activity, respectively. We observed a higher prevalence of IR among women with higher VAT, VAT/SAT, and WHR values compared to women with normal values of those abdominal obesity indices. Moreover, VAT/SAT seemed to be the best predictor of IR measured by HOMA-IR and HOMA-AD. However, VAT appeared to be the best and strongest predictor of IR measured by the L/A ratio. We also observed that higher adherence to the diet recommended in IR and higher levels of vigorous physical activity were associated with lower values of central fat accumulation indices and a greater chance of their normal values. Our findings indicate that central obesity increases the odds of IR and supports the beneficial role of diet and physical activity in the management of abdominal obesity in PCOS women.

Acne vulgaris presents multifactorial pathogenesis, which may include insulin resistance. To investigate whether insulin resistance is a causative factor in acne vulgaris development, this cohort study and a systematic review were conducted. A cohort of 41 acne vulgaris patients and 47 healthy BMI-matched controls were recruited. Glucose and insulin fasting serum levels were obtained and the HOMA-IR was calculated; insulin resistance was diagnosed in cases with a HOMA-IR value over 2.1. The mean ± SD values for glucose fasting serum level were as follows: 94.88 ± 7.731 (mg/dL) in the study group and 79.51 ± 7.175 (mg/dL) in the controls (p < 0.001). The mean ± SD insulin fasting serum levels were 14.47 ± 6.394 (µIU/mL) and 11.83 ± 4.309 (µIU/mL) (p = 0.059), respectively. The HOMA-IR mean ± SD value calculated for the study group was 3.4 ± 1.49 and, in the control group, it was 2.34 ± 0.909 (p < 0.001). Out of 41 patients, 32 were diagnosed with insulin resistance (78%), and 26 of the 47 controls were diagnosed with IR (55%) (p = 0.026). An insulin resistance diagnosis was statistically more common among the acne patients, compared to the controls. In the articles reviewed in this paper, insulin resistance was found to be more frequent in acne vulgaris patients. Both our study and the papers analyzed in the review indicate that insulin resistance might be an independent factor in acne vulgaris development and should be considered when diagnosing and treating acne.

Research into early predictors of effective weight loss could help determine more effective therapeutic interventions. In this study, 106 subjects with class I obesity, genotyped with the fat mass and obesity-associated (FTO) rs9930506 gene variant, were enrolled into a 12-week weight loss program (WLP). Anthropometric and body composition measurements were controlled with bioelectrical impedance analysis (BIA) at baseline and after 4 and 12 weeks. Biopsies of abdominal subcutaneous adipose tissue (AT) and venous blood samples were collected to monitor changes in interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) mRNA levels in white blood cells (WBCs) and to assess if changes in WBC gene expression reflected changes in adipose tissue. The FTO rs9930506 variant had no effect on weight loss and no reduction in proinflammatory transcripts in WBCs or AT. Changes in anthropometric parameters were associated with changes in carbohydrate metabolism. A linear regression model showed that initial weight loss (after 4 weeks of the WLP) was the most predictive factor of weight loss success after 12 weeks of the WLP. Changes in plasma lipids or proinflammatory transcript levels in WBCs or AT were not associated with weight loss effectiveness. However, the gene expression in WBCs did reflect changes occurring in subcutaneous AT.

Prosthechea karwinskii is an endemic orchid of Mexico with cultural significance for its ornamental, food, religious, and medicinal uses. In traditional medicine, diabetic patients use the leaves of this plant to lower glucose levels. The present study evaluated the effect of P. karwinskii leaves extract on the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in a model of obese rats with insulin resistance for its nutraceutical potential to reduce insulin resistance and oxidative stress. Obesity and insulin resistance were induced with 40% sucrose in water for 20 weeks. Four groups (control rats, obese rats, obese rats administered the extract, and obese rats administered metformin) were evaluated. Extract compounds were identified by UHPLC-ESI-qTOF-MS/MS. Glucose, insulin, triglyceride, and insulin resistance indices (HOMA-IR and TyG), as well as the activity of the antioxidant enzymes, increased in rats in the obese group. Administration of P. karwinskii extract and metformin reduced glucose, insulin, triglyceride, and insulin resistance indices and antioxidant enzyme activity to values similar to those of the control group. Therefore, this study shows the nutraceutical potential of P. karwinskii extract as an ingredient in the formulation of dietary supplements or functional foods to help treat diseases whose pathophysiology is related to oxidative stress and insulin resistance.

Altered body composition and cytokine production due to SARS-CoV-2 antigens may affect homeostasis model assessment for insulin resistance (HOMA-IR) after SARS-CoV-2 infection. To elucidate this phenomenon, we conducted a longitudinal study involving 47 COVID-19 patients, who were followed up for 12 months. During recruitment, body composition and glucose indices were measured, and heparin blood samples were collected for measuring cytokine production. HOMA-IR was considered an elevated or non-elevated group based on the ratio between HOMA-IR at 12 months and 1 month of convalescence. Those with elevated HOMA-IR had a significantly higher body mass index, body fat percentage, and visceral fat rating and had a lower lean mass and lean/fat mass ratio than their counterparts. During the convalescent period, the elevated HOMA-IR group had lower TNFα, IFNγ, IL-2, IL-10, and granzyme B expression levels but had higher TNFα/IL-10, IFNγ/IL-10, IL-2/IL-10, and granzyme B/IL-10 ratios than the other group. The reduced cytokine production and pro-/anti-inflammatory imbalance in patients with elevated HOMA-IR may suggest immune cell dysfunction toward SARS-CoV-2. Patients with elevated HOMA-IR after SARS-CoV-2 infection may experience an increase in BMI and body fat percentage, leading to increased immune dysfunction and chronic inflammatory condition. A nutritional approach and promotion of physical activity may help reduce HOMA-IR and ameliorate glucose indices in these patients.

