Anti-and non-tumor necrosis factor-α-targeted therapies effects on insulin resistance in rheumatoid arthritis,psoriatic arthritis and ankylosing spondylitis

In addition toβ-cell failure with inadequate insulin secretion,the crucial mechanism leading to establishment of diabetes mellitus(DM)is the resistance of target cells to insulin,i.e.insulin resistance(IR),indicating a requirement of beyond-normal insulin concentrations to maintain euglycemic status and an ineffective strength of transduction signaling from the receptor,downstream to the substrates of insulin action.IR is a common feature of most metabolic disorders,particularly type II DM as well as some cases of type I DM.A variety of human inammatory disorders with increased levels of proinflammatory cytokines,including tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1β,have been reported to be associated with an increased risk of IR.Autoimmunemediated arthritis conditions,including rheumatoid arthritis(RA),psoriatic arthritis(PsA)and ankylosing spondylitis(AS),with the involvement of proinflammatory cytokines as their central pathogenesis,have been demonstrated to be associated with IR,especially during the active disease state.There is an increasing trend towards using biologic agents and small molecule-targeted drugs to treat such disorders.In this review,we focus on the effects of anti-TNF-α-and non-TNF-α-targeted therapies on IR in patients with RA,PsA and AS.Anti-TNF-αtherapy,IL-1 blockade,IL-6 antagonist,Janus kinase inhibitor and phosphodiesterase type 4 blocker can reduce IR and improve diabetic hyper-glycemia in autoimmune-mediated arthritis.

Hepatitis C virus infection and insulin resistance

Approximately 170 million people worldwide are chronically infected with hepatitis C virus(HCV).Chronic HCV infection is the leading cause for the development of liver fibrosis,cirrhosis,hepatocellular carcinoma(HCC)and is the primary cause for liver transplantation in the western world.Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of typeⅡdiabetes.Insulin resistance plays an important role in the development of various complications associated with HCV infection.Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis,steatosis,HCC and resistance to anti-viral treatment.Thus,HCV associated insulin resistance is a therapeutic target at any stage of HCV infection.HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway.Various mechanisms have been proposed in regard to HCV mediated insulin resistance,involving up regulation of inflammatory cytokines,like tumor necrosis factor-α,phosphorylation of insulin-receptor substrate-1,Akt,up-regulation of gluconeogenic genes like glucose 6 phosphatase,phosphoenolpyruvate carboxykinase 2,and accumulation of lipid droplets.In this review,we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.

Advances in TCM Research of Insulin Resistance

Insulin resistance (IR) refers to subnormal response to a certain amount of insulin and is the most characteristic phenomenon in non-insulin dependent diabetes mellitus (NIDDM). It is also an element of the pathogenic mechanism shared with obesity, systemic hypertension, abnormal lipid metabolism and atherosclerosis. In recent years, studies on its treatment with traditional Chinese medicine (TCM) have gradually been carried out and the following is a report of them.Mechanisms of Diabetic IR in TCM TermsAction of insulin antagonizing hormones in peripheral tissues is one of the causes of diabetic IR. Cyclic nucleosides cAMP and cGMP, important intracellular messengers, are considered to be the second messenger of insulin, and cAMP is related to the amount of insulin receptors. Early in 1980s, some authors investigated the relationship among the symptoms of diabetes and such hormones and cAMP/cGMP ratio. Although they did not give due attention to IR, their studies provided evidences for differentiation of symptoms and signs in IR typing.

