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)

Fatty liver in obese patients is emerging as one of the most common causes of chronic liver disease. Obese patients are at risk of developing type 2 diabetes mellitus (DM), and aggravating non-alcoholic fatty liver disease (NAFLD), developing into steatohepatitis (NASH) and hepatic fibrosis. Little is known of the possible impact on liver fibrogenesis of diabetes type 2 associated with obesity and NAFLD. Fifty-two morbidly obese patients were evaluated with complete clinical and laboratory medical assessment. Liver biopsy material was fixed in formalin, routinely processed to paraffin blocks, cut into 4-microm sections, stained with HE, PAS, Masson's trichrome and reticulin. Immunohistochemical stains included collagen IV, SMA and laminin. Within the initial group of 52, 25 patients had DM type 2, mean age 45.8 years. Patients with diabetes were older; had higher BMI, liver enzyme tests, glucose, cholesterol, and triglycerides; and lower albumin concentration. Livers of diabetics had significantly more severe steatosis and rich perisinusoidal collagen IV, laminin and SMA accumulation without histologically detectable NASH and irrespective of the degree of steatosis. Obese patients with type 2 DM and insulin resistance develop more severe NAFLD and early sinusoidal fibrosclerosis.
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PMID:Fibrogenesis in fatty liver associated with obesity and diabetes mellitus type 2. 1784 88

Recent studies have added to the evidence that type 1 and type 2 diabetes are associated with increased risk of hip fracture and other fractures. More frequent falls probably account for some of this increased risk, but reduced bone strength may also play a role. Although type 1 diabetes is associated with lower bone density, those with type 2 diabetes usually have elevated bone density. Yet for both types of diabetes, bone appears to be more fragile for a given density. Diabetes can affect bone through multiple pathways-some with contradictory effects-including obesity, insulin levels, hyperglycemia, and advanced glycation end products in collagen. Treatment with thiazolidinediones may increase fracture risk, at least in older women. Clinicians need to be aware of the increased fracture risk associated with diabetes. Additional research is needed to clarify the mechanisms underlying this increased risk and the best approaches to fracture prevention.
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PMID:Diabetes, fracture, and bone fragility. 1792 91

Pulmonary fibrosis is characterized by the accumulation of fibroblasts, myofibroblasts, collagen, and other extracellular matrix proteins in the interstitium of the lung, with subsequent scarring and destruction of the alveolar capillary interface. In some cases, pulmonary fibrosis is preceded by lung inflammation and can be treated with anti-inflammatory therapies. However, idiopathic pulmonary fibrosis is characterized by a relative paucity of underlying inflammation and currently has no effective treatment. There is increasing evidence that the transcription factor peroxisome proliferator-activated receptor (PPAR) gamma plays an important role in controlling cell differentiation and that PPARgamma ligands can modify inflammatory and fibrotic responses. Peroxisome proliferator-activated receptor gamma ligands, including the thiazolidinedione class of antidiabetic drugs and novel triterpenoid compounds derived from oleanic acid, inhibit TGF-beta-stimulated profibrotic differentiation of lung fibroblasts in vitro and reduce lung scarring in animal models of fibrosis. The mechanism of action of the PPARgamma ligands is under investigation but seems to involve both PPARgamma-dependent and PPARgamma-independent pathways. These in vitro and in vivo data highlight the potentially exciting role of PPARgamma ligands as novel therapies for fibrosis of the lung and other organ systems prone to scarring. Many of the synthetic PPARgamma ligands are orally active, and several are currently available and Food Drug Administration approved for use in therapy of type 2 diabetes. Further research is urgently required to more clearly elucidate the mechanism of action of these drugs and to develop more potent antifibrotic agents for patients with scarring diseases for whom there are currently few effective therapies.
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PMID:The antifibrogenic potential of PPARgamma ligands in pulmonary fibrosis. 1831 37

