Homeostasis Model Assessment Of Insulin Resistance Research Articles

Independent relationship between sleep apnea-specific hypoxic burden and glucolipid metabolism disorder: a cross-sectional study.

Obstructive sleep apnea (OSA) is associated with abnormal glucose and lipid metabolism. However, whether there is an independent association between Sleep Apnea-Specific Hypoxic Burden (SASHB) and glycolipid metabolism disorders in patients with OSA is unknown. We enrolled 2,173 participants with suspected OSA from January 2019 to July 2023 in this study. Polysomnographic variables, biochemical indicators, and physical measurements were collected from each participant. Multiple linear regression analyses were used to evaluate independent associations between SASHB, AHI, CT90 and glucose as well as lipid profile. Furthermore, logistic regressions were used to determine the odds ratios (ORs) for abnormal glucose and lipid metabolism across various SASHB, AHI, CT90 quartiles. The SASHB was independently associated with fasting blood glucose (FBG) (β = 0.058, P = 0.016), fasting insulin (FIN) (β = 0.073, P < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (β = 0.058, P = 0.011), total cholesterol (TC) (β = 0.100, P < 0.001), total triglycerides (TG) (β = 0.063, P = 0.011), low-density lipoprotein cholesterol (LDL-C) (β = 0.075, P = 0.003), apolipoprotein A-I (apoA-I) (β = 0.051, P = 0.049), apolipoprotein B (apoB) (β = 0.136, P < 0.001), apolipoprotein E (apoE) (β = 0.088, P < 0.001) after adjustments for confounding factors. Furthermore, the ORs for hyperinsulinemia across the higher SASHB quartiles were 1.527, 1.545, and 2.024 respectively, compared with the lowest quartile (P < 0.001 for a linear trend); the ORs for hyper-total cholesterolemia across the higher SASHB quartiles were 1.762, 1.998, and 2.708, compared with the lowest quartile (P < 0.001 for a linear trend) and the ORs for hyper-LDL cholesterolemia across the higher SASHB quartiles were 1.663, 1.695, and 2.316, compared with the lowest quartile (P < 0.001 for a linear trend). Notably, the ORs for hyper-triglyceridemia{1.471, 1.773, 2.099} and abnormal HOMA-IR{1.510, 1.492, 1.937} maintained a consistent trend across the SASHB quartiles. We found SASHB was independently associated with hyperinsulinemia, abnormal HOMA-IR, hyper-total cholesterolemia, hyper-triglyceridemia and hyper-LDL cholesterolemia in Chinese Han population. Further prospective studies are needed to confirm that SASHB can be used as a predictor of abnormal glycolipid metabolism disorders in patients with OSA. ChiCTR1900025714 { http://www.chictr.org.cn/ }; Prospectively registered on 6 September 2019; China.

Positive association of the anti-aging protein α-Klotho with insulin resistance and its inverse L-shaped relationship with glycaemic control in the middle-aged and elderly population.

α-Klotho has been linked to insulin resistance (IR) in basic research. However, experimental evidence is inconsistent, and there is a lack of data from human research. This study seeks to elucidate the association of α-Klotho with IR in a nationwide, multiracial population. A total of 5289 participants aged 40-79 years were included in the National Health and Nutrition Examination Survey (NHANES) spanning 2007-2016. Serum α-Klotho was measured using enzyme-linked immunosorbent assays (ELISA), and IR was evaluated by the homeostatic model assessment of insulin resistance (HOMA-IR). Weighted multivariate logistic and linear regression analysis, subgroup analysis stratified by demographic characteristics, medical condition or obesity status, and sensitivity analysis using propensity score matching (PSM) were performed. Restricted cubic splines (RCS) were performed to explore the nonlinear relationship. In the fully adjusted logistic regression model, a significant positive association was observed between log-transformed α-Klotho and IR (OR = 3.63, 95% CI: 1.56, 8.45), particularly in males or nonobese individuals (Pinteraction < 0.05). In the linear regression model, log10(α-Klotho) was associated with fasting blood glucose (FBG, β = 1.25, 95% CI: 0.74, 1.76) and glycosylated hemoglobin (HbA1c, β = 0.49, 95% CI: 0.20, 0.77). RCS revealed an inverse L-shaped dose-response relationship of α-Klotho with FBG and HbA1c (Pnonlinear <0.05). Beyond the inflection point of log10(α-Klotho) at 2.79, β coefficients sharply rose for these glycaemic control indicators. The study provides clinical evidence supporting a positive association between α-Klotho and IR. Moreover, the inverse L-shaped relationship suggests that α-Klotho should reach a certain level to predict glycaemic changes effectively.

Effectiveness of the ALT/AST ratio for predicting insulin resistance in a Korean population: A large-scale, cross-sectional cohort study.