Metabolic dysfunctions are among the best documented hallmarks of ageing. Cardiovascular disease, Alzheimer's disease, cancer, type 2 diabetes mellitus, metabolic-dysfunction-associated steatosis liver disease, and fragility fractures are diseases of hyperinsulinaemia that reduce life and healthspan. We studied the effect of suppressing ketosis in 10 lean (BMI 20.5 kg/m 2 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9 years) maintaining nutritional ketosis (NK) for an average of 3.9 years (± 2.3) who underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Ketosis suppression significantly increased insulin, 1.83-fold ( p = 0.0006); glucose, 1.17-fold ( p = 0.0088); homeostasis model assessment for insulin resistance (HOMA-IR), 2.13-fold ( p = 0.0008); leptin, 3.35-fold ( p = 0.0010); total osteocalcin, 1.63-fold ( p = 0.0138); and uncarboxylated osteocalcin, 1.98-fold ( p = 0.0417) and significantly decreased beta-hydroxybutyrate, 13.50-fold ( p = 0.0012) and glucagon-like peptide-1 (GLP-1), 2.40-fold ( p = 0.0209). Sustained NK showed no adverse health effects and may mitigate hyperinsulinemia. All biomarkers returned to basal P1 levels after removing the intervention for SuK, indicating that metabolic flexibility was maintained with long-term euketonaemia.

Insulin resistance (IR) is a prominent feature of polycystic ovary syndrome (PCOS). The importance of lifestyle interventions in the management of PCOS is strongly highlighted and it is suggested that diet and physical activity may significantly influence insulin sensitivity. Therefore, we evaluated the link between diet and physical activity and various indices of insulin resistance, including adipokines secreted by the adipose tissue in 56 PCOS and 33 healthy control women. The original food frequency questionnaire and Actigraph GT3X-BT were used to assess the adherence to the diet recommended in IR and the level of physical activity, respectively. We observed that higher levels of physical activity were associated with lower HOMA-IR and a greater chance of its normal value in PCOS group. No such relationship was observed for other IR indices and adipokines or for the diet. However, we noted a strong correlation between HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) and HOMA-AD (Homeostatic Model Assessment-Adiponectin) in PCOS women. Additionally, when we used HOMA-AD we observed a higher prevalence of IR among PCOS women. Our study supports the beneficial role of physical activity in the management of insulin resistance in PCOS women. Moreover, our findings indicate that HOMA-AD may be a promising surrogate marker for insulin resistance assessment in women with PCOS.

To examine the associations of sociodemographic, lifestyle, and clinical factors with cardiometabolic risk and each of its components during pregnancy in a pregnant population from Catalonia (Spain). A prospective cohort study of 265 healthy pregnant women (39 ± 5 years) in the first and third-trimesters. Sociodemographic, obstetric, anthropometric, lifestyle and dietary variables were collected, and blood samples were taken. The following cardiometabolic risk markers were evaluated: BMI, blood pressure, glucose, insulin, HOMA-IR, triglycerides, LDL, and HDL-cholesterol. From these, a cluster cardiometabolic risk (CCR)-z score was created by summating all z-scores (except insulin and DBP) computed for each risk factor. Data were analyzed using bivariate analysis and multivariable linear regression. In the multivariable models, the first-trimester CCRs was positively associated with overweight/obesity status (β: 3.54, 95%CI: 2.73, 4.36) but inversely related to the level of education (β: −1.04, 95%CI: −1.94, 0.14) and physical activity (PA) (β: −1.21, 95%CI: −2.24, −0.17). The association between overweight/obesity and CCR (β:1.91, 95%CI: 1.01, 2.82) persisted into the third-trimester, whereas insufficient GWG (β: −1.14, 95%CI: −1.98, −0.30) and higher social class (β: −2.28, 95%CI: −3.42, −1.13) were significantly associated with a lower CCRs. Starting pregnancy with normal weight, higher socioeconomic and educational levels, being a non-smoker, non-consumer of alcohol, and PA were protective factors against cardiovascular risk during pregnancy.

Insulin resistance (IR) is considered the precursor and the key pathophysiological mechanism of type 2 diabetes (T2D) and metabolic syndrome (MetS). However, the pathways that IR shares with T2D are not clearly understood. Meta-analysis of multiple DNA microarray datasets could provide a robust set of metagenes identified across multiple studies. These metagenes would likely include a subset of genes (key metagenes) shared by both IR and T2D, and possibly responsible for the transition between them. In this study, we attempted to find these key metagenes using a feature selection method, LASSO, and then used the expression profiles of these genes to train five machine learning models: LASSO, SVM, XGBoost, Random Forest, and ANN. Among them, ANN performed well, with an area under the curve (AUC) > 95%. It also demonstrated fairly good performance in differentiating diabetics from normal glucose tolerant (NGT) persons in the test dataset, with 73% accuracy across 64 human adipose tissue samples. Furthermore, these core metagenes were also enriched in diabetes-associated terms and were found in previous genome-wide association studies of T2D and its associated glycemic traits HOMA-IR and HOMA-B. Therefore, this metagenome deserves further investigation with regard to the cardinal molecular pathological defects/pathways underlying both IR and T2D.

The hypertriglyceridemic waist (HTGW) phenotype is characterized by abdominal obesity and elevated serum triglycerides. We aimed to assess the prevalence of the HTGW phenotype among children with overweight or obesity and its association with indices of insulin resistance (IR) and dyslipidemia. A total of 145 children with mean age of 10.2 years (SD = 2.31 years), 97.2% of whom with obesity, were analyzed. The HTGW phenotype was defined as WC > 90th Centers for Disease Control and Prevention (CDC) percentile and triglyceride levels of ≥100 mg/dL and ≥130 mg/dL for children 0 to 9 or >10 years of age, respectively. In total, 77.9% of the children had a waist circumference above the 90th percentile and 22.8% had elevated triglycerides. The prevalence of the HTGW phenotype in this sample was 19.3%. Patients with the HTGW phenotype had significantly lower levels of High-Density Lipoprotein (p < 0.001) and were insulin-resistant, as evident by an increased mean Triglycerides Glucose Index 8.64 (SD = 0.24) vs. 7.92 (SD = 0.41) for those without the HTGW phenotype (p < 0.001), and increased prevalence (54.5%) of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in ≥2.5 in patients with HTGW (p = 0.045). Children with the HTGW phenotype were more likely to have increased HOMA-IR [OR 7.9 95% CI (1.94, 32.1)]. The HTGW phenotype is a low-cost and easily available index that might help to identify children with increased cardiometabolic risk.

