Insulin reference intervals in Brazilian adolescents by direct and indirect approaches: validation of a data mining method from laboratory data

Abstract Objective To determine reference intervals (RI) for fasting blood insulin (FBI) in Brazilian adolescents, 12 to 17 years old, by direct and indirect approaches, and to validate indirectly determined RI. Methods Two databases were used for RI determination. Database 1 (DB1), used to obtain RI through a posteriori direct method, consisted of prospectively selected healthy individuals. Database 2 (DB2) was retrospectively mined from an outpatient laboratory information system (LIS) used for the indirect method (Bhattacharya method). Results From DB1, 29345 individuals were enrolled (57.65 % female) and seven age ranges and sex partitions were statistically determined according to mean FBI values: females: 12 and 13 years-old, 14 years-old, 15 years-old, 16 and 17 years-old; and males: 12, 13 and 14 years-old, 15 years-old, 16 and 17 years-old. From DB2, 5465 adolescents (67.5 % female) were selected and grouped according to DB1 partitions. The mean FBI level was significantly higher in DB2, on all groups. The RI upper limit (URL) determined by Bhattacharya method was slightly lower than the 90 % CI URL directly obtained on DB1, except for group female 12 and 13 years old. High agreement rates for diagnosing elevated FBI in all groups on DB1 validated indirect RI presented. Conclusion The present study demonstrates that Bhattacharya indirect method to determine FBI RI in adolescents can overcome some of the difficulties and challenges of the direct approach.

Impact of Nigella sativa oil on glycemic control in alloxan-induced diabetic Wistar rats

Background: To effectively manage diabetes, it is crucial to achieve optimal glycemic control by ensuring that A1C levels remain below 7.0%. This study aimed to investigate the impact of Nigella sativa oil (black seed oil, BSO) on glycemic control in alloxan-induced diabetic Wistar rats. Methods: Forty (40) male Wistar rats weighing 200-250 gm were randomly allocated into eight (8) groups of five (5) animals per group. Group 1 received normal saline as the normoglycemic control, while groups 2 to 8 were given alloxan monohydrate to induce hyperglycemia, following the method of Osikwe et al. Following the induction of hyperglycemia, group 2 received normal saline, group 3 received 200 mg/kg of metformin, group 4 received 2 mg/kg of glimepiride, group 5 received 2.5 ml/kg of BSO, group 6 received glimepiride and BSO, group 7 received metformin and BSO, and group 8 received BSO, glimepiride, and metformin. Results: The results showed that BSO significantly reduced fast blood glucose levels compared to the diabetic control group (p<0.05), lowered glycosylated hemoglobin to <7%, and improved pancreatic beta cell function. Conclusions: Black seed oil reduces fasting blood glucose, exhibits synergism with glimepiride, and improves pancreatic beta-cell function in alloxan-induced diabetic Wistar rats.

Resistencia a la Insulina en adultos con sobrepeso y obesidad / Insulin resistance in overweight and obese adults

Resumen El objetivo de esta investigación fue analizar la relación de resistencia a la insulina, sobrepeso y obesidad. Con una población de 2574 pacientes con diagnóstico de obesidad y sobrepeso, se obtuvo una muestra de 334 pacientes. Se realizó un estudio de tipo descriptivo, documental, retrospectivo, transversal y correlacional. Para la recolección de datos se empleó las historias clínicas registradas en el sistema operativo AS400 de IBM, de atención médica del Instituto Ecuatoriano de Seguridad Social. El resultado total de los pacientes perteneció al sexo femenino con un porcentaje del 77.84 %, residencia urbana (73.65 %) e instrucción superior (60.5 %). El 52.8 % de los individuos registró un IMC >30kg/m2. Los pacientes adultos jóvenes de instrucción superior, sexo masculino y sector urbano registraron la mayor prevalencia de resistencia a la insulina, siendo ésta del 61.7 %. En el análisis bivariado los pacientes con obesidad mórbida presentaron mayor riesgo de resistencia a la insulina (RP:1.5; IC95 %:1. 29; 1.77). Se estableció una relación significativa entre el antecedente familiar de diabetes mellitus tipo 2 y el riesgo de presentar resistencia a la insulina (p<0.001; RP: 1.32; IC 95 %: 1.12: 1.56). Los valores de hiperglucemia, hiperinsulinemia e hiperuricemia, así como de AST Y ALT elevadas registraron una relación significativamente con HOMA-IR >3. Se concluye que la resistencia a la insulina es una entidad frecuente en pacientes con sobrepeso y obesidad, identificándose una mayor prevalencia en el género masculino, misma que predispone a la progresión de enfermedades crónicas.

