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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus is composed of a heterogeneous group of disorders characterized by high blood glucose levels. Four major types of diabetes have been defined by the National Diabetes Data Group. Insulin-dependent diabetes (IDDM), also called type I diabetes, is characterized by abrupt clinical onset, insulinopenia, proneness to ketosis even in the basal state, and dependence on exogenous insulin to sustain life. Non-insulin-dependent diabetes (NIDDM), also called type II diabetes, may remain relatively asymptomatic for years. Insulin levels may be normal, lower than normal, or elevated as a consequence of insulin resistance. Ketosis is not part of the general clinical picture except in times of metabolic stress, although the classic complications of diabetes can be expected to develop in long-duration diabetics. Gestational diabetes (GDM) refers to the recognition of abnormal glucose intolerance in pregnancy, although unrecognized abnormal tolerance may indeed have predated the pregnancy. Rates of macrosomia are higher than in non-GDM pregnancies, but fetal mortality and congenital anomalies appear to be no greater than in the general population. Other types of diabetes include a number of diverse conditions in which glucose intolerance is a feature and in which it may be etiologically related. Impaired glucose tolerance (IGT) is a class that encompasses persons whose glucose tolerance is intermediate between normal and diabetic. These individuals do not manifest the microvascular complications of diabetes, but they appear to have higher rates of macrovascular disease associated with the known cardiovascular risk factors. Two statistical risk categories have also been defined that replace the older terms prediabetes, potential diabetes, and latent diabetes. Diabetes can be diagnosed by the presence of classical signs and symptoms of diabetes and unequivocally elevated blood glucose levels; by a fasting plasma glucose greater than or equal to 140 mg/dl; or by an abnormal oral glucose tolerance test, with a venous plasma glucose value greater than or equal to 200 mg/dl at 2 hours after 75 grams oral glucose, being a hallmark criterion for diabetes. For the latter two criteria, the abnormality should be reconfirmed at a later occasion before a definitive diagnosis of diabetes is made. The oral glucose tolerance test has been standardized at a 75-gram glucose (or carbohydrate equivalent) load, given in the morning after an overnight fast. Glucose should be determined for two hours after administration of the challenge.
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PMID:Classification and diagnostic criteria for diabetes mellitus and other categories of glucose intolerance. 329 Sep 16

The rhesus monkey (Macaca mulatta), which has been found to develop spontaneous obesity, non-insulin dependent diabetes mellitus (NIDDM; Type 2), and hypertension, was used to evaluate the potential blood pressure-lowering effects of captopril as well as the specific effects, if any, on the prediabetic state. Intravenous and oral glucose tolerance testing was carried out with oral captopril dosing. Results showed that captopril significantly decreased both systolic and diastolic blood pressure in all monkeys and significantly decreased fasting plasma glucose levels. Based on these preliminary studies in monkeys, we conclude that captopril exerted antihypertensive effects without adverse effects on glucose metabolism.
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PMID:Antihypertensive effects of captopril without adverse effects on glucose tolerance in hyperinsulinemic rhesus monkeys. 756 5

Despite recent progress in therapy and management of diabetes mellitus, diabetes remains a serious disease with life-threatening complications. It is by far the most common metabolic disease and affects 5% of the population in industrialized countries. Noninsulin-dependent diabetes mellitus (NIDDM) is a complex disorder characterized by insulin resistance and impaired insulin secretion and is associated with an increased risk of coronary heart disease, peripheral vascular disease, arterial hypertension and dyslipidemia. Predisposing factors for NIDDM are obesity and a family history of diabetes. Greater physical activity has been associated inversely with the prevalence of NIDDM in several cross-sectional studies. Physical activity increases the sensitivity to insulin, and regular endurance exercise can induce and maintain weight loss, improve glucose tolerance and ameliorate most of the abnormalities in the metabolic syndrome. Type I diabetes mellitus arises as a consequence of immunologically mediated pancreatic islet beta-cell destruction in genetically susceptible individuals. It is an insidious process that may occur over years. During the stage of disease evolution (prediabetes), individuals may be identified by the presence of immunological markers and a decline of beta-cell function. The autoimmune nature of the disease process has led to attempts to stop this process by immune intervention strategies. A variety of immune interventions has been used, some immunosuppressive and some immunomodulatory. Several screening programs are used in order to identify high-risk subjects (i.e. first-degree relatives of individuals with type I diabetes) who may benefit from an early intervention. The ultimate goal of all these efforts is to prevent the development of overt type I diabetes mellitus in those at risk for the disease, using strategies that are both safe and specific. This review summarizes the results of the various studies conducted to date and outlines the approaches currently being tested.
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PMID:[Is prevention of diabetes mellitus possible?]. 783 27

