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)

Thiazolidinediones, synthetic ligands for the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) receptor, are insulin-sensitizing drugs licensed for use in selected patients with type 2 diabetes mellitus. The potential therapeutic applications of the thiazolidinediones extend to other clinical specialties such as dermatology. Rosiglitazone and pioglitazone are being evaluated for the treatment of psoriasis. Type 2 diabetes and psoriasis may coexist prompting speculation that dual benefits might accrue for patients with both conditions. A recent open pilot study suggests that oral pioglitazone may be beneficial for moderate chronic plaque psoriasis. However, changes in antidiabetic medication must be made in the knowledge of the cautions and contraindications to oral agents as well as the impact on metabolic control. Further studies are required before the use of thiazolidinediones for psoriasis can be advocated.
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PMID:Type 2 diabetes, psoriasis and thiazolidinediones. 1649 55

A 27-year-old white woman was referred for consultation with regard to the presence of extensive multiple keratotic lesions. She began to develop these lesions at the age of 9 years, with healing of the lesions resulting in scar formation. A biopsy was performed at the age of 16 years, but the patient was unsure of the results. Since then, she had not had any treatment or biopsies, and stated that she had not suffered from any health problems during the intervening period. She was most concerned about the tumors on her heels and soles, which caused difficulty with ambulation. The family history was negative for skin diseases, including melanoma, nonmelanoma skin cancer, psoriasis, and eczema, and positive for Type II diabetes mellitus. A relative reported that the patient's grandfather had similar lesions, but the patient's parents and siblings were healthy. She was married and had one child, a 9-year-old daughter. Her child had no skin lesions. The patient's only medication was Ortho-Tricyclene birth control pills. She had no known drug allergies. Physical examination revealed the presence of multiple lesions on her body (Fig. 1). Her left superior helix contained a well-demarcated, dome-shaped nodule with a rolled, mildly erythematous border with a central hyperkeratotic plug. A similar lesion was present in the scaphoid fossa of the left ear and smaller lesions were scattered on her face. Numerous lesions were present on the arms and legs bilaterally, with the majority of lesions being located on the anterior lower legs. There were also lesions present on the palms and soles. The lesions ranged in size from 5 mm to 3 cm, the largest being a verrucous exophytic nodule on the anterior aspect of her left leg. Overall, there appeared to be two distinct types of lesion. One type appeared round, oval, and symmetric with a central keratotic plug, similar to that on the ear. The other type was larger, more exophytic, and verrucous, including the lesions on the volar surfaces. Also present were numerous, irregularly shaped atrophic scars where previous lesions had healed spontaneously. There were no oral lesions or lesions on her fingernails or toenails, and her teeth and hair were normal. A biopsy was obtained from an early lesion on the right dorsal forearm. Histology revealed an exo-/endophytic growth having a central crater containing keratinous material (Fig. 2). The crater was surrounded by markedly hyperplastic squamous epithelium with large squamous epithelial cells having abundant glassy cytoplasm. Some cells were dyskeratotic. Within the dermis was a dense, chiefly mononuclear inflammatory infiltrate. A buttress of epidermis surrounded the crater. The clinical and pathologic data were consistent with keratoacanthomas. Initial laboratory screenings revealed elevated triglycerides and total cholesterol, 537 mg/dL (normal, < 150 mg/dL) and 225 mg/dL (normal, < 200 mg/dL), respectively, with all other laboratory results within normal limits. In anticipation of starting oral retinoid therapy for her multiple keratoacanthomas, she was referred to her primary care physician for control of hyperlipidemia. After her lipids had been controlled, she was placed on isotretinoin (Accutane) 40 mg/day. There was some interval improvement with regression of some lesions leaving atrophic scars. She was also started on topical application of tazarotene (Tazorac) for all nonresolving lesions. Possible side-effects from the isotretinoin occurred, including dry mouth and eyes. After 8 months of isotretinoin, the patient was switched to acitretin (Soriatane) 25 mg to determine whether it might have a more beneficial effect on the resistant lesions. Many of the larger lesions regressed leaving atrophic scars. The dose of acitretin was subsequently increased to 35 mg because the lesions on her heel and the ball of her foot persisted. Almost all of the lesions resolved, except those on her feet, which are slowly regressing. Currently, the patient is on a regimen of acitretin 25 mg once a day with tazarotene 0.1% gel applied directly to the few residual keratoacanthomas on her feet, which are slowly improving.
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PMID:Multiple keratoacanthomas in a young woman: report of a case emphasizing medical management and a review of the spectrum of multiple keratoacanthomas. 1791 Jul 28