Abstract This research aimed to analyze the relationship between insulin resistance, overweight and obesity. A population of 2,574 patients diagnosed with obesity and overweight was obtained, considering a sample of 334 patients. A descriptive, documentary, retrospective, cross-sectional, and correlational study was conducted. For data collection, the medical records recorded in the IBM AS400 operating system for the Ecuadorian Social Security Institute's medical care were used. The total result of the patients belonged to the female sex with a percentage of 77.84%, urban residence (73.65%), and higher education (60.5%). 52.8% of the individuals registered a BMI > 30kg/m2. Young adult patients with higher education, male sex, and urban sector registered the highest insulin resistance prevalence, 61.7%. In the bivariate analysis, patients with morbid obesity presented a higher risk of insulin resistance (PR: 1.5; 95% CI: 1. 29, 1.77). A significant relationship was established between family history of type 2 diabetes mellitus and the risk of developing insulin resistance (p<0.001; PR: 1.32; 95% CI: 1.12: 1.56). The values of hyperglycemia, hyperinsulinemia, hyperuricemia, and elevated AST and ALT were significantly related to HOMA-IR > 3. It was concluded that insulin resistance is a frequent entity in overweight and obese patients, with a higher prevalence identified in the male gender, which predisposes to the progression of chronic diseases.

A prática do autocuidado no tratamento do diabetes mellitus tipo II por usuários de insulina / The practice of self-care in the treatment of Type II Diabetes Mellitus by insulin users

Este estudo objetivou avaliar o nível de aderência ao autocuidado no tratamento do DMII entre pacientes usuários de insulina atendidos em uma unidade de saúde da família em Palmas, Tocantins, em 2023. Trata-se de uma pesquisa com abordagem quantitativa com 24 portadores de DMII em uso de insulina que responderam a dois questionários, um com perguntas sociodemográficas e o outro sobre atividades de autocuidado relacionadas ao diabetes. Os resultados mostraram que os entrevistados demonstraram baixa adesão ao exercício e à atividade física, com uma média abaixo de 2, o que representou o pior resultado obtido no QAD. Em contrapartida, a adesão ao uso dos medicamentos orais e insulina foi satisfatória, com médias superiores a seis dias por semana. A maioria dos entrevistados apresentou melhor adesão ao tratamento medicamentoso, seja de forma isolada ou associada com cuidados específicos, como cuidado com os pés, ou baixa ingestão de doces. No entanto, a prática de exercício e a atividade física e a adesão às orientações alimentares foram as áreas de menor comprometimento. Diante disso, recomenda-se que os profissionais da saúde desenvolvam estratégias clínico-educativas direcionadas aos portadores de DMII, com o intuito de promover a saúde e incentivar o uso correto dos fármacos e a adesão aos autocuidados, objetivando prevenir complicações relacionadas a essa patologia, além de reforçar a importância do autocuidado para prevenir complicações associadas à doença.

This study aimed to evaluate the level of adherence to self-care in the treatment of DMII among insulin-using patients treated at a family health unit in Palmas, Tocantins, in 2023. This is a quantitative study with 24 DMII patients using insulin who answered two questionnaires, one with sociodemographic questions and the other about self-care activities related to diabetes. The results showed that the interviewees demonstrated low adherence to exercise and physical activity, with an average below 2, which represented the worst result obtained in the QAD. In contrast, adherence to the use of oral medications and insulin was satisfactory, with averages of more than six days per week. The majority of interviewees showed better adherence to medication treatment, whether alone or associated with specific care, such as foot care, or low intake of sweets. However, exercise and physical activity and adherence to dietary guidelines were the areas of least impairment. Therefore, it is recommended that health professionals develop clinical-educational strategies aimed at people with DMII, with the aim of promoting health and encouraging the correct use of drugs and adherence to self-care, aiming to prevent complications related to this pathology, and reinforces the importance of self-care to prevent complications associated with the disease.