Fatty liver (FL) is one of the most prevalent diseases in the world, characterized by insulin resistance and hyperlipidemia, which consequently lead to neurodegenerative disorders through the induction of oxidative stress-inflammatory axis, which alters the neurotransmitters’ levels. Calluna vulgaris (CV), also known as heather, has anti-inflammatory and antidepressant properties, making it a promising candidate for treating steatosis and brain lesions. This study aimed to assess the prophylactic and therapeutic effect of CV extract on brain dysfunction associated with steatosis. FL was induced in rats by CCl4 oral administration (50 µL/Kg in olive oil three times/week) for six weeks. The protection group received 200 mg/kg CV extract orally for two weeks before and two weeks during FL induction, while the treatment group was orally administered CV extract after FL induction for one month. The biochemical parameters revealed that CCl4 administration induced hepatotoxicity as blood-liver function parameters (AST, ALT, ALP, protein, and LDH) were increased by 1.8, 1.4, 2, 2.4, and 1.2-fold, respectively. Moreover, insulin resistance was characterized by a two-fold increase in the glucose, insulin, and lipid profile when compared to control one, at p < 0.05. Steatosis liver demonstrated a two-fold increase in all following parameters— acetaldehyde (AC), prooxidant (TBARS), acetylcholine esterase (AChE), monoamine oxidase (MAO), hyaluronidase, and ATPase—when compared to control one, at p < 0.05. CCl4 administration led to brain lesions where the brain level of TBARS, insulin, cholesterol, AChE, and MAO was progressively increased by 2, 1.6, 2.2, 4, and 1.6-fold, respectively, that was associated with reduced glucose (8-fold) and GSH (2-fold) than that of control level, at p < 0.05. CV extract as a prophylactic and therapeutic agent increased GSH and decreased TBARS of both the liver and brain than that of induced group, at p < 0.05, normalized the activities of AChE and MAO, and increased insulin sensitivity where they successfully decreased the HOMA-IR, glucose, TG, and cholesterol compared to than that of induced group, at p < 0.05. This positive effect of CV extract contributed to the presence of polyphenolic compounds such as catechins (5.501 ± 0.056 µg/g extract), gallic (3.525 ± 0.143 µg/g) extract, and protocatechuic acid (2.719 ± 0.132 µg/g extract). Therefore, we concluded that FL induced brain dysfunction through the formation of ROS and elevation of insulin and lipid inside the brain tissue, which alter the amount of neurotransmitter and cellular energy production. Rich in polyphenolic compounds, CV extract functions as an antioxidant, antidiabetic, hepatoprotective, inhibitor of neurotransmitter catabolizing enzymes, and a regulator for energy production. Therefore, it can be used as a preventative or treatment for NAFLD and brain damage.

There is interest in the impact that dietary interventions can have on preventing the transition from insulin resistance to type 2 diabetes, including a suggestion that the bioactive components of cocoa may enhance fasting insulin sensitivity. However, a role for cocoa flavanols (CF) in reducing insulin resistance in the insulin-stimulated state, an important risk factor for cardiovascular disease, is unresolved. This study investigated whether CF consumption improved whole-body insulin-mediated glucose uptake (‘M’) in females with overweight/obesity, using a randomized, double-blinded, placebo-controlled, parallel-group design. Thirty-two premenopausal females (19–49 years; 27–35 kg·m−2) with elevated HOMA-IR (HOMA-IR >1.5) supplemented their habitual diet with two servings/day of a high-flavanol cocoa drink (HFC; 609 mg CF/serving; n = 16) or low-flavanol cocoa drink (LFC; 13 mg CF/serving; n = 16) for 4 weeks. Assessment of HOMA-IR and ‘M’ during a 3-h, 60 mIU insulin·m−2·min−1 euglycemic clamp was performed before and after the intervention. Data are the mean (SD). Changes to HOMA-IR (HFC −0.003 (0.57); LFC −0.0402 (0.86)) and ‘M’ (HFC 0.99 (7.62); LFC –1.32 (4.88) µmol·kg−1·min−1) after the intervention were not different between groups. Four weeks’ consumption of ~1.2 g CF/day did not improve indices of fasting insulin sensitivity or insulin-mediated glucose uptake. A recommendation for dietary supplementation with cocoa flavanols to improve glycemic control is therefore not established.

Objective: To investigate the ability of homeostasis model assessment of insulin resistance (HOMA-IR) in early pregnancy for predicting gestational diabetes mellitus (GDM) in Chinese women with different first-trimester body mass index (FT-BMI) values. Methods: Baseline characteristics and laboratory tests were collected at the first prenatal visit (6–12 weeks of gestation). GDM was diagnosed by a 75 g oral glucose tolerance test (OGTT) at 24–28 weeks of gestation. Partial correlation analysis and binary logistic regression were applied to identify the association between HOMA-IR and GDM. The cutoff points for predicting GDM were estimated using receiver operating characteristic (ROC) curve analysis. Results: Of the total of 1343 women, 300 (22.34%) were diagnosed with GDM in the 24–28 weeks of gestation. Partial correlation analysis and binary logistic regression verified HOMA-IR as a significant risk factor for GDM in the normal weight subgroup (FT-BMI < 24 kg/m2) (adjusted OR 2.941 [95% CI 2.153, 4.016], P < 0.001), overweight subgroup (24.0 kg/m2 ≤ FT-BMI < 28.0 kg/m2) (adjusted OR 3.188 [95% CI 2.011, 5.055], P < 0.001), and obese subgroup (FT-BMI ≥ 28.0 kg/m2) (adjusted OR 9.415 [95% CI 1.712, 51.770], p = 0.01). The cutoff values of HOMA-IR were 1.52 (area under the curve (AUC) 0.733, 95% CI 0.701–0.765, p < 0.001) for all participants, 1.43 (AUC 0.691, 95% CI 0.651–0.730, p < 0.001) for normal weight women, 2.27 (AUC 0.760, 95% CI 0.703–0.818, p < 0.001) for overweight women, and 2.31 (AUC 0.801, 95% CI 0.696–0.907, p < 0.001) for obese women. Conclusions: Increased HOMA-IR in early pregnancy is a risk factor for GDM, and HOMA-IR can be affected by body weight. The cutoff value of HOMA-IR to predict GDM should be distinguished by different FT-BMI values.

