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OBJECTIVES Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-Reactive Protein (CRP) are markers of inflammation that are elevated in bipolar disorder (BD) and are also related to a higher risk of metabolic syndrome (MetS). This study aimed at investigating for the first time the association between NLR, PLR, and CRP and the metabolic status in BD. METHODS We assessed the association between biomarkers and the metabolic status: number of metabolic risk factors, presence of MetS, insulin sensitivity (Quantitative Insulin Sensitivity Check Index, QUICKI) and insulin resistance (Homeostatic Model Assessment for Insulin Resistance, HOMA-IR index), in a sample of 219 outpatients with BD. RESULTS 25.9% of the sample met the criteria for MetS. High levels of CRP were found in 12% of the sample. Older age, low PLR, high NLR, and high CRP levels significantly predicted a higher number of MetS risk factors (p

Ketotic dairy cows exhibit a state of negative energy balance (NEB) characterized by elevated circulating levels of β-hydroxybutyrate (BHB) and fatty acids. Impaired hepatic insulin signaling in dairy cows occurs frequently during the transition into lactation, but its role on liver function during this period is not well known. In nonruminants, endoplasmic reticulum (ER) stress is a causal factor contributing to impaired insulin signaling in the liver. Thus, the aim of this study was to investigate the status of hepatic insulin and ER stress signaling and whether ER stress contributes to impaired insulin signaling in dairy cows with ketosis. Healthy (control cows, n = 10, BHB ≤0.6 mM) and ketotic (ketotic cows, n = 10, BHB ≥1.2 mM) cows at 3 to 10 d in milk were selected for liver biopsy and blood sampling before feeding. In vitro experiments were conducted with isolated hepatocytes from 5 healthy calves (1 d old, fasted female, 30-40 kg of body weight). Treatments included BHB (0, 0.9, 1.8, 3.6 mM), tauroursodeoxycholic acid (TUDCA, a canonical inhibitor of ER stress), and different incubation times (0.5, 1, 2, 3, 5, 7, 9, or 12 h). Ketotic cows had lower daily milk yield (median: 29.50 vs. 23.00 kg), higher plasma nonesterified fatty acid (NEFA) (median: 0.33 vs. 1.17 mM), BHB (median: 0.43 vs. 3.22 mM), aspartate aminotransferase (median: 70.58 vs. 155.70 U/L), alanine aminotransferase (median: 18.31 vs. 37.90 U/L), lower plasma glucose (median: 4.32 vs. 2.37 mg/dL), and revised quantitative insulin sensitivity check index (median: 0.39 vs. 0.37) compared with healthy cows. Increased abundance of phosphorylated insulin receptor substrate-1 (IRS1) and decreased abundance of phosphorylated protein kinase B (AKT) and glycogen synthase kinase-3β (GSK3β) in ketotic cows indicated a state of insulin resistance. In addition, abundance of phosphorylated protein kinase RNA-like ER kinase (PERK) and inositol requiring protein-1α (IRE1α), and cleavage of activating transcription factor-6 (ATF6) were greater in the liver of ketotic cows. In vitro, at the early stages of incubation, treatment with BHB upregulated abundance of phosphorylated of IRE1α, PERK, and the cleavage of ATF6, as well as several unfolded protein response genes [X-box-binding protein-1 (XBP1), 78 kDa glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP)]. Furthermore, in response to increasing doses of BHB, the phosphorylation level of PERK, IRE1α, and the cleavage of ATF6, and the abundance of XBP1, GRP78, and CHOP increased. In addition, BHB treatment increased phosphorylation of IRS1 and decreased phosphorylation of AKT and GSK3β, and upregulated abundance of gluconeogenic genes (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase). Importantly, these changes were reversed by inhibiting ER stress with TUDCA treatment. Overall, the present study indicated that reversing ER stress during ketosis might help alleviate hepatic insulin resistance. Targeting ER stress may represent a potential therapeutic target for controlling the negative aspects of ketosis on liver function.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. Insulin resistance and dyslipidemia are linked to PCOS. l-Carnitine supplementation as a management strategy for women with PCOS has been proposed. The effect of l-carnitine supplementation on insulin resistance, sex hormone-binding globulin (SHBG) and lipid profile in overweight/obese women with PCOS was investigated. This randomized, double-blind, controlled clinical trial, was conducted on 62overweight/obese women with PCOS. Participants were randomly assigned into two groups to receive 1000 mg/day l-carnitine or placebo (1000 mg starch) for 12 weeks. l-Carnitine supplementation compared to the placebo showed a significant improvement in insulin [− 0.7 (− 7.3 to 4.0) vs. 0.7 (− 3.0 to 5.2); P = 0.001], homeostatic model assessment for insulin resistance [− 0.4 (− 1.7 to 1.1) vs. 0.0 (− 0.7 to 1.3); P = 0.002], quantitative insulin sensitivity check index (+ 0.01 ± 0.02 vs. − 0.01 ± 0.01; P = 0.02) and a non-significant change toward improvement in SHBG (+ 11.5 ± 40.2 vs. − 3.2 ± 40.2; P = 0.2). However, there was no significant differences between the two groups in serum levels of fasting plasma glucose, total cholesterol, triglyceride, low density lipoprotein-cholesterol and high density lipoprotein cholesterol (P > 0.05). 12-week l-carnitine supplementation in overweight or obese women with PCOS ameliorate insulin resistance, but has no effect on SHBG and lipid profile. Studies with higher dosages and duration of l-carnitine intake are required. The trial was registered on 30 December 2019 at Iranian Registry of Clinical Trials IRCT20191016045131N1. Registered on 30th December 2019 at Iranian Registry of Clinical Trials (IRCT20191016045131N1).

This review aims to evaluate if there are clinical benefits of curcumin (CUR) in patients with polycystic ovary syndrome (PCOS). Electronic databases (PubMed, EMBASE, Scopus, Web of Science, Cochrane Central, and Google Scholar) were systematically searched to identify only randomized clinical trials (RCTs) that assessed CUR in patients with PCOS from inception to May 5, 2021. Five RCTs were included with a total of 296 patients, with 148 among the CUR groups and 148 patients among the control group. Revised Cochrane risk-of-bias tool for randomized trials was used to assess the risk of bias, three RCTs provided a low risk of bias and two provided a high risk of bias. Compared with the control group, CUR was associated with a statistically significant improvement in the glycemic control including fasting blood glucose (MD = -3.67; 95% CI = [-5.25, -2.08], p < .00001), insulin level (MD = -1.91; 95% CI = [-2.97, -0.84], p = .0005), homeostasis model assessment of insulin resistance (MD = -0.55; 95% CI = [-0.83, -0.27], p = .0001), and quantitative insulin sensitivity check index (MD = 0.01; 95% CI = [0.00, 0.02], p = .0005). The mean difference in total cholesterol was also statistically significant (MD = -15.55; 95% CI = [-30.33, -0.76], p < .04). The rest of the secondary outcomes, including LDL, HDL, sex hormone, body weight, and CRP, were not statistically significant. This review concluded that among patients with PCOS, the use of CUR demonstrated a significant difference from the control group for glycemic control. Those findings suggest that CUR confers clinical benefits in patients with PCOS. However, due to the limited number of the included studies, further high-quality studies are needed to establish the clinical efficacy of the CUR.

This experiment aimed to investigate the correlations between surrogate indices of insulin resistance (IR)—namely, the homeostasis model of IR, the quantitative insulin sensitivity check index, and the revised quantitative insulin sensitivity check index—and measures of IR obtained from an intravenous glucose tolerance test (IVGTT) performed in early-lactation dairy goats. Saanen goats (n = 26) with varying levels of milk production (1.7–4.8 kg/d) were selected and underwent an IVGTT on 43 ± 0.7 d postpartum (mean ± standard deviation). Data from the IVGTT were fitted in the minimal model to calculate parameters of glucose–insulin dynamics such as insulin sensitivity index and acute insulin response to glucose. Surrogate indices were computed using the average of the IVGTT basal samples. Correlation analysis revealed no relationship between surrogate indices of IR and measures of IR derived from the IVGTT (e.g., insulin sensitivity index, glucose clearance rate, glucose area under the curve). Therefore, our results suggest that surrogate indices of IR are not suitable for assessing the insulin sensitivity of peripheral tissue in early-lactation goats.

