Complement activation in obesity, insulin resistance, and type 2 diabetes mellitus

Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity,insulin resistance,diabetes,dyslipidemia,and atherosclerosis.The complement system was originally viewed as a supportive first line of defense against microbial invaders,and research over the past decade has come to appreciate that the functions of the complement system extend beyond the defense and elimination of microbes,involving in such diverse processes as clearance of the immune complexes,complementing T and B cell immune functions,tissue regeneration,and metabolism.The focus of this review is to summarize the role of the activation of complement system and the initiation and progression of metabolic disorders including obesity,insulin resistance and diabetes mellitus.In addition,we briefly describe the interaction of the activation of the complement system with diabetic complications such as diabetic retinopathy,nephropathy and neuropathy,highlighting that targeting complement system therapeutics could be one of possible routes to slow down those aforementioned diabetic complications.

Detection of vitamin D in patients with gestational diabetes mellitus and its effects on insulin resistance, adipokines and TNF-α

Objective:To detect vitamin D levels in patients with gestational diabetes mellitus and the influence and clinical effect of Vitamin D supplement on insulin resistance, fatty factors and TNF-α.Methods:A total of 100 patients with GDM from September 2014 to May 2015 in our hospital were selected as object of observation (GDM Group). 52 cases patients with Vitamin D deficiency were randomly divided into two groups. At the same time, 50 cases of healthy pregnant women were selected as normal group. Biochemical indexes of observation group and normal group were detected. Biosynthetic Human Insulin Injection were given to the patients in the control group. The patients in the observation group were supplemented with vitamin D drops on the basis of the treatment of control group. The level of insulin resistance, adipokines and TNF-α were detected in the 2 groups.Results:FBG, PBG, FINS, TG, Visfatin, TNF-α and HOMA-IR in GDM group were higher compared with that in normal group. 25(OH)D3 and APN in GDM group decreased significantly compared with that in normal group. The comparison of TC, HDL-C and LDL-C in the two groups were not statistically significant. PBG, FINS, HOMA-IR, Visfatin and TNF-α in both groups after treatment significantly decreased compared with that before treatment. PBG, Visfatin and TNF-α in treatment group after treatment decreased more significantly than that in control group. FINS, HOMA-IR in treatment group after treatment increased more significantly than that in control group. The decrease of FBG was not obvious and there was no significant difference between the two groups after treatment. APN and 25(OH)D3 in both groups after treatment significantly increased compared with that before treatment. And they in treatment group after treatment increased more significantly than that in control group. In the correlation analysis, 25(OH) D3in serum was positively correlated to the the level of APN. Also, it was negatively correlated to HOMA-IR, Visfatin and TNF-α.Conclusion:Vitamin D levels in patients with gestational diabetes mellitus decreased more significantly compared with that in healthy pregnant women. And the patients with vitamin D deficiency have higher risk to get GDM. Vitamin D can treat GDM by regulating the degree of insulin resistance and the level of adipokines. And it has clinical value in the treatment of GDM.

Molecular mechanisms of noncoding RNA and epigenetic regulation in obesity with consequent diabetes mellitus development

Diabetes mellitus(DM)and obesity have become two of the most prevalent and challenging diseases worldwide,with increasing incidence and serious complications.Recent studies have shown that noncoding RNA(ncRNA)and epigenetic regulation play crucial roles in the pathogenesis of DM complicated by obesity.Identification of the involvement of ncRNA and epigenetic regulation in the pathogenesis of diabetes with obesity has opened new avenues of investigation.Targeting these mechanisms with small molecules or RNA-based therapies may provide a more precise and effective approach to diabetes treatment than traditional therapies.In this review,we discuss the molecular mechanisms of ncRNA and epigenetic regulation and their potential therapeutic targets,and the research prospects for DM complicated with obesity.

