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PubMed1978

[New viewpoints on the pathogenesis of diabetes mellitus].

Diabetes mellitus is a syndrome characterised primarily by an increase in blood glucose and an absolute or relative deficiency of insulin. Etiologically, it is a complex disorder because many different genetic, environmental, immunological, metabolic and hormonal influences interact to produce the clinical picture diabetes. By introducing HLA typing in diabetes research in the last four years, it became possible to clearly distinguish between the juvenile-onset, insulin-dependent type and the non-insulin-dependent, maturity-onset type of diabetes mellitus. On the basis of this and other evidence, at least five nosologically distinct types of diabetes can be identified.

Autoimmune Diseases↗

PubMed1998

[Heart pathology of extracardiac origin. XI. Cardiac repercussions of diabetes mellitus].

Diabetes mellitus is one of the diseases with the greatest risk of developing coronary disease (CD), with the estimation of this risk in relation to the general population being from 2 to 4-fold greater. The existence of diabetes worsens the prognosis of CD and thus, postinfarction mortality in these patients is double that observed in non-diabetic patients. Together with the risk factors found in the general population, those of special interest are those derived from diabetes itself, such as hyperglycemia, dyslipemia, coagulation disorders and hyperinsulinemia or insulin resistance. Among these, the most important is probably the hyperglycemia which may contribute to the appearance of CD by different mechanisms such as proteic glycosylation, accumulation of sorbitol, increase in the synthesis of protein kinase C or oxidative stress. It must not be forgotten that an old controversy has recently been brought up suggesting that sulphonylureas may have a certain cardiotoxic effect, probably acting on the potassium channels dependent on ATP. Acute myocardial infarction in diabetic patients carries a greater risk of congestive heart failure, recurrent infarction, arrhythmia and cardiogenic shock, with one of its characteristics being the possibility of being silent when autonomic neuropathy is present. The prognosis of CD may be markedly improved by obtaining optimum glycemic control during the hours following infarction using intensified treatment. Diabetic myocardiopathy as a differentiated nosology responsible for alterations in myocardial contractile function and greater prevalence of heart failure in these patients seems to be clearly demonstrated although its etiology remains unknown.

Adult↗

PubMed2003

Treatment of non-insulin-dependent diabetes mellitus.

Diabetes mellitus has been declared to be at an epidemic level by the World Health Organization. The syndrome is characterised as either Type I (insulin-dependent) or Type II (non-insulin-dependent) diabetes mellitus. Impaired glucose tolerance for extended periods of time results in serious complications such as kidney damage and impaired blood circulation and is the main cause for blindness and amputations in patients with diabetes. A combination of life-style change, dietary change and oral medications can treat Type II diabetes mellitus effectively and prevent long-term complications. Combination therapy appears to be the most effective approach in controlling blood glucose levels. This review updates the progress made in medicinal chemistry towards promising biological targets, with the development of a new generation of small molecules having improved efficacy and safety profiles.

Animals↗

PubMed2003

[The influence of simultaneous pancreas and kidney transplantation on long-term diabetic complications in patients with insulin dependent diabetes mellitus].

Diabetic nephropathy affects 20-35% patients with diabetes mellitus. After 25-30 years of nephropathy, chronic renal failure (CRF) develops in these patients. The aim of the study is to present the influence of simultaneous pancreas and kidney transplantation (SPK) on long-term diabetic complications in patients with CRF in course of insulin dependent diabetes mellitus and the length and quality of life of these patients. SPK has positive influence on nerves function of peripheral and autonomic nerve system, as well as heart ventricle function, but brings only limited benefits as regards progression of diabetic retinopathy and nephropathy. The life time of the patients in which SPK was performed is significantly longer that in dialysed patients treated with insulin and patients, in which only cadaveric kidney transplantation was performed. In patients after SPK an improvement of quality of life is also observed. SPK should be considered at the moment of appearance of renal failure symptoms in patients with long lasting insulin dependent diabetes mellitus. Proceeding like this may significantly improve prognosis in this patients, outstandingly disadvantageous if only intermittent dialysis is applied.

Adult↗

PubMed1989

The role of chemicals in the etiology of diabetes mellitus.

