[Objectives]To evaluate the impact of nasal insulin administration on postoperative delirium(POD)through meta-analysis.[Methods]The Cochrane Library,PubMed,Embase,Web of Science,China National Knowledge Infrastructure...[Objectives]To evaluate the impact of nasal insulin administration on postoperative delirium(POD)through meta-analysis.[Methods]The Cochrane Library,PubMed,Embase,Web of Science,China National Knowledge Infrastructure(CNKI),Wanfang Database,and China Science and Technology Journal Database(CSTJ)were systematically searched for relevant literature published prior to February 27,2025.Literature screening and data extraction were conducted by two independent researchers in accordance with predetermined inclusion and exclusion criteria.The primary observation indicator was the incidence of POD across various treatment populations.The risk ratio for the primary outcome was calculated using the Mantel-Haenszel method.The secondary outcomes included the adverse effects associated with insulin treatment,which encompassed the glycemic variability indices,the incidence of nasal irritation symptoms following administration,hypoglycemic reactions,and insulin allergic reactions.The study protocol was registered on PROSPERO(CRD420250607492)before data extraction.[Results]A total of five randomized controlled trials involving 357 patients were included in the analysis.In the adult population undergoing surgical procedures,the administration of insulin via nasal delivery was found to significantly reduce the incidence of POD[RR=0.35,95%CI(0.23-0.53),P<0.001].The results of the subgroup analysis indicated that there were notable differences in the effectiveness of various doses of insulin administered nasally in preventing POD.Specifically,both the 20 U dose group[RR=0.45,95%CI:(0.29,0.70),P<0.001]and the 30 U dose group[RR=0.01,95%CI:(0.03,0.42),P<0.001]showed a significantly lower incidence of POD compared to the control group,with statistically significant conclusions.Conversely,the 40 U dose group[RR=0.47,95%CI:(0.17,1.34),P=0.16]yielded no statistically significant difference.Furthermore,the efficacy in preventing POD was found to be greater in the 30 U dose group compared to the 20 U dose group.Additionally,two cases of hypoglycemic reactions and increased nasal irritation symptom scores were reported in the 40 U dose group across the entire study population(P<0.05),suggesting potential adverse risks associated with this dosage.[Conclusions]The nasal administration of insulin significantly decreases the incidence of POD at a specific dosage,with optimal efficacy and high safety observed at a dosage of 30 U.展开更多
Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central com...Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.展开更多
The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurode...The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.展开更多
The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evi...The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.展开更多
AIM:To study the expression of human insulin gene in gastrointestinal tracts of diabetic rats. METHODS: pCMV.Ins, an expression plasmid of the human insulin gene, wrapped with chitosan nanoparticles, was transfected t...AIM:To study the expression of human insulin gene in gastrointestinal tracts of diabetic rats. METHODS: pCMV.Ins, an expression plasmid of the human insulin gene, wrapped with chitosan nanoparticles, was transfected to the diabetic rats through lavage and coloclysis, respectively. Fasting blood glucose and plasma insulin levels were measured for 7 d. Reverse transcription polymerase chain reaction (RT-PCR) analysis and Western blot analysis were performed to confirm the expression of human insulin gene. RESULTS: Compared with the control group, the fasting blood glucose levels in the lavage and coloclysis groups were decreased significantly in 4 d (5.63 ± 0.48 mmol/L and 5.07 ± 0.37 mmol/L vs 22.12 ± 1.31 mmol/L, respectively, P < 0.01), while the plasma insulin levels were much higher (32.26 ± 1.81 μIU/mL and 32.79 ± 1.84 μIU/mL vs 14.23 ± 1.38 μIU/mL, respectively, P < 0.01). The human insulin gene mRNA and human insulin were only detected in the lavage and coloclysis groups. CONCLUSION: Human insulin gene wrapped with chitosan nanoparticles can be successfully transfected to rats through gastrointestinal tract, indicating that chitosan is a promising non-viral vector.展开更多
Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is...Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.展开更多
BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring except...BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.展开更多
BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient ...BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.展开更多
