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)

Neutrophil bactericidal activity was assessed in patients with type 1 (n = 45) and Type 2 diabetes mellitus (n = 68) and non-diabetic control subjects (n = 40) by measurement of whole blood chemiluminescence. Though chemiluminescence values tended to be highest in the non-diabetic subjects these differences were not statistically significant (mean +/- SD) (2.73 +/- 1.65 mV (controls), 2.33 +/- 1.41 mV (Type 1 diabetes) and 2.38 +/- 1.12 mv (Type 2 diabetes), F = 1.12, p = 0.33). Significant negative correlations were evident, however, in patients with both Type 1 and Type 2 diabetes between chemiluminescence and glycated haemoglobin (rs = -0.35, p = 0.005 (Type 1), rs = -0.45, p = 0.002 (Type 2), fructosamine (rs = -0.36, p = 0.003 (Type 1), r = -0.42, p = 0.004 (Type 2)), and random blood glucose (rs 0 -0.25, p = 0.04 (Type 1), rs = -0.48, p = 0.001 (Type 2)). Changes in whole blood chemiluminescence in a further group of 10 patients with Type 2 diabetes mellitus commenced on insulin therapy were followed for 21 days. Serum fructosamine concentrations fell significantly over this time (524 +/- 58 mumol l-1 to 405 +/- 47 mumol l-1, p < 0.001), however, although chemiluminescence values tended to rise these changes were not statistically significant (1.01 +/- 0.38 mV to 1.60 +/- 0.91 mV, S = 4.24, df = 5, p = 0.52). These results suggested that impaired neutrophil bactericidal function is associated with poor blood glucose control. While it is likely that neutrophil bactericidal function will improve as blood glucose control improves, further studies are required both to confirm this and to demonstrate a reduction in the incidence of clinical bacterial infection.
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PMID:Neutrophil bactericidal function in diabetes mellitus: evidence for association with blood glucose control. 884 84

To evaluate whether granulocyte-colony stimulating factor (G-CSF) improves an impaired production of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients, we studied the effect of G-CSF on myeloperoxidase (MPO) activity and chemiluminescence amplified by a Cypridina luciferin analog (CLA-DCL), which is dependent on O2 generation, and luminol (L-DCL), which is dependent on OCl(-) generation, in response to formyl-methonyl-leucyl-phenylalanine. Both CLA-DCL and L-DCL by neutrophils from the diabetic group (n = 15, HbA(1c) >10%) were significantly decreased (26 and 37%, respectively: P < 0.01) compared with the age-matched normal control group (n = 15), and L-DCL was more sensitive to this inhibition than CLA-DCL (P < 0.05). In both control and diabetic neutrophils, G-CSF significantly enhanced both CLA-DCL (175% in control and 156% in diabetic) and L-DCL (283% in control and 346% in diabetic). In diabetic neutrophils, the enhancing effect of G-CSF on L-DCL was more sensitive than on CLA-DCL (P < 0.001). There was a positive correlation between HbA(1c) and the enhancing effect of G-CSF on L-DCL in diabetic patients (P < 0.05), but not on CLA-DCL. MPO activity was also decreased in the diabetic group (63%, P < 0.05), and G-CSF improved this impaired MPO activity (184%, P < 0.01). Furthermore, there was a positive correlation between HbA(1c) and the improving effect of G-CSF on MPO activity (P < 0.05). Because bacterial infection still accounts for an important cause of morbidity and mortality in diabetic patients, these data suggest that G-CSF may be useful as a drug to prevent the aggravation of bacterial infection by improving neutrophil function, especially through H2O2-MPO-OCl(-) mechanism, in poorly controlled diabetic patients.
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PMID:Effect of granulocyte-colony stimulating factor on generation of oxygen-derived free radicals and myeloperoxidase activity in neutrophils from poorly controlled NIDDM patients. 897 Oct 93

