Homeostasis Model Assessment Index Research Articles

Metformin-induced changes of the gut microbiota in patients with type 2 diabetes mellitus: results from a prospective cohort study.

The influence of the microbiota on hypoglycemic agents is becoming more apparent. The effects of metformin, a primary anti-diabetes drug, on gut microbiota are still not fully understood. This prospective cohort study aims to investigate the longitudinal effects of metformin on the gut microbiota of 25 treatment-naïve diabetes patients, each receiving a daily dose of 1500 mg. Microbiota compositions were analyzed at baseline, and at 1, 3, and 6 months of medication using 16S rRNA gene sequencing. Prior to the 3-month period of metformin treatment, significant improvements were noted in body mass index (BMI) and glycemic-related parameters, such as fasting blood glucose (FPG) and hemoglobin A1c (HbA1c), alongside homeostasis model assessment indices of insulin resistance (HOMA-IR). At the 3-month mark of medication, a significant reduction in the α-diversity of the gut microbiota was noted, while β-diversity exhibited no marked variances throughout the treatment duration. The Firmicutes to Bacteroidetes ratio. markedly decreased. Metformin treatment consistently increased Escherichia-Shigella and decreased Romboutsia, while Pseudomonas decreased at 3 months. Fuzzy c-means clustering identified three longitudinal trajectory clusters for microbial fluctuations: (i) genera temporarily changing, (ii) genera continuing to decrease (Bacteroides), and (iii) genera continuing to increase(Lachnospiraceae ND3007 group, [Eubacterium] xylanophilum group, Romboutsia, Faecalibacterium and Ruminococcaceae UCG-014). The correlation matrix revealed associations between specific fecal taxa and metformin-related clinical parameters HbA1c, FPG, Uric Acid (UA), high-density lipoproteincholesterol (HDL-C), alanine aminotransferase (ALT), hypersensitive C-reactive protein (hs-CRP), triglyceride (TG) (P < 0.05). Metacyc database showed that metformin significantly altered 17 functional pathways. Amino acid metabolism pathways such as isoleucine biosynthesis predominated in the post-treatment group. Metformin's role in glucose metabolism regulation may primarily involve specific alterations in certain gut microbial species rather than an overall increase in microbial species diversity. This may suggest gut microbiota targets in future studies on metabolic abnormalities caused by metformin.

Protective effects of copper nanoparticles green-formulated by Ginkgo biloba leaf extract on cardiac function in obese insulin-resistant rats

Ginkgo biloba has been revealed to have cardioprotective and antioxidant potentials. But, the efficacy of the copper nanoparticles green-formulated by Ginkgo biloba on the cardiac mitochondria, heart rate variability, and cardiac function are poorly defined. Initially, the plan, Ginkgo biloba extract was coated on the surface of graphene oxide. The as-prepared nanoparticles were analyzed using transmission electron microscopy (TEM), ultraviolet–visible spectroscopy (UV–Vis), field emission-scanning electron microscopy (FE-SEM), and fourier-transform infrared spectroscopy (FT-IR) analysis. It has been shown that the Cu NPs with spherical shape and uniform size were dispersed on the NPs surface. In the animal part, 60 % of energy from fat was used for inducing obesity. Then, the animals were divided to four groups: control rats were fed with the usual diet, untreated rats were fed with high-fat-diet, and treated rats were fed with high-fat-diet + Cu NPs@Ginkgo biloba (30 and 60 µg/kg/day). In this study, the cardiac mitochondrial function, cardiac function, heart rate variability (HRV), and metabolic parameters were determined. The levels of oxidative stress, total cholesterol, plasma insulin levels, visceral fat, and body weight increased and cardiac mitochondrial dysfunction and HRV reduced in the untreated group. Treatment with Cu NPs@Ginkgo biloba reduced oxidative stress, homeostasis model assessment index, total cholesterol, and plasma insulin and regulated cardiac mitochondrial function and HRV in rats. The above results confirm the cardioprotective effects of Cu NPs@Ginkgo biloba. According to the above findings, the recent nanoparticles may be used as a cardioprotective drug or supplement for the treatment of cardiovascular diseases after doing the clinical trial studies in humans.

Relationship between inflammatory biomarkers and insulin resistance in excess-weight Latin children.