Insulin resistance is a common pathophysiology in patients with type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease. Thus, screening for the risk of insulin resistance is important to prevent disease progression. We evaluated the alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio to predict insulin resistance in the general population, regardless of comorbidities. Datasets from the 2015, 2019, and 2020 Korea National Health and Nutrition Examination Surveys were used, and the following four indices were implemented to indicate insulin resistance: fasting serum glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), and β-cell function. We analyzed the degree of association between the liver enzyme profile and insulin resistance indices using Pearson's correlation coefficient and determined the associations using linear or logistic regression analysis. Accordingly, ALT levels in both sexes were positively and consistently correlated with the four aforementioned insulin resistance indices in stratification analyses based on diabetes, dyslipidemia, alcohol consumption, and obesity status. In multivariate linear regression, when comparing with ALT levels, the ALT/AST ratio exhibited superior predictive performance for fasting serum glucose and HOMA-β in Korean men and improved outcomes for all insulin resistance indices in Korean women. In this analysis that included a large community-based population, the ALT/AST ratio was a more useful predictive marker than the HOMA-IR. Regarding the predicted presence or absence of insulin resistance, the ALT/AST ratio could better predict HOMA-IR than the ALT level alone in Koreans. A simple, precise marker that represents the ALT/AST ratio could be a practical method to screen for insulin resistance in the general population, regardless of diabetes mellitus, alcohol intake, and sex.

EVALUATION OF ELABELA LEVELS IN OBESE INDIVIDUALS

Aim: Obesity is a condition that occurs as a result of excessive weight gain. Obesity is related with the high risk of several diseases like cardiovascular diseases and diabetes mellitus. Elabela is a peptide that has emerged recently and is known to affect food intake by binding to apelinergic receptors. This study aimed to investigate the serum levels of Elabela in obese and non-obese individuals. Material and methods: This study involved 24 people with obesity and 25 healthy adult people as control group. Height, weight, gender, age, waist-hip circumference, blood pressure of participants were recorded and routine blood tests were measured. Serum concentrations of Elabela were determined using enzyme-linked immunosorbent assay. Results: When comparing the obese group to the controls, no statistically significant differences were observed between the two groups in terms of diastolic blood pressure, blood urea nitrogen, creatinine, total cholesterol, low density lipoprotein cholesterol and C-reactive protein. Similarly, both groups did not differ statistically regarding Elabela levels. The obese group exhibited significantly elevated levels of body mass index, waist/hip ratio, systolic blood pressure values, glucose, aspartate aminotransferase, alanine aminotransferase, triglyceride, insulin, homeostatic model assessment for insulin resistance (HOMA-IR) compared to the control group. The obese group demonstrated a significantly lower level of high-density lipoprotein cholesterol in comparison to the control group. Conclusions: In this study, it was found that there was no relationship between Elabela levels and obesity. However, this issue needs to be supported by further studies to clarify.

Differential Associations of Erythrocyte Membrane Saturated Fatty Acids with Glycemic and Lipid Metabolic Markers in a Chinese Population: A Cross-Sectional Study.

Mounting evidence indicates a complex link between circulating saturated fatty acids (SFAs) and cardiovascular disease (CVD) risk factors, but research on erythrocyte membrane SFA associations with metabolic markers remains limited. Our study sought to investigate the correlations between erythrocyte membrane SFAs and key metabolic markers within glycemic and lipid metabolism in a Chinese population of 798 residents aged 41 to 71 from Guangzhou. Using gas chromatography-mass spectrometry, we assessed the erythrocyte membrane saturated fatty acid profile and performed multiple linear regression to evaluate the relationship between different SFA subtypes and metabolic markers. Our findings revealed that the odd-chain SFA group (C15:0 + C17:0) exhibited negative associations with fasting blood glucose (FBG), homeostatic model assessment for insulin resistance (HOMA-IR), and triglycerides (TG). Conversely, the very-long-chain SFA group (C20:0 + C22:0 + C23:0 + C24:0) exhibited positive associations with fasting insulins (FINS), HOMA-IR, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Furthermore, there was no evidence supporting an association between the even-chain group (C14:0 + C16:0 + C18:0) and metabolic markers. Our findings suggest that different subtypes of SFAs have diverse effects on glycemic and lipid metabolic markers, with odd-chain SFAs associated with a lower metabolic risk. However, the results concerning the correlations between even-chain SFAs and very-long-chain SFAs with markers of glycemic and lipid metabolism pathways are confusing, highlighting the necessity for further exploration and investigation.

Associations of appendicular lean mass and abdominal adiposity with insulin resistance in older adults: A cross-sectional study.