Context Insulin resistance (IR) and abnormal insulin secretion play a key role for the development of type 2 diabetes mellitus (DM). Aims We investigated the surrogate markers of IR, i.e., Homeostasis Model Assessment (HOMA), Quantitative Insulin Sensitivity Check Index (QUICKI), McAuley, and Fasting Insulin Resistance Index (FIRI) in type 2 DM patients. Also, fasting insulin (FI) levels were estimated in type 2 diabetics. Further, the correlation of FI with other surrogate markers of IR in type 2 DM was done. Settings and Design A hundred newly diagnosed patients with type 2 DM from Malwa population, Punjab, were considered for evaluation. Another 100 healthy individuals (age and sex-matched) were examined as controls. Methods and Material Fasting blood glucose, FI, and lipid profile were estimated, and IR was calculated using McAuley index (McA), HOMA, QUICKI, and FIRI. Statistical Analysis Used The statistical analysis was performed on the above-mentioned clinical interpretations. The Cohen’s kappa test was used to affirm the agreement. Results FI levels in patients with type 2 diabetes were significantly higher (20.8 ± 9.05 µIU/L) than controls (7.93 ± 1.01 µIU/L). IR by surrogate markers was found significant in the study group. The 76% patients with type 2 diabetes ended up as resistant to insulin by FI measurement, almost equivalent to McA, 80%; HOMA, 88%; FIRI, 88%; and QUICKI, 90%. A notable correlation was highlighted between FI and McA manifesting IR (p < 0.01, r = −0.85). We calculated the statistical correlation of FI with HOMA, QUICKI, and FIRI indices (p < 0.01, r = 0.93; p < 0.01 r = −0.92; and p < 0.01, r = +0.93, respectively). The agreement visible from Cohen’s kappa test also affirms the same (k = 0.9 for McA). Conclusion We concluded that all the surrogate markers for IR were specific when compared with FI, but in terms of sensitivity McA was found to be more sensitive as it includes markers of dyslipidemia, which is the precipitating factor of metabolic derangements so as the IR in type 2 DM.

OBJECTIVE There is a paucity of data on the relations of insulin resistance with incident blood pressure (BP) changes among Blacks. We investigated the associations of insulin resistance and metabolic syndrome (MetS) with BP progression in a community-based sample of African Americans. METHODS We analyzed 1064 participants without hypertension at baseline (2000-2004) who attended at least one follow-up visit in 2005-2008 or 2009-2013. Four insulin resistance indices [fasting insulin, insulin-to-glucose ratio (IGR), homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI)] and MetS (excluding hypertension in the definition) were assessed at baseline. Robust Poisson regression was used to generate risk ratios (RRs) and 95% confidence intervals (CI) for BP progression and incident hypertension. RESULTS Over a median of 7 years, 69.6% progressed to a higher BP category and 62.7% developed hypertension. After multivariable adjustment, participants in the highest quartile of HOMA-IR had higher risks of BP progression [RR 1.25 (95% CI 1.09-1.43), Ptrend = 0.004] and hypertension [RR 1.35 (95% CI 1.16-1.58), Ptrend

Background Some studies have investigated the relationship between Behcet's disease (BD) and insulin resistance; however, since they did not exclude obese patients from their sample, it remains unclear whether BD itself causes insulin resistance independently of obesity. Methods The study included 60 patients with BD and 45 age-, gender-, and body mass index (BMI)-matched healthy controls. Obese patients with a BMI of ≥30 kg/m² were excluded. Insulin resistance according to the homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI), fasting plasma glucose, and one-hour and two-hour plasma glucose in the oral glucose tolerance test (OGTT 1-h and OGTT 2-h PG, respectively) were evaluated in all patients. Results The mean fasting plasma glucose levels and the rate of those with impaired glucose tolerance according to OGTT 2-h PG were significantly higher in the BD patients compared to the controls. The rates of those with insulin resistance according to HOMA-IR and QUICKI were significantly higher in the BD patients than in the controls. When compared to the control group, the rates of those with impaired fasting glucose and impaired glucose tolerance were significantly higher, and the mean QUICKI value was significantly lower in the active group, in contrast to the inactive group. Conclusions Insulin resistance occurs in BD patients independently of obesity. In the follow-up of BD patients, especially in the active phase, not only fasting blood glucose but also other diagnostic tests for insulin resistance should be added to the examination panels.

BACKGROUND: Long-haul truck drivers are disproportionately exposed to metabolic risk; however, little is known about their metabolic health and the role of physical activity and other risk factors in metabolic outcomes. OBJECTIVE: This study compares truck drivers’ insulin sensitivity, and associations between metabolic risk factors and insulin sensitivity, with those of the general population. METHODS: Survey, anthropometric, and biometric data were collected from 115 long-haul truckers, which were then compared to the general population data using the National Health and Nutrition Examination Survey (NHANES) dataset. The quantitative insulin sensitivity check index (QUICKI) was used to estimate insulin sensitivity. RESULTS: Truck drivers had lower QUICKI scores than the general population cohort. Sagittal abdominal diameter and exercise were predictive for QUICKI among combined cohorts. Waist circumference and perceived health were more predictive for QUICKI among truck drivers, and sagittal abdominal diameter and income were more predictive for QUICKI among the general population. CONCLUSIONS: Long-haul truckers appear to represent a subset of the general population regarding the impact of physical activity and other metabolic risk factors on QUICKI. Accordingly, comprehensive efforts which target these factors are needed to improve truckers’ physical activity levels and other metabolic risks.

Background Type 2 Diabetes is a major risk factor for cardiovascular (CV) mortality. Insulin resistance can be evaluated non-invasively by insulin sensitivity indices (ISI) such as the Mcauley index (MCAi), which is a function of the fasting insulin and triglycerides. Currently, the association between ISIs and ECG findings and all-cause and CV mortality is still not established in a large scale and heterogeneous population. Method In a prospective study of the Israel cohort on Glucose Intolerance, Obesity and Hypertension (GOH) second phase (1979–1982) 1830 men and women were followed until December-2016 for CV-mortality and December-2019 for all-cause mortality. ECGs were recorded and OGTTs performed during baseline. ISIs were categorized into quartiles and evaluated against ECG findings and all-cause and CV-mortality. Results Mean age at baseline was 52.0 ± 8.1 years, and 75 (15.2%) and 47 (25.3%) participants in the upper quartiles (Q2-4) and the lower quartile (Q1) of the MCAi, presented with Ischemic changes on ECG respectively (p = 0.02). Multivariable analysis showed higher odds for ECG ischemic changes, for individuals in Q1-MCAi (adjusted-OR = 1.7, 95% CI 1.02–2.8), compared with Q2-4-MCAi, which attenuated when excluding individuals with diabetes (adjusted-OR = 1.6, 95% CI 0.9–2.7, p = 0.09). Median follow up for all-cause and for cardiovascular mortality was 31 years and 37 years, respectively. Cox proportional-hazards regression showed an increased risk for all-cause mortality for individuals in Q1-MCAi (HR = 1.2, 95% CI 1.02–1.3) as well as an increased risk for CV-mortality (HR = 1.4, 95%CI 1.1–1.8) compared with Q2-4-MCAi. Individuals in Q4-Ln Homeostatic model assessment- Insulin Resistance (HOMA-IR) and Q1- Quantitative Insulin Sensitivity Check Index (QUICKI) also presented with increased risk for all-cause-mortality (HR = 1.2, 95%CI 1.04–1.4; and HR = 1.2, 95% CI 1.04–1.4, respectively). Other ISIs did not show significant associations with CV-mortality. Conclusion Higher insulin-resistance, according to the MCAi, associated with ECG-changes, and with greater risk for all-cause and CV-mortality over a 40-year follow-up. The MCAi may be considered as an early predictive and prognostic biomarker for CV-morbidity and mortality in adults.

