Evaluation of glucose utilization in patients with insulin-independent diabetes mellitus by using breathing test

Commonly used clinical and biochemical parameters, such as the content of glucose, insulin, somatotropic hormone, triglycerides, lactate, pyruvate, and free fatty acids (FFA) in blood of practically healthy subjects and in patients with insulin-independent diabetes mellitus (IIDM), were compared with the parameters obtained by mass-spectrometric analysis of 13CO2 in expired air after 13C-glucose loading. It was shown that, as opposed to healthy subjects, the content of blood glucose and free fatty acids in patients with IIDM increased, the level of glucose dropped in progression upon short-term fasting, and the concentration of lactate changed both upon fasting and after the administration of small test doses of glucose. The use of the 13C-glucose breathing test (13C-GBT), which presupposes the loading of safe small doses of glucose enriched in 13C-isotope permitted one to reveal a number of novel quantitative diagnostic criteria for the evaluation of glucose metabolism in patients with IIDM: a decrease in the rate of 13C withdrawal as a constituent of expired carbon dioxide after the administration of 13C-glucose; a reduction in the amount of exogenous glucose metabolized to carbon dioxide; and increased oxidation of endogenous substrates participating in carbon dioxide formation. Small glucose loads proposed by the authors in 13C-GBT are safe for patients with diabetes mellitus and have no effect on the level of blood glucose in healthy persons. The parameters determined by noninvasive 13C-GBT are more sensitive for diagnosis than commonly used biochemical characteristics of blood in patients with IIDM. The diagnostic criteria obtained allow the prediction of the maximum prohibited glucose loading for every patient.     

Cellular immunity in insulin-dependent diabetes mellitus (type 1)

Cell-mediated immunity was investigated with T-cell blastic transformation stimulated by phytohaemagglutinin and/or insulin in patients with diabetes mellitus type 1. T-cell blastic transformation was determined in the whole blood by the intake of labelled thymidine intake by the lymphocytic DNA. Healthy individuals and patients with diabetes mellitus type 2 served as control groups. It was found that T-cell blastic transformation stimulated with phytohaemagglutinin is markedly diminished in patients with diabetes mellitus type 1 and to a lesser degree in patients with diabetes mellitus type 2. Insulin increased T-cell blastic transformation in insulin-dependent diabetic patients but has no effect in diabetes mellitus type 2. The obtained results suggest that induction and central phases of the cell-mediated immunological response are diminished in diabetes mellitus independently on its type. Such disorders may have different etiology depending on the type of diabetes mellitus.     

Effect of C111T polymorphism in exon 9 of the catalase gene on blood catalase activity in different types of diabetes mellitus

Hydrogen peroxide plays a major role in the pathomechanism of diabetes mellitus and its main regulator is enzyme catalase. The blood catalase and the C111T polymorphism in exon 9 was examined in type 1, type 2 and gestational diabetes mellitus. Compared to the control group (104.7 +/- 18.5 MU/l) significantly decreased (p < 0.001) blood catalase activities were detected in type 2 (71.2 +/- 14.6 MU/l), gestational (68.5 +/- 12.2 MU/l) diabetes mellitus and without change in type 1 (102.5 +/- 26.9 MU/l). The blood catalase decreased (p = 0.043) with age for type 2 diabetics and did not change (p>0.063) for type 1, gestational diabetic patients and controls. Blood catalase showed a weak association with hemoglobin A1c for type 1 diabetic patients (r = 0.181, increasing). The mutant T allele was increased in type 1 and gestational diabetes mellitus, and CT+TT genotypes showed decreased blood catalase activity for type 1 and increased activities for type 2 diabetic patients. The C111T polymorphism may implicate a very weak effect on blood catalase activity in different types of diabetes mellitus.     

