Insulin Resistance Parameters Research Articles

Abstract PO2-08-10: Effect of 6 months of bazedoxifene + conjugated estrogens on body composition and insulin resistance

Abstract Menopause transition is often marked by an acceleration of visceral fat accumulation. Excess visceral fat is associated with insulin resistance and increased risk for breast cancer as well as heart disease and diabetes. We measured change in body composition (via iDXA), fasting insulin and glucose as part of an ongoing, Phase IIB trial (NCT04821141) of 6 months of bazedoxifene (BZA) + conjugated estrogen (CE) vs control with primary endpoints of change in mammographic density and breast tissue Ki-67. Participants are women ages 45-60 with vasomotor symptoms at increased risk for development of breast cancer. Methods: Visceral and total fat, lean, and total mass, were measured with iDXA (GE CoreScan™). Fasting plasma was assayed same day as drawn for total insulin using a chemiluminescence assay and glucose using a hexokinase method. Values generated were used to calculate HOMA IR (as a measure of insulin resistance) using the formula insulin µl/ml x glucose mg/dl/405. HOMA %S was calculated as 1/HOMA IR X100 as a measure of insulin sensitivity. Optimal HOMA IR is considered as ≤1; HOMA IR >1.5 is considered abnormal with >2.0 as evidence of insulin resistance. Optimal HOMA %S is 100%. Results: 24 women (12 BZA+CE, 12 Control) have completed baseline and 6-month body composition and insulin resistance assessments. Women randomized to BZA+CE were more likely to experience reduction in insulin resistance and improved insulin sensitivity despite a small weight gain over the initial 6 months. 7/12 randomized to BZA+CE had ≥15% reduction in HOMA IR vs only 2/12 controls. Three participants had HOMA IR >2 at baseline. Of these, one was randomized to BZA+CE and had a normal HOMA IR value at 6 months. The remaining two women were in the control group and saw no improvement in HOMA IR at 6 months. In addition, one woman randomized to control with normal HOMA-IR at baseline had HOMA IR > 2 at 6 months. Next Steps: The improvements in insulin resistance parameters with BZA+CE are similar to those observed in our rodent studies, supporting this combination as promising for use in breast cancer risk reduction in women with vasomotor symptoms at high-risk for metabolic disease. Citation Format: Carol Fabian, Adrian Zelenchuk, Kandy Powers, Amy Kreutzjans, Krystal Pittman, Bill Hendry, Christy Altman, Erin Giles, Katherine L. Cook, Stephen Hursting, Bruce Kimler. Effect of 6 months of bazedoxifene + conjugated estrogens on body composition and insulin resistance [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-08-10.

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) > 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 < 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 < 0.05. HDL-cholesterol (HDL-C) was significantly lower in subjects with insulin resistance, all with P < 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 < 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 < 0.05. Serum adiponectin demonstrated positive correlations with HDL-C and pNN50 (R = 0.329-0.473), all with P < 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 < 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 < 0.05. LDL-cholesterol (LDL-C) had negative correlations with percent fat and pNN50 (R = (-0.313)-(-0.340)), all with P < 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.

The effect of a combined lifestyle intervention with and without protein drink on inflammation in older adults with obesity and type 2 diabetes

BackgroundChronic low-grade inflammatory profile (CLIP) is one of the pathways involved in type 2 diabetes (T2D). Currently, there is limited evidence for ameliorating effects of combined lifestyle interventions on CLIP in type 2 diabetes. We investigated whether a 13-week combined lifestyle intervention, using hypocaloric diet and resistance exercise plus high-intensity interval training with or without consumption of a protein drink, affected CLIP in older adults with T2D. MethodsIn this post-hoc analysis of the PROBE study 114 adults (≥55 years) with obesity and type 2 (pre-)diabetes had measurements of C-reactive protein (CRP), pro-inflammatory cytokines interleukin (IL)-6, tumor-necrosis-factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1, anti-inflammatory cytokines IL-10, IL-1 receptor antagonist (RA), and soluble tumor-necrosis-factor receptor (sTNFR)1, adipokines leptin and adiponectin, and glycation biomarkers carboxymethyl-lysine (CML) and soluble receptor for advanced glycation end products (sRAGE) from fasting blood samples. A linear mixed model was used to evaluate change in inflammatory biomarkers after lifestyle intervention and effect of the protein drink. Linear regression analysis was performed with parameters of body composition (by dual-energy X-ray absorptiometry) and parameters of insulin resistance (by oral glucose tolerance test). ResultsThere were no significant differences in CLIP responses between the protein and the control groups. For all participants combined, IL-1RA, leptin and adiponectin decreased after 13 weeks (p = 0.002, p < 0.001 and p < 0.001), while ratios TNF-α/IL-10 and TNF-α/IL-1RA increased (p = 0.003 and p = 0.035). CRP increased by 12 % in participants with low to average CLIP (pre 1.91 ± 0.39 mg/L, post 2.13 ± 1.16 mg/L, p = 0.006) and decreased by 36 % in those with high CLIP (pre 5.14 mg/L ± 1.20, post 3.30 ± 2.29 mg/L, p < 0.001). Change in leptin and IL-1RA was positively associated with change in fat mass (β = 0.133, p < 0.001; β = 0.017, p < 0.001) and insulin resistance (β = 0.095, p = 0.024; β = 0.020, p = 0.001). Change in lean mass was not associated with any of the biomarkers. Conclusion13 weeks of combined lifestyle intervention, either with or without protein drink, reduced circulating adipokines and anti-inflammatory cytokine IL-1RA, and increased inflammatory ratios TNF-α/IL-10 and TNF-α/IL-1RA in older adults with obesity and T2D. Effect on CLIP was inversely related to baseline inflammatory status.

