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.

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.

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

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.

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 nonalcoholic 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, T2 DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

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.

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.

Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR

Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.

Measurement of bone mineral density in patients with type 2 diabetes mellitus

AIM:To investigate into the changes in bone mineral density(BMD)in patients with Type 2diabetes mellitus.METHODS:BMD of lumbar ver-tebrae 2-4and femur in 63cases of patients with type 2diabetes mel-litus were measured with dual energy X-ray absorptiometry(DEXA)and were compared with age,sex and BMI-m atched normal control group.RESULTS:No significant differences were fou nd in BMD of lumbar vertebrae 2-4in female of menopause with Type 2diabetes mellitus(P>0.05),but BMD of total were lower than that of the controls(P<0.05),BMD of neck were significantly lowe r than that of the controls(P<0.01);No significant differences were fo und in BMD of L 2-4 and femur in male of 50years old above with Type2diabetes mellitus(P>0.05).CONCLUSION:BMD of Type 2diabetes mellitus is dif ferent according to different sex,BMD of female of menop ause with type 2diabetes mellitus were descended easily,especially i n areas of neck BMD,it should cause to pay attention to in order to prevent p athologic bone fracture;BMD of male of 50years old above with Type 2diabetes mellitus have no the obvious changes than that of the controls.

CHANGESO NAILFOLD MICROCIRCULATION IN PATIENTS OF TYPE IIDIABETES MELLITUS WITH DIABETIC RETINOPATHY

INTRODUCTION Diabeticcapillariespathologicalchangesarethebaseofchroniccomplicationsindiabetesmellitus.Thechangesofmicrocirculationhaveanimportantinfluenceonoccurrenceanddevelopmentofcapillariespathologicalchanges.Diabeticretinopathyisoneofthemosti...

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.

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.

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.

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 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.

Elevated alanine aminotransferase activity is not associated with dyslipidemias,but related to insulin resistance and higher disease grades in non-diabetic non-alcoholic fatty liver disease

Objective:To explore demographic and metabolic factors associated with increased alanine aminotransferase(ALT)activity in non-diabetic non-alcoholic fatty liver disease(NAFLD)patients.Methods:Overall 372 patients who consecutively attended to Gastroenterology Clinic of Baqiyatallah University of Medical Sciences,Tehran,Iran awere diagnosed as NAFLD entered into analysis.Exclusion criteria were having diabetes mellitus and fasting blood glucose over126 mg/dL,active hepatitis B virus infection,having hepatitis C virus positive serology,and to be under corticosteroid therapy.ALT levels were considered pathologically high when it was over30 IU/L for men and over 19 IU/L for women.Results:Bivariate analyses using t test and chisquare test showed that patients with pathologically augmented ALT levels had significantly higher NAFLD grades in their ultrasonographic evaluations(P=0.003).Moreover,these patients represented significantly higher homeostatic model assessment levels(P=0.003),levels of serum insulin(P=0.002),fasting blood glucose(P<0.001),and uric acid(P=0.02).The prevalence of insulin resistance was also higher in patients with increased serum ALT concentrations.Multifactorial logistic regression models showed that ultrasonographic grading of NAFLD(P=0.027)and insulin resistance(P=0.013)were the only variables significantly associated with abnormal ALT levels.Conclusions:This study shows that the associations of increased ALT serum levels in NAFLD patients are different from what are supposed before.By excluding diabetic patients from our population,we find that increased ALT levels are not associated with dyslipidemias but are independently associated with insulin resistance and NAFLD grading on ultrasonographic evaluations.Further studies are needed to confirm our results.

Insulin producing cells established using non-integrated lentiviral vector harboring PDX1 gene

