Postmenopausal women treated for breast cancer with insulin resistance: clinical, analytical, cross-sectional.

This study aims to investigate the potential association between serum levels of cytokines, HSP60, HSP70 and IR (HOMA-IR) in postmenopausal women. We conducted a cross-sectional study involving 381 postmenopausal women, including 94 with a breast cancer diagnosis and 278 without. We analyzed anthropometric and laboratory measurements. Immunoassays were used to measure cytokines (TNF-α, IL-10, and IL-6) as well as heat shock proteins (HSP) 60 and 70 in the serum using the ELISA technique. Women diagnosed with breast cancer showed higher levels of HOMA-IR, IL-6, TNF, and HSP60, and lower levels of IL-10 and HSP70 compared to women without cancer. An association was found between HSP70 and HOMA-IR only in women with breast cancer (ß = 0.22, p = .030; without cancer: ß = 0.04, p = .404), regardless of age, waist circumference, smoking, and physical activity. No associations were observed between cytokines, HSP60, and HOMA-IR in both groups of women. HSP70 is positively associated with IR in women diagnosed with breast cancer.

Value of the triglyceride-glucose index and related parameters in heart failure patients.

The triglyceride-glucose (TyG) index, proven to be a crucial insulin resistance biomarker (better than the Homeostasis Model Assessment for Insulin Resistance), is simple and non-invasive. Recently, indisputable evidence has shown that the TyG index is strongly associated with cardiovascular disease [CVD, including atherosclerosis, heart failure (HF), and hypertension] prognosis and mortality. Nevertheless, the value of the TyG index in HF patients treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) has not been systematically evaluated. Therefore, in this review, we summarized the value of the TyG index and its related parameters as markers of CVD, especially HF. Furthermore, we addressed the use of SGLT2is and GLP-1 receptor antagonists in HF patients. Finally, we summarized the mechanism of the "obesity paradox."

Association of Serum Adipsin Level with Insulin Resistance and Inflammatory Markers in Newly Diagnosed Type two Diabetes Mellitus Patients.

Adipsin is an anti-inflammatory adipokines and its altered level was seen in obesity and type II DM. Our study investigated the clinical significance of serum adipsin levels as a risk marker for type 2 diabetes and its relationships with insulin resistance and various adipo-cytokines. The study included 110 treatment-naïve T2DM cases and 100 controls of similar age and gender from northern India. Clinical, biochemical, and anthropometric characteristics were all profiled. Serum adipo-cytokines were measured using ELISA methods. Adipsin was significantly inversely correlated with body mass index (BMI), waist circumference, fasting plasma glucose, glycated haemoglobin (HbA1C), total cholesterol (TC), triglyceride (TG), homeostasis model assessment-estimated insulin resistance (HOMA-IR), tumour necrosis factor- α (TNF-α) and interleulin-6 (IL-6) and positively correlated with high-density lipoprotein cholesterol (HDL-C) and homeostasis model assessment of ß-cell function (HOMA-B) (P < 0.05). T2DM occurrence decreased with increasing concentration of adipsin with an odds ratio (OR) of 0.68 (95% CI = 0.58-0.79), P < 0.001. The area under curve (95% CI) for adipsin was 0.70 (0.63 to 0.76) with P < 0.001. The best cutoff value for adipsin to predict T2DM was < 5.50 µg/ml with 47.27% sensitivity and 82.00% specificity. FPG and WC were both independent predictors of serum adipsin levels. Our findings showed that high adipsin levels reduced the likelihood of T2DM and emerged as a potential risk marker in the prediction of T2DM.