Excess weight, inflammation, and insulin resistance (IR) are associated, but the prevalence of and biomarkers for IR in Latin children are unknown. This study aimed to determine the prevalence of IR in prepubertal and pubertal Latin children with excess weight and explore the usefulness of different biomarkers of low-grade inflammation for identifying IR status. Sixty-eight children (31 boys, 37 girls; approximately 11 years of age) with excess weight (overweight and obese) and 20 healthy normal-weight children (12 boys, 8 girls; approximately 12 years of age) were included. Anthropometric parameters, insulin, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, tumor necrosis factor- α (TNF-α), interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), soluble CD40 ligand (sCD40L), high-sensitivity C-reactive protein (hs-CRP), and myeloperoxidase were assessed and IR was determined by homeostasis model assessment index (cutoff points: 2.67 and 2.22 in prepubertal boys and girls and 5.55 and 3.82 in pubertal boys and girls, respectively). Intergroup differences were compared, correlations were investigated using Pearson correlation coefficient, and stepwise multiple linear regression analyses were performed to estimate the relationship between inflammatory biomarkers and IR. The prevalence of IR among overweight children was 62%. IL-6 levels differed between overweight and obese boys, while erythrocyte sedimentation rate, MCP-1, TNF-α, IL-6, hs-CRP, and sCD40L differed between obese and normal-weight boys. In contrast, sCD40L levels were increased in overweight versus normal-weight girls, while MCP-1, TNF-α, IL-6, and sCD40L differed between obese and normal-weight girls. Furthermore, MCP-1 and sCD40L levels and erythrocyte sedimentation rate were positively correlated with IR; however, a stepwise regression analysis that adjusted for the body mass index (BMI) z score, sex, and age showed that none were good predictors of IR status. The prevalence of IR is high among Latin children with excess weight. Although some inflammatory biomarkers differed among groups, none robustly predicted IR.

Additive interactions between obesity and insulin resistance on hypertension in a Chinese rural population

BackgroundAdiposity and insulin resistance (IR) are closely associated with hypertension; however, the role of interactions between obesity phenotypes and IR in hypertension is unclear. This study aimed to evaluate the interactions of body mass index (BMI), waist circumference (WC), and body fat percentage (BF%) with IR on hypertension risk.MethodsWe analyzed data from 4888 participants (mean age 57 years, 41.2% men) in the China Northwest Natural Population Cohort, Ningxia Project. BMI, WC, and BF% were determined using bioelectrical impedance analysis devices. IR was estimated using a homeostasis model assessment index (HOMA-IR). Multivariable-adjusted logistic regression was used to evaluate the association between HOMA-IR and hypertension risk. We calculated the relative excess risk and attributable proportion with their 95% confidence intervals (CIs) to assess whether adiposity phenotypes modified the effect of HOMA-IR on hypertension risk.ResultsThe crude prevalence of hypertension was 52.2%. The multivariable-adjusted odds ratio of HOMA-IR was 1.80 (95% CI: 1.23–2.65) for the risk of hypertension in the highest versus the lowest quartiles, but this association became marginal in models further adjusting for BMI, WC, and BF% (P for trend = 0.056). Relative excess risk and attributable proportion for interaction between high HOMA-IR and high BF% were 0.32 (0.04–0.59) and 0.33 (0.06–0.60), respectively. Additionally, high truncal and leg BF% and high HOMA-IR accounted for the hypertension risk in women, but not in men. We did not observe any significant interactions between BMI or WC and HOMA-IR on hypertension.ConclusionBF% modified the association between IR and increased risk of hypertension in women with high truncal and leg BF%, but not in men.

Anti-diabetic mechanism and potential bioactive peptides of casein hydrolysates in STZ/HFD-induced diabetic rats.