Relationship between β3-AR Gene and Obesity, Type 2 Diabetes, Insulin Resistance in Chinese Han Population

Objective: To explore the relationship between the β 3-adrenergic receptor(β 3-AR)gene and obesity, T2DM, insulin resistance in Chinese Han population. Methods: Fifty-three healthy subjects, 105 subjects with simple obesity, 63 type 2 diabetic patients without obesity, and 114 type 2 diabetic patients with obesity were studied with the technique of PCR-RFLP in codon 64 of the exon region of β 3-AR gene representing the variation Trp/Arg. Results: Compared with the subjects of Trp homozygous group, the individuals with Arg allele were more elevated in WHR,MBP,SBP,DBP,FBS,PBS,FINS,PINS,FCP,PCP and lower in ISI. Frequency of Arg allele was higher in HINS subgroup without T2DM. Conclusion: The results indicate that the Trp/Arg variation might lead to insulin resistance, obesity and T2DM.β 3-AR gene is supposed to be the candidate gene of insulin resistance, obesity and T2DM in Chinese Han population.

Adiponectin: Probe of the molecular paradigm associating diabetes and obesity

Type 2 diabetes is an emerging health challenge all over the world as a result of urbanization, high prevalence of obesity, sedentary lifestyle and other stress related factors compounded with the genetic prevalence. The health consequences and economic burden of the obesity and related diabetes mellitus epidemic are enormous. Different signaling molecules secreted by adipocytes have been implicated in the development of obesity and associated insulin resistance in type 2 diabetes. Human adiponectin, a 244-amino acid collagen-like protein is solely secreted by adipocytes andacts as a hormone with anti-inflammatory and insulinsensitizing properties. Adiponectin secretion, in contrast to secretion of other adipokines, is paradoxically decreased in obesity which may be attributable to inhibition of adiponectin gene transcription. There are several mechanisms through which adiponectin may decrease the risk of type 2 diabetes, including suppression of hepatic gluconeogenesis, stimulation of fatty acid oxidation in the liver, stimulation of fatty acid oxidation and glucose uptake in skeletal muscle, and stimulation of insulin secretion. To date, no systematic review has been conducted that evaluate the potential importance of adiponectin metabolism in insulin resistance. In this review attempt has been made to explore the relevance of adiponectin metabolism for the development of diabetes mellitus. This article also identifies this novel target for prospective therapeutic research aiming successful management of diabetes mellitus.

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age?

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

Recent advances in the managements of type 2 diabetes mellitus and natural hypoglycemic substances

Diabetes has become a global concern at present,among which type 2 diabetes mellitus(T2DM)accounts for approximately 90%-95%of patients.T2DM is a type of metabolic disorder syndrome that results from a genetic defect,and it is based on insulin resistance and an insulin secretion disorder.The occurrence of T2DM is usually the outcome of both genetic and environmental factors and their interactions.The etiology and pathogenesis of diabetes have not been fully elucidated,and no radical therapeutic cure has been found.Patients with T2DM suffer from complications such as the development of a chronic hyperglycemic condition and even serious metabolic disorders and organ damage in the body and depression and dementia,in addition to other chronic complications.Many studies have suggested that diet is crucial in the development of diabetes and the control of blood glucose.Natural substances have the characteristics of low toxicity and few side effects and may be key to the development of diabetic health products and preventive treatments.This paper reviews the etiology,pathogenesis,risks,treatments and diets related to T2DM to summarize the types of recently available natural products,from both local and foreign sources,for lowering blood glucose at home and their application in supplementary hypoglycemic foods.The key findings and conclusions suggest that there are various known T2DM-inducing factors,including genetic and environmental factors and three types of hybrid factors.

Mechanism of immune attack in the progression of obesity-related type 2 diabetes

Obesity and overweight are widespread issues in adults,children,and adolescents globally,and have caused a noticeable rise in obesity-related complications such as type 2 diabetes mellitus(T2DM).Chronic low-grade inflammation is an important promotor of the pathogenesis of obesity-related T2DM.This proinflammatory activation occurs in multiple organs and tissues.Immune cellmediated systemic attack is considered to contribute strongly to impaired insulin secretion,insulin resistance,and other metabolic disorders.This review focused on highlighting recent advances and underlying mechanisms of immune cell infiltration and inflammatory responses in the gut,islet,and insulin-targeting organs(adipose tissue,liver,skeletal muscle)in obesity-related T2DM.There is current evidence that both the innate and adaptive immune systems contribute to the development of obesity and T2DM.