Polycystic ovary syndrome (PCOS) is associated with insulin resistance. Few randomized controlled trials (RCT) compared myoinositol (MI) with metformin (MET) regarding insulin resistance in PCOS. This was an open-label six-month RCT in women with PCOS (n = 45) with interventions MI 4 g/day or MET 2 g/day. Primary outcome was the homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were fasting glucose, weight, cycle length, lipids, testosterone, adverse effects, quality of life, and depression scores. Median age was 26 years. Body mass was index was 34.4 kg/m2. HOMA-IR was unchanged during MI (p = 0.31) and MET (p = 0.11) (MI vs. MET, p = 0.09). Median fasting glucose changed +0.2 mmol/L during MI (p < 0.001) and −0.1 mmol/L during MET (p = 0.04) (MI vs. MET p < 0.001). Median weight changed −2.3 kg during MI (p = 0.98) and −6.1 kg during MET (p < 0.001) (MI vs. MET, p = 0.02). Median cycle length decreased nine days during MI (p = 0.03) and 13 days during MET (p = 0.03) (MI vs. MET, p = 0.93). High-density lipoprotein (HDL) changed +0.1 mmol/L during MET (p = 0.04) (MI vs. MET, p = 0.07). All other blood parameters and scores of quality of life and depression remained unchanged during MI and MET (all p > 0.06) (MI vs. MET, all p > 0.27). Adverse effects appeared in four women during MI and 16 women during MET (MI vs. MET, p = 0.001). In conclusion, there was no effect on the metabolic outcomes during MI, but positive effects on fasting blood glucose, weight, and HDL during MET. The effect on cycle length was comparable during MI and MET. Adverse effects were less frequent during MI.

Interruptins A and B exhibited anti-diabetic, anti-inflammatory, and anti-oxidative effects. This study aimed to investigate the therapeutic ability of extract enriched by interruptins A and B (EEI) from an edible fern Cyclosorus terminans on insulin resistance and non-alcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD)-induced obese rats and elucidate their possible mechanisms. HFD-induced obese rats were treated with EEI for 2 weeks. Real-time polymerase chain reaction (PCR) was used to examine the molecular basis. We found that EEI supplementation significantly attenuated body and liver weight gain, glucose intolerance, and insulin resistance. Concurrently, EEI increased liver and soleus muscle glycogen storage and serum high-density lipoprotein (HDL) levels. EEI also attenuated NAFLD, as indicated by improving liver function. These effects were associated with enhanced expression of insulin signaling genes (Slc2a2, Slc2a4, Irs1 and Irs2) along with diminished expression of inflammatory genes (Il6 and Tnf). Furthermore, EEI led to the suppression of lipogenesis genes, Srebf1 and Fasn, together with an increase in fatty acid oxidation genes, Ppara and Cpt2, in the liver. These findings suggest that EEI could ameliorate HFD-induced insulin resistance and NAFLD via improving insulin signaling pathways, inflammatory response, lipogenesis, and fatty acid oxidation.

Results of previous studies about the acute effects of fine particulate matter (PM2.5) on blood lipids were inconsistent. This study aimed to quantify the short-term effects of PM2.5 on blood lipids and estimate the modifying role of insulin resistance, reflected by the homeostasis model assessment of insulin resistance (HOMA-IR). From September 2019 to January 2020, the study recruited 70 healthy adults from Wuhan University for a total of eight repeated data collections. At each visit, three consecutive days were monitored for personal exposure to PM2.5, and then a physical examination was carried out on the fourth day. The linear mixed-effect models were operated to investigate the impact of PM2.5 over diverse exposure windows on blood lipids. With the median of the HOMA-IR 1.820 as the cut-off point, participants were assigned to two groups for the interaction analyses. We found the overall mean level (standard deviation, SD) of PM2.5 was 38.34 (18.33) μg/m3. Additionally, with a 10 μg/m3 rise in PM2.5, the corresponding largest responses in triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), as well as high-density lipoprotein cholesterol (HDL-C), were −0.91% (95% confidence interval (CI): −1.63%, −0.18%), −0.33% (95% CI: −0.64%, −0.01%,), −0.94% (95% CI: −1.53%, −0.35%), and 0.67% (95% CI: 0.32%, 1.02%), respectively. The interaction analyses revealed that a significantly greater reduction in the four lipids corresponded to PM2.5 exposure when in the group with the lower HOMA-IR (2.5 exposure over specific time windows among healthy adults was associated with reduced TG, TC, as well as LDL-C levels, and elevated HDL-C. Additionally, the association of PM2.5–lipids may be modulated by insulin resistance.

Background: Obesity is a chronic inflammatory disorder that increases the risk of cardiovascular diseases (CVDs). Given the high CVD mortality rate among individuals with obesity, early screening should be considered. Plasminogen activator inhibitor (PAI-1), a cytokine that links obesity and CVDs, represents a promising biomarker. However, PAI-1 is not part of the clinical routine due to its high cost. Therefore, it is necessary to find good predictors that would allow an indirect assessment of PAI-1., Methods: This study enrolled 47 women with severe obesity (SO). The obtained anthropometric measurements included weight, height, neck (NC), waist (WC), and hip circumference (HC). Blood samples were collected to analyse glucose and lipid profiles, C-reactive protein, liver markers, adiponectin, and PAI-1 (determined by ELISA immunoassay). Homeostasis model assessment-adiponectin (HOMA-AD), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), triglyceride-glucose index (TyG), and atherogenic index of plasma (AIP) were calculated. The women were grouped according to PAI-1 levels. The data were analysed using IBM SPSS Statistics, version 21. The significance level for the analysis was set at 5%., Results: Women with SO who have higher levels of PAI-1 have lower values of high-density lipoprotein cholesterol (HDL) ( p = 0.037) and QUICKI (0.020) and higher values of HOMA-AD (0.046) and HOMA-IR (0.037). HOMA-IR was demonstrated to be a good predictor of PAI-1 in this sample (B = 0.2791; p = 0.017)., Conclusions: HOMA-IR could be used as a predictor of PAI-1 levels, pointing out the relevance of assessing glycaemic parameters for the prevention of CVDs in women with SO.