Casein hydrolysates have attracted much interest as anti-diabetic food, but their hypoglycemic mechanism and biopeptides are not well understood. This study aimed to explore the anti-diabetic mechanism and potential biopeptides of casein hydrolysates in streptozotocin/high-fat-diet-induced diabetic rats and HepG2 cells. Oral administration of casein hydrolysate prepared with papain-Flavourzyme combination (P-FCH) decreased fasting blood glucose, improved oral glucose tolerance, and reduced HbA1c values in diabetic rats. P-FCH was ineffective in alleviating insulin resistance (homeostasis model assessment and insulin sensitivity index) and enhancing hepatic insulin signaling transduction (phosphorylated Akt, hexokinase activity, and pyruvate kinase activity) in diabetic rats. However, P-FCH significantly upregulated adenosine monophosphate-activated protein kinase phosphorylation and glucose transporter-2 expression, inhibited phosphoenolpyruvate carboxylase kinase activity, and elevated glycogen content in liver tissue of diabetic rats. Furthermore, P-FCH increased glucose consumption independently in normal and insulin-resistant HepG2 cells without the presence of insulin. The peptide composition of P-FCH was characterized. The potential biopeptides in P-FCH showed the sequence characteristic of a Val at the N-terminal or a Pro at the P2 position, and the hypoglycemic activity of Val-Pro-Leu-Gly (the most potential biopeptide in P-FCH) was verified by oral glucose tolerance test in mice. These results suggested that activation of the non-insulin-mediated AMPK pathway might be the determinant mechanism of P-FCH on the hypoglycemic effect. The novel peptide Val-Pro-Leu-Gly in P-FCH was effective in reducing blood glucose levels when orally administered to mice. © 2023 Society of Chemical Industry.

Preparation and formulation of Ag NPs for the anticancer activities and its protective effects on cardiac function, heart rate variability, and cardiac mitochondria in obese insulin-resistant rats

Panax ginseng as an ethnomedicinal plant has many therapeutic effects in the traditional medicine. This medicinal plant, having antioxidant substances, can protect body cells from various damages and prevent cancer. Also, folic acid in this plant helps the body to produce new cells and reduces the possibility of heart disease and colon cancer. In the recent years, the silver nanoparticles green-mediated by ethno medicinal plants have been used for the treatment of several kinds of cancers and heart disease. Now, we investigated the silver nanoparticles green-synthesized according to green chemistry rules using the aqueous extract of Panax ginseng leaf for the treatment of lung carcinoma and protective effects on cardiac function, heart rate variability, and cardiac mitochondria in obese insulin-resistant rats. The green-synthesized silver nanoparticles were characterized using different techniques such as FE-SEM, UV–Vis, XRD, and TEM. The FE-SEM and TEM results confirm spherical morphology for the nanoparticles with size of 12.11 to 43.33 nm. The IC50 of the silver nanoparticles was 311, 293, 375, and 250 against EKVX, HOP-62, A549 and NCI-H460, respectively. In the in vivo part of this study, after treating 12 weeks with high-fat-diet, then 28 days with Ag NPs (20 and 40 µg/kg/day, respectively), the metabolic parameters, heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined. Silver nanoparticles at both concentrations significantly decreased the plasma insulin, total cholesterol, homeostasis model assessment index, and oxidative stress levels and restored the HRV, cardiac function, and cardiac mitochondrial function. We concluded that silver nanoparticles at both concentrations exerted cardioprotective effects against mitochondrial dysfunction and cardiac dysfunction in obese insulin-resistant rats.

One-hour post-load glucose levels are associated with hepatic steatosis assessed by transient elastography.

To examine the association between 1-hour plasma glucose (PG) concentration and markers of non-alcoholic fatty liver disease (NAFLD) assessed by transient elastography (TE). We performed TE in 107 metabolically well-characterized non-diabetic White individuals. Controlled attenuation parameter (CAP) was used to quantify liver steatosis, while liver stiffness marker (LS) was used to evaluate fibrosis. Controlled attenuation parameter correlated significantly with 1-hour PG (r = 0.301, P < 0.01), fasting insulin (r = 0.285, P < 0.01), 2-hour insulin (r = 0.257, P < 0.02), homeostasis model assessment index of insulin resistance (r = 0.252, P < 0.01), high-density lipoprotein cholesterol (r = -0.252, P < 0.02), body mass index (BMI; r = 0.248, P < 0.02) and age (r = 0.212, P < 0.03), after correction for age, sex and BMI. In a multivariable linear regression analysis, 1-hour PG (β = 0.274, P = 0.008) and fasting insulin levels (β = 0.225, P = 0.029) were found to be independent predictors of CAP. After excluding subjects with prediabetes, 1-hour PG was the sole predictor of CAP variation (β = 0.442, P < 0.001). In a logistic regression model, we observed that the group with 1-hour PG ≥ 8.6 mmol/L (155 mg/dL) had a significantly higher risk of steatosis (odds ratio 3.98, 95% confidence interval 1.43-11.13; P = 0.008) than individuals with 1-hour PG < 8.6 mmol/L, after correction for potential confounders. No association was observed between 1-hour PG and LS. Our data confirm that 1-hour PG ≥ 8.6 mmol/L is associated with higher signs of NAFLD, even among individuals with normal glucose tolerance, categorized as low risk by canonical diagnostic standards. TE is a safe low-impact approach that could be employed for stratifying the risk profile in these patients, with a high level of accuracy.