Big brains and blood glucose: common ground for diabetes mellitus in humans and healthy dolphins

Healthy Atlantic bottlenose dolphins (Tursiops truncatus) have a sustained postprandial hyperglycemia, producing a prolonged glucose tolerance curve and a transient, diabetes mellitus-like state during 6 to 72 h of fasting. To further assess dolphins as comparative models for diabetes in humans, we hypothesized that a suite of hematological and clinical biochemistry changes during the fasting state may mimic those reported in humans with diabetes. We conducted a retrospective analysis of covariance to compare fasting and nonfasting hematologic and serum biochemical data, including 1161 routine blood samples from 52 healthy bottlenose dolphins (age, 1 to 49 y; male and female) collected during 1998 through 2005. Most changes found in dolphins during the fasting state--including significantly increased glucose, platelets, gamma-glutamyl transpeptidase, and alkaline phosphatase; significantly decreased serum uric acid; and shifts toward a metabolic acidodic state (significantly increased blood CO2)--have been previously associated with diabetes mellitus in humans. Therefore, healthy bottlenose dolphins may be the first complete and natural comparative animal model for diabetes mellitus in humans. Similarities between dolphins and humans, including metabolic changes associated with high-protein, low-carbohydrate diets; large brain-to-mass ratios; high central nervous system demands for glucose; and similarly unique blood glucose-carrying capacities should be further assessed to better understand the potential evolutionary paths of diabetes mellitus in these 2 species.     

Effect of C111T polymorphism in exon 9 of the catalase gene on blood catalase activity in different types of diabetes mellitus

Hydrogen peroxide plays a major role in the pathomechanism of diabetes mellitus and its main regulator is enzyme catalase.

The blood catalase and the C111T polymorphism in exon 9 was examined in type 1, type 2 and gestational diabetes mellitus.

Compared to the control group (104.7 ± 18.5 MU/l) significantly decreased (p < 0.001) blood catalase activities were detected in type 2 (71.2 ± 14.6 MU/l), gestational (68.5 ± 12.2 MU/l) diabetes mellitus and without change in type 1 (102.5 ± 26.9 MU/l). The blood catalase decreased (p = 0.043) with age for type 2 diabetics and did not change (p>0.063) for type 1, gestational diabetic patients and controls. Blood catalase showed a weak association with hemoglobin A1c for type 1 diabetic patients (r = 0.181, increasing).

The mutant T allele was increased in type 1 and gestational diabetes mellitus, and CT+TT genotypes showed decreased blood catalase activity for type 1 and increased activities for type 2 diabetic patients.

The C111T polymorphism may implicate a very weak effect on blood catalase activity in different types of diabetes mellitus.     

Increased myeloperoxidase activity is a risk factor for ischemic heart disease in patients with diabetes mellitus

Using a previously developed spectrophotometric method (Bioorg. Khim. 2009, vol. 35, pp. 629–639) a significant increase of myeloperoxidase (MPO) activity (versus healthy control) was found in blood plasma of patients with type 2 diabetes mellitus (DM2) without cardiovascular complications, and also in patients with ischemic heart disease (IHD). The plasma MPO concentration measured by an enzyme-linked immunosorbent assay was significantly higher only in blood plasma of patients with DM2 and IHD. A significant positive correlation between blood MPO activity and blood MPO content was observed only in blood plasma samples from healthy donors. Increased MPO activity did not correlate with MPO concentration in blood plasma of patients with DM2 and DM2 with IHD. Taken together, these results indicate that studies on the MPO role in the development of pathological processes should include simultaneous determination of both the amount of enzyme and its peroxidase activity in blood of patients. The proposed approach gives comprehensive information about the relationship between MPO activity and MPO concentration in patient’s blood. Since the high concentration of MPO is a diagnostically important parameter for the prediction of development of endothelial dysfunction and cardiovascular diseases, the obtained results point to the contribution of MPO-dependent reactions in cardiovascular complications associated with diabetes mellitus. MPO activity may serve as an additional diagnostic criterion for determination of risk of IHD in DM patients.     