Objective:We investigated the association of dietary Mg intake with insulin resistance and markers of endothelial function among Iranian women.Design:A cross-sectional study.Setting:Usual dietary intakes were assessed using a validated FFQ. Dietary Mg intake was calculated by summing up the amount of Mg in all foods. A fasting blood sample was taken to measure serum concentrations of glycemic indices (fasting plasma glucose and insulin) and endothelial function markers (E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1). Insulin resistance and sensitivity were estimated using the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), Homeostasis Model Assessment β-cell function (HOMA-β) and quantitative insulin sensitivity check index (QUICKI).Participants:Iranian female nurses (n 345) selected by a multistage cluster random sampling method.Results:The Mg intake across energy-adjusted quartiles was 205 (se 7), 221·4 (se 8), 254·3 (se 7) and 355·2 (se 9) mg/d, respectively. After adjustments for potential confounders, QUICKI level was significantly different across quartiles of Mg intake (Q1: 0·34 (se 0·02), Q2: 0·36 (se 0·01), Q3: 0·40 (se 0·01), and Q4: 0·39 (se 0·02), P = 0·02); however, this association disappeared after considering markers of endothelial function, indicating that this relation might be mediated through endothelial dysfunction. After controlling for all potential confounders, Mg intake was inversely, but not significantly, associated with serum concentrations of sICAM (Q1: 239 (se 17), Q2: 214 (se 12), Q3: 196 (se 12), and Q4: 195 (se 17), P = 0·29). There was no other significant association between dietary Mg intake and other indicators of glucose homoeostasis or endothelial markers.Conclusions:Higher dietary Mg intake was associated with better insulin sensitivity in Iranian females. This linkage was mediated through reduced endothelial dysfunction.

Purpose Chronic kidney disease (CKD) is a major health problem worldwide. Evidence supporting the use of probiotic, prebiotic, and synbiotic supplementation in the management of CKD is mixed, although some studies suggest they may be useful. A systematic review and meta-analysis was performed to evaluate the effectiveness of probiotic, prebiotic, and synbiotic supplementation for improving cardiometabolic and oxidative stress parameters in patients with CKD. Methods A comprehensive key word search was performed in EMBASE, Medline, Scopus, Cochrane Central, and Web of Science until April 2020. Randomized controlled trials investigating the effectiveness of probiotic, synbiotic, and prebiotic supplementation for the management of adults with CKD were included. Primary outcomes were measures of cardiometabolic parameters such as cholesterol and fasting blood glucose. Secondary outcomes were measures of oxidative stress (eg, malondialdehyde levels) and body mass index. Random effects meta-analyses were used to estimate mean treatment effects. Results are reported as standardized mean differences (SMDs) and 95% CIs. Findings Fourteen articles were included. In patients with CKD, probiotic, prebiotic, and synbiotic supplementation significantly reduced total cholesterol (SMD, −0.25; 95% CI, −0.46 to −0.04; I2 = 00.0%), fasting blood glucose (SMD, −0.41; 95% CI, −0.65 to −0.17; I2 = 00.0%), homeostatic model assessment of insulin resistance (SMD, −0.63; 95% CI, −0.95 to −0.30; I2 = 43.3%), insulin levels (SMD, −0.49; 95% CI, −0.90 to −0.08; I2 = 65.2%), high-sensitivity C-reactive protein levels (SMD, −0.52; 95% CI, −0.81 to −0.22; I2 = 52.7%), and malondialdehyde levels (SMD, −0.79; 95% CI, −1.22 to −0.37; I2 = 69.8%) compared with control interventions. Supplementation significantly increased the quantitative insulin sensitivity check index (SMD, 0.78; 95% CI, 0.51 to 1.05; I2 = 00.0%), total antioxidant capacity (SMD, 0.42; 95% CI, 0.18 to 0.66; I2 = 00.0%), and glutathione levels (SMD, 0.52; 95% CI, 0.19 to 0.86; I2 = 37.0%). Implications Probiotic, prebiotic, and synbiotic supplementation seems to be a promising intervention for improving cardiometabolic and oxidative stress parameters in patients with CKD.

The objective of this experiment was to determine the effects of altering the dietary cation-anion difference (DCAD) fed for the last 21 or 42 d of gestation on glucose metabolism and tissue insulin responsiveness. Ninety parous Holstein cows at 232 d of gestation were assigned randomly to dietary treatments with 2 levels of DCAD (-70 or -180 mEq/kg) fed for 2 durations (short: the last 21 d of gestation; long: the last 42 d of gestation). For the short treatments, a diet with +110 mEq/kg was fed from 232 to 254 d of gestation. Intravenous glucose tolerance tests (IVGTT) were performed at either 250 or 270 d of gestation by infusing 0.25 g of dextrose/kg of body weight within 1 min. The following day, cows underwent an insulin challenge (IC) and received 0.1 IU of insulin/kg of body weight intravenously. Blood was sampled at min -15, -5, and 0 to establish a baseline and from 5 to 180 min relative to infusions; plasma concentrations of glucose, insulin, and fatty acids were determined, and the respective areas under the curves (AUC) were calculated. Liver was sampled after the IVGTT, and adipose tissue was sampled after the IVGTT and IC for quantification of mRNA expression and protein abundance. Reducing the DCAD altered acid-base balance compatible with a compensated metabolic acidosis. At 250 d, reducing the DCAD increased the AUC for glucose and reduced that of insulin following the IVGTT, whereas during the IC, clearance rate decreased and time to half-life of insulin increased with reducing DCAD, resulting in a tendency to a larger AUC for fatty acids. At 270 d, quantitative insulin sensitivity check index and the revised quantitative insulin sensitivity check index were smaller in cows fed the acidogenic diets for the last 42 d of gestation compared with the last 21 d of gestation, thereby suggesting reduced insulin sensitivity. In addition, cows fed for the long duration tended to have greater AUC for glucose but smaller AUC for insulin following an IVGTT than those fed for the short duration, thereby suggesting reduced insulin release and glucose disposal. Treatments did not affect hepatic mRNA expression of G6PC, PCK1, PCK2, and PC or adipose tissue mRNA expression of ATGL, ACC, B2AR, HSL, and PLIN1. On the other hand, for proteins, reducing the DCAD linearly reduced abundance of rabbit anti-mouse protein kinase B (AKT) and tended to reduce rabbit anti-human phosphorylated (Ser-9) glycogen synthase kinase-3 β (pGSK) and the pGSK:rabbit anti-human glycogen synthase kinase-3 β (GSK) ratio in hepatic tissue, whereas a linear increase in rabbit anti-human hormone-sensitive lipase (HSL) and rabbit anti-mouse phosphorylated (Ser-660) hormone-sensitive lipase (pHSL) in adipose tissue was observed after the IVGTT at 250 d. Moreover, reducing the DCAD resulted in a linear reduction of AKT and tended to reduce rabbit anti-human acetyl-CoA carboxylase (ACC) but increased pHSL linearly in adipose tissue after an IC at 250 d. Cows fed acidogenic diets for a short duration tended to have less pHSL in adipose tissue than those fed for a long duration after an IVGTT at 270 d. Associations were observed between blood pH and mRNA and protein abundance in hepatic and adipose tissues. Diet-induced metabolic acidosis altered insulin release and insulin signaling, resulting in a shift in adipose tissue metabolism that would favor lipolysis over lipogenesis.