A reasonable interpretation of the present evidence indicates that diabetes, when a complication of periodontitis, acts as a modifying and aggravating factor in the severity of periodontal infection. Diabetics with periodontitis who were young and poorly controlled, those who were long-duration diabetics, especially those over 30 years old, demonstrated more attachment loss, bone loss, and deeper probing pocket depths than their nondiabetic controls. It seems that the earlier the onset of diabetes and the longer the duration, especially without consistent control, the more susceptible the individual will be to periodontal disease. Consequently, once a diabetic contracts periodontal disease, it is usually more destructive. Although plaque scores of diabetics may be comparable to or even less than those of nondiabetics, diabetics often exhibit higher gingival index scores. The elevation of this particular clinical parameter is indicative of the microangiopathy associated with diabetes. Diabetic microangiopathy contributes to compromised delivery of nutrients to surrounding tissues and poor elimination of metabolic waste products. The complications associated with diabetes such as macroangiopathy, microangiopathy (i.e., retinopathy), ketoacidosis, and hyperglycemia result in impaired wound healing, immunosuppression, and susceptibility to bacterial infection. Individuals ages 30 to 40 suffering from diabetic retinopathy had significantly more gingival inflammation than controls or diabetics without complications. Collagen metabolism is defective in diabetics and is one component underlying delayed wound healing. Animal studies have been instrumental in elucidating the details of delayed wound healing. Hyperglycemia was associated with increased collagenase and protease activity in the gingiva of rats. Vascular wound healing in rats, particularly new re-endothelialization across vascular anastomoses, was significantly impaired. Diabetic abnormalities in immune response include impaired neutrophil chemotaxis, phagocytosis, and adhesion. Decreased neutrophilic chemotactic response seems to be attributable to protein factors in diabetic serum that competitively bind neutrophil receptors, thereby preventing complement-mediated phagocytosis. Because diabetics are not able to eliminate circulating immune complexes (CIC) effectively, serum CIC levels are elevated. There are microbiological differences in the characteristic flora of NIDDM patients and IDDM patients with periodontitis. These differences are not associated with diabetic impaired immune response. Ultimately, bacterial plaque is the primary etiology of periodontal diseases. Evidently, the host's response to bacterial plaque and ability to heal following surgery is altered by diabetic disease. Therefore, a thorough history regarding onset of diabetes, duration, and diabetic control would prove useful in the clinical management of diabetics presenting for treatment of periodontal disease.
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PMID:Periodontal disease, diabetes, and immune response: a review of current concepts. 947 64

To explore the possibility that b type recombinant human granulocyte-colony stimulating factor (rhG-CSF) is a useful drug to prevent the morbidity and mortality caused by infections in diabetic patients, we have studied effects of rhG-CSF on chemiluminescence amplified by a luciferin analog (CLA-DCL) and luminol (L-DCL) in response to formyl-Methionyl-Leucyl-Phenylalanine (fMLP) in neutrophils from patients with non insulin dependent diabetes mellitus (NIDDM) (diabetic neutrophils) and healthy subjects (control neutrophils). Both CLA-DCL and L-DCL in diabetic neutrophils were significantly reduced, and L-DCL was more sensitive to this suppression than CLA-DCL. RhG-CSF did not change the basal chemiluminescence in control and diabetic neutrophils, but it primed CLA-DCL and L-DCL. Although, in diabetic neutrophils, the priming effect of rhG-GSF on both CLA-DCL and L-DCL was less compared to that in control neutrophils, L-DCL was more sensitive to this priming effect than CLA-DCL. Because bacterial infection is still an important cause of the morbidity and mortality in diabetic patients, these data suggest that rhG-CSF is a useful drug to prevent the aggravation of bacterial infection in patients with NIDDM.
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PMID:Improvement of an impaired chemiluminescence response to formyl-methionyl-leucyl-phenylalanine in neutrophils from patients with non insulin dependent diabetes mellitus by recombinant human granulocyte-colony stimulating factor. 1058 72

The effect of hyperglycemia upon susceptibility to bacterial infection in diabetes mellitus is incompletely elucidated. The present experiments assessed the effect of hyperglycemia upon neutrophil-mediated phagocytosis of type III group B Streptococcus (GBS). Type III GBS was chosen for study because the incidence of invasive GBS disease is substantially increased in type 2 diabetic compared with nondiabetic subjects. The hypothesis tested was that severe hyperglycemia would alter neutrophil metabolism by diverting NADPH from superoxide production into the aldose reductase-dependent polyol pathway that converts glucose into sorbitol and thus would impair opsonophagocytosis (OP) of type III GBS. Neutrophils from 10 adults with type 2 diabetes had no intrinsic phagocytic defect under baseline glycemic conditions. After equilibration in 60 or 120 mM glucose or in 60 mM choline chloride, OP activity was reduced significantly (P < or = 0.03). Neutrophil superoxide production correlated with glucose concentration and also was significantly reduced during hyperglycemia (P < 0.05). Addition of III GBS capsular polysaccharide-specific IgG in a sufficient concentration supported efficient OP, even during hyperglycemia. Alrestatin, an aldose reductase inhibitor, increased superoxide production and significantly improved OP of type III GBS (P = 0.03). Thus, diversion of NADPH into the polyol pathway is one mechanism by which OP of GBS III is impaired during hyperglycemia, and this effect is mitigated when levels of capsular polysaccharide-specific IgG are sufficient.
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PMID:Impairment of type III group B Streptococcus-stimulated superoxide production and opsonophagocytosis by neutrophils in diabetes. 1146 Nov 93