Effect of insulin on the adipose tissue of patients with diabetes mellitus]

A study was made of insulin sensitivity of the adipose tissue biopsied in 11 healthy women, and in 10 women with normal weight suffering from newly-detected diabetes mellitus. In difference from healthy persons in the adipose tissue of patients suffering from diabetes, insulin in a concentration of 50 mu/ml failed to enhance the oxidation of glucose to CO2, and in a concentration of 50 and 100 mu/ml failed to enhance the glycogen synthesis from glucose. Reduction of the sensitivity of different ways of glucose metabolism in the adipose tissue to insulin in patients suffering from diabetes mellitus pointed to the possibility of disturbance of insulin interaction with the cell membrane in this disease.     

Activation of carboxylation as a factor in correcting the metabolic disorder in diabetes mellitus

The paper deals with studies of the effect of the 10-day complex therapy with carbostimulin application on the content of the tricarboxylic cycle and glycolysis metabolites, total lipids, cholesterol, triglycerides in blood and potassium and sodium in blood serum of patients with diabetes mellitus. It is established that under the effect of carbostimulin the content of oxaloacetate, lactate and alpha-glycerophosphate becomes normal, the lactate/pyruvate ratio elevated in diabetes decreases, which evidences for intensification of reduction processes in the cytoplasm.     

Isolation of Oct4+, Nanog+ and SOX2− mesenchymal cells from peripheral blood of a diabetes mellitus patient

Diabetes mellitus is a chronic metabolic disorder that affects millions of people worldwide. The most common form is type 2 diabetes mellitus, which results in impaired beta cell function combined with insulin resistance in peripheral organs. One recently proposed treatment approach is the use of adult stem cells derived from bone marrow in autologous stem cell transplantation. Alternatively, peripheral blood can be obtained in a more non-invasive manner. In this study, we isolated and cultured mesenchymal cells (MCs) from the peripheral blood of a diabetes mellitus patient. The cultured cells were large and elongated and had an in vitro migratory capacity in the culture dish. They expressed embryonic stem cell pluripotency markers Nanog and Oct 4 as well as mesenchymal markers CD105 and CD13, and they lacked expression of hematopoietic marker CD45. These characteristics suggest that these cells have a mesenchymal phenotype similar to that obtained from bone marrow cells. The SOX2 gene was downregulated in both the peripheral blood cells and the isolated mesenchymal cell line, indicating a defective mechanism of SOX2 in diabetes mellitus. The overall results of study demonstrate that peripheral blood can be used as a source of MCs from diabetes mellitus patients for use in future regenerative stem cell therapy and that this particular model system may be useful to study the mechanism of diabetes mellitus involving downregulation of the SOX2 cascade.     

Impaired cerebral CO2 vasoreactivity: association with endothelial dysfunction

Conflicting data exist on the role of nitric oxide (NO) in cerebral blood flow (CBF) autoregulation. Previous studies involving human and animal subjects seem to indicate that NO involvement is limited to the CO(2)-dependent mechanism (chemoregulation) and not to the pressure-dependent autoregulation (mechanoregulation). We tested this hypothesis in patients with impaired endothelial function compared with healthy controls. Blood pressure, heart rate, end-tidal Pco(2), CBF velocities (CBFV), forearm blood flow, and reactive hyperemia were assessed in 16 patients with diabetes mellitus and/or hypertension and compared with 12 age- and sex-matched healthy controls. Pressure-dependent autoregulation was determined by escalating doses of phenylephrine. CO(2) vasoreactivity index was extrapolated from individual slopes of mean CBFV during normocapnia, hyperventilation, and CO(2) inhalation. Measurements were repeated after sodium nitroprusside infusion. Indexes of endothelial function, maximal and area under the curve (AUC) of forearm blood flow (FBF) changes, were significantly impaired in patients (maximal flow: 488 +/- 75 vs. 297 +/- 31%; P = 0.01, AUC DeltaFBF: 173 +/- 17 vs. 127 +/- 11; P = 0.03). Patients and controls showed similar changes in cerebrovascular resistance during blood pressure challenges (identical slopes). CO(2) vasoreactivity was impaired in patients compared with controls: 1.19 +/- 0.1 vs. 1.54 +/- 0.1 cm.s(-1).mmHg(-1); P = 0.04. NO donor (sodium nitroprusside) offsets this disparity. These results suggest that patients with endothelial dysfunction have impaired CO(2) vasoreactivity and preserved pressure-dependent autoregulation. This supports our hypothesis that NO is involved in CO(2)-dependent CBF regulation alone. CBFV chemoregulation could therefore be a surrogate of local cerebral endothelial function.     