Non-insulin-dependent diabetes mellitus is a complex metabolic disorder that involves numerous biochemical abnormalities, a heterogenous clinical picture, and a polygenic hereditary component. The pathophysiologic state involves increased basal hepatic glucose production, decreased insulin-mediated glucose utilization in target tissues, and altered pancreatic function with decreased beta cell function and enhanced glucagon secretion. Prospective studies indicate that insulin resistance and hyperinsulinemia exist in the prediabetic state at a time when glucose tolerance is normal. When hyperglycemia supervenes, both insulin secretion and insulin-mediated glucose utilization are further compromised, mediated in part by sustained hyperglycemia itself. Insulin resistance may occur at any level in the biologic action of insulin, from initial binding to cell surface receptors to the phosphorylation cascade that is initiated by autophosphorylation of the insulin receptor. Receptors isolated from patients with non-insulin-dependent diabetes mellitus have compromised autophosphorylation-kinase activity when isolated from adipocytes, liver, erythrocytes, and skeletal muscle. The magnitude of the decrease in insulin receptor kinase activity is correlated with the degree of fasting hyperglycemia. However, the defect in insulin receptor kinase activity is normalized after weight reduction or other measures that reduce hyperglycemia, indicating the secondary nature of the defect. Clarification of the mechanisms underlying insulin resistance in non-insulin-dependent diabetes mellitus will lead to new treatment modalities for this disease.
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PMID:Insulin resistance and non-insulin-dependent diabetes mellitus: cellular and molecular mechanisms. 790 Jun 97

Non-insulin-dependent diabetes (NIDDM) is a heterogeneous state involving various degrees of beta-cell dysfunction and insulin resistance, although the relative importance of these two factors is controversial. Several single gene disorders of carbohydrate metabolism have their main pathophysiological defect largely restricted to the beta-cell or to insulin-sensitive tissues. We have noted that with insulin resistance the fasting plasma glucose is often normal and severe hyperglycaemia occurs after a glucose load. By contrast, in glucokinase-deficient diabetes, which is characterised by reduced insulin secretion, the reverse is the case. Supportive evidence showing that beta-cell dysfunction and insulin resistance may have different effects on fasting and post-prandial glucose concentrations comes from studies of identical twins of NIDDM patients, hemi-pancreatectomised normal subjects, and insulin-resistant Asian subjects. NIDDM is usually preceded by a period of less severe hyperglycemia, referred to as impaired glucose tolerance (IGT). Studies of the IGT phase usually conclude that insulin resistance is the major abnormality and is thus the primary defect in NIDDM. However, the definition of IGT is based on the 2 h plasma glucose after an oral glucose-tolerance test without consideration of the fasting glucose concentrations (provided these concentrations are non-diabetic). Our observations suggest that this definition of IGT may result in the over-representation of insulin-resistant individuals and the under-representation of subjects with beta-cell dysfunction in any cross sectional study of IGT. The belief that the prediabetic state of IGT is dominated by insulin resistance may be a self-fulfilling prophesy because of the excessive emphasis put on the post-prandial rather than the fasting state.
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PMID:Insulin resistance as the major cause of impaired glucose tolerance: a self-fulfilling prophesy? 799 82

The pathogenesis of autoimmune insulin-dependent (Type 1) diabetes mellitus (IDDM) is far from being resolved, despite extensive genetic and immunological research. However, recent experimental data from immune and endocrine studies using spontaneous or transgenic models of the disease have emphasized the role of the islet of Langerhans, and particularly beta cells, in IDDM pathogenesis. Part I of this review (Diabetes Metab, 1997, 23, 181-194) considered the various ways normal beta cells cope with increased demands on their resources in different models of hyperglycaemia in order to provide a better delineation and comparison of the mechanisms implicating these cells in the pathogenesis of IDDM and non-insulin-dependent (Type 2) diabetes mellitus (NIDDM). Part II attempts to improve our understanding of the various mechanisms through which beta cells, and perhaps the entire islet of Langerhans, may influence the immune system from the perinatal period to adulthood. Genetics and beta-cell behaviour are considered during prediabetes in human and experimental models of IDDM and NIDDM. Attention is focused on the spontaneous model of the disease, the non-obese diabetic (NOD) mouse, which in addition to providing genetic data, appears to be useful for sequential study of the early developmental, immune and endocrine events that occur in IDDM pathophysiology.
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PMID:Beta-cell behaviour during the prediabetic stage. Part II. Non-insulin-dependent and insulin-dependent diabetes mellitus. 949 55