Thiazolidinediones, also known as glitazones, represent a relatively new class of medication used for glycemic control in patients with type II diabetes mellitus. These drugs interact with the peroxisome proliferator-activated receptor gamma, a member of the nuclear receptor superfamily, which in turn heterodimerizes with retinoid X receptors to stimulate gene transcription. At a physiologic level, glitazones stimulate adipocyte differentiation, enhance insulin-sensitive glucose uptake by muscle and fat cells, suppress angiogenesis, inhibit tumor cell growth, and normalize keratinocyte differentiation. They have also demonstrated the capacity to diminish inflammatory cytokine production, most notably, that of tumor necrosis factor alpha. Patients with such disparate conditions as psoriasis, hirsutism, melanoma, angiosarcoma, lipodystrophy, and necrobiosis lipoidica have benefited from the administration of thiazolidinediones. Clinicians should become familiar with glitazones as they are experiencing a burgeoning use among patients with non-insulin-dependent diabetes mellitus and have demonstrated clinical efficacy in treating certain skin conditions.
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PMID:Thiazolidinediones in dermatology. 1755 May 51

Tumor necrosis factor-alpha (TNF-alpha) inhibitors have been used in the treatment of psoriasis, which is associated with the insulin resistance syndrome. The purpose of this study was to determine the effect of etanercept, a TNF-alpha inhibitor, on insulin secretion and insulin sensitivity in psoriatic patients with high risk factors to develop type 2 diabetes mellitus. Randomized double blind clinical trial with 2 weeks of follow-up. The allocation was done by simple randomization. The investigation was performed in 12 psoriatic patients with indication of systemic treatment and 2 or more risk factors for type 2 diabetes mellitus. Patients with infections, topical corticosteroids or salicylic acid ointments for 6 weeks before the study, diabetes, acromegaly, cancer and other systemic diseases were excluded. All subjects gave written informed consent to participate in the study and the protocol was approved by the hospital-based Ethical Committee. Etanercept was injected in a subcutaneous dose of 25 mg in 1 ml twice by week for 2 weeks or 1 ml of saline solution as placebo. Insulin secretion was estimated with the formula for the homeostasis model analysis beta-cell function index and insulin sensitivity was assessed using the euglycemic-hyperinsulinemic clamp technique. There was no significant difference in insulin secretion and insulin sensitivity with etanercept. Fasting serum insulin levels were decreased in the etanercept group (146 +/- 117-111 +/- 87 pmol/l, P = 0.04). Etanercept did not modify insulin secretion and insulin sensitivity in psoriatic patients with risk factors for type 2 diabetes mellitus.
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PMID:Effect of etanercept on insulin secretion and insulin sensitivity in a randomized trial with psoriatic patients at risk for developing type 2 diabetes mellitus. 1772 11

We report a patient with type 2 diabetes mellitus who, while treated with the antitumor necrosis factor-alpha blocking agent etanercept for severe plaque psoriasis, experienced persistent hypoglycemia requiring the lowering and eventual elimination of his previous insulin regimen. After 20 months of therapy on etanercept, his plaque psoriasis markedly improved, whereas both his fasting blood sugars and glycosylated hemoglobin A(1c) decreased. Hypoglycemia can be a serious side effect of etanercept in patients already on antidiabetic medications known to cause hypoglycemia, such as sulfonylureas, meglitinides, and insulin. Thus, it is important for dermatologists treating patients with diabetes and antitumor necrosis factor-alpha agents for psoriasis to be aware of potential hypoglycemia and to adjust antidiabetes therapy accordingly.
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PMID:Persistent hypoglycemia in a patient with diabetes taking etanercept for the treatment of psoriasis. 1921 93

We evaluated risk factors such as socio-demographic characteristics, smoking habits and alcohol consumption, associated with hypertension, diabetes and obesity in psoriasis patients, in order to plan health education programs that could prevent the onset or progression of co-morbidities. The study population consisted of 1376 patients with psoriasis who were consecutively recruited at 21 Italian Departments of Dermatology. Information concerning socio-demographic variables, smoking and alcohol consumption, and the presence of chronic disorders such as hypertension, type 2 diabetes and obesity was collected. The risk of co-morbidities according to the various exposure variables was calculated using logistic regression models. Psoriasis patients living in extremely urban areas showed the highest risk of diabetes (OR = 1.99, 95% CI 1.06-5.23) and obesity (OR = 2.60, 95% CI 1.10-16.12), as compared to patients living in rural areas. The OR for hypertension was higher for smokers (> 15 cigarettes per day, OR = 1.37, 95% CI 1.01-2.03) and drinkers (> 2 glasses/day of wine, OR = 2.11, 95% CI 1.31-3.40). The OR for diabetes or obesity was higher for drinkers: 1 drink/day (OR = 1.93, 95% CI 1.01-3.67) and > 1 drink/day of spirits (OR = 2.90, 95% CI 1.43-5.82), respectively. The results of our survey highlight the need to detect psoriasis patients with different susceptibilities to co-morbidities in order to plan specific health campaigns aimed at changing people's lifestyles with respect to smoking, drinking and diet.
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PMID:Risk factors of hypertension, diabetes and obesity in Italian psoriasis patients: a survey on socio-demographic characteristics, smoking habits and alcohol consumption. 1922 Sep 83