Some hemostatic parameters after treatment with ozone in a group of patients with obliterative atherosclerosis of the lower extremities and in a group of patients with diabetes]

Basic hemostasis and fibrinolysis parameters have been analysed in the group of 35 patients with obliterative atherosclerosis and in 41 patients with diabetes mellitus treated with intra-arterial ozone in concentration of O2/O3 54 micrograms/cm3 O3. Assayed parameters were within normal values. However, a tendency to decreased blood coagulation following ozone therapy was more pronounced in patients with obliterative atheromatosis, than in these with diabetes mellitus.     

回春医疗保健操运动对老年2 型糖尿病患者血糖和血脂水平的影响

目的：探讨规律性回春医疗保健操运动对2 型糖尿病老年患者血糖、血脂水平的影响。方法：选择28例老年2 型糖尿病患者 为研究对象,并将其随机分为运动干预组和对照组。运动干预组在前期药物治疗和饮食控制不变的情况下,采用为期12 周回春 医疗保健操进行运动干预,对照组仅给予药物治疗和饮食控制,而不进行运动干预,监测和比较两组患者实验前后血糖、血脂等 指标的变化。结果：运动干预组患者接受12 周回春医疗保健操干预后,受试者空腹血糖、胆固醇、低密度脂蛋白水平均较运动干 预前显著下降,差异均具有统计学意义(P<0.05)。结论：长期的规律性回春医疗保健操运动可有效降低老年2 型糖尿病患者血糖、 血脂水平,且安全易操作,可作为老年2 型糖尿病的临床辅助疗法。     

Sulfathiazole treats type 2 diabetes by restoring metabolism through activating CYP19A1

Globally, diabetes mellitus has been a major epidemic bringing metabolic and endocrine disorders. Currently, 1 in 11 adults suffers from diabetes mellitus, among the patients >90% contract type 2 diabetes mellitus (T2DM). Therefore, it is urgent to develop new drugs that effectively prevent and treat type 2 diabetes through new targets. With high-throughput screening, we found that sulfathiazole decreased the blood glucose and improved glucose metabolism in T2DM mice. Notably, we discovered that sulfathiazole treated T2DM by activating CYP19A1 protein to synthesize estrogen. Collectively, sulfathiazole along with CYP19A1 target bring new promise for the better therapy of T2DM.     

膀胱尿路上皮肿瘤合并2型糖尿病患者临床和病理特点的比较性研究

目的:对比分析膀胱尿路上皮肿瘤合并2型糖尿病患者的临床和病理特点,为临床诊疗工作提供一定的参考。方法:回顾性分析2015年1月至2019年2月于我院泌尿外科手术治疗且经病理确诊为原发性膀胱尿路上皮肿瘤的患者资料,合并2型糖尿病的膀胱肿瘤患者59例设为糖尿病组(T2DM组),根据性别和年龄按照1:2的比例匹配同时期未合并2型糖尿病的膀胱肿瘤118例患者为非糖尿病组(NT2DM组),比较两组患者的临床特征和病理特点。结果:T2DM组的高血压患者比例和血肌酐值高于NT2DM组(P<0.05),而在教育程度、吸烟、饮酒、BMI、前列腺增生、泌尿系感染、血常规、肝功、尿常规、肿瘤大小、数量方面无明显统计学差异(P>0.05)。T2DM组和NT2DM组在膀胱尿路上皮肿瘤良恶性分类、肿瘤数量、肿瘤大小的构成比上无明显统计学差异(P>0.05);然而,对膀胱恶性肿瘤患者进行亚组分析显示,T2DM亚组中肌层浸润性癌的比例和高级别癌的比例明显高于NT2DM亚组,差异有统计学意义(P<0.05)。结论:2型糖尿病可能使膀胱癌的病理分级和分期更高,导致患者预后更差,临床上应更加关注膀胱恶性肿瘤合并2型糖尿病患者的诊治。     