Loss of lean muscle mass and accumulation of adipose tissue are changes associated with aging. Previous studies have documented various components of body composition as predictors for insulin resistance. The objective of this study was to investigate whether components of body composition-appendicular lean mass (ALM) and/or abdominal fat mass (AFM)-correlate with insulin resistance in older men and women. This was a cross-sectional study of 92 older men and women. Weight was classified according to body mass index (BMI)-normal (BMI <25), overweight (BMI 25-30), and obese (BMI >30). All body composition data was determined by dual energy x-ray absorptiometry (DEXA), and insulin resistance was assessed by the homeostatic model assessment of insulin resistance (HOMA-IR). Multivariable regression models with two-way interaction terms were employed to assess whether the associations between components of body composition and log HOMA varied by BMI categories. Adjusted regression showed that log HOMA was significantly associated with AFM (estimate ± standard error: 0.055 ± 0.026) and ALM (0.057 ± 0.029) for the overweight participants (p-values <0.05). Additionally, the adjusted associations between log HOMA and ALM were significantly greater for participants who were either obese or overweight compared to those with a normal BMI (p<0.002). Less consistent relationships were observed between insulin resistance and abdominal fat mass across BMI categories, whereas more consistent associations were observed between insulin resistance and appendicular lean mass in individuals with greater BMI. Further research is needed to clarify if lipid deposition within muscle tissue promotes muscle dysfunction and thereby increases risk for insulin resistance.

THE EFFICACY OF VERY LOW CALORIE KETOGENIC DIET (VLCKD) ON CARDIO–METABOLIC PROFILE IN PATIENTS WITH OBESITY

Abstract Background Obesity is associated with alterations in cardiac structure and haemodynamics leading to cardiovascular mortality and morbidity. Very low calorie ketogenic diet (VLCKD) has been proposed as an effective intervention to achieve a significant weight loss in obese patients in a short time period. Furthermore, hyperketonemia induced by VLCKD is associated with beneficial cardiovascular effects. In addition, ketogenic diet is able to prevent mitochondrial fission, improve mitochondrial function, suppress oxidative stress and attenuate cardiac myocytes apoptosis in the heart of mice. Aim To evaluate the role of VLCKD on cardio–metabolic risk factors, cardiac dysfunction and myocardial remodelling in obese patients. Materials and Methods Ten obese patients treated with VLCKD were enrolled. All patients were characterized from an anthropometric, cardio–metabolic and echocardiographic point of view at baseline and 8 weeks after VLCKD treatment. In addition, each patient underwent measurement of global myocardial work efficiency (GWE), a novel indicator that accounts for deformation and afterload, which may provide additional value for assessment of myocardial function. The insulin resistance (IR) was evaluated by HOMA–IR. Results As expected, all the patients showed a significant reduction in body weight and an overall improvement of body composition parameters after VLCKD. Weight (kg) (from 105.1 ± 18.2 to 83.7 ± 16.7, P &amp;lt;0.05), BMI (kg/m2) (from 40.1 ± 4.7 to 31.8 ± 4.8, P= 0.002) and waist circumference (cm) (from 115 ± 13.6 to 101.8 ± 12.4, p &amp;lt; 0.05) were significantly lower after VLCKD treatment. VLCKD treatment improved also significantly fasting glucose levels (P &amp;lt;0.05), fasting insulin levels (P =0.004), HOMA–IR values (P &amp;lt;0.001), lipid profile and systolic and diastolic blood pressure levels. In addition, the echocardiogram evaluation showed an improved in end–diastolic left ventricular volume, end–systolic left ventricular volume, left ventricular mass and left ventricular mass index. Interestingly, a significantly changes in GWE was observed (P&amp;lt;0.05). Conclusion Although preliminary, our data suggest that VLCKD treatment is able to reduce cardio–metabolic risk factors and to improve cardiac dysfunction and myocardial function.

The impact of the obesity onset on the inflammatory and glycemic profile of women with severe obesity

BackgroundThe stage of life at the onset of obesity is an important factor in assessing inflammatory state and cardiometabolic risk. ObjectivesThis study aimed to evaluate the relationship between the obesity onset and the inflammatory profile in women with severe obesity. SettingPublic hospital, Brazil. MethodsForty-eight women with severe obesity (20–59 yr old) were evaluated according to weight, height, neck circumference (NC), waist circumference (WC), and hip circumference, as well blood metabolic and inflammatory parameters. The participants were grouped according to obesity onset stage of life (early group: ≤19 yr; late group: >19 yr). ResultsThe demographic means of the participants were: age of 39.7 years, weight of 122.7 kg and body mass index (BMI) of 48.4 kg/m2. The late group presented significantly higher values of leptin (lep)/adiponectin (adipo) ratio and homeostatic model assessment for insulin resistance (HOMA-IR) than the early group. The late group also had a lower adipo/lep ratio. Moreover, the late group showed correlations between the lep/adipo ratio and BMI (r = .460, P = .021), NC (r = .478, P = .016), and WC (r = .535, P = .006). Adipo was also correlated with NC (r = −.418, P = .038), WC (r = −.437, P = .029), and glycated hemoglobin (HbA1C) (r = −.485, P = .019). By contrast, in the early group, the lep/adipo ratio showed correlations with insulin (r = .647, P = .004) and HOMA-B (r = .564, P = .015). ConclusionsThe inflammatory profile is correlated with anthropometric values in women with late-onset obesity. Inflammatory markers seemed to correlate with the glycemic profile in women with early-onset obesity. Furthermore, inflammation was higher in women with late-onset obesity compared to those with early-onset obesity.