The mechanisms of Gardeniae Fructus (GF) for anti-hyperglycemic action were demonstrated in streptozotocin (STZ)-diabetic mice. Six hours after single intraperitoneal administration of GF (300 mg/kg) or H2O into 3 hou...The mechanisms of Gardeniae Fructus (GF) for anti-hyperglycemic action were demonstrated in streptozotocin (STZ)-diabetic mice. Six hours after single intraperitoneal administration of GF (300 mg/kg) or H2O into 3 hour-fasted STZ-diabetic mice, glucose and insulin tolerances were assessed by intraperitoneal glucose (1.5 g/kg) tolerance test (IPGTT) and intraperitoneal insulin (0.65 U/kg) tolerance test (IPITT), respectively. Effects of GF on insulin signaling pathways in soleus muscle such as glucose uptake, expression of glucose transporter 4 (GLUT4) in the plasma membrane and phosphorylation of Akt (P-Akt) in cytosolic fraction were examined in STZ-diabetic mice. In IPGTT test, GF significantly accelerated clearance of exogenous glucose and its glucose-lowering action was greater than H2O-treated controlin STZ-diabetic mice. GF also promoted an exogenous glucose-increased insulin level in STZ-diabetic mice. In IPITT test, GF decreased glucose level to the greater extent than H2O-treated control in STZ-diabetic mice. Furthermore, GF significantly decreased high HOMA-IR in STZ-diabetic mice from 21.6 ± 2.4 to 12.4 ± 1.9 (mg/dl × μU/ml). These results implied that GF improved insulin resistance in STZ-diabetic mice. GF increased glucose uptake of soleus muscle 1.5 times greater than H2O-treated control in STZ-diabetic mice. GF enlarged insulin (10 nmol/ml)-increased glucose uptake to 1.8 time-greater. Correspondingly, GF increased expression of GLUT4 in the plasma membrane of soleus muscle to 1.4 time-greater, and P-Akt in the cytosolic fraction of soleus muscle to 1.9 time-greater than those in H2O-treated control. In conclusion, the improvement of GF on insulin resistance is associated with the repair of insulin signaling via P-Akt, GLUT4 and glucose uptake pathway in soleus muscle of STZ-diabetic mice.展开更多
Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close rel...Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM)often leads to vascular complications,such as albuminuria.The role of insulin autoantibodies(IAA)and their interaction with D-dimer in this context remains unclear.AIM To inves...BACKGROUND Type 2 diabetes mellitus(T2DM)often leads to vascular complications,such as albuminuria.The role of insulin autoantibodies(IAA)and their interaction with D-dimer in this context remains unclear.AIM To investigate the characteristics of IAA and its effect on albuminuria in T2DM patients.METHODS We retrospectively analyzed clinical data from 115 T2DM patients with positive IAA induced by exogenous insulin,and 115 age-and sex-matched IAA-negative T2DM patients as controls.Propensity scores were calculated using multivariate logistic regression.Key variables were selected using the least absolute shrinkage and selection operator(LASSO)algorithm.We constructed a prediction model and analyzed the association between IAA and albuminuria based on demographic and laboratory parameters.RESULTS The IAA-positive group had significantly higher D-dimer levels[0.30(0.19-0.55)mg/L vs 0.21(0.19-0.33)mg/L,P=0.008]and plasma insulin levels[39.1(12.0-102.7)μU/mL vs 9.8(5.5-17.6)μU/mL,P<0.001]compared to the IAA-negative group.Increases in the insulin dose per weight ratio,diabetes duration,and urinary albumin-to-creatinine ratio(UACR)were observed but did not reach statistical significance.The LASSO model identified plasma insulin and D-dimer as key factors with larger coefficients.D-dimer was significantly associated with UACR in the total and IAA-positive groups but not in the IAA-negative group.The odds ratio for D-dimer elevation(>0.5 g/L)was 2.88(95%confidence interval:1.17-7.07)in the IAA-positive group(P interaction<0.05).CONCLUSION D-dimer elevation is an independent risk factor for abnormal albuminuria and interacts with IAA in the development of abnormal albuminuria in T2DM patients.展开更多
Parkinson's disease(PD),a chronic and com-mon neurodegenerative disease,is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-...Parkinson's disease(PD),a chronic and com-mon neurodegenerative disease,is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein.Type 2 diabetes mellitus(T2DM)is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion.Extensive evidence has con-firmed shared pathogenic mechanisms underlying PD and T2DM,such as oxidative stress caused by insulin resistance,mitochondrial dysfunction,inflammation,and disorders of energy metabolism.Conventional drugs for treating T2DM,such as metformin and glucagon-like peptide-1 receptor ago-nists,affect nerve repair.Even drugs for treating PD,such as levodopa,can affect insulin secretion.This review sum-marizes the relationship between PD and T2DM and related therapeutic drugs from the perspective of insulin signaling pathways in the brain.展开更多
BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contribut...BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contributing to new-onset diabetes after transplantation and negatively affecting islet function.AIM To study the effects of tacrolimus on the insulin signaling pathway of hepatocytes.METHODS HL7702 cells were treated with different concentrations of tacrolimus(0.1 mg/L,1 mg/L,5 mg/L)for 24 hours.The proteins involved in insulin signaling were detected by Western blotting.RESULTS Compared with the control group,phosphorylation of insulin receptor substrate(IRS)1 at Ser 307 and Ser 323 were increased significantly when the tacrolimus concentration reached 1 and 5 mg/L.Phosphorylation of IRS1 at Ser 1101 was also increased,although not significantly.However,phosphorylation of Ribosomal protein S6 kinase beta-1 at Thr 389 was decreased significantly.The levels of phosphorylated glycogen synthase kinase 3αSer 21 and Ser 9 were increased.Surprisingly,phosphorylation of glycogen synthase at Ser 641 was increased.There was no significant change in the activity of glycogen phosphorylase.CONCLUSION Tacrolimus has no direct effect on hepatic glucose metabolism,but inhibits IRS1-mediated insulin signaling.This may be one of the underlying mechanisms by which tacrolimus induces insulin resistance.展开更多
BACKGROUND Thyrotoxic periodic paralysis(TPP)is an endocrine emergency caused by thyrotoxicosis,manifesting mainly as periodic myasthenia and hypokalemia,and posing a serious threat to the patient's health.Fatigue...BACKGROUND Thyrotoxic periodic paralysis(TPP)is an endocrine emergency caused by thyrotoxicosis,manifesting mainly as periodic myasthenia and hypokalemia,and posing a serious threat to the patient's health.Fatigue,strenuous exercise,alcohol abuse,high carbohydrate intake and insulin injections are common triggers of paralysis.This article reports a case of severe TPP induced by insulin injection,elucidates the characteristics and pathogenesis of the disease,analyses the risk factors for triggering TPP,and hopefully provides more clinical data for TPP patients.CASE SUMMARY A 38-year-old Asian man presented to the emergency department with a oneweek history of limb weakness and worsening half-day.His medical history included poorly controlled type 2 diabetes and he had been switched to Aspart50 a week earlier.He was alert and oriented with upper extremity strength grade 3 and lower extremity strength grade 1.Emergency department tests showed hypokalemia of 1.6 mmol/L.The paramedics administered 1.5 g of potassium intravenously,followed by 4.0 g orally.Weakness in the arms and legs improved.He was referred to endocrinology where he was diagnosed with Graves'disease,with suboptimal control and insulin injections possibly causing TPP.We stopped his insulin and he was discharged with a potassium level of 4.0 mmol/L.CONCLUSION Insulin is a trigger for TPP and should be avoided in patients with hyperthyroidism.Early recognition and treatment of TPP is crucial,especially in patients presenting with hypokalemic periodic paralysis.展开更多
Insulin is a peptide hormone secreted by pancreaticβ-cells,which plays a key role in regulating glucose metabolism and is the only hormone in the body capable of lowering blood glucose level.The development of insuli...Insulin is a peptide hormone secreted by pancreaticβ-cells,which plays a key role in regulating glucose metabolism and is the only hormone in the body capable of lowering blood glucose level.The development of insulin preparations has undergone nearly 100 years of history,from early animal insulin extraction to modern synthetic insulin and insulin analogs,which have greatly advanced the treatment of diabetes.The insulin receptor has a wide distribution in the body,and its activation leads to intracellular signaling mainly through two pathways,PI3K/Akt and Ras/MAPK.Clinically,insulin is crucial in the treatment and management of diabetes and its complications,especially in the cases where oral medications fail to control blood glucose.The role of insulin is not limited to the regulation of blood glucose but has a wide range of functions throughout the body,such as regulation of mitochondrial function and metabolism,the promotion of protein synthesis,adipogenesis,and cellular proliferation.However,insulin overdose may lead to severe hypoglycemia,which,if left untreated,poses the risk of irreversible neurological damage or even fatality.In this paper,we review the history of the development of insulin preparations,the molecular structure of insulin,the biological processes initiated by insulin and insulin deficiency/resistance.The overview of side effects from insulin is also included in this review.We assume that future research could focus on refining insulin analogs for greater therapeutic precision,minimizing side effects,and extending benefits beyond glycemic control.Exploring insulin’s additional effects may unlock potential applications in treating multiple diseases.展开更多