Zn-Fe primary battery-enabled controlled hydrogen release in stomach for improving insulin resistance in obesity-associated type 2 diabetes

Chronic systemic inflammation in obesity-associated type 2 diabetes (T2D) is a key inducing factor of insulin resistance (IR). Hydrogen molecule (H2) has been proved to be a safe and effective anti-inflammatory agent, but conventional H2 administration methods cannot provide a high dosage and a long duration of H2 treatment in IR-related tissues and thus lead to limited therapeutic efficacies. We here propose a new strategy of controlled H2 release to match the time window of gastric emptying for maximizing the bioavailability and therapeutic outcome of H2. This work enhances the hydrolysis rate of Zn by constructing a Zn-Fe primary-battery micro-/ nano-structure, and the H2-releasing rate is adjusted by tuning the ratio of Zn to Fe. The Zn-Fe micro-/nano-structure is orally administrated once daily to alleviate obesity-associated T2D in a leptin-deficient (ob/ob) mouse model. The H2 generation time of the Zn-Fe primary-battery micro-/nano-structure with the Fe/Zn ratio of 1:100 in gastric acid is about 3 h, just matching with the time window of gastric emptying in mice. In vivo monitoring results show that H2 generated by Zn-Fe micro-/nano-structure in stomach can effectively accumulate in major IR-sited tissues including liver, adipose tissue, and skeletal muscle at a high dose for a relatively long time compared to H2-rich water drinking. Oral administration of Zn-Fe micro-/nano-structure at 200 mg/kg body weight has realized an efficient IR improvement and remarkably ameliorated systemic inflammation in ob/ ob mice. In addition, a high-dose administration of Zn-Fe shows no visible toxicity in mice. This work provides a new strategy to maximize the outcome of hydrogen therapy.

Effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing gastrectomy

AIM: To investigate the effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing radical distal gastrectomy. METHODS: Within 24 h of intensive care unit management, patients with gastric cancer were enrolled after written informed consent and randomized to the intensive insulin therapy (IIT) group to keep glucose levels from 4.4 to 6.1 mmol/L or the conventional insulin therapy (CIT) group to keep levels less than 10 mmol/L. Resting energy expenditure (REE), respiratory quotient (RQ), resting energy expenditure per kilogram (REE/kg), and the lipid oxidation rate were monitored by the indirect calorimeter of calcium citrate malate nutrition metabolism investigation system. The changes in body composition were analyzed by multi-frequency bioimpedance analysis. Blood fasting glucose and insulin concentration were measured for assessment of Homeostasis model assessment of insulin resistance. RESULTS: Sixty patients were enrolled. Compared with preoperative baseline, postoperative REE increased by over 22.15% and 11.07%; REE/kg rose up to 27.22 ± 1.33 kcal/kg and 24.72 ± 1.43 kcal/kg; RQ decreased to 0.759 ± 0.034 and 0.791 ± 0.037; the lipid oxidation ratio was up to 78.25% ± 17.74% and 67.13% ± 12.76% supported by parenteral nutrition solutions from 37.56% ± 11.64% at the baseline; the level of Ln-HOMA-IR went up dramatically (P < 0.05, respectively) on postoperative days 1 and 3 in the IIT group. Meanwhile the concentration of total protein, albumin and triglyceride declined significantly on postoperative days 1 and 3 compared with pre-operative levels (P < 0.05, respectively). Compared with the CIT group, IIT reduced the REE/kg level (27.22 ± 1.33 kcal/kg vs 29.97 ± 1.47 kcal/kg, P = 0.008; 24.72 ± 1.43 kcal/kg vs 25.66 ± 1.63 kcal/kg, P = 0.013); and decreased the Ln-HOMA-IR score (P = 0.019, 0.028) on postoperative days 1 and 3; IIT decreased the level of CRP on postoperative days 1 and 3 (P = 0.017, 0.006); the total protein and albumin concentrations in the IIT group were greater than those in the CIT group (P = 0.023, 0.009). Postoperative values of internal cell fluid (ICF), fat mass, protein mass (PM), muscle mass, free fat mass and body weight decreased obviously on postoperative 7th day compared with the preoperative baseline in the CIT group (P < 0.05, respectively). IIT reduced markedly consumption of fat mass, PM and ICF compared with CIT (P = 0.009 to 0.026). CONCLUSION: There were some benefits of IIT in decreasing the perioperative insulin resistance state, reducing energy expenditure and consumption of proteins and lipids tissue in patients undergoing gastrectomy.