Metabolic and biological changes in children with obesity and diabetes

The World Health Organization has stated that obesity in childhood is one of themost serious public health challenges of the 21st century. Overweightness andobesity in early childhood lead to a higher risk of overweightness and obesity inadulthood, thus conferring an increased risk of chronic inflammatory conditions,including type 2 diabetes mellitus, cardiovascular diseases, non-alcoholic fattyliver disease, and some cancers. Therefore, metabolome analysis, targeted atscreening and intervening in childhood obesity, is very important. Recent studieshave indicated that amino acid and lipid metabolism could influence metabolicpathways in children with obesity. For this review, we searched clinical dataaddressing metabolomic profiles and insulin resistance (IR) in children withobesity from inception to February 2021 in Medline, Web of Science, and Scopus.According to our search, branched-chain amino acids (BCAAs), aromatic aminoacids, and acylcarnitines have reportedly been associated with IR as biomarkersfor diabetes in children. BCAAs, tyrosine, and phenylalanine could be predictorsof the future development of diabetes in nondiabetic subjects. In addition, it iswell known that insulin regulates BCAA metabolism, and BCAA is a biomarkerfor IR. To interpret the mechanism behind metabolic changes in obesity, it is veryimportant to understand the pathways and combinations related with amino acid,lipid and glucose metabolism. In this review, we summarize studies on metabolicchanges to understand metabolomics in children with obesity.

WJD 5^(th) Anniversary Special Issues(2): Type 2 diabetes Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?

Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin.Compared with individuals without diabetes,patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality,and are disproportionately affected by cardiovascular disease.Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension,dyslipidaemia and obesity in these patients.However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors.Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus.Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events.Many of these risk factors could be common history for both di-abetes mellitus and cardiovascular disease,reinforcing the postulate that both disorders come independently from"common soil".The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.

New role for ceramide in hypoxia and insulin resistance

Ceramides are significant metabolic products of sphingolipids in lipid metabolism and are associated with insulin resistance and hepatic steatosis. In chronic inflammatory pathological conditions, hypoxia occurs, the metabolism of ceramide changes, and insulin resistance arises. Hypoxia-inducible factors(HIFs)are a family of transcription factors activated by hypoxia. In hypoxic adipocytes,HIF-1α upregulates pla2 g16(a novel HIF-1α target gene) gene expression to activate the NLRP3 inflammasome pathway and stimulate insulin resistance, and adipocyte-specific Hif1 a knockout can ameliorate homocysteine-induced insulin resistance in mice. The study on the HIF-2α-NEU3-ceramide pathway also reveals the role of ceramide in hypoxia and insulin resistance in obese mice.Under obesity-induced intestinal hypoxia, HIF-2α increases the production of ceramide by promoting the expression of the gene Neu3 encoding sialidase 3,which is a key enzyme in ceramide synthesis, resulting in insulin resistance in high-fat diet-induced obese mice. Moreover, genetic and pathophysiologic inhibition of the HIF-2α-NEU3-ceramide pathway can alleviate insulin resistance, suggesting that these could be potential drug targets for the treatment of metabolic diseases. Herein, the effects of hypoxia and ceramide, especially in the intestine, on metabolic diseases are summarized.

