High fat diet- induced obesity decreases ErbB receptors expression in liver and adipose tissue in C57BL/6 mice

Neuregulins (NRGs) are a family of signaling proteins that bind to receptor tyrosine kinases of the ErbB family (ErbB2 to ErbB4), which can homo- or heterodimerize depending on their structural features and cell type. Many studies have proposed that decreased NRG levels are a common characteristic of obesity. In liver and adipose tissue, the increase in NRG expression has protective effects against obesity. However, it is still unknown whether ErbBs expression is altered in this pathology. We hypothesized that high fat diet-induced obesity downregulates ErbB receptors expression in obese mice compared to normal weight mice. Males C57BL/6 mice (n=6-7 for each group) were fed for 12 weeks and divided into: (i) control diet (CD; 10%-kcal fat, 20%-kcal protein, 70%-kcal carbohydrates), and (ii) high fat diet (HFD; 60%-kcal fat, 20%-kcal protein, 20%-kcal carbohydrates). General parameters and ErbBs expression (qPCR, immunohistochemistry and Western blot) were evaluated. We observed a significant increase in final body weight (47%), adipose tissue to body weight ratio (244%) and HOMA-IR (69%), among other parameters, in obese mice. In HFD group significantly decreased ErbB2 (48%) and ErbB3 (66%) mRNA levels in liver (no change in ErbB4), and ErbB2 (43%), ErbB3 (76%) and ErbB4 (35%) in adipose tissue, compared to CD. Furthermore, ErbB2 and ErbB3 protein levels decreased significantly in HFD group compared to the CD in liver. Therefore, our results suggest that HFD-induced obesity significantly decreases ErbBs expression in liver and adipose tissue in this murine model, that may be associated with alterations in the NRG pathway in obese mice.

Las neuregulinas (NRGs) son una familia de proteínas de señalización que se unen a receptores tirosina quinasas de la familia ErbB (ErbB2 a ErbB4), que pueden homo- o heterodimerizar dependiendo de sus características estructurales y del tipo celular. Estudios han propuesto que la disminución de los niveles de NRG es una característica común de la obesidad. En el hígado y el tejido adiposo (TA), el aumento de la expresión de NRG tiene efectos protectores contra la obesidad. Sin embargo, aún se desconoce si la expresión de ErbBs está alterada en esta patología. Nuestra hipótesis es que la obesidad inducida por una dieta alta en grasas (DAG) disminuye la expresión de los ErbB en ratones obesos. Ratones machos C57BL/6 (n=6-7 para c/grupo) fueron alimentados durante 12 semanas y divididos en: (i) dieta control (DC; 10%-kcal grasa, 20%-kcal proteína, 70%-kcal carbohidratos), y (ii) DAG (60%-kcal grasa, 20%-kcal proteína, 20%-kcal carbohidratos). Se evaluaron los parámetros generales y la expresión de ErbBs (qPCR, inmunohistoquímica y Western blot). Observamos un aumento significativo del peso corporal final (47%), de la relación tejido adiposo/peso corporal (244%) y del HOMA-IR (69%), entre otros parámetros, en ratones obesos. En este grupo disminuyó significativamente los niveles de ARNm de ErbB2 (48%) y ErbB3 (66%) en el hígado (sin cambios en ErbB4), y de ErbB2 (43%), ErbB3 (76%) y ErbB4 (35%) en el TA. Además, los niveles de proteína ErbB2 y ErbB3 disminuyeron significativamente, en comparación con el grupo DC en el hígado. Nuestros resultados sugieren que la obesidad inducida por DAG disminuye significativamente la expresión de ErbBs en el hígado y el TA, que puede estar asociado con alteraciones en la vía NRG en ratones obesos.

Association between plasma leptin/adiponectin ratio and insulin resistance indexes in prepubertal children

ABSTRACT Objective: To assess the association between leptin/adiponectin ratio (LAR) and insulin resistance surrogates in prepubertal children. Subjects and methods: Study based on data from the Growth and Obesity Chilean Cohort Study (GOCS) involving 968 Chilean prepubertal children. Plasma insulin, leptin, and adiponectin were determined by immunoassays. Several common insulin resistance surrogates were calculated, including the homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride/HDL cholesterol index, triglyceride-glucose (TyG) index, and the TyG index corrected for body mass index (BMI; TyG-BMI) and waist circumference (WC; TyG-WC). Associations among variables were assessed using multiple linear and logistic regression analysis. Results: There was a significant direct association between plasma leptin and LAR with BMI z-score but no association between plasma adiponectin and adiposity. After adjustments for sex and age, LAR was significantly associated with all insulin resistance surrogates (which were categorized using the 75th percentile as the cutoff point), with the TyG-WC index emerging as the surrogate with the highest magnitude of association (odds ratio [OR] 2.44, 95% confidence interval [CI] 2.05-2.9). After additional adjustment for BMI z-score, only the association between LAR and TyG-WC remained significant (OR 1.64, 95% CI 1.27-2.12). Conclusion: Plasma leptin and LAR were strongly associated with several common insulin resistance surrogates in prepubertal children, most notably with the TyG-WC index. Associations between LAR and insulin resistance indexes were mainly driven by the effect of plasma leptin, which is also directly associated with increased adiposity.