Effect of Acupressure Therapy on Anti-inflammatory Mechanism in Obesity-induced IR Rats

[Objectives] To study the effect of "acupressure therapy" on anti-inflammatory mechanism in obesity-induced IR rats. [Methods] 10 rats were randomly selected and fed with normal diet as blank group, and the remaining 30 rats were fed with high-fat diet for 8 weeks. The obesity-induced IR model was induced and divided into two groups: model group and acupressure group. The acupressure group was treated by "acupressure therapy" three times a week for 6 weeks;the model group was taken 3 times at the same time every week, and the supine binding experiment lasted for 10 min for 6 weeks. Morphological observation was carried out before and after the experiment, mainly observing the general conditions and body weight. After the last intervention, the animals were killed and samples were collected. Western Blot method was used to detect the expression of TNF-α and IL-6 protein in adipose tissue of the three groups. [Results] Compared with the blank group, the expression of TNF-α and IL-6 protein in adipose tissue of the model group increased significantly ( P <0.01);compared with the model group, the expression of TNF-α and IL-6 protein in adipose tissue of the acupressure group decreased significantly ( P <0.01). [Conclusions] After intervening in the obesity-induced IR rats with acupressure method, the status of insulin resistance in obese rats was improved by inhibiting the expression of inflammatory factors.

奥利司他对多囊卵巢综合征伴胰岛素抵抗患者的疗效及安全性

目的 探讨奥利司他对多囊卵巢综合征(PCOS)伴胰岛素抵抗(IR)患者的治疗效果及安全性。方法 依据稳态模型法评估的胰岛素抵抗指数(HOMA-IR)选取2020年8月至2023年8月泰州市中医院收治的104例PCOS-IR患者,按随机数字表法分为对照组52例(失访2例)和试验组52例(失访5例)。对照组患者给予炔雌醇环丙孕酮,试验组患者给予奥利司他,两组均治疗3个月。对比两组患者机体测量学指标、糖脂代谢水平、激素水平及产生的不良反应。结果 治疗后,试验组患者BMI、体质量、腰围[分别为(25.74±1.08) kg·m^(-2)、(59.23±2.80) kg、(94.10±5.13) cm]均低于对照组[分别为(26.23±1.26) kg·m^(-2)、(60.51±2.31) kg、(96.5±5.20) cm](t=2.050、2.462、2.287,均P<0.05),总胆固醇(TC)、甘油三酯(TG)、空腹血糖(FPG)、HOMA-IR[分别为(3.86±0.73) mmol·L^(-1)、(1.68±0.72) mmol·L^(-1)、(3.75±0.88) mmol·L^(-1)、(1.61±0.37)]均低于对照组[分别为(5.12±0.13) mmol·L^(-1)、(1.98±0.43) mmol·L^(-1)、(4.78±0.35) mmol·L^(-1)、(2.78±0.43)](t=12.007、2.508、7.659、14.323,均P<0.05);两组患者治疗后卵泡雌激素(FSH)差异无统计学意义[(6.71±0.69) mIU·mL^(-1) vs(6.79±0.72) mIU·mL^(-1),t=0.558,P>0.05)],试验组总睾酮(T)、血清黄体生成素(LH)、LH/FSH[(1.38±0.22) nmol·L^(-1)、(6.24±0.78) IU·L^(-1)、(0.93±0.15)]均低于对照组[(1.84±0.27) nmol·L^(-1)、(7.12±0.83) IU·L^(-1)、(1.05±0.17)](t=9.165、5.373、3.677,均P<0.05);两组不良反应发生率差异无统计学意义(8.50%vs 10.00%,χ^(2)=0.064,P>0.05)。结论 奥利司他治疗PCOS-IR患者能有效减重,调节糖脂代谢及性激素水平,改善胰岛素抵抗,且安全性良好。