Objective of the present study was to evaluate the effect of vitamin D supplementation on glycose homeostasis, islet function, and diabetes progress. Literatures were searched via electronic databases, websites, and previous reviews from the earliest available time to the end of May 2020. Randomized controlled trials initially designed for diabetes and prediabetes with 25-dihydroxyvitamin D [25(OH)D]

The current study was designed to investigate the possible effects of aqueous extract of Pterocarpus santalinus heart wood and Brassica nigra seeds on streptozotocin (STZ) induced diabetic rats. Adult male albino rats of 24 numbers were used in this study and were divided into four groups, each group contain 6 animals. For induction of diabetes rats were received STZ (65 mg/kg body weight). After STZ induction the remaining three groups were split as follow: group 2 served as diabetic untreated group, group 3 served as diabetic group treated with aqueous Pterocarpus santalinus extract and group 4 served as diabetic group treated with aqueous Brassica nigra extract. STZ administration produced significant increase in serum glucose, HbA1c, Homeostatic Model Assessment insulin resistance (HOMA-IR), lipids, creatinine and urea levels; also, significant decrease in insulin level, Homeostatic Model Assessment insulin sensitivity (HOMA-IS), Quantitative Insulin Sensitivity Check Index (QUICKI) and Glomerular filtration rate (GFR). At molecular level, STZ administration produced significant up-regulation in the mRNA of Thioredoxin-interacting protein (TXNIP), The Nod-like receptor protein 3(NLRP3) and inflammasome and Apoptosis-enhancing nuclease (AEN). The effects of aqueous extracts of P. santalinus wood and B. nigra seeds were evidenced by significant decreased in serum levels of glucose, HbA1c, lipids, creatinine and urea as well as significant increase in insulin, HDL and GFR level. Further treatment with aqueous extracts of Pterocarpus santalinus and Brassica nigra down-regulated the mRNA of TXNIP, NLRP3 and AEN. The results of this study concluded that aqueous extracts of P. santalinus and B. nigra reduced the effects of STZ- induced diabetes and they can be used for the treatment of diabetes and its complication.

Introduction: Transient neonatal diabetes mellitus (TNDM) is a rare condition that is characterized by the presence of diabetes mellitus during the first 6 months of life and remission by 18 months of age. It usually relapses at a median age of 14 years. Hyperinsulinaemic hypoglycaemia is a relatively common complication during remission. Although β-cell function is reported to be impaired at relapse, the clinical course of glycaemic profiles during remission in patients with TNDM remains largely unknown. Case Presentation: Longitudinal glycaemic profiles were investigated annually from remission (185 days) to relapse (14.5 years) in a patient with TNDM due to paternal 6q24 duplication using the oral glucose tolerance test (glucose intake: 1.75 g/kg to a maximum of 75 g). The patient’s β-cell function and insulin sensitivity were assessed by calculating the insulinogenic index, homeostasis model assessment of β-cell function (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index, and Matsuda index. Early insulin response to glucose intake was impaired throughout remission, whereas fasting insulin and β-cell function by HOMA-β gradually increased in the first few years since remission, followed by a gradual decline in function. In contrast, HOMA-IR fluctuated and peaked at 6.5 years of age. Conclusion: This is the first report of annual longitudinal glycaemic profiles in a patient with 6q24-related TNDM during remission. We identified fluctuations in β-cell function and insulin resistance during remission.

Introduction: The effectiveness of probiotics in patients with abnormal glucose metabolism has not been clearly demonstrated. It is also unclear if outcomes are consistent across different probiotic formulations. Methods: A literature search was conducted using PubMed, EMBASE, and Cochrane CENTRAL database from inception through May 2020. Randomized controlled trials that evaluated the effect of probiotics on fasting blood glucose (FBG) or hemoglobin A1c (HbA1c) in patients with prediabetes, type 2 diabetes mellitus, or gestational diabetes were included. Outcomes of interest included FBG, HbA1c, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of β-cell function (HOMA-B), and quantitative insulin sensitivity check index (QUICKI). Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated using the DerSimonian and Laird random-effects model. Results: 31 studies involving 1,948 participants were included in this analysis. Compared to control, probiotics had a significant favorable effect on FBG (WMD −5.77 mg/dL, 95% CI −8.48 to −3.06), HbA1c (WMD −0.32%, 95% CI −0.47 to −0.18), fasting insulin (WMD −2.95 µIU/mL, 95% CI −3.76 to −2.14), HOMA-IR (WMD −0.82, 95% CI −1.05 to −0.59), HOMA-B (WMD −14.86, 95% CI −24.57 to −5.16), and QUICKI (WMD 0.015, 95% CI 0.011–0.019). Further, probiotics were associated with favorable outcomes on all parameters at doses between 1 and 10 × 109 colony-forming unit per day (p < 0.004 for all) and formulations containing 2–4 strains (p < 0.05 for all). Discussion/Conclusion: Probiotics appear to have a modest effect on glycemic parameters in patients with abnormal glucose metabolism. Due to the limited number of trials conducted in patients with prediabetes, more studies are warranted in this population.

Background Obese adipose tissue secretes a variety of adipocytokines that act as metabolic regulators with complex mechanisms. These mechanisms are largely unknown. Our objective was to compare serum concentration of a panel of adipocytokines between obese and non-obese individuals and identify any distinct patterns correlating with insulin sensitivity in obesity. Methods We designed a cross-sectional study among obese (body mass index [BMI] ≥30 kg/m2, n=62) and non-obese (BMI

Background Metabolic syndrome (MetS) comprises a set of risk variables associated with an increased risk of cardiovascular disease. Insulin resistance (IR) is a collective clinical entity that exacerbates MetS. It is challenging to quantify IR in a medical setting because the gold-standard test involves intravenous insulin loading and repeated blood glucose monitoring. Therefore, many indices have been developed for IR assessment, but their value in detecting MetS is questionable. This study tested the ideal cut-off values and clinical utility of IR indices in identifying MetS. Methods We recruited 150 subjects, 75 MetS patients and 75 healthy controls, then obtained written informed consent to participate in this study. We collected fasting blood samples for glucose and lipid profiles and calculated nineteen indices of IR and secretion using validated formulae. We determined the precision of these IR indices using the area under the curve (AUC) in a receiver operating characteristic analyses. Results Subjects with MetS have significantly higher IR coupled with lower insulin sensitivity and beta-cell function than controls. Among the surrogate markers of IR tested, the homeostatic model assessment of insulin resistance (HOMA-IR), HOMA-adiponectin (HOMA-AD), triglyceride-glucose (TyG) index, HOMA-1%S (insulin sensitivity), quantitative insulin sensitivity check index (QUICKI), McAuley index, single-point insulin sensitivity estimator (SPISE), and HOMA-2%B (beta-cell function) showed the highest AUCs for detecting MetS. Conclusion Our study results suggest that the ideal cut-off and AUC values identified for HOMA-IR, HOMA-AD, the TyG index, HOMA-1%S, QUICKI, the McAuley index, SPISE, and HOMA-2%B offer a clinical approach to the early detection and risk stratification for MetS among people in southern India.

Summary In type 2 diabetes, liver insulin resistance and excess hepatic glucose production results in elevated fasting glucose. A bedtime snack has been recommended to improve fasting glucose, yet there is little evidence supporting this recommendation. Moreover, the optimal composition of a bedtime snack is unknown. Purpose To determine whether a low-carbohydrate protein-rich bedtime snack (Egg) could reduce fasting plasma glucose levels in people with type 2 diabetes when compared to a high-carbohydrate protein-rich bedtime snack (Yogurt) or a No Bedtime Snack condition. Secondary outcomes included glucose control assessed by continuous glucose monitoring (CGM) and fasting insulin sensitivity markers. Methods Using a randomized crossover design, participants with type 2 diabetes (N = 15) completed three separate isocaloric conditions: i) Egg, ii) Yogurt, and iii) No Bedtime Snack, each lasting three days. CGM was collected throughout and duplicate fasting blood samples were obtained on the morning of day 4 in each condition. Results Fasting plasma glucose (P = 0.04, d = 0.68), insulin (P = 0.04, d = 0.45), and nocturnal glucose (P = 0.02, d = 0.94) were significantly lower, and quantitative insulin sensitivity check index (QUICKI; P = 0.003) was improved, in the Egg compared to the Yogurt bedtime snack. There were no significant differences between either bedtime snack and No Bedtime Snack. Conclusion In the short-term, a low-carbohydrate bedtime snack (Egg) lowered fasting glucose and improved markers of insulin sensitivity when compared to a high-carbohydrate protein-matched bedtime snack (Yogurt). However, consuming a low- or high-carbohydrate bedtime snack did not appear to lower fasting glucose compared to consuming an isocaloric diet with no bedtime snack. Clinical trial registry clinicaltrials.gov ( NCT03207269 ).