Athletes often use branched-chain amino acid (BCAAs) supplements with a ratio of 2:1:1 (leucine:isoleucine:valine) for their impact on muscle building. Research suggests that by altering the ratio, an improvement in g...Athletes often use branched-chain amino acid (BCAAs) supplements with a ratio of 2:1:1 (leucine:isoleucine:valine) for their impact on muscle building. Research suggests that by altering the ratio, an improvement in glucose metabolism might be possible. The purpose of this study was to examine how isoleucine would influence glucose tolerance. We recruited healthy male (n = 13) and female (n = 5) participants who were asked to fast for 12 hours before coming to the laboratory. A fasting blood sample was collected, followed by the subjects consuming a breakfast containing 113 g carbohydrates, 8 g protein, 1.5 g fat, and BCAA powder in the 2:1:1 ratio (Control) or BCAA powder enriched with Isoleucine (2:6:1), both added to orange juice. The opposite meal was consumed on a second visit one week apart. Blood was collected at 30, 60, 90, and 120 minutes post-meal. No differences were observed between the Control and Isoleucine for changes in serum glucose or insulin response when examining all subjects together. However, when comparing between genders, males tended to have a significantly lower serum glucose response compared to females when consuming the Isoleucine, with no difference between the genders when consuming the Control. Also, males had significantly lower serum glucose responses when consuming the Isoleucine compared to when they consumed the Control, while females had significantly higher serum glucose responses when consuming the Isoleucine compared to when they consumed the Control. In general, males tended to have a lower serum insulin response than females when consuming both the Control and the Isoleucine. Our study indicates a significant difference in the way genders respond to BCAA supplementation, where isoleucine may improve glucose tolerance and insulin response in males but not females.展开更多
Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin...Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin cell receptors (type II DM). Type I DM usually presents with florid manifestations contrary to a slowly-progressive type II. Patients and methods: Over the past 10 years, we encountered 9 obese patients with controlled insulin-requiring type II DM for years, at a dose of 62 ± 5 units/day, who developed sudden and severe insulin resistance (IR) that required 210 ± 25 units daily. All patients had very high levels of anti-Glutamic Acid Decarboxylase (GAD) antibodies. Despite a lack of previous testing for anti-GAD antibodies, they were treated, with Cyclosporin A (Cy), as an autoimmune disorder superimposed on their type II MD. Initially all patients were treated with 100 mg, of Cy, twice daily aiming at an initial trough level of 100 - 150 ng/ml. Three months later, the dose was reduced to 50 mg twice daily for a total of 2 years. Results: Amelioration of IR was achieved by 1 month with a reduction of daily insulin requirement to 123 ± 16 units that further decreased to 76 ± 11 by the end of the 3rd month. Such improvement persisted for 2 years and >1 year after Cy discontinuation. Moreover, a decline in insulin requirements was associated with a parallel decrease in anti-GAD antibody levels and an increase in C-peptide insulin without kidney disease. Conclusion: Anti-GAD antibodies can induce acute IR in type II DM, and this phenomenon can be treated safely and effectively with Cy.展开更多
This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obe...This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obese compared with hea-lthy peers,demonstrating a negative correlation between SEPP1 levels and mea-sures of adiposity and insulin resistance.These findings suggest that SEPP1 is a biomarker useful in the early identification of insulin resistance in pediatric populations.This editorial emphasizes the clinical implications of the study and calls for further research to validate and explore the role of SEPP1 in metabolic health.展开更多
A series of measures to implement national volume‐based procurement(NVBP)and follow‐on NVBP in China have significantly reduced insulin prices and increased patient affordability.However,NVBP may lead to a higher bu...A series of measures to implement national volume‐based procurement(NVBP)and follow‐on NVBP in China have significantly reduced insulin prices and increased patient affordability.However,NVBP may lead to a higher burden of insulin‐related consumables(such as injection pens and needles),which might discourage patients from using insulin in the pooled list and increase the risk of needle reuse.This article emphasizes that it is essential NVBP be implemented for both drugs and consumables,which will contribute to the achievement of universal insulin access.展开更多