Diabetes mellitus is a collection of diseases that culminate in defects in carbohydrate metabolism and result in inappropriate hyperglycemia. Most individuals with this disease can be categorized into 1 of 2 groups, depending upon their insulin requirements. Individuals who require insulin therapy to maintain life have been designated as having insulin-dependent diabetes mellitus (IDDM), while individuals who can live without insulin treatment have been classified as having noninsulin-dependent diabetes mellitus (NIDDM). The single most important pathological finding in IDDM is a substantial reduction in the number of insulin-secreting pancreatic beta cells. Compelling experimental and epidemiological evidence indicates that, at least in some forms of IDDM, environmental factors, such as chemical toxins, play an important role in the etiology of this disease. Chemical toxins can precipitate IDDM through a variety of mechanisms. They can poison beta cells directly and cause the destruction of a critical mass of beta cells; alternatively, they can trigger autoimmune processes directed against beta cells; or, finally, they can augment the diabetogenic properties of another agent, such as a virus, to hasten the onset of clinical manifestations. In NIDDM, impaired beta cell function appears to be the initial event observed at the onset of this syndrome. Functional defects similar to those seen in NIDDM can be produced in laboratory animals using a specific beta cell toxin. These animals develop permanent glucose intolerance and insulin resistance as a consequence of beta cell alteration. A variety of other chemicals also have been found to produce glucose intolerance; however, this condition is transient and is resolved when the chemical is removed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

The epidemiology of insulin-dependent diabetes mellitus.

Diabetes mellitus is a uniquely interesting disorder to study from an epidemiologic perspective. Information that can be gathered from carefully designed and executed epidemiologic studies carried out on a population-based group of individuals with insulin-dependent diabetes mellitus (IDDM) provides insight into this disorder that cannot be obtained by traditional methods of basic or clinical research. The application of epidemiology as an investigative tool can be illustrated in 3 important areas of diabetes mellitus: (1) the etiology of IDDM, (2) the natural history or clinical course of IDDM, and (3) long-term complications of IDDM.

Adolescent↗

PubMed2003

Antioxidant status and lipid peroxidation in type II diabetes mellitus.

Diabetes Mellitus (DM), a state of chronic hyperglycaemia, is a common disease affecting over 124 million individuals worldwide. In this study, erythrocyte glutathione levels, lipid peroxidation, superoxide dismutase, catalase, and glutathione peroxidase and some extracellular antioxidant protein levels of patients with type II diabetes mellitus and healthy controls were investigated. Thirty-eight patients (21 males; with age of mean +/- SD, 53.1+/-9.7 years) and 18 clinically healthy subjects (10 males; with age of mean +/- SD, 49.3+/-15.2 years) were included in the study. Levels of erythrocyte lipid peroxidation, serum ceruloplasmin and glucose levels, HbA1C levels, and erythrocyte catalase activity were significantly increased, whereas serum albumin and transferrin levels, erythrocyte glutathione levels, and glutathione peroxidase activity were significantly decreased compared to those of controls. There was no significant difference in superoxide dismutase activity compared to controls. The results suggest that the antioxidant deficiency and excessive peroxide-mediated damage may appear in non-insulin dependent diabetes mellitus.

Adult↗

PubMed1990

Cognitive function in diabetes mellitus.

Diabetes mellitus is characterized by recurrent metabolic abnormalities which postmortem studies suggest might be associated with degenerative changes in the central nervous system. Acute hypoglycemia does indeed lead to cognitive impairment, whereas acute hyperglycemia in the absence of ketoacidosis or hyperosmolarity does not. Insulin-dependent diabetes mellitus is associated with cognitive deficits that tend to be relatively slight, inconsistent between different studies, and unrelated to clinical indicators; they can be ascribed as plausibly to psychogenic factors as to degenerative disease. In contrast, cognitive impairment in noninsulin-dependent diabetes mellitus is more conspicuous in tests of learning and memory, consistently associated with a patient's level of glycemic control, and more plausibly to be ascribed to structural neuropathology. Nevertheless, in both cases the deficits in question are unlikely to interfere significantly with patients' everyday functioning.

Cognition Disorders↗

PubMed1998

Nitric oxide availability in diabetes mellitus.

Diabetes mellitus is associated with early development of cardiovascular complications. Under physiological conditions the endothelium protects against the development of atherosclerosis. Endothelial cells produce, e.g., nitric oxide (NO), a substance which is capable of keeping vascular tone, coagulation and inflammation well balanced. However, in pathological conditions, such as in diabetes mellitus, impaired NO activity may be present. Decreased NO activity can be caused by impaired production of NO, due to uncoupling of receptor-mediated signal transduction, a deficiency of the NO synthase (NOS) substrate L-arginine, or a decreased availability of one or more cofactors essential for optimal functioning of NOS. However, hyperglycaemia also stimulates the production of advanced glycosylated end products, enhances the polyol pathway and activates protein kinase C. These conditions may lead to increased oxidative stress. Reactive oxygen species rapidly inactivate NO leading to the formation of peroxynitrite. Peroxynitrite is a toxic oxidant capable of damaging many biological molecules. Reduced NO availability may not only be of relevance to the development of atherosclerotic complications in diabetes but may also interfere with insulin-mediated postprandial glucose disposal and possibly contribute to the development of insulin resistance. Understanding of the complex metabolic disturbances interacting with the NO system may provide us with further therapeutic options to decrease cardiovascular morbidity and mortality in diabetes mellitus.