Psoriasis is a chronic inflammatory disease with specific cutaneous and nail lesions. Recent data has emphasized its systemic nature, highlighting metabolic conditions found in patients. Insulin resistance was identified in adult psoriasis, sometimes related to psoriasis severity. Data regarding this relationship in children are limited. Consequently, we tested the association between the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Psoriasis Area and Severity Index (PASI) using a retrospective dataset of 43 children with various types of psoriasis. First, we attempted to replicate the relationship between the HOMA-IR and PASI. Second, we explored potential associations between these variables and others in the dataset. The results illustrated no association between HOMA-IR and PASI ( p -value = 0.512). The exploratory findings hinted at a connection between nail pitting and insulin resistance ( p -value = 0.038), yet Bonferroni adjustments suggested the risk of a false-positive finding. Noteworthy associations were found between the HOMA-IR and body mass index (BMI) ( p -value = 0.001), the PASI and quality of life impairment ( p -value = 0.005), and psoriasis severity and type ( p -value = 0.001). The null hypothesis that insulin resistance in children is not positively associated with psoriasis severity cannot be rejected. Pilot estimates of variables and covariates of interest are provided for further confirmatory studies assessing this hypothesis.

Background: Repetitive episodes of apnea and hypopnea during sleep in patients with obstructive sleep apnea (OSA) are known to increase the risk of atherosclerosis. Underlying obesity and related disorders, such as insulin resistance, are indirectly related to the development of atherosclerosis. In addition, OSA is independently associated with insulin resistance; however, data regarding this relationship are scarce in Japanese populations. Methods: This study aimed to examine the relationship between the severity of OSA and insulin resistance in a Japanese population. We analyzed the data of consecutive patients who were referred for polysomnography under clinical suspicion of developing OSA and who did not have diabetes mellitus or any cardiovascular disease. Multiple regression analyses were performed to determine the relationship between the severity of OSA and insulin resistance. Results: The data from a total of 483 consecutive patients were analyzed. The median apnea-hypopnea index (AHI) was 40.9/h (interquartile range: 26.5, 59.1) and the median homeostasis model assessment for insulin resistance (HOMA-IR) was 2.00 (interquartile range: 1.25, 3.50). Multiple regression analyses revealed that the AHI, the lowest oxyhemoglobin saturation (SO 2 ), and the percentage of time spent on SO 2 < 90% were independently correlated with HOMA-IR (an adjusted R-squared value of 0.01278821, p = 0.014; an adjusted R-squared value of -0.01481952, p = 0.009; and an adjusted R-squared value of 0.018456581, p = 0.003, respectively). Conclusions: The severity of OSA is associated with insulin resistance assessed by HOMA-IR in a Japanese population.

(1) Background: Type 2 diabetes mellitus (T2DM) contributes to cardiovascular disease and related mortality through the insidious effects of insulin resistance and chronic inflammation. Mitral annular calcification (MAC) is one such degenerative process promoted by T2DM. (2) Methods: This is a post hoc analysis of insulin resistance, inflammation, and hepatic steatosis markers in T2DM patients without atherosclerotic manifestations, but with incidental echocardiographic detection of mild MAC. (3) Results: 138 consenting patients were 49.3% men, 57.86 years old, with a history of T2DM of 6.16 years and HbA1c 8.06%, of whom sixty had mild MAC (43.47%). The statistically significant differences between patients with/without MAC were higher HOMA C-peptide and C-peptide index for insulin resistance, higher TNF-α for inflammation, and lower estimated glomerular filtration rate. High-sensitive C-reactive protein (hsCRP) was significantly associated with insulin resistance and the strength of the relationship was higher in the MAC group. Predictive of MAC were TNF-α, HOMA C-peptide, and especially hepatic steatosis and hypertension. (4) Conclusions: MAC was more prevalent than reported in the literature. Insulin resistance and inflammation were predictive of MAC, but significant markers differ across studies. Widely available routine tests and echocardiographic assessments are useful in the early identification of mitral annular calcifications in diabetes patients.

Diabetes mellitus is a major public health problem with a wide range of prevalence among different ethnic groups. Early recognition of pre-diabetes is important to prevent the development of the disease, its complications, co-morbidities, and consequently early death. Insulin resistance (IR) is considered a condition that precedes type 2 diabetes; thus, understanding its underlying causes (genetic and non-genetic factors) will bring us closer to preventing it. The present study aimed to investigate the genetic susceptibility to IR and its impact on estimated longevity in populations with different ethnic origins using randomly selected samples of 372 Hungarian general (HG, as a reference with Caucasian origin) and 334 Roma participants (largest ethnic minority in Europe, with a northern India origin). In the present study, we used the Homeostasis Model Assessment—Insulin Resistance (HOMA—IR) to identify people with IR (>3.63) at the population level. To investigate the genetic predisposition to IR, 29 single nucleotide polymorphisms (SNPs) identified in a systematic literature search were selected and genotyped in sample populations. In the analyses, the adjusted p < 0.0033 was considered significant. Of these 29 SNPs, the commutative effects of 15 SNPs showing the strongest association with HOMA—IR were used to calculate an optimized genetic risk score (oGRS). The oGRS was found nominally significantly (p = 0.019) higher in the Roma population compared to HG one, and it was more strongly correlated with HOMA—IR. Therefore, it can be considered as a stronger predictor of the presence of IR among the Roma (AUCRoma = 0.673 vs. AUCHG = 0.528). Furthermore, oGRS also showed a significant correlation with reduced estimated longevity in the Roma population (β = −0.724, 95% CI: −1.230–−0.218; p = 0.005), but not in the HG one (β = 0.065, 95% CI: −0.388–0.518; p = 0.779). Overall, IR shows a strong correlation with a genetic predisposition among Roma, but not in the HG population. Furthermore, the increased genetic risk of Roma is associated with shorter estimated longevity, whereas this association is not observed in the HG one. Increased genetic susceptibility of Roma to IR should be considered in preventive programs targeting the development of type 2 diabetes, which may also reduce the risk of preventable premature death among them.