Fat Mass Accounts for Insulin Resistance Impact on Functional Decline and Mortality in Nondiabetic Older Adults

ObjectiveTo assess the potential role of body composition in the association of insulin resistance (IR) with functional decline and mortality in nondiabetic older persons. DesignLongitudinal population-based cohort of community-dwelling people from Toledo, Spain, aged 65 years or older. Setting and ParticipantsA total of 1114 nondiabetic persons from the Toledo Study of Healthy Aging cohort (mean age: 74.5, 56.10% female) with complete data at baseline were included. Only 914 participants had fully assessment of functional evaluation during the follow-up period. MethodsIR was determined by the homeostasis model assessment index (HOMA-IR) at baseline while frailty was assessed by the Frailty Trait Scale-5 (FTS-5) at baseline and after 2.99 years’ median follow-up period. A total of 319 participants experienced functional decline (2.5-point reduction in the FTS-5 score). A total of 143 deaths were recorded (6.31 years median follow-up) from the Spanish National Death Index. Body compositions were determined using dual-energy x-ray absorptiometry. Multivariate regression models analyzed the effect of HOMA-IR on outcomes, with age, sex, Charlson index, and number of medications included in the basic adjustment model. ResultsA 1-logaritmic unit increment in HOMA-IR increased the risk of functional decline after basic adjustment [odds ratio (95% confidence interval): 1.41 (1.09–1.83), P = .009]. This significant association was lost when further adjusted for total fat mass [1.14 (0.86–1.50)] and trunk fat mass [1.03 (0.77–1.37)], which accounted for 62.92% and 91.49% of the association. HOMA-IR was inversely associated with mortality risk [hazard ratio 0.66 (0.49–0.87), P = .0037], an association lost after adjustment for total fat mass [0.74 (0.55–1.01)] and trunk fat mass [0.80 (0.58–1.09)], accounting for 29.05% and 45.78% of the association. Adjustment by lean mass did not modify any of the associations. Conclusions and ImplicationsBody fat mass, especially in the trunk region, mediates the association of IR with functional decline and to a lesser extent with reduced risk of mortality in nondiabetic older subjects.

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

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

Cortisol secretion and abnormalities of glucose metabolism in nondiabetic patients with hypertension.

Glycometabolic changes are associated with hypercortisolism in Cushing's syndrome. Because impaired glucose tolerance (IGT) and insulin resistance are frequently detected in patients with essential hypertension, we hypothesized that in these patients, early glycometabolic abnormalities might be related to differences in regulation of cortisol secretion. In a cross-sectional study, we included 155 nondiabetic, essential hypertensive patients who were free of organ complications. The homeostasis model assessment (HOMA) index and the area under the curve of plasma glucose (AUC-glucose) and insulin (AUC-insulin) concentration following an oral glucose tolerance test were measured, together with daily plasma cortisol (8 a.m., 3 p.m. and 12 a.m.; AUC-cortisol) and 8 a.m. cortisol after 1 mg overnight dexamethasone suppression test (DST). IGT was present in 27% of patients who were older and had higher BMI, plasma triglycerides and uric acid, AUC-cortisol and DST-cortisol, and lower HDL-cholesterol. Frequency of IGT increased progressively across tertiles of DST-cortisol, together with levels of glycated hemoglobin, fasting insulin and C-peptide, HOMA-index, AUC-glucose, and AUC-insulin. AUC-cortisol and DST-cortisol were directly correlated with insulin, C-peptide, HOMA-index, AUC-glucose, and AUC-insulin. Multivariate regression analysis showed that DST-cortisol was directly and independently correlated with HOMA index, AUC-glucose, and AUC-insulin. In a logistic regression model, both AUC-cortisol and DST-cortisol independently predicted IGT. Daily cortisol and cortisol response to DST are independent determinants of IGT and insulin resistance in nondiabetic patients with hypertension, suggesting that even subtle differences in regulation of cortisol secretion might increase the risk of these patients to develop diabetes.