Animals↗

PubMed1992

[Myocardial disease in diabetes mellitus].

Diabetes mellitus is associated with excessive cardiovascular morbidity and mortality. Patients with diabetes mellitus suffer premature and severe atherosclerosis, and the relative impact is greater in women than in men. Clinical, experimental and pathological studies support the existence of a specific cardiomyopathy associated with diabetes mellitus. The cardiomyopathy plays an essential role in the pathogenesis of primary myocardial involvement, resulting in ventricular dysfunction, diminished cardiac pump performance and eventually overt heart failure. The authors discuss coronary heart disease and diabetic cardiomyopathy and indicate relevant treatment regimens.

Cardiomyopathies↗

PubMed1997

Risk of endometrial and breast cancer in patients with diabetes mellitus.

Diabetes mellitus patients have metabolic and endocrine alterations that could contribute to an increased incidence of hormone-related cancers. We assessed the incidence of endometrial and breast cancer among 80,005 women and the incidence of breast cancer among 73,847 men (total of 153,852 patients) identified in the Swedish In-patient Register as having been hospitalized for diabetes mellitus in the period 1965-1983. These patients underwent follow-up through 1989 via the Swedish Cancer Register and other nation-wide Swedish registers. The outcome measures were standardized incidence ratios (SIR) based on age-, sex- and calendar period-specific incidence rates from the entire Swedish population. To minimise the effect of selection bias, we excluded from the calculation of incidence ratios the first year of observation and cases diagnosed incidentally at autopsy. Only first cancers were considered for the estimates. A total of 328 endometrial cancers (SIR = 1.8; 95% confidence interval [CI] = 1.6-2.0), 1,145 female breast cancers (SIR = 1.3; 95% CI = 1.2-1.4) and 13 male breast cancers (SIR = 2.0; 95% CI = 1.0-3.4) were observed. We conclude that compared with the general population, patients with diabetes mellitus have an increased incidence of endometrial and breast cancers.

Adult↗

PubMed1986

[New findings on the pathogenesis of diabetes mellitus].

Diabetes mellitus is a heterogeneous syndrome. Insulin-dependent type 1 diabetes is characterized by progressive deterioration of B-cells in the islets of Langerhans resulting in a fall in insulin secretion. According to recent studies, autoimmune mechanisms are the reason for the B-cell destruction. These mechanisms can be triggered by viral infections which result in expression of HLA-DR antigens in macrophages and possibly in B-cells of the islets. B-cells are destroyed by cytotoxic T-lymphocytes; plasma cells form islet cell antibodies. The autoimmune process probably starts months to years before clinical manifestation of the disease. A viral infection immediately before clinical manifestation may reactivate the autoimmune process and lead to overt diabetes. T-lymphocytes reject pancreatic B-cells in type 1 diabetics throughout life. Pilot studies using cyclosporin as immunosuppressive agent in newly diagnosed type 1 diabetics have demonstrated that after discontinuation of this treatment diabetics again became insulin-dependent. Type 2 diabetics are usually elderly and non-insulin-dependent; there is a predominant defect in insulin action on peripheral tissues but also a concomitant impairment of B-cell secretion. Fasting plasma insulin levels are normal or increased; fasting C-peptide concentrations may be used to distinguish this type of diabetes from type 1 diabetes. Plasma fasting C-peptide concentrations less than 300 pmol/l usually indicate type 1 diabetes and levels above 300 pmol/l type 2 diabetes. Classification of diabetics according to pathogenesis is important, since different therapeutic and preventive measures are necessary.

Autoimmune Diseases↗

PubMed1978

The genetics of diabetes mellitus.

Diabetes mellitus is a geneticist's nightmare. We examine herein what causes the nightmare, how bad it is and how it is being alleviated by modern advances. Diabetes is more than one disease, it is indefinable, probably genetically multifactorial, and presents several facets with varying degrees of heredity and environment in their constitution.

Animals↗

PubMed2003

Rheumatologic manifestations of diabetes mellitus.

Diabetes mellitus has been linked to disorders of bones and joints, including neuroarthropathy, limited joint mobility, and hyperostosis. Some of the relations have known pathogenic mechanisms, but most are based on epidemiologic findings. This article reviews the associations between diabetes mellitus and its putative rheumatologic manifestations, and proposes a classification composed of four categories: consequences of diabetic complications, consequences of metabolic derangements inherent to diabetes, syndromes that may share etiologic mechanisms with microvascular disease, and probable associations. This approach may facilitate a clearer understanding of the musculoskeletal conditions that are prevalent in patients with diabetes mellitus.