Efficacy of Integrated Ayurveda Treatment in Type 2 Diabetes mellitus with special reference to Prameha: A Randomised controlled Trial

Background: Diabetes mellitus (DM) is marked by persistent hyperglycemia, often due to insulin resistance. Type 2 diabetes mellitus (T2DM) constitutes 90% of cases and shares similarities with Prameha, a disorder characterized by frequent urination. Aims and objectives: This study aimed to compare Integrated Ayurveda Treatment (IAT) with standard diabetic treatment for Prameha. Materials and methods: A randomized, controlled open-label trial involved 200 T2DM subjects with HbA1C above 7%, taking metformin (≥1g /day). They were assigned to Standard Dietary Treatment (SDT) or IAT. SDT comprised metformin, dietary, and lifestyle modifications, while IAT included metformin with Ayurvedic medicine, specific Ayurveda diet, and yoga. Observation and result: Observations favoured Ayurveda treatment over standard diabetes treatment for most Prameha preliminary symptoms (purvarupa). Regarding Prameha rupa (symptoms), IAT significantly outperformed than SDT. Also, Ayurveda treatment group, led to improvements in HbA1C, fasting and postprandial blood sugar, and insulin resistance parameters compared to standard treatment group. Conclusion: Integrating Madhumeha ghana vati, ayurveda diet, and yoga with standard treatment yielded positive subjective and objective outcomes for Prameha, without significant adverse events. This suggests the potential benefits of combining Ayurvedic approaches with conventional care in managing prameha.

Adolescents diagnosed with polycystic ovary syndrome under the Rotterdam criteria but not meeting the diagnosis under the updated guideline.

What are the characteristics of adolescents diagnosed with polycystic ovary syndrome (PCOS) based on the 2003 Rotterdam criteria, but who do not meet the diagnosis according to the international evidence-based guideline? Adolescents who had features of PCOS but did not meet the evidence-based guideline adolescent criteria exhibited unfavorable metabolic profiles compared to controls and shared considerable metabolic and hormonal features with adolescents who did meet the adolescent criteria. The international evidence-based PCOS guideline recommended that ultrasound should not be used for the diagnosis of PCOS in girls with a gynecological age of <8 years. Thus far, few studies have evaluated the clinical characteristics of the girls diagnosed with PCOS based on the Rotterdam criteria but who do not meet the diagnosis according to the updated guideline. This is a retrospective study, and subjects attended for care from 2004 to 2022. Adolescent girls with PCOS diagnosed according to the 2003 Rotterdam criteria and healthy controls. All participants were between 2 and 8 years since menarche. Of the 315 girls diagnosed with PCOS according to the Rotterdam criteria, those with irregular menstruation (IM)/hyperandrogenism (HA)/polycystic ovary (PCO), IM/HA, HA/PCO, and IM/PCO phenotypes accounted for 206 (65.4%), 30 (9.5%), 12 (3.8%), and 67 (21.3%) participants, respectively. According to the evidence-based guideline, 79 girls (25.1%) with the HA/PCO or IM/PCO phenotypes were not diagnosed with PCOS, and aligned to the international guideline; they were designated as the 'at-risk' group. As expected, the girls meeting the evidence-based guideline adolescent criteria showed the worst metabolic profiles (degree of generalized or central obesity, frequency of insulin resistance, prediabetes or diabetes, and metabolic syndrome) and higher hirsutism scores than the at-risk group or controls. Approximately 90% of the at-risk group were not overweight or obese, which was similar to the controls. However, they showed worse metabolic profiles, with higher blood pressure, triglyceride, and insulin resistance parameters than controls; furthermore, these profiles were similar to those of the girls meeting the adolescent criteria. The at-risk group showed similarly elevated serum LH levels and LH/FSH ratio with the girls meeting adolescent criteria. We could not evaluate hormonal or ultrasound parameters in controls. Compared to the conventional Rotterdam criteria, the recent international evidence-based guideline-avoiding ultrasound in PCOS diagnosis in adolescents-still gives the opportunity to identify young girls at risk, aligned to the findings in this study. A practical approach to this adolescent population would involve establishing IM or HA (with ultrasound not indicated) and designating 'at-risk' PCOS status with regular check-ups for newly developed or worsening PCOS-related symptoms or metabolic abnormalities, with subsequent reassessment including ultrasound or anti-Müllerian hormone, once 8 years post-menarche. No funding was received in support of this study. The authors have no conflicts of interest to disclose. N/A.

