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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 a metabolic disorder that is characterized by inappropriate hyperglycemia and is associated with both acute and chronic complications. Currently, diabetes mellitus is diagnosed by blood or plasma glucose levels. A random plasma glucose level > or = 200 mg/dL in an individual with classic symptoms is sufficient to make the diagnosis. Otherwise, a fasting plasma glucose level > or = 126 mg/dL or a 2-hour plasma glucose level > or = 200 mg/dL after an oral glucose challenge of 75 g on 2 occasions is sufficient evidence upon which to diagnose diabetes mellitus. The major types of diabetes mellitus are type 1 diabetes (insulin deficient) and type 2 diabetes (combination of insulin resistance and insulin deficiency). In both types, there is a genetic predisposition as well as environmental factors that contribute to the expression of the genetic predisposition. In type 1 diabetes, the primary abnormality is extensive deficiency of beta cell function. In type 2 diabetes, insulin resistance occurs, and the marked compensatory increases in insulin secretion necessary to maintain normal glucose tolerance cannot be achieved or maintained. As beta cell function continues to decrease, the individual progresses from normal glucose tolerance to impaired glucose tolerance to diabetes with primarily postprandial hyperglycemia to diabetes with fasting hyperglycemia. Drugs can cause diabetes by interfering with beta cell insulin secretion, by increasing insulin resistance, or by a combination of both. Atypical antipsychotic drugs have been reported to cause diabetic ketoacidosis, obesity and insulin resistance, type 2 diabetes, and hypertriglyceridemia. A monitoring system should be in place in patients started on treatment with these agents to detect metabolic abnormalities as they are evolving so that adequate and timely treatment can be initiated.
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PMID:Diagnosis, classification, and pathogenesis of diabetes mellitus. 1180 89

Insulin resistance is a common metabolic disorder. It plays an important role in the metabolic syndrome (or syndrome X), type 2 diabetes, obesity and in the lipodystrophic syndromes recently described, associated with treatments of HIV disease and represent a worrying cardiovascular risk. However, its pathophysiology remains poorly understood in these situations. Syndromes of major insulin resistance, although rare, allow investigations of the mechanisms leading to alterations in the insulin transduction pathways. Mutations of the insulin receptor gene have been discovered in rare patients. Therefore alterations at the post-receptor level are probably causative in other cases. Furthermore, the role of body fat repartition seems determinant in the apparition of insulin resistance, as attested by the clinical characteristics of lipodystrophies, either congenital or acquired. The two lipodystrophic syndromes which molecular defect is identified are the familial partial lipodystrophy of the Dunnigan type, due to mutations of the lamin A/C gene, and the congenital generalized lipodystrophy, linked to alterations in the protein seipin. However, their physiopathology remains mysterious. Lamin A/C is indeed an ubiquitous nuclear protein, which is also mutated in a genetic squelettic and/or cardiac myopathy, and seipin is a protein of unknown function mainly expressed in brain. Progresses in the understanding of these syndromes, in particular lipodystrophies which can be considered as caricatural models of the metabolic syndrome, will probably allow to clarify the physiopathology of the more common forms of insulin resistance.
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PMID:[Major insulin resistance syndromes: clinical and physiopathological aspects]. 1183 62

Extracts of leaves from the plant Stevia rebaudiana Bertoni have been used in the traditional treatment of diabetes in Paraguay and Brazil. Recently, we demonstrated a direct insulinotropic effect in isolated mouse islets and the clonal beta cell line INS-1 of the glycoside stevioside that is present in large quantity in these leaves. Type 2 diabetes is a chronic metabolic disorder that results from defects in both insulin and glucagon secretion as well as insulin action. In the present study we wanted to unravel if stevioside in vivo exerts an antihyperglycaemic effect in a nonobese animal model of type 2 diabetes. An i.v. glucose tolerance test (IVGT) was carried out with and without stevioside in the type 2 diabetic Goto-Kakizaki (GK) rat, as well as in the normal Wistar rat. Stevioside (0.2 g/kg BW) and D-glucose (2.0 g/kg BW) were administered as i.v. bolus injections in anaesthetized rats. Stevioside significantly suppressed the glucose response to the IVGT in GK rats (incremental area under the curve (IAUC): 648 +/- 50 (stevioside) vs 958 +/- 85 mM x 120 min (control); P < 0.05) and concomitantly increased the insulin response (IAUC: 51116 +/- 10967 (stevioside) vs 21548 +/- 3101 microU x 120 min (control); P < 0.05). Interestingly, the glucagon level was suppressed by stevioside during the IVGT, (total area under the curve (TAUC): 5720 +/- 922 (stevioside) vs 8713 +/- 901 pg/ml x 120 min (control); P < 0.05). In the normal Wistar rat stevioside enhanced insulin levels above basal during the IVGT (IAUC: 79913 +/- 3107 (stevioside) vs 17347 +/- 2882 microU x 120 min (control); P < 0.001), however, without altering the blood glucose response (IAUC: 416 +/- 43 (stevioside) vs 417 +/- 47 mM x 120 min (control)) or the glucagon levels (TAUC: 5493 +/- 527 (stevioside) vs 5033 +/- 264 pg/ml x 120 min (control)). In conclusion, stevioside exerts antihyperglycaemic, insulinotropic, and glucagonostatic actions in the type 2 diabetic GK rat, and may have the potential of becoming a new antidiabetic drug for use in type 2 diabetes.
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PMID:Stevioside induces antihyperglycaemic, insulinotropic and glucagonostatic effects in vivo: studies in the diabetic Goto-Kakizaki (GK) rats. 1192 70

Type 2 diabetes is a metabolic disorder that, if untreated, can result in macrovascular and microvascular complications. Lowering blood glucose levels primarily reduces microvascular risk; other treatment strategies are necessary to lower the risk for macrovascular disease. Because most patients with diabetes die of macrovascular disease, it is vitally important that patients with diabetes receive aggressive therapies to lessen this risk. It has been found that the risk for macrovascular complications begins even earlier than the risk for microvascular complications. Therefore, patients with insulin resistance (now called prediabetes) should be identified and treated to lower their risk of cardiovascular disease and reduce their risk for progression to diabetes. Two cases are reviewed--a patient with prediabetes and the metabolic syndrome, and a second patient with type 2 diabetes and advanced cardiovascular disease. A review of potential cardiovascular therapies is included.
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PMID:Treating diabetes: cardiovascular benefits of antidiabetes drugs. 1202 37

There has been only limited research investigating the possible association between raised haematocrit levels, glucose intolerance and type 2 diabetes. In the present study, we explored the association between high haematocrit levels and impaired glucose tolerance by performing oral glucose tolerance tests in 46 patients with chronic obstructive pulmonary disease and no previous history of diabetes mellitus or glucose intolerance. A glucose metabolism disorder was observed in 12 (26%) patients (type 2 diabetes in six patients and impaired glucose tolerance in a further six). There was a significant association between high haematocrit levels and the presence of a glucose metabolism disorder, which was independent of other risk factors. High haematocrit levels may be an independent risk factor for type 2 diabetes and impaired glucose tolerance.
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PMID:The effects of high haematocrit levels on glucose metabolism disorders. 1223 27

Three cases of diabetic ketoacidosis precipitated by thyrotoxicosis are presented. Two of them are young women with type 1 diabetes mellitus; the third case is a middle-aged woman with type 2 diabetes mellitus. All of them were diagnosed with Graves' disease. They typically showed tachycardia at rest in spite of correction of the metabolic disorder. Hyperthyroidism worsens glycemic control in diabetic patients and may precipitate diabetic ketoacidosis. On the other hand, women with diabetes have a higher prevalence of Graves' disease. Thus, in diabetic ketoacidosis without an obvious triggering factor, the presence of hyperthyroidism should be investigated, particularly in women.
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PMID:Association between diabetic ketoacidosis and thyrotoxicosis. 1248 99

Type II diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular, renal, neurologic, and retinal complications. While several drugs are currently prescribed to treat type II diabetes, their efficacy is limited by mechanism-related side effects (weight gain, hypoglycemia, gastrointestinal distress), inadequate efficacy for use as monotherapy, and the development of tolerance to the agents. Consequently, combination therapies are frequently employed to effectively regulate blood glucose levels. We have focused on the mitochondrial sodium-calcium exchanger (mNCE) as a novel target for diabetes drug discovery. We have proposed that inhibition of the mNCE can be used to regulate calcium flux across the mitochondrial membrane, thereby enhancing mitochondrial oxidative metabolism, which in turn enhances glucose-stimulated insulin secretion (GSIS) in the pancreatic beta-cell. In this paper, we report the facile synthesis of benzothiazepines and derivatives by S-alkylation using 2-aminobenzhydrols. The syntheses of other bicyclic analogues based on benzothiazepine, benzothiazecine, benzodiazecine, and benzodiazepine templates are also described. These compounds have been evaluated for their inhibition of mNCE activity, and the results from the structure-activity relationship (SAR) studies are discussed.
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PMID:Efficient syntheses of benzothiazepines as antagonists for the mitochondrial sodium-calcium exchanger: potential therapeutics for type II diabetes. 1251 66

Type 2 diabetes mellitus is a complex metabolic disorder with adverse cardiovascular risk. The role of micronutrients has not yet been well clarified in this condition, especially in India.THE OBJECTIVES OF THIS STUDY WERE TO: (1) evaluate chromium status in Indian subjects with type 2 diabetes mellitus, (2) assess the effect of chromium picolinate (200 &mgr;g trivalent chromium twice daily) administration on glycaemic control and lipid profile in these subjects and (3) comment on the possible mechanism of any beneficial effect noted above.Fifty subjects were studied in a double blind, placebo-controlled, crossover fashion, with each treatment arm (chromium/placebo) lasting 12 weeks and 4 weeks' wash-off period in between. 50 healthy age- and sex-matched volunteers served as controls. Serum chromium level appeared to be higher in the general population in our country compared to western countries (36.5-59.5 nmol/L as compared to 2.3-40.3 nmol/L) However, the local diabetics were found to have a lower serum chromium level than the healthy controls (32.3 nmol/L against 44.7 nmol/L; p < 0.0001) and a mean increase of 3.5 nmol/L was noted after 12 weeks of chromium supplementation that was, expectedly, not seen in the placebo phase (p < 0.0001).Significant improvement in glycaemic control was noted in the chromium-treated group (DeltaFasting serum glucose = 0.44 mmol/L, p < 0.001; DeltaPost-prandial serum glucose = 1.97 mmol/L, p < 0.001; Deltaglycated hemoglobin = 0.01; p = 0.04, in comparison to placebo) This was accompanied by a significant greater fall in fasting serum insulin in the chromium-treated group, p < 0.05.The change in lipid parameters (total serum cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides) did not show significant difference between the chromium and placebo groups.Clinically significant hematological, renal or hepatic toxicity were excluded by routine hemogram, serum urea, creatinine, alanine amino transferase (ALT) and alkaline phosphatase estimations.In conclusion, chromium supplementation seems to improve glycaemic control in type 2 diabetic patients, which appears to be due to an increase in insulin action rather than stimulation of insulin secretion.
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PMID:Role of chromium supplementation in Indians with type 2 diabetes mellitus. 1255 67

The insulin sensitivity in hypertensive patients with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) and the insulin resistance (IR) under the disorder of glucose metabolism and hypertension were studied. By glucose tolerance test and insulin release test, insulin sensitivity index (ISI) and the ratio of area under glucose tolerance curve (AUCG) to area under insulin release curve (AUCI) were calculated and analyzed. The results showed that ISI was decreased to varying degrees in the patients with hypertension, the mildest in the group of NGT with hypertension, followed by the group of IGT without hypertension, the group of IGT with hypertension and DM (P = 0). There was very significant difference in the ratio of AUCG/AUCI between the hypertensive patients with NGT and controls (P = 0). It was concluded that a significant IR existed during the development of IGT both in hypertension and nonhypertension. The increase of total insulin secretion (AUCI) was associated with nonhypertension simultaneously. IR of the hypertensive patients even existed in NGT and was worsened with the deterioration of glucose metabolism disorder, but the AUCI in the HT group changed slightly. A relative deficiency of insulin secretion or dysfunction of beta-cell of islet existed in IGT and DM of the hypertensive patients.
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PMID:Insulin resistance and hypertension. 1267 74

Type 2 diabetes mellitus is a chronic metabolic disorder associated with high morbidity and mortality from long-term microvascular and macrovascular complications. Evidence from randomized controlled trials indicates that aggressive treatment directed at improving glycemic control reduces the incidence of diabetes-related microvascular complications. Traditionally, oral monotherapy for type 2 diabetes is initiated when diet and exercise do not control hyperglycemia, followed by the sequential, stepwise addition of oral agents as glycemic control deteriorates. Insulin is the last therapeutic option used, generally reserved for advanced stages of the disease when multiple oral combination treatment fails. Despite a better understanding of the pathophysiologic disease mechanisms in the past decade, the expanded armamentarium of targeted oral antidiabetic drugs, and the conclusive evidence of the benefits of stringent glycemic control, actual treatment outcomes in clinical practice remain suboptimal relative to established treatment goals (glycosylated hemoglobin A1c level <7%). Earlier detection and aggressive treatment are critical to address the natural progression of diabetes because multiple defects (insulin resistance, insulin insufficiency, glucotoxicity, and lipotoxicity) and vascular complications may be present at the time of diagnosis. Acknowledging the inadequacy of traditional strategies and underscoring the importance of insulin as an integral part of the therapeutic armamentarium, clinical trends are moving toward earlier use of insulin combined with 1 or more oral agents. Such strategies can address the multiple abnormalities present early in the disease course and may restore optimal control. A new treatment paradigm for patients with type 2 diabetes to achieve and maintain near-normal glycemic control is warranted.
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PMID:Pharmacological management of type 2 diabetes mellitus: rationale for rational use of insulin. 1268 92


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