Apolipoprotein E phenotype frequency in type II diabetic patients with different forms of hyperlipoproteinemia

Atherosclerosis is the main cause of death in diabetes mellitus. This may at least in part be due to lipoprotein abnormalities which have been described in these patients. Apolipoprotein-E is a component of most lipoprotein fractions and plays an important role in the catabolism of VLDL. The different apolipoprotein-E phenotypes determined genetically are associated with certain hyperlipoproteinemias in a various degree in nondiabetic patients. In most cases apolipoprotein-E phenotype E2/2 is characteristic for familial dysbetalipoproteinemia. Phenotype E3/2 was found to be more frequent in hypertriglyceridemia while phenotype E4/3 was associated with hypercholesterolemia as well as with type V hyperlipoproteinemia. We studied apolipoprotein-E phenotypes and serum lipids in 141 type II diabetic patients (36 normolipidemic 41 type IIa hyperlipidemic, 32 type IIb hyperlipidemic, 24 type II hyperlipidemic, 8 type V hyperlipidemic). the phenotype E3/3 was more common in normolipidemic diabetic (77.8%) than in hyperlipoproteinemic diabetic patients (42.9%) or in the control group (57.5%). On the other hand phenotype E3/2 was more frequent in hypertriglyceridemic (50%) than in normolipidemic (5.6%) or hypercholesterolemic (hyperlipoproteinemia IIa: 4.9%, IIb: 9.4%) diabetic patients. The phenotype E4/3 was more frequent in all hyperlipoproteinemic diabetic patients, especially in those having hypercholesterolemia (34.2%) or mixed hyperlipidemia (50%). In conclusion we found a strong association between apo-E2 and hypertriglyceridemia in diabetic patients. This association was stronger than the one found in the general population. The association between apo-E4 and hypercholesterolemia in diabetic patients was similar to the one described in non-diabetic patients. We therefore conclude that type II diabetes mellitus is a possible cofactor in the apolipoprotein-E2 associated hyperlipoproteinemia.     

Why are diabetic patients treated at rheumatological hospitals?]

Retrospective analysis included 316 case histories of diabetic patients treated at the Silesian Rheumatology Hospital in 1987-1988. An analysis included causes of disorders, calcium-phosphorus metabolism disturbances, lipid and purine disorders. Statistical parameters were compared with the type of diabetes mellitus, duration of the disease, sex, age and obesity. There were 10% of inflammatory rheumatic disorders (6.4% rheumatic arthritis, 1.7% of rheumatoid spondylosis and 2% of other disorders) in the analysed case histories, and 32% of degenerative disorders (19% of vertebral column joints and 12.7% of other joints). Degenerative disorders were noted more frequently in patients with diabetes mellitus type 2, treated with insulin, while spondylopathies were particularly frequent in female patients of this group. Biochemical disorders in the form of hypocalcemia and hypophosphatemia, hypertriglyceridemia, hyperuricemia, signs of lesions to the liver and kidneys were more increasing with the duration of the disease and the degree of insulin-dependence. Locomotive system disorders are not related only to primary articular lesions. They depend also on diabetic neuro-vascular complications and osteopenia.     

Lactate dehydrogenase isoenzymes in diabetic patients

Lactate dehydrogenase (LDH) isoenzyme profiles in human platelets and the sera of patients with type I and II diabetes mellitus and vascular complications, as well as normal subjects were measured utilizing a recently established, modified micromethod. LDH-3 was the predominating species in platelets (37.5 +/- 3.0%), with LDH-2, 1, 4 and 5 following in decreasing order of concentration. The LDH-3/LDH-4 ratio in platelets varied from 6.2 to 1.38. Type I and type II diabetic patients with vascular complications showed a significantly higher ratio for LDH-3/LDH-4 (3.99 +/- 1.20 for DM I, 2.16 +/- 0.25 for DM II patients) than the mean ratio for normal subjects (1.14 +/- 0.08). This platelet-specific LDH isoenzyme pattern may be the result of frequent in vivo platelet-vessel wall interactions in the diabetic patients whose platelets are known to be hyperaggregable in in vitro test systems. Since non-diabetic patients patients with vascular complications also displayed a similarly elevated LDH-3/LDH-4 ratio, a wider classification is preferable, although the measurement of the LDH isoenzyme pattern will be helpful in assessing diabetic vascular complications.     