Effects of Plant-Based Diets on Markers of Insulin Sensitivity: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

The aim of this systematic review and meta-analysis was to examine the effects of plant-based diets on markers of insulin sensitivity in people with overweight/obesity, prediabetes, or type 2 diabetes (T2D). A systematic literature search in MEDLINE, Embase, CINAHL, and CENTRAL was conducted, and randomised controlled trials (RCTs) investigating the effect of plant-based diets (vegan, ovo-vegetarian, lacto-vegetarian, and lacto-ovo-vegetarian) for ≥14 d on markers of insulin sensitivity in adults (≥18 years) with BMI ≥ 25 kg/m2, prediabetes, or T2D were eligible. We identified eight RCTs, including 716 participants. In comparison with control diets, plant-based diets improved Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (-0.97, 95% confidence interval (CI) (-1.67, -0.27), p = 0.007) and fasting insulin (-4.13 µU/mL, 95% CI (-7.22, -1.04), p = 0.009) in people with overweight/obesity. In people with prediabetes, one study compared vegan and vegetarian diets and found no difference in HOMA-IR, or fasting insulin. One study of people with T2D reported no difference in immunoreactive insulin and metabolic glucose clearance compared with a conventional diabetes diet. In conclusion, adhering to plant-based diets for ≥14 d improved HOMA-IR and fasting insulin in people with overweight/obesity. Long-term RCTs are needed to determine whether plant-based diets can result in prolonged improvements in insulin sensitivity in people at risk of or with T2D.

Evaluation of Fasting Glucose-Insulin-C-Peptide-Derived Metabolic Indices for Identifying Metabolic Syndrome in Young, Healthy Adults.

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.

The Role of Piromelatine on Peripheral and Hippocampal Insulin Resistance in Rat Offspring Exposed to Chronic Maternal Stress.

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.

The biological variation of insulin resistance markers: data from the European Biological Variation Study (EuBIVAS).

OBJECTIVES: An insulin resistant state is characteristic of patients with type 2 diabetes, polycystic ovary syndrome, and metabolic syndrome. Identification of insulin resistance (IR) is most readily achievable using formulae combining plasma insulin and glucose results. In this study, we have used data from the European Biological Variation Study (EuBIVAS) to examine the biological variability (BV) of IR using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and the Quantitative Insulin sensitivity Check Index (QUICKI). METHODS: Ninety EuBIVAS non-diabetic subjects (52F, 38M) from five countries had fasting HOMA-IR and QUICKI calculated from plasma glucose and insulin samples collected concurrently on 10 weekly occasions. The within-subject (CVI) and between-subject (CVG) BV estimates with 95 % CIs were obtained by CV-ANOVA after analysis of trends, variance homogeneity and outlier removal. RESULTS: The CVI of HOMA-IR was 26.7 % (95 % CI 25.5-28.3), driven largely by variability in plasma insulin and the CVI for QUICKI was 4.1 % (95 % CI 3.9-4.3), reflecting this formula's logarithmic transformation of glucose and insulin values. No differences in values or BV components were observed between subgroups of men or women below and above 50 years. CONCLUSIONS: The EuBIVAS, by utilising a rigorous experimental protocol, has produced robust BV estimates for two of the most commonly used markers of insulin resistance in non-diabetic subjects. This has shown that HOMA-IR, in particular, is highly variable in the same individual which limits the value of single measurements.

The impact of a culturally adapted lifestyle intervention on the glycaemic profile of mothers with GDM one year after delivery - a community-based, cluster randomized trial in Sri Lanka.

BACKGROUND: A woman with a history of GDM has a high risk of developing type two diabetes (T2DM) in her future life. Lifestyle modifications are known to attenuate the progression of GDM to T2DM. Therefore, the aim of this study was to assess the impact of a simple, cost effective, culturally acceptable lifestyle intervention programme on the trajectory towards T2DM in women with a history of GDM. METHODS: This cluster randomized trial was conducted in 100 postpartum women in three selected districts of Sri Lanka. The subjects were divided into intervention (n = 50) and control groups (n = 50) by cluster randomization method. A culturally adapted protocol (comprised of dietary and physical activity modifications) was administered to the intervention group. The glycemic profile was assessed using fasting and 2-hour post-OGTT plasma glucose and HbA1c, and insulin resistance by HOMA-IR at baseline and after one year of intervention. RESULTS: The mean age (SD) of the subjects in the intervention and control groups were 33.0 (5.1) and 34.3 (6.5) years respectively. All glycemic and insulin resistance parameters (i.e. Fasting plasma glucose- FPG, 2-hour post-OGTT plasma glucose, HbA1c and HOMA-ir) were comparable (p > 0.05) between the two groups at baseline. FPG, 2 h post OGTT, HbA1c and HOMA-ir values between intervention vs. control (p) at 12 months were 87.3 vs. 123.2 (< 0.01); 106.5 vs. 156.1 (0.01); 5.3 vs. 6.8 (< 0.01) and 0.9 vs. 2.3 (< 0.01) respectively. All glycemic parameters showed a significant reduction in the intervention group at 12 months compared to baseline. In contrast, the control group showed a significant increase in FPG, 2-hour post-OGTT plasma glucose and HbA1c at 12 months compared to baseline. In multiple linear regression model adjusted for age, parity and family history, the control group showed an approximately 33 times risk of developing insulin resistance compared to the intervention group. CONCLUSION: The culturally acceptable and individualized lifestyle intervention was able to produce remarkable reductions in glycaemic and insulin resistance parameters among postpartum women with a history of GDM. TRIAL REGISTRATION: Ethical clearance was obtained from the Ethics Review Committee of the University of Sri Jayewardenepura, Sri Lanka (ERC 52/14), Sri Lanka Clinical trial registration number Sri Lanka Clinical Trials Registry (SLCTR/2015/021 date 25.09.2015).