Background: Chronic kidney disease (CKD) is a complex syndrome without a definitive treatment. For these patients, insulin resistance (IR) is associated with worse renal and patient outcomes. Until now, no predictive model using machine learning (ML) has been reported on IR in CKD patients. Methods: The CKD population studied was based on results from the National Health and Nutrition Examination Survey (NHANES) of the USA from 1999 to 2012. The homeostasis model assessment of IR (HOMA-IR) was used to assess insulin resistance. We began the model building process via the ML algorithm (random forest (RF), eXtreme Gradient Boosting (XGboost), logistic regression algorithms, and deep neural learning (DNN)). We compared different receiver operating characteristic (ROC) curves from different algorithms. Finally, we used SHAP values (SHapley Additive exPlanations) to explain how the different ML models worked. Results: In this study population, 71,916 participants were enrolled. Finally, we analyzed 1,229 of these participants. Their data were segregated into the IR group (HOMA IR > 3, n = 572) or non-IR group (HOMR IR ≤ 3, n = 657). In the validation group, RF had a higher accuracy (0.77), specificity (0.81), PPV (0.77), and NPV (0.77). In the test group, XGboost had a higher AUC of ROC (0.78). In addition, XGBoost also had a higher accuracy (0.7) and NPV (0.71). RF had a higher accuracy (0.7), specificity (0.78), and PPV (0.7). In the RF algorithm, the body mass index had a much larger impact on IR (0.1654), followed by triglyceride (0.0117), the daily calorie intake (0.0602), blood HDL value (0.0587), and age (0.0446). As for the SHAP value, in the RF algorithm, almost all features were well separated to show a positive or negative association with IR. Conclusion: This was the first study using ML to predict IR in patients with CKD. Our results showed that the RF algorithm had the best AUC of ROC and the best SHAP value differentiation. This was also the first study that included both macronutrients and micronutrients. We concluded that ML algorithms, particularly RF, can help determine risk factors and predict IR in patients with CKD.

Background and objectives: Chinese type 2 diabetes mellitus (T2DM) patients are characterized by a low body mass index (BMI), and significant insulin resistance (IR). The triglyceride glucose (TyG) index has not been studied as a means of assessing IR in Chinese T2DM patients with a BMI < 35 kg/m2. Materials and Methods: An open-label cross-sectional study recruited 102 Chinese T2DM patients with a BMI < 35 kg/m2. The hyper-insulinemic euglycemic clamp, homeostatic model assessment of IR (HOMA-IR), and TyG index were used to determine the level of IR. Based on Pearson’s correlations, glucose disposal rate (GDR), TyG index, and HOMA-IR were analyzed. HOMA-IR and TyG index for IR were evaluated using multiple linear regression and multivariate logistic regression analyses. On the basis of the receiver operating characteristic (ROC) curve, the sensitivity, specificity, and optimal cut-off value of HOMA-IR and the TyG index were determined. Results: The mean values of GDR, HOMA-IR, and TyG index were 4.25 ± 1.81, 8.05 ± 7.98, and 8.12 ± 0.86 mg/kg/min, respectively. Pearson’s correlation coefficient was −0.418 between GDR and TyG index and −0.324 between GDR and HOMA-IR. ROC curve analysis showed that, among both sexes, the TyG index was a better discriminator of IR than HOMA-IR. The area under the ROC curve (AUC) of the TyG index (0.785, 0.691–0.879) was higher than that of HOMA-IR (0.73, 0.588–0.873) in all genders. The optimal cut-off values of the TyG index and HOMA-IR were 7.99 and 3.39, respectively. Conclusions: The TyG index showed more effectiveness in identifying IR in Chinese T2DM patients with a BMI < 35 kg/m2 compared to HOMA-IR.

Background: Gestational diabetes mellitus (GDM) is a pregnancy complication characterized by second trimester hyperglycemia. Untreated, GDM is related to an increased risk for adverse pregnancy outcomes. Both beta cell dysfunction and insulin resistance underlie impaired glucose tolerance. Understanding the dominant mechanism predisposing to GDM may be important to provide effective treatment in order to improve perinatal outcomes. We hypothesize that insulin resistance rather that beta cell dysfunction predisposes to GDM. Methods: A 75g oral glucose tolerance test (OGTT) was performed on 2112 second-trimester pregnant women to determine the relationship between insulin resistance (HOMA-IR), beta cell function (HOMA-β), and the prevalence of abnormal glucose handling. Results: High insulin resistance raised the risk of GDM (relative risk (RR) 6.1, 95% confidence interval (CI) (4.4–8.5)), as did beta cell dysfunction (RR 3.8, 95% CI (2.7–5.4)). High insulin resistance, but not beta cell function, enhances the necessity for additional glucose lowering medication on top of a low carbohydrate diet in women diagnosed with GDM. Conclusions: Both high insulin resistance and beta cell dysfunction increase the risk of GDM. As increased insulin resistance, rather than beta cell function, is related to an insufficient response to a low carbohydrate diet, we speculate that insulin sensitizers rather than insulin therapy may be the most targeted therapeutic modality in diet-insensitive GDM.

Our purpose is to study the evolution of mitochondrially derived peptides (MDPs) and their relationship with changes in insulin sensitivity from the early stages of pregnancy in a cohort of pregnant women with and without gestational diabetes (GDM). MDPs (humanin and MOTSc) were assessed in the first and second trimesters of gestation in 28 pregnant women with gestational diabetes mellitus (GDM) and a subgroup of 45 pregnant women without GDM matched by BMI, age, previous gestations, and time of sampling. Insulin resistance (IR) was defined as a HOMA-IR index ≥70th percentile. We observed a significant reduction in both humanin and MOTSc levels from the first to the second trimesters of pregnancy. After adjusting for predefined variables, including BMI, statistically nonsignificant associations between lower levels of humanin and the occurrence of a high HOMA-IR index were obtained (adjusted OR = 2.63 and 3.14 for the first and second trimesters, linear p-trend 0.260 and 0.175, respectively). Regarding MOTSc, an association was found only for the second trimester: adjusted OR = 7.68 (95% CI 1.49–39.67), linear p-trend = 0.012. No significant associations were observed in humanin change with insulin resistance throughout pregnancy, but changes in MOTSc levels were significantly associated with HOMA-IR index: adjusted OR 3.73 (95% CI 1.03–13.50). In conclusion, MOTSc levels, especially a strong decrease from the first to second trimester of gestation, may be involved in increasing insulin resistance during early gestation.