Association Between the Serum α-Klotho Level and Insulin Resistance in Adults: NHANES 2007–2016

ABSTRACT Objective This study aimed to investigate the relationship between serum α-Klotho levels and insulin resistance (IR), a precursor to type 2 diabetes. Methods The study analyzed data from 4,758 adult participants in the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016. The relationship between α-Klotho concentration and IR was assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and odds ratios (OR) derived from logistic regression models. Results Results showed that every 1-ln increase in α-Klotho concentration raised the HOMA-IR value by 0.55 (95% confidence interval 0.35–0.74) and the odds of IR by 64% (odds ratio 1.64; 95% confidence interval 1.28–2.1). The odds of IR was 40% greater in highest tertile than in the lowest tertile. Conclusion The findings of this study underscore a significant correlation between increased serum α-Klotho levels and the prevalence of IR.

The effect of PAP on UACR and metabolic indexes in patients with MS and OSAHS

PurposeTo investigate the effects of positive airway pressure (PAP) device on urinary albumin to creatinine ratio (UACR) and metabolic indexes in patients with metabolic syndrome (MS) and obstructive sleep apnea-hypopnea syndrome (OSAHS).MethodsThis study is a retrospective cohort study. Grouped according to whether to use PAP treatment, there were 25 cases in the PAP group and 44 cases in the no OSAHS treatment group. The PAP group received positive airway pressure device and routine treatment of MS. The no OSAHS treatment group received routine treatment of OSAHS and MS. The treatment period is 3 months.Results1. The PAP group demonstrated significant reductions in Body Mass Index (BMI), Waist circumference (WC), Neck circumference (NC), Visceral fat area (VFA), Fasting C peptide (FCP), high-sensitivity C-reactive protein (hs-CRP), and UACR compared to the no OSAHS treatment group, with significant differences (P all <0.05). Among them, the UACR in the PAP group decreased significantly (from 86.05(52.55,131.61)mg/g to 16.76(8.70,25.12)mg/g, P<0.001). 2. Linear regression analysis using the decrease in UACR values as the dependent variable demonstrated a positive linear relationship with the decrease in BMI, VFA, fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR). Furthermore, multiple linear regression analysis indicated that the decrease in VFA (B=0.537 [95% confidence interval, 0.084 to 0.989]; P = 0.021) and HOMA-IR (B=1.000 [95% confidence interval, 0.082 to 1.917]; P = 0.033) values independently correlated with decrease in UACR values.ConclusionsPAP treatment can reduce UACR in patients with MS and OSAHS, and has the effect of improving metabolic disorders. The decrease of UACR in patients may be related to the decrease of visceral fat and the improvement of insulin resistance.

Associations between estimated glucose disposal rate and arterial stiffness and mortality among US adults with non-alcoholic fatty liver disease.

The estimated glucose disposal rate (eGDR), an effective indicator of insulin resistance, has been related to acute coronary syndrome, ischemic stroke and heart failure. This study aims to explore the relationship between eGDR and arterial stiffness, all-cause mortality and cardiovascular mortality in patients with non-alcoholic fatty liver disease (NAFLD). Participants with NAFLD were chosen from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. The main outcomes are arterial stiffness (represented by estimated pulse wave velocity, ePWV), all-cause and cardiovascular mortality. Multiple cox regression models, restricted cubic spline, sensitivity analysis and subgroup analysis were carried out to investigate the correlation between the insulin resistance indicators and mortality and arterial stiffness. Furthermore, receiver operating characteristic curves were used to compare the predictive value of the eGDR with the triglyceride-glucose (TyG) index and the homeostasis model assessment of insulin resistance (HOMA-IR) for all-cause and cardiovascular mortality. In this study, a total of 4,861 participants were included for analysis. After adjusting confounding factors in the multivariate weighted cox regression model, the eGDR was inversely associated with the all-cause mortality (Q4 vs. Q1, HR =0.65 (0.48-0.89, P=0.01) and cardiovascular mortality (Q4 vs. Q1, HR =0.35 (0.19-0.65, P<0.001). Compared with TyG index and HOMA-IR, the eGDR shows excellent predictive value in all-cause mortality (0.588 vs. 0.550 vs. 0.513, P < 0.001) and cardiovascular mortality (0.625 vs. 0.553 vs. 0.537, P < 0.001). In addition, we found a significant negative correlation between eGDR and arterial stiffness (β=-0.13(-0.14-0.11, P< 0.001). However, TyG index and HOMA-IR showed no significant correlation to arterial stiffness. Low eGDR (an indicator of insulin resistance) levels are related to an increased risk of arterial stiffness and mortality in NAFLD patients in the United States.

Gender Differences in Liver Steatosis and Fibrosis in Overweight and Obese Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease before and after 8 Weeks of Very Low-Calorie Ketogenic Diet.