电针对胰岛素抵抗大鼠下丘脑自噬活性的影响

目的观察电针对胰岛素抵抗(insulin resistance,IR)大鼠下丘脑自噬调控基因Atg1、Atg13和Beclin-1表达及糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK3β)表达的影响,探究针刺治疗IR的潜在机制。方法将45只清洁级Wistar大鼠随机分为正常组(15只)和模型制备组(30只)。正常组予常规饲养,模型制备组予高脂饲料和10%的果糖水饲养8周,制备IR模型。造模成功后,将模型制备组30只大鼠随机分为模型组(15只)和电针组(15只)。电针组大鼠行电针干预。分别于造模成功后及干预后,采用微量血糖仪和酶联免疫吸附法测定大鼠空腹血糖(fasting blood glucose,FBG)及空腹胰岛素(fasting insulin,FINS),计算胰岛素抵抗指数(insulin resistance index,IRI),评定大鼠IR程度。用Western blot和real-time PCR法检测下丘脑组织Atg1、Atg13、Beclin-1、GSK3βmRNA和蛋白表达,评价电针对胰岛素抵抗大鼠下丘脑自噬活性的影响。结果造模后,与正常组比较,模型制备组大鼠IRI均明显升高(P<0.05)。干预后,与正常组比较,模型组大鼠Atg1、Atg13、Beclin-1、GSK3βmRNA和蛋白表达升高(P<0.05);与模型组比较,电针组Atg1、Atg13、Beclin-1、GSK3βmRNA和蛋白表达均降低(P<0.05),IRI降低(P<0.05)。结论电针可明显改善高脂高糖诱导的IR,其机制可能与下调自噬相关因子Atg1、Atg13、Beclin-1表达从而抑制下丘脑细胞过度自噬以及降低GSK3β的表达有关。

极低热量生酮饮食的管理及临床应用

膳食治疗是超重与肥胖人群体重管理的关键措施之一。研究表明,相较于其他膳食治疗方案,极低热量生酮饮食(very low-calorie ketogenic diet,VLCKD)具有短期减重效果明显、改善胰岛素抵抗等优势,具备较高的潜在临床应用价值。然而VLCKD在调节血脂、共病改善、长期减重及副作用严重程度等方面仍存在一定争议,对其临床应用产生一定困扰。本文在概述VLCKD概念与临床应用的基础上,重点阐述VLCKD对肥胖人群体重、血糖、血脂、其他疾病等的影响以及副作用的产生与预防,进而为肥胖临床膳食治疗提供参考与证据支持。

肌肉肌醇与D-手性肌醇在多囊卵巢综合征中的研究及应用

肌醇是一种“生物活素”,参与体内代谢和免疫调节等活动,在预防和治疗某些疾病中显示潜在的应用价值。其中肌肉肌醇(Myo-inositol,MI)是最普遍存在的形式,高等动物若缺乏肌醇,将会出现生长停滞和毛发脱落等现象。D-手性肌醇(D-chiro-inositol,DCI)是肌醇9种异构体中具有旋光性的一种。近年来研究者们发现DCI除了具有肌醇促进肝脏脂代谢的功能外,还具有胰岛素增敏作用、降血糖、改善多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者的排卵情况等功能。研究表明,MI联合DCI不仅可以改善卵巢功能和生育能力,而且还能调节激素平衡,改善月经失调,还具有抗氧化、抗衰老、抗炎等特殊的生理功能。MI和DCI联合应用在PCOS治疗的优势、MI和DCI联合用药的剂量等尚需更多动物基础实验和临床研究,还需注意长期应用的安全性以及个体差异性应答等。

Challenges and pitfalls of youth-onset type 2 diabetes

The incidence and prevalence of youth-onset type 2 diabetes mellitus(T2DM)are increasing.The rise in frequency and severity of childhood obesity,inclination to sedentary lifestyle,and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes complications.Indeed,youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM,with greater insulin resistance and more rapid deterioration of beta cell function.Therefore,intermediate complications such as microalbuminuria develop in late childhood or early adulthood,while end-stage complications develop in mid-life.Due to the lack of efficacy and safety data,several drugs available for the treatment of adults with T2DM have not been approved in youth,reducing the pharmacological treatment options.In this mini review,we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.