Ketosis Suppression and Ageing (KetoSAge) Part 2: The Effect of Suppressing Ketosis on Biomarkers Associated with Ageing, HOMA-IR, Leptin, Osteocalcin, and GLP-1, in Healthy Females.

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 in Patients with Elevated HOMA-IR after SARS-CoV-2 Infection: A 12-Month Longitudinal Study.

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.

Triglyceride glucose-related indexes and lipid accumulation products-reliable markers of insulin resistance in the Chinese population.

Background: Insulin resistance (IR) is a pivotal pathogenic component of metabolic diseases. It is crucial to identify convenient and reliable indicators of insulin resistance for its early detection. This study aimed at assessing the predictive ability of seven novel obesity and lipid-related indices. Methods: A total of 5,847 female and 3,532 male healthy subjects were included in the study. The triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), lipid accumulation products (LAP), body roundness index (BRI), body adiposity index (BAI), and visceral adiposity index (VAI) were measured and calculated using the established formulae. IR was diagnosed using the homeostatic model assessment of insulin resistance (HOMA-IR) index over the third quantile. Results: The levels of all seven lipid-related indices were significantly higher in subjects with higher HOMA-IR values than in those with lower HOMA-IR values. These indices displayed moderate to high effectiveness [receiver operating characteristic (ROC) curve-area under the curve (AUC) > 0.6] in predicting IR. Among them, TyG-BMI (AUC: 0.729), LAP (AUC: 0.708), and TyG-WC (AUC: 0.698) showed the strongest association with HOMA-IR. In the female population, the AUC for TyG-BMI, LAP, and TyG-WC in predicting IR was 0.732, 0.705, and 0.718, respectively. Logistic regression analysis showed the optimal cut-off values of those indicators in predicting IR as follows: TyG-BMI: male subjects - 115.16 [odds ratio (OR) = 6.05, 95% CI: 5.09-7.19], female subjects - 101.58 (OR = 4.55, 95% CI: 4.00-5.16); LAP: male subjects - 25.99 (OR = 4.53, 95% CI: 3.82-5.38), female subjects - 16.11 (OR = 3.65, 95% CI: 3.22-4.14); and TyG-WC: male subjects - 409.43 (OR = 5.23, 95% CI: 4.48-6.24), female subjects - 342.48 (OR = 4.07, 95% CI: 3.59-4.61). Conclusion: TyG-index-related parameters and LAP appear to be effective predictors of IR in the Chinese population. Specifically, TyG-BMI may be the most appropriate predictor of IR.

Oxidative Stress in Prediabetic Young Adults.