SAT077 Association Of Mitochondrial DNA With Type-2-diabetes, Glucose Level, And Insulin Resistance

Abstract Disclosure: M. Heydarpour: None. L. Pojoga: None. J.R. Romero: None. G.H. Williams: None. J.S. Williams: None. Background: Mitochondrial dysfunction leads to decreased Adenosine-3-phosphate (ATP) production and increased ROS production, leading to insulin resistance, and diabetes (T2D). Mutations in mitochondrial DNA (mtDNA) have been associated with increased ROS production. Current studies have shown a role for mtDNA variants in the pathogenesis of both T2D and insulin resistance. Despite both of these disorders are controlled by many features involving interplay between genetic and environmental factors, however amongst genetic factors, variations in mtDNA have shown a potential role in the risk of T2D. We analyzed the genomic influence of mtDNA on T2D, insulin resistance, and fasting plasma glucose in humans. Methods: Participants (113 cases with T2D and 303 controls) from the HyperPATH Cohort were selected and genotyped using a Multi-Ethnic-Genotyping-Array. Individuals consumed two study diets containing high (&amp;gt;200mEq/day) and low (&amp;lt;10mEq/day) sodium content for 7 days each. The Homeostasis Model Assessment (HOMA-IR) index was used to assess insulin resistance. We performed association analyses between 275 mitochondrial genetic markers (SNVs) and three outcomes (T2D, insulin resistance, and fasting plasma glucose) using PLINK program. Results: We identified 2 significant SNVs within mtDNA that associated with T2D after adjusting the model for sex, age, study site, and BMI. One SNV (rs2248727, OR=3.15, P=0.00035) was within the coding region of Cytochrome C Oxidase III (COX3) and another (rs2857284, OR=3.13, P=0.00037) within the coding region of NADH Dehydrogenase subunit 4 (ND4). Further, we identified 2 SNVs associated with fasting plasma glucose; rs28359176, beta=22.7, P=0.0006 in the coding region of NADH Dehydrogenase subunit 5 (ND5), and rs367951226 beta=22.7, P=0.0006) in the region of ATP Synthase membrane subunit 6 (ATP6). We also identified a significant signal (rs376888742, beta=5.61, P=6.09E-06) associated with insulin-resistance in the coding region of Cytochrome B (CYB). Conclusion: These results show a significant association between mitochondrial ND4 and COX3 gene variants with T2D and CYP with insulin resistance. Gene variants of mitochondrial ND5 and ATP6 were associated with increase plasma glucose. Presentation: Saturday, June 17, 2023

Red and golden tomato administration improves fat diet-induced hepatic steatosis in rats by modulating HNF4α, Lepr, and GK expression.

Nonalcoholic fatty liver disease (NAFLD), characterized by lipid accumulation within hepatocytes exceeding 5% of liver weight, is strongly related to metabolic disorders, obesity, and diabetes and represents a health emergency worldwide. There is no standard therapy available for NAFLD. Lifestyle intervention, including phytonutrient intake, is key in preventing NAFLD development and progression. We used a rat model of NAFLD to evaluate the effect of dietary supplementation with red tomato (RT) and golden tomato (GT)-a patented mix of fruit with varying degrees of ripeness and particularly rich in naringenin and chlorogenic acid-after steatosis development. We assessed the effects on body weight, metabolic profile, and hepatic steatosis. We found a correlation between the amelioration of all the parameters and the liver gene expression. Our results showed that, together with the reversion of steatosis, the consumption of RT and GT can cause a significant reduction in triglycerides, low-density lipoprotein-cholesterol, fasting glucose, and homeostasis model assessment index. Meanwhile, we observed an increase in high-density lipoprotein-cholesterol according to the amelioration of the general lipidic profile. Regarding hepatic gene expression, we found the upregulation of Gk and Hnf4α involved in metabolic homeostasis, Lepr involved in adipokine signaling, and Il6 and Tnf involved in inflammatory response. Taken together, our results suggest that dietary intake of red and golden tomatoes, as a nutraceutical approach, has potential in preventing and therapeutics of NAFLD.