Análise da efetividade do grupo de gestantes na modalidade online como ferramenta de aprendizagem gravídico puerperaleral / Analysis of the effectiveness of the online pregnancy group as a pregnancy and puerperal learning tool

Objetivo: Analisar a efetividade do grupo de gestantes na modalidade online como ferramenta de aprendizagem. Método: Estudo epidemiológico, transversal, observacional e descritivo. As participantes foram pacientes que participaram do grupo de gestantes, em um centro de parto normal, na modalidade presencial ou online. Os dados foram coletados através de um questionário estruturado, contendo 16 perguntas fechadas, acerca dos assuntos abordados no curso. Resultado: Verificamos a predominância de maiores acertos de questões no grupo presencial em comparação ao grupo online. Porém, observou-se que a média de acertos do grupo online gira em torno de 12,44 de um total de 16 questões, o que é muito efetivo. Conclusão: O grupo de gestante na modalidade online, se mostra como uma ferramenta efetiva no processo de ensino-aprendizagem, na medida que os ensinamentos e compartilhamentos de informações são absorvidos em sua maioria pelas gestantes.(AU)

Objective: to identify improvement through risk management applied to the acquisition and distribution processes of NPH human insulins. Method: The study was carried out in stages: in the 1st moment, meetings were held (Brainstorming) and in the 2nd moment, an electronic form was elaborated in the form of a questionnaire, showing the risk "events" with the weights inherent to the probability and impact they generated the risk inherent in the acquisition and distribution processes of NPH and Regular human insulins by the Ministry of Health. Results: Considering the processes, there was a higher incidence of medium risks. No very low risk was indicated, no extreme risk was identified and only 02 (two) high risks were presented. Conclusion: The risk management of the aforementioned study is an improvement tool for the processes of acquisition and distribution of NPH and Regular human insulins by the Ministry of Health.(AU)

Objetivo: identificar la mejora a través de la gestión de riesgos aplicada a los procesos de adquisición y distribución de insulinas humanas NPH. Método: El estudio se realizó por etapas: en el 1er momento se realizaron reuniones (Brainstorming) y en el 2do momento se elaboró un formulario electrónico en forma de cuestionario, mostrando los "eventos" de riesgo con los pesos inherentes a la probabilidad e impacto que generaron los riesgos inherentes a los procesos de adquisición y distribución de insulinas humanas NPH y Regular por parte del Ministerio de Salud. Resultados: Considerando los procesos, hubo una mayor incidencia de riesgos medios. No se indicó riesgo muy bajo, no se identificó riesgo extremo y solo se presentaron 02 (dos) riesgos altos. Conclusión: La gestión de riesgos del mencionado estudio es una herramienta de mejora para los procesos de adquisición y distribución de insulina humana NPH y Regular por parte del Ministerio de Salud.(AU)

Hipertrigliceridemia asociada a resistencia a la insulina en niños con obesidad / Hypertriglyceridemia associated with insulin resistance in children with obesity

RESUMEN Introducción: La hipertrigliceridemia se ha vinculado con la resistencia a la insulina. Objetivos: Evaluar la relación y capacidad predictiva de la hipertrigliceridemia para la resistencia a la insulina en niños obesos. Métodos: Se realizó un estudio transversal y analítico en niños de 6 a 14 años con obesidad, atendidos en el Hospital Belén de Trujillo entre 2014 y 2019. Se analizaron 58 historias clínicas elegidas aleatoriamente. La resistencia a la insulina se midió mediante el índice Homeostasis Model Assessment (HOMA) (≥3). Se usaron análisis descriptivos, correlacionales y cálculos de Odds Ratio (OR), además de indicadores de predicción como sensibilidad y especificidad. Resultados: De los 58 niños estudiados, el 58,6% presentaba niveles elevados de triglicéridos y el 74,1% mostró resistencia a la insulina. Hubo una correlación significativa entre los niveles de triglicéridos y el índice HOMA (coef.: 0,543; p<0,001). Los niveles elevados de triglicéridos (OR=18,91; IC 95%: 3,67-97,36; p<0,001), glicemia en ayunas (OR=46,20; IC 95%: 5,39-396,06; p=0,010), de insulina en ayunas (OR=52,89; IC 95%: 6,11-457,55; p<0,001) y la presencia de acantosis nigricans (OR=36,17; IC 95%: 4,28-305,98; p<0,001) se asociaron significativamente con la resistencia a la insulina. La hipertrigliceridemia mostró una sensibilidad del 74,4% y una especificidad del 86,7% para predecir la resistencia a la insulina. Conclusión: La hipertrigliceridemia está significativamente asociada con la resistencia a la insulina en niños obesos y tiene un rendimiento aceptable como predictor de la misma. Este factor puede servir como un marcador temprano y predictor para implementar medidas preventivas adecuadas en poblaciones vulnerables.