Objectives We hypothesized that reproductive years, a marker of total estrogen exposure, may play an important role in insulin resistance. Study design A total of 3327 middle-aged and older women (age range 40–69 years) from the Korean Genome and Epidemiology Study were included in this large prospective cohort study with a mean follow-up of 10.8 years. Main outcome measures Insulin resistance and sensitivity were calculated using the homeostatic model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI). A linear mixed model for a repeated-measures covariance pattern with unstructured covariance within participants was used to assess longitudinal associations between baseline reproductive years and subsequent changes in HOMA-IR and QUICKI. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for new-onset insulin resistance according to quartiles of reproductive years. Results Changes in HOMA-IR were significantly greater in Q1 (fewest reproductive years) than in Q4 (most reproductive years) (beta[SE] = 0.038[0.016]; p-value = 0.022), while changes in QUICKI were significantly smaller in Q1 than in Q4 (beta[SE] = −0.001[0.000]; p-value = 0.048) after adjusting for possible confounders over time. Compared with Q1, HRs (95 % CIs) for the incidence of new-onset insulin resistance were 0.807 (0.654−0.994) for Q2, 0.793 (0.645−0.974) for Q3, and 0.770 (0.622−0.953) for Q4 after adjusting for possible confounders. Conclusion A short reproductive period is associated with elevated levels on the HOMA-IR and decreased levels on the QUICKI over time. The lowest quartile of reproductive years was significantly associated with a higher risk of new-onset insulin resistance.

Objective: We aimed to investigate a possible role of the endocrine disruptors phthalates, di-2-ethylhexyl phthalate (DEHP) and mono (2-ethylhexyl) phthalate (MEHP), in polycystic ovary syndrome (PCOS) aetiopathogenesis. We also wished to evaluate the relationship between phthalates and metabolic disturbances in adolescents with PCOS. Methods: A total of 124 adolescents were included. Serum MEHP and DEHP levels were determined by high-performance liquid chromatography. Insulin resistance was evaluated using homeostasis model assessment-insulin resistance, quantitative Insulin Sensitivity Check Index, fasting glucose/insulin ratio, Matsuda index, and total insulin levels during oral glucose tolerance test. Participants were further subdivided into lean and obese subgroups according to body mass index (BMI). Results: Sixty-three PCOS and 61 controls, (mean age 15.2±1.5; range: 13-19 years) were enrolled. Serum DEHP and MEHP concentrations were not significantly different between PCOS and control groups. The mean (95% confidence interval) values of DEHP and MEHP were 2.62 (2.50-2.75) μg/mL vs 2.71 (2.52-2.90) μg/mL and 0.23 (0.19-0.29) μg/mL vs 0.36 (0.18-0.54) μg/mL in PCOS and the control groups respectively, p>0.05. Correlation analysis, adjusted for BMI, showed that both phthalates significantly correlated with insulin resistance indices and serum triglycerides in adolescents with PCOS. Conclusion: Serum DEHP and MEHP concentrations were not different between adolescents with or without PCOS. However, these phthalates are associated with metabolic disturbances such as dyslipidemia and insulin resistance, independently of obesity, in girls with PCOS.

Background Insulin resistance has a vital role in the pathophysiology of polycystic ovary syndrome (PCOS). Previous investigations have shown that some lipid ratios could be a simple clinical indicator of insulin resistance (IR) in some disorders and ethnicities. The present study was conducted to evaluate the correlation between triglyceride to HDL-cholesterol (TG/HDL-C), total cholesterol to HDL-cholesterol (TC/HDL-C), as well as fasting triglyceride-glucose (TyG) indices with IR (as measured by homeostasis model assessment of IR (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and fasting glucose to insulin ratio (FGIR)) among the Iranian women diagnosed with PCOS. Methods In the current study, a total of 305 women with PCOS were evaluated. TG/HDL-C, TC/HDL-C, and TyG indices were calculated. Fasting insulin level was measured using ELISA technique. IR was defined as a HOMA-IR value of ≥2.63, FG-IR value of Results The insulin-resistant (IR) and insulin-sensitive (IS) groups, established by the HOMA-IR, FG-IR, and QUICKI values were different in terms of TG/HDL-C, TC/HDL-C, and TyG indices. These indices were associated with IR even after adjusting for age and BMI. ROC curve analyses showed that TyG, TG/HDL-C, and TC/HDL-C strongly predicted HOMA-IR with area under the curve (AUC) of 0.639, 0.619, and 0.623, respectively (P P = 0.04). Conclusion TyG, TG/HDL-C, and TC/HDL-C indices might be good indicators of IR among Iranian women diagnosed with PCOS.

Objective The aim of this study was to investigate the effect of oral vitamin K2 (Menaquinone‐7 [MK‐7]) on clinical and biochemical parameters in polycystic ovary syndrome (PCOS) patients. Methods In this randomized, double‐blind, placebo‐controlled clinical trial, 84 PCOS patients were randomly assigned into the treatment (90 µg Menaquinone‐7 daily for 8 weeks) and placebo groups. Insulin resistance, lipid profile, endocrine biomarkers, and body composition of the participants were measured before and after the intervention. This study was performed in Ghadir Mother & Child Hospital affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. Results Menaquinone‐7 supplementation, when compared to placebo, significantly decreased serum fasting insulin (p = .002), homeostasis model of assessment insulin resistance (p = .002), and homeostasis model of assessment β‐cell function (p = .02) in addition to a significant increase in quantitative insulin sensitivity check index (p = .001). Also, MK‐7 administration led to significant declines in serum triglyceride (p = .003) and dihydrotestosterone (DHT; p = .03) levels, free androgen index (p, The aim of this randomized, double‐blind, placebo‐controlled clinical trial was to investigate the effect of oral vitamin K2 (Menaquinone‐7) on some clinical and biochemical parameters in Polycystic OvarySyndrome (PCOS) patients. Results showed the beneficial effect of 8‐week supplementation with Menaquinone‐7 on insulin resistance, fat mass, skeletal muscle, and serum levels of triglyceride, DHT, and SHBG in the study participants.

Background Human glucagon-like peptide-1 analogue, Liraglutide, has shown cardioprotective effects in animal and clinical studies of type 2 diabetes mellitus. This study was conducted to assess the effect of Liraglutide on diabetes-induced myocardial electrical remodeling. Materials and Methods A rat model of type 2 diabetes mellitus was induced by high-fat diet and low dose Streptozotocin (35 mg/kg). Diabetic rats were randomized into 4 subgroups (n=6–7): diabetic-untreated, diabetics treated with Liraglutide, diabetics treated with Ramipril, and diabetics treated with Metformin in addition to a control group. Changes in serum glucose, insulin, lipid profile and revised quantitative insulin sensitivity check index (QUICKI index) were assessed. QT and QTc intervals were measured and the degree of cardiac interstitial and perivascular fibrosis was examined. The expression of myocardial Ito channel α subunits, gap junction protein; Kv 4.2/4.3 and connexin 43 (Cx43) respectively, were assessed by western blotting and immunohistochemistry. Results Similar to Ramipril, both Liraglutide and Metformin effectively inhibited the diabetes-induced myocardial hypertrophy and fibrosis. However, Liraglutide treatment significantly improved Kv 4.2/4.3 and Cx43 expression/distribution and prevented diabetes-related QTc interval prolongation. Conclusions We have shown that pathological alterations in myocardial Cx43 expression and distribution, in addition to reduced Ito channel expression, may underlie the QTc interval prolongation in high-fat diet/STZ rat model of type 2 diabetes mellitus. The beneficial effects of Liraglutide, as those of Ramipril, on cardiac electrophysiology could be at least attributed to its direct ability to normalize expression and distribution of Cx43 and Ito channels in the diabetic rat heart.

