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.

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.

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

Effect of Nutrition Education Using Self-Monitoring of Blood Glucose (SMBG) on Glycemic Control in Non-Insulin-Treated Obese Type 2 Diabetes Patients

The effect of nutrition education using self-monitoring of blood glucose on glycemic control was investigated in the present study. Of 36 males and 25 females aged 30 - 69 years under outpatient treatment at 3 hospitals in Niigata prefecture, Japan, 61 non-insulin-treated obese type 2 diabetes patients with HbA1c of 6.9% - 9.3% and body mass index of 25 kg/m2 or higher were randomly allocated. Thirty and 31 patients were analyzed in intervention and control groups, respectively. The intervention group performed self-monitoring of blood glucose 2 hours after supper twice a week for 6 months and underwent nutrition education on the association between meals and postprandial blood glucose once every 2 months. The primary outcome was glycated hemoglobin, with the secondary outcome of body mass index. Stages of change for eating the appropriate supper amount were investigated to verify the process of the educational effect, and satisfaction with diabetes treatment and well-being were investigated to verify the continuity of treatment. On intention-to-treat analysis, glycated hemoglobin (mean ± SD) decreased from 7.9% ± 0.6% to 7.7% ± 0.6% in the intervention group but increased from 7.9% ± 0.6% to 8.1% ± 0.6% in the control group, showing a significant difference in the change after intervention between the groups (p = 0.027). In the intervention group, body mass index decreased from 28.9 ± 3.8 to 28.4 ± 3.7 kg/m2 (p = 0.019), the stages of change to learn the appropriate amount of supper progressed (p = 0.026), and satisfaction with diabetes treatment increased (p = 0.031).

Type 2 diabetes with good glycemic control have improved insulin response and lower non-esterified fatty acid level after a meal challenge

Background: Pathogenesis of type 2 diabetes (T2DM) involves defects in β-cell function with impaired first and second phase insulin response, and reduced insulin sensitivity. Diabetic dyslipidemia is an important and common risk factor for coronary heart disease (CHD). Aims: This study examined the effect of glycemic control on post prandial insulin and lipid parameters in response to a standardised meal challenge among Type 2 diabetes patients with good and poor glycemic control. Methods: We cross-sectionally studied 31 T2DM patients with good glycemic control and 32 T2DM patients with poor glycemic control. Subjects were given, after minimum 10 hours of fasting, a standard meal containing 58% fat. Fasting and serial postprandial blood samples were taken over 8 hours to determine levels of triglyceride, direct LDL-C, apoB lipoprotein, non-esterified-fatty-acid, insulin and blood glucose. Results: Post prandial NEFA was significantly higher in poor controlled diabetes patients compared to good control diabetes patients (p = 0.019), and post-hoc analysis showed significant difference from 3 hours post prandial to 4 hours post prandial, where p= 0.021. Although the difference in insulin between the 2 groups did not reach statistical significance (p =0.058), post-hoc analysis showed significant difference between the 2 groups from fasting to 1 hour post prandial (p = 0.034) despite postprandial glucose being significantly higher in poor controlled diabetes patients (p < 0.001), throughout the postprandial period. Conclusion: T2DM patients with good glycemic control have improved insulin response with lower non-esterified fatty acid.

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.

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.

Amelioration of type 1 diabetes following treatment of non-obese diabetic mice with INGAP and lisofylline

Type 1 diabetes mellitus results from the autoimmune and inflammatory destruction of insulin-producing islet β cells, rendering individuals devoid of insulin production. Recent studies suggest that combination therapies consisting of anti-inflammatory agents and islet growth-promoting factors have the potential to cause sustained recovery of β cell mass, leading to amelioration or reversal of type 1 diabetes in mouse models. In this study, we hypothesized that the combination of the anti-inflammatory agent lisofylline (LSF) with an active peptide fragment of islet neogenesis associated protein (INGAP peptide) would lead to remission of type 1 diabetes in the non-obese diabetic (NOD) mouse. We treated groups of spontaneously diabetic NOD mice with combinations of LSF, INGAP peptide, or control saline parenterally for up to 6 weeks. Our results demonstrate that the mice receiving combined treatment with LSF and INGAP peptide exhibited partial remission of diabetes with increased plasma insulin levels. Histologic assessment of pancreata in mice receiving combined therapy revealed the presence of islet insulin staining, increased β cell replication, and evidence of Pdx1-positivity in ductal cells. By contrast, diabetic animals showed severe insulitis with no detectible insulin or Pdx1 staining. We conclude that the novel combination treatment with LSF and INGAP peptide has the potential to ameliorate hyperglycemia in the setting of established type 1 diabetes via the recovery of endogenous β cells and warrant further studies.