ABSTRACT Introduction: Hypertriglyceridemia has been linked to insulin resistance. Objectives: To evaluate the relationship and predictive capacity of hypertriglyceridemia for insulin resistance in obese children. Methods: A cross-sectional analytical study was conducted in obese children aged 6 to 14 years, treated at the Belén Hospital of Trujillo between 2014 and 2019. Fifty-eight randomly selected medical records were analyzed. Insulin resistance was measured using the Homeostasis Model Assessment (HOMA) index (≥3). Descriptive, correlational analyses, and Odds Ratio (OR) calculations were used, along with predictive indicators such as sensitivity and specificity. Results: Of the 58 children studied, 58.6% had elevated triglyceride levels and 74.1% showed insulin resistance. There was a significant correlation between triglyceride levels and the HOMA index (coef.: 0.543; p<0.001). Elevated triglyceride levels (OR=18.91; 95% CI: 3.67-97.36; p<0.001), fasting glucose (OR=46.20; 95% CI: 5.39-396.06; p=0.010), fasting insulin (OR=52.89; 95% CI: 6.11-457.55; p<0.001), and the presence of acanthosis nigricans (OR=36.17; 95% CI: 4.28-305.98; p<0.001) were significantly associated with insulin resistance. Hypertriglyceridemia showed a sensitivity of 74.4% and a specificity of 86.7% for predicting insulin resistance. Conclusion: Hypertriglyceridemia is significantly associated with insulin resistance in obese children and has an acceptable performance as a predictor. This factor may serve as an early marker and predictor to implement appropriate preventive measures in vulnerable populations.

A case report of severe hypertriglyceridemia induced acute pancreatitis managed with continuous insulin infusion

31-year-old male, chronic alcoholic presented to the emergency room with epigastric pain, nausea and vomiting. On examination he was febrile, had abdominal distention with tenderness in the epigastric region. His lipase was elevated and computed tomography of abdomen showed evidence of acute pancreatitis. His past history was significant for chronic myeloid leukemia on imatinib and poorly controlled type 2 diabetes mellitus. Laboratory studies revealed elevated triglyceride levels (5254 mg/dl) and uncontrolled blood sugars (HbA1c-10.77%). Due to the severity of his pancreatitis presentation, he was admitted to the intensive care unit. He received aggressive intravenous fluid hydration and was started on continuous insulin infusion. He improved significantly with insulin therapy. His triglyceride levels decreased from 5254 mg/dl to 1891 mg/dl after 48 hours of initiating insulin therapy, by fifth day of admission triglycerides were below 500 mg/dl and was clinically better. He was discharged with a basal dose of insulin and fenofibrates. Intravenous insulin infusion is an effective, affordable, and accessible therapy for acute pancreatitis due to severe hypertriglyceridemia.

Metabolic syndrome: a comprehensive review

Metabolic syndrome (syndrome X) includes several components like diabetes, hypertension, hyperlipidemia etc. Every patient should undergo detailed assessment for the silent presence of the components of metabolic syndrome. Genetic predisposition, increased nutrient- dense food, decreased physical activity and chronic stress are common in metabolic syndrome. Insulin resistance, obesity and hyperglycaemia are commonly seen which can later lead to serious consequences like cardiovascular complications, thrombotic events etc. Clinical features depend on the components of the metabolic syndrome in a patient. Some may present with complications and advanced disease. For non-diabetic individuals, oral glucose tolerance test is indicated. It is better to study serum uric acid level and to screen for silent kidney stones. Specific drugs are prescribed as indicated. Drugs for stress and insomnia are also prescribed. Thrombotic status of the patient should be considered, and antiplatelet drugs are prescribed if risk factors are present. Non-pharmacological measures like diet modification and increased physical activity should be given on a priority basis. Patient compliance of these two measures should be monitored regularly. Future deployment of “artificial intelligence – powered” predictive diagnostic tests will help in detecting and controlling metabolic syndrome. “At risk” individuals and patients showing some components of metabolic syndrome should undergo full investigations to detect other components of metabolic syndrome. Full range of therapeutic drugs, diet modification and increased physical activity should be prescribed.