梗阻性黄疸患者经内镜逆行胰胆管造影术后胆道感染的病原菌分布、耐药性及影响因素分析

目的:探讨梗阻性黄疸患者经内镜逆行胰胆管造影(ERCP)术后胆道感染病原菌分布、耐药性以及导致术后胆道感染的影响因素。方法:选择2016年3月至2019年10月我院收治的310例行ERCP治疗的梗阻性黄疸患者,根据ERCP术后是否发生胆道感染将其分为感染组(50例)和未感染组(260例)。检测胆道感染患者病原菌种类及其耐药性,多元Logistic回归分析影响梗阻性黄疸患者ERCP术后胆道感染的影响因素。结果:ERCP术后胆道感染发生率为16.13%,大肠埃希菌、铜绿假单胞菌、粪肠球菌、屎肠球菌是主要致病菌,检出率分别为40.79%、13.16%、9.21%、6.58%。大肠埃希菌、铜绿假单胞菌对头孢类、氨基糖苷类抗生素耐药率高,粪肠球菌、屎肠球菌对利福平、喹诺酮类抗生素耐药率高,大肠埃希菌、铜绿假单胞菌、粪肠球菌、屎肠球菌均对利奈唑胺、亚胺培南敏感。多元Logistic回归分析结果显示,恶性病变、ERCP2次及以上、胆胰管汇流异常、术后胆管引流不畅是梗阻性黄疸患者ERCP术后胆道感染的危险因素(P0.05),术后预防性使用抗生素是保护因素(P0.05)。结论:梗阻性黄疸患者ERCP术后存在一定胆道感染风险,革兰氏阴性菌是主要致病菌,临床应注重对高危因素预防,有必要术后选择敏感抗生素预防性治疗。     

A new diabetic strain of rat (WBN/Kob)

A new, spontaneously occurring diabetic syndrome has been observed in the aged males of an inbred strain of Wistar rats, WBN/Kob. The main clinical sign, glycosuria, was first detected at about 60 weeks of age, and thereafter some animals developed hyperlipidaemia and gradual emaciation. Prior to the onset of glucosuria, male rats showed impaired glucose tolerance after a glucose load at 21 weeks of age. The histopathologic lesions of the pancreas in the diabetic males consisted of multifocal fibrosis, decreased in number and size of islets and atrophy of exocrine tissue. Multifocal inflammatory foci of varying stages were the main pancreatic lesion in prediabetic male rats. This inflammatory change was detected even in 12-week-old rats and tended to occur around the islets. Therefore focal fibrosis and the decrease in the number and size of islets were considered to result from post-inflammatory scarring. The maturity-onset of this syndrome and the impaired glucose tolerance in younger animals suggested that diabetes mellitus of this rat strain is insulin-independent type II. However, the histological lesions of the pancreas were somewhat different from previous reports of both type I and II diabetes mellitus in man and animals.     

Enhanced growth hormone responses to growth hormone releasing hormone in male type I diabetic patients.

In a previous paper we have demonstrated that growth hormone (GH) responses to growth hormone releasing hormone (GHRH) are higher in premenopausal normal women than in age matched healthy men. As in type I diabetes mellitus various disturbances of GH secretion have been reported, the aim of our study was to assess the effect of sex on basal and GHRH stimulated GH secretion in type I diabetes mellitus. In 21 female and 23 male type I diabetic patients and 28 female and 30 male control subjects GH levels were measured before and after stimulation with GHRH (1 microgram/kg body weight i.v.) by radioimmunoassay. GH responses to GHRH were significantly higher in female than in male control subjects (p less than 0.02), whereas the GH levels following GHRH stimulation were similar in female and male type I diabetic patients. GH responses to GHRH were significantly higher in the male type I diabetic patients than in the male control subjects (p less than 0.001); in the female type I diabetic patients and the female control subjects, however, GH responses to GHRH were not statistically different. The absence of an effect of sex on GHRH stimulated GH responses in type I diabetes mellitus provides further evidence of an abnormal GH secretion in this disorder.     