Background Malondialdehyde (MDA) and nitric oxide (NO) are considered specific biomarkers for oxidative stress. Oxidative stress in prediabetics with an augmented potential for the onset of diabetes is at least partly responsible for the various complications of diabetes. Evidence shows that the early features of cell injury are due to transient acute elevations in blood glucose. This study aims to determine whether oxidative stress in prediabetic young adults increases the risk of developing diabetes. Aim and objectives We envisaged a study to determine whether the parameters representing oxidative stress are deranged in prediabetics. Materials and methods The study was conducted on prediabetic young individuals from 18 to 35 years, screened from the tertiary-level hospital, and a similar group of non-prediabetic young individuals identified from the same in a tertiary-level hospital in India. Results We observed significant elevations in prediabetics in the following oxidative stress parameters: MDA (P= <0.001), and NO (P= <0.001); indicating that these parameters were significantly higher among the prediabetics than the controls. We also observed significantly greater body weight, waist circumference, and BMI among the prediabetics than the controls. Conclusion Early identification and appropriate treatment of hyperglycemia in prediabetics is essential, as impairments in pancreatic beta-cell functioning and resistance to insulin are already present before the onset of type 2 diabetes mellitus (T2DM). Owing to the high potential for mortality and morbidity due to cardiovascular diseases (CVDs) as a complication of diabetes, treatment plans must be put in place early enough so that complications can be prevented. Inflammation and oxidative stress may be viewed as valuable targets to hinder the evolution of T2DM from prediabetes.

Discriminating insulin resistance in middle-aged nondiabetic women using machine learning approaches.

Objective: We employed machine learning algorithms to discriminate insulin resistance (IR) in middle-aged nondiabetic women. Methods: The data was from the National Health and Nutrition Examination Survey (2007-2018). The study subjects were 2084 nondiabetic women aged 45-64. The analysis included 48 predictors. We randomly divided the data into training (n = 1667) and testing (n = 417) datasets. Four machine learning techniques were employed to discriminate IR: extreme gradient boosting (XGBoosting), random forest (RF), gradient boosting machine (GBM), and decision tree (DT). The area under the curve (AUC) of receiver operating characteristic (ROC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score were compared as performance metrics to select the optimal technique. Results: The XGBoosting algorithm achieved a relatively high AUC of 0.93 in the training dataset and 0.86 in the testing dataset to discriminate IR using 48 predictors and was followed by the RF, GBM, and DT models. After selecting the top five predictors to build models, the XGBoost algorithm with the AUC of 0.90 (training dataset) and 0.86 (testing dataset) remained the optimal prediction model. The SHapley Additive exPlanations (SHAP) values revealed the associations between the five predictors and IR, namely BMI (strongly positive impact on IR), fasting glucose (strongly positive), HDL-C (medium negative), triglycerides (medium positive), and glycohemoglobin (medium positive). The threshold values for identifying IR were 29 kg/m2, 100 mg/dL, 54.5 mg/dL, 89 mg/dL, and 5.6% for BMI, glucose, HDL-C, triglycerides, and glycohemoglobin, respectively. Conclusion: The XGBoosting algorithm demonstrated superior performance metrics for discriminating IR in middle-aged nondiabetic women, with BMI, glucose, HDL-C, glycohemoglobin, and triglycerides as the top five predictors.

Prediabetes: A Benign Intermediate Stage or a Risk Factor in Itself?

Prediabetes is a condition when the blood glucose levels are above the normal range but below the threshold for defining diabetes. Previously considered benign, it is now recognized to be associated with various macrovascular and microvascular complications, with increases in the risk of cardiovascular events, nephropathy neuropathy, and retinopathy. Early identification of prediabetics may help detect the risk for these future complications at an earlier stage. Moreover, therapeutic options for prediabetes are available, which can retard its progression to diabetes and the subsequent development of complications. Hence, we make a case for the early identification of prediabetes through screening methods and appropriate institution of management strategies.

Long-term insulin resistance is associated with frailty, frailty progression, and cardiovascular disease.