An Investigation of Type II Anti-diabetic activity of Biologically Active phytochemical(s) of Coccinia Indica Fruits in High Sugar Diet Induced Diabetic Rats

Unhealthy diets and lifestyles cause a resistance to and/or relative deficiency of insulin production. Therefore, it is thought worthwhile to develop a natural remedy that may effectively manage the disease symptoms to a certain extent without causing adverse consequences. The objective was to develop the active biological constituent(s) for the use of Coccinia indica and its relationship to treating type II diabetic rats. The soxhlet extraction method was used to get the cocktail of phytochemicals of C. indica by using methanol. The composition of a high-sugar diet, followed by fructose (66%), was used to induce T2DM in rats. The preliminary predictive markers were body weight (pre- and post-treatment), blood glucose level (pre- and post-treatment), serum insulin, and pancreatic insulin. And the secondary outcomes were the pro-inflammatory mediators interleukin 6 (IL-6), transforming growth factor-? (TGF-?), and tumour necrosis factor alpha (TNF alpha). Additionally, pancreatic tissue was used to estimate beta cell mass, size, and necrosis, and the cell supernatant was used to observe superoxide dismutase (SOD), lipid peroxidation (LPO), and catalase (CAT). High sugar diet showed significant increase in body weight (p < 0.01), fasting blood glucose level (p < 0.001), and decrease in serum and pancreatic insulin levels (p < 0.001), whereas rats treated with methanolic extract of C. indica showed significant reduction in post-treatment body weight (p < 0.01), blood glucose levels (p < 0.01), and increase in serum and pancreatic insulin (p < 0.001), especially in higher doses, i.e., 400 mg/kg. Pro-inflammatory cytokines (IL-6, TGF-beta, and TNF-?) can increase insulin resistance, which results in poor glucose homeostasis, which has been reduced by treatment with C. indica (p<0.001). Superoxide radicals and a deficiency in catalase, both of which are linked to diabetes, but the extract of the plant has been shown to enhance the secretion of enzymes SOD and CAT (p<0.001). It has been proven to have a crucial role in the regulation of apoptosis because it lowers oxidative stress and similarly reduces the level of LPO (p<0.01). Additionally, the treated rat pancreas shows islets of Langerhans that are normal in number and size. No necrosis or reduction in size was seen. The current study conclusively shows that the phytoconstituents of C. indica have the potential to tackle long-term health complications and manage symptoms.

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.

Management of diabetic ketoacidosis in internal medicine: insulin protocols, electrolyte balance, and clinical outcomes

Diabetic ketoacidosis (DKA) is a critical complication of diabetes mellitus (DM), characterized by hyper-glycemia, acidosis, and ketosis. It poses a substantial risk of morbidity and mortality, especially in type 1 DM patients. DKA can be triggered by various factors, including insulin deficiency, infections, alcohol abuse, and other medical conditions. Hospital admissions for DKA are increasing, with mortality rates of up to 5-9%, often linked to severe underlying illnesses and complications such as myocardial infarction and stroke. Effective DKA management involves rehydration, correction of electrolyte imbalances, insulin administration, and addressing precipitating factors. Fluid resuscitation with isotonic saline is vital to restore hydration, and continuous intravenous insulin infusion is the preferred method to control blood glucose and suppress ketone production. Electrolyte imbalances, particularly potassium, sodium, phosphate, and magnesium, require careful monitoring and correction. Clinical outcomes in DKA management include resolving acidosis, normalizing blood glucose, and restoring electrolyte balance, all while achieving and maintaining clinical stability. Complications like cerebral edema and acute respiratory distress syndrome can significantly impact the prognosis. Long-term considerations encompass diabetes management, patient education, and follow-up care.