Transplantation for the treatment of type 1 diabetes

Transplantation of pancreatic tissue,as either the intact whole pancreas or isolated pancreatic islets has become a clinical option to be considered in the treatment of patients with type 1 insulin-dependant diabetes mellitus. A successful whole pancreas or islet transplant offers the advantages of attaining normal or near normal blood glucose control and normal hemoglobin A1c levels without the risks of severe hypoglycemia associate with intensive insulin therapy. Both forms of transplants are also effective at eliminating the occurrence of significant hypoglycemic events (even with only partial islet function evident). Whereas whole pancreas transplantation has also been shown to be very effective at maintaining a euglycemic state over a sustained period of time,thus providing an opportunity for a recipient to benefit from improvement of their blood glucose control,it is associated with a significant risk of surgical and post-operative complications. Islet transplantation is attractive as a less invasive alternative to whole pancreas transplant and offers the future promise of immunosuppression-free transplantation through pre-transplant culture. Islet transplantation however,may not always achieve the sustained level of tight glucose control necessary for reducing the risk of secondary diabetic complications and exposes the patient to the adverse effects of immunosuppression. Although recent advances have led to an increased rate of obtaining insulin-independence following islet transplantation,further developments are needed to improve the long-term viability and function of the graft to maintain improved glucose control over time.

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.

Prevalences of Diabetes and Hypertension and Their Relationship in Community Population of Jiangsu Province

To determine the prevalences of non-insulin-dependent-diabetes mellitus (NIDDM),impaired glucose tolerance (IGT) and hypertension on urban and rural communities of Jiangsu province,8734 subjects sampled from six areas of Jiangsu were investigated. Blood glucose of 2 h after oral administration of 75 g glucose (2 h BG) was measured. WHO criteria were used for the diagnosis of NIDDMand IGT. Meanwhile epidemiological data were collected. Blood pressure, height, weight, waist and hip girths were measured. The crude prevalence was found to be 5. 82% (men 4.62%,woman 6. 69%) for NIDDM, 5. 87% (men 5. 30%, women 6. 29% ) for IGT and 14. 72% (men 16. 50%, women 13. 43 % ) for hypertension in the population obove 20 years of age. Age-adjusted prevalence was 4. 63% for NIDDM, 5. 07 % for IGT and 11. 19% for hypertension. Age increase (>40 years), obesity (BMI≥27) and central fat distribution (WHR≥0.88) were the risk factors for both diabetes and hypertension. The subjects≥40 years of age and obesity were the high risk population of NIDDM, IGT and hypertension. They were the target population for theprevention and treatment of diabetes and hypertension in the community level. High prevalences of NIDDM,IGT and hypertension were observed in the community population in Jiangsu province. To reinforce the prevention and treatment of these disorders in the province is imperative.

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.

MicroRNAs in hepatic pathophysiology in diabetes

MicroRNAs(miRNAs or miRs) are small approximately 22 nucleotide RNA species that are believed to regulate diverse metabolic and physiological processes.In the recent past,several reports have surfaced that demonstrate the role of miRNAs in various biological processes and numerous disease states.For a disease as complex as diabetes,the emergence of miRNAs as key regulators leading to the disease phenotype has added a novel dimension to the area of diabetes research.On the other hand,the liver,a metabolic hub,contributes in a major way towards maintaining normal glucose levels in the body as it can both stimulate and inhibit hepatic glucose output.This equilibrium is frequently disturbed in diabetes and hence,the liver assumes special significance considering the correlation between altered hepatic physiology and diabetes.While the understanding of the mechanisms behind this altered hepatic behavior is not yet completely understood,recent reports on the status and role of miRNAs in the diabetic liver have further added to the complexities of the knowledge of hepatic pathophysiology in diabetes.Here,we bring together the various miRNAs that play a role in the altered hepatic behavior during diabetes.

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 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.

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

INTRODUCTION Diabeticcapillariespathologicalchangesarethebaseofchroniccomplicationsindiabetesmellitus.Thechangesofmicrocirculationhaveanimportantinfluenceonoccurrenceanddevelopmentofcapillariespathologicalchanges.Diabeticretinopathyisoneofthemosti...

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.