Brain insulin resistance and Alzheimer's disease: a systematic review / Resistência insulínica cerebral e a doença de Alzheimer: uma revisão sistemática

ABSTRACT. The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been well-researched in organs such as adipose tissue, muscle, and liver, has been linked to neurodegenerative diseases like Alzheimer's disease (AD) when it occurs in the brain. Objective: The authors aimed to gather data from the current literature on brain insulin resistance (BIR) and its likely repercussions on neurodegenerative disorders, more specifically AD, through a systematic review. Methods: A comprehensive search was conducted in multiple medical databases, including the Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline), and PubMed®, employing the descriptors: "insulin resistance", "brain insulin resistance", "Alzheimer's disease", "neurodegeneration", and "cognition". The authors focused their search on English-language studies published between 2000 and 2023 that investigated the influence of BIR on neurodegenerative disorders or offered insights into BIR's underlying mechanisms. Seventeen studies that met the inclusion criteria were selected. Results: The results indicate that BIR is a phenomenon observed in a variety of neurodegenerative disorders, including AD. Studies suggest that impaired glucose utilization and uptake, reduced adenosine triphosphate (ATP) production, and synaptic plasticity changes caused by BIR are linked to cognitive problems. However, conflicting results were observed regarding the association between AD and BIR, with some studies suggesting no association. Conclusion: Based on the evaluated studies, it can be concluded that the association between AD and BIR remains inconclusive, and additional research is needed to elucidate this relationship.

RESUMO. A incapacidade das células de reagir à insulina, ocasionando intolerância à glicose e hiperglicemia, é chamada de resistência à insulina. Essa condição clínica, que tem sido bem pesquisada em órgãos como tecido adiposo, músculo e fígado, tem sido associada às doenças neurodegenerativas como a doença de Alzheimer (DA) quando ocorre no cérebro. Objetivo: O objetivo dos autores foi reunir os dados da literatura atual sobre a resistência insulínica cerebral (RIC) e sua provável repercussão em doenças neurodegenerativas, mais especificamente na DA, por meio de uma revisão sistemática da literatura. Métodos: Foi realizada uma pesquisa abrangente em vários bancos de dados médicos, incluindo o Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline) e PubMed, empregando os descritores: "resistência à insulina", "resistência insulínica cerebral", "doença de Alzheimer", "neurodegeneração" e "cognição". Os autores concentraram sua busca em estudos no idioma inglês publicados entre 2000 e 2023 que investigaram a influência da RIC em distúrbios neurodegenerativos ou ofereceram insights sobre os mecanismos subjacentes da RIC. Dezessete estudos que atenderam aos critérios de inclusão foram selecionados. Resultados: Os resultados demonstram que a RIC é um fenômeno observado em uma variedade de doenças neurodegenerativas, incluindo a DA. Estudos sugerem que a utilização e captação prejudicadas de glicose, a produção reduzida de trifosfato de adenosina (ATP) e as alterações na plasticidade sinápticas causadas pela RIC estão ligadas a problemas cognitivos. No entanto, foram observados resultados conflitantes com relação à associação entre DA e RIC, com alguns estudos sugerindo nenhuma associação. Conclusão: Com base nos estudos avaliados, pode-se concluir que a associação entre DA e RIC ainda é inconclusiva, e pesquisas adicionais são necessárias para elucidar essa relação.

Impact of pre-operative weight loss on non-alcoholic fatty liver disease histopathology and insulin resistance in individuals undergoing bariatric surgery: a propensity matched cross-sectional comparison

ABSTRACT BACKGROUND: The effect of weight loss (WL) on histopathological aspects of non-alcoholic fatty liver disease (NAFLD) may provide further insights into the dynamics of hepatic recovery after WL. OBJECTIVE: To analyze the effects of pre-operative WL on insulin resistance- and NAFLD-related histology in individuals undergoing bariatric surgery (BS) with or without pre-operative WL. DESIGN AND SETTING: A matched cross-sectional study was conducted at a public university hospital and a private clinic in Campinas, Brazil. METHODS: An analytical, observational, cross-sectional study was conducted using prospectively collected databases of individuals who underwent BS and liver biopsy at either a public tertiary university hospital (with pre-operative WL) or a private clinic (without pre-operative WL). Random electronic matching by gender, age, and body mass index (BMI) was performed and two paired groups of 24 individuals each were selected. RESULTS: Of the 48 participants, 75% were female. The mean age was 37.4 ± 9.6. The mean BMI was 38.9 ± 2.6 kg/m2. Fibrosis was the most common histopathological abnormality (91.7%). Glucose was significantly lower in the WL group (92 ± 19.1 versus 111.8 ± 35.4 mg/dL; P = 0.02). Significantly lower frequencies of macrovesicular steatosis (58.3% versus 95.8%; P = 0.004), microvesicular steatosis (12.5% versus 87.5%; P < 0.001), and portal inflammation (50% versus 87.5%; P = 0.011) were observed in the WL group. CONCLUSION: Pre-operative WL was significantly associated with lower frequencies of macro- and mi- crovesicular steatosis, portal inflammation, and lower glycemia, indicating an association between the recent trajectory of body weight and histological aspects of NAFLD.

Falciparum malaria is associated with risk markers of type 2 diabetes mellitus in individuals with or without COVID-19 exposure