Antioxidant status and levels of different vitamins determined by high performance liquid chromatography in diabetic subjects with multiple complications

Plasma vitamin A, C and E levels and erythrocyte antioxidant enzyme activities were investigated in type I and type II diabetic subjects with and without complications, i.e., hypertension, coronary artery disease and renal failure. Reverse phase HPLC was used to quantify vitamin A and E levels. We observed that the vitamin C levels were not significantly different between control and diabetic subjects. However, vitamin A and E levels were significantly lower in type I and type II diabetic subjects compared to controls. Superoxide dismutase (SOD) activity was significantly lower in type II, but not in type I, diabetic patients compared to controls. Interestingly, glutathione reductase and peroxidase activities were diminished in type I, but not in type II, diabetic subjects as compared to controls. Catalase activity was lower in both types of diabetic patients in comparison with their respective controls. Altogether these results suggest that diabetes mellitus may be associated with altered antioxidant status regardless to various complications.     

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.     

Funduscopic examination of patients with diabetes who are admitted to hospital.

The charts of 123 patients with diabetes mellitus who were admitted to hospital were reviewed; 35 (28%) did not undergo funduscopic examination to detect diabetic retinopathy, and in 27 (22%) the examination was inadequate. Only four patients were referred to an ophthalmologist. Evidence of nephropathy and admission for diabetes control did not increase the probability of funduscopic examination. The findings suggest that house staff lack awareness of the natural history of diabetic retinopathy and of the success of current treatment. Annual funduscopic examination by an ophthalmologist in patients with diabetes is recommended, from the time of diagnosis in those with type II diabetes and starting 8 to 10 years after diagnosis in those with type I diabetes.     

ERCP治疗急性胆源性胰腺炎

急性胆源性胰腺炎(ABP)是消化内科常见急腹症之一,是急性胰腺炎中最常见的类型,占急性胰腺炎每年发病人数的40%-60%,病死率较高,常规药物治疗不能从根本上解除病因,易导致复发,手术治疗风险较大,创伤较大,费用较高,住院时间较长,易引起其术后并发症,不利于患者恢复。而经内镜逆行胰胆管造影(ERCP)作为一种内镜与放射技术相结合的诊断治疗方法,对胆管内结石并发急性胰腺炎的诊断率是最高的,诊断结石的敏感性大于95%。在20世纪70年代被认为是急性胆源性胰腺炎的禁忌症,近年来随着ERCP技术的不断发展和广泛应用,ERCP已成为治疗胆胰疾病的一种安全有效的技术。ERCP可清除胆管结石,从而达到通畅胆道,减少胆汁向胰管反流,迅速改善患者病情,阻断病情进展的目的,并有效缩短住院时间,减轻患者痛苦,减少复发和改善总体预后,为广大ABP患者带来了福音,此外,还能减少患者住院费用,节省医疗资源,对于个人及社会均具有积极意义,值得推广。     

Apoptosis and oxidative status in peripheral blood mononuclear cells of diabetic patients