Baihe Wuyaotang Ameliorates NAFLD by Enhancing mTOR-mediated Liver Autophagy / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10-3 g·kg-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β1/drosophila mothers against decapentaplegic protein2/3（TGF-β1/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β1 proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

Activation of Nrf2/HO-1/NQO1 Signaling Pathway by Shenqi Tangluo Pill Improves Oxidative Stress Injury of Skeletal Muscle of Type 2 Diabetes Mellitus Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Shenqi Tangluo pill （SQTLP） on oxidative stress injury of skeletal muscle of type 2 diabetes mellitus （T2DM） mice based on nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） pathway. MethodA total of 60 7-week-old male db/db mice ［specific pathogen-free （SPF） grade］ were selected and fed for one week for adaption. They were divided into the model control group， SQTLP low-， medium- and high-dose （19， 38， and 76 g·kg-1） groups and metformin group （0.26 g·kg-1） by gavage. Each group consisted of 12 mice. Twelve male db/m mice of the same age were selected as the blank group. The intervention was implemented continuously for 8 weeks. Fasting blood glucose （FBG） was detected. Fasting serum insulin （FINS） levels were detected by enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment-insulin resistance （HOMA-IR） index and the homeostasis model assessment-insulin sensitivity index （HOMA-ISI） were calculated. Oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were conducted. The activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） and the contents of malondialdehyde （MDA） and reduced nicotinamide adenine dinucleotide phosphate （NADPH） in skeletal muscle tissues were detected by biochemical kits. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in skeletal muscle tissues. The levels of reactive oxygen species （ROS） and 4-hydroxynonenal （4-HNE） in skeletal muscle tissue were detected by immunofluorescence （IF）. The expression levels of Nrf2， HO-1， NQO1 and glutamate-cysteine ligase catalytic subunit （GCLC） proteins in skeletal muscle tissues were detected by Western blot. ResultCompared with those in the blank group， FBG， FINS and HOMA-IR in the model group were significantly increased （P<0.05）， while HOMA-ISI was decreased （P<0.05）. The results of OGTT and ITT showed that blood glucose was significantly increased at all time points （P<0.05）， and glucose tolerance and insulin tolerance were significantly impaired. SOD and GSH-Px activities in skeletal muscle tissues were significantly decreased （P<0.05）， and MDA and NADPH contents were significantly increased （P<0.05）. In skeletal muscle tissues， the arrangement of muscle fibers was loose， the nucleus was disordered， and inflammatory cells were infiltrated. The expression levels of ROS and 4-HNE in skeletal muscle tissues were significantly increased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly decreased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the metformin group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that blood glucose in the metformin group was significantly decreased at all time points （P<0.05）. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue of the metformin group. The expressions of ROS and 4-HNE in skeletal muscle tissues were decreased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly increased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the SQTLP medium- and high-dose groups were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the glucose tolerance and insulin tolerance of mice were improved in each dose group of SQTLP. The GSH-Px activity in the SQTLP low-dose group was significantly increased （P<0.05）， and the NADPH content was decreased （P<0.05）. The activities of SOD and GSH-Px in the SQTLP medium- and high-dose groups were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. The skeletal muscle tissue injury of mice in each dose group of SQTLP was ameliorated to different degrees. In the SQTLP medium- and high-dose groups， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05）. Compared with those in the SQTLP low-dose group， FBG and HOMA-IR in the SQTLP high-dose group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the SQTLP high-dose group significantly improved the glucose tolerance and insulin tolerance of mice. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05） in the skeletal muscle tissue of the SQTLP high-dose group. ConclusionSQTLP can significantly improve IR in T2DM mice， and the mechanism is related to SQTLP activating the Nrf2/HO-1/NQO1 signaling pathway， promoting the expression of antioxidant enzymes， and thus improving the oxidative stress injury in the skeletal muscle.

Research Progress on Active Ingredients of Chinese Medicine Based on AMPK Signaling Pathway to Improve Insulin Resistance in T2DM / 中国实验方剂学杂志

Insulin resistance （IR） is an important pathological and physiological mechanism of type 2 diabetes （T2DM）， and the treatment of IR has become the key to the prevention and treatment of T2DM. IR is a state of insensitivity or reduced sensitivity of insulin-stimulated tissue cells to glucose， resulting in cells that are unable to efficiently take up glucose in the bloodstream and thus causing hyperglycemia. Adenosine monophosphate-activated protein kinase （AMPK） is an energy-sensing enzyme that can regulate multiple metabolic pathways and maintain the stability of adenosine triphosphate （ATP） in the cell. In recent years， traditional Chinese medicine （TCM） has played an increasingly important role in the prevention and treatment of T2DM. The research on exploring the AMPK signaling pathway of TCM intervention in the progress of T2DM has gradually increased. Many pharmacological studies have shown that TCM has advantages such as safety and high efficiency in the prevention and treatment of T2DM. AMPK signaling pathway is one of the key pathways for the active ingredients of TCM and TCM extracts to improve IR. Active ingredients such as phenols， flavonoids， polysaccharides， alkaloids， and saponins， as well as other herbal extracts can improve IR by activating the AMPK signaling pathway cascade response， thereby improving IR by regulating glucolipid metabolism， inhibiting inflammatory response， anti-oxidative stress and maintaining mitochondrial homeostasis. Based on this， this paper reviews the pharmacological and experimental research results of TCM intervening the AMPK signaling pathway to improve IR in recent years， expecting to provide reference for further research， development and application of TCM in intervening IR and treating T2DM.