文摘[Objectives]To evaluate the impact of nasal insulin administration on postoperative delirium(POD)through meta-analysis.[Methods]The Cochrane Library,PubMed,Embase,Web of Science,China National Knowledge Infrastructure(CNKI),Wanfang Database,and China Science and Technology Journal Database(CSTJ)were systematically searched for relevant literature published prior to February 27,2025.Literature screening and data extraction were conducted by two independent researchers in accordance with predetermined inclusion and exclusion criteria.The primary observation indicator was the incidence of POD across various treatment populations.The risk ratio for the primary outcome was calculated using the Mantel-Haenszel method.The secondary outcomes included the adverse effects associated with insulin treatment,which encompassed the glycemic variability indices,the incidence of nasal irritation symptoms following administration,hypoglycemic reactions,and insulin allergic reactions.The study protocol was registered on PROSPERO(CRD420250607492)before data extraction.[Results]A total of five randomized controlled trials involving 357 patients were included in the analysis.In the adult population undergoing surgical procedures,the administration of insulin via nasal delivery was found to significantly reduce the incidence of POD[RR=0.35,95%CI(0.23-0.53),P<0.001].The results of the subgroup analysis indicated that there were notable differences in the effectiveness of various doses of insulin administered nasally in preventing POD.Specifically,both the 20 U dose group[RR=0.45,95%CI:(0.29,0.70),P<0.001]and the 30 U dose group[RR=0.01,95%CI:(0.03,0.42),P<0.001]showed a significantly lower incidence of POD compared to the control group,with statistically significant conclusions.Conversely,the 40 U dose group[RR=0.47,95%CI:(0.17,1.34),P=0.16]yielded no statistically significant difference.Furthermore,the efficacy in preventing POD was found to be greater in the 30 U dose group compared to the 20 U dose group.Additionally,two cases of hypoglycemic reactions and increased nasal irritation symptom scores were reported in the 40 U dose group across the entire study population(P<0.05),suggesting potential adverse risks associated with this dosage.[Conclusions]The nasal administration of insulin significantly decreases the incidence of POD at a specific dosage,with optimal efficacy and high safety observed at a dosage of 30 U.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC)+6 种基金STI2030-Major Projects(2021ZD0202700,to HY)the National Natural Science Foundation of China(32241004,to HY)the Natural Science Foundation of Zhejiang Province of China(LR24C090001,to HY)Key R&D Program of Zhejiang Province(2024SSYS0017,to HY)CAMS Innovation Fund for Medical Sciences(2019-12M-5-057,to HY)Fundamental Research Funds for the Central Universities(226-2022-00193,to HY)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-01,to HY)。
文摘Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.
文摘The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC).
文摘The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.
文摘AIM:To study the expression of human insulin gene in gastrointestinal tracts of diabetic rats. METHODS: pCMV.Ins, an expression plasmid of the human insulin gene, wrapped with chitosan nanoparticles, was transfected to the diabetic rats through lavage and coloclysis, respectively. Fasting blood glucose and plasma insulin levels were measured for 7 d. Reverse transcription polymerase chain reaction (RT-PCR) analysis and Western blot analysis were performed to confirm the expression of human insulin gene. RESULTS: Compared with the control group, the fasting blood glucose levels in the lavage and coloclysis groups were decreased significantly in 4 d (5.63 ± 0.48 mmol/L and 5.07 ± 0.37 mmol/L vs 22.12 ± 1.31 mmol/L, respectively, P < 0.01), while the plasma insulin levels were much higher (32.26 ± 1.81 μIU/mL and 32.79 ± 1.84 μIU/mL vs 14.23 ± 1.38 μIU/mL, respectively, P < 0.01). The human insulin gene mRNA and human insulin were only detected in the lavage and coloclysis groups. CONCLUSION: Human insulin gene wrapped with chitosan nanoparticles can be successfully transfected to rats through gastrointestinal tract, indicating that chitosan is a promising non-viral vector.
基金supported by the National Natural Science Foundation of China[31872674]the Jilin Talent Development Foundation Grant[20200301018RQ]the Fundamental Research Funds for the Central Universities[CGZH202206].
文摘Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.
文摘BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.