BACKGROUND: Insulin resistance and diabetes are associated with an increased risk of frailty, and frailty is associated with cardiovascular disease and premature mortality. We aim to investigate the impact of long-term insulin resistance trajectories on future frailty and cardiovascular risk among young adults. METHODS: In total, 3168 participants with a 30-year follow-up period. The baseline period covered the first 15 years as the exposure period. Insulin resistance was determined using the homeostasis model assessment for insulin resistance (HOMA-IR), and three trajectories (low, moderate, and high) were constructed. The subsequent 15 years constituted the event accrual period. Frailty was assessed using a deficit accumulation mode, and cardiovascular outcomes were obtained from the 15-year event accrual period. RESULTS: The mean age of all 3168 participants was 41.0 (37.0-43.0) years, with 1750 (55.2%) being women. Participants in the high level of insulin resistance trajectory had an increased prevalence of frailty (OR: 1.55, 95% CI: 1.05-2.30, P = 0.028). Although no statistically significant associations were observed after full adjustment, single-factor analysis indicated association between the moderate and high trajectories and frailty progression. Additionally, participants with high level of insulin resistance trajectory were associated with an increased risk of cardiovascular disease, coronary heart disease, and stroke. A notable correlation between HOMA-IR trajectory and cardiovascular diseases was still discernible within the subgroup where the frailty index ≥0.12 (HR: 2.12, 95% CI: 1.17-3.83, P = 0.013) (P for interaction >0.05). CONCLUSIONS: Long-term high level of insulin resistance is associated with high prevalence of frailty, and an increased risk of cardiovascular events. Emphasizing the importance of early prevention and intervention for abnormal glucose metabolism in young adults to prevent frailty and cardiovascular disease.

The relationship between dietary intake of live microbes and insulin resistance among healthy adults in the US: a cross-sectional study from NHANES 2003-2020.

Dietary intake of live microbes may benefit human health, but less is known about the role in insulin resistance. This study was developed with the goal of evaluating potential relationships between IR and dietary live microbes. The National Health and Nutrition Examination Survey (NHANES) dataset was leveraged to collect data from 6,333 subjects 18 + years of age. The Sanders system for the classification of dietary live microbe intake (containing Low (< 104 CFU/g), Medium (104-107 CFU/g), or High (> 107 CFU/g) levels of live microbes) was then used to separate these patients into three groups (low, medium, or high). Fasting blood glucose and insulin levels were used to approximate IR based on the homeostasis model of insulin resistance (HOMA-IR). Weighted linear regressions were used to assess the relationship between IR and live microbe intake. After fully adjusting for confounding factors, subjects in the groups exhibiting medium and high levels of live microbe intake exhibited HOMA-IR scores that were below those of subjects in the low group. The relationship between live microbe intake and HOMA-IR scores was also potentially impacted by ethnicity. In summary, a negative correlation was detected between dietary live microbe intake and HOMA-IR values.

Triglyceride-Fasting Glucose Index and Homeostatic Model Assessment for Insulin Resistance as Predictors of Type 2 Diabetes Mellitus in South Indians With Normal Body Mass Index.

INTRODUCTION:  Early detection of type 2 diabetes mellitus (T2DM) is imperative to prevent the complications associated with the disease. Current guidelines for diagnosis rely on the assessment of serum glucose (fasting and post-prandial) and glycosylated hemoglobin (HbA1c) levels. Insulin resistance, a phenomenon associated with T2DM, has been observed before the changes in these metrics. The homeostatic model assessment for insulin resistance (HOMA-IR) has been widely used to assess the degree of insulin resistance. The triglyceride-fasting glucose (TyG) index is a newer marker of insulin resistance that merits further study.  Aim: The study aimed to assess the validity of the TyG index and HOMA-IR as markers for the development of T2DM in non-obese individuals.  Materials and methods: One hundred eight non-obese patients without T2DM were included in this prospective cohort study and followed up for eight years. Anthropometric and biochemical parameters, including fasting glucose levels, HbA1c, fasting serum insulin, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG), were measured at enrolment and eight years follow-up, and HOMA-IR and TyG index were calculated.  Results: Twenty participants out of 108 (18.5%) developed T2DM over eight years. On performing the area under the curve (AUC)-receiver operating characteristic curve analysis, TyG of >8.61 and HOMA-IR of >1.5 had the highest validity (ability) to predict new-onset T2DM in the study population (TyG: AUC: 0.612 (95% CI: 0.514-0.705); HOMA-IR: AUC: 0.529 (95% CI: 0.431-0.626)); however, this was not statistically significant.  Conclusion: At an eight-year follow-up, TyG and HOMA-IR were unreliable predictors of the development of T2DM in non-obese individuals.