Obesity and metabolic syndrome are linked to steatotic liver disease (SLD), the most common form of chronic liver disease. Lifestyle modifications and dieting are strategies that can prevent metabolic dysfunction-associated steatotic liver disease (MASLD). The very low-calorie ketogenic diet (VLCKD) is a helpful treatment for MASLD and has been recommended for people affected by obesity; we evaluated the effect of gender on steatosis and fibrosis in a cohort of 112 overweight or obese patients undergoing an eight-week treatment with a VLCKD. Differences between the genders in terms of anthropometric measures, body composition, and metabolic indicators were examined before, during, and after the nutritional intervention. At baseline, there were significant differences between men and women in terms of anthropometric parameters, blood pressure, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fasting insulin, hepatic markers, and lipid profile. Men had considerably higher levels of liver steatosis (measured by CAP) and liver stiffness (measured by E) under basal conditions than women. After the VLCKD, there were reductions in both genders of controlled attenuation parameter (CAP), body weight, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, insulin resistance, fat mass (FM), free fat mass (FFM), and fasting blood glucose, insulin, glycated hemoglobin (HbA1c), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, alanine transaminase (ALT), gamma-glutamyl transferase (γGT), and uric acid levels. Only in men, liver stiffness, aspartate aminotransferase (AST), creatinine, and C-reactive protein (CRP) levels significantly decreased. Moreover, men had significantly greater levels of liver steatosis: the male gender featured an increase of 23.96 points of the Fibroscan CAP. Men exhibited higher levels of steatosis and fibrosis than women, and these differences persist despite VLCKD. These gender-specific variations in steatosis and fibrosis levels could be caused by hormonal and metabolic factors, suggesting that different therapeutic strategies might be required depending on the gender.

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

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

Interplays between Metabolic Hormones, Metabolic Factors, Kidney Function Parameters, and Heart Rate Variability

Metabolic Syndrome (MetS) is associated with autonomic cardiac dysregulation, reflected by changes in heart rate variability (HRV) and detrimental effects on kidney function. This study aimed to 1) compare metabolic factors and hormones, kidney function profiles, and HRV parameters, including SDSD, RMSSD, pNN50, high-frequency power (HF), low-frequency power (LF), LF/HF ratio, between subjects with/without MetS or insulin resistance and 2) determine the correlations among these variables. We hypothesized that these factors differed between subjects with and without metabolic disturbances. Furthermore, we expected that metabolic factors and hormones and kidney function parameters were associated with HRV. In Thai obese subjects, characterized by BMI ≥ 25 kg/m2 for an Asian population (n = 45), fasting blood samples and spontaneous 5-minute HRV were obtained. The criteria for MetS were defined by The NCEP ATP III 2005 definition, except waist circumference which is ≥ 90 cm in men and 80 cm in women for Asians. Insulin resistance was determined by homeostatic model assessment for insulin resistance (HOMA-IR) &gt; 2.3. In subjects with MetS (n = 19), percent fat, HOMA-IR, and serum leptin were significantly higher than those without MetS (n = 26), all with P &lt; 0.05. Serum adiponectin, SDSD, RMSSD, and LF in ms2 tended to decrease in subjects with MetS. In subjects with insulin resistance (n = 30), BMI and serum leptin were significantly higher than those without insulin resistance (n = 15), all with P &lt; 0.05. HDL-cholesterol (HDL-C) was significantly lower in subjects with insulin resistance, all with P &lt; 0.05. Serum leptin exhibited positive correlations with BMI, creatinine clearance (CrCl), serum insulin, and HOMA-IR (R = 0.433-0.778) but had a negative correlation with HDL-C (R = -0.303), all with P &lt; 0.05. Serum insulin showed positive correlations with BMI, CrCl, and serum leptin (R = 0.328-0.437); while it had negative correlations with age and HDL-C (R = (-0.310)-(-0.438)), all with P &lt; 0.05. Serum adiponectin demonstrated positive correlations with HDL-C and pNN50 (R = 0.329-0.473), all with P &lt; 0.05. CrCl had positive correlations with BMI, HOMA-IR, serum insulin and leptin, and HF in normal unit (nu) (R = 0.304-0.617); and negative correlations with LFnu, and LF/HF ratio (R = (-0.317)-(-0.386)), all with P &lt; 0.05. HDL-C demonstrated significant positive correlations with serum adiponectin, SDSD, and RMSSD (R = 0.329-0.331); while showed negative correlations with the number of criteria met for MetS, BMI, triglyceride, serum insulin and leptin, and HOMA-IR (P = (-0.303)-(-0.595)), all with P &lt; 0.05. LDL-cholesterol (LDL-C) had negative correlations with percent fat and pNN50 (R = (-0.313)-(-0.340)), all with P &lt; 0.05. Subjects with metabolic syndrome tended to have decreased insulin sensitivity, serum adiponectin, as well as parasympathetic (SDSD, RMSSD) and sympathetic (LF) HRV. Those with insulin resistance showed lower level of HDL-C. Leptin and insulin were correlated with obesity, metabolic factors, insulin resistance, and kidney function parameters but not HRV. Interestingly, serum adiponectin exhibited a positive correlation with HDL-C, and both serum adiponectin and HDL-C, which are protective factors, had positive correlations with parasympathetic HRV (pNN50, SDSD, and/or RMSSD). Conversely, LDL-C showed a negative correlation with parasympathetic HRV (pNN50). Creatinine clearance was positively correlated with parasympathetic HRV (HF) and negatively correlated with sympathetic HRV (LFnu and LF/HF ratio). In conclusion, MetS was linked to shifts in HRV, with reductions in both parasympathetic and sympathetic components. HDL-C exhibited a protective role in metabolic disturbances. Parasympathetic HRV was positively correlated with protective factors but negatively with LDL-C. Deteriorating kidney function was associated with increased sympathetic HRV and decreased parasympathetic HRV. The research was funded by the Faculty of Medicine Siriraj Hospital Research Fund ((IO) R015932003, R0159333013 and R016132012. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Interplay Between the American Diabetes Association's ABC Targets for Diabetes, Insulin Resistance Indices, and Dyslipidemia in Indian Type 2 Diabetes Patients.