Background: Scientific information on the impact of malaria on the risk of developing type 2 diabetes mellitus (T2DM) after recovery from the coronavirus disease 2019 (COVID-19) is limited in the Ghanaian context. The purpose of this study was to examine the association between selected risk markers of T2DM in falciparum malaria patients post-COVID-19 or not at a tertiary hospital in Ghana. Methodology: This was a descriptive cross-sectional comparative study of 38-recovered COVID-19 adult participants with malaria and 40 unexposed COVID-19 adults with malaria at the Tamale Teaching Hospital, Ghana. Demographic, anthropometric and levels of glucose, insulin, C-reactive protein and lipid profiles were measured in the two groups of participants under fasting conditions. Parasitaemia was assessed microscopically but insulin resistance and beta-cell function were assessed by the homeostatic model. Results: The COVID-19 exposed participants were older (p=0.035) with lower parasitaemia (p=0.025) but higher mean levels of insulin, insulin resistance, and beta-cell function compared with their unexposed counterparts (p<0.05). Parasitaemia correlated positively with a number of the measured indices of diabetogenic risk markers in the COVID-19 exposed group only, and predicted (Adjusted R2=0.751; p=0.031) by beta-cell function, C-reactive protein and triglycerides with the model explaining about 75% of the observed variation. Parasitaemia could only be predicted (Adjusted R2=0.245; p=0.002) by C-reactive protein with the model explaining just about a quarter of the observed variation in the COVID-19 unexposed group. Insulin resistance and sub-optimal beta-cell function were detected in both groups of participants. Conclusion: Falciparum malaria is associated with risk markers for development of T2DM irrespective of COVID-19 exposure. Insulin resistance, inflammation and sub-optimal beta-cell secretory function may drive the risk. The observed diabetogenic risk is higher in the recovered COVID-19 participants.

Influence factors of bone mineral density and its correlation with insulin resistance in obese children in Qianjiang area / 公共卫生与预防医学

Objective To explore the influencing factors of bone mineral density (BMD) in obese children in Qianjiang area and analyze the correlation between BMD and insulin resistance. Methods The data on pediatric cases from the outpatient department of Jianghan Oilfield General Hospital in Qianjiang from January 2018 to December 2022 were collected. A total of 183 obese children who met the inclusion and exclusion criteria were included in the study and selected in the observation group. A total of 352 children undergoing physical examination during the same period were selected as the control group. Results The body mass, waist circumference, waist to hip ratio, and BMI of obese children were significantly higher than those of the control group (P<0.001). Biochemical indexes including FBG, FINS, Home-IR, ALP, and LDL-C in obese children were significantly higher than those in the control group (P<0.05), while bone mineral density, Ca, P, sOC and HDL-C were significantly lower than those in the control group (P<0.001). The bone mineral density of obese children was significantly correlated with their exercise intensity, sunshine exposure duration, sitting time, intake of milk and dairy products, intake of sweets, supplementation of trace elements, BMI, Home-IR, and sex (all P<0.05). BMI, Home-IR, sex, exercise intensity, and sunshine exposure length were independent risk factors affecting bone mineral density of obese children (all P<0.05). Bone mineral density was negatively correlated with BMI and Home-IR (P=0.028 and0.017, respectively), and positive correlation with exercise intensity and sunlight exposure (P=0.033). Conclusion BMD of obese children in Qianjiang area is affected by gender, body mass index, diet, vitamin intake, and physical activity, and is negatively correlated with insulin resistance. Home-IR can be used as a reference for screening BMD of obese children.

Improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome and its mechanism / 中国药房

OBJECTIVE To study the improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome （PCOS） and its mechanism. METHODS One hundred and twenty-six female rats were randomly separated into blank group， PCOS group， poria acid low-dose group （8.33 mg/kg）， pachymic acid high-dose group （33.32 mg/kg）， ethinylestradiol cyproterone group （positive control group， 0.34 mg/kg）， recombinant rat high mobility group protein B1 protein （rHMGB1） group （8 μg/kg）， and poria acid high dose+rHMGB1 group （33.32 mg/kg poria acid+8 μg/kg rHMGB1）， with 18 rats in each group. Except for the blank group， the rats in all other groups were given Letrozole suspension intragastrically to construct the PCOS model. After successful modeling， administration was performed once a day for 4 weeks. After medication， the fasting blood glucose and fasting insulin levels， and insulin resistance index （HOMA-IR） were measured in rats； the levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH） and testosterone （T） in rat serum， and the levels of interleukin-1β （IL-1β） and tumor necrosis factor- α （TNF- α） in ovarian tissue were detected； ovarian coefficients of rats were calculated； the pathological changes of ovarian tissue were observed； the expressions of HMGB1， receptor for advanced glycosylation elaine_ tanghong@sina.com end product （RAGE） and phosphorylated nuclear factor κB p65 （p-NF-κB p65） proteins were determined in ovarian tissue of rats. RESULTS Compared with the blank group， the pathological injury of ovarian tissue of rats in the PCOS group was serious， the levels of fasting blood glucose and fasting insulin， HOMA-IR and ovarian coefficient were increased， the levels of serum LH and T were increased， while the levels of FSH were decreased； the levels of IL-1β and TNF-α， the expressions of HMGB1， RAGE and p-NF-κB p65 protein in ovarian tissue were increased， with statistical significance （P＜0.05）. Compared with the PCOS group， pathological damage of ovarian tissue was reduced in poria acid low-dose and high-dose groups and ethinylestradiol cyproterone group， and fasting blood glucose， fasting insulin levels， HOMA-IR and ovarian coefficient were decreased； serum LH and T levels were decreased， while FSH levels were increased； the levels of IL-1β and TNF-α and the expressions of HMGB1， RAGE and p-NF-κB p65 protein in ovarian tissue were decreased， with statistical significance （P＜0.05）. The trend of corresponding indexes in rHMGB1 group was opposite to the above （P＜0.05）. Compared with poria acid high-dose group， the changes of the above indexes were reversed significantly in poria acid high-dose+rHMGB1 group （P＜0.05）. CONCLUSIONS Poria acid may improve insulin resistance and inhibit inflammatory reaction in PCOS rats by inhibiting HMGB1/ RAGE pathway.