We have compared the concentrations of intracellular glutathione (GSH), glutathione-dependent antioxidative enzymes, the cell death rate and immunophenotype profile of peripheral blood mononuclear cells (PBMC) from healthy donors and from patients with insulin-dependent type I (IDDM) or non insulin-dependent type II (NIDDM) diabetes mellitus. The IDDM and NIDDM patients had above-normal absolute lymphocyte counts, whereas the percentages of CD3, CD4 and CD8 T lymphocytes were significantly reduced. In contrast, the absolute number and percentage of B lymphocytes was higher in diabetic patients than in healthy donors. The low intracellular reduced glutathione (GSH) and the unbalanced profile of key enzymes involved in GSH metabolism, gamma glutamyltransferase (-GT) and glutathione-S-transferase (GST), account for the increased oxidative status of PBMC from diabetic patients. The plasma membranes of PBMC from diabetic patients were less permeable to propidium iodide than those of PBMC from healthy donors, indicating that the apoptotic cell death rate was lower in the cells from diabetic patients. These differences are potentially useful markers of pathogenic metabolic changes which occur during clinical diabetes and if they are confirmed could be used to identify the onset of diabetes.     

An elderly man with cholestatic jaundice due to biliary hydatidosis

Hydatid disease is found throughout the world, with a higher prevalence in the Mediterranean area. In Spain, the most endemic regions are Rioja and Aragon, with rates above 10 cases/100,000 inhabitants, followed by Castilla-La Mancha and Castilla y Leon (5-10 cases/100,000 inhabitants). This parasitic disease is caused by the larval stage of Echinococcus granulosus (EG) and the main organs affected are the liver and the lung (85 % cases). We present a case of obstructive jaundice and secondary cholangitis due to a biliary hydatidosis. Abdominal computed tomography scan showed dilatation of the entire biliary tract. The technique used for diagnosis and treatment was endoscopic retrograde cholangiopancreatography.     

Methylene tetrahydrofolate reductase C677T mutation and left ventricular hypertrophy in Turkish patients with type II diabetes mellitus

This study was designed to investigate, in the Turkish population, the association of methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism and left ventricular hypertrophy (LVH) in patients with type II diabetes mellitus. Our study included 249 patients with type II diabetes mellitus (102 men, 147 women) and 214 healthy volunteers as controls (91 men, 123 women). MTHFR C677T genotypes were determined by polymerase chain reaction, restriction fragment length polymorphism techniques. No differences were observed in the distribution of MTHFR genotypes or allele frequencies in the cases versus the controls. The frequency of the MTHFR-mutated allele (T) was 31.7% in the type II diabetes mellitus versus 31.1% of the controls. The homozygous mutation (T/T) in the MTHFR gene was identified in 12% of the type II diabetes mellitus versus 9.3% of the controls. Patients with the TT genotype showed a higher prevalence of LVH when compared to patients with the CC and CT genotypes (p = 0.01). The MTHFR gene C677T mutation may be a possible risk factor for the development of LVH in the type II diabetic patients.     

Pancreatic mitochondrial complex I exhibits aberrant hyperactivity in diabetes

It is well established that NADH/NAD⁺ redox balance is heavily perturbed in diabetes, and the NADH/NAD⁺ redox imbalance is a major source of oxidative stress in diabetic tissues. In mitochondria, complex I is the only site for NADH oxidation and NAD⁺ regeneration and is also a major site for production of mitochondrial reactive oxygen species (ROS). Yet how complex I responds to the NADH/NAD⁺ redox imbalance and any potential consequences of such response in diabetic pancreas have not been investigated. We report here that pancreatic mitochondrial complex I showed aberrant hyperactivity in either type 1 or type 2 diabetes. Further studies focusing on streptozotocin (STZ)-induced diabetes indicate that complex I hyperactivity could be attenuated by metformin. Moreover, complex I hyperactivity was accompanied by increased activities of complexes II to IV, but not complex V, suggesting that overflow of NADH via complex I in diabetes could be diverted to ROS production. Indeed in diabetic pancreas, ROS production and oxidative stress increased and mitochondrial ATP production decreased, which can be attributed to impaired pancreatic mitochondrial membrane potential that is responsible for increased cell death. Additionally, cellular defense systems such as glucose 6-phosphate dehydrogenase, sirtuin 3, and NQO1 were found to be compromised in diabetic pancreas. Our findings point to the direction that complex I aberrant hyperactivity in pancreas could be a major source of oxidative stress and β cell failure in diabetes. Therefore, inhibiting pancreatic complex I hyperactivity and attenuating its ROS production by various means in diabetes might serve as a promising approach for anti-diabetic therapies.     