A total of 105 male and 60 female patients were screened in the respiratory medicine outpatients' department, Institute of Postgraduate Medical Education & Research, Kolkata between December, 2002 and January, 2005. Chronic obstructive pulmonary disease patients were diagnosed on the basis of history and clinical examination while patients with body mass index > or =25 and otherwise disease-free were grouped as overweights. Patients suffering from other diseases like systemic hypertension, etc, were referred from other departments after proper evaluation. The patients and controls (n=10) each for male and female groups were subjected to spirometry using computerised electronic spirometer while exercise tolerance was evaluated by modified Harvard step test. Thirty-nine male and 21 female patients were diagnosed and grouped in chronic obstructive pulmonary disease group. Both purely obstructive [forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC)% pred<70 and reduced FEV1% pred] and mixed (both obstructive and restrictive pattern ie, FEV1/FVC% pred normal or supernormal, FVC% pred <80 indicating restrictive pattern and forced expiratory flow between 25% and 75% of the vital capacity (FEF(25-75)) pred or peak expiratory flow rate (PEFR)% pred <70 indicating early small airway obstruction pattern were seen in both sexes. Although the exercise tolerance values were non-significant in both sexes in chronic obstructive pulmonary disease obstructive pattern group, in mixed pattern group it was seen significant reduction compared to control. Hypertensives (21 males and 7 females) showed obstructive spirometric pattern. Exercise tolerance values were significantly reduced compared to controls. Male overweights (n=13) showed restrictive pattern while female overweights (n=8) showed obstructive pattern in spirometry. Exercise tolerance values were non-significant compared to control in both the groups. In ischaemic heart disease patients (n=6) FEV1%pred showed significant reduction in spirometry. In patients suffering from type 2 diabetes mellitus (n=4), post-tuberculous group (n=7), hypothyroid (n=6), collagen vascular disease group (n=6) showed restrictive spirometric pattern and the above groups including IHD patients showed significant reduction in exercise tolerance values. Some authors have stated that mixed ventilatory defect is characterised by low FEV1/FVC% pred in spirometry and low lung volumes where the lung volumes have to be ascertained by other methods but in the present investigation it was observed that mixed ventilatory defect can be estimated by spirometry; PEFR and/or FEF(25-75%). pred <70% whereas FEV1/FVC% pred is normal or supernormal. This finding is completely new one to predict mixed ventilatory defect.
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PMID:A hospital-based study on pulmonary function tests and exercise tolerance in patients of chronic obstructive pulmonary disease and other diseases. 1838 52

Succinic acid monoethyl ester (EMS) was recently proposed as an insulinotropic agent for the treatment of type 2 diabetes. The aim of the study was to investigate the effect of EMS and metformin administration on tail collagen content and its characteristics in streptozotocin-nicotinamide-induced type 2 diabetic rats. EMS was administered intraperitoneally for 30 days to normal and diabetic rats. In the diabetic rats, a significant increase in the levels of glucose, glycated hemoglobin, hydroxyproline, collagen content, extent glycation, fluorescence, neutral salt, acid and pepsin soluble collagen content was absorbed with a significant decrease in the level of insulin, hemoglobin in streptozotocin-nicotinamide diabetic rats. Moreover, a daily administration of nonglucidic nutrient EMS and metformin significantly decreased the levels of glucose, glycated hemoglobin, hydroxyproline, collagen content, extent glycation, fluorescence, neutral salt, acid and pepsin soluble collagen content, whereas it increased insulin, hemoglobin levels in diabetic rats. The positive influence of nonglucidic nutrient on both collagen content and its properties suggests a potential mechanism for the ability of EMS to delay diabetic complications.
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PMID:Effect of succinic acid monoethyl ester on hemoglobin glycation and tail tendon collagen properties in type 2 diabetic rats. 1848 47