2型糖尿病内脏脂肪含量与胰岛β细胞功能及胰岛素抵抗的关系研究

目的:研究2型糖尿病患者内脏脂肪含量与胰岛β细胞功能及胰岛素抵抗的关系。方法:对65例初诊2型糖尿病患者采用256 CT平脐经L4、5水平进行扫描并测量皮下及内脏脂肪含量,并以BMI不同进行分组,即体重正常组、超重组、肥胖组。采用稳态模式评估法(HOMA)计算胰岛素抵抗指数、胰岛B细胞分泌功能,测量入组患者的相关人体指标、空腹血生化检查指标。结果:超体重组、肥胖组患者腰围、体重指数(body mass index, BMI)、甘油三酯(triglyceride, TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol, LDL-C)、空腹血糖,(fasting blood-glucose, FBG)、空腹胰岛素(fasting insulin, FINS)INS、稳态模型胰岛素抵抗指数(Homeostatic Model Assessment for Insulin Resistance, HOMA-IR)、胰岛β细胞功能指数(Homeostasis model assessment-β,HOMA-β)指标肥胖组、超重组均明显高于正常体重组(P0.05),超体重组、肥胖组内脏脂肪含量、内脏脂肪面积、皮下脂肪含量、脂肪总含量、脂肪百分比,超重组、肥胖组均明显高于正常体重组(P0.05),且肥胖组各项指标明显高于超重组(P0.05)。多元回归分析显示腹部脂肪总含量、内脏脂肪含量、皮下脂肪含量、内脏脂肪面积、BMI与胰岛素抵抗呈正相关,而其中内脏脂肪含量及面积关系最密切。结论:内脏脂肪含量是2型糖尿病胰岛素抵抗及B细胞功能变化的独立影响因素。     

Diabetes mellitus and its complications in a Hungarian population

The aim of this study was to examine the disease characteristics and complications of diabetes mellitus in patients in a Hungarian rural community. Data relating to age, sex, date of onset of diabetes, fasting blood glucose values and all diseases associated with diabetics were retrieved from the medical records of patients. Almost six percent (5.7%) of the population has diabetes mellitus. The percentage of Type I diabetic patients in this population was 5.8 percent. The prevalence of diabetes was slightly but not significantly higher in females than in males. The mean age of the diabetic population was 52.1 +/- 11.3 for male and 53.47 +/- 15.7 for the female patients. The peak age of onset of diabetes mellitus was in the sixth decade of life. The mean fasting blood sugar value was 10.64 +/- 0.6 and 10.57 +/- 0.5 mmol L(-1), in male and female diabetic patients (n = 103), respectively. Diabetic patients presented with many signs and symptoms in the general practice setting. The findings of this study showed that diabetics present with many disease conditions and signs and symptoms in the general practice setting. Many of these conditions are known to be associated with diabetes while others are not. As a result of the adverse effects of diabetes mellitus on the cardiovascular system and on body metabolism as a whole, the damage and morbidity caused by diabetes mellitus may have been underestimated. The results of this study have shed light on the unrecognised complications of diabetes mellitus.     

Role of islet amyloid in type 2 diabetes mellitus

Diabetes mellitus is one of the most common metabolic diseases worldwide and its prevalence is rapidly increasing. Due to its chronic nature (diabetes mellitus can be treated but as yet not cured) and its serious complications, it is one of the most expensive diseases with regard to total health care costs per patient. The elevated blood glucose levels in diabetes mellitus are caused by a defect in production and/or secretion of the polypeptide hormone insulin, which normally promotes glucose-uptake in cells. Insulin is produced by the pancreatic 'beta-cells' in the 'islets of Langerhans', which lie distributed within the exocrine pancreatic tissue. In type 2 diabetes mellitus, the initial defect in the pathogenesis of the disease in most of the patients is believed to be 'insulin resistance'. Hyperglycemia (clinically overt diabetes mellitus) will not develop as long as the body is able to produce enough insulin to compensate for the reduced insulin action. When this compensation fails ('beta-cell failure') blood glucose levels will become too high. In this review, we discuss one of the mechanisms that have been implicated in the development of beta-cell failure, i.e. amyloid formation in the pancreatic islets. This islet amyloid is a characteristic histopathological feature of type 2 diabetes mellitus and both in vitro and in vivo studies have revealed that its formation causes death of islet beta-cells. Being a common pathogenic factor in an otherwise heterogeneous disease, islet amyloidosis is an attractive novel target for therapeutic intervention in type 2 diabetes mellitus.     