Insulin Secretion Defect in Children and Adolescents with Obesity: Clinical and Molecular Genetic Characterization.

Childhood obesity is increasing worldwide and presents as a global health issue due to multiple metabolic comorbidities. About 1% of adolescents with obesity develop type 2 diabetes (T2D); however, little is known about the genetic and pathophysiological background at young age. The objective of this study was to assess the prevalence of impaired glucose regulation (IGR) in a large cohort of children and adolescents with obesity and to characterize insulin sensitivity and insulin secretion. We also wanted to investigate adolescents with insulin secretion disorder more closely and analyze possible candidate genes of diabetes in a subcohort. We included children and adolescents with obesity who completed an oral glucose tolerance test (OGTT, glucose + insulin) in the outpatient clinic. We calculated Matsuda index, the area under the curve (AUC (Ins/Glu)), and an oral disposition index (ISSI-2) to estimate insulin resistance and beta-cell function. We identified patients with IGR and low insulin secretion (maximum insulin during OGTT < 200 mU/l) and tested a subgroup using next generation sequencing to identify possible mutations in 103 candidate genes. The total group consisted of 903 children and adolescents with obesity. 4.5% showed impaired fasting glucose, 9.4% impaired glucose tolerance, and 1.2% T2D. Matsuda index and Total AUC (Ins/Glu) showed a hyperbolic relationship. Out of 39 patients with low insulin secretion, we performed genetic testing on 12 patients. We found five monogenetic defects (ABCC8 (n = 3), GCK (n = 1), and GLI2/PTF1A (n = 1)). Using surrogate parameters of beta-cell function and insulin resistance can help identify patients with insulin secretion disorder. A prevalence of 40% mutations of known diabetes genes in the subgroup with low insulin secretion suggests that at least 1.7% of patients with adolescent obesity have monogenic diabetes. A successful molecular genetic diagnosis can help to improve individual therapy.

Glycoprotein Acetyls Associate With Intraglomerular Hemodynamic Dysfunction, Albuminuria, Central Adiposity, and Insulin Resistance in Youth With Type 1 Diabetes

ObjectivesGlycoprotein acetyls (GlycA's) are biomarkers of systemic inflammation and cardiovascular disease, yet little is known about their role in type 1 diabetes (T1D). In this study we examined the associations among GlycA's, central adiposity, insulin resistance, and early kidney injury in youth with T1D. MethodsGlomerular filtration rate and renal plasma flow by iohexol and p-aminohippurate clearance, urine albumin-to-creatinine ratio (UACR), central adiposity by dual-energy x-ray absorptiometry, and estimated insulin sensitivity were assessed in 50 youth with T1D (16±3.0 years of age, 50% female, glycated hemoglobin 8.7±1.3%, T1D duration 5.7±2.6 years). Concentrations of GlycA were quantified by targeted nuclear magnetic resonance spectroscopy. Correlation and multivariable linear regression analyses were performed. ResultsGlycA's were higher in girls vs boys (1.05±0.26 vs 0.84±0.15 mmol/L, p=0.001) and in participants living with overweight/obesity vs normal weight (1.12±0.23 vs 0.87±0.20 mmol/L, p=0.0004). GlycA's correlated positively with estimated intraglomerular pressure (r=0.52, p=0.001), UACR (r=0.53, p<0.0001), and trunk mass (r=0.45, p=0.001), and inversely with estimated insulin sensitivity (r=−0.36, p=0.01). All relationships remained significant after adjustment for age, sex, and glycated hemoglobin. ConclusionsAs biomarker of inflammation, GlycA's were higher in girls and those with overweight or obese body habitus in T1D. GlycA's associated with parameters of early kidney dysfunction, central adiposity, and insulin resistance.