OBJECTIVE: To assess the effect of low and high dose of glycyrrhizin on body weight, fasting blood sugar level (FBSL), serum insulin and glycemic indices in high fat diet induced type 2 diabetic rats. METHODS: In this experimental study with intervention period of 34 weeks, rats were grouped into four experimental groups; Group-A: normal control; Group-B: diabetic control; Group-C: glycyrrhizin-150 and Group-D: glycyrrhizin-300. Diabetes mellitus was induced in rats by giving high fat diet with injection dexamethasone. At 32 weeks, body weight, FBSL, serum insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Homeostatic Model Assessment of beta cells (HOMA-β) and Quantitative Insulin Sensitivity Check Index (QUICKI) were estimated. Two experimental groups received glycyrrhizin 150 mg/kg and 300 mg/kg per oral per day till completion of 34 weeks in addition to the high fat diet. At 34 weeks all the parameters were re-estimated. RESULTS: It was observed that both doses of glycyrrhizin significantly reduced FBSL and insulin levels in group-C (95.00±8.23 mg/dl, 671.60±55.51 µIU/ml) and group-D (94.00±6.27 mg/dl, 675.00±44.96 µIU/ml) as compared to group-B (236.10±13.26 mg/dl, 1052.80±37.82 µIU/ml) [p-value0.05) but significantly in group-D (293.20±42.54) as compared to group-B (372.00±24.03) [P-value

Background & aims: Short bouts of severe energy restriction may have additional, beneficial cardiometabolic effects beyond that of weight loss. We aimed to assess the short-term effects of intermittent fasting on insulin sensitivity and related cardiometabolic mechanisms. Methods: This parallel arm, randomized controlled trial compared the short-term effects of intermittent and continuous energy restriction (IER and CER) diets on markers of cardiometabolic health in individuals with central obesity, aiming for equivalent weight loss on both diets. Outcomes were assessed in non-smoking men and women (35–75 y), following 4-wk IER (48 h 600 kcal/d followed by 5-day healthy eating advice) or CER diets (-500 kcal/d healthy eating advice). The primary outcome was the revised quantitative insulin sensitivity check index (R-QUICKI), an indirect estimate of insulin sensitivity. Secondary outcomes included ambulatory blood pressure (ABP), indicators of sympathetic activity (heart rate variability (HRV) and normetanephrine), and markers of glucose homeostasis/insulin resistance, adiposity, lipids and inflammation. Results: Forty-three participants completed the study. Reductions in body weight were equivalent in both groups: mean loss (%) -2.6; 95% CI -3.3, -1.9 and -2.9; -3.6, -2.1 for CER and IER, respectively, P = 0.464). R-QUICKI increased following IER and CER, with no between-diet differences (overall mean increase (%) 6.6; 3.6, 9.6). Fasting plasma glucose concentrations decreased after CER but not after IER (mean difference CER - IER - 4.8% (0.7, 8.9), P

Objective: This study aimed to determine the prevalence of insulin resistance among women with polycystic ovary syndrome (PCOS), describe the clinical and biochemical characteristics of women with PCOS, and determine the association between Antimullerian Hormone (AMH) and PCOS. Patients and Methods: In a clinical case series, 544 women with PCOS were included in this study. Body mass index (BMI), Homeostasis Model Assessment (HOMA), Quantitative Insulin Sensitivity Check Index (QUICKI), and Matsuda index were calculated. Sixty-three women with PCOS and 50 age- and BMI-matched control patients underwent blood sampling for AMH level. Results: The most common clinical presentation of PCOS in this study was menstrual irregularity followed by hirsutism and infertility. There was no statistically significant difference in the clinical presentation or hormonal profile in women with PCOS according to different BMI categories. The prevalence of insulin resistance among women with PCOS was 37.7%, 69.3%, and 75.8% using HOMA, QUICKI, and Matsuda index, respectively. Furthermore, the Matsuda index had the highest detection rate of insulin resistance, especially in underweight women with PCOS (94.1%). AMH levels in women with PCOS were significantly higher than that in the control group (P-value = 0.015). Conclusion: Insulin resistance is prevalent among women with PCOS. The detection rate of insulin resistance varies according to the insulin sensitivity index used. Menstrual irregularity was the most common presentation of PCOS. Women with PCOS have significantly higher levels of AMH levels compared to women in the control group.

To define reference values for various insulin sensitivity (IS) indices in healthy women in a population-based study of the five provinces in Iran In this cross-sectional study, 250 normal-weighted women without hypertension, diabetes, polycystic ovary syndrome, hormonal disorders, pregnancy, or menopause were evaluated in this study. After a 12-h fasting, blood samples were obtained from all participants, levels of metabolic markers (fasting plasma glucose, lipid profile, insulin, etc.) were measured using enzymatic colorimetric and ultrasensitive enzyme-linked radioimmunoassay methods. Multiple insulin sensitivity indices were calculated using well-known predetermined formulas. K-means cluster analysis was used to determine reference values for each insulin sensitivity index. The threshold values of homeostasis model assessment (HOMA-%β, HOMA-βcell) and fasting insulin resistance index (FIRI) were 400.41, 198.55, and 2.57 corresponding to 97th, 93rd, and 92nd percentiles, respectively. Reference values of quantitative insulin sensitivity check index (QUICKI) and TG/HDL-c were 0.44 and 4.40, both of which relate to 92nd percentile. The recently introduced single-point insulin sensitivity estimator (SPISE) was analyzed and showed a threshold of 10.10 (87th percentile) in this study. Threshold values of reciprocal insulin (1/Insulin) and glucose-to-insulin ratio (G/I) were 0.51 (95th percentile) and 76.91 (99th percentile), respectively. This study determined reference values for various insulin sensitivity indices in healthy Iranian women. These values can be used to define insulin sensitivity in women in epidemiological and clinical studies.

Nowadays, among the herbal medicines utilized to treat diabetes, Citrullus colocynthis (CCT) is highly noticeable as it reduces blood glucose (BG) and stimulating insulin secretion. However, long-term oral consumption of this herbal medicine has often associated with digestive complications. In this study, skin absorption of CCT as a new therapeutic approach in the treatment of type II diabetic patients has been surveyed. 40 patients with type II diabetic (aged 45–65) were selected. Participants were asked for placing their metatarsus daily in a decoction containing 2% CCT solution for 40–60 min each day and continuing that for 10 days. Blood and urine samples of patients collected at the beginning and the end of the study. The samples were examined for the BG levels, serum insulin content, lipid profiles, hepatic enzymes, urea, creatinine, and microalbuminuria, The quantitative insulin sensitivity check index (QUICKI), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-β) and disposition index (DI) indicators were also calculated. Local treatment of CCT could significantly decrease BG levels, stimulate insulin secretion and improve the function of pancreatic beta cells. It also decreased serum urea levels comparing to pre-treatment levels (p

Background Overconditioned dairy cows are prone to greater insulin resistance in transition to successfully adapt to negative energy balance. The associations among body condition score (BCS), insulin resistance, lipid metabolism and oxidative stress in cows during late lactation with positive energy balance remain to be elucidated. Methods The objectives of this study were to investigate insulin sensitivity and oxidative status in late lactating dairy cows with different BCS but similar milk production, parity and days in milk. Forty-two multiparous Holstein cows were fed the same diet under the same management and divided into three groups based on BCS: low BCS (LBCS; BCS ≤ 2.75; n = 12), medium BCS (MBCS; 3.0 ≤ BCS ≤ 3.5; n = 15) or high BCS (HBCS; BCS ≥ 3.75; n = 15). Blood samples used for analysis of biochemical and hematological parameters were collected from the coccygeal vein at the end of experiment. Results The concentrations of insulin and nonesterified fatty acid were higher and the revised quantitative insulin sensitivity check index (RQUICKI) was lower in HBCS cows than in LBCS and MBCS cows. These results suggest that insulin resistance exacerbates lipolysis in HBCS cows. Serum concentrations of very low-density lipoprotein, apolipoprotein A-I, and apolipoprotein B were lower in HBCS cows than in LBCS or MBCS cows. Although LBCS and MBCS cows had higher reactive oxygen species levels than did HBCS cows, the malondialdehyde concentration was not different among cows with different BCS. Ceruloplasmin activity was higher in MBCS and HBCS cows than in LBCS cows, but superoxide dismutase, glutathione peroxidase, and paraoxonase activities were not different among cows with different BCS. Despite the higher percentage of granulocytes in MBCS cows than in HBCS cows, no differences were found in leukocyte counts, red blood cell profiles and platelet profiles among the cows in the three groups. Conclusions Results of this study showed that compared with MBCS and LBCS cows, HBCS cows at late lactation stage may have accumulated more hepatic triacylglycerol and lower antioxidant potential due to greater insulin resistance.