The effects of therapy with aspirin 300 mg/day and with combined aspirin 100 mg/day plus clopidogrel 75 mg/day on platelet function were compared in patients with diabetes mellitus and coronary artery disease and impaired antiplatelet responses to aspirin 100 mg/day. The study population consisted of 151 outpatients with type II diabetes mellitus and coronary artery disease who were taking aspirin 100 mg/day. Of the 151 patients, a subgroup of subjects with impaired aspirin response were selected on the basis of the results of platelet aggregometry. Nonresponsiveness to aspirin was defined as mean aggregation > or =69% with 3 micromol/L adenosine diphosphate and mean aggregation > or =70% with 2 micromol/L collagen. Aspirin semiresponders were defined as meeting 1 but not both of these criteria. Nonresponders and semiresponders were randomized equally to aspirin 300 mg/day and aspirin 100 mg/day plus clopidogrel 75 mg/day, and aggregation tests were repeated after 2 weeks. Sixty of the 151 patients with diabetes (40%) were found to respond to aspirin inadequately. Platelet aggregation induced by adenosine diphosphate and collagen decreased significantly after aspirin 300 mg/day or combined therapy. Combined treatment was found to have a stronger inhibitory effect on platelet aggregation induced by adenosine diphosphate than aspirin 300 mg/day (p = 0.002). Impaired aspirin response was resolved by increasing the aspirin dose or adding clopidogrel to aspirin (p <0.0001 for each). However, desired platelet inhibition was achieved in significantly more patients by combined treatment than by aspirin 300 mg/day (p <0.05). In conclusion, aspirin 100 mg/day does not inhibit platelet function adequately in a significant number of patients with diabetes mellitus and coronary artery disease. Increasing the aspirin dose to 300 mg/day or adding clopidogrel to aspirin can provide adequate platelet inhibition in a significant number of those patients with impaired responses to low-dose aspirin.
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PMID:Comparison of increased aspirin dose versus combined aspirin plus clopidogrel therapy in patients with diabetes mellitus and coronary heart disease and impaired antiplatelet response to low-dose aspirin. 1867 94

It is unclear whether metformin, one of the anti-hyperglycemic agents commonly used for type 2 diabetes, could affect bone formation through activation of AMP-activated protein kinase (AMPK). In order to clarify this issue, we investigated the effects of metformin on the differentiation and mineralization of osteoblastic MC3T3-E1 cells as well as intracellular signal transduction. Metformin (50 microM) significantly increased collagen-I and osteocalcin mRNA expression, stimulated alkaline phosphatase activity, and enhanced cell mineralization. Moreover, metformin significantly activated AMPK in dose- and time-dependent manners, and induced endothelial nitric oxide synthase (eNOS) and bone morphogenetic protein-2 (BMP-2) expressions. Supplementation of Ara-A (0.1mM), a specific AMPK inhibitor, significantly reversed the metformin-induced eNOS and BMP-2 expressions. Our findings suggest that metformin can induce the differentiation and mineralization of osteoblasts via activation of the AMPK signaling pathway, and that this drug might be beneficial for not only diabetes but also osteoporosis by promoting bone formation.
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PMID:Metformin enhances the differentiation and mineralization of osteoblastic MC3T3-E1 cells via AMP kinase activation as well as eNOS and BMP-2 expression. 1872 96