Effects of Administration of Bouillon Cubes on Insulin Resistance, Lipid Profile and Renal Function Parameters in Female Albino Rats

Aim: To evaluate the effects of administration of bouillon cubes on insulin resistance, lipid profile and renal function parameters in female albino rats. Methodology: A total of thirty-five (35) female albino rats, weighing between 120 and 150 grams, were used for the study. The bouillon cubes, Star Maggi and Knorr were administered daily to the rats, using an oral gavage tube for 90days. Fasting plasma glucose (FPG) was determined using the Glucose oxidase method. Fasting plasma insulin (FPI) and Cystatin C levels were quantitatively determined by a rat-specific sandwich-enzyme linked immunosorbent assay (ELISA) method. Insulin resistance was determined using the homeostatic model assessment for insulin resistance (HOMA-IR) method. The electrolytes, sodium (Na+) and potassium (K+) and were determined using ion selective electrode method. Urea was determined using Urease-bertholet method. Creatinine was determined using the Jaffe-Slot method. Total Cholesterol (TC), Triglyceride (TG) and High-Density Lipoprotein Cholesterol (HDL-C) were determined by enzymatic methods. Low Density Lipoprotein Cholesterol (LDL-C) was calculated from the Friedewald’s equation. Kidney sections were stained using haematoxylin and eosin (H&amp;E) staining technique. Quantitative analysis of monosodium glutamate (MSG) content of the bouillon cubes was analyzed using ultraviolet (UV) spectroscopy while the sodium content was analyzed using atomic absorption spectrophotometry according to the method of the American Public Health Association. Results: There were no significant differences (P&gt;.05) in FPG, FPI and HOMA-IR in all the treatment groups. The mean cystatin C value in group E (High Dose Knorr) was significantly higher (P &lt;.05) than the negative control and all other treatment groups. The results also show the mean sodium values in groups D (High Dose Maggi) and E (High Dose Knorr) were significantly lower (P &lt;.05) when compared to the negative control. There were no significant differences (P &gt;.05) in TC and HDL-C levels in the negative control, compared to the treatment groups. There were no significant differences (P &gt;.05) in TG levels, except for group B (Low Dose Maggi) which significantly lower (P &lt;.05) than the negative control. Also, there were no significant differences (P &gt;.05) in LDL-C levels, except for group B (Low Dose Maggi) which significantly higher (P &lt;.05) than the negative control. Histologic analysis of the kidneys of the treated groups showed histological changes in the architecture of the tissues indicating tissue distortion, acute tissue damage, glomerular nephritis and distorted capillaries and degeneration compared to the negative control group which showed no tissue distortion. Conclusion: Chronic exposure to bouillon cubes did not impact fasting plasma glucose, insulin and insulin resistance in the treated rats. Chronic administration of Knorr cubes impacted the integrity of the kidney as levels of cystatin C and sodium were altered in the albino rats. Histoarchitecture of the kidneys of the treated rats showed histological changes indicating tissue distortion, acute tissue damage, glomerular nephritis and distorted capillaries. Lipid profile/metabolism was relatively not affected by the administration of bouillon cubes.

Insulin resistance and CGM-derived parameters in people with type 1 diabetes: are they associated?

Insulin resistance (IR) is increasingly more prevalent in people with type 1 diabetes (T1D). We investigated whether IR is associated with continuous glucose monitor (CGM)-derived parameters (glucometrics) such as time in range (TIR), time above range (TAR), time below range (TBR) and glycaemic variability (CV). This is a retrospective analysis of two databases: IR was quantified according to the estimated glucose disposal rate (eGDR) (NCT04664036) and by performing a hyperinsulinaemic-euglycaemic clamp (HEC) (NCT04623320). All glucometrics were calculated over 28 days. A total of 287 subjects were included. Mean age was 46 ± 17 years, 55% were male, TIR was 57 ± 14% and eGDR was 7.6 (5.6 - 9.3) mg/kg min. The tertile of people with the lowest eGDR (highest level of IR) had a higher TAR compared to the tertile with the highest eGDR (39 ± 15% versus 33 ± 14, p = 0.043). Using logistic regression, a higher eGDR was associated with a higher chance to fall in a higher TIR- (OR 1.251, p < 0.001), a lower TAR- (OR 1.281, p < 0.001) and a higher TBR-tertile (OR 0.893, p = 0.039), adjusted for age, sex, diabetes duration, smoking status and alcohol intake. In the 48 people undergoing a HEC, no significant association between glucometrics and the HEC-determined glucose disposal rate (M-value) was observed. In people with T1D, an association between IR, measured by eGDR, and worse CGM profiles was observed.