2型糖尿病患者血糖漂移水平与动脉脉搏波速度的相关性研究

目的:研究2型糖尿病患者血糖漂移水平与动脉脉搏波速度的关系。方法:共入选82例2型糖尿病患者作为研究对象。所有研究对象应用自动脉搏波速度测定仪测定颈动脉-股动脉脉搏波速度(CFPw V);采用动态血糖检测系统(CGMS)及全自动生化分析仪进行检测,收集空腹血糖(FBG)、餐后2小时血糖(2hPG)、糖化血红蛋白(HbA1c)、血糖水平标准差(SDBG)、平均血糖波动幅度(MAGE)、最大血糖波动幅度(LAGE)、昼间血糖漂移幅度(MODD)等血糖参数。根据CGMS检测结果将82例2型糖尿病患者分为血糖低漂移组(47例)和血糖高漂移组(35例),比较两组中各血糖参数及CFPw V水平,计算两组动脉硬化发生率,并将各血糖参数与CFPw V进行Pearson相关性分析。结果:与血糖低漂移组比较,2hPG、SDBG、MAGE、LAGE、MODD、CFPw V在血糖高漂移组中升高(P0.05);血糖高漂移组中动脉硬化的发生率高于血糖低漂移组(P0.05);Pearson相关性分析分析显示2hPG、MAGE、LAGE、MODD与CFPw V相关(P0.05)。结论:本研究中,82例2型糖尿病患者存在不同程度的动脉硬化;2hPG、MAGE、LAGE、MODD是2型糖尿病患者CFPw V升高的相关因素,提示血糖漂移进一步加重动脉硬化,参与动脉硬化的发生发展。应该重视对血糖漂移的控制,减少动脉硬化的发生率,延缓动脉硬化的发展。     

ABO and Rh blood groups in diabetes mellitus

The present investigation was conducted with a view to testing the hypothesis that there is some association between blood groups (ABO and Rh) and diabetes mellitus. 520 proven cases of adult diabetes mellitus from the Diabetic Clinic of Rajendra Hospital, Patiala, were studied in 1979-1980. A large sample of 6204 normal individuals studied by Jolly et al. (1969) for ABO and Rh blood groups was taken as control for comparison with the patients. There is a strong indication of an association of diabetes mellitus with blood groups, especially with A, AB and Rh-positive blood groups. The maximum differences are in the AB groups in the two series and minimum in the A group. Individuals with gene p seem to be more susceptible to this disease. Thus the association between blood groups and diabetes mellitus is not a chance finding, but implies an aetiological relationship.     

Two birds with one stone: novel glucokinase activator stimulates glucose-induced pancreatic insulin secretion and augments hepatic glucose metabolism

The hormones glucagon and insulin delicately regulate the concentration of blood glucose. When patients become resistant to the effects of insulin or produce too little of it to properly regulate glucose concentrations, then diabetes can result. Unfortunately, not all patients with insulin-resistant, type 2 diabetes mellitus respond to drugs that improve insulin sensitivity. However, there is reason to be hopeful. A new molecule that targets glucokinase (GK), the enzyme responsible for phosphorylating glucose in pancreatic beta cells and hepatic cells, acts to significantly reduce blood glucose concentrations in rodents. The GK activator RO-28-1675 increased the glucose affinity and Vmax of GK, and rats treated with RO-28-1675 had improved glucose tolerance and elevated glucose uptake in liver. These results provide the basis for improved drug design that may alleviate diabetes mellitus and the disorders that accompany it in patients.