Insulin-resistance in paediatric age:Its magnitude and implications

Insulin resistance(IR)is insulin failure in normal plasma levels to adequately stimulate glucose uptake by the peripheral tissues.IR is becoming more common in children and adolescents than before.There is a strong association between obesity in children and adolescents,IR,and the metabolic syndrome components.IR shows marked variation among different races,crucial to understanding the possible cardiovascular risk,specifically in high-risk races or ethnic groups.Genetic causes of IR include insulin receptor mutations,mutations that stimulate autoantibody production against insulin receptors,or mutations that induce the formation of abnormal glucose transporter 4 molecules or plasma cell membrane glycoprotein-1 molecules;all induce abnormal energy pathways and end with the development of IR.The parallel increase of IR syndrome with the dramatic increase in the rate of obesity among children in the last few decades indicates the importance of environmental factors in increasing the rate of IR.Most patients with IR do not develop diabetes mellitus(DM)type-II.However,IR is a crucial risk factor to develop DM type-II in children.Diagnostic standards for IR in children are not yet established due to various causes.Direct measures of insulin sensitivity include the hyperinsulinemia euglycemic glucose clamp and the insulin-suppression test.Minimal model analysis of frequently sampled intravenous glucose tolerance test and oral glucose tolerance test provide an indirect estimate of metabolic insulin sensitivity/resistance.The main aim of the treatment of IR in children is to prevent the progression of compensated IR to decompensated IR,enhance insulin sensitivity,and treat possible complications.There are three main lines for treatment:Lifestyle and behavior modification,pharmacotherapy,and surgery.This review will discuss the magnitude,implications,diagnosis,and treatment of IR in children。

Exploring new treatment options for polycystic ovary syndrome: Review of a novel antidiabetic agent SGLT2 inhibitor

Polycystic ovary syndrome(PCOS)is the most common endocrinopathy in women of reproductive age associated with long-term metabolic and cardiovascular consequences.A plethora of symptoms and their severity differentiate on an individual level,giving the syndrome numerous phenotypes.Due to menstrual cycle abnormalities,women suffer from irregular menstrual bleeding,difficulty in conception,and infertility.Furthermore,the risk of pregnancy complications such as gestational diabetes mellitus,hypertensive disorders of pregnancy,and preterm birth are higher in women with PCOS than in the general population.Often,women with PCOS have comorbidities such as dyslipidemia,obesity,glucose intolerance or diabetes type 2,non-alcoholic fatty liver disease,and metabolic syndrome,which all influence the treatment plan.Historic insulinsensitizing agents,although good for some of the metabolic derangements,do not offer long-term cardiovascular benefits;therefore,new treatment options are of paramount importance.Sodium-glucose co-transporter-2(SGLT-2)inhibitors,a new class of antidiabetic agents with beneficial cardiovascular,bodyweight,and antihyperglycemic effects,although not approved for the treatment of PCOS,might be an attractive therapeutic addition in the PCOS armamentarium.Namely,recent studies with SGLT-2 inhibitors showed promising improvements in anthropometric parameters and body composition in patients with PCOS.It is important to further explore the SGLT-2 inhibitors potential as an early therapeutic option because of the PCOS-related risk of metabolic,reproductive,and psychological consequences.

Relationship between IRS-2G1057D variant and type 2 diabetes mellitus in Han population in Liaoning Province, China

The two major pathogeneses of type 2 diabetes mellitus (T2DM) are insulin resistance and insulin secretion deficiency. During recent years, researches on the molecular target sites of insulin resistance and the mechanism of the signal transduction has made great progress: especially, the study of insulin receptor substrate-2 (IRS-2). Human IRS-2 gene is located at 13q8.6. IRS-2G1057D is a replacement of G (glycine) by D (aspartic acid) at site 1057 of insulin receptor substrate-2, which is caused by simple nucleotide polymorphism. The role of this variant is still not clear. We detected IRS-2G1057D variant in Han population in Liaoning Province by measuring body mass index (BMI), waistline/hip ratio (WHR) and other parameters of insulin secretion, as well as insulin action to explore the relationship between IRS-2G1057D variant and T2DM.

