Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently reported that ingestion of Ginkgo biloba extract (EGb 761) (a) significantly reduced collagen-induced platelet aggregation and thromboxane B2 (TXB2) production in both non-diabetic individuals as well as those with type 2 diabetes mellitus (T2DM), (b) significantly reduced platelet malondialdehyde (MDA), an index of lipid peroxidation, in non-diabetic subjects. In the present study we report that ingestion of EGb 761 (120 mg daily for 3 months), significantly decreased platelet MDA-thiobarbituric acid reacting substances (TBARS) (41 +/- 9 pmol/10(7) platelets versus 30 +/- 11 pmol/10(7) platelets) (p < 0.005) in T2DM subjects with normal cholesterol levels (total cholesterol, 164 +/- 22 mg/dl; age, 54 +/- 9 years; BMI, 35.0 +/- 8.8 kg/m2, n = 12). In T2DM subjects with high cholesterol (total cholesterol, 218 +/- 15 mg/dl; age, 52 +/- 5 years; BMI, 36.2 +/- 6.6 kg/m2, n = 7), EGb 761 ingestion reduced the platelet TBARS from 29 +/- 9 to 22 +/- 9 pmol/10(7) platelets (p < 0.04). Because ingestion of EGb 761 did not alter platelet counts it is concluded that EGb 761, probably due to the flavonoid fraction, reduced the TBARS by inhibiting cyclooxygenase (COX)-1-mediated arachidonic acid oxygenation or by reducing the arachidonic acid pool. This is likely to lead to a reduction of platelet hyperactivity, a significant contributor to the development of cardiovascular disease in T2DM patients. Because of other reported beneficial properties of EGb 761, such as stimulation of pancreatic beta-cell function in T2DM subjects with pancreatic exhaustion, it appears that T2DM subjects might benefit from ingesting EGb 761 as a dietary supplement.
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PMID:Short-term oral ingestion of Ginkgo biloba extract (EGb 761) reduces malondialdehyde levels in washed platelets of type 2 diabetic subjects. 1581 63

Sulfonylureas are still largely used for treatment of type 2 diabetic patients, and they still occupy a central position in many international therapy guidelines. More recently concern has been raised with respect to possible adverse effects associated with the use of these agents. Sulfonylureas are, indeed, believed to favor the development of hypoglycemia, to accelerate beta cell apoptosis and beta-cell exhaustion, and to impair endothelial function with increased risk for ischemic complications. However, because of the intrinsic pathogenetic heterogeneity of type 2 diabetes, sulfonylureas are likely to remain a therapeutic option. Careful choice of a specific sulfonylurea should be made on the basis of efficacy, safety, convenience, tissue specificity, and neutrality with respect to the beta cell. In this review the advantage:disadvantage ratio of available sulfonylureas is analyzed with the purpose of providing a critical clinical appraisal of the role of sulfonylureas in the modern treatment of type 2 diabetes.
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PMID:The place of sulfonylureas in the therapy for type 2 diabetes mellitus. 1663 7

Type 2 diabetes mellitus (DM) is a progressive disease characterized by insulin resistance and impaired insulin secretion. To compensate for these metabolic dysfunctions, pancreatic beta-cells begin to overproduce insulin; however, it is this compensatory mechanism that eventually results in beta-cell exhaustion, impaired insulin secretion, and relative insulin deficiency. The metabolic abnormalities associated with diabetes also contribute to vascular dysfunction and an increased risk of coronary heart disease. Among patients with type 2 DM, cardiovascular disease, particularly macrovascular disease, is the primary cause of mortality, accounting for 55% of deaths. Management of the disease, therefore, must address all of the contributing factors, including a sedentary lifestyle and diet that contribute to overweight/obesity, and comorbidities such as hypertension and dyslipidemia. In this paper, we present a case study based on actual clinical experience to illustrate an evidence-based rationale for early and aggressive intervention for patients with type 2 DM, including lifestyle modification, oral antidiabetic agents, and insulin.
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PMID:Early intervention to achieve optimal outcomes in type 2 diabetes: a case presentation. 1693 76

Anaerobic threshold (AT) has been considered the optimal exercise intensity for type 2 diabetes mellitus (DM 2) patients, but there is little information about the comparison between lactate (LT) and ventilatory (VT) thresholds in this population, particularly during treadmill exercise. Therefore, we evaluated DM 2 women in order to compare and analyze the relationships between VT and LT intensities. Fifteen women with DM 2 without complications and comorbidities (50.7 +/- 8.0 years; 71.3 +/- 8.6 kg; 154 +/- 5 cm; 37.8 +/- 3.9% fat; 4.7 +/- 3.2 years of disease diagnose and 138 +/- 45 mg/dl fasting glucose) were subjected to a graded treadmill test-initial velocity and increments of 1 km/h every 2 min until voluntary exhaustion. VT was determined from V(E)/V(O(2)) and V(E)-V(CO(2)) ratios and LT was defined as the point at which a first increase in blood lactate occurs during incremental test. Our results showed no significant differences (p > 0.05) and significant correlations between VT and LT expressed in velocity (4.7 +/- 0.7 versus 4.6 +/- 0.7 km/h, r = 0.62), absolute V(O(2)) (1.27 +/- 0.33 versus 1.24 +/- 0.28 l min(-1), r = 0.93); relative V(O(2)) (18.3 +/- 5.7 versus 17.6 +/- 4.6 ml kg(-1) min(-1), r = 0.84) and %V(O(2)(max)) (80 +/- 12 versus 78 +/- 10%, r = 0.82). These results suggest that both VT and LT can be used to access AT in DM 2 women during graded treadmill exercise.
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PMID:Lactate and ventilatory thresholds in type 2 diabetic women. 1695 65