Metabolic syndrome (MetS) risks cardiovascular diseases due to its associated Dyslipidemia. It is proposed that a low-carbohydrate, high-fat (LCHF) diet positively ameliorates the MetS and reverses insulin resistance. Therefore, we aimed to investigate the protecting effect of the LCHF diet on MetS-associated Dyslipidemia in an experimental animal model. Forty male Sprague-Dawley rats were divided into four groups (10/group): the control group, dexamethasone-induced MetS (DEX) (250 µg/kg/day), LCHF-fed MetS group (DEX + LCHF), and High-Carbohydrate-Low-Fat-fed MetS group (DEX + HCLF). At the end of the four-week experiment, fasting glucose, insulin, lipid profile (LDL-C, HDL-C, Triglyceride), oxidized-LDL, and small dense-LDL using the ELISA technique were estimated. HOMA-IR, Apo B/Apo A1 ratio, and TG/HDL were calculated. Moreover, histological examination of the liver by H & E and Sudan III stain was carried out. In the DEX group, rats showed a significant (p < 0.05) increase in the HOMA-IR, atherogenic parameters, such as s-LDL, OX-LDL, Apo B/Apo A1 ratio, and TG/HDL. The LCHF diet significantly improved the parameters of Dyslipidemia (p < 0.05) by decreasing the Apo B/Apo A1 and TG/HDL-C ratios. Decreased steatosis in LCHF-fed rats compared to HCLF was also revealed. In conclusion, the LCHF diet ameliorates MetS-associated Dyslipidemia, as noted from biochemical results and histological examination.

Obesity is a public health crisis in Kuwait. However, not all obese individuals are metabolically unhealthy (MuHO) given the link between obesity and future cardiovascular events. We assessed the prevalence of the metabolically healthy obese (MHO) phenotype and its relationship with high sensitivity C-reactive protein (hs-CRP), serum alanine aminotransferase (ALT), and insulin resistance (HOMA-IR) in Arab and South Asian ethnic groups in Kuwait. The national cross-sectional survey of diabetes and obesity in Kuwait adults aged 18–60 years were analysed. The harmonised definition of metabolic syndrome was used to classify metabolic health. Multinomial logistic regression analysis was used to model the relationship between the MHO and MuHO phenotypes and hs-CRP, ALT and HOMA-IR levels. Overall, the prevalence of MHO for body mass index (BMI)- and waist circumference (WC)-defined obesity was 30.8% and 56.0%, respectively; it was greater in women (60.4% and 61.8%, respectively) than men (39.6% and 38.2%, respectively). Prevalence rates were also lower for South Asians than for Arabs. The MHO phenotype had hs-CRP values above 3 µg/mL for each age group category. Men compared to women, and South Asians compared to Arabs had a lower relative risk for the MHO group relative to the MuHO group. This study shows there is high prevalence of MHO in Kuwait.

In the present study, we aimed to investigate the effect of coriander oil on dexamethasone-induced insulin resistance in rats and characterize its chemical composition using gas chromatography-mass spectrometry (GC-MS). Rats were divided into five groups (n = 6): Normal control, insulin resistance (IR) control, IR + metformin (50 mg/kg/day, PO, Per Oral), IR + coriander oil low dose (0.5 mL/kg, PO), and IR + coriander oil high dose (1 mL/kg, PO). IR groups were injected with a dose of 10 mg/kg dexamethasone subcutaneously for four consecutive days. All groups received either vehicle or drugs daily for four days. Animal weights and pancreatic weights were measured, and oral glucose tolerance test was performed at the end of study. Fasting glucose, triglycerides (TG), total cholesterol (TC), HDL and insulin levels in serum, MDA, and GSH levels in pancreatic tissue were measured and HOMA-IR was calculated. Immunoexpression of apoptosis markers BAX, and BCL2 was measured in pancreatic tissues and BAX/BCL2 ratio was calculated. Histopathological examination of pancreatic tissues was also performed. Pancreatic weight, serum HDL, pancreatic GSH, and BCL2 were decreased while serum glucose, insulin, TG, TC levels, AUC of OGGT, HOMA-IR, pancreatic MDA, BAX, and BAX/BCL2 ratio were increased in IR rats. Histopathological examination showed congestion, vacuolation and hemorrhage in pancreatic islets. These changes were reversed by metformin and the high dose of coriander oil treatments. The obtained activities could be attributed to the presence of 21 volatile compounds, identified by GC-MS. Our study indicates that coriander oil can be used as an adjuvant antihyperglycemic agent in type 2 diabetes. Further experiments are needed to determine the therapeutic dose and the treatment time.

The aim of this study was to assess the relationship between the dietary total antioxidant capacity (DTAC) and occurrence of prediabetes, diabetes and insulin resistance in the Bialystok PLUS (Polish Longitudinal University Study) population. Daily food consumption was estimated by 3-days 24-h dietary recalls. DTAC was calculated using the date of food consumption and antioxidant potential of foods measured by FRAP (ferric ion reducing antioxidant potential) method. The following measurements were performed to identify prediabetes, diabetes and HOMA-IR: fasting glucose (FG), 2h postprandial glucose level (2h-PG), fasting insulin (FI), glycated hemoglobin HbA1c. Logistic regression models were used to assess the relationship between DTAC and prediabetes and diabetes. This study demonstrated that higher quartile of DTAC, after adjustment for confounding variables, was significantly associated with a reduced odds ratio for the prevalence of prediabetes in Bialystok PLUS population aged 35–65 years. DTAC was also significantly inversely associated with HOMA-IR in multivariate linear regression model. DTAC was positively related to individual dietary antioxidants (polyphenols, antioxidant vitamins and minerals). Reduced DTAC may be considered as an additional risk factor for the development of diabetes. Therefore, dietary recommendations for prevention and therapy of diabetes should take into account the high DTAC.