Background The increasing incidence of type 2 diabetes (T2D) in India underscores the pressing need for effective management strategies. Meeting the American Diabetes Association (ADA) ABC targets for diabetes (glycated hemoglobin (HbA1c), blood pressure, and serum low-density lipoprotein cholesterol (LDL-C)) is crucial for effectively managing T2D, as it reflects the optimal control of key metabolic parameters. Insulin resistance (IR) and impaired beta cell function (BCF) have been found to have a significant impact on glycemic control, lipid metabolism, and hypertension, contributing to the complex cardiovascular risk profile of patients with T2D. This study aimed to explore the association between ABC targets for diabetes, IR, BCF, and dyslipidemia in a cross-sectional cohort of T2D patients. Methods This retrospective study examined data from 681 T2D patients with comorbid hypertension and dyslipidemia. The patients were part of a one-year online lifestyle intervention program for diabetes management at the Freedom from Diabetes Clinic in Pune, India, between January 2021 and December 2022. Baseline data (at the time of enrollment in the program) on medical history and anthropometric and biochemical parameters were retrospectively extracted from medical records and used to assess ABC targets and other clinical parameters. The ABC targets for diabetes include three goals: an HbA1c level of less than 7.0%, a blood pressure level of less than 140/90 mmHg, and an LDL-C level of less than 100 mg/dL. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Homeostatic Model Assessment of Beta Cell Function (HOMA-B), and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated using standard formulas. Results Cross-sectional analysis at baseline showed that 152 (22.3%) participants met all three ABC targets, 306 (45.0%) and 183 (26.8%) participants met two or one targets, respectively, and 40 (5.9%) did not meet any of the ABC targets. Participants meeting all three targets showed significantly lower IR, higher sensitivity (HOMA-IR, median 2.1; QUICKI, median 0.34), higher BCF (HOMA-B, median 62.9), and healthier lipid profiles (mg/dL) (total cholesterol, median 126; triglycerides, median 114; and non-high-density lipoprotein (HDL), median 84) than those who did not meet any of the ABC targets (HOMA-IR, median 3.4; QUICKI, median 0.31; HOMA-B, median 31.7; total cholesterol, median 221; triglycerides, median 187; and non-HDL, median 182) (p < 0.01). A significant association was observed between lower BMI (< 25 kg/m2), lower IR (HOMA-IR <2.5), and meeting all three ABC targets (p < 0.01). No significant association was observed between the duration of diabetes and ABC target status (p > 0.1). Lower IR was identified as a predictor of achievement of all three ABC targets (p < 0.01). Conclusion This study highlights the significance of meeting ABC targets for diabetes in relation to not only a better lipid profile but also lower IR and higher BCF. These preliminary findings provide novel insights into the interplay between IR, BCF, dyslipidemia, and meeting ABC targets in an Indian T2D population. These findings highlight the need for effective diabetes management strategies and improved patient outcomes, considering factors such as BMI and IR indices.

Insulin resistance and glucose homeostasis in Egyptian children with sickle cell anemia

Background A single gene mutation produces sickle cell anemia (SCA), an autosomal recessive illness. The body can keep the glycemic state in normal range via various mechanisms depending mainly on pancreatic hormones. Aim Evaluation of glucose homeostasis and insulin resistance in a group of Egyptian sickle cell children. Patients and methods This cross-sectional comparative study was carried out on 80 participants aged from 5 to 16 years old of both sexes, 40 patients with sickle cell hemoglobinopathies and in a steady state (case group), and 40 healthy individuals as control (control group). Fasting blood glucose, fasting serum insulin, glycosylated hemoglobin were measured in all participants, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated. Serum fructosamine (SF) was measured in the cases group. Results Glucose homeostasis was kept normal in most patients with only 10% of them showed abnormal glycemia. HOMA–IR was significantly different between the two groups with 15% of patients had pathological HOMA-IR. The study found a strong positive correlation (r=0.479, &lt;0.001) between the HOMA-IR and the frequency of vaso-occlusive crisis per year before participants were recruited and between SF and fasting blood glucose (r=0.772, &lt;0.001). On comparing glycosylated hemoglobin between both groups there was no statistically significant difference between both groups (P value = 0.874) Conclusions and recommendations Normal glucose homeostasis was proved in the majority of patients. Insulin resistance was detected in a limited number of sickle cell anemia patients. Follow-up of glucose homeostasis is indicated in sickle cell cases.