Effect of Qiwei Baizhusan on Cognitive Dysfunction in Rats with Diabetic Encephalopathy Based on PI3K/Akt/GSK-3β Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

Mechanism Exploration of TG Regulating PI3K/Akt to Improve Insulin Resistance in Liver of T2DM Rats Based on Transcriptomics / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Tangzhi pills on the improvement of insulin resistance （IR） in the liver with type 2 diabetes （T2DM） by regulating phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway based on differential genes and its possible molecular mechanism. MethodT2DM rat models were prepared by high fat （HFD） diet combined with streptozotocin （STZ） intraperitoneal injection. The experiment was divided into blank group， model group， metformin hydrochloride group （0.18 g·kg-1）， Tangzhi pills high （1.08 g·kg-1）， medium （0.54 g·kg-1） and low （0.27 g·kg-1） dose groups. Rat serum， liver， and pancreatic tissue were collected， and the pathological tissue of the liver and pancreas was observed using hematoxylin-eosin （HE） staining. The fasting blood glucose level （FBG） was detected， and oral glucose tolerance （OGTT） tests were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect fasting serum insulin （FINS） and glycated hemoglobin （GHb） levels in rats. IR homeostasis model index （HOMA-IR）， β cellular homeostasis index （HOMA-β）， and insulin sensitivity index （ISI） were calculated. Biochemical methods were used to determine the levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL-C）， and high-density lipoprotein （HDL-C） in rat serum. Transcriptomics obtained differentially expressed mRNA from liver tissue and enriched differentially expressed pathways. Real-time reverse transcriptase polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of cyclic adenylate responsive element binding protein 3-like protein 2 antibody （CREB3l2）， B-lymphocyte tumor 2 （Bcl-2）， Toll-like receptor 2 （TLR2）， cyclin-dependent kinase inhibitor 1A （CDNK1A）， and DNA damage induced transcription factor 4-like protein （DDIT4） in liver tissue. Western blot was used to detect the protein expression of phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， glucose transporter 4 （GLUT4）， insulin receptor （INSR）， and insulin receptor substrate 2 （IRS2）. ResultThe pharmacodynamic experiment results showed that compared with model group， Tangzhi pills groups repaired liver and pancreatic tissue to varying degrees， reduced blood sugar （P<0.01）， and promoted a decrease in serum FINS， GHb， and HOMA-IR （P<0.05， P<0.01）. In addition， HOMA-β and ISI increased （P<0.05， P<0.01）. The levels of TC， TG， and LDL-C decreased （P<0.05， P<0.01）， while the levels of HDL-C increased （P<0.05， P<0.01）. The transcriptomics experimental results confirmed that the PI3K/Akt signaling pathway was significantly expressed in both the blank group and model group， as well as in the high-dose Tangzhi pills group and model group. CDNK1A， DDIT4， CREB3l2， Bcl-2， and TLR2 were significantly differentially expressed mRNA during TG intervention in T2DM. Compared with the model group， the protein expression of p-PI3K， p-Akt， GLUT4， INSR， and IRS2 increased in all Tangzhi pills groups （P<0.01）. The mRNA expression of CREB3l2， Bcl-2， and TLR2 increased （P<0.01）， while that of CDNK1A and DDIT4 decreased （P<0.01）. ConclusionTangzhi pills may regulate the PI3K/Akt signaling pathway based on the differential mRNA expression of CREB3l2， Bcl-2， TLR2， CDNK1A， and DDIT4， thereby improving IR in the liver with T2DM.

Gegen Qinliantang Ameliorates Glucose and Lipid Metabolism Disorders in Rat Model of Catch-up Growth by Regulating SIRT1/PGC1α/Nrf1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Gegen Qinliantang on glucose and lipid metabolism in the rat model of catch-up growth （CUG） induced by a high-fat diet and the underlying mechanism. MethodA total of 60 SD rats were randomized into a normal control group （n=18） and a modeling group （n=42）. The rat model of CUG was established with a restricted diet followed by a high-fat diet， and the changes of general status and body weight were observed. The levels of fasting blood glucose （FBG）， fasting insulin （FINS）， triglyceride （TG）， and total cholesterol （TC） were measured in 6 rats in each group at the end of the 4th and 8th week， respectively. The homeostasis model assessment of insulin resistance index （HOMA-IR） was calculated， and the insulin sensitivity and body composition changes of CUG rats were evaluated. The successfully modeled rats were assigned into 6 groups： normal control， model， high-， medium-， and low-dose Gegen Qinliantang （2.5， 5， 10 g·kg-1）， and pioglitazone （3.125 mg·kg-1）. The rats were administrated with corresponding drugs by gavage for 6 weeks， and the normal control group and model group were administrated with the same amount of normal saline. During the experiment period， the changes of body weight were recorded， and the FBG， FINS， HOMA-IR， TG， and TC were determined at the end of the experiment. Hematoxylin-eosin （HE） staining was employed to observe the pathological changes of skeletal muscle in rats. The levels of reactive oxygen species （ROS） and malondialdehyde （MDA） in the skeletal muscle were measured strictly according to the manuals of the reagent kits. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was performed to measure the mRNA levels of silencing information regulator 1 （SIRT1）， peroxisome proliferator-activated receptor-gamma coactivator1α （PGC1α）， and nuclear respiratory factor 1 （Nrf1） in the skeletal muscle. Western blot and immunohistochemistry were employed to assess the expression of SIRT1， PGC1α， and Nrf1 in the skeletal muscle. ResultCompared with the normal control group， the model group presented elevated levels of FBG， FINS， TG， and TC （P<0.05， P<0.01）， increased HOMA-IR （P<0.01）， increased diameter of muscle fibers and adipocytes between muscle cells in the skeletal muscle， rising levels of ROS and MDA in the skeletal muscle （P<0.01）， and down-regulated mRNA and protein levels of SIRT1， PGC1α， and Nrf1 （P<0.05， P<0.01）. Compared with the model group， Gegen Qinliantang （especially the medium and high doses） and pioglitazone decreased the body weight， FINS， HOMA-IR， and TG （P<0.05， P<0.01） and reduced interstitial components such as intermuscular fat in the skeletal muscles and the diameter of muscle fibers. Furthermore， the drugs lowerd the levels of ROS and MDA （P<0.05， P<0.01） and up-regulated the mRNA and protein levels of SIRT1， PGC1α， and Nrf1 （P<0.05， P<0.01） in the skeletal muscle. ConclusionGegen Qinliantang can ameliorate the glucose and lipid metabolism disorders and insulin resistance in CUG rats by regulating the SIRT1/PGC1α/Nrf1 signaling pathway.