Mechanisms of insulin resistance in subjects at risk for type 2 diabetes remain to be elucidated. Insulin acts slowly in vivo, but rapidly in vitro, suggesting that the pathway insulin traverses from B-cell to insulin sensitive tissue may be altered in diabetes. An important component of that pathway is transport of insulin across the capillary endothelium. Several groups have demonstrated that insulin resistance may result from reduced capillary permeability to insulin--it remains to be determined whether reduced permeability contributes to insulin resistance in any stage leading to type 2 diabetes. Interestingly, the transport of insulin across the endothelial barrier not only limits the rate of insulin to stimulate glucose uptake by skeletal muscle, but appears also to determine the rate at which insulin suppresses liver glucose output. Because the liver circulation is fenestrated, it is not possible that insulin transport into the liver is the rate determining step for suppression of liver glucose output. An alternative hypothesis was considered--that insulin is transported into an extrahepatic tissue. A "second signal" is generated by the extrahepatic tissue, the signal is released into the blood, and the signal in turn controls hepatic glucose output. Several lines of evidence suggest that the second signal is free fatty acids (FFA): 1) There is a strong correlation between FFA and liver glucose output under a variety of experimental conditions. 2) If FFA are maintained at basal concentrations during insulin administration, glucose output fails to decline. 3) If FFA are reduced independent of insulin administration, glucose output is reduced. These three points support the concept that insulin, by regulating adipocyte lipolysis, controls liver glucose production. Thus, the adipocyte is a critical mediator between insulin and liver glucose output. Evidence that FFA also suppress skeletal muscle glucose uptake and insulin secretion from the B-cell supports the overall central role of the adipocyte in the regulation of glycemia. Insulin resistance at the fat cell may be an important component of the overall regulation of glycemia because of the relationships between FFA and glucose production, glucose uptake, and insulin release. It is possible that insulin resistance at the adipocyte itself can be a major cause of the dysregulation of carbohydrate metabolism in the prediabetic state.
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PMID:Central role of the adipocyte in insulin resistance. 1021 35

We previously reported that a decreased TCR mediated activity of the GTP-GDP binding p21ras protooncogene is associated with prediabetes in non-obese diabetic (NOD) mice. Furthermore, prevention of autoimmune diabetes is associated with reversal of the p21ras signaling defect in NOD T cells. Based on these animal studies we determined the activation of p21ras in PBMC from patients with Insulin Dependent Diabetes Mellitus (IDDM), Non-Insulin Dependent Diabetes Mellitus (NIDDM) and normal healthy controls. Stimulation by PHA induced a decrease of 3.7 +/- 1.4% and an increase of 2.44 +/- 2.3%, p < 0.02 and 2.6 +/- 1.6%,p < 0.003 in the basal unstimulated p21ras activity in the IDDM, NIDDM and normal control groups, respectively. Expression of p21ras and its regulatory elements, the GTPase activating protein p120ras-GAP and the guanine nucleotide releasing factor (GNRF) hSOS, was comparable in the three groups. The in vitro proliferative response to PHA was comparable in the IDDM and control groups: stimulation index (SI) of 8.6 +/- 2.5 and 9.4 +/- 3.5 respectively, p < 0.44. No correlations were found in the IDDM patients between the degree of p21ras activation and the mitogen induced in vitro proliferative response or the various clinical parameters including age, gender, disease duration, daily insulin requirements and metabolic control. Taken together these data indicate that PBMC from IDDM patients are characterized by a persistent impairment in the activation of their p21ras. They also suggest that p21ras stimulated activity is a sensitive and independent parameter of PBMC activation in these patients.
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PMID:Defective activation of p21ras in peripheral blood mononuclear cells from patients with insulin dependent diabetes mellitus. 1043 77

Obesity, especially visceral adiposity, is a major determinant of the development of type 2 diabetes. Both visceral adiposity and insulin resistance are strongly related to cardiovascular risk factors in diabetic and non-diabetic subjects. One of the areas where the correlation between visceral fat (upper body adiposity) and cardiovascular risk is most apparent is the prediabetic state. We have recently shown that only prediabetic subjects (those who later develop type 2 diabetes) who are insulin resistant and with upper body adiposity have increased triglycerides, decreased HDL cholesterol and high blood pressure.
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PMID:Obesity and the metabolic syndrome: the San Antonio Heart Study. 1088 94

Both diabetic and prediabetic patients have abnormal vascular reactivity and should be considered to have occult cardiovascular disease. Angiotensin-converting-enzyme (ACE) inhibitors are particularly beneficial in diabetes because they reduce the incidence of both cardiovascular events and diabetes-related complications. In prediabetic patients, ACE inhibitors also reduce the risk of a new diagnosis of type 2 diabetes. Managing hypertension is even more beneficial for diabetic patients than for nondiabetic patients. To further reduce the risk of heart disease in patients with diabetes or prediabetes, dyslipidemia should also be treated aggressively.
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PMID:In diabetes, treat hidden heart disease. 1110 30


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