Mechanism of Rhei Radix et Rhizoma-Coptidis Rhizoma Improving Liver Insulin Resistance in db/db Mice by Regulating AMPK/ULK1/Beclin1 Pathway / 中国实验方剂学杂志

ObjectiveThis study aims to examine the effect of Rhei Radix et Rhizoma-Coptidis Rhizoma on reducing insulin resistance in db/db mice by regulating the adenylate activated protein kinase （AMPK）/UNC-51-like kinase 1 （ULK1）/key molecule of autophagy， benzyl chloride 1 （Beclin1） pathway and elucidate the underlying mechanism. MethodSixty 6-week-old male db/db mice were studied. They were randomly divided into the model group， metformin group （0.26 g·kg-1）， and low-， middle-， and high-dose groups （2.25， 4.5， 9 g·kg-1） of Rhei Radix et Rhizoma-Coptidis Rhizoma. A blank group of db/m mice of the same age was set， with 12 mice in each group. After eight weeks of continuous intragastric administration， the blank group and model group received distilled water intragastrically once a day. The survival status of the mice was observed， and fasting blood glucose （FBG） was measured using a Roche blood glucose device. Fasting serum insulin （FINS） was measured using an enzyme-linked immunosorbent assay， and the insulin resistance index （HOMA-IR） was calculated. Hematoxylin-eosin （HE） staining was performed to observe the pathological changes in the liver of the mice. The protein expression levels of AMPK， Beclin1， autophagy associated protein 5 （Atg5）， and p62 in liver tissue were determined by using Western blot. The protein expression levels of autophagy associated protein 1 light chain 3B （LC3B） and ULK1 in liver tissue were determined using immunofluorescence. Real-time fluorescence quantitative PCR （Real-time PCR） was used to measure mRNA expression levels of AMPK， Beclin1， Atg5， ULK1， and p62. ResultCompared with the blank group， the model group exhibited a significant increase in body mass （P<0.01）. Additionally， the levels of FBG， FINS， and HOMA-IR significantly changed （P<0.01）. The structure of liver cells was disordered. The protein expression levels of AMPK， Beclin1， and Atg5 in liver tissue were significantly decreased （P<0.01）， while the expression level of p62 protein was significantly increased （P<0.01）. The expression levels of mRNA and proteins were consistent. Compared with the model group， the body mass of the metformin group and high and medium-dose groups of Rhei Radix et Rhizoma-Coptidis Rhizoma was significantly decreased （P<0.05）. FBG， FINS， and HOMA-IR were significantly decreased （P<0.05，P<0.01）. After treatment， the liver structure damage in each group was alleviated to varying degrees. The protein expressions of AMPK， Beclin1， Atg5， LC3B， and ULK1 were increased （P<0.05，P<0.01）， while the protein expression of p62 was decreased （P<0.01）. The expression levels of mRNA and proteins were generally consistent. ConclusionThe combination of Rhei Radix et Rhizoma-Coptidis Rhizoma can effectively improve liver insulin resistance， regulate the AMPK autophagy signaling pathway， alleviate insulin resistance in db/db mice， and effectively prevent the occurrence and development of type 2 diabetes.

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.

