The relationship between obese protein and noninsulin-dependent diabetes mellitus

To explore the role of obese protein (OP), the product of the obese gene, in the development of non-insulin-dependent diabetes mellitus (NIDDM). Metbods: Plasma obese protein level was measured by radioimmunoassay in 21 normal subjects, 24 adult obese patients and 20 patients with NIDDM. Results: The levels of the plasma obese protein in NIDDM patients (81. 0±17. 5 pg/ml) were very significantly lower than those in normal subjects (194. 3±17. 7 pg/ml) and obese patients (109.1±16. 4 pg/ml ) (P<0.01). The levels of the plasma obese protein in non-obese NIDDM patients were very significantly lower than those in non-obese normal subjects (P<0.01), and the levels of the plasma obese protein in obese NIDDM patients were very significantly lower than those in obese patients (P<0. 01). The leve1s of the plasma obese protein in NIDDM patients were significantly correlated with polyphagia (P<0.05), but not correlated with the body weight indexes after strict dieting, and the plasma levels of cholesterol, triglyceride, fasting glucose, hemoglobiti A, and the insulin levels during glucose tolerance test (P>0.05). Couclusion: Low plasma level of obese protein is one of the important factors contributing to obesity,and plasma obese protein may be closely related to the generation of NIDDM.

Simultaneous liver, pancreas-duodenum and kidney transplantation in a patient with hepatitis B cirrhosis, uremia and insulin dependent diabetes mellitus

Simultaneous liver,pancreas-duodenum,and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis,renal failure,and insulin dependent diabetes mellitus(IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus,mycophenolate mofetil,and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation,and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.

Modified upper abdominal cluster transplantation in patients with end-stage liver diseases associated with insulin dependent type 2 diabetes mellitus

Objective Modified upper abdominal cluster transplantation ( MCT) ,which was inspired by classical cluster transplant technique,has been proven more effective and feasible in the treatment of patients with end stage liver diseases associated with insulin - dependent

A Study of Factors Related to the Incidence of Cataract in Patients with Non-Insulin Dependent Diabetes Mellitus

Purpose: To investigate the factors related to the development of cataract in patientswith non-insulin dependent diabetes mellitus(NIDDM).Methods: 792 NIDDM patients received ophthalmologic examinations including visualacuity, external status of the eyes, slit lamp microscopy and ophthalmoscopy. Glucose,urea nitrogen (BUN), creatinine (Cr), urine acid (UA), N-acetyl-β2-D-glucosaminidase(NAG), β2-microglobulin(β2-MG) and serum albumin in blood were quantitativelytested. Glucose, pH value, protein, cells, cast and ketobodies in urine were assayed.Diagnosis of cataract was based on lens opacities classification system Ⅱ. Any patientmeeting "NⅡ", "CⅡ" or "PⅡ" level was diagnosed as cataract.Results: The incidence of cataract in this group of NIDDM was 62.37 % (494/792),which significantly related to the duration of the disease course, but not to the sex of thepatient. The occurrence rate of cataract in patients suffering from NIDDM of less thanfive years duration, from five to ten years, and more than ten years was 49.67 % (228/459), 71.84 % (125/174), and 88.68 % (141/159), respectively. The occurrence ofcataract in patients diagnosed of the disease from five to ten years and more than tenyears was much higher than that of those with the course of the disease less than fiveyears( P ＜ 0.05 and P ＜ 0. 001, respectively) . Rising concentrations of blood ureanitrogen, creatinine, glycosylated hemoglobin HbA1c(G-HbA1c), N-acetyl-β2-D-glucosaminidase(NAG) and β2-microglobulin(β2-MG) indicated malfunction of thekidneys, and the rate of cataract occurrence in these patients was higher.Conclusion: This study indicates that prolongation of the duration of non-insulindependent diabetes mellitus, renal dysfunction, as well as poor blood glucose control,may accelerate the development of cataract.

CLINICAL ANALYSIS OF 52 CASES OF JUVENILE DIABETES MELLITUS

The clinical significance of 52 cases of juvenile diabetes mellitus is reported in the article.The ratio of male to female was 1:2.5. 21.2% had the episode of infection prior to the onset of the disease;6.5% had positive family history.It is suggested from the article that more attention should be paid to nontypical cases which would incur misdiagnosis and improper treatment;and it might be necessary to differentiate the ketoacidosis from just positive ketonuria reaction. As for the latter,insulin hypodermic injection probably is more feasible than intravenous effusion.

