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PubMed1995

Mechanisms of pathogenesis in diabetes mellitus.

Diabetes mellitus is a syndrome of complex etiology and pathogenesis involving abnormal insulin synthesis, release, binding, and target cell activation. These are manifested differently in the two most common forms of this disease: insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM). Although there still remains much to be discovered to complete our understanding, significant contributions have been made in the last few years by molecular genetics and immunology. This paper reviews many of these facets in contrast to others, which deal primarily with issues of management.

Aldehyde Reductase↗
PubMed1991

Large platelets circulate in an activated state in diabetes mellitus.

Diabetes mellitus is associated with aggravated development of vascular complications. Yet, it has not been established whether platelet hyperreactivity contributes as a pathogenetic factor. In order to study the role of activated platelets in diabetes mellitus, we investigated the expression of the membrane activation markers CD63 (GP53) and CD62 (GMP-140) as direct indicators of in vivo activation. The CD63-positive fraction was significantly higher in patients (6.1% X 3.7 +/- 1) than in controls (2.7% X 3 +/- 1). In parallel, the CD62-positive fraction was significantly elevated in patients to 5% X 2.5 +/- 1 in comparison to controls (3% X 2 +/- 1). Patients with angiopathy had a mean increase of 304% in CD63-positive and of 223% in CD62-positive platelets. Patients without clinically detectable angiopathy showed a trend to an increased fraction in CD63-/CD62-positive platelets. There was no correlation of the activation markers with fasting blood glucose, HbA1 or platelet count. CD63 platelet bound fluorescence significantly increased with platelet size in the patient group. We conclude that in diabetes mellitus an increased number of large platelets circulate in an activated state predominantly in patients with angiopathy. This could imply that platelets become activated by vascular lesions. The trend in patients without vascular disease, however, suggests that activated platelets may also basically contribute to the prethrombotic state in diabetes mellitus.

Adult↗
PubMed2001

Glucose and lactate in vitreous humor compared with the determination of fructosamine for the postmortem diagnosis of diabetes mellitus.

Diabetes mellitus is a chronic metabolic illness responsible for a great number of deaths. In postmortem diagnosis, because of the difficulty involved in interpreting blood glucose levels and relatively nonspecific pathologic features, biochemical markers in vitreous humor are useful. The aim of this study was to compare the results obtained for the combined determination of lactate and glucose with fructosamine levels recorded in the vitreous humor of two diagnostic groups (one diabetic and the other nondiabetic). The authors intended to ascertain the capacity of different markers measured in vitreous humor to diagnose diabetes mellitus. Fifty-one cadavers (mean age, 58.7 years; standard deviation, 17.09) were studied. The mean postmortem interval was 16.4 hours (standard deviation, 9.05). Cases were assigned to two diagnostic groups according to whether they were previously diagnosed as either diabetic or nondiabetic. Statistically significant differences for glucose, fructosamine, and the sum values of glucose and lactate were found between the two diagnostic groups. The highest levels were obtained in the group of cases with a previous diagnosis of diabetes mellitus. After the comparison of receiver operating characteristic curves, the sum values of glucose and lactate in vitreous humor is a better predictor of antemortem diabetes mellitus than the fructosamine.

Adult↗
PubMed1995

Altered platelet activating factor metabolism in insulin dependent diabetes mellitus.

Diabetes mellitus is associated with several abnormalities of platelet function. Recent studies have shown that the blood level of platelet activating factor (PAF), a potent inducer of platelet aggregation, is elevated in insulin dependent diabetes mellitus (IDDM) and remains unchanged in non-insulin dependent diabetes mellitus (NIDDM) patients. However, the mechanism of this increase in PAF levels has not been determined. In this study we have measured the activity of plasma PAF acetylhydrolase (an enzyme that regulates PAF levels) and lipoprotein levels in control subjects and diabetic patients. The data presented show that plasma PAF acetylhydrolase activity is significantly decreased in IDDM and is not altered in NIDDM patients. The lipoprotein levels were similar in control and diabetic subjects and there was no correlation between lipoprotein levels and PAF acetylhydrolase activity. These results suggest that the elevated levels of PAF in IDDM patients could be due to a decrease in plasma PAF acetylhydrolase activity.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2006

[Vaccine for prevention of type 1 diabetes mellitus].