Hormonal-metabolic trajectory of menopausal transition in a normoglycemic cohort of women with different blood pressure levels

Introduction. The gradual clustering of cardio-metabolic factors in women depending on age and decline of ovarian function justifies attention to the phenotype of the formation of the metabolic syndrome during the menopausal transition depending on the presence of hypertension without dysglycemia. Aim: to evaluate the association of indicators of the functional state of the pituitary-ovarian axis with markers of metabolic syndrome (MetS) and parameters of insulin resistance (IR) in a cohort of normoglycemic women aged 35-59 years with different levels of blood pressure (BP). Patients and methods. In a cohort of women 35–59 years old without dysglycemia (n = 88), 58 women had hypertension, 30 were normotensive. It was determined: body mass index (BMI), waist circumference (WC), levels of BP, triglycerides (TG), HDL-C, insulin, follicle-stimulating hormone (FSH) and estradiol, fasting glucose (FG); TyG and HOMA2-IR indices. Using SPSS (version 17) assessed the median (25; 75%); intergroup differences using the Mann-Whitney test; correlation analyzes: Spearman (R) and partial correlation (R рс ) to level out the influence of age. Results. In the general cohort of women, the influence of postmenopausal duration (PMD), FSH and E2 levels on MetS and TyG parameters depended on age, except for the correlation of PMD with FG (R pc = 0.313; p = 0.004). The range of associations of MetS markers with each other and TyG in the group of patients with hypertension is similar to those in the general cohort of women. In both cohorts, the interrelations between FG, OT, insulin and TyG remained relevant with partial correlation. The TyG index, associated with HOMA2-IR (R=0.600; p&lt;0.001; R pc =0.426; p&lt;0.001), had a greater range of connections with MetS components, as well as with FSH (R=0.312; p=0.017; R pc =0.286; p=0.030) and E2 (R= -0.393; p=0.002; R pc = -0.376; p=0.004) in the presence of hypertension. Conclusion. The influence of indicators of the functional state of the pituitary-ovarian axis on MetS and TyG markers was revealed, along with a spectrum of associations of parameters and factors in the formation of menopausal MetS with IR indices, especially TyG. Correlation relations between FG with PMD and MetS components, as well as estradiol in case of hypertension, reflect a high risk of progression to dysglycemia.

Autologous intraarterial pancreatic bone-marrow mononuclear cells infusion in T2D patients: Changes on beta-cells function, insulin resistance, and inflammatory marker

BackgroundType 2 diabetes (T2D) is a progressive disease. Many drugs currently being used for the management of T2D have minimal effect on pancreatic beta cells regeneration. Cell-based therapies might provide potential benefits in this aspect. MethodsA pilot study in five T2D patients with 12 months follow-up was performed to evaluate the effect of autologous bone marrow mononuclear stem cells (BM-MNCs) infusion into pancreatic arteries on the insulin requirement, beta-cell function, insulin resistance, and systemic inflammatory marker (CRP). ResultsThe primary endpoint, a 50 % reduction of total insulin doses from baseline, was not achieved in this study. However, a trend of increasing fasting C-peptide (p = 0.07) and C-peptide 60′ (p = 0.07) and 90′ (p = 0.07) after a mixed-meal tolerance test was observed 12 months post-infusion compared to baseline levels. A similar result was observed for the homeostatic model assessment of beta cell function (HOMA1-B), an index for beta cell function. No improvement was observed for insulin resistance measured by homeostasis model assessment of insulin resistance (HOMA1-IR) and systemic inflammatory parameter. ConclusionIntraarterial pancreatic autologous BM-MNCs infusion might potentially improve beta cell function in T2D patients, although further study is needed to confirm this finding.

Altered Placental Insulin Signaling in the Absence of Systemic Insulin Resistance in Hypertensive Disorders of Pregnancy among South Indian Tamil Population

A cross sectional study was conducted to explore the possible derangements in placental insulin signaling and also to investigate the presence or absence of maternal systemic insulin resistance in different types of hypertensive disorders of pregnancy (HDP). Study Design: Healthy pregnant women (n=32) and pregnant women with gestational hypertension (GH) (n=18), late onset Pre-eclampsia (LP) (n=18) and early onset Pre-eclampsia (EP) (n=19) were recruited for the study. Maternal venous blood and placental samples were collected from the study subjects at 35±7 weeks of gestation. Insulin resistance parameters such as fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, beta cell function and insulin sensitivity and glycated hemoglobin were estimated in the maternal venous blood samples. Placental protein expressions of insulin signaling molecules were analyzed by western blotting method. Results: Maternal venous blood insulin resistance parameters were not significantly different between the study groups. However, placental content of phospho insulin receptor beta was significantly decreased in GH, LP and EP groups in comparison to controls. We also found a significant decrease in placental protein expression of phosphatidyl inositol 3-kinase p85 alpha in LP group when compared to other groups.