2型糖尿病合并肥胖患者血清肌联素水平与胰岛素抵抗的相关性

目的 观察2型糖尿病(T2DM)合并肥胖患者血清肌联素(myonectin)水平的变化,探讨血清myonectin水平的影响因素及其与胰岛素抵抗的相关性。方法 选择2020年11月至2022年6月在河北北方学院附属第一医院内分泌科住院的186例T2DM患者,根据体重指数(BMI)分为糖尿病正常体重组(60例)、糖尿病超重组(65例)和糖尿病肥胖组(61例)。另选取同期于医院体检且BMI正常的健康者作为正常对照组(60例)。测定各组血清myonectin、空腹血糖(FPG)、空腹胰岛素(FINS)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,计算BMI及稳态胰岛素抵抗指数(HOMA-IR)。比较各组血清myonectin水平,并分析血清myonectin水平与胰岛素抵抗的相关性。结果 与正常对照组比较,糖尿病正常体重组、糖尿病超重组和糖尿病肥胖组的血清myonectin水平降低,差异有统计学意义(P<0.05)。与糖尿病正常体重组比较,糖尿病超重组和糖尿病肥胖组的myonectin水平降低,差异有统计学意义(P<0.05)。与糖尿病超重组比较,糖尿病肥胖组的myonectin水平降低,差异有统计学意义(P<0.05)。多元逐步回归分析表明,影响T2DM患者BMI的主要因素为myonectin、HOMA-IR、LDL-C、HDL-C、HbA1c。影响HOMA-IR的主要因素为myonectin、BMI、HbA1c、HDL-C。结论 血清myonectin水平在T2DM合并肥胖患者中显著降低,myonectin与胰岛素抵抗密切相关,与糖脂代谢共同参与了肥胖及糖尿病的发生、发展。

苍柴调中方辅助改善肝郁脾虚型肥胖2型糖尿病的疗效及对胰岛素抵抗、FFA、LDL-C水平的影响

目的:探讨苍柴调中方辅助改善肝郁脾虚型肥胖2型糖尿病(T2DM)的疗效,并分析其对胰岛素抵抗、游离脂肪酸(FFA)、低密度脂蛋白胆固醇(LDL-C)水平的影响。方法:选取2020年4月至2023年4月该院收治的肝郁脾虚型肥胖T2DM患者100例,根据随机数字表法分为两组,各50例。对照组患者使用二甲双胍治疗,观察组患者在对照组基础上联合苍柴调中方辅助治疗。观察两组患者的治疗效果,比较两组患者治疗前后中医症状积分、糖代谢指标[空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)]、血清FFA、LDL-C、肿瘤坏死因子α(TNF-α)水平的差异,并对不良反应发生率进行统计。结果:观察组患者的治疗总有效率高于对照组,不良反应发生率低于对照组,差异均有统计学意义(P<0.05)。治疗后,观察组患者倦怠乏力、精神抑郁、脘腹闷胀及大便黏滞等中医症状积分均低于对照组,差异均有统计学意义(P<0.05)。与治疗前比较,两组患者治疗后的FBG、HOMA-IR、FINS水平均明显降低,其中观察组患者治疗后的FINS、FBG及HOMA-IR水平低于对照组,差异均有统计学意义(P<0.05)。观察组患者治疗后的血清LDL-C、FFA、TNF-α水平均低于对照组,差异均有统计学意义(P<0.05)。结论:苍柴调中方辅助治疗可明显提高肝郁脾虚型肥胖T2DM患者的治疗效果,改善胰岛素抵抗,下调血清FFA、LDL-C水平。

孕早期血清脂肪因子CTRP6与妊娠糖尿病的关系

目的研究孕早期妇女血清补体C1q/肿瘤坏死因子相关蛋白6(C1q/tumor necrosis factor-related protein 6,CTRP6)的表达水平,探讨其与妊娠糖尿病(gestational diabetes mellitus,GDM)的关系。方法前瞻性连续选取2021年3月至2022年3月在郑州大学第二附属医院门诊产检的孕10~13周孕妇,收集孕妇的年龄、身高、体质量、末次月经时间,检测孕早期总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、高密度脂蛋白(high density lipoprotein,HDL)、低密度脂蛋白(low density lipoprotein,LDL)、空腹血糖(fasting plasma glucose,FPG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、空腹胰岛素(fasting insulin,FINS)、CTRP6水平,计算孕前体质量指数(body mass index,BMI)、基线BMI、产前BMI和胰岛素抵抗指数(亦称胰岛素抵抗的稳态模型评估,homeostatic model assessment of insulin resistance,HOMA-IR)。所有孕妇均于孕24~28周行75g口服葡萄糖耐量试验,根据试验结果分为GDM组和糖耐量正常(normal glucose tolerance,NGT)组。比较两组孕妇孕早期的临床资料及实验室指标,分析孕早期血清CTRP6与各指标的相关性及其与GDM的关系。结果共纳入孕妇213例,完整随访203例,其中52例孕妇被诊断为GDM,GDM发病率25.62%。GDM组孕妇的孕早期血清CTRP6、年龄、孕前BMI、基线BMI、产前BMI、TC、LDL、FPG、HbA1c、FINS、HOMA-IR均较NGT组升高,差异有统计学意义(P<0.05)。孕早期CTRP6与年龄、孕前BMI、基线BMI、产前BMI、TG、LDL、FPG、HbA1c、FINS、HOMA-IR呈正相关,与HDL呈负相关(P<0.05)。校正年龄、BMI、糖脂代谢指标及HOMA-IR后,孕早期CTRP6为GDM发病的独立影响因素。结论孕早期血清CTRP6升高与GDM相关,是GDM的独立危险因素。