The glucagon-like peptides (GLP-1 and GLP-2) are proglucagon-derived peptides cosecreted from gut endocrine cells in response to nutrient ingestion. GLP-1 acts as an incretin to lower blood glucose via stimulation of insulin secretion from islet beta cells. GLP-1 also exerts actions independent of insulin secretion, including inhibition of gastric emptying and acid secretion, reduction in food ingestion and glucagon secretion, and stimulation of beta-cell proliferation. Administration of GLP-1 lowers blood glucose and reduces food intake in human subjects with type 2 diabetes. GLP-2 promotes nutrient absorption via expansion of the mucosal epithelium by stimulation of crypt cell proliferation and inhibition of apoptosis in the small intestine. GLP-2 also reduces epithelial permeability, and decreases meal-stimulated gastric acid secretion and gastrointestinal motility. Administration of GLP-2 in the setting of experimental intestinal injury is associated with reduced epithelial damage, decreased bacterial infection, and decreased mortality or gut injury in rodents with chemically induced enteritis, vascular-ischemia reperfusion injury, and dextran sulfate-induced colitis. GLP-2 also attenuates chemotherapy-induced mucositis via inhibition of drug-induced apoptosis in the small and large bowel. GLP-2 improves intestinal adaptation and nutrient absorption in rats after major small bowel resection, and in humans with short bowel syndrome. The actions of GLP-2 are mediated by a distinct GLP-2 receptor expressed on subsets of enteric nerves and enteroendocrine cells in the stomach and small and large intestine. The beneficial actions of GLP-1 and GLP-2 in preclinical and clinical studies of diabetes and intestinal disease, respectively, has fostered interest in the potential therapeutic use of these gut peptides. Nevertheless, the actions of the glucagon-like peptides are limited in duration by enzymatic inactivation via cleavage at the N-terminal penultimate alanine by dipeptidyl peptidase IV (DP IV). Hence, inhibitors of DP IV activity, or DP IV-resistant glucagon-like peptide analogues, may be alternative therapeutic approaches for treatment of human diseases.
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PMID:Biological actions and therapeutic potential of the glucagon-like peptides. 1183 66

Periodontal disease is the result of a complex interplay of bacterial infection and host responses, and is often modified by various systemic diseases such as diabetes mellitus. Such diseases are capable of affecting the periodontium and/or the treatment of periodontal disease. However, recent research has changed our concept of how periodontal disease should be treated. Here we present several concerns directed towards the periodontal therapy of patients with diabetes mellitus based on our studies. When treating periodontitis patients who have diabetes mellitus it is important to consider the type of diabetes. Patients with non-insulin dependent diabetes mellitus can be further classified according to the degree of insulin resistance, since recent epidemiological studies have suggested that successful anti-microbial therapy might result in improved insulin resistance in highly insulin resistant patients. Because the major contributing factor for insulin resistance is currently considered to be the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), and because periodontal surgery may cause transient bacteremia which may up-regulate the serum TNF-alpha level, which in turn suppresses insulin action, patients should be strictly treated non-surgically and their serum TNF-alpha levels should be periodically monitored. On the other hand, diabetic patients positive for serum anti-glutamate decarboxylase auto-antibody should be examined for the source of this antibody, since 1) gingival and periodontal ligament fibroblasts were found to express glutamate decarboxylase, and 2) some otherwise healthy periodontitis patients develop anti-glutamate decarboxylase antibody. Thus, chronic periodontitis may influence the level of this antibody which is widely used as a predictive marker for slowly progressive insulin dependent diabetes mellitus. Not only is periodontal disease thereby affected by systemic diseases, but carefully managed periodontal therapy may also have a positive effect on the general health of patients with systemic diseases.
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PMID:Negative effects of chronic inflammatory periodontal disease on diabetes mellitus. 1266 61