Diabetic Nephropathies↗

PubMed1992

Ocular manifestations of diabetes mellitus.

Diabetes mellitus afflicts approximately 14 to 15 million Americans and is a leading cause of new blindness in the United States. Since eye disease represents an end-organ response to a generalized medical condition, all structures of the eye are susceptible. Furthermore, diabetes produces multiple effects on visual function and visual acuity that require specific clinical consideration. This paper offers a review of some of the key ocular manifestations of diabetes mellitus.

Cataract↗

PubMed1991

The future of calcium channel blocker therapy in diabetes mellitus.

Diabetes mellitus is associated with significant morbidity and mortality caused by the micro- and macro-vascular complications that all too frequently develop during the lifetime of the diabetic patient. In attempts to treat the complications of diabetes, several different treatment strategies have been investigated. The role of tight blood glucose control in the treatment of diabetic vascular complications has recently been challenged, as the existing data in support of this mode of therapy are currently inconclusive. Perhaps more effective in preventing many of the vascular complications is the rigorous treatment of hypertension that frequently accompanies diabetes mellitus. Epidemiological studies have demonstrated that the presence of hypertension significantly contributes to the development and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and possibly neuropathy. Preliminary clinical studies demonstrate that the progression of diabetic renal disease can be slowed by vigorous antihypertensive therapy. Among the various antihypertensive agents used to treat the hypertension associated with diabetes mellitus, calcium channel blockers are emerging as one of the agents of first choice. This is because of their very low side effect profile and their absence of detrimental effects on serum lipid levels and glucose tolerance. Calcium channel blockers may be of additional potential benefit to the diabetic patient by slowing the progression of atherosclerosis, reversing the intracellular calcium defects that may contribute to the pathogenesis of diabetic cardiomyopathy, and protecting against the progression of chronic renal disease.

Calcium Channel Blockers↗

PubMed1988

Screening for diabetes mellitus.

Diabetes mellitus in nonpregnant adults is a chronic affliction that leads to significant vascular and neuropathic disease. Diabetes during pregnancy can lead to perinatal complications. Both of these types of diabetes are common, often asymptomatic, and readily diagnosable by glucose tolerance testing. As a result, screening can identify many previously undiagnosed patients. However there is only limited evidence that screening results in net therapeutic benefit. In the case of gestational diabetes, controlled trials indicate that hypoglycemic therapy decreases the frequency of macrosomia, but has no effect on perinatal mortality. Our analyses indicate that screening for gestational diabetes is a low-cost intervention that produces a small expected benefit. Screening for diabetes in the nonpregnant adult (almost always a type II diabetic) is not recommended, because the link between improving glucose control and reducing diabetic complications is currently too weak. Screening might be reasonable for particular patients, for example, obese persons who would be spurred to lose weight by a demonstration of glucose intolerance. Screening for type I diabetes followed by immunomodulating therapy is still too experimental for confident analysis.

Cost-Benefit Analysis↗

PubMed1994

Assessment and management of pregnancies complicated by pregestational and gestational diabetes mellitus.

Diabetes mellitus is a commonly encountered medical complication of pregnancy that affects more than 100,000 pregnancies annually. The discovery of insulin and numerous scientific advances, including both fetal heart rate and glucose monitoring, dramatically improved the outlook for women with diabetes and their offspring. However, despite these recent advances, women with diabetes and their infants still remain at higher risk for a number of complications. Pregnancy has frequently been characterized as having a diabetogenic effect on normal carbohydrate metabolism, as evidenced by hyperglycemia and hyperinsulinemia in response to feeding. This leads to gestational diabetes in 2% to 3% of women and a worsened metabolic state in women with insulin-dependent diabetes mellitus. Since the availability of nutrients for the fetus is primarily dependent on the maternal metabolic state, these aberrations in fuel metabolism are believed to result in a host of perinatal complications, including diabetic embryopathy. In fact, the frequency of congenital anomalies is increased among infants of women with diabetes; they are responsible for approximately 40% of all perinatal deaths. Recent evidence suggests that normalization of blood glucose levels coupled with contemporary management strategies can reduce the frequency of congenital anomalies as well as improve maternal and neonatal outcomes. However, to impact on the congenital anomalies, euglycemia must begin in the preconceptual period and continue throughout organogenesis. Preconception counseling and intensive therapy regimens remain the focus of management programs targeted at women with diabetes.

Adolescent↗