Rendimiento diagnóstico de once indicadores para resistencia a la insulina en una muestra de pobladores peruanos

Introducción: La resistencia a la insulina (RI) es una de las principales causas del desarrollo de patologías crónicas. Es indispensable su detección temprana, por ello es importante estudiar métodos más asequibles y menos costosos como los biomarcadores. Objetivo: Determinar la precisión diagnóstica de once biomarcadores para RI en una muestra de pobladores peruanos. Metodología: Estudio de pruebas diagnósticas. Análisis de base de datos secundario del estudio PERU MIGRANT. Para medir RI se utilizó como referencia la evaluación del modelo homeostático (HOMA-IR) ≥ 2,8. Los biomarcadores se basaron en la ratio de lípidos, los indicadores de lípido visceral, los indicadores con triglicéridos y glucosa (TyG), y los indicadores con cintura abdominal. Para la precisión se utilizó el análisis de la curva de características operativas del receptor y el área bajo la curva (AUC) con sus respectivos intervalos de confianza al 95% (IC95%). Resultados: Se estudió a 938 participantes. La prevalencia de RI fue del 9,91%. En relación con el análisis ROC, el índice TyG - índice de masa corporal (TyG - IMC) tuvo el mayor AUC, tanto en hombres: AUC=0,85 (0,81 - 0,90), corte=241,55; sens=92,5 (79,6 - 98,4) y esp=78,3 (73,9 - 82,2); como en mujeres: AUC=0,81 (0,76 - 0,85), corte=258,77; sens=79,2 (70,3 - 86,5) y esp= 82,1 (78,0 - 85,8). Discusión: Según los datos analizados, el índice TyG-IMC es el mejor indicador para medir RI. Es un índice simple que se puede tomar de manera rutinaria en la práctica clínica diaria. Es conveniente añadir futuros estudios prospectivos que confirmen su capacidad predictiva.

Introduction: Insulin resistance (IR) is one of the main causes of chronic disease. Early detection is essential, which is why it is important to study more affordable and less expensive methods, such as biomarkers. Objective: To determine the diagnostic accuracy of 11 biomarkers of IR in a sample of Peruvian residents. Method: diagnostic tests. Secondary Database Analysis of the PERU-MIGRANT Study. To measure RI, a homeostatic model evaluation (HOMA-IR) ≥ 2.8 was used as a reference. Biomarkers were based on the lipid ratio, visceral lipid indicators, indicators of triglycerides and glucose (TyG), and indicators of abdominal waist. For precision, the receiver operating characteristic curve and area under the curve (AUC) with their respective 95% confidence intervals (95%CI) were used. Results: A total of 938 participants were studied. The prevalence of IR was 9.91%. In relation to the ROC analysis, the TyG index - body mass index (TyG - BMI) had the highest AUC, both in men: AUC=0.85 (0.81 - 0.90), cut-off=241.55; sens=92.5 (79.6 - 98.4) and sp=78.3 (73.9 - 82.2); as in women: AUC=0.81 (0.76 - 0.85), cut-off=258.77; sens=79.2 (70.3 - 86.5) and esp= 82.1 (78.0 - 85.8). Discussion: According to the data analyzed, the TyG-IMC index is the best indicator for measuring IR. It is a simple index that can be routinely used in clinical practice. Future prospective studies are needed to confirm its predictive capacity.

Associação entre a doença pancreática gordurosa não alcoólica e o índice triglicérides/glicose / Association between nonalcoholic fatty pancreatic disease and triglyceride/glucose index

ABSTRACT Background: Nonalcoholic fatty pancreatic disease (NAFPD) is an increase of fat in the pancreas, and has an important association with insulin resistance (IR) and type 2 diabetes mellitus. Research has confirmed that the triglyceridemia/glycemia (TyG) index determines IR as much as does the hyperinsulinemic-euglycemic clamp assessment as the homeostasis model testing of IR (HOMA-IR). Objective: To eva­luate the association between degree of NAFPD and TyG index. Methods: In 72 patients undergoing ultrasound of abdomen with a diagnosis of NAFPD, insulin, glucose, and triglycerides levels were evaluated. The HOMA-IR and TyG indexes were used as a reference for IR. The degrees of NAFPD and the TyG index were presented through the receiver operating characteristics (ROC) curves in order to evaluate the association between different degrees of NAFPD, and the correlation of NAFPD with HOMA-IR was also evaluated. Results: There was a statistically significant correlation between the degree of NAFPD and the TyG index. The AUROC curve for the TyG index for predicting the degree of NADPD was 0.855 (0.840-0.865). The intensity-adjusted probabilities of the degree of NAFPD were more strongly associated with TyG values when compared with HOMA-IR. Conclusion: In this study the TyG index correlated positively with the degree of NAFPD, performing better than HOMA-IR.