Assessment of Serum Apelin Levels and Its Relation to Insulin Resistance in Acne Vulgaris Patients

Abstract Introduction Apelin is one of the adipokines. Acne vulgaris is a very common dermatological disease with a multifactorial background and hyperinsulinemia and insulin resistance are considered to play a pivotal role in its development and severity. Aim To evaluate serum apelin levels in acne vulgaris patients and to reveal the possible relation between its serum levels and the insulin resistance state in acne vulgaris patients. Material and methods Thirty-two acne vulgaris patients and thirty-two healthy controls were enrolled into the study. The blood levels of apelin, insulin and glucose were measured in patients and controls. Homeostasis model assessment index (HOMA-IR) was calculated to evaluate the insulin resistance state. Results Acne vulgaris patients experienced significant higher levels of fasting insulin, serum apelin, and HOMA-IR compared to controls. Conclusions These results suggest that serum apelin and insulin resistance may have a role in the pathogenesis of acne.

Insulin Resistance Is Associated With Reduced Capillary Permeability of Thigh Muscles in Patients With Type 2 Diabetes.

Insulin-mediated microvascular permeability and blood flow of skeletal muscle appears to be altered in the condition of insulin resistance. Previous studies on this effect used invasive procedures in humans or animals. The aim of this study was to demonstrate the feasibility of a noninvasive assessment of human muscle microcirculation via dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) of skeletal muscle in patients with type 2 diabetes (T2D). A total of 56 participants (46 with T2D, 10 healthy controls [HC]) underwent DCE-MRI of the right thigh at 3 Tesla. The constant of the musculature's microvascular permeability (Ktrans), extravascular extracellular volume fraction (ve), and plasma volume fraction (vp) were calculated. In T2D patients, skeletal muscle Ktrans was lower (HC 0.0677 ± 0.002 min-1, T2D 0.0664 ± 0.002 min-1; P = 0.042) while the homeostasis model assessment (HOMA) index was higher in patients with T2D compared to HC (HC 2.72 ± 2.2, T2D 6.11 ± 6.2; P = .011). In T2D, Ktrans correlated negatively with insulin (r = -0.39, P = .018) and HOMA index (r = -0.38, P = .020). The results signify that skeletal muscle DCE-MRI can be employed as a noninvasive technique for the assessment of muscle microcirculation in T2D. Our findings suggest that microvascular permeability of skeletal muscle is lowered in patients with T2D and that a decrease in microvascular permeability is associated with insulin resistance. These results are of interest with regard to the impact of muscle perfusion on diabetic complications such as diabetic sarcopenia.

Diabetic cardiac autonomic neuropathy: insulin resistance, lipid profile, and omega-3 polyunsaturated fatty acids

The significance of cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM) has been not fully appreciated and there is no unified treatment algorithm. Aim: The aim of study was to investigate the effects of -3 polyunsaturated fatty acids (-3 PUFAs) on blood lipid profile and insulin resistance (IR) parameters in patients with T2DM and definite CAN. The study involved 33 patients with T2DM and definite CAN. Patients were allocated into two treatment groups: 1st group - 15 patients received standard hypoglycaemic therapy - control (n = 15); 2nd group (n = 18) - standard hypoglycaemic therapy and 1 capsule/day of the ω-3 PUFAs (1 g, including 90 % ω-3 PUFAs) for three months. The concentrations of glucose, glycated haemoglobin A1c, immunoreactive insulin in the blood were determined. Lipid metabolism was assessed by the concentration of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) measurements. The insulin resistance Homeostasis model assessment, atherogenic coefficient (AC), TG/LDL-C, TG/TC, TG/LDL-C and TG glucose (TyG) index were calculated. Obtained results of our study could witness that the prescription of -3 PUFAs was accompanied by a statistically significant decrease in TG concentration; AC, TG/LDL-C, TG/TC, TG/LDL-C, TyG index parameters and increase in HDL-C levels (compared to control). Conclusions. Obtained results justify the appropriateness of -3 PUFAs prescriptions to patients with T2DM and definite CAN.