Diabetes mellitus type 1, known as insulin dependent diabetes mellitus (IDDM), results from a chronic autoimmune destruction of the insulin secreting pancreatic beta cells. This autoimmune process is marked by circulating auto antibodies to beta cell antigens. GAD 65 (Glutamic Acid Decarboxylase) auto antibodies are present in 70-80% of newly diagnosed patients with type 1 diabetes, and it can be detected many years before clinical onset of the disease. New knowledge in the imunopathogenesis have given expectation that imunotherapy will become routine manner for cure of diabetes mellitus type 1.

Autoantibodies↗
PubMedDate not supplied

[Plasmosorption in the combined treatment of patients with phlegmons of the maxillofacial area in diabetes mellitus].

Diabetes mellitus and surgical infection coursing intermittently aggravate each other, and therefore search for methods of treatment permitting a simultaneous impact on the pyoinflammatory process and on diabetes mellitus is a priority. Plasmasorption method used at present at Chair for maxillofacial surgery and dentistry of the Russian State Medical University meets these requirements to a great measure. Clinical and laboratory studies showed that plasmasorption used in multiple-modality treatment helps effectively control a purulent process, reduces intoxication of the body, corrects the development of insulin resistance in patients with maxillofacial phlegmons coursing in the presence of diabetes mellitus. In patients with grave and medium-severe diabetes the same insulin doses injected after plasmasorption reduce blood sugar levels by 1.5-1.7 times on an average, and in slight forms of the condition even normalize them. Secondary healing of postoperative wounds is accelerated in diabetics with maxillofacial phlegmons, and hospital stay of such patients is reduced by 9.5-10 days, on an average.

Adult↗
PubMed1995

[Infections in diabetes mellitus].

Diabetes mellitus is one of the most frequent metabolic distortions predisposing for infectious diseases. Characteristic features of patients with diabetes mellitus are dysfunctions of professional phagocytes, in particular of polymorphonuclear leucocytes. Infections of skin and soft tissue in particular of the lower extremities, rhinocerebral mucormycosis, invasive external otitis and urinary tract infections are typically associated with diabetes mellitus. Frequently, a rapidly progressive infection requires urgent surgical intervention and parenteral antimicrobial therapy. Short-interval metabolic controls, improvement of metabolic functions, extended vaccination and strict hygiene measures are supportive to prevent infections or to reduce a complicated outcome of infections.

Bacterial Infections↗
PubMed1982

Dogs with induced or spontaneous diabetes as models for the study of human diabetes mellitus.

Diabetes mellitus can be produced readily in dogs by any of several chemical or surgical methods, and in recent years genetically diabetic dogs have also become available for study. These models are suitable for investigating a wide variety of questions relevant to human diabetes mellitus. Especially noteworthy is the occurrence in diabetic dogs of a number of ocular and other complications typical of human diabetes mellitus. Procedures by which canine models of diabetes may be established or maintained have been outlined in this report.

Animals↗
PubMed2002

[A case of diabetic glomerulosclerosis without concurrent diabetes mellitus].

Diabetic nephropathy is a complication of diabetes mellitus that is characterized by the appearance of diffuse and nodular glomerulosclerosis A 46-year-old man presented with generalized edema. He had severe nephrotic syndrome, renal insufficiency and hypertension without a family history or clinical evidence of diabetes mellitus. Oral glucose tolerance test showed impaired glucose tolerance, but several fasting plasma glucose determinations and serum hemoglobin A1c levels were normal. Renal biopsy revealed nodular and diffuse glomerulosclerosis characteristic of diabetic nephropathy. The present case demonstrates that nodular glomerulosclerosis may be present without clinically overt diabetes mellitus.

Diabetes Mellitus↗
PubMed2002

The role of thiazolidinediones in the treatment of patients with type 2 diabetes mellitus.