AIM: To investigate reprogramming of human adipose tissue derived stem cells into insulin producing cells using non-integrated lentivirus harboring PDX1 gene.METHODS: In this study, human adipose tissue derived stem cells(hADSCs) were obtained from abdominal adipose tissues by liposuction, selected by plastic adhesion, and characterized by flow cytometric analysis.Human ADSCs were differentiated into adipocytes and osteocytes using differentiating medium to confirm their multipotency. Non-integrated lentiviruses harboring PDX1(Non-integrated LV-PDX1) were constructed using specific plasmids(pLV-HELP, pMD2G, LV-105-PDX1-1).Then, hADSCs were transduced with non-integrated LVPDX1. After transduction, ADSCsPDX1+were cultured in high glucose DMEM medium supplement by B27, nicotinamide and βFGF for 21 d. Expressions of PDX1 andinsulin were detected at protein level by immunofluorescence analysis. Expressions of PDX1, neurogenin3(Ngn3), glucagon, glucose transporter2(Glut2) and somatostatin as specific marker genes were investigated at mRNA level by quantitative RT-PCR. Insulin secretion of hADSCsPDX1+in the high-glucose medium was detected by electrochemiluminescence test. Human ADSCsPDX1+were implanted into hyperglycemic rats.RESULTS: Human ADSCs exhibited their fibroblast-like morphology and made colonies after 7-10 d of culture.Determination of hADSCs identified by FACS analysis showed that hADSCs were positive for mesenchymal cell markers and negative for hematopoietic cell markers that guaranteed the lack of hematopoietic contamination. In vitro differentiation of hADSCs into osteocytes and adipocytes were detected by Alizarin red and Oil red O staining and confirmed their multilineage differentiation ability. Transduced hADSCs+PDX1became round and clusters in the differentiation medium. The appropriate expression of PDX1 and insulin proteins was confirmed using immunocytochemistry analysis.Significant expressions of PDX1, Ngn3, glucagon, Glut2and somatostatin were detected by quantitative RTPCR. hADSCsPDX1+revealed the glucose sensing ability by expressing Glut2 when they were cultured in the medium containing high glucose concentration. The insulin secretion of hADSCsPDX1+in the high glucose medium was 2.32 μU/mL. hADSCsPDX1+implantation into hyperglycemic rats cured it two days after injection by reducing blood glucose levels from 485 mg/dL to the normal level.CONCLUSION: Human ADSCs can differentiate into IPCs by non-integrated LV-PDX1 transduction and have the potential to be used as a resource in type 1 diabetes cell therapy.

Metabolic syndrome and non-alcoholic fatty liver disease:Asian definitions and Asian studies

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), as conventionally recognized, is a metabolic disorder largely confined to residents of affluent industrialized Western countries. However, obesity and insulin resistance are not restricted to the West, as witnessed by their increasingly universal distribution. In particular, there has been an upsurge in metabolic syndrome in the Asia-Pacific region, although there are critical differences in the extent of adiposity between Eastern and Western populations. DATA SOURCES: An English-language literature search using PubMed (1999-2007) on obesity, metabolic syndrome and NAFLD, focusing on Asian definitions and Asian studies. RESULTS: NAFLD appears to be of long-standing insulin resistance and likely represents the hepatic manifestation of the metabolic syndrome. With insulin resistance as a common factor, the disease is associated with atherosclerosis and cardiovascular risk. All features of the metabolic syndrome and related events are assessed for practical management of NAFLD, although the criteria for the diagnosis of obesity and central obesity differ across racial groups. CONCLUSIONS: The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension and ultimately metabolic syndrome, puts a very large population at risk of developing NAFLD in the coming decades. The simultaneous identification and appropriate treatment of the components of metabolic syndrome are crucial to reduce hepatic as well as cardiovascular morbidity and mortality.

糖尿病大鼠肾脏病变及其SnoN蛋白表达的变化

目的:复制2型糖尿病动物模型,并观察其肾脏病变及SnoN蛋白表达的变化。方法:SD大鼠随机分为正常对照组(NC)、高脂高糖组(HG)。高脂、高糖饮食12周后又随机分为高脂高糖对照组(HC)、糖尿病组(DM)。采用高脂、高糖饮食12周加小剂量链脲佐菌素注射(30 mg/kg)的方法复制2型糖尿病动物模型,成模大鼠随机分别于糖尿病8周(DM8)、12周(DM12)和16周(DM16)处死;Western印迹法检测肾皮质SnoN蛋白的水平;生物化学方法测血糖、血清胰岛素水平、甘油三酯、总胆固醇、血肌酐及24 h尿蛋白;光镜检查肾组织形态学改变。结果:DM组大鼠出现高血糖、高血脂、肾功能和肾组织形态学改变;HG组血清胰岛素水平、甘油三酯和总胆固醇明显升高,血糖与NC组相比差异无统计学意义;Western印迹检测发现DM8组肾组织中SnoN蛋白的表达明显低于NC组,且随病程进展逐渐减少,至DM16时减至NC组的64.20%。结论:成功复制了2型糖尿病动物模型;SnoN蛋白的表达变化可能参与了2型糖尿病肾脏病变的发生、发展过程。

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。