Background: Insulin resistance is a common etiology of metabolic syndrome, but receiver operating characteristic (ROC) curve analysis shows a weak association in Koreans. Using a machine learning (ML) approach, we aimed to generate the best model for predicting insulin resistance in Korean adults aged > 40 of the Ansan/Ansung cohort using a machine learning (ML) approach. Methods: The demographic, anthropometric, biochemical, genetic, nutrient, and lifestyle variables of 8842 participants were included. The polygenetic risk scores (PRS) generated by a genome-wide association study were added to represent the genetic impact of insulin resistance. They were divided randomly into the training (n = 7037) and test (n = 1769) sets. Potentially important features were selected in the highest area under the curve (AUC) of the ROC curve from 99 features using seven different ML algorithms. The AUC target was ≥0.85 for the best prediction of insulin resistance with the lowest number of features. Results: The cutoff of insulin resistance defined with HOMA-IR was 2.31 using logistic regression before conducting ML. XGBoost and logistic regression algorithms generated the highest AUC (0.86) of the prediction models using 99 features, while the random forest algorithm generated a model with 0.82 AUC. These models showed high accuracy and k-fold values (>0.85). The prediction model containing 15 features had the highest AUC of the ROC curve in XGBoost and random forest algorithms. PRS was one of 15 features. The final prediction models for insulin resistance were generated with the same nine features in the XGBoost (AUC = 0.86), random forest (AUC = 0.84), and artificial neural network (AUC = 0.86) algorithms. The model included the fasting serum glucose, ALT, total bilirubin, HDL concentrations, waist circumference, body fat, pulse, season to enroll in the study, and gender. Conclusion: The liver function, regular pulse checking, and seasonal variation in addition to metabolic syndrome components should be considered to predict insulin resistance in Koreans aged over 40 years.

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

The study was conducted to comprehensively assess the association of the concentration of vitamin D in the blood and insulin resistance in non-diabetic subjects. The objective was to pool the results from all observational studies from the beginning of 1980 to August 2021. PubMed, Medline and Embase were systematically searched for the observational studies. Filters were used for more focused results. A total of 2248 articles were found after raw search which were narrowed down to 32 articles by the systematic selection of related articles. Homeostatic Model Assessment of Insulin Resistance (HOMAIR) was used as the measure of insulin resistance and correlation coefficient was used as a measure of the relationship between vitamin D levels and the insulin resistance. Risk of bias tables and summary plots were built using Revman software version 5.3 while Comprehensive meta-analysis version 3 was used for the construction of forest plot. The results showed an inverse association between the status of vitamin D and insulin resistance (r = −0.217; 95% CI = −0.161 to −0.272; p = 0.000). A supplement of vitamin D can help reduce the risk of insulin resistance; however further studies, like randomized controlled trials are needed to confirm the results.

To verify the accuracy of different indices of glucose homeostasis in recognizing the metabolic syndrome in a group of adult patients with Prader–Willi syndrome (PWS), 102 PWS patients (53 females/49 males), age ±SD 26.9 ± 7.6 yrs, Body Mass Index (BMI) 35.7 ± 10.7, were studied. The following indices were assessed in each subject during an oral glucose tolerance test (OGTT): 1 h (>155 mg/dL) and 2 h (140–199 mg/dL) glucose levels, the oral disposition index (ODI), the insulinogenic index (IGI), the insulin resistance (HOMA-IR) were evaluated at baseline, 1 h and 2 h. Although minor differences among indices were found, according to the ROC analysis, no index performed better in recognizing MetS. Furthermore, the diagnostic threshold levels changed over the years and therefore the age-related thresholds were calculated. The easily calculated HOMA-IR at baseline may be used to accurately diagnose MetS, thus avoiding more complicated procedures.

Menopause is characterized by endocrine and physiological changes and is often accompanied by increased body weight and cholesterol, glucose intolerance, and/or hypertension. These alterations are associated with increased risk for cardiovascular diseases (CVDs) and Type II diabetes mellitus (T2DM) that may be moderate by dietary plant phenolic compounds. In this review, we examine the current evidence of the impact of a variety of plant products (foods, extracts, beverages) rich in a mixture of phenolics and polyphenols on: (i) glucose and insulin levels; (ii) lipid profile; (iii) blood pressure; and (iv) biomarkers of inflammation and oxidative stress in postmenopausal women. We critically evaluate both the results of a range of intervention studies conducted in this specific subpopulation and the level of evidence supporting the benefits of consuming those products after the menopause. Overall, the current available evidence does not allow for specific dietary recommendations of these plant products rich in phenolics and polyphenols in this high-risk subpopulation. Our data show rather variable and small effects of the different products examined on the cardiometabolic biomarkers and further support the need to: (1) improve the quality of the study designs and data reporting; and (2) understand the variability in the response of the different biomarkers and establish clear differences between healthy and cardiometabolic disease levels.

Background/Aim: The recovery pattern of hepatitis C virus (HCV)-associated metabolic alteration after sustained virological response (SVR) following direct-acting antivirals (DAAs) remains elusive. Methods: A prospective cohort study of chronic HCV-infected (CHC) patients (n = 415) receiving DAAs (n = 365) was conducted. Metabolic profiles were examined in SVR patients (n = 360) every 3–6 months after therapy and compared with those of sex- and age-matched controls (n = 470). Results: At baseline, of 415, 168 (40.5%) had insulin resistance (IR). The following were associated: levels of high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), HCV RNA, fibrosis-4 score, and interferon-λ3-rs12979860 genotype with total cholesterol (TC) levels; and TG levels and BMI with HOMA-IR. Over a 3-year follow-up, in SVR patients, BMI and TC levels and TG/HDL-C ratios increased from baseline, while HOMA-IR trended downward by 72 weeks after therapy and then increased. The increased HDL-C levels began to decrease after 72 weeks after therapy. TC and HOMA-IR were negatively associated with each other until 24 weeks after therapy. Earlier increases in BMI and decreases in HOMA-IR were noted in SVR patients with than in those without baseline IR. Compared with controls, in the subgroup without baseline IR, SVR patients had increased BMI and HOMA-IR levels. Metabolic profiles were similar between SVR patients and controls in the subgroup with baseline IR. Conclusions: In SVR patients treated with DAAs, the recovery of altered lipid and glucose metabolism was not coupled until 72-week post-therapy, when HOMA-IR reached its nadir. SVR patients with baseline IR recovered from HCV-associated metabolic alterations earlier than those without baseline IR.