Diabetes mellitus is a significant and growing health concern worldwide. Unfortunately, type 2 diabetes mellitus is generally under-managed, and this may explain the increasing prevalence of diabetic complications throughout the world. The introduction of newer classes of antihyperglycemic agents should enhance the ability of clinicians to achieve optimal blood glucose control. One recent addition to the pharmacologic armamentarium is the thiazolidinedione class. The main effect of thiazolidinediones is amelioration of insulin resistance. These agents may also preserve beta-cell function, although evidence in favor of this effect is still inconclusive. The mechanism of action of thiazolidinediones is not completely understood. Similarly, the current state of knowledge cannot explain the differences in the lipid effects of pioglitazone and rosiglitazone. Thiazolidinediones are commonly used as add-on therapy for those requiring large daily doses of insulin therapy, or in addition to sulfonylurea agents and metformin for those reluctant to start insulin therapy. The potential role of thiazolidinediones as first-line therapy is now emerging. It is possible that in certain subgroups, particularly patients with renal failure, elderly individuals or those with corticosteroid-induced diabetes mellitus, the use of thiazolidinediones as a first-line therapy is justifiable. However, the lack of a long-term safety record, and the cost, would limit the widespread acceptance of this class of agents as first-line therapy.

Diabetes Mellitus, Type 2↗
PubMed1991

[The epidemiology of diabetes mellitus].

Diabetes mellitus is a heterogeneous disease that might present as insulin-dependent (type I), non-insulin-dependent (type II), and other forms associated with other endocrine and genetic conditions, as well as those secondary to different infiltrative or destructive pancreatic diseases, parasitosis and post-pancreatectomy patients. Insulin-dependent diabetes mellitus is mainly associated to immunological problems, probably by derangement caused by external factors, such as viral infections that favor destruction of beta cells of the pancreas. On type II diabetes the hereditary component is more important and does not present immunological problems. Different etiological considerations are included, as well as associated genetic markers that are described in the text.

Autoimmune Diseases↗
PubMed1993

Diabetes mellitus.

Diabetes mellitus occurs commonly in the older patient and is frequently undiagnosed. In many cases, the initial manifestations of diabetes mellitus are lower extremity complications with which this disease is known to be associated. Unfortunately, these complications are similar to other age-related degenerative processes; therefore, vigilance for the detection of undiagnosed diabetes mellitus is essential in the evaluation and treatment of lower extremity pathologic conditions.

Adult↗
PubMed1987

Alterations in cardiac sarcolemmal Ca2+ pump activity during diabetes mellitus.

Diabetes mellitus is frequently associated with a primary cardiomyopathy. The mechanisms responsible for this heart disease are not clear, but an alteration in myocardial Ca2+ transport is believed to be involved in its development. Even though sarcolemma plays a crucial role in cellular Ca2+ transport, little appears to be known about its Ca2+ transporting capability in the diabetic myocardium. In this regard, we have examined the status of the cardiac sarcolemmal Ca2+ pump during diabetes mellitus. Purified sarcolemmal membranes were isolated from male Wistar diabetic rat hearts 8 wk after streptozotocin injection (55 mg/kg iv). Ca2+ pump activity assessed by measuring its Ca2+-stimulated adenosine triphosphatase and Ca2+-uptake ability in the absence and presence of calmodulin was significantly depressed in the diabetic myocardium relative to controls. These results did not appear to have been influenced by the minimal sarcoplasmic reticular and mitochondrial contamination of this membrane preparation. Hence, it appears that the sarcolemmal Ca2+ pump is defective in the diabetic myocardium and may be involved in the altered Ca2+ transport of the heart during diabetes mellitus.

Adenosine Triphosphatases↗
PubMed2003

Point-of-care testing in diabetes mellitus.

Diabetes mellitus is an excellent case study of the evolution, and successful application, of point-of-care testing. It offers a valuable history of the way in which technology has evolved, and continues to evolve, to meet the needs of patients whilst also providing for a more optimal delivery of care. Diabetes mellitus is also a good exemplar of where test and treatment regimes must operate in complete harmony in order to achieve the greatest benefit. Thus whilst the measurement of blood glucose is central to the screening, diagnosis and management of diabetes, it is in the latter use, largely related to supporting compliance with therapy, that point-of-care testing is of greatest relevance. In addition, there are other tests, more associated with the management of diabetes and early detection of the complications associated with diabetes, that are appropriate to the point-of-care testing modality. This Review will focus on the developments in technology and the harnessing of this innovation to support the delivery of clinical, organisational and economic benefits in the care of patients with diabetes mellitus.