METS-IR/HOMA-IR and MAFLD in U.S. adults: dose-response correlation and the effect mediated by physical activity.

OBJECTIVES: Metabolic dysfunction-associated fatty liver disease (MAFLD), a globally prevalent disease, is closely linked to insulin resistance (IR). Physical activity (PA) is closely linked to both MAFLD and IR. We aim to explore the dose-response relationship between metabolic score for IR (METS-IR)/homeostasis model assessment of IR (HOMA-IR) and MAFLD, and investigate the relationship between PA, IR and MAFLD. METHODS: Participants from the NHANES study were included in this cross-section study. Logistic regression and the receiver operating characteristic were used to assess the predictive performance of METS-IR/HOMA-IR for MAFLD. Restrictive cubic splines were performed to visualize their dose-response relationship. Decision tree analysis was used to identify high-risk populations of MAFLD. PA's mediating effect in the association between METS-IR/HOMA-IR and MAFLD was also examined. RESULTS: Of all 1,313 participants, 693 had MAFLD (52.78%). There were a positive association between METS-IR (OR = 1.162, 95% CI = 1.126-1.199) and HOMA-IR (OR = 1.630, 95% CI = 1.431-1.856) and MAFLD risk. The AUCs of the METS-IR and HOMA-IR were 0.831 (0.809, 0.853) and 0.767 (0.741, 0.791), respectively, with significantly different predictive performance (P < 0.001). Adding METS-IR/HOMA-IR to the basic model greatly improved the statistical significance for MAFLD. Five high-risk subgroups were identified for MAFLD. PA mediated about 0.81% and 0.78% (indirect effect/total effect) in the association between METS-IR/HOMA-IR and MAFLD. CONCLUSIONS: MAFLD risk might be predicted by METS-IR/HOMA-IR, among which METS-IR performed better. And PA mediated the association between them. More attention should be paid to the therapeutic effect of lifestyle changes on MAFLD. HIGHLIGHTS: 1. Positive associations were found between METS-IR and HOMA-IR and MAFLD risk. 2. METS-IR has better predictive performance for MAFLD risk than HOMA-IR. 3.Two high-risk subgroups were identified for MAFLD by METS-IR: individuals with METS-IR ≥ 40; Hispanic black individuals with 34 ≤ METS-IR < 40 and aged ≥ 46. 4. In the significant association between METS-IR/HOMA-IR and MAFLD, about 0.81% and 0.78% (indirect effect/total effect), respectively, were mediated by physical activity.

The Correlation between the Severity of Obstructive Sleep Apnea and Insulin Resistance in a Japanese Population.

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.

Anthropometry and blood biomarkers of diabetes and their possible association with obesity and metabolic syndrome.

Background: Diabetes, a rapidly increasing heterogeneous disorder, is closely linked to the epidemic of obesity and metabolic syndrome (MetS). At present, we do not understand completely the blood biomarkers, molecular aetiology, and role of lifestyle modification and interventions to combat diabetes hand in hand with obesity and the MetS epidemic. Methods: To measure different anthropometric and blood biomarkers in pre-diabetic and diabetic patients, we collected data and blood samples from patients in a hospital OPD. This was a cross-sectional study that included the identification of possible relationships between different parameters to predict early diagnostic markers of diabetes. Results: We found increased body mass index (BMI), fasting blood glucose, neck, waist, and hip circumference, sagittal abdominal diameter, and skin fold thickness in the diabetic as compared to the pre-diabetic group. Also, serum uric acid and insulin resistance (HOMA-IR) values were significantly increased in diabetic individuals. We found a significant positive correlation between serum uric acid and BMI, fasting blood glucose, serum insulin, and HOMA-IR values. Conclusions: Here, we found that pre-diabetic and diabetic patients have increased fasting glucose levels while we did not find any difference in insulin levels. Both pre-diabetic and diabetic patients show high serum uric acid, positively associated with a higher prevalence of diabetes and HOMA-IR. Uric acid may hence be an important parameter for early diagnostics. These findings may be used as a basis for future studies that aim to identify the mechanistic details of the association of uric acid with insulin signaling and hence better understanding of the phenomenon associated with diabetes. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01276-4.