Protective Effect of Hydroalcoholic Extract of Punica granatum Leaves on High Fructose Induced Insulin Resistance in Experimental Animals.

Insulin resistance (IR) is a condition characterized by reduced sensitivity of body tissues to insulin, leading to impaired regulation of downstream metabolic pathways and elevated blood glucose levels. Diets rich in fructose have been proven to cause insulin resistance in test rats, resulting in decreased insulin sensitivity, particularly in the liver, and compromised disposal of glucose from the body. In the search for effective treatments, Plant-derived formulations have gained popularity because to their ability for treating a variety of ailments. One such plant is Punica granatum Linn. from the Punicaceae family, which has long been used in the treatment of diabetes and its consequences. This study investigates the insulin-resistant activity of an extract from Punica granatum leaves. The study goal is to assess the possible protective role of Punica granatum against insulin resistance through various analyses, including serum glucose and insulin levels, lipid profile assessment, measurement of liver enzymes (ALP, SGOT, SGPT), and histopathological examination of liver sections. The study involves several key methods to evaluate the insulin-resistant activity of Punica granatum extract in high fructose diet induced insulin resistance animal model. The extract was administered orally to the experimental animals. These methods include the measurement of serum glucose and serum insulin levels, analysis of the lipid profile, quantification of liver enzymes such as ALP, SGOT, and SGPT, and a detailed histopathological examination of liver tissue sections. These analyses collectively provide insights into the impact of Punica granatum extract on insulin resistance and related metabolic parameters. Findings of this study provide insight on the possible benefits of Punica granatum extract on insulin resistance. Through the assessment of serum glucose and insulin levels, lipid profile analysis, and measurement of liver enzymes, the study elucidates the impact of the extract on key metabolic indicators. Additionally, the histopathological examination of liver sections provides visual insights into the structural changes that may occur as a result of the treatment. In conclusion, this study highlights the ability of Punica granatum extract as a candidate for addressing insulin resistance. The findings suggest that the extract may have a protective role against insulin resistance, as evidenced by improvements in serum glucose and insulin levels, lipid profile, liver enzyme levels, and histopathological characteristics. Further research and investigations are warranted to fully understand the mechanisms underlying these observed effects and to validate the potential of Punica granatum extract as a therapeutic option for managing insulin resistance and its associated complications.

Beneficial Effects of RESMENA Diet on Anthropometric, Metabolic, and Reproductive Profile in Adolescents with Obesity and Polycystic Ovary Syndrome: A Randomized Controlled Intervention Study

Introduction: The optimal dietary strategy to improve the metabolic and reproductive endocrine profile in adolescents with obesity and polycystic ovary syndrome (PCOS) is undefined. This study was conducted to evaluate the efficacy of the MEtabolic Syndrome REduction in NAvarra (RESMENA) diet versus a control diet based on American Heart Association (AHA) recommendations for the treatment of PCOS in adolescents with PCOS. Methods: A total of 40 adolescents diagnosed with PCOS between the ages of 13–18 years were randomized to either a RESMENA or control diet for 6 months. Dietary status, anthropometry, body composition, biochemical parameters, and reproductive endocrine hormones were compared between the 2 groups before and after the intervention. Results: Both diet groups showed significant decreases in anthropometric parameters, whereas the RESMENA diet provided a greater decrease in all these parameters except neck circumference and fat percentage (p p p Conclusions: Both dietary patterns resulted in significant improvement in anthropometric measurements and body composition, but the RESMENA diet showed beneficial effects on insulin resistance parameters and androgen levels.

Serum MMP3 Correlates with Renal Function Tests and Insulin Resistance Parameters in Patients with End-stage Renal Disease

End-stage renal disease (ESRD) is associated with changes in serum biomarkers. However, except for the renal function test, there is no definite useful biomarker correlated with the disease and its consequences, such as insulin resistance (IR). In the present study, matrix metalloproteinases-3 (MMP3) and its inhibitor, the tissue inhibitor of metalloproteinase-1 (TIMP1) were examined and correlated with IR parameters. MMP3, TIMP1, renal function tests, and IR parameters were measured in 60 ESRD patients and the results were compared with thirty healthy controls. After controlling for all cofounders, ESRD patients showed a substantial rise in serum MMP3, glucose, insulin, and beta-cell function percentage compared to the control group. While the patients had a lower insulin sensitivity percentage when compared to the controls. TIMP1, insulin/glucose ratio, and insulin resistance index did not vary significantly across groups. MMP3 had a strong relationship with serum creatinine, urea, and eGFR. TIMP1 had a strong relationship with height and weight. High serum MMP3 is associated with increased renal function tests and with changes in the IR parameters in ESRD patients.