Hereditary severe insulin resistance syndrome:Pathogenesis,pathophysiology,and clinical management

Severe insulin resistance has been linked to some of the most globally prevalent disorders,such as diabetes mellitus,nonalcoholic fatty liver disease,polycystic ovarian syndrome,and hypertension.Hereditary severe insulin resistance syndrome(H-SIRS)is a rare disorder classified into four principal categories:primary insulin receptor defects,lipodystrophies,complex syndromes,and obesity-related H-SIRS.Genes such as INSR,AKT2,TBC1D4,AGPAT2,BSCL2,CAV1,PTRF,LMNA,PPARG,PLIN1,CIDEC,LIPE,PCYT1A,MC4R,LEP,POMC,SH2B1,RECQL2,RECQL3,ALMS1,PCNT,ZMPSTE24,PIK3R1,and POLD1 have been linked to H-SIRS.Its clinical features include insulin resistance,hyperglycemia,hyperandrogenism,severe dyslipidemia,fatty liver,abnormal topography of adipose tissue,and low serum leptin and adiponectin levels.Diagnosis of H-SIRS is based on the presence of typical clinical features associated with the various H-SIRS forms and the identification of mutations in H-SIRS-linked genes by genetic testing.Diet therapy,insulin sensitization,exogenous insulin therapy,and leptin replacement therapy have widely been adopted to manage H-SIRS.The rarity of H-SIRS,its highly variable clinical presentation,refusal to be tested for genetic mutations by patients’family members who are not severely sick,unavailability of genetic testing,and testing expenses contribute to the delayed or underdiagnoses of H-SIRS.Early diagnosis facilitates early management of the condition,which results in improved glycemic control and delayed onset of diabetes and other complications related to severe insulin resistance.The use of updated genetic sequencing technologies is recommended,and long-term studies are required for genotype–phenotype differentiation and formulation of diagnostic and treatment protocols.

苍附导痰汤加味治疗脾虚痰湿型多囊卵巢综合征伴胰岛素抵抗临床观察

目的:观察苍附导痰汤加味治疗脾虚痰湿型多囊卵巢综合征伴胰岛素抵抗的临床疗效。方法:将80例多囊卵巢综合征伴胰岛素抵抗患者按随机数字表法分为两组各40例,对照组予二甲双胍治疗,治疗组在对照组基础上加苍附导痰汤加味治疗。两组均治疗3个月经周期,比较两组临床疗效。结果:治疗组总有效率为92.5%,对照组为87.5%,两组比较,差异有统计学意义(P﹤0.05)。治疗后,治疗组胰岛素抵抗相关指标、中医证候评分、子宫内膜容受性相关指标、性激素水平(PRL、FSH、LH、T)、总胆固醇(TC)、甘油三酯(TG)水平均较对照组改善明显,差异有统计学意义(P﹤0.05)。结论:苍附导痰汤加味治疗脾虚痰湿型多囊卵巢综合征伴胰岛素抵抗患者,可以缓解临床症状,一定程度上纠正胰岛素抵抗状态,调节性激素水平。