Novel and emerging diabetes mellitus drug therapies for the type 2 diabetes patient

Type 2 diabetes mellitus is a metabolic disorder of deranged fat, protein and carbohydrate metabolism resulting in hyperglycemia as a result of insulin resistance and inadequate insulin secretion. Although a wide variety of diabetes therapies is available, yet limited efficacy, adverse effects, cost, contraindications, renal dosage adjustments, inflexible dosing schedules and weight gain significantly limit their use. In addition, many patients in the United States fail to meet the therapeutic HbA1c goal of 【 7% set by the American Diabetes Association. As such new and emerging diabetes therapies with different mechanisms of action hope to address some of these drawbacks to improve the patient with type 2 diabetes. This article reviews new and emerging classes, including the sodium-glucosecotransporter-2 inhibitors, 11β-Hydroxysteroid dehydrogenase type 1 inhibitors, glycogen phosphorylase inhibitors; protein tyrosine phosphatase 1B inhibitors, G Protein-Coupled receptor agonists and glucokinase activators. These emerging diabetes agents hold the promise of providing benefit of glucose lowering, weight reduction, low hypoglycemia risk, improve insulin sensitivity, pancreatic β cell preservation, and oral formulation availability. However, further studies are needed to evaluate their safety profile, cardiovascular effects, and efficacy durability in order to determine their role in type 2 diabetes management.

Association Studies of 3 Candidate Genes with Type 2 Diabetes Mellitus in a Chinese Population

Objectives To explore the relationship between the polymorphisms of the selected short tandem repeats (STRs) of the candidate genes and type 2 diabetes mellitus (DM) in a Chinese population,the role of genetic and environmental factors in the development of type 2 diabetes. Methods STRs including D11S916 of uncoupling protein 3 (UCP3) gene,binucleotide repeat (CA)n within intron 6 [HSLi6(CA)] of hormone-sensitive lipase(HSL)gene and D20S501 of protein tyrosine phosphatase-1B (PTP-1B)gene polymorphisms were detected, by poiymerase chain reaction(PCR) ,poly-acrylamide gel electrophoresis and silver staining in 106 patients with type 2 DM and 102 control subjects. Results The allele distribution of UCP3 and HSL gene differed significantly between patients with type 2 diabetes and control subjects (X2 = 26. 12,P<0. 005; X2 = 10. 33,P<0. 005,respectively). For UCP3 and HSL gene,the frequencies of alleles A6,A7,A8 and allele B9 were much higher in diabetic patients than in control subjects (0. 090 vs 0. 020,P<0. 005; 0. 109 vs 0. 015,P <0. 005; 0. 033 vs 0. 000,P<0. 05; 0. 033 vs 0. 005,P<0. 05,respectively),while the frequencies of allele A1 and allele B5 were lower in diabetic patients than in control subjects (0. 090 vs 0. 206,P<0. 005; 0. 057 vs 0. 118,P<0. 05,respectively). At D20S501 locus,The allele distribution of PTP-1B gene had no significant difference in two groups (X2 = 3. 77, P>0. 05). Multi-variate logistic regression analysis showed positive correlation between alleles A6,A7 of UCP3 gene,systolic blood pressure, apolipoprotein B, lipoprotein (a) and type 2 diabetes. Conclusion Our data show that D11S916 of UCP3 gene and HSLi6(CA) of HSL gene polymorphisms are associated with type 2 diabetes in Chinese suggesting that UCP3 and HSL might represent susceptibility genes for type 2 diabetes. D20S501 of PTP-IB gem polymorphism is not associated with type 2 diabetes in Chinese. Alleles A6, A7 of UCP3 gene, systolic blood pressure, apolipoprotein B,Upoprotein (a) may play some role in the development of type 2 diabetes.

Case-control analysis of the <i>ERAP1</i>polymorphism rs30187 in Italian type 1 diabetes mellitus patients

Autoimmune diseases are a heterogeneous group of disorders affecting different organs and tissues whose incidence are increasing worldwide. New tools, such as genome-wide association studies, have provided evidence for new susceptibility loci and candidate genes in the disease process including common susceptibility genes involved in the immunological synapse and T cell activation. Close linkages have been found in a number of diseases, including ankylosing spondylitis, multiple sclerosis, Crohn’s disease and insulin-dependent diabetes mellitus (Type 1 diabetes mellitus). The evidence for some associations with Type 1 diabetes was previously found in the region containing 5q15/ERAP1 (endoplasmic reticulum aminopeptidase 1) (rs30187, ARTS1). Our aim was to conduct the first casecontrol study to test the association between the rs30187 polymorphism of ERAP1 and the development of Type 1 diabetes mellitus in patients selected from continental Italy. All control subjects were matched for the sex, age, ethnic origin and geographical area. Genotyping of the rs30187 polymorphism of ERAP1 was carried out by the allelic discrimination assay on DNA extracted from whole blood. We did not observe a statistically significant prevalence of the rs30187 polymorphism of ERAP1 in our cohort of patients than in controls suggesting a minor contribution of this gene to the pathogenesis of Type 1 diabetes mellitus in Italian patients.