RESUMO Contexto: A doença pancreática gordurosa não alcoólica (DPGNA) é um aumento de gordura pancreática, e tem uma importante associação com a resistência à insulina (RI) e com diabetes mellitus tipo 2. Pesquisas confirmaram que o índice triglicérides/glicemia (TyG) determina a RI tanto quanto a avaliação da clamp hiperinsulinêmico-euglicêmico como o teste do modelo de homeostasia da RI (HOMA-IR). Objetivo: Avaliar a associação entre o grau de DPGNA e o índice TyG. Métodos: Em 72 pacientes submetidos a ultrassonografia do abdome com diagnóstico de DPGNA, foram avaliados os níveis de insulina, glicose e triglicérides. Os índices HOMA-IR e TyG foram usados como referência para RI. Os graus de DGPNA e o índice TyG foram apresentados através da curva ROC com o objetivo de avaliar a associação entre diferentes graus de DPGNA, e a correlação do DGPNA com o HOMA-IR também foi avaliada. Resultados: Houve uma correlação estatisticamente significativa entre o grau de DPGNA e o índice TyG. A curva AUROC para o índice TyG para prever o grau do NADPD foi 0,855 (0,840-0,865). As probabilidades ajustadas de intensidade do grau de NAFPD foram mais fortemente associadas aos valores de TyG quando comparadas com o HOMA-IR. Conclusão: Neste estudo, o índice TyG correlacionou-se positivamente com o grau de DPGNA, tendo um desempenho melhor que o índice HOMA-IR.

Clinical and metabolic characteristics of males with early-onset androgenetic alopecia

Background: Men with early-onset androgenetic alopecia (AGA) often have an abnormal hormonal milieu. Objective: To ascertain the clinico-phenotypic characteristics and the prevalence of hormonal and metabolic changes in men with early-onset AGA. Methods: Consecutive male patients less than 30 years of age with a Norwood-Hamilton grade ?3 AGA were recruited in this comparative cross-sectional study. After endocrine evaluation they were classified into two groups, that is, Group A consisting of subjects with an altered hormonal profile and Group B with normal hormonal profiles. The groups were assessed for differences in disease phenotype and severity (Norwood-Hamilton grade), insulin resistance and parameters of metabolic syndrome (ATP III guidelines). Results: Altered hormonal profiles were seen in 34 of the 100 subjects with AGA, while insulin resistance and metabolic syndrome were noted in 44 and 26 respectively. Altered hormonal profiles were significantly associated with insulin resistance and severe alopecia (grade 4 and above Hamilton-Norwood Scale). Insulin resistant Group A patients had a significantly higher prevalence of severe alopecia (>grade 4) (P = 0.0036). The prevalence of metabolic syndrome was similar in both groups. Limitation: The cross sectional study design was a drawback of this study. Further, a control arm without AGA was not included and the sample size of 100 was selected arbitrarily. Conclusion: An altered hormonal profile and insulin resistance was noted in a third of the males with early-onset AGA. Subjects with altered hormonal profiles had a higher prevalence of insulin resistance and were likely to have severe grades of AGA

Evaluation of an association between maternal prenatal psychological stress and insulin resistance during pregnancy and postpartum

Objectives: Various physiological mechanisms counteract insulin resistance (IR) during normal pregnancy. Psychological stress is a known, independent risk factor for developing IR. Pregnancy-specific psychological stress may cause IR and increase the risk of overt diabetes. Hence, the study aims to evaluate maternal psychological stress using multiple stress markers and their association with changes in IR during pregnancy and postpartum. Materials and Methods: Anthropometric measurements such as height, weight and skinfold thickness were measured using standard techniques. The stress markers were assessed using perceived stress scales (K10 questionnaire), a physiological marker of stress (Heart rate variability [HRV] measures) and biochemical stress markers (Saliva, hair cortisol levels). IR was estimated using homeostasis model assessment-estimated IR (HOMA-IR). The association of stress markers with IR was studied among fifty healthy pregnant women during pregnancy and postpartum. Results: The psychological stress scores and saliva cortisol were significantly higher during pregnancy than postpartum (P = 0.000). A comparison of cardiac autonomic function as assessed by HRV measures shows that high frequency in normalised units (HFnu) was significantly higher during the postnatal period than in the prenatal period (P = 0.000). High frequency (HF) spectral power in absolute units was also significantly higher (P = 0.002) in the postpartum period (2612.30 ± 432.24) when compared with the prenatal period (1446.10 ± 299.15). Low frequency in normalised units (LFnu), low frequency (LF)/HF ratio was significantly higher during the prenatal period than in the postnatal period (P = 0.000). As assessed by HOMA-IR values, IR was significantly higher during the prenatal period than postpartum (P = 0.04). There was a significant positive correlation between prenatal psychological stress scores, HRV parameters (LFnu, LF/HF) and postnatal IR. Conclusion: Pregnancy is associated with higher psychological stress levels and IR than postpartum. Furthermore, the maternal cardiac autonomic marker could predict postnatal IR among healthy pregnant women.

Triglyceride-glucose index levels in patients with Klinefelter syndrome and its relationship with endothelial dysfunction and insulin resistance: a cross-sectional observational study

ABSTRACT Objectives: This study aimed to investigate the triglyceride-glucose (TyG) index, which is a simple surrogate marker of insulin resistance that is associated with various cardiometabolic diseases, in patients with Klinefelter syndrome (KS). Subjects and methods: A total of 30 patients with KS (mean age: 21.53 ± 1.66 years) and 32 healthy controls (mean age: 22.07 ± 1.01 years) were included in the study.The clinical and laboratory parameters,TyG index, asymmetric dimethylarginine (ADMA) level, homeostatic model assessment of insulin resistance (HOMA-IR) score, and high-sensitivity C-reactive protein level were measured in patients with KS and healthy subjects. Results: Patients with KS had higher HOMA-IR score (p = 0.043), ADMA levels (p < 0.001), and TyG index (p = 0.031) and lower high-density lipoprotein cholesterol levels (p < 0.001) than healthy subjects. TyG index was positively correlated with plasma ADMA (r = 0.48, p < 0.001) and HOMA-IR (r = 0.36, p = 0.011). Multivariate analyses showed that total testosterone level (β = −0.44, p = 0.001) and TyG index (β = 0.29, p = 0.045) were independent determinants of plasma ADMA levels. Conclusion: Patients with KS had higher TyG indices than healthy subjects. Moreover, TyG index was independently associated with endothelial dysfunction in patients. TyG index may be a practical and useful measure to show the increased endothelial dysfunction in patients with KS.