基金Supported by CAMS Innovation Fund for Medical Sciences,No.2023-I2M-C&T-B-043National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-015+1 种基金CAMS Innovation Fund for Medical Sciences,No.2021-1-12M-002Beijing Municipal Natural Science Foundation,No.M22014.
文摘BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.
文摘The mechanisms of Gardeniae Fructus (GF) for anti-hyperglycemic action were demonstrated in streptozotocin (STZ)-diabetic mice. Six hours after single intraperitoneal administration of GF (300 mg/kg) or H2O into 3 hour-fasted STZ-diabetic mice, glucose and insulin tolerances were assessed by intraperitoneal glucose (1.5 g/kg) tolerance test (IPGTT) and intraperitoneal insulin (0.65 U/kg) tolerance test (IPITT), respectively. Effects of GF on insulin signaling pathways in soleus muscle such as glucose uptake, expression of glucose transporter 4 (GLUT4) in the plasma membrane and phosphorylation of Akt (P-Akt) in cytosolic fraction were examined in STZ-diabetic mice. In IPGTT test, GF significantly accelerated clearance of exogenous glucose and its glucose-lowering action was greater than H2O-treated controlin STZ-diabetic mice. GF also promoted an exogenous glucose-increased insulin level in STZ-diabetic mice. In IPITT test, GF decreased glucose level to the greater extent than H2O-treated control in STZ-diabetic mice. Furthermore, GF significantly decreased high HOMA-IR in STZ-diabetic mice from 21.6 ± 2.4 to 12.4 ± 1.9 (mg/dl × μU/ml). These results implied that GF improved insulin resistance in STZ-diabetic mice. GF increased glucose uptake of soleus muscle 1.5 times greater than H2O-treated control in STZ-diabetic mice. GF enlarged insulin (10 nmol/ml)-increased glucose uptake to 1.8 time-greater. Correspondingly, GF increased expression of GLUT4 in the plasma membrane of soleus muscle to 1.4 time-greater, and P-Akt in the cytosolic fraction of soleus muscle to 1.9 time-greater than those in H2O-treated control. In conclusion, the improvement of GF on insulin resistance is associated with the repair of insulin signaling via P-Akt, GLUT4 and glucose uptake pathway in soleus muscle of STZ-diabetic mice.
基金support from Region Stockholm,ALF-project(FoUI-960041)Open Access funding is provided by Karolinska Institute(both to IM)。
文摘Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)often leads to vascular complications,such as albuminuria.The role of insulin autoantibodies(IAA)and their interaction with D-dimer in this context remains unclear.AIM To investigate the characteristics of IAA and its effect on albuminuria in T2DM patients.METHODS We retrospectively analyzed clinical data from 115 T2DM patients with positive IAA induced by exogenous insulin,and 115 age-and sex-matched IAA-negative T2DM patients as controls.Propensity scores were calculated using multivariate logistic regression.Key variables were selected using the least absolute shrinkage and selection operator(LASSO)algorithm.We constructed a prediction model and analyzed the association between IAA and albuminuria based on demographic and laboratory parameters.RESULTS The IAA-positive group had significantly higher D-dimer levels[0.30(0.19-0.55)mg/L vs 0.21(0.19-0.33)mg/L,P=0.008]and plasma insulin levels[39.1(12.0-102.7)μU/mL vs 9.8(5.5-17.6)μU/mL,P<0.001]compared to the IAA-negative group.Increases in the insulin dose per weight ratio,diabetes duration,and urinary albumin-to-creatinine ratio(UACR)were observed but did not reach statistical significance.The LASSO model identified plasma insulin and D-dimer as key factors with larger coefficients.D-dimer was significantly associated with UACR in the total and IAA-positive groups but not in the IAA-negative group.The odds ratio for D-dimer elevation(>0.5 g/L)was 2.88(95%confidence interval:1.17-7.07)in the IAA-positive group(P interaction<0.05).CONCLUSION D-dimer elevation is an independent risk factor for abnormal albuminuria and interacts with IAA in the development of abnormal albuminuria in T2DM patients.
基金supported by the National Natural Science Foundation of China(32161143021)the Iran National Science Foundation(4001873)+1 种基金the Henan Province Natural Science Foundation of China(182300410313)Henan University graduate Talent Program of Henan Province(SYLYC2023092).