Obesity and type 2 diabetes mellitus have reached epidemic proportions in the US, and indeed, globally. While microvascular complications contribute to considerable morbidity, much of the excess mortality (around 70%) is due to macrovascular disease. Hyperglycemia has predictable toxic effects on multiple organs ('glucotoxicity') including the pancreas, where it impairs insulin secretion and insulin gene expression through mechanisms that lead to glucose densensitization and beta-cell exhaustion, eventually resulting in irreversible beta-cell failure. There is robust evidence to suggest that strict glycemic control reduces diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) in both primary- and secondary-prevention settings. While unequivocal evidence that intensive glycemic control reduces the risk of death due to macrovascular disease is lacking, meta-analytic data and controlled clinical trial data suggest there may still be clinically significant lowering of the risk for macrovascular endpoints through strict glycemic control. Cardiovascular disease in a diabetic patient is a collusion of several factors besides hyperglycemia, such as hypertension, dyslipidemia, diffuse endothelial dysfunction, hypercoagulability, and inflammation. It is important to address lifestyle issues such as maintenance of ideal bodyweight, good dietary practice, smoking cessation, and regular exercise in the comprehensive risk management of a diabetic patient, in order to reduce the vascular complications. Large, ongoing clinical trials such as ACCORD (Action to Control Cardiovascular Risk in Diabetes) are likely to establish the potential benefits of glycemic control in preventing or postponing macrovascular complications of diabetes.
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PMID:The effectiveness of intensive glycemic control for the prevention of vascular complications in diabetes mellitus. 1700 87

The aims of the study were to modify the training impulse (TRIMP) method of quantifying training load for use with intermittent team sports, and to examine the relationship between this modified TRIMP (TRIMP(MOD)) and changes in the physiological profile of team sport players during a competitive season. Eight male field hockey players, participating in the English Premier Division, took part in the study (mean+/-s: age 26+/-4 years, body mass 80.8+/-5.2 kg, stature 1.82+/-0.04 m). Participants performed three treadmill exercise tests at the start of the competitive season and mid-season: a submaximal test to establish the treadmill speed at a blood lactate concentration of 4 mmol . l(-1); a maximal incremental test to determine maximal oxygen uptake ([V]O(2max)) and peak running speed; and an all-out constant-load test to determine time to exhaustion. Heart rate was recorded during all training sessions and match-play, from which TRIMP(MOD) was calculated. Mean weekly TRIMP(MOD) was correlated with the change in [V]O(2max) and treadmill speed at a blood lactate concentration of 4 mmol x l(-1) from the start of to mid-season (P<0.05). The results suggest that TRIMP(MOD) is a means of quantifying training load in team sports and can be used to prescribe training for the maintenance or improvement of aerobic fitness during the competitive season.
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PMID:A modified TRIMP to quantify the in-season training load of team sport players. 1745 29

Genetic mutations resulting in obesity and type 2 diabetes mellitus (T2D) are described for both inbred and outbred mice. However, no known mouse model completely recapitulates human T2D and its comorbidities. We identified a cohort of obese, male, outbred Swiss-Webster (SW) mice as polyuric, polydipsic, glucosuric, and hyperglycemic. Prevalence of glucosuria in the SW colony reached 60% (n=70) in males 8 weeks to 6 months of age. Despite severe obesity in some females, no females were diabetic. Pathologic findings in affected males included cachexia, dilated gastrointestinal tracts with poor muscular tone, pancreatic islet degeneration and atrophy with compensatory metaplasia and/or neogenesis, bacterial pyelonephritis, membranous glomerulopathy, and late-onset hepatic tumors with macrosteatosis, microsteatosis, and hydropic change in aged males. Serum insulin correlated with blood glucose in a nonlinear pattern, suggestive of islet exhaustion. Circulating leptin levels showed a weak inverse correlation with glucose. Diabetic males were bred with obese colony females to produce 20 male and 20 female offspring. Prevalence of diabetes in male offspring was 80% (16/20) with a median age of onset of 18 weeks. By contrast, no diabetic females were identified, despite being significantly more obese than males. Male predominance is likewise a feature of T2D in humans. To our knowledge, this is the first documentation of hepatocellular carcinoma and islet metaplasia and/or neogenesis in a spontaneous outbred mouse model of T2D. The SW availability and histopathologic features represent a promising new model for the study of T2D.
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PMID:Obesity and non-insulin-dependent diabetes mellitus in Swiss-Webster mice associated with late-onset hepatocellular carcinoma. 1866 86