Fenofibrate alleviates insulin resistance by reducing tissue inflammation in obese ovariectomized mice

BackgroundFenofibrate is a hypolipidemic peroxisome proliferator-activated receptor α (PPARα) agonist used clinically to reduce hypercholesterolemia and hypertriglyceridemia.ObjectiveWe investigated the effects of fenofibrate on insulin resistance and tissue inflammation in a high-fat diet (HFD)-fed ovariectomized (OVX) C57BL/6J mice, a mouse model of obese postmenopausal women.MethodsFemale OVX mice were randomly divided into 3 groups and received a low-fat diet, an HFD, or an HFD supplemented with 0.05% (w/w) fenofibrate for 9 weeks. Parameters of insulin resistance and tissue inflammation were measured using blood analysis, histological analysis, immunohistochemistry, and quantitative real-time polymerase chain reaction.ResultsWhen fenofibrate was administered to HFD-fed OVX mice for 9 weeks, we observed reductions in body weight gain, adipose tissue mass, and the size of visceral adipocytes without the change of food intake. Fenofibrate improved mild hyperglycemia, severe hyperinsulinemia, and glucose tolerance in these mice. It also reduced pancreatic islet size and insulin-positive β-cell area to levels similar to those in OVX mice fed a low-fat diet. Concomitantly, administration of fenofibrate not only suppressed pancreatic lipid accumulation but also decreased CD68-positive macrophages in both the pancreas and visceral adipose tissue. Treatment with fenofibrate reduced tumor necrosis factor α (TNFα) mRNA levels in adipose tissue and lowered serum TNFα levels.ConclusionThese results suggest that fenofibrate treatment attenuates insulin resistance in part by reducing tissue inflammation and TNFα expression in HFD-fed OVX mice.

Fibroblast Growth Factor 21 in Gestational Diabetes Mellitus and Type 2 Diabetes Mellitus.

Women who develop GDM present a metabolic condition similar to that found in type 2 diabetes, characterized by impaired insulin response. Due to similar pathophysiologic mechanisms found between type 2DM and GDM, there is a great interest in finding markers that will lead to the understanding of a possible common origin to both diseases. The aim of this study was to determine serum FGF21 levels in 2DM and GDM and its correlation with selected metabolic parameters. The study included 54 2DM patients and 52 nondiabetic individuals (control group 1) as well as 74 GDM women and 32 healthy pregnant controls (control group 2). Serum FGF21 was determined by enzyme-linked immunosorbent assay (ELISA), in all groups, and correlated with biochemical parameters of glucose metabolism and insulin resistance (HbA1c, HOMA index, TG, and HDL cholesterol). FGF21 concentration was significantly higher in 2DM as compared with control group 1 (p < 0.01). In the 2DM group, FGF21 was positively correlated with HOMA index (p = 0.022, R = 0.398). In the GDM group, the positive relationships with FGF21 were observed with glucose (p = 0.020, R = 0.264) and TG (p = 0.013, R = 0.283) while HDL-C levels were correlated negatively (p = 0.004, R = -0.326). Serum FGF21 levels were significantly higher in 2DM patients than those without diabetes. Moreover, serum FGF21 levels were associated with selected metabolic parameters, suggesting that it may play acrolein glucose and lipid metabolism.

The Ratio of Monocytes to HDL-Cholesterol Is Associated with Cardiovascular Risk and Insulin Resistance in Patients with Rheumatoid Arthritis.

