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)

Hyperinsulinemia may be related to colon carcinogenesis. Several studies have suggested that diabetes mellitus is related to increased risk of colon cancer. We examined cross-sectionally the relation of fasting plasma insulin levels and glucose tolerance status to colon adenomas. In a consecutive series of 951 men undergoing total colonoscopy for a health examination at the Japan Self Defense Forces Fukuoka Hospital from April 1998 to August 1999, we identified 233 cases of colon adenomas and 497 controls with normal colonoscopy. Glucose tolerance status was determined by a 75-g oral glucose tolerance test, and subjects were classified as normal, impaired glucose tolerance (IGT) or non-insulin dependent diabetes mellitus (NIDDM). Plasma insulin levels were measured after subjects had fasted overnight. Logistic regression analysis and analysis of covariance was used to control for age and obesity. While plasma insulin levels were unrelated to colon adenomas, NIDDM was associated with a significantly increased risk of colon adenomas. There was no association between IGT and colon adenomas. NIDDM was more strongly associated with proximal colon adenomas. The findings suggest that long-term hyperinsulinemic status associated with NIDDM may increase the risk of colon adenomas, and subsequently of colon cancer.
Jpn J Cancer Res 2001 Aug
PMID:Glucose intolerance, plasma insulin levels, and colon adenomas in Japanese men. 1150 14

Obesity is associated with an increased risk for developing type 2 diabetes, insulin resistance, hypertension, dyslipidemia, cardiovascular disease, respiratory dysfunction, and certain forms of cancer. Insulin resistance in many type 2 diabetic patients is the result of increased visceral adiposity. To identify novel genes implicated in type 2 diabetes and/or obesity and to elucidate the molecular mechanisms underlying both diseases, we analyzed gene expression in omental fat from lean and obese nondiabetic subjects and obese type 2 diabetic patients using mRNA differential display and subtracted library techniques. After screening over 13,800 subtracted cDNA clones and 6,912 cDNA amplification products, we identified 2,078 cDNAs that showed potential differential expression in the omental fat of lean versus obese nondiabetic subjects versus obese type 2 diabetic patients. Data analysis showed that 70.7% of these clones corresponded to unknown genes (26.7% matched express sequence tags [ESTs]) and 29.3% corresponded to known genes. Reverse Northern and classic Northern analyses further confirmed that the expression of five of these cDNA clones was elevated in obese nondiabetic subjects and obese type 2 diabetic patients. Four candidate genes were further evaluated for tissue distribution, which showed expression primarily in adipose and skeletal muscle tissue, and chromosomal localization. We concluded that both mRNA differential display and subtracted cDNA libraries are powerful tools for identifying novel genes implicated in the pathogenesis of obesity and type 2 diabetes.
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PMID:Identification of novel genes differentially expressed in omental fat of obese subjects and obese type 2 diabetic patients. 1172 66

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are used as cancer chemopreventative agents, their mechanism is unclear because NSAIDs have cyclooxygenase-independent actions. We investigated an alternative target for NSAIDs, peroxisome proliferator-activated receptor-gamma (PPARgamma), activation of which decreases cancer cell proliferation. NSAIDs have been shown to activate this receptor, but only at high concentrations. Here, we have examined binding of diclofenac to PPARgamma using a cis-parinaric acid displacement assay and studied the effect of diclofenac effect on PPARgamma trans-activation in a COS-1 cell reporter assay. Unexpectedly, diclofenac bound PPARgamma at therapeutic concentrations (K(i) = 700 nM) but induced only 2-fold activation of PPARgamma at a concentration of 25 microM and antagonized PPARgamma trans-activation by rosiglitazone. This antagonism was overcome with increasing rosiglitazone concentrations, indicating that diclofenac is a partial agonist. No effect of diclofenac was seen without exogenous receptor, confirming that it was working through a PPARgamma-specific mechanism. This is the first description of an NSAID that can antagonize PPARgamma. In addition, this is the first time that an NSAID has been shown to bind this receptor at clinically meaningful concentrations. The physiological relevance of these findings was tested using adipocyte differentiation and cancer cell proliferation assays. Diclofenac decreased PPARgamma-mediated adipose cell differentiation by 60% and inhibited the action of rosiglitazone on the prostate cancer cell line, DU-145, allowing a 3-fold increase in proliferation. This work shows that standard doses of diclofenac may have pharmacodynamic interactions with rosiglitazone and this has therapeutic implications, both in the management of type 2 diabetes and during cancer treatment.
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PMID:Diclofenac antagonizes peroxisome proliferator-activated receptor-gamma signaling. 1175