Developmental expression of the type I diabetes related antigen sulfatide and sulfated lactosylceramide in mammalian pancreas

Previous studies have shown that sulfatide is present and functionally involved in beta cells, and that anti-sulfatide antibodies (ASA) exist during development of type I diabetes mellitus. To further explore the possible role of sulfatide in type I diabetes, developmental expression was examined in human pancreas and in pancreas of the type I diabetes models BB rat and NOD mouse compared to Lewis rat and BALB/c mouse, respectively. Sulfatide was not only expressed in adult pancreas, but also in human fetal and rodent neonatal pancreas, i.e., during the growing period of the immunological self. Sulfatide had a different expression pattern in human beings and rodents, concerning both the amounts of sulfatide and expression during development. There was no change in the sulfatide fatty acid isoform expression during development. The pancreatic expression of another sulfated glycosphingolipid, sulfated lactosylceramide, indicated that this molecule is a potential fetal/neonatal marker, which was further expressed in the type I diabetic models. In conclusion, these findings give further support to the possibility that sulfatide is a relevant autoantigen in type I diabetes and that sulfated lactosylceramide might function as a potential risk factor for disease development, at least in the animal models.     

Monocyte attachment to laminin in diabetes mellitus: The role of ATP

Monocyte-extracellular matrix interactions have been implicated in atherosclerosis pathophysiology. Laminin, the main basement membrane protein contains cell binding domains that can be cryptic, presented only after protein modification. In the present study we evaluated monocyte attachment to laminin-1 in the presence of ATP. Monocytes were derived from either healthy volunteers or patients with diabetes mellitus type II. For the estimation of monocyte attachment to laminin the myeloperoxidase assay was used. Monocytes derived from diabetic patients, showed an increased ability to attach to laminin (p = 0.0055). The presence of ATP increased the attachment of control monocytes to laminin (p = 0.0022). On the contrary, the presence of ATP did not affect the attachment of monocytes derived from diabetic patients to laminin. Our results indicate a modified interaction between monocytes and laminin-1 in diabetes mellitusKey words: monocytes, ATP, laminin-1, diabetes mellitus, attachment     

Hypercalciuria in patients with diabetes mellitus type 1 and 2--studies of its pathogenesis using the oral calcium tolerance test

The study was aimed at the evaluation of changes in the urinary excretion of calcium in patients with diabetes of type I and II. The investigations were carried out in 34 patients with type I diabetes, 28 patients with type II diabetes and 30 control subjects having the normal glucose tolerance. The oral calcium tolerance test according to Pak was performed in all the patients and the controls. Besides normocalciuria, also hypercalciuria of renal origin, as well as hipercalciuria resulting from an elevated intestinal absorption of calcium have been found in diabetic patients. These disturbances occurred much more frequently in patients with type I diabetes, especially in those of age below 40.     

Diabetes, lipids, and adipocyte secretagogues.

That obesity is associated with insulin resistance and type II diabetes mellitus is well accepted. Overloading of white adipose tissue beyond its storage capacity leads to lipid disorders in non-adipose tissues, namely skeletal and cardiac muscles, pancreas, and liver, effects that are often mediated through increased non-esterified fatty acid fluxes. This in turn leads to a tissue-specific disordered insulin response and increased lipid deposition and lipotoxicity, coupled to abnormal plasma metabolic and (or) lipoprotein profiles. Thus, the importance of functional adipocytes is crucial, as highlighted by the disorders seen in both "too much" (obesity) and "too little" (lipodystrophy) white adipose tissue. However, beyond its capacity for fat storage, white adipose tissue is now well recognised as an endocrine tissue producing multiple hormones whose plasma levels are altered in obese, insulin-resistant, and diabetic subjects. The consequence of these hormonal alterations with respect to both glucose and lipid metabolism in insulin target tissues is just beginning to be understood. The present review will focus on a number of these hormones: acylation-stimulating protein, leptin, adiponectin, tumour necrosis factor alpha, interleukin-6, and resistin, defining their changes induced in obesity and diabetes mellitus and highlighting their functional properties that may protect or worsen lipid metabolism.     