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

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

Positive effects of dietary supplementation with nutraceuticals on male subclinical hypogonadism: a pilot study.

Lifestyle modifications (i.e., physical activity [PA] and lower dietary intake) often are not sufficient to improve testosterone (TE) levels and promote weight loss in men with metabolic hypogonadism. The aim of the study was to investigate the effects of a nutraceutical formulation containing myoinositol, alpha lipoic acid, folic acid and SelectSIEVE® as add-on treatment to lifestyle modifications in improving obesity-related subclinical hypogonadism. Body composition, insulin resistance, testicular and erectile function were investigated in 15 males (age=39.5±14.5 years; Body Mass Index [BMI]=30.2±3.8 kg/m2, with subclinical hypogonadism (TE levels <14 and normal luteinizing hormone [LH]). After a run-in three months unsupervised PA period (T<inf>1</inf>), the nutraceutical supplement was administered two-times per day for three additional months (T<inf>2</inf>). BMI, the percentage fat mass, insulinemia and Homeostasis Model Assessment Index (P<0.01) along with glycemia (P<0.05) were significantly reduced at T<inf>2</inf> compared to T<inf>1</inf>, respectively; fat free mass (FFM) was significantly higher at T<inf>2</inf> compared to T<inf>1</inf> (P<0.01). Also, TE, LH and 5-item international index of erectile function score were significantly increased at T<inf>2</inf> compared to T<inf>1</inf> (P<0.01), respectively. The combination of unsupervised PA and nutraceutical supplement improves body composition, insulin sensitivity and TE production in overweight-obese men with metabolic hypogonadism. Further controlled studies in the long-term are warranted to elucidate potential changes in fertility.

Therapeutic exploration of polyherbal formulation against letrozole induced PCOS rats: A mechanistic approach

ObjectiveThis study aimed to develop an effective alternative medicine with multi potential herbs against polycystic ovarian syndrome (PCOS) in rats induced by letrozole treatment. Materials and methodPolyherbal syrup was prepared with a combination of S. asoca bark, G. sylvestre leaves, P. daemia aerial parts, C. zeylanium stem bark, C. bonduc seeds, and W. somnifera roots ethanolic extract. In vitro cell viability study, adenosine monophosphate-activated protein kinase (AMPK), and glucose transporter 4 (GLUT4) gene expression assay were carried out on the Chinese Hamster Ovarian (CHO) cell line. For the PCOS induction letrozole (1 mg/kg p. o.) was given for 21 consecutive days. The PCOS induction was confirmed by measuring estrus irregularity, insulin resistance by oral glucose tolerance test (OGTT), and hyperandrogenism by measuring serum total testosterone level 21 days after completion of letrozole treatment. After induction of PCOS, metformin (155 mg/kg p. o.), and polyherbal syrup (100 mg/kg, 200 mg/kg, and 400 mg/kg p. o.) were administered for further 28 days. The treatment efficacy was measured by measuring serum lipid profile, fasting insulin level, sex hormones level, ovarian steroidogenic enzymes, ovarian tissue insulin receptor, AMPK, and GLUT4 protein expression levels, and histomorphological studies. The post-treatment effect was confirmed by reproductive performance studies. ResultsLetrozole-induced PCOS rats showed significant estrus irregularity, abnormal sex hormones levels, and hyperandrogenism indicated by showing increased free androgenic index and decreased sex hormones binding globulin (SHBG) level. The insulin resistance in PCOS rats was indicated by increased fasting glucose levels with impaired glucose clearance in the OGT test. Homeostasis Model Assessment Index of Insulin Resistance (HOMA-IR) increased level, also decreases INSR, GLUT4, and AMPK mRNA expression in ovarian cells confirming the insulin resistance in PCOS rats. Ovarian histology in PCOS rats also showed many follicular cysts, atretic follicles, and the absence of corpus luteum. The administration of polyherbal syrup, in a dose-dependent manner, effectively restored these alterations. The treatment of polyherbal formulation 400 mg/kg possesses highly significant efficacy over the treatment of metformin in PCOS rats. It mainly acts by reducing peripheral and ovarian hyperandrogenism and improves insulin sensitivity via activating the insulin receptor and AMP-activated kinase-mediated transcription and translation of GLUT4 from the cytoplasm to the ovarian membrane improves glucose uptake and promotes the follicular development and ovulation. The higher fertility rate, delivery index, and survival of delivered pups confirm the broader and superior efficacy of PCOS. These beneficial actions are mainly attributable to the formulation's inclusion of the key secondary metabolites flavonoids and phytosterols. In conclusion, the prepared polyherbal syrup was found to be the safest and most effective alternative medicine for both endocrinal and metabolic complications of PCOS women.