Type 2 diabetes and dyslipidemia oftentimes present in combination. However, the relative roles of diabetes and diet-induced dyslipidemia in mediating changes in vascular structure, mechanics, and function are poorly understood. Our hypothesis was that addition of a high-fat diet would exacerbate small artery remodeling, compliance, and vascular dysfunction in type 2 diabetes. Vascular remodeling indices [media/lumen (M/L) ratio, collagen abundance and turnover, and matrix metalloproteinase dynamics], mechanical properties (vessel stiffness), and reactivity to pressure and vasoactive factors were measured in third-order mesenteric arteries in control Wistar and type 2 diabetic Goto-Kakizaki (GK) rats fed either a regular or high-fat diet. M/L ratios, total collagen, and myogenic tone were increased in diabetes. Addition of the high-fat diet altered collagen patterns (mature versus new collagen) in favor of matrix accumulation. Addition of a high-fat diet caused increased constriction to endothelin-1 (0.1-100 nM), showed impaired vasorelaxation to both acetylcholine (0.1 nM-1 microM) and sodium nitroprusside (0.1 nM-1 microM), and increased cardiovascular risk factors in diabetes. These results suggest that moderate elevations in blood glucose, as seen in our lean GK model of type 2 diabetes, promote resistance artery remodeling resulting in increased medial thickness, whereas addition of a high-fat diet contributes to diabetic vascular disease predominantly by impairing vascular reactivity in the time frame used for this study. Although differential in their vascular effects, both hyperglycemia and diet-induced dyslipidemia need to be targeted for effective prevention and treatment of diabetic vascular disease.
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PMID:Differential effects of diet-induced dyslipidemia and hyperglycemia on mesenteric resistance artery structure and function in type 2 diabetes. 1894 Nov 21

Although patients with type 2 diabetes show no bone mineral density (BMD) reduction, fracture risks are known to increase. It is unclear why the patients have an increased risk of fracture despite sufficient BMD. We investigated the relationships of body mass index (BMI), HbA(1c), and urinary C-peptide (uC-peptide) versus BMD, bone metabolic markers, serum adiponectin, and prevalent vertebral fracture (VF). A total of 163 Japanese type 2 diabetic men were consecutively recruited, and radiographic and biochemical data were collected. BMI was positively correlated with BMD at the whole body, lumbar spine, and femoral neck (P < 0.05) and negatively correlated with osteocalcin and urinary N-terminal cross-linked telopeptide of type-I collagen (uNTX) (P < 0.01). HbA(1c) was negatively correlated with osteocalcin (P < 0.01) but not BMD at any site. Subjects were classified into four groups based on BMI and HbA(1c) (group LL BMI < 24 and HbA(1c) < 9, group LH BMI < 24 and HbA(1c) > or = 9, group HL BMI > or = 24 and HbA(1c) < 9, group HH BMI > or = 24 and HbA(1c) > or = 9). Serum adiponectin, osteocalcin, and uNTX were lower and the incidence of VF was higher despite sufficient BMD in the HH group. Multivariate logistic regression analysis adjusted for age, duration of diabetes, uC-peptide, and estimated glomerular filtration rate showed that the HH group was associated with the presence of a VF and multiple VFs (odds ratio [OR] = 3.056, 95% confidence interval [CI] 1.031-9.056, P = 0.0439, and OR = 5.415, 95% CI 1.126-26.040, P = 0.0350, respectively). Combination of obesity with hyperglycemia was a risk factor for VF despite sufficient BMD in diabetic men.
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PMID:Combination of obesity with hyperglycemia is a risk factor for the presence of vertebral fractures in type 2 diabetic men. 1894 27

Ultrastructural observations reveal a continuous interstitial matrix connection between the endocrine and exocrine pancreas, which is lost due to fibrosis in rodent models and humans with type 2 diabetes mellitus (T2DM). Widening of the islet-exocrine interface appears to result in loss of desmosomes and adherens junctions between islet and acinar cells and is associated with hypercellularity consisting of pericytes and inflammatory cells in T2DM pancreatic tissue. Organized fibrillar collagen was closely associated with pericytes, which are known to differentiate into myofibroblasts-pancreatic stellate cells. Of importance, some pericyte cellular processes traverse both the connecting islet-exocrine interface and the endoacinar interstitium of the exocrine pancreas. Loss of cellular paracrine communication and extracellular matrix remodeling fibrosis in young animal models and humans may result in a dysfunctional insulino-acinar-ductal-incretin gut hormone axis, resulting in pancreatic insufficiency and glucagon-like peptide deficiency, which are known to exist in prediabetes and overt T2DM in humans.
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PMID:Attenuation of endocrine-exocrine pancreatic communication in type 2 diabetes: pancreatic extracellular matrix ultrastructural abnormalities. 1904 May 93


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