Body adiposity markers and insulin resistance in patients with type 1 diabetes

ABSTRACT Objectives: Body composition changes are associated with adverse effects such as increased insulin resistance (IR) in individuals with diabetes mellitus. This study aims to evaluate the association between different body adiposity markers and IR in adults with type 1 diabetes (T1D). Subjects and methods: The cross-sectional study included outpatient adults with T1D from a university public hospital in southern Brazil. The body adiposity markers studied were waist circumference (WC), waist-height ratio (WHtR), body mass index (BMI), conicity index (CI), lipid accumulation product (LAP) and body adiposity index (BAI). IR was calculated using an Estimated Glucose Disposal Rate (EGDR) equation (analyzed in tertiles), considering an inverse relation between EGDR and IR. Poisson regression models were used to estimate the odds ratio (OR) and 95% CIs of association of adiposity markers with IR. Results: A total of 128 patients were enrolled (51% women), with a median EGDR of 7.2 (4.4-8.7) mg.kg−1.min−1. EGDR was negatively correlated with WC (r = −0.36, p < 0.01), WHtR (r = −0.39, p < 0.01), CI (r = −0.44, p < 0.01), LAP (r = −0.41, p < 0.01) and BMI (r = −0.24, p < 0.01). After regression analyses, WC (OR = 2.07; CIs: 1.12-3.337; p = 0.003), WHtR (OR = 2.77; CIs: 1.59-4.79; p < 0.001), CI (OR = 2.59; CIs: 1.43-4.66; p = 0.002), LAP (OR = 2.27; CIs: 1.25-4.11; p = 0.007) and BMI (OR = 1.78; CIs: 1.09-2.91; p = 0.019) remained associated with IR. Conclusions: The authors suggest using the studied adiposity markers as a routine since they were shown to be suitable parameters in association with IR.

Impact of hepatitis C virus eradication with direct-acting antivirals on glycidic metabolism

ABSTRACT Objective: To compare the glucose metabolism of patients with chronic hepatitis C virus infection treated with direct-acting antivirals (DAAs) in pretreatment and sustained viral response (SVR) periods. Materials and methods: This was an intervention pre-post study of 273 patients with chronic hepatitis C virus infection treated with DAAs from March 2018 to December 2019. Glycidic metabolism was evaluated through homeostasis model assessment (HOMA) - insulin resistance (IR) and HOMA-β indices and assessments of insulinemia and HbA1c levels. These parameters were analyzed with a T test by paired comparison of the means of the variables and Wilcoxon's test paired for the median; in the variables with an abnormal distribution, the Z score was generated for the mean in both the pretreatment and SVR periods. Statistical significance was considered at p ≤ 0.05. Results: Among 273 participants, 125 (45.8%) had prediabetes, and 50 (18.3%) had diabetes. In SVR, there was a significant increase in platelets, albumin, alkaline phosphatase, cholesterol and triglycerides and a significant decrease in aspartate aminotransferase, alanine aminotransferase, gamma GT and bilirubin. The HOMA-IR and HOMA-β indices increased in SVR from 1.95 to 2.29 (p = 0.087) and 71.20 to 82.60 (p = 0.001), respectively. Insulinemia increased from 7.60 μU/mL to 8.90 μU/mL (p = 0.011). HbA1c decreased from 5.6 to 5.4 (p < 0.001). Among patients with prediabetes and those with diabetes, the reduction in HbA1c values was significant (p = 0.006 and p = 0.026, respectively). Conclusion: SVR significantly impacts and leads to improvement in glucose metabolism in patients with chronic liver disease induced by hepatitis C virus.

Relationship between vitamin B12 levels and insulin resistance in postmenopausal women from Colombia Caribbean / Relação entre níveis de vitamina B12 e resistência à insulina em mulheres na pós-menopausa da Colômbia Caribe

Introduction: The high prevalence of low vitamin B12 serum levels has been recognized as a public health problem in Latin America; however, the current magnitude of this deficiency in Colombia is uncertain. Low levels of vitamin B12 can induce clinical and subclinical hematological and neurological disorders. Epidemiological studies have demonstrated a relationship between vitamin B12 deficiency and cardiovascular diseases (CVDs). However, the role of vitamin B12 in insulin resistance has been poorly studied. Objective: This study aimed to evaluate the relationship between vitamin B12 serum levels and biochemical and anthropometric markers related to CVDs and insulin resistance in postmenopausal women from Colombia Caribbean. Methods: Correlational, descriptive study. By convenience sampling, 182 postmenopausal women from the medical consultation service of a health institution were linked. Serum vitamin B12 levels, anthropometric variables (body mass index, abdominal perimeter), and biochemical variables (glycemia, insulin, lipid profile, HOMA IR) were evaluated. Results: The average value of the vitamin B12 serum level was 312.5 ± 122.5 pg/mL (230.6 ± 90.4 pmol/L); 46.7% of the women had less than adequate levels of 300 pg/mL (> 221 pmol/L), and 9. 9% were deficient, with levels of less than 200 pg/mL (148 pmol/L). The women with metabolic syndrome were 63.7%, and according to HOMA IR, 52.7 % had insulin resistance. A significant inverse relationship was shown between serum vitamin B12 levels with basal glycemic (P =0.002) and HOMA-IR (P =0.040). Conclusions: A significant inverse relationship between vitamin B12 levels and basal glycemia and HOMA-IR was observed. These findings highlight vitamin B12 deficiency in postmenopausal women and suggest nutritional supplementation.Keywords: Vitamin B12, Insulin resistance, Diet, Postmenopause, Cardiovascular diseases (AU).