Impact of type 2 diabetes mellitus on short- and long-term mortality after coronary artery bypass surgery

Background

Type 2 diabetes mellitus (DM) is a frequent co-morbidity among patients undergoing coronary artery bypass grafting (CABG) surgery. The aim of this study was to evaluate the impact of DM on the early- and long-term outcomes of patients who underwent isolated CABG.

Methods

We performed an observational cohort study in a large tertiary medical center over a period of 11 years. All data from patients who had undergone isolated CABG surgery between 2004 and 2014 were obtained from our departmental database. The study population included 2766 patients who were divided into two groups: Group I (1553 non-diabetic patients), and Group II (1213 patients suffering from type 2 DM). Group II patients were then divided into two subgroups: subgroup IIA (981 patients treated with oral antihyperglycemic medications) and subgroup IIB (232 insulin-treated patients with or without additional oral antihyperglycemic drugs). In-hospital, 1-, 3-, 5- and 10-year mortality outcome variables were evaluated. Mean follow-up was 97?±?41 months.

Results

In-hospital mortality was similar between Group I and Group II patients (1.87% vs. 2.31%, p?=?0.422) and between the subgroups IIA and IIB (2.14% vs. 3.02%, p?=?0.464). Long-term mortality (1, 3, 5 and 10 years) was higher in Group II (DM type 2) compared with Group I (non-diabetic patients) (5.3% vs. 3.6%, p?=?0.038; 9.3% vs. 5.6%, p?<?0.001; 15.3% vs. 9.3%, p?<?0.001 and 47.3% vs. 29.6% p?<?0.001). Kaplan–Meier analysis demonstrated that all-cause mortality was higher in Group II compared with Group I (p?<?0.001) and in subgroup IIB compared with subgroup IIA (p?=?0.001). Multivariable analysis showed that DM increased the mortality hazard by twofold, and among diabetic patients, insulin treatment increased the mortality hazard by twofold.

Conclusions

Diabetic and non-diabetic patients have similar in-hospital mortality rates. Survival rates of diabetic patients start to deteriorate 3 year after surgery. Type 2 DM is an independent predictor for long-term mortality after isolated CABG surgery. Mortality is even higher when the diabetes treatment strategy included insulin.

     

A method for early diagnosis of reduced mobility of hand joints in diabetes mellitus type I

The study aimed at elaborating the technique of an early diagnosis of cheiroarthropathy. The study involved 170 patients with diabetes mellitus type I aged between 16 and 45 years and disease duration ranging from 1 year to 33 years. Advanced cheiroarthropathy with shining waxy skin was diagnosed in 41 patients (group I). No lesions characteristic for cheiroarthropathy was diagnosed in 122 patients (group II) while in 7 patients (group III) only skin lesions without contractures were noted. Proliferative retinopathy was significantly more frequent (p less than 0.001) in the group with cheiroarthropathy--39% to 8%. Mean age of patients of group I is 31.5 +/- 5.9 years, in group II--31.0 +/- 6.6 years. Duration of diabetes mellitus is 17.8 +/- 6.2 and 9.6 +/- 7.2 years respectively (p less than 0.05). An angle of metacarpophalangeal joint of the V finger extension was measured in all patients with goniometer. A significant difference was noted in both groups: 34.4 +/- 8.08 degrees and 56.5 +/- 7.1 degrees, respectively (p less than 0.01). Mathematic models were designed basing on the value of measured angle and duration of the disease. These models facilitate possible risk of cheiroarthropathy. Systematic measurements of metacarpophalangeal joint extension seems valuable means of early diagnosis of diabetic cheiroarthropathy and follow-up of such patients.