Diabetes Mellitus↗
PubMed2000

[Dyslipoproteinemia and diabetes mellitus].

Diabetes mellitus is, as compared with the non-diabetic population, associated with a much higher mortality of ischaemic heart disease and other cardiovascular diseases. In this risk participates in a major way also diabetic dylipidaemia. The latter is characterized in particular by hypertriglyceridemia which reflects the increase of VLDL and IDL lipoproteins. Elevated and prolonged postprandial lipaemia participates in the development of qualitative lipoprotein changes. Highly athergenic "small dense LDL" are formed which are liable to an oxidative modification and are then in an unregulated manner taken up in the vascular wall. Reduction of HDL-cholesterol and a change in the different HDL sub-populations leads then to a deteriorated reverse cholesterol transport. Type 2 diabetes mellitus is associated with dyslipidaemia in the majority of patients even under conditions of satisfactory compensation of diabetes, in particular during the postprandial stage. On the other hand, in type 1 diabetes the lipid values usually become normal when the blood sugar level becomes normal, however qualitative changes of lipoproteins frequently persist. Increased glycation and oxidation of lipoproteins is a common sign of both types of diabetes. For prevention of cardiovascular complications treatment of diabetic dyslipidaemia is at least equally important as efforts to achieve optimal compensation of diabetes. Successful treatment of diabetic dyslipidaemia includes efforts to achieve compensation of diabetes, optimation of body weight, increase of physical activity, modification of diet, treatment of other secondary causes of hyperlipidaemia, and if these provisions are not successful, pharmacological hypolipidaemic treatment. The risk of macrovascular complications is so high in diabetics that according to recent knowledge it is not necessary to differentiate between primary and secondary prevention but aggressive treatment is necessary to achiebe target values of total cholesterol < 5.0 mmol/l and LDL-cholesterol < 3.0 mmol/l. Triglycerides > 2 mmol/l and HDL-cholesterol < 1 mmol/l are signs of a high cardiovascular risk. Optimation of the whole lipid profile is ideal.

Cardiovascular Diseases↗
PubMed1998

The urea cycle as a source of nitric oxide implicated in the pathogenesis of insulin-dependent diabetes mellitus.

Diabetes mellitus has long been considered an autoimmune disorder whereby the immune system attacks pancreatic tissue, destroying the insulin-producing cells of the pancreas. In this way, diabetes mellitus may be the only metabolic disorder in which the disease state is in no way related to any metabolic pathway. The specific role that nitric oxide plays in the pathogenesis of diabetes mellitus has yet to be established. However, researchers have shown that nitric oxide will independently destroy the beta cells (insulin-producing cells) of the pancreas in the absence of any pathogenic mediators. It is my hypothesis that a breakdown in the urea cycle (via activation of nitric oxide synthase (NOS)), a primary metabolic pathway, whereby nitric oxide production is competitively favored over urea production, is responsible for generating the major source of pathogenic nitric oxide resulting in the death of the beta cells of the pancreas.

Animals↗
PubMed1987

Micronutrient status in diabetes mellitus.

Diabetes mellitus is a chronic metabolic disorder, which can alter the nutritional status of the individual. Some micronutrients, in particular zinc and chromium, have been implicated in the pathogenesis of carbohydrate intolerance. This review evaluates the available published data on the status of 10 mineral elements and seven vitamins in diabetic patients and experimental animal models of diabetes. The role of these micronutrients in insulin secretion and carbohydrate metabolism is discussed in an attempt to determine whether the reported alterations in serum or tissue content of minerals or vitamins contribute to the carbohydrate intolerance of diabetic patients. It is concluded that both Type I and Type II diabetes mellitus can result in changes in certain micronutrients. However, adequately controlled studies to establish the role of trace elements in the pathogenesis of diabetes mellitus are not available.

Bone Diseases, Metabolic↗