A 52-year-old man was given a diagnosis of type 2 diabetes mellitus at age 39. At age 46, he stopped taking medication. Two weeks after burning his legs at low temperature, he fell, using his right arm to protect his legs. The next day, he complained of pain and slight swelling from his right shoulder to his anterior chest and came to our hospital. At that time, a plain computed tomography scan suggested gasogenic bacterial infection and we discussed the indications for debridment. Although his widespread inflammation required extensive treatment including thoracostomy, we abandoned surgical treatment and administered several antibiotics in appropriate combination because of his severe condition. After admission, the mass grew rapidly and it was diagnosed as necrotizing fasciitis based on percutaneous needle biopsy and clinical findings. Although both inflammatory reactions and mass size tended to improve, he had repeated recurrence of pain and swelling in his right anterior chest. When he had a second recurrence, he received additional short-term steroid therapy. Afterwards he had no further recurrence. In this case, early clinical diagnosis, using broad-spectrum antibiotics prior to definite diagnosis, and additional short-term steroid therapy at the time of the recurrence were effective.
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PMID:[A case of successful medical treatment for necrotizing fasciitis of the chest wall with diabetic nephropathy]. 1580 Dec 85

TNFalpha is a proinflammatory cytokine secreted by macrophages in response to bacterial infection. Recently new evidence has emerged suggesting that stressed or injured myocytes produce TNFalpha that then acts as an autocrine and/or paracrine mediator. TNFalpha receptors types 1 and 2 are present in skeletal muscle cells, and muscle cells can secrete, in addition to TNFalpha, other cytokines such as IL-1beta or IL-6. Furthermore, the plasma concentration of TNFalpha is elevated in insulin-resistant states associated with obesity and type 2 diabetes. Here we show that TNFalpha increased the amount of glucose transporter (GLUT)-4 at the plasma membrane and also glucose uptake in the L6 muscle cell line stably expressing GLUT4 tagged with the c-myc epitope. Regardless of the state of differentiation of the L6 cells, TNFalpha did not affect the rate of proliferation or of apoptosis. The stimulatory effects of TNFalpha on cell surface GLUT4 and glucose uptake were blocked by nuclear factor-kappaB and p38MAPK pathway specific inhibitors (Bay 11-7082 and SB220025), and these two pathways were stimulated by TNFalpha. Furthermore, although TNFalpha increased IL-6 mRNA and protein expression, IL-6 did not mediate the effects of TNFalpha on cell surface GLUT4 levels, which also did not require de novo protein synthesis. The results indicate that TNFalpha can stimulate glucose uptake in L6 muscle cells by inducing GLUT4 translocation to the plasma membrane, possibly through activation of the nuclear factor-kappaB and p38MAPK signaling pathways and independently of the production of IL-6.
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PMID:The proinflammatory cytokine tumor necrosis factor-alpha increases the amount of glucose transporter-4 at the surface of muscle cells independently of changes in interleukin-6. 1816 26

The prevalence rate and spectrum of fungi infecting deep tissues of diabetic lower-limb wounds (DLWs) have not been previously studied. Five hundred eighteen (382 male and 136 female) consecutive patients with type 2 diabetes hospitalized due to infected lower-limb wounds were enlisted in this study. Deep tissue (approximately 0.5- x 0.5-cm size) taken perioperatively from the wound bed was cultured for fungi. Fungi was found in 27.2% (141/518) of the study population. Candida parapsilosis (25.5%), Candida tropicalis (22.7%), Trichosporon asahii (12.8%), Candida albicans (10.6%), and Aspergillus species (5.0%) were the most predominant fungal isolates. Of the fungal isolates, 17.7% were resistant to itraconazole, 6.9% were resistant to amphotericin B, 6.9% were resistant to voriconazole, 3.9% were resistant to fluconazole, and 1.5% were resistant to flucytosine. Of the population, 79.7% (413/518) had bacterial infection in deep tissue. The predominant isolates were Enterococcus faecalis (14.1%), Staphylococcus aureus (12.2%), and Pseudomonas aeruginosa (10.8%). Mixed fungal and bacterial infections were seen in 21.4% of patients, while 5.8% had only fungal infection and 58.3% had only bacterial infections. Another 14.5% had neither bacteria nor fungi in the deep tissue. Patients with higher glycosylated hemoglobin levels had significantly more fungal infections. Our study reveals that deep-seated fungal infections are high in DLWs. In the context of delayed wound healing and amputation rates due to DLWs, it is important to study the pathogenicity of fungi in deep tissues of DLWs and their possible contribution to delayed wound healing. The role of antifungal agents in wound management needs to be evaluated further.
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PMID:Spectrum and prevalence of fungi infecting deep tissues of lower-limb wounds in patients with type 2 diabetes. 2041 Mar 45


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