We report an 85 years-old patient with type 2 diabetes mellitus and both clinical and biochemical nephrotic syndrome. The renal biopsy showed membranous nephropathy at stage I-II. There was no evidence of malignancy. The patient was treated with steroids, and two months later the proteinuria had not improved. The objects under discussion are the factors that should lead to suspect the existence of glomerulonephritis, other than diabetic glomerulosclerosis, suggesting the need for kidney biopsy. We also focus on the prognostic and therapeutic relevance, as well as on the common pathogenic aspects.
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PMID:[Idiopathic membranous nephropathy in an elderly patient with type 2 diabetes mellitus]. 1181 18

Almost all major causes of ill-health and premature death in human societies worldwide - including cancer, cardiovascular disease, diabetes and many infectious diseases - are, at least in part, genetically determined. Typically, risk of succumbing to one of these illnesses is thought to depend on both the individual repertoire of variation within a number of key susceptibility genes and the history of exposure to relevant environmental factors. For many of these conditions, the molecular basis of disease pathogenesis remains obscure. This represents a major obstacle to development of improved, rational strategies for disease treatment, prevention and eradication. It is easy therefore to appreciate the importance attached to efforts to deliver more comprehensive understanding of the molecular basis of disease pathogenesis. Nor is it hard to understand that identification of major susceptibility genes should highlight those components of molecular machinery that are critical for the preservation of normal health. The benefits promised are great, but progress to gene identification in multifactorial traits has been rather disappointing to date. Why is this? This review aims to answer this question by describing current and future approaches to gene discovery in multifactorial traits. The examples quoted will mostly relate to type 2 diabetes, but the issues and approaches are generic, and apply equally to other multifactorial traits in the endocrine and metabolic arena - type 1 diabetes; obesity; hyperlipidaemia; autoimmune thyroid disease; polycystic ovarian syndrome - and beyond.
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PMID:Susceptibility gene discovery for common metabolic and endocrine traits. 1185 95

To examine the association between snoring and risk of developing type II diabetes mellitus, the authors analyzed data from the Nurses' Health Study cohort. This analysis included 69,852 US female nurses aged 40-65 years without diagnosed diabetes, cardiovascular disease, or cancer at baseline in 1986. Snoring patterns were ascertained by questionnaire. During 10 years of follow-up, 1,957 women were diagnosed with type II diabetes. In analyses adjusted for age and body mass index, snoring was associated with risk of diabetes (for occasional snoring vs. nonsnoring, relative risk (RR) = 1.48 (95% confidence interval (CI): 1.29, 1.70); for regular snoring vs. nonsnoring, RR = 2.25 (95% CI: 1.91, 2.66); p for trend < 0.0001). Further adjustment for other diabetes risk factors and sleeping-related covariates only slightly attenuated the risk (for occasional snoring, RR = 1.41 (95% CI: 1.22, 1.63); for regular snoring, RR = 2.03 (95% CI: 1.71, 2.40); p for trend < 0.0001). Analyses stratified by body mass index, smoking history, or parental history of diabetes showed a consistent association between snoring and diabetes within the categories of these variables. These results suggest that snoring is independently associated with elevated risk of type II diabetes.
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PMID:Snoring as a risk factor for type II diabetes mellitus: a prospective study. 1186 48

This article describes important issues for the nutritional health of adolescents. The issues discussed include dietary factors involved in cardiovascular and cancer disease risk; osteoporosis and bone mineralization; overweight and obesity; related risk factors such as type 2 diabetes; and eating disorders. The discussion focuses on nutritional issues for the general adolescent population, rather than high-risk adolescents. Data are primarily drawn from large, population-based studies using representative samples of adolescents.
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PMID:Nutritional issues for adolescents. 1190 96