血清microRNA-155、microRNA-21、趋化素、瘦素与糖尿病肥胖患者胰岛素抵抗的相关性

目的 探讨糖尿病肥胖患者血清microRNA-155(miR-155)、microRNA-21(miR-21)、趋化素、瘦素水平与胰岛素抵抗(IR)的相关性。方法 选取2022年1月—2023年4月山东中医药大学第二附属医院收治的138例2型糖尿病(T2DM)患者为研究对象,其中肥胖患者73例(肥胖组),非肥胖患者65例(非肥胖组)。肥胖组中有IR 45例(IR组),无IR 28例(非IR组)。收集患者一般资料,包括性别、体质量指数(BMI)、年龄、颈围(NC)、腰围(WC)、空腹血糖(FPG)、甘油三酯(TG)、空腹胰岛素(FINS)、高密度脂蛋白胆固醇(HDL-C)、miR-155、miR-21、趋化素、瘦素、胰岛素抵抗指数(HOMA-IR)水平;通过多因素逐步Logistic回归模型分析T2DM肥胖患者发生IR的危险因素;绘制受试者工作特征(ROC)曲线,分析miR-155、miR-21、趋化素、瘦素诊断T2DM肥胖患者IR的效能;Pearson法分析miR-155、miR-21、趋化素、瘦素与HOMA-IR的相关性。结果 肥胖组miR-155相对表达量低于非肥胖组(P <0.05),miR-21、趋化素、瘦素、HOMA-IR高于非肥胖组(P <0.05)。IR组miR-155相对表达量低于非IR组(P <0.05),NC、WC、miR-21、趋化素、瘦素水平高于非IR组(P<0.05)。多因素逐步Logistic回归分析结果显示:NC [O^R=1.416(95%CI:1.038,1.932)]、WC [O^R=1.227(95%CI:1.049,1.435)]、miR-155 [O^R=1.763(95%CI:1.205,2.579)]、miR-21[O^R=1.932(95%CI:1.356,2.753)]、趋化素[O^R=2.074(95%CI:1.492,2.883)]、瘦素[O^R=1.628(95%CI:1.246,2.127)]是T2DM肥胖患者发生IR的危险因素(P <0.05)。ROC曲线分析结果显示,miR-155、miR-21、趋化素、瘦素诊断T2DM肥胖患者IR的曲线下面积分别为0.865、0.909、0.874和0.871;敏感性为77.8%(95%CI:0.614,0.825)、86.7%(95%CI:0.792,0.917)、95.6%(95%CI:0.713,0.965)和80.0%(95%CI:0.692,0.917);特异性为85.7%(95%CI:0.647,0.903)、82.1%(95%CI:0.732,0.914)、75.0%(95%CI:0.675,0.928)和89.3%(95%CI:0.656,0.944)。miR-155与HOMA-IR呈负相关(r=-0.573,P=0.000),miR-21、趋化素、瘦素与HOMA-IR均呈正相关(r=0.531、0.558和0.568,均P=0.000)。结论 T2DM肥胖患者中IR较多,且miR-155、miR-21、趋化素、瘦素是T2DM肥胖患者发生IR的危险因素。