伏格列波糖联合西格列汀对2型糖尿病患者糖脂代谢及胰岛素抵抗的影响

目的分析应用伏格列波糖、西格列汀联合方案对2型糖尿病(type 2 diabetes mellitus,T2DM)患者糖脂代谢及胰岛素抵抗的改善作用。方法选取2022年8月—2023年8月建瓯市立医院收治的108例T2DM患者为研究对象,以随机信封法分为对照组和观察组,每组54例。对照组采用单纯伏格列波糖进行治疗,观察组采用伏格列波糖+西格列汀进行治疗,对比两组的临床疗效、糖脂代谢指标、胰岛功能指标、炎性因子水平。结果观察组临床总有效率为94.44%,高于对照组的81.48%,差异有统计学意义(χ^(2)=7.930,P=0.005)。治疗后两组空腹血糖、餐后2 h血糖、甘油三酯、低密度脂蛋白胆固醇均较治疗前下降,且观察组各指标水平均低于对照组,差异有统计学意义(P均<0.05)。治疗后两组胰岛功能指标均低于治疗前,且观察组低于对照组,差异有统计学意义(P均<0.05)。治疗后两组白细胞介素-6、肿瘤坏死因子-α水平均低于治疗前,且观察组低于对照组,差异有统计学意义(P均<0.05)。结论伏格列波糖、西格列汀联合方案,应用于T2DM治疗中疗效显著,对糖脂代谢、胰岛素抵抗有良好改善作用。

有氧运动治疗应用在单纯性肥胖儿童中对其糖脂代谢、胰岛素抵抗及血管内皮功能的影响分析

目的研究分析有氧运动治疗对单纯性肥胖儿童糖脂代谢、胰岛素抵抗以及血管内皮功能的影响。方法简单随机选取2020年5月—2023年5月福建省泉州市洛江区妇幼保健院收治的60例单纯性肥胖的儿童作为研究对象,依据随机数表法分组,对照组(n=30)予以常规饮食及行为干预,观察组(n=30)基于对照组干预条件予以有氧运动治疗,比较两组儿童不同干预时间的糖脂代谢指标、机体胰岛素抵抗状况以及血管内皮功能。结果干预后,观察组空腹血糖(Fasting Plasma Glucose,FPG)、胆固醇(Cholesterol,TC)以及三酰甘油(Triglyceride,TG)水平依次为(4.83±0.53)、(4.03±0.42)、(1.56±0.21)mmol/L,均低于对照组,分别为(5.19±0.61)、(4.65±0.53)、(1.79±0.24)mmol/L,差异有统计学意义(t=2.440、5.021、3.950,P均<0.05)。干预后,观察组2项胰岛素抵抗指标[空腹胰岛素(Fasting Insulin,FINS)、胰岛素抵抗指数(Insulin Resistance Index,HOMA-IR)]均低于对照组,差异有统计学意义(t=3.472、2.544,P均<0.05)。干预后,观察组一氧化氮(Nitric Oxide,NO)较对照组更高,内皮素-1(Endothelin-1,ET-1)较对照组更低,差异有统计学意义(t=2.719、3.298,P均<0.05)。结论对单纯性肥胖儿童实施有氧运动疗法干预,能够有效改善其糖脂代谢状况以及胰岛素抵抗问题,并且对血管内皮功能的恢复有良好助益。

低血糖指数膳食对妊娠期糖尿病营养治疗的干预效果分析

目的分析低血糖指数膳食对妊娠期糖尿病营养治疗的干预效果。方法选取2021年11月—2022年11月甘肃省张掖市山丹县妇幼保健院妇产科收治的86例妊娠期糖尿病患者为研究对象,并按照随机分组法分为观察组(43例,低血糖指数膳食营养治疗)和对照组(43例,常规营养治疗),比较两组血糖(FPG、2hPBG、HbAlc)控制情况、胰岛素抵抗指数、能量摄入情况、不良事件发生率、满意度。结果干预后,观察组FPG、2h PBG、HbAlc、胰岛素抵抗指数均低于对照组,组间差异有统计学意义(P<0.05)。观察组脂肪摄入量高于对照组,组间差异有统计学意义(P<0.05);观察组碳水化合摄入量少于对照组,组间差异有统计学意义(P<0.05);两组蛋白质、摄入总能量比较无差异(P>0.05)。观察组不良事件(胎儿宫内窘迫、巨大儿、产后出血、低血糖、妊高征)发生率低于对照组,组间差异有统计学意义(P<0.05)。观察组满意度高于对照组,组间差异有统计学意义(P<0.05)。结论低血糖指数膳食可控制妊娠期糖尿病患者血糖水平,降低胰岛素抵抗指数、碳水化合物摄入量,增加脂肪摄入量,降低不良事件发生率,提升患者满意度,可应用。