Beta-thalassemia major (β-TM) comprises a group of inherited blood disorders characterized by the reduced synthesis of β-globin chains. Iron overload following blood transfusion can affect major tissues involved in glucose metabolism, leading to different glucose metabolic disorders in these patients. The aim of the present study was to compare glucose metabolism and iron overload indices in β-TM patients with prediabetic and normoglycemic states. This analytical study was performed on 49 patients with β-TM (age > 18 years), receiving regular blood transfusions. The fasting plasma glucose (FPG) and glucose tolerance tests indicated 32 normoglycemic and 17 prediabetic cases. The serum levels of C-peptide, fructosamine, fasting serum insulin, and serum ferritin were measured. In addition, T2*-weighted magnetic resonance imaging (MRI) of the heart and liver was carried out. Glycemic metabolism indices, including quantitative insulin sensitivity check index (QUICKI) and homeostatic model assessment for insulin resistance (HOMA-IR), were also calculated. The HOMA-IR score was significantly higher, while the QUICKI score was significantly lower in prediabetic patients, compared to normoglycemic patients (median [IR], 2.59 [2.19] vs. 1.46 [1.03], p = 0.007; mean ± SD, 0.34 ± 0.03 vs. 0.37 ± 0.04, p = 0.01). On the other hand, β-cell function was not significantly different between the groups. The liver iron concentration (LIC) at a cutoff point of 5.82 mg/g dry weight showed 93% sensitivity and 70% specificity for differentiation of prediabetic and normoglycemic states (AUC, 0.81 [95% CI, 0.65–0.95]; p = 0.002). Based on the findings, HOMA-IR and QUICKI can be applied as useful glycemic metabolism indices for predicting prediabetic and normoglycemic states among β-TM patients. Also, LIC was an independent risk factor for the prediabetic state.

Background Glycemia is related to energy production during exercise. Coenzyme Q10 is an antioxidant that participates in adenosine triphosphate synthesis in mitochondria. The aim of this study was to investigate the level of coenzyme Q10, glucose parameters, and antioxidant capacity in athletes. Methods This study was designed as a cross-sectional study. Well-trained college athletes (n = 43) and age-gender matched healthy subjects (n = 25) were recruited from a college. The levels of glucose parameters, oxidative stress, antioxidant enzymes activity, Trolox equivalent antioxidant capacity (TAC), and coenzyme Q10 status were measured in the present study. Results The athletes had a significantly lower level of white blood cells (WBC) coenzyme Q10 than the healthy subjects (0.34 ± 0.24 vs. 0.65 ± 0.43 nmol/g, p

Background Irisin is a myokine that leads to increased energy expenditure by stimulating the browning of white adipose tissue. We aimed to investigate the association of serum irisin levels with metabolic parameters in middle aged Chinese population. Methods The study was based on a cross-sectional analysis of data from 524 nondiabetic subjects aged 40~65. All participants were recruited from a screening survey for Metabolic Syndrome in a community in Southwest China, including 294 subjects categorized as overweight (defined as BMI≧25 kg/m2) and 230 subjects as normal control (defined as 18.5≦BMI 2). Serum irisin concentration was quantified by enzyme linked immunosorbent assay (ELISA). The relationship of irisin with metabolic factors was determined by Pearson correlation. Multivariate linear regression was used to analyze the association of irisin with insulin resistance. Logistic regression was performed to assess the association of irisin with odds of overweight. Results Serum irisin levels were significantly lower in nondiabetic overweight subjects compared with control (11.46 ± 4.11vs14.78 ± 7.03 μg/mL, p = 0.02). Circulating irisin was positively correlated with quantitative insulin sensitivity check index (QUICKI, r = 0.178, p = 0.045) and triglycerides (r = 0.149, p = 0.022); while irisin was negatively correlated with waist circumference (WC, r = − 0.185, p = 0.037), waist-to-hip ratio (WHR, r = − 0.176, p = 0.047), fasting insulin (r = − 0.2, p = 0.024), serum creatinine (r = − 0.243, p = 0.006), homeostasis model assessment for insulin resistance (HOMA-IR, r = − 0.189, p = 0.033). Multiple linear regression showed that irisin was inversely associated with HOMA-IR (β = − 0.342 ± 0.154, p = 0.029). Higher irisin was associated with decreased odds of being overweight (OR = 0.281, β = − 1.271, p = 0.024). Conclusions We found that serum irisin levels were lower in overweight subjects. Moreover, serum irisin levels were inversely correlated with adverse metabolic parameters including WC, WHR, creatinine, HOMA-IR and fasting insulin, suggesting that irisin may play a role in obesity related insulin resistance.

Background Obesity is a health problem in many countries, and maintaining a perfect weight is challenging. Moringa oleifera leaf extract (ME) is rich in polyphenols with antioxidant and pharmaceutical potential. The present study investigated the potential protective effect of Moringa oleifera leaf extract against obesity induced from a high-fat diet (HFD), oxidative stress and disruption of metabolic hormones compared to simvastatin (SIM) or their combination. Results Rats fed a HFD for 6 weeks exhibited a significant increase in body weight and levels of serum glucose and lipid fractions, verifying an obesity state. There were also higher levels of insulin and leptin and lower gherlin in sera of HFD rats compared to the levels in control rats. Homeostasis model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and the atherogenic index were elevated, indicating the development of insulin resistance and dyslipidaemia in these rats. These changes were accompanied with a significant increase in oxidative stress, as indicated by elevated lipid peroxidation and protein oxidation with low levels of antioxidants in liver. The activities of liver function enzymes, including aspartate amino transferase, alanine amino transferase, alkaline phosphatase and gamma glutamyltransferase, were also significantly increased in serum. Concurrent treatment with 300 mg/kg ME for 6 weeks ameliorated the increase in body weight and improved the levels of glucose, lipid fractions and metabolic hormones, indicating the anti-obesity effect and amelioration of tissue insulin resistance potential of ME. ME treatment also normalized oxidative stress and antioxidants in liver and improved liver function enzymes, indicating the antioxidant potential of ME. The effects of ME were similar to SIM, and the combination of these agents was better than each agent alone. Conclusion We propose that ME extract has anti-obesity and antioxidant potential and may be used as a lipid-lowering drug to control weight, obesity and its pathophysiological consequences.

Background: Insulin resistance (IR) is closely associated with the pathogenesis of type 2 diabetes mellitus (T2DM). However, remission of insulin sensitivity after bariatric surgery in patients with T2DM and a body mass index (BMI) of 27.5–32.5 kg/m2 has not been fully elucidated.Methods: Thirty-six T2DM patients with a BMI of 27.5–32.5 kg/m2 were prospectively consecutively recruited for laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG). Hyperinsulinemic euglycemic clamp, oral glucose tolerance test (OGTT), and other indicators were tested at baseline and 6 months postoperative. Glucose disposal rate (GDR), time to reach euglycemia, homeostatic model assessment of IR, quantitative insulin sensitivity check index (QUICKI), triglyceride glucose (TyG) index, 30-min insulinogenic index (IGI30), and disposition index (DI) were calculated at baseline and 6 months after surgery. The criterion for remission in T2DM patients was the achievement of the triple composite endpoint.Results: Anthropometric and glucolipid metabolism parameters significantly improved following surgery. The GDR increased significantly from baseline to 6 months after LRYGB (from 4.28 ± 1.70 mg/kg/min to 8.47 ± 1.89 mg/kg/min, p < 0.0001) and LSG (from 3.18 ± 1.36 mg/kg/min to 7.09 ± 1.69 mg/kg/min, p < 0.001). The TyG index decreased after surgery (RYGB group, from 9.93 ± 1.03 to 8.60 ± 0.43, p < 0.0001; LSG group, from 10.04 ± 0.79 to 8.72 ± 0.65, p = 0.0002). There was a significant reduction in the IGI30 (RYGB group, from 2.04 ± 2.12 to 0.83 ± 0.47, p = 0.005; LSG group, from 2.12 ± 1.73 to 0.92 ± 0.66, p = 0.001). The mean DI significantly increased from 1.14 ± 1.35 to 7.11 ± 4.93 in the RYGB group (p = 0.0001) and from 1.25 ± 1.78 to 5.60 ± 4.58 in the LSG group (p = 0.003). Compared with baseline, HOMR-IR, QUICKI, area under the curve-C-peptide release test (AUC-CRT), and AUC-OGTT were significantly changed at 6 months postoperative. Overall, 52.63% of patients in the LRYGB group versus 29.41% of patients in the LSG group achieved the triple composite endpoint.Conclusion: Both LRYGB and LSG effectively induced remission of IR in patients with T2DM and a BMI of 27.5–32.5 kg/m2.