超重/肥胖合并2型糖尿病患者血清ANGPTL4、HSP70、IL-34水平与胰岛素抵抗的相关性

目的 探讨超重/肥胖合并2型糖尿病(T2DM)患者血清血管生成素样蛋白4(ANGPTL4)、热休克蛋白(HSP)70、白细胞介素-34(IL-34)水平与胰岛素抵抗的相关性。方法 选取2020年5月—2022年5月保定市第一中心医院T2DM患者182例(T2DM组)。参考相关诊断标准,将T2DM患者分为超重/肥胖T2DM组(90例)和体重正常T2DM组(92例)。另选取同期健康体检者90名作为正常对照组,其中超重/肥胖者40名(超重/肥胖对照组)、体重正常者50名(体重正常对照组)。检测所有研究对象血清ANGPTL4、HSP70、IL-34、胰岛素和血糖水平,计算稳态模型胰岛素抵抗指数(HOMA-IR)。T2DM患者治疗3个月后,再次检测其血清ANGPTL4、HSP70、IL-34水平和HOMA-IR。采用Pearson相关分析评估血清ANGPTL4、HSP70、IL-34与HOMA-IR的相关性。结果 与正常对照组和体重正常T2DM组比较,超重/肥胖T2DM组血清ANGPTL4和HSP70显著降低(P<0.05),血清IL-34和HOMA-IR显著升高(P<0.05)。与正常对照组比较,体重正常T2DM组血清ANGPTL4和HSP70显著降低(P<0.05),血清IL-34和HOMA-IR显著升高(P<0.05)。Pearson相关分析结果显示,血清ANGPTL4、HSP70与HOMA-IR呈负相关(r值分别为-0.733、-0.758,P<0.001),IL-34和HOMA-IR呈正相关(r=0.705,P<0.001)。治疗后,超重/肥胖T2DM组和体重正常T2DM组血清ANGPTL4和HSP70均明显升高,血清IL-34和HOMA-IR明显降低;且相对于超重/肥胖T2DM组,体重正常T2DM组血清ANGPTL4和HSP70升高更显著(P<0.05),血清IL-34和HOMA-IR降低更显著(P<0.05)。结论 超重/肥胖合并T2DM患者ANGPTL4、HSP70和IL-34与胰岛素抵抗显著相关,或可作为超重/肥胖合并T2DM的疗效监测指标。

司美格鲁肽联合恩格列净与二甲双胍治疗初诊肥胖2型糖尿病患者的临床效果

目的观察司美格鲁肽联合恩格列净与二甲双胍治疗初诊肥胖2型糖尿病(T2DM)患者的临床效果。方法选取2021年4月—2023年4月三明市第二医院内分泌科收治的初诊肥胖T2DM患者160例,按照随机数字表法分为二联药物组与三联药物组,各80例。二联药物组予二甲双胍片+恩格列净片治疗,三联药物组在二联药物组基础上给予司美格鲁肽注射液皮下注射,2组均治疗12周。比较2组临床疗效,治疗前后血糖指标[空腹血糖(FPG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA1c)]、胰岛素抵抗指数(HOMA-IR)、血糖变异性指标[葡萄糖目标范围内时间所占百分比(TIR%)、平均血糖波动幅度(MAGE)、血糖标准差(SDBG)、血糖变异系数(CVBG)],不良反应。结果三联药物组治疗总有效率为92.50%,高于二联药物组的78.75%(χ^(2)=6.144,P=0.013)。治疗12周后,2组FPG、2 hPG水平与HbA1c、HOMA-IR较治疗前均下降,且三联药物组下降幅度大于二联药物组(P<0.01);2组TIR%较治疗前升高,MAGE、SDBG、CVBG较治疗前下降,且三联药物组升高/下降幅度大于二联药物组(P<0.01)。二联药物组与三联药物组不良反应总发生率比较,差异无统计学意义(3.75%vs.6.25%,χ^(2)=0.132,P=0.717)。结论司美格鲁肽联合恩格列净与二甲双胍治疗初诊肥胖的T2DM患者临床疗效确切,可明显降低患者血糖,改善胰岛素抵抗,提高TIR%,降低血糖变异性,且安全性高。