文摘Parkinson's disease(PD),a chronic and com-mon neurodegenerative disease,is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein.Type 2 diabetes mellitus(T2DM)is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion.Extensive evidence has con-firmed shared pathogenic mechanisms underlying PD and T2DM,such as oxidative stress caused by insulin resistance,mitochondrial dysfunction,inflammation,and disorders of energy metabolism.Conventional drugs for treating T2DM,such as metformin and glucagon-like peptide-1 receptor ago-nists,affect nerve repair.Even drugs for treating PD,such as levodopa,can affect insulin secretion.This review sum-marizes the relationship between PD and T2DM and related therapeutic drugs from the perspective of insulin signaling pathways in the brain.
文摘BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contributing to new-onset diabetes after transplantation and negatively affecting islet function.AIM To study the effects of tacrolimus on the insulin signaling pathway of hepatocytes.METHODS HL7702 cells were treated with different concentrations of tacrolimus(0.1 mg/L,1 mg/L,5 mg/L)for 24 hours.The proteins involved in insulin signaling were detected by Western blotting.RESULTS Compared with the control group,phosphorylation of insulin receptor substrate(IRS)1 at Ser 307 and Ser 323 were increased significantly when the tacrolimus concentration reached 1 and 5 mg/L.Phosphorylation of IRS1 at Ser 1101 was also increased,although not significantly.However,phosphorylation of Ribosomal protein S6 kinase beta-1 at Thr 389 was decreased significantly.The levels of phosphorylated glycogen synthase kinase 3αSer 21 and Ser 9 were increased.Surprisingly,phosphorylation of glycogen synthase at Ser 641 was increased.There was no significant change in the activity of glycogen phosphorylase.CONCLUSION Tacrolimus has no direct effect on hepatic glucose metabolism,but inhibits IRS1-mediated insulin signaling.This may be one of the underlying mechanisms by which tacrolimus induces insulin resistance.
文摘BACKGROUND Thyrotoxic periodic paralysis(TPP)is an endocrine emergency caused by thyrotoxicosis,manifesting mainly as periodic myasthenia and hypokalemia,and posing a serious threat to the patient's health.Fatigue,strenuous exercise,alcohol abuse,high carbohydrate intake and insulin injections are common triggers of paralysis.This article reports a case of severe TPP induced by insulin injection,elucidates the characteristics and pathogenesis of the disease,analyses the risk factors for triggering TPP,and hopefully provides more clinical data for TPP patients.CASE SUMMARY A 38-year-old Asian man presented to the emergency department with a oneweek history of limb weakness and worsening half-day.His medical history included poorly controlled type 2 diabetes and he had been switched to Aspart50 a week earlier.He was alert and oriented with upper extremity strength grade 3 and lower extremity strength grade 1.Emergency department tests showed hypokalemia of 1.6 mmol/L.The paramedics administered 1.5 g of potassium intravenously,followed by 4.0 g orally.Weakness in the arms and legs improved.He was referred to endocrinology where he was diagnosed with Graves'disease,with suboptimal control and insulin injections possibly causing TPP.We stopped his insulin and he was discharged with a potassium level of 4.0 mmol/L.CONCLUSION Insulin is a trigger for TPP and should be avoided in patients with hyperthyroidism.Early recognition and treatment of TPP is crucial,especially in patients presenting with hypokalemic periodic paralysis.
基金supported by grants from National Natural Science Foundation of China(Grant No.82301577).
文摘Insulin is a peptide hormone secreted by pancreaticβ-cells,which plays a key role in regulating glucose metabolism and is the only hormone in the body capable of lowering blood glucose level.The development of insulin preparations has undergone nearly 100 years of history,from early animal insulin extraction to modern synthetic insulin and insulin analogs,which have greatly advanced the treatment of diabetes.The insulin receptor has a wide distribution in the body,and its activation leads to intracellular signaling mainly through two pathways,PI3K/Akt and Ras/MAPK.Clinically,insulin is crucial in the treatment and management of diabetes and its complications,especially in the cases where oral medications fail to control blood glucose.The role of insulin is not limited to the regulation of blood glucose but has a wide range of functions throughout the body,such as regulation of mitochondrial function and metabolism,the promotion of protein synthesis,adipogenesis,and cellular proliferation.However,insulin overdose may lead to severe hypoglycemia,which,if left untreated,poses the risk of irreversible neurological damage or even fatality.In this paper,we review the history of the development of insulin preparations,the molecular structure of insulin,the biological processes initiated by insulin and insulin deficiency/resistance.The overview of side effects from insulin is also included in this review.We assume that future research could focus on refining insulin analogs for greater therapeutic precision,minimizing side effects,and extending benefits beyond glycemic control.Exploring insulin’s additional effects may unlock potential applications in treating multiple diseases.