Diabetes mellitus has reached epidemic proportions worldwide as we enter the new millennium. The World Health Organization (WHO) has commented there is 'an apparent epidemic of diabetes which is strongly related to lifestyle and economic change'. Over the next decade the projected number will exceed 200 million, possibly reaching 250 million persons. Most will have type 2 diabetes and all are at risk of the development of complications. Better education, improved nutrition, more exercise, early diagnosis and prompt treatment are imperative. Diabetes is a serious disease, subject to the development of many complications affecting large vessels (heart, cerebral and peripheral), small vessels (kidney and retina), nerves and other organs. In type 2 diabetes these complications may precede diagnosis of the disease by many years. The process continues inexorably, with premature mortality and morbidity mainly from the development of vascular disease. Data from the WHO confirm the principal role of non-communicable disease on mortality in developed countries, while mortality in developing countries is rising rapidly, now often exceeding communicable disease. The non-communicable diseases are divided into cancer and degenerative diseases. In the developed world, degenerative diseases are grouped to include ischaemic heart disease, stroke, renal failure, hypertension and other macro- and microvascular diseases. The major complications of diabetes encountered most frequently and with the greatest impact are: 1. Neuropathy, both peripheral and autonomic, with principal manifestations in the lower limbs 2. Microvascular disease, mainly affecting the retina and kidney, resulting in blindness and renal failure 3. Macrovascular disease, presenting with atherosclerosis in the coronary arteries causing ischaemic heart disease, cerebrovascular disease causing stroke and peripheral vascular disease contributing to diabetic gangrene.
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PMID:The economic burden of insulin resistance. 1196 27

Diabetes is associated with alterations in liver metabolism and immune response that may influence postoperative recovery and long-term survival after hepatectomy for cancer. Patients with type I or type II diabetes mellitus submitted to a potentially curative hepatic resection for metastatic colorectal cancer were identified from the prospective database, and compared with patients with hepatic colorectal metastases submitted to resection during the same time interval, but without diabetes mellitus. Data on operative morbidity and mortality and long-term survival were analyzed. Between December 1990 and July 1999, a total of 727 patients underwent hepatic resection, 61 of whom (8.1%) had type I and type II diabetes mellitus. Operative mortality in the diabetic patients was significantly greater than in nondiabetic patients (8% vs. 2%, P < 0.02). Among patients with diabetes mellitus, four of the five perioperative deaths were due to liver failure after major hepatic resection (lobectomy or greater). All four of these patients had significant parenchymal abnormality (three with steatosis). Long-term survival was identical to that in nondiabetic control subjects. We conclude that the presence of diabetes is associated with a higher incidence of perioperative mortality. In patients with diabetes mellitus and parenchymal steatosis, major hepatic resection should be undertaken with caution.
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PMID:Diabetes is associated with increased perioperative mortality but equivalent long-term outcome after hepatic resection for colorectal cancer. 1198 23

Obesity is a risk factor for many diseases including cardio-vascular disease, type 2 diabetes, and certain forms of cancer, among others. Obesity results from a chronic imbalance between calorie intake and energy expenditure. Genetic factors obviously play an important role in weight gain, but only in certain environments. The principal cause of the obesity epidemic is not clear: is obesity due to excessive food intake, a dynamic reduction in energy expenditure, or an association of these two factors? However, most obese subjects gain weight because of an inaptitude to adjust energy expenditure in response to excessive food intake. In this article, we review briefly the respective role of genes and environment in the development of obesity, then describe metabolic risk factors involved. Longitudinal studies conducted in Pima Indians have demonstrated that a relative decrease in basal metabolism, weak lipid oxidation in the fasting state, reduced spontaneous physical activity, and lower sympathetic nervous system activity are risk factors for obesity. Unlike our growing knowledge of food intake regulation, little is known about the control of energy expenditure. New discoveries should provide information on obesity susceptibility genes and increase the chances of developing new anti-obesity treatments.
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PMID:[Determinants and control of energy expenditure]. 1199 69


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