The monocytes to high-density lipoprotein (HDL)-cholesterol ratio (MHR) indicates inflammation based on the anti-inflammatory properties of HDL-cholesterol as well as the pro-inflammatory effect of monocytes. Several studies have investigated MHR in various disorders, specifically in cardiovascular diseases. Consequently, MHR has been significantly associated with cardiovascular and all-cause mortality in the general population, regardless of established risk factors. However, its role in the augmented risk of cardiovascular disease found in rheumatoid arthritis (RA) has not been studied to date. This is a cross-sectional study that encompassed 430 patients with RA and 208 controls matched by sex and age. Complete blood cell count and complete lipid profile were evaluated. Multivariable analysis was made to analyze the relationship between MHR and RA disease and features subclinical carotid atherosclerosis, and traditional CV factors including insulin resistance and beta cell function indices. MHR values did not differ between controls and patients after multivariable adjustment (12 ± 6 vs. 11 ± 6, p = 0.18). No relationship between this ratio and the characteristics of the disease was found excluding ESR, which showed a significant and positive association with MHR after adjustment for covariates. MHR significantly correlated with Systematic Coronary Risk Evaluation-2 (SCORE2) cardiovascular risk algorithm, and insulin resistance and beta cell function parameters after adjustment. In conclusion, MHR does not differ between patients with RA and controls. The relationship of this biomarker with disease-related data is poor. However, MHR is highly and positively related to cardiovascular risk and insulin resistance in RA.

B-218 Role of Delta Tocotrienol and Resveratrol Supplementation in Regulation of Micro RNAs in Patients With Metabolic Syndrome: A Randomized Controlled Trial

Abstract Background Micro-RNAs (miRNAs) are involve in the regulation of central obesity, insulin resistance, inflammation and dyslipidemia in development of MetS. δ-tocotrienol and resveratrol improve the insulin resistance, inflammation and clinico-biochemical parameters in the patients with MetS. Objective To determine the effect of δ-tocotrienol and Resveratrol Mixture (TRM) supplementation for 24 weeks in comparison with placebo, on the relative expression of metabolic related miR-130b, miR-221, miR-15b-, miRNA-122, and miR-376b in the patients with MetS. Methods This randomized placebo-controlled trial was conducted at AFIP, NUMS, Pakistan. A total of 82 adult MetS patients, aged 18 to 60 years of both genders, were enrolled and randomly grouped into TRM (n = 41) and Placebo (n = 41). The TRM group was given 400 mg capsules of (δ-tocotrienol 250 mg; Resveratrol 150 mg), and placebo received 400 mg cellulose capsules twice daily for 24 weeks. miRNA was extracted by Trizole L S reagent with cel-miR-39 (Spike-In control). The cDNA was prepared by Reverse Transcriptase Kit. miRNAs expression profile was done by using qRT-PCR Kit (Qiagen) protocol on the Rotor-Gene. Results The TRM supplementation significantly (P &amp;lt; 0.001) upregulated miR-130b-5p (3.05fold), miR-221-5p (2.45fold), and downregulated miR-122-5p by 2.22fold as compared to placebo after 24 weeks. No significant difference was observed in miR-15b-5p and miR-376b-5p. Furthermore, patients in the TRM group had significant (P &amp;lt; 0.05) correlation in improvement of MetS biomarkers and miRNAs including hs-CRP, miR-130b; miR-221, TNF-α; miR-221, fasting plasma glucose, miR-122, triglyceride and miR-130b with waist circumference. No significant side effect was reported. Conclusion TRM daily supplementation in addition to dietary restriction, is effective in the improvement of the metabolic syndrome components by upregulation of miR-130b-5p involve in central obesity, inflammation; miR-221-5p by decreasing insulin resistance and downregulation of miRNA 122 to improve dyslipidemia in the patients with MetS.

Maternal Tryptophan Catabolites and Insulin Resistance Parameters in Preeclampsia.

Preeclampsia (PE) is a pregnancy-related disorder characterized by high blood pressure and proteinuria in the third trimester. The disease is associated with many metabolic and biochemical changes. There is a need for new biomarkers for diagnosis and follow-up. The present study examined the diagnostic ability of tryptophan catabolites (TRYCATs) and insulin resistance (IR) parameters in women with PE. This case-control study recruited sixty women with preeclampsia and 60 healthy pregnant women as a control group. Serum levels of TRYCATs (tryptophan, kynurenic acid, kynurenine, and 3-hydroxykynurenine) and IR parameters (insulin and glucose) were measured by ELISA and spectrophotometric methods. The results showed that PE women have a significantly lower tryptophan level than healthy pregnant women. However, there was a significant increase in kynurenic acid, kynurenic acid/kynurenine, kynurenine/tryptophan, and 3-hydroxykynurenine levels. PE women also have a state of IR. The correlation study indicated various correlations of IR and TRYCATs with clinical data and between each other, reflecting the role of these parameters in the pathophysiology of PE. The ROC study showed that the presence of IR state, reduced tryptophan, and increased 3-HK predicted PE disease in a suspected woman with moderate sensitivities and specificities. In conclusion, the pathophysiology of PE involves a state of IR and an alteration of the TRYCAT system. These changes should be taken into consideration when PE is diagnosed or treated.