Hepatitis C and insulin action:An intimate relationship

Chronic hepatitis C virus(HCV) infection has been shown to be linked to a higher prevalence of type 2 diabetes compared with the general population or with patients with chronic hepatitis B infection and diabetes is the most common extra-hepatic manifestation of HCV. The HCV-diabetes association is due to insulin resistance(IR) that occurs early in the course of the disease even in patients without or with minimal fibrosis. The mechanisms for HCV-induced IR are only partly understood and include a direct inhibitory effect of HCV on insulin signaling pathway. IR in chronic HCV results in an increased progression rate of hepatic fibrosis, cirrhosis and hepatocellular carcinoma. Some but not all studies found that IR reduces the response rate to interferon/ribavirin therapy. Whether IR affects the response to the new direct-acting antiviral treatments is still unknown.

2型糖尿病胰岛素抵抗机制、因素分析与防治策略

胰岛素抵抗作为2型糖尿病发生及发展的关键病理基础,其病因及发病机制复杂,主要病理机制包括胰岛素受体前、受体结合及分子转导功能异常等多个环节,主要影响因素涉及多种细胞因子、氧化应激损伤、自噬功能失常、MicroRNAs、肠道内环境紊乱等。临床中旨在减轻高血糖状态、调节机体新陈代谢水平以及提供先进的科学诊疗手段,但随着新型降糖药物及作用靶点不断深入研究,目前仍不能发现2型糖尿病发生及发展有效且关键的切入点,因此深入研究胰岛素抵抗的发病机理,从多个研究方向出发则成为当今破解2型糖尿病难题的关键,该方法可为2型糖尿病的多靶向治疗或综合整体治疗提供明确的思路和方向,为2型糖尿病的基础研究及临床诊疗提供新的思路。文章归纳和总结了胰岛素抵抗研究的最新进展,并进行了深入分析,进一步明晰了胰岛素抵抗产生的原因和多重发病机制,明确了微观调控代谢平衡及防治胰岛素抵抗的作用机制,结合多靶向新药开发从而制定出了宏观与微观的控糖策略,为2型糖尿病整体综合治疗策略的制定提供更多的理论依据。

卡格列净联合胰岛素强化治疗T2DM患者胰岛素抵抗的变化

目的 探讨卡格列净联合胰岛素强化治疗2型糖尿病(T2DM)患者胰岛素抵抗的变化情况。方法 回顾性选择T2DM患者100例,按治疗方式分为联合组和胰岛素组。比较两组治疗期间空腹血糖(FBG)、餐后2h血糖(2hPG)、胰岛素用量、血糖达标时间、治疗前后胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β),以及不良反应发生情况。结果 与治疗前比较,治疗后两组FBG、2hPG均降低,且联合组降低更为显著(P<0.05)。治疗后联合组日胰岛素用量低于胰岛素组;治疗后联合组HOMA-IR低于胰岛素组,HOMA-β高于胰岛素组(P<0.05)。两组不良反应总发生率差异无显著性(P>0.05)。结论 卡格列净联合胰岛素强化治疗T2DM,可改善患者胰岛素抵抗(IR),且安全性高,值得临床推广应用。

倪青教授治疗2型糖尿病合并肥胖临床经验总结

目前全球2型糖尿病合并肥胖患病人数逐年增加,约2/3的2型糖尿病合并超重或肥胖,我国已成为全球超重及肥胖患者最多的国家,中医药在治疗2型糖尿病合并肥胖具有独特优势,既可调节糖脂代谢,又能够改善胰岛素抵抗,减轻体质量等。倪青教授认为本病的病机关键是脾胃亏虚为本,湿邪、瘀血、痰浊为标,治疗以健脾益胃为主,祛湿活血、化痰泄浊为辅,强调固护脾胃,因人制宜,改善不良饮食习惯及生活方式,达到健康降糖减肥的疗效。