Study of the Pathogenesis of Hypertension Associated with Non-Insulin Dependent Diabetes Mellitus

In order to study the pathogenesis of hypertension associated with noninsulin dependent diabetes mellitus (NIDDM), Plasma glucose, insulin levels at fasting and following an oral glucose load were measured. Na +K +pump and Ca 2+ pump activities of red blood cell membrane were also assessed. Hypertensive patients with normal or impaired glucose tolerance (NGT, or IGT) had hyperinsulinemia. Obese hypertensive patients also had hyperinsulinemia, while nonobese hypertensive patients had no hyperinsulinemia, but exhibited a delay in insulin response to oral glucose tolerance test (OGTT). In multivariate analysis, considering the factors of age, BMI and plasma glucose level, DBP were still positively related to both 30 min insulin level and IAUC, but negatively correlated to activities of Na +K +pump and Ca 2+ pump. These results demonstrated that a link between obesity, hpertension and NIDDM is the insulin resistance and/or hyperinsulinemia.

Effects of Supplemented Taohe Chengqi Decoction (桃核承气汤) in Treating Insulin Resistance in Rats with Non-Insulin Dependent Diabetes Mellitus

Objective: To investigate the effect of supplemented Taohe Chengqi Decoction (桃核承气汤,STHCQD) in treating non-insulin dependent diabetes mellitus (NIDDM). Methods: The model of rats withNIDDM was formed with injection of streptozotocin and fed on high calorie diet to study the effects of STHCQDon the release of insulin sensitivity. Results: (l ) Fasting serum glucose, serum insulin, intake of food and waterwere significantly decreased (P < 0. 05 -- 0. 01 ) in STHCQD-treated diabetic rats as compared with untreated diabetic rats, while the insulin sensitivity was significantly increased (P < 0. 05 ). (2) The liver cell membranesfrom STHCQD-treated diabetic rats released the quantity of insulin receptor which inhibited adenylate cyclaseactivity, but this effect was blunted in untreated diabetic rats (P < 0. 05). (3) A significantly increased glucoseoxidation in adipocyte of STHCQD-treated diabetic rats was found as compared with those of untreated diabeticrats (P< 0. 05). Conclusions: STHCQD therapy Increased sensitivity and responsiveness of target cells to insulin, i. e. it might decrease insulin resistance at receptor sites and POst--receptor sites in rats with NIDDM, butcould not.reverse the insulin resistance.

Clinical Study on Jiang Tang San（降糖散）in Treating Non－Insulin Dependent Diabetes Mellitus Patiente

The therapeutic effect of Jiang Tang San (JTS) on 30 cases with non-insulin dependent dia-betes mellitus (NIDDM) , was observed, whose fasting blood glucose ranged trom 11. 1 mmol/L to 13. 8mmol/L. The results suggested that JTS has significant effect on NIDDM patients in lowering blood glucose,blood lipid and blood pressure levels. Clinical symptoms and blood glucose improved rapidly. JTS promotedthe elevation of serum insulin level 1 hour after meal. The total effective rate of lowering blood glucosereached 86. 7% . The results showed JTS is better than berberine on lowering blood glucose ( P< 0. 01 ) andwhen patients failed to respond to other hypoglycemics or on recurrence JTS was still effective. There wereno marked side-effects during the course of treatment.

Therapeutic Effect of Berberine on 60 Patients with Non－Insulin Dependent Diabetes Mellitus and Experimental Research

The effects of berberine on 60 cases with noninsulin dependent diabetes mellitus and ex-perimental research results were observed in this study. The results suggest berberine has significant ef-fects on noninsulin dependent diabetes mellitus patients and experimental diabetes in animals in the re-duction of blood glucose levels. The clinical symptoms basically disappeared and the level of serum insulinrose. The total effective rate was up to 90 percent and there were no signiticant side-effects. It was foundthat berberine has an effect on the recovery of pancreas islet cells, through pathological examination onthe animal subjects.