Introdução: A alta prevalência de baixos níveis séricos de vitamina B12 foi reconhecida como um problema de saúde pública na América Latina, mas a magnitude atual dessa deficiência na Colômbia é incerta. Baixos níveis de vitamina B12 podem induzir distúrbios hematológicos e neurológicos clínicos e subclínicos. Na verdade, estudos epidemiológicos demonstram uma relação entre deficiência de vitamina B12 e doenças cardiovasculares (DCVs). No entanto, o papel da vitamina B12 na resistência à insulina tem sido pouco estudado. Objetivo: O objetivo deste estudo foi avaliar a relação entre os níveis séricos de vitamina B12 e marcadores bioquímicos e antropométricos relacionados com doenças cardiovasculares e resistência à insulina em mulheres pós-menopáusicas da Colômbia Caribe. Métodos: Estudo correlacional, descritivo. Por amostragem de conveniência, foram vinculadas 182 mulheres na pós-menopausa do serviço de consulta médica de uma instituição de saúde. Níveis séricos de vitamina B12, variáveis antropométricas (índice de massa corporal, perímetro abdominal) e variáveis bioquímicas (glicemia, insulina, perfil lipídico, HOMA IR) foram avaliadas. Resultados: O valor médio do nível sérico de vitamina B12 foi de 312,5 ± 122,5 pg/mL (230,6 ± 90,4 pmol/L); 46,7% das mulheres tinham níveis abaixo do adequado de 300 pg/mL (> 221 pmol/L), e 9,9% eram deficientes, com níveis abaixo de 200 pg/mL (148 pmol/L).As mulheres com síndrome metabólica foram 63,7% e, segundo o HOMA IR, 52,7% apresentavam resistência à insulina. Uma relação inversa significativa entre os níveis séricos de vitamina B12 com glicemia basal (P = 0,002) e HOMA-IR (P = 0,040) foi mostrada. Conclusões: Foi observada uma relação inversa significativa entre os níveis de vitamina B12 e glicemia basal e HOMA-IR. Esses achados destacam a deficiência de vitamina B12 em mulheres na pós-menopausa e sugerem suplementação nutricional (AU).

Síndrome metabólico en el adulto mayor vinculado a los programas de actividad física comunitaria / Metabolic Syndrome in the Elderly Adult Involved in the Community Physical Activity Programs

Introducción: El síndrome metabólico es una situación clínica compleja que se asocia a un incremento de la morbilidad y mortalidad. Los elementos que lo componen aumentan el riesgo de diabetes mellitus tipo II y enfermedad cardiovascular. Objetivo: Determinar el comportamiento del síndrome metabólico en el adulto mayor vinculado a los programas de actividad física comunitaria del proyecto Lindo Amanecer del municipio Arroyo Naranjo. Métodos: Se realizó un estudio observacional descriptivo de corte transversal. El universo de estudio lo constituyeron 120 adultos mayores, de los que se entrevistaron a 106, en el período de abril a octubre de 2018. Se siguieron los criterios del Adult Treatment Panel III para el diagnóstico de síndrome metabólico. Las variables descriptivas se expresaron en porcientos y para la comparación de variables en estudio se utilizó el método estadístico de ji al cuadrado. Resultados: Los resultados obtenidos mostraron un 41,51 por ciento de personas con síndrome metabólico, predominaron las personas de 70 y más años de edad (54,54 por ciento y el sexo femenino (93,18 por ciento). El 100 por ciento tuvieron cifras de presión arterial ≥ 130/85 mmHg. El 100 por ciento de los pacientes desconocían su enfermedad. Conclusiones: Se encontró predominio en los pacientes con síndrome metabólico del sexo femenino y del grupo de edad de 70 y más años. El diagnóstico a nivel de la Atención Primaria de Salud es deficiente. Se asocia a la hipertensión arterial, obesidad abdominal y al riesgo de enfermedad cardiovascular(AU)

Introduction: Metabolic syndrome is a complex clinical situation associated with an increase in morbidity and mortality. The elements that mark it up increase the risk of type 2 diabetes mellitus and cardiovascular disease. Objective: To determine the behavior of metabolic syndrome in elderly adults involved in the community physical activity programs of the Lindo Amanecer project in the municipality of Arroyo Naranjo. Methods: A cross-sectional descriptive observational study was carried out. The study universe was made up of 120 elderly adults, 106 of which were interviewed in the period from April to October 2018. The Adult Treatment Panel III criteria for the diagnosis of metabolic syndrome were followed. The descriptive variables were expressed in percentages and, for the comparison of variables under study, the chi-square statistical method was used. Results: The obtained results showed 41.51percent of people with metabolic syndrome, with a predominance of people aged 70 years and older (54.54percent) and the female sex (93.18percent). One hundred percent had blood pressure values over or equal to 130/85 mmHg. One hundred percent of the patients did not have any knowledge of their disease. Conclusions: In patients with metabolic syndrome, the predominance corresponded to the female sex, as well as the age group of 70 years and older. Diagnosis at the primary healthcare level is deficient. It is associated with arterial hypertension, abdominal obesity and the risk of cardiovascular disease(AU)