Maximum Heart Rate- and Lactate Threshold-Based Low-Volume High-Intensity Interval Training Prescriptions Provide Similar Health Benefits in Metabolic Syndrome Patients

Exercise is an integral part of metabolic syndrome (MetS) treatment. Recently, low-volume high-intensity interval training (LOW-HIIT) has emerged as a time-efficient approach to improving cardiometabolic health. Intensity prescriptions for LOW-HIIT are typically based on maximum heart rate (HRmax) percentages. However, HRmax determination requires maximal effort during exercise testing, which may not always be feasible/safe for MetS patients. This trial compared the effects of a 12-week LOW-HIIT program based on: (a) HRmax (HIIT-HR), or (b) submaximal lactate threshold (HIIT-LT), on cardiometabolic health and quality of life (QoL) in MetS patients. Seventy-five patients were randomized to HIIT-HR (5 × 1 min at 80-95% HRmax), HIIT-LT (5 × 1 min at 95-105% LT) groups, both performed twice weekly on cycle ergometers, or a control group (CON). All patients received nutritional weight loss consultation. All groups reduced their body weight (HIIT-HR: -3.9 kg, p < 0.001; HTT-LT: -5.6 kg, p < 0.001; CON: -2.6 kg, p = 0.003). The HIIT-HR and HIIT-LT groups similarly, improved their maximal oxygen uptake (+3.6 and +3.7 mL/kg/min, p < 0.001), glycohemoglobin (-0.2%, p = 0.005, and -0.3%, p < 0.001), homeostasis model assessment index (-1.3 units, p = 0.005, and -1.0 units, p = 0.014), MetS z-score (-1.9 and -2.5 units, p < 0.001) and QoL (+10 points, p = 0.029, and +11 points, p = 0.002), while the CON did not experience changes in these variables. We conclude that HIIT-LT is a viable alternative to HIIT-HR for patients who are not able/willing to undergo maximal exercise testing.

Associations of Clusters of Cardiovascular Risk Factors with Insulin Resistance and Β-Cell Functioning in a Working-Age Diabetic-Free Population in Kazakhstan

Cardiovascular risk factors aggregate in determined individuals. Patients with Type 2 diabetes mellitus (T2DM) have higher cardiovascular This study aimed to investigate insulinresistance (IR) and β-cell function using the homeostasis model assessment (HOMA) indexes in a general Kazakh population and determine the effect he effect that cardiovascular factors may have on those indexes. We conducted a cross-sectional study among employees of the Khoja Akhmet Yassawi International Kazakh-Turkish University (Turkistan, Kazakhstan) aged between 27 and 69 years. Sociodemographic variables, anthropometric measurements (body mass, height, waist circumference, hip circumference), and blood pressure were obtained. Fasting blood samples were collected to measure insulin, glucose, total cholesterol (TC), triglycerides (TG), and high- (HDL) andlow-density lipoprotein (LDL) levels. Oral glucose tolerance tests were performed. Hierarchical and K-means cluster analyses were obtained. The final sample was composed of 427 participants. Spearmen correlation analysis showed that cardiovascular parameters were statistically associated with HOMA-β (p < 0.001) and not with HOMA IR. Participants were aggregated into the three clusters where the cluster with a higher age and cardiovascular risk revealed deficient β-cell functioning, but not IR (p < 0.000 and p = 0.982). Common and easy to obtain biochemical and anthropometric measurements capturing relevant cardiovascular risk factors have been demonstrated to be associated with significant deficiency in insulin secretion. Although further longitudinal studies of the incidence of T2DM are needed, this study highlights that cardiovascular profiling has a significant role not just for risk stratification of patients for cardiovascular prevention but also for targeted vigilant glucose monitoring.