Psoriasis is a disease mediated by Th1 and Th17 cytokines that has different phenotypes (plaque, guttate, pustular, and erythrodermic type). Aside from the well known psoriatic arthritis, associated disorders may occur more frequently than expected, including Crohn's disease, anxiety/depression, and metabolic syndrome. This is based on a constellation of different factors, including abdominal obesity, atherogenic dyslipidemia, hypertension, and glucose intolerance, and is a strong predictor of type 2 diabetes, cardiovascular disease, and stroke. People with moderate to severe psoriasis have more risk for cardiac disease, presumably due to the inflammatory nature of psoriasis, causing inflammatory changes in coronary arteries. The strong association between psoriasis and obesity potentially makes psoriasis an important healthcare issue. Since cardiovascular risk factors are higher in psoriatic patients, dermatologists treating moderate to severe psoriasis should screen for their presence, thus approaching psoriasis as a potential multisystem disorder.
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PMID:Clinical aspects and comorbidities of psoriasis. 1966 31

Psoriasis is an inflammatory, immune-mediated cutaneous disorder that has recently been recognized as systemic disease that is associated with multiple comorbidities such as depression, obesity, and the metabolic syndrome. The metabolic syndrome is the constellation of abdominal obesity, dyslipidemia, hypertension and insulin resistance, and presence of the metabolic syndrome significantly increases a patient's risk for cardiovascular disease, stroke and type 2 diabetes. Recent studies have found that psoriasis patients are at increased risk for metabolic syndrome as well as the individual components of metabolic syndrome, and the two diseases appear linked through a common mechanism of inflammation. Speculation exists as to whether this association is causative or whether it is the result of other habits seen in psoriasis patients, such as increased rates of smoking, alcohol consumption, and sedentary lifestyle, which add to the complexity of the association between psoriasis and the metabolic syndrome. However, psoriasis treatments have been shown to reduce the risk of developing metabolic syndrome components and comorbidities. Future studies are needed to better understand the nature of this relationship and the implications this could have for management and treatment of patients with psoriasis.
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PMID:Psoriasis and the metabolic syndrome. 2041 20

Recently, it has emerged a strong association between increased adiposity, obesity, and psoriasis. Body Mass Index (BMI) is a simple index of weight-for-height that is commonly used to classify underweight, overweight and obesity in adults. Psoriasis has also been associated with systemic obesity-related disorders including type 2 diabetes, hypertension, ischemic heart disease, and combined hyperlipidemia, as a part of metabolic syndrome. Not only the obesity may be associated with higher psoriasis incidence and activity, and prevalence of obesity-related syndromes, but it may also influence the therapeutic approach to disease and the clinical response to systemic treatment. Consequently, the approach of the experienced dermatologist will take into account all the aspects of the patient clinical conditions including the analysis of BMI for the choice of the best suitable therapy.
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PMID:Psoriasis and body mass index. 2041 22

Obesity and related metabolic conditions are of epidemic proportions in most of the world, affecting both adults and children. The accumulation of lipids in the body in the form of white adipose tissue in the abdomen is now known to activate innate immune mechanisms. Lipid accumulation causes adipocytes to directly secrete the cytokines interleukin (IL) 6 and tumor necrosis factor alpha (TNFalpha), but also monocyte chemoattractant protein 1 (MCP-1), which results in the accumulation of leukocytes in fat tissue. This sets up a chronic inflammatory state which is known to mediate the association between obesity and conditions such as cardiovascular disease, type 2 diabetes, and cancer. There is also a substantial literature linking inflammation with risk for depression. This includes the observations that: (1) people with inflammatory diseases such as multiple sclerosis, cardiovascular disease, and psoriasis have elevated rates of depression; (2) many people administered inflammatory cytokines such as interferon alpha develop depression that is indistinguishable from depression in non-medically ill populations; (3) a significant proportion of depressed persons show upregulation of inflammatory factors such as IL-6, C-reactive protein, and TNFalpha; (4) inflammatory cytokines can interact with virtually every pathophysiologic domain relevant to depression, including neurotransmitter metabolism, neuroendocrine function, and synaptic plasticity. While many factors may contribute to the association between inflammatory mediators and depression, we hypothesize that increased adiposity may be one causal pathway. Mediational analysis suggests a bi-directional association between adiposity and depression, with inflammation possibly playing an intermediary role.
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PMID:Eating ourselves to death (and despair): the contribution of adiposity and inflammation to depression. 2041 47


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