Comprehensive analysis of insulin products complex disulfide bonds structure by high resolution mass spectrum / 药学学报

The correct pairing of disulfide bonds maintains the correct folding mode and high-level structure formation of peptides and protein drugs, which is crucial for the quality control of products. In order to ensure that the disulfide bonds are correctly paired, disulfide bond analysis is an essential part of peptides and protein drug characterization. Mass spectrometry can be used to analyze disulfide bonds. However, insulin and its analogues have two pairs of disulfide bonds without restriction enzyme cutting site. Conventional collision-induced dissociation (CID) and high-energy induced cleavage (HCD) cannot accurately locate the complex disulfide bond. In our study, three methods were used to localize the complex disulfide, including enzyme digestion combined with key peptide fragment in source decay (ISD) fragmentation method, enzyme digestion combined with partial reduction alkylation method, intact protein source ISD and electron transfer dissociation (ETD) cleavage method, The applicability of insulin aspart, insulin lispro and insulin glargine were also investigated. This study provides a new way for the quality control of disulfide bonding mode of insulin and its analogues, and also provides a reference for the disulfide bond localization of peptides or proteins containing this complex disulfide bond.

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.

Expression of insulin-like growth factor binding protein 3 in cerebral infarction rats and its involvement in Smad signaling pathway / 中华老年心脑血管病杂志

Objective To investigate the role of Smad signaling pathway in rat model of cerebral in-farction and explore the expression of insulin-like growth factor binding protein 3(IGFBP-3)in brain tissue and its relationship with neural function.Methods Sixty healthy adult male SD rats were randomly and equally divided into model group,sham-operation group,and normal control group.The model of cerebral infarction was established by using intraluminal thread occlusion,and the rats of the sham-operation group were only given exposure of the internal carotid artery and direct suture of the incision.In 1 week after successful modeling,Modified Neurological Seve-rity Score(mNSS)was used to evaluate the neurological function.HE staining was employed to observe the histopathological changes in the brain tissues.Western blotting and RT-PCR were adopted to detect the brain expression of IGFBP-3,Smad2 and Smad4 at protein and mRNA le-vels.Spearman correlation analysis was conducted to analyze the correlation among the expression levels of IGFBP-3,Smad2,Smad4 and P21.Results HE staining displayed that obvious brain ede-ma,characterized by disordered arrangement of brain cells,increased microglia,and blurred nucleo-lus of brain cells were observed in the rats of the model group,with the area of cerebral infarct of 20.55％.The mNSS score and the protein and mRNA levels of IGFBP-3,Smad2 and Smad4 were significantly higher,but the P21 protein and mRNA levels were obviously reduced in the model group than the sham-operation group and normal control group(P＜0.05,P＜0.01).Spearman correlation analysis showed that the mRNA level of IGFBP-3 in cerebral infarction rats was posi-tively correlated with the mNSS score and mRNA expression levels of Smad2 and Smad4(r=0.568,r=0.623,r=0.597;P＜0.01),and negatively with P21 mRNA level in the brain tissue(r=-0.573;P＜0.01).Conclusion The level of IGFBP-3 is significantly increased in brain tissue of rats with cerebral infarction,and it is closely associated with neural function of these rats,which may be related to Smad signaling pathway.

Association between the visceral adiposity index and cognitive decline in community-dwelling elderly residents / 中华老年医学杂志

Objective:To investigate the relationship between the visceral adiposity index(VAI) and cognitive decline.Methods:A cross-sectional study was conducted.Between October 2020 and March 2023, 483 elderly residents living in communities in Hefei were recruited and divided into four groups based on VAI scores, Q1(VAI ≤ 1.14), Q2(VAI>1.15 and ≤1.85), Q3(VAI>1.86 and ≤2.81) and Q4(VAI>2.82).General cognitive function was assessed by(MMSE)and(MoCA).Attention and working memory were tested by forward and backward digit span tasks.Logistic regression was utilized to analyze the relationship between different VAI scores and insulin resistance.The correlation between different VAI scores and cognitive function domains was analyzed by partial correlation.Results:The values of BMI, fasting plasma glucose, fasting insulin, HbA1c, high-sensitivity C-reactive protein, HOMA-IR and HOMA-β increased with increasing VAI scores(all P<0.01).VAI was significantly correlated with insulin sensitivity after adjusting for confounding factors including sex.The risk of insulin resistance in Q4 was 7.40 times that in Q1( OR=7.40, 95% CI: 4.30-12.74, P<0.05).In addition, the correlation coefficients between VAI and forward digital span and between VAI and backward digital span were -0.116 and -0.105, respectively(both P<0.05), but there was no correlation between VAI and MMSE or MoCA. Conclusions:VAI is closely related to insulin resistance and also associated with early cognitive decline in elderly people with visceral obesity.