Association Between Triglyceride-Glucose Index and Homeostasis Model Assessment for Insulin Resistance with Estimated Glucose Disposal Rate.

This cross-sectional study was aimed to compare insulin resistance, Triglyceride- Glucose (TyG) index, fatty liver index (FLI) and hepatic steatosis index (HSI), glycaemic and lipids among groups/quartiles based upon estimated Glucose Disposal Rate (eGDR) from August 2022 to December 2022 among 249 male participants. The eGDR results in (mg/kg/min) were divided into four quartiles as: Group-I: {<6.88, n = 62}, Group-II: {<6.88-9.45, n = 63}, Group-III: {9.46-10.39, n = 62}, and Group-IV: {>10.39, n = 62}. Fasting plasma glucose (FPG), HbA1c, low density lipoprotein (LDL), homeostasis model assessment for insulin-resistance (HOMAIR), and TyG index demonstrated significant worsening increase from high to low eGDR groups. Receiver operating curve (ROC) analysis to calculate area under curve (AUC) for diagnostic efficiency candidate indices for eGDR demonstrated highest AUC for FLI as AUC: 0.736 (95% CI: 0.669-0.803), p < 0.001, followed by FPG: AUC: 0.682 (95% CI: 0.606-0.757), HOMAIR: AUC: 0.670 (95% CI: 0.602-0.739), HSI: AUC: 0.660 (95% CI: 0.589-0.731), TyG index: 0.658 (95% CI: 0.583-0.732), and HbA1c: 0.639 (95% CI: 0.583-0.732). Glycaemic measures, lipid indices, insulin resistance and TyG index deteriorated with declining eGDR. Diagnostic performance as evaluated by AUC for eGDR was highest for FLI, followed by FPG, HOMAIR, HSI, TyG index, HbA1c, and triglycerides. Key Words: Triglyceride, Insulin, Glucose, Diabetes.

HIGHER FATTY LIVER INDEX VALUES AT SIMILAR BLOOD PRESSURE CLASSIFICATION INDICATE HIGH INSULIN RESISTANCE AND POTENTIAL INFLAMMATION

Objective: The relationship between fatty liver, which is visceral fat accumulation, and insulin resistance and inflammation as seen in hypertension classification is not clear. The Fatty Liver Index (FLI) is an established score for metabolic dysfunction-associated fatty liver disease (MASLD), which is associated with a risk of diabetes and cardiovascular disease. FLI is derived from a formula based on body mass index, waist circumference, and triglyceride and gamma-glutamyltransferase values. Design and method: A cross-sectional study enrolling consecutive individuals was conducted at a health checkup center in Japan from January 2022 to November 2022. A total of 3553 men (mean Age 50.6), excluding those with diabetes mellitus and those undergoing treatment for inflammatory diseases, were included in the study, and divided according to the Classification of hypertension in the ESH guideline. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and C-reactive protein (CRP) levels were divided into two groups by FLI (&lt;26 (group L) and &gt; or = 26 (group H)) and compared by Mann-Whitney U test. The cutoff value for fatty liver by FLI was determined by prior abdominal ultrasonography, and was set at 26(sensitivity 0.82, specificity 0.72). Results: Results of single regression analysis with FLI showed significant correlations in systolic blood pressure(r=0.31, p &lt; 0.0001), diastolic blood pressure(r=0.36, p &lt; 0.0001), HOMA-IR(r=0.36, p &lt; 0.0001), and CRP(r=0.08, p &lt; 0.0001). Optimal blood pressure(n=1783, mean FLI; 23.1, mean HOMA-IR; 1.28, mean CRP; 0.098mg/dL), Normal blood pressure(n=807, 33.9, 1.61, 0.14), High-normal blood pressure(n=535, 37.8, 1.90, 0.12), Grade 1 hypertension(n=124, 44.8, 2.0, 0.14), Grade 2 hypertension(n=53, 49.0, 1.71, 0.09), Grade 3 hypertension(n=18, 54.6, 2.89, 0.22), Isolated systolic hypertension(n=118, 36.2, 1.59, 0.09), Isolated diastolic hypertension(n=115, 44.1, 1.94, 0.12). HOMA-IR and CRP of H group were significantly higher than L group (all p &lt; 0.001). Conclusions: Higher FLI values at similar blood pressure levels may indicate high insulin resistance and potential inflammation, suggesting the need for strict management.