文摘Athletes often use branched-chain amino acid (BCAAs) supplements with a ratio of 2:1:1 (leucine:isoleucine:valine) for their impact on muscle building. Research suggests that by altering the ratio, an improvement in glucose metabolism might be possible. The purpose of this study was to examine how isoleucine would influence glucose tolerance. We recruited healthy male (n = 13) and female (n = 5) participants who were asked to fast for 12 hours before coming to the laboratory. A fasting blood sample was collected, followed by the subjects consuming a breakfast containing 113 g carbohydrates, 8 g protein, 1.5 g fat, and BCAA powder in the 2:1:1 ratio (Control) or BCAA powder enriched with Isoleucine (2:6:1), both added to orange juice. The opposite meal was consumed on a second visit one week apart. Blood was collected at 30, 60, 90, and 120 minutes post-meal. No differences were observed between the Control and Isoleucine for changes in serum glucose or insulin response when examining all subjects together. However, when comparing between genders, males tended to have a significantly lower serum glucose response compared to females when consuming the Isoleucine, with no difference between the genders when consuming the Control. Also, males had significantly lower serum glucose responses when consuming the Isoleucine compared to when they consumed the Control, while females had significantly higher serum glucose responses when consuming the Isoleucine compared to when they consumed the Control. In general, males tended to have a lower serum insulin response than females when consuming both the Control and the Isoleucine. Our study indicates a significant difference in the way genders respond to BCAA supplementation, where isoleucine may improve glucose tolerance and insulin response in males but not females.
文摘Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin cell receptors (type II DM). Type I DM usually presents with florid manifestations contrary to a slowly-progressive type II. Patients and methods: Over the past 10 years, we encountered 9 obese patients with controlled insulin-requiring type II DM for years, at a dose of 62 ± 5 units/day, who developed sudden and severe insulin resistance (IR) that required 210 ± 25 units daily. All patients had very high levels of anti-Glutamic Acid Decarboxylase (GAD) antibodies. Despite a lack of previous testing for anti-GAD antibodies, they were treated, with Cyclosporin A (Cy), as an autoimmune disorder superimposed on their type II MD. Initially all patients were treated with 100 mg, of Cy, twice daily aiming at an initial trough level of 100 - 150 ng/ml. Three months later, the dose was reduced to 50 mg twice daily for a total of 2 years. Results: Amelioration of IR was achieved by 1 month with a reduction of daily insulin requirement to 123 ± 16 units that further decreased to 76 ± 11 by the end of the 3rd month. Such improvement persisted for 2 years and >1 year after Cy discontinuation. Moreover, a decline in insulin requirements was associated with a parallel decrease in anti-GAD antibody levels and an increase in C-peptide insulin without kidney disease. Conclusion: Anti-GAD antibodies can induce acute IR in type II DM, and this phenomenon can be treated safely and effectively with Cy.
文摘This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obese compared with hea-lthy peers,demonstrating a negative correlation between SEPP1 levels and mea-sures of adiposity and insulin resistance.These findings suggest that SEPP1 is a biomarker useful in the early identification of insulin resistance in pediatric populations.This editorial emphasizes the clinical implications of the study and calls for further research to validate and explore the role of SEPP1 in metabolic health.
基金SUSTech Medical Research Innovation Project,Grant/Award Number:G030410001National Natural Science Foundation of China,Grant/Award Number:72342016+1 种基金Shenzhen Science and Technology Program,Grant/Award Number:JCYJ20250604144558076China Scholarship Council Scholarship,Grant/Award Number:202506280122。
文摘A series of measures to implement national volume‐based procurement(NVBP)and follow‐on NVBP in China have significantly reduced insulin prices and increased patient affordability.However,NVBP may lead to a higher burden of insulin‐related consumables(such as injection pens and needles),which might discourage patients from using insulin in the pooled list and increase the risk of needle reuse.This article emphasizes that it is essential NVBP be implemented for both drugs and consumables,which will contribute to the achievement of universal insulin access.