Background The association between hepatitis C virus (HCV), insulin resistance (IR), and metabolic syndrome has been extensively investigated. Direct-acting antivirals (DAAs) have a high sustained virologic response (SVR) rate, reaching > 90%. The effect of SVR after DAA treatment on metabolic parameters and IR in nondiabetic patients could be an important factor in the patient’s long-term outcome. The aim of the study is to evaluate the impact of different DAA regimens on IR and sensitivity in naïve chronic HCV-infected nondiabetic patients (before and after 12 weeks of treatment). Methods This prospective cohort study was conducted on 100 HCV-infected Child A nondiabetic patients eligible for DAA treatment in the Department of Gastroenterology and Hepatology, Ain Shams University, and Kobry El-Kobba Military Hospital among patients attending the outpatient clinic. Patients were categorized into four groups according to the HCV regimens they received for 12 weeks. All patient were subjected to the following tests before and 12 weeks after treatment: HCV quantitative PCR, Fibroscan, fasting insulin level (using insulin quantitative test kit), fasting and postprandial blood glucose (PPG), lipid profile, liver enzymes, BMI, and waist circumference. Results All patients achieved SVR at 12 weeks. In all treatment groups, lab was assessed before and after treatment, the 2-h PPG, high-density lipoprotein, and low-density lipoprotein levels showed statistically significant increases, whereas triglyceride, fasting glucose, hemoglobin A1C, and fasting plasma insulin levels showed statistically significant decreases. The homeostasis model assessment of insulin resistance (HOMA-IR) exhibited statistically significant decreases, whereas the quantitative insulin sensitivity check index (QUICKI) and Matsuda index showed statistically significant increases, across the four groups. Conclusions DAA treatment in naïve nondiabetic HCV-infected patients affects metabolic profile and insulin resistance/sensitivity, with similar effect among different DAA regimens.

BACKGROUND Over the past few years, the benefits of omega-3 fatty acids have been reported in the management of non-alcoholic fatty liver disease (NAFLD) complications.This study evaluated the effects of Camelina sativa oil (CSO) supplementation as one of the richest dietary sources of omega-3 fatty acids on glucose homeostasis,inflammation, metabolic endotoxemia, and oxidative stress in NAFLD patients. METHODS A total of 46 patients with NAFLD were allocated to either an intervention (20 g/d CSO) or placebo (20 g/d sunflower oil) group receiving a calorie-restricted diet for 12 weeks. Fasting plasma levels of glycemic indices, hs-CRP, lipopolysaccharide (LPS), antioxidant enzymes activity, total antioxidant capacity (TAC), malondialdehyde (MDA), 8-iso-prostaglandin F2α (8-iso-PGF2α), and uric acid were measured at baseline and post-intervention. RESULTS The CSO supplementation led to significant differences in insulin concentration, homeostasis model assessment of insulin resistance (HOMA-IR), hs-CRP, LPS, TAC, superoxide dismutase (SOD) activity, MDA and 8-iso-PGF2α between the two groups at end of the study (ANCOVA, P

Objective To evaluate the effects of vitamin D supplementation in the postpartum period of women with previous gestational diabetes mellitus (GDM). Methods Randomized clinical trials of pregnant women with GDM of any chronological, gestational age and parity, with no history of previous disease who received vitamin D supplementation in the prenatal and/or postpartum period and were evaluated in the postpartum period were included. The PubMed, EMBASE, Cochrane, and LILACS databases were consulted until July 2019. Serum vitamin D concentration (25- hydroxyvitamin D in nmol/L), fasting blood glucose, glycated hemoglobin, serum calcium concentration, homeostatic model assessment of insulin resistance (HOMAIR), quantitative insulin sensitivity check index (QUICKI), parathyroid hormone (PTH) and body mass index (BMI) were evaluated. Similar results in at least two trials were plotted using the RevMan 5; Cochrane Collaboration, Oxford, Reino Unido. The quality of the evidence was generated according to the classification, development, and evaluation of the classification of the recommendations. Results Four studies were included in the present review (200 women). The findings indicate that there is no difference in the postpartum period in women diagnosed with previous GDM who received vitamin D supplementation in the prenatal and/or in the postpartum period, showing only that there was a significant increase in the concentration of vitamin D (relative risk [RR]: 1.85; 95% confidence interval [CI]: 1.02-2.68). Conclusion This increase in the concentration of vitamin D should be interpreted with caution, since the assessment of the quality of the evidence was very low. For the other analyzed outcomes, there was no significance between the intervention and control groups, and the outcomes, when analyzed in their strength of evidence, were considered very low and low in their evaluation. Resumo Objetivo Avaliar os efeitos da suplementação de vitamina D no pós-parto de mulheres com diabetes mellitus gestacional (DGM) anterior. Métodos Foram incluídos ensaios clínicos randomizados com gestantes com GDM de qualquer idade cronológica, gestacional e paridade, sem história de doença prévia, que receberam suplementação de vitamina D no pré-natal e/ou no pós-parto e foram avaliadas no pós-parto. As bases de dados consultadas foram PubMed, EMBASE, Cochrane e LILACS, até julho de 2019. Foram avaliados concentração sérica da vitamina D (25-hidroxivitamina D em nmol/L), glicemia de jejum, hemoglobina glicada, concentração sérica de cálcio, modelo de avaliação da homeostase de resistência à insulina (HOMA-IR, na sigla em inglês), índice qualitativo de verificação da sensibilidade à insulina (QUICKI, na sigla em inglês), hormônio da paratireoide (PTH) e índice de massa corpórea (IMC). Resultados semelhantes em pelo menos dois ensaios foram plotados no software RevMan 5; Cochrane Collaboration, Oxford, Reino Unido. A qualidade das evidências foi gerada de acordo com a classificação, o desenvolvimento e a avaliação da classificação das recomendações. Resultados Quatro estudos foram incluídos na presente revisão (200 mulheres). Os achados indicam que não há diferença no período pós-parto em mulheres com diagnóstico prévio de DMG que receberam suplementação de vitamina D no período pré-natal e/ou pós-parto, mostrando apenas que houve um aumento significativo na concentração de vitamina D (risco relativo [RR]: 1,85; IC [intervalo de confiança] 95%: 1,02-2,68). Conclusão Este aumento na concentração de vitamina D deve ser interpretado com cautela, uma vez que a avaliação da qualidade das evidências foi muito baixa. Para os demais desfechos analisados, não houve significância entre os grupos intervenção e controle, e os desfechos, quando analisados em sua força da evidência, foram considerados muito baixa e baixa em sua avaliação. PROSPERO CRD42018110729

BackgroundObesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain.AimTo evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity.MethodsRetrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of β-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery).ResultsThere were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (β = −1.04 [−1.82 to −0.26], pConclusionβ-cell function at baseline seems to be associated to long-term weight loss, explicitly after the first year post bariatric surgery. This might be a helpful predictor of weight loss in clinical practice.