Astragalus mongholicus polysaccharides alleviate insulin resistance through modulation of PI3K/AKT, TLR4/NF-kB signaling pathway and microbiota in rats with Type 2 Diabetes Mellitus

Background and aimAstragali Radix has been widely used in traditional Chinese medicine to treat diabetes and a variety of other diseases. This study aims to evaluate the alleviating effects and mechanisms of Astragalus mongholicus Polysaccharide (mAPS) against diet combined with streptozotocin (STZ)-induced Type 2 Diabetes Mellitus (T2DM). Experimental procedureT2DM rats were orally administrated either with 200 mg/kg mAPS or 300 mg/kg Metformin (MET) once daily for four weeks. Body weight and Fasting Blood Glucose (FBG) were detected every 6 days. Serum fasting insulin (FINS) was measured by ELISA and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated accordingly. Histological change was studied by Hematoxylin and eosin (HE) staining. 16S rDNA sequencing was used to detect the changes in gut microbiota. Results and conclusionOral administration of mAPS significantly decreased body weight, FBG, and HOMA-IR in T2DM rats (p＜0.05). Moreover, HE staining showed that mAPS could alleviate histological distortion in the liver and pancreas. Treatment with mAPS elevated the hepatic levels of phosphatidylinositol-3 kinase (PI3K), phospho-protein kinase B (AKT), and glucose transporter type 4 (GLUT4), while reducing phospho-nuclear factor kappa-B (NF-κB), Toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) (p＜0.05). Furthermore, mAPS supplementation could reverse the ratio of Firmicutes/Bacteroidetes (F/B) and reduce the abundance of Clostridia and Proteobacteria (p＜0.05). These results indicate that mAPS have the potential to enhance insulin sensitivity in diabetic rats by modifying gut microbiota and controlling the hepatic glycolipid metabolism and inflammation.

EGCG’s effects on Mean Arterial Pressure and Heart Rate Variability and Their Correlations with Metabolic and Hormonal Profiles in Obese Subjects

This study aimed to investigate the effects of epigallocatechin gallate (EGCG), a potent polyphenol found in green tea, on mean arterial pressure (MAP) and heart rate variability (HRV) in obese subjects along with their associations with metabolic factors. We hypothesized that EGCG treatment could significantly reduce MAP and sympathetic tone, represented by decreased low-frequency power (LF) and LF-to-high frequency power (HF) ratio. Furthermore, we expected that systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP would be positively correlated with obesity parameters, LF, and LF-to-HF ratio. This study is a double-blind, randomized controlled trial. Thai obese subjects with a body mass index (BMI) ≥ 25 kg/m2 (criteria for an Asian population) were randomly allocated into EGCG and placebo groups and received a capsule of 150 mg of EGCG or starch, respectively, twice a day without any dietary restrictions. Clinical and anthropometric data, as well as spontaneous 5-minute HRV measurements in both time and frequency domains, were assessed at baseline (week 0), week 4, and week 8. Additionally, 8-hour fasting blood samples were collected at weeks 0 and 8 to measure metabolic and hormonal levels. EGCG treatment for 8 weeks significantly reduced MAP compared to week 0 and week 4 (P &lt; 0.05 for all). In the EGCG treatment group, there was a significant increase in the LF-to-HF ratio and a nonsignificant decrease in HF at week 8 compared to week 0. LF showed a trend toward increasing in week 8 of EGCG treatment compared to week 4. For correlation analysis at week 0, SBP had significant positive correlations with BMI, percent fat, fat mass, serum leptin and insulin levels, and the homeostatic model assessment for insulin resistance (HOMA-IR) (R = 0.468-0.593, p&lt;0.05 for all) but had negative correlations with the quantitative insulin sensitivity check index (QUICKI) and HDL-cholesterol (R = (-0.437)-(-0.468), P &lt;0.05 for all). DBP was positively correlated with age and HF in normal units (nu) (R = 0.412-0.568, p&lt;0.05 for all), but was negatively correlated with height, HDL-cholesterol, LF in ms (R = (-0.379)-(-0.509), P &lt;0.05 for all). MAP showed significant positive correlations with age, BMI, percent fat, fat mass, serum leptin levels, and HOMA-IR (R = 0.370-0.459, P &lt; 0.05 for all), but had a negative correlation with HDL-cholesterol (R = -0.522, P = 0.004). EGCG treatment over an 8-week duration reduced MAP, a pivotal component of overall blood pressure in obese individuals, and exhibited a significant increase in the LF/HF ratio, tending toward an increase in LF and a non-significant decrease in HF. We postulate that the decrease in MAP may be attributed to EGCG's direct or indirect vasodilatory effects, potentially through the stimulation of nitric oxide production, reduced oxidative stress, and/or decreased levels of kisspeptin, a vasoconstrictive substance, as reported by previous studies. An increase in the LF/HF ratio could reflect a shift toward sympathetic nervous system dominance (LF) and/or a decrease in parasympathetic nervous system activity (HF) indicating a compensatory response to the reduced blood pressure post-vasodilation. HDL cholesterol showed negative correlations with SBP, DBP, and MAP, reflecting its protective benefit against high blood pressure. In summary, 8 weeks of EGCG treatment resulted in a significant decrease in MAP and an increase in the LF/HF ratio, reflecting EGCG’s primary vasodilatory effects and a compensatory increase in sympathetic nervous system activity. The research was funded by the Faculty of Medicine Siriraj Hospital Research Fund ((IO) R015932003, R0159333013 and R016132012). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.