Clinical and Experimental Study of Persical Decoction forPurgation with Addition in the Treatment of Non-lnsulin Dependent Diabetes Mellitus

This study conducted clinical observation of the treatment of noninsulin dependent dia-betes mellitus (type ) with Semen Persical decoction for purgation with addition (SPDPA) in compari-son with a control group treated with glyburide. The results of the clinical observations show the total effective rate of SPDPA on 106 cases was 79%. which was equivalent to levels in the control group, butSPDPA was more effective in relieving symptoms. The animal experimental study showed SPDPA couldreduce tasting blood sugar in diabetic patients and rats. Its mechanism may be due to improved secretionof insulin, inhibited excretion by the endocrine cell, increased endocrine pellet inhibition ot insular cellsand improved composition of hepatic glycogen. In traditional Chinese medical theory, the mechanism oftherapeutic action of SPDPA in diabetes mellftus is based on synergistic regulation benefiting the vital en-ergy and nourishing Yin, the activation of blood circulation to dissipate blood stasis and the loosening ofthe bowel to relieve constipation.

CLINICAL OBSERVATION ON THERAPEUTIC EFFECTS OF COMBINED TREATMENT OF NONINSULIN DEPENDENT DIABETES

Objective: To observe the therapeutic effect of combined treatment of diabetes mellitus (DM) and its complications. Methods: 30 cases of noninsulin dependent diabetes were treated by electroacupuncture (EA)of Tianzhu (天柱 BL 10), Dashu (大杼 BL 11), Fengmen (风门 BL 12), Jueyinshu (厥阴俞 BL 14), etc, massage at the acupoints along the Bladder Meridian, point injection of Vitamin B1, B6, B 12plus lidocaine at Neiguan (内关 PC 6) and Sanyinjiao (三阴交 SP 6, once every 3 days), cupping and physiotherapy comprehensively. The therapeutic effect was analyzed after 40 treatments. Results: After treatment, of the 30 cases, 23 (76.7%) experienced remarkable improvement in their symptoms and the rest 7 (23.3%) had improvement, with the total effective rate being 100%. Conclusion: The abovementioned combined treatment method works well in improving clinical symptoms of type Ⅱ DM patients.

CHANGES OF NAILFOLD MICROCIRCULATION IN PATIENTS OF TYPE II DIABETES MELLITUS WITH DIABETIC RETINOPATHY

Objective. To study the changes of microcirculation in patients with diabetic retinopathy(DR). Methods. Examination were performed in 153 cases of type Ⅱ diabetes mellitus, among them, 72 cases were male, 81 cases were female, mean age 57.0±10.0 years, mean disease course 8.2±7.5 years. All cases were examined fundi by ophthalmologist, urinary albumin excretion rate (UAE) in 24 hours was measured by radioimmunoassay. Moreover, we examined the blood glucose, blood pressure, blood viscosity and observed the changes of naifold microcirculation. Results.It was found that there were more evident disturbance of microcirculation, markedly slowed velocity of blood flow(P<0.05), significantly increased aggregation of blood cells(P<0.05) and exudation around the loop(P<0.05) in the group with DR, compared with the group without DR. Conclusion. It was more evident disturbance of nailfold microcirculation in patients with diabetic retinopathy.

2型糖尿病患者肾功能损伤及氧合水平的BOLD MRI分析

目的 探讨采用血氧水平依赖磁共振成像(BOLD MRI)技术分析2型糖尿病(diabetes mellitus type2,T2DM)患者的估算肾小球滤过率(estimated glomerular filtration rate,eGFR)不同水平的肾缺氧改变。方法 选取T2DM患者以及同期健康正常者共78例,其中64例T2DM患者作为T2DM组,14例同期健康正常者作为对照组,均进行BOLD MRI检查。根据eGFR将64例T2DM患者又分为eGFR正常组(A组)、轻度功能损害组(B组)、中重度肾功能损害组(C组),测定肾脏髓质、皮质R2*(MR2*、CR2*)。采用单因素方差分析数据MR2*、CR2*的组间差异及其与eGFR的相关性,并采用受试者工作特征曲线(receiver operating characteristic cure, ROC)分析MR2*、CR2*值的诊断效能。结果 与对照组相比,A、B、C组MR2*、CR2*值均显著升高,差异有统计学意义(P均<0.05),均与eGFR呈正相关(P均<0.05),均可鉴别T2DM组与对照组,但MR2*值的鉴别敏感度稍高。结论 BOLD MRI可无创评估T2DM患者早期肾脏功能性缺氧改变,监测eGFR不同阶段的肾脏氧合水平,对临床治疗具有指导意义。

达格列净对2型糖尿病非增殖期视网膜病变的影响

目的:探讨达格列净对2型糖尿病非增殖期视网膜病变(non-proliferative diabetic retinopathy,NPDR)的影响。方法:选取2021年10月—2023年6月湖南师范大学附属湘东医院收治的88例2型糖尿病NPDR患者。随机将其分为观察组及对照组,各44例。两组均给予常规降糖治疗,观察组加用达格列净治疗。比较两组治疗前后血糖指标及相关指标。分析血管内皮生长因子(vascular endothelial growth factor,VEGF)与血糖波动指标的相关性。结果:治疗后,两组空腹血糖(fasting blood glucose,FBG)、餐后2 h血糖(2 h postprandial blood glucose,2 h PBG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、血糖水平标准差(standard deviation of blood glucose,SDBG)、餐后血糖波动幅度(postprandial glucose excursion,PPGE)、最大血糖波动幅度(large amplitude glycemic excursion,LAGE)均下降,观察组SDBG、PPGE、LAGE均低于对照组,差异有统计学意义(P<0.05)。治疗后,两组VEGF、黄斑中心凹厚度均下降,最佳矫正视力(best-corrected visual acuity,BCVA)升高,观察组VEGF、黄斑中心凹厚度均低于对照组,BCVA高于对照组,差异有统计学意义(P<0.05)。Pearson相关性分析结果显示:VEGF与SDBG、PPGE、LAGE均呈正相关(P<0.05)。结论:达格列净能够改善血糖波动,降低VEGF水平,对2型糖尿病NPDR有保护作用。

胰高血糖素样肽-1类似物研发进展

目的总结胰高血糖素样肽-1(GLP-1)类似物的研发进展。方法检索PubMed和Web of Science数据库自建库起至2024年2月20日的GLP-1类似物相关文献,从研发概况、单分子多靶点GLP-1受体激动剂(GLP-1RA)、除治疗糖尿病外的其他适应证及其药物研发新趋势方面,总结GLP-1类似物的研发进展。结果与结论GLP-1类似物的研发经历了从短效到长效,从注射剂到口服剂,并扩展到多靶点治疗的过程。目前,多靶点GLP-1RA包括GLP-1R/葡萄糖依赖性促胰岛素释放多肽受体、GLP-1R/胰高血糖素受体(GCGR)、GLP-1R/GLP-2R、GLP-1R/胰淀素3受体(AMY3R)、GLP-1R/成纤维细胞生长因子21受体(FGF-21R)等双靶点激动剂,以及GLPR/GLP-1R/GCGR、GLP-1R/GCGR/FGF-21R等三靶点激动剂。GLP-1类似物展现了在2型糖尿病、超重、肥胖症、心血管疾病、多囊卵巢综合征、非酒精性脂肪性肝炎、慢性肾脏病等疾病治疗的巨大潜力,疗效优于单靶点的双靶点和三靶点GLP-1RA是近年来研发的重点。GLP-1类似物的重组腺相关病毒载体基因治疗为研发新趋势,其现阶段存在的安全性、依从性等问题和可供参考的解决方法也一并被提出。

胰高血糖素样肽-1/葡萄糖依赖性促胰岛素多肽双受体激动剂替西帕肽

新型胰高血糖素样肽-1/葡萄糖依赖性促胰岛素多肽(GLP-1/GIP)双受体激动剂替西帕肽,临床显示具有较强的降糖效果,并且减轻体质量效果非常显著,可以提高胰岛素敏感性,同时具有优越的心血管保护作用和改善非酒精性脂肪性肝病/非酒精性脂肪性肝炎(NAFLD/NASH)的作用,并且副作用小,依从性好。替西帕肽作为双肠道激素激动剂对改善代谢水平显示出强大的潜力。该文就GLP-1/GIP双受体激动剂替西帕肽的作用机制和临床研究进行综述。

替西帕肽用于2型糖尿病治疗的研究进展

替西帕肽是一种新一代糖尿病药物,由礼来公司开发,并于2022年5月获得美国食品药物监督管理局(FDA)批准上市。替西帕肽基于多靶点激动剂与单一激动剂相比具有多重药理作用,是一种葡萄糖依赖性的促胰岛素多肽和胰高血糖素样肽-1受体双重激动剂。FDA批准替西帕肽皮下注射作为单一疗法或联合疗法,配合饮食和体育锻炼,以改善糖尿病患者的血糖水平。替西帕肽除了改善血糖控制外,该药物还能有效减轻体重、改善心脏代谢参数、改善血压、降低低密度脂蛋白、胆固醇和三酰甘油等。替西帕肽的有效性和安全性在一项超过1~5期临床试验项目中进行了评估,目前正在进行其他临床试验,以评估其在其他疾病中的应用。