Insulin resistance or diabetes is associated with limited exercise capacity, which can be caused by the abnormal energy metabolism in skeletal muscle. Oxidative stress is involved in mitochondrial dysfunction in diabetes. We hypothesized that increased oxidative stress could cause mitochondrial dysfunction in skeletal muscle and make contribution to exercise intolerance in diabetes. C57/BL6J mice were fed on normal diet or high fat diet (HFD) for 8 wk to induce obesity with insulin resistance and diabetes. Treadmill tests with expired gas analysis were performed to determine the exercise capacity and whole body oxygen uptake (Vo(2)). The work (vertical distance x body weight) to exhaustion was reduced in the HFD mice by 36%, accompanied by a 16% decrease of peak Vo(2). Mitochondrial ADP-stimulated respiration, electron transport chain complex I and III activities, and mitochondrial content in skeletal muscle were decreased in the HFD mice. Furthermore, superoxide production and NAD(P)H oxidase activity in skeletal muscle were significantly increased in the HFD mice. Intriguingly, the treatment of HFD-fed mice with apocynin [10 mmol/l; an inhibitor of NAD(P)H oxidase activation] improved exercise intolerance and mitochondrial dysfunction in skeletal muscle without affecting glucose metabolism itself. The exercise capacity and mitochondrial function in skeletal muscle were impaired in type 2 diabetes, which might be due to enhanced oxidative stress. Therapies designed to regulate oxidative stress and maintain mitochondrial function could be beneficial to improve the exercise capacity in type 2 diabetes.
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PMID:Oxidative stress in skeletal muscle impairs mitochondrial respiration and limits exercise capacity in type 2 diabetic mice. 1961 6

Diabetes mellitus results from inadequate insulin action, which can be viewed as a consequence of the limited ability to restore beta cells after they are lost as the result of metabolic exhaustion, autoimmune destruction, or surgical insult. Arguably, a uniformly effective therapeutic pathway to address all forms of diabetes would be to reverse the restrictions on beta-cell and islet regeneration. The development from progenitor cells of islets with normal endocrine function does occur in adult humans; it is referred to as islet neogenesis. The induction of islet neogenesis is an important, if not essential, therapeutic approach for curing type 1 diabetes mellitus (T1DM) and could be valuable in the treatment of type 2 diabetes mellitus (T2DM) as well. Islet neogenesis associated protein (INGAP) is the first therapeutic candidate to be identified as the result of a purposeful search for an endogenous molecule with islet neogenic activity. It was found that partial obstruction of the pancreatic duct in hamsters induced islet neogenesis; under this condition, a neogenesis-promoting activity was identified and partially purified from a soluble tissue fraction. A 168-kDa protein product of the cloned gene was found to be responsible for the neogenesis activity. This molecule named INGAP contains an active core sequence of amino acids called INGAP peptide. Results from in vitro, animal, and human studies suggest that INGAP and INGAP peptide are neogenic in at least several vertebrate species, including humans. INGAP has since been found to be a member of the family of Reg proteins, which are found across and in multiple versions within species and are closely associated with embryonic and regenerative processes. Clinical results suggest that INGAP peptide can be a suitable neogenesis therapy, but optimization of the therapy and more data are required to fully access this potential. Understanding of the signaling pathways of INGAP and other related Reg proteins is a promising means of advancing therapeutic development for people with T1DM and T2DM. The quest for the fundamental restorative approach to lost insulin secretion is an enticing target for drug development.
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PMID:Prospects and challenges for islet regeneration as a treatment for diabetes: a review of islet neogenesis associated protein. 1988 12

Type 1 diabetic patients who have endured their condition for prolonged periods are not uncommon, but there are few well-documented cases of type 2 diabetic patients with duration of over fifty years. In the present case study, we analyzed the history of a diabetic patient whose duration was 53 years. Her case was consequently diagnosed not as the common type 2 diabetes, but as the slowly progressive type 1 diabetes (SPIDDM) identified by Japanese medical researchers. The patient, now 73 years old, was first diagnosed with diabetes in 1953 when she was 17 years of age and started insulin injections. In 1962 she was referred to our hospital, and two years later she vaginally delivered a healthy baby (birth weight 3100 g) at the 40(th) week of gestation. She was the first case of a diabetic mother delivering an infant treated at Tokyo Women's Medical College Hospital. Her data shows that her C-peptide responses by meal tolerance test in 1978 was at least partly preserved though it decreased year by year. Her anti-GAD antibody was found to be positive in 2000 and remained so in 2009. This leads us to conclude that the etiology of her SPIDDM was most likely has insulin secretion exhaustion.
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PMID:The over 50 year clinical course of a patient with slowly progressive type